title: Pretreatment of food waste with high voltage pulse discharge towards methane production enhancement.

text: Anaerobic batch tests were performed to investigate the methane production enhancement and solid transformation rates from food waste (FW) by high voltage pulse discharge (HVPD) pretreatment. The total cumulative methane production with HVPD pretreatment was 134% higher than that of the control. The final volatile solids transformation rates of FW with and without HVPD pretreatment were 54.3% and 32.3%, respectively. Comparison study on HVPD pretreatment with acid, alkali and ultrasonic pretreatments showed that the methane production and COD removal rates of FW pretreated with HVPD were more than 100% higher than the control, but only about 50% higher can be obtained with other pretreatments. HVPD pretreatment could be a promising pretreatment method in the application of energy recovery from FW.


title: Systemic inflammatory response after single-incision laparoscopic surgery versus standard laparoscopic approach.

text: PURPOSE The extent of surgical trauma is reflected by systemic inflammatory response (SIR). The aim of this study was to assess SIR after single-incision laparoscopic surgery (SILS) versus the standard laparoscopic approach. MATERIALS AND METHODS Twenty pigs were assigned into 4 groups: SILS (group SILS), laparoscopy using 4 trocars (group LAPSC), pneumoperitoneum (group PNE), or a sham-operation (group Sham) group. Blood samples were taken at 0, 1, 3, 6, 24, and 48 hours and 1 week postoperation to measure tumor necrosis factor-α, interleukin (IL)-6, IL-18, and C-reactive protein serum levels. RESULTS No significant changes were noted among groups for each time point studied regarding tumor necrosis factor-α, IL-6, and IL-18. C-reactive protein levels were significantly lower (P<0.05) in group PNE compared with the other groups at 24 hours, 48 hours, and 1 week. CONCLUSIONS There is no difference in SIR after SILS versus the standard laparoscopic approach.


Managing patients with choroidal melanoma in the COVID-19 era: a personal perspective.


title: Effect of xenograft (ABBM) particle size on vital bone formation following maxillary sinus augmentation: a multicenter, randomized, controlled, clinical histomorphometric trial.

text: The purpose of this study was a histomorphometric comparison of vital bone formation following maxillary sinus augmentation with two different particle sizes of anorganic bovine bone matrix (ABBM). Bilateral sinus floor augmentations were performed in 13 patients. Trephine bone cores were taken from the lateral window areas of 11 patients 6 to 8 months after augmentation for histologic and histomorphometric analysis. Bone samples from both the large and small particle size groups showed evidence of vital bone formation similar to that seen in previous studies, confirming the osteoconductivity of ABBM. Significant bone bridging was seen creating new trabeculae composed of the newly formed bone and residual ABBM particles. Histologic evaluation revealed the newly formed bone to be mostly woven bone with some remodeling to lamellar bone. Osteocytes were seen within the newly formed bone as well as osteoblast seams with recently formed osteoid. Isolated osteoclasts were observed on the ABBM surfaces. Vital bone formation (primary outcome measure) was more extensive in the large particle grafts compared with the small particle grafts (26.77% ± 9.63% vs 18.77% ± 4.74%, respectively). The histologic results reaffirm the osteoconductive ability of ABBM when used as the sole grafting material in maxillary sinus augmentation. The histomorphometric results at 6 to 8 months revealed a statistically significant increase (P = .02) in vital bone formation when the larger particle size was used. Additional studies should be performed to confirm these results.


title: Controversial Relationship between Renin-Angiotensin System Inhibitors and Severity of COVID-19: Announcing a Large Multicentre Case-Control Study in Italy.

text: The hypothesis has been proposed that patients COVID-19 positive, under anti-hypertensive treatment with angiotensin enzyme inhibitors or angiotensin receptor-blockers, might have a worse or a better clinical prognosis. This might be due to the fact that ACE2 is the receptor for the virus to enter human cells, but, on the contrary, that ACE2 expression is downregulated following SARS-1 infection, resulting in disproportionate activation of renin-angiotensin-aldosterone system and exacerbated pneumonia progression. However, no solid clinical data are available at the present moment to support or disprove such hypotheses. We announce in this letter that a large multicentre case-control study has been started in Italy that is the country with a very high impact of COVID-19 infection. We hope that our letter will encourage other clinical centres, even outside Italy, to join our study.


Post discharge positive re-tests in COVID-19: common but clinically non-significant.


title: Doubling Time of the COVID-19 Epidemic by Province, China.

text: In China, the doubling time of the coronavirus disease epidemic by province increased during January 20-February 9, 2020. Doubling time estimates ranged from 1.4 (95% CI 1.2-2.0) days for Hunan Province to 3.1 (95% CI 2.1-4.8) days for Xinjiang Province. The estimate for Hubei Province was 2.5 (95% CI 2.4-2.6) days.


title: Experimental study of a novel mechanical connector for sutureless open arterial anastomosis.

text: OBJECTIVES This study assessed the feasibility and efficacy of a new sutureless connector for end-to-end arterial anastomosis. METHODS The anastomotic device is a connector consisting of a bare-metal stent with spikes covering its outer surface, which is introduced through the prosthesis. The seal of the anastomosis is obtained by inflating a balloon anchoring the stent with the spikes in the prosthesis and in the receiving artery. This experiment was conducted in three phases: (1) A feasibility study was done on four cadaveric femoral arteries using a polytetrafluoroethylene prosthesis, with measurement of the penetration of the spikes into the layers of the arterial wall. (2) Bench tests were conducted in seven automated and in seven sutured anastomoses. Anastomosis sealing was tested using a pump system (≤250 mm Hg) in a water-filled closed circuit. (3) The infrarenal aorta of seven pigs was replaced with a 6- to 8-mm diameter prosthesis, using this automated device for the proximal anastomosis. The distal anastomosis was handsewn on the aortic bifurcation. After completion angiography, animals were euthanized for macroscopic and histologic studies of the aorta, connector, and prosthesis. Explantations were done immediately (2 pigs), and at 15 (2 pigs), at 30 (2 pigs), and 42 days (1 pig). Study end points were the automated anastomosis time compared with manual suturing, leakage, mechanical strength, and patency of the anastomosis together with the histologic changes of the aortic wall in contact with the spiked stent. RESULTS Tests performed on four cadaveric arteries showed complete penetration of the spikes into the arterial wall layers without metal fracture. Tests of traction showed that the median force needed to rupture the automated anastomosis was 18.3 N (interquartile range [IQR], 17.7-19.9 N), with no significant difference from the handmade anastomosis (19.5 N; IQR, 17.9-20.2 N, P = .33). No leakage was demonstrated in vitro with a pulsatile flow and a pressure up to 250 mm Hg. The median automated anastomosis time on pig aorta was 2.4 minutes (IQR, 1.4-3.3 min) vs 17.0 minutes (IQR, 15.1-17.2 minutes) for the handmade aortic anastomosis performed on the same animals (P = .002). There was no anastomotic leak. Histology showed incorporation of the connector spikes in the aortic wall, without intimal hyperplasia or false aneurysm. CONCLUSIONS This preliminary study confirms the feasibility of this sutureless system, suggesting its usefulness for a faster and simpler anastomosis in hybrid arterial surgery.


title: Bicycling and Walking are Associated with Different Cortical Oscillatory Dynamics.

text: Although bicycling and walking involve similar complex coordinated movements, surprisingly Parkinson's patients with freezing of gait typically remain able to bicycle despite severe difficulties in walking. This observation suggests functional differences in the motor networks subserving bicycling and walking. However, a direct comparison of brain activity related to bicycling and walking has never been performed, neither in healthy participants nor in patients. Such a comparison could potentially help elucidating the cortical involvement in motor control and the mechanisms through which bicycling ability may be preserved in patients with freezing of gait. The aim of this study was to contrast the cortical oscillatory dynamics involved in bicycling and walking in healthy participants. To this end, EEG and EMG data of 14 healthy participants were analyzed, who cycled on a stationary bicycle at a slow cadence of 40 revolutions per minute (rpm) and walked at 40 strides per minute (spm), respectively. Relative to walking, bicycling was associated with a stronger power decrease in the high beta band (23-35 Hz) during movement initiation and execution, followed by a stronger beta power increase after movement termination. Walking, on the other hand, was characterized by a stronger and persisting alpha power (8-12 Hz) decrease. Both bicycling and walking exhibited movement cycle-dependent power modulation in the 24-40 Hz range that was correlated with EMG activity. This modulation was significantly stronger in walking. The present findings reveal differential cortical oscillatory dynamics in motor control for two types of complex coordinated motor behavior, i.e., bicycling and walking. Bicycling was associated with a stronger sustained cortical activation as indicated by the stronger high beta power decrease during movement execution and less cortical motor control within the movement cycle. We speculate this to be due to the more continuous nature of bicycling demanding less phase-dependent sensory processing and motor planning, as opposed to walking.


title: Assumptions for disparities in case-fatality rates of coronavirus disease (COVID-19) across the globe.

text: In a short span, Coronavirus disease (COVID-19) has become the world pandemic by rapidly spreading almost to all the countries around the globe, irrespective of the continent, population size, economic status and healthcare system. Despite the number of cases increasing exponentially in most of the countries, there exist certain disparities in terms of case-fatality rates. As of April 24, 2020, the case-fatality rate of COVID-19 is about 7.0%, with 193,671 deaths and 2,761,121 confirmed cases around the world. Although the United States of America (USA), Spain, Italy, France, and Germany are the top-most affected counties in terms of confirmed cases; France, Italy and Spain are leading the list in terms of case-fatality rates. Therefore, through this mini-review, authors sought to brief on possible assumptions (five D's) that might contribute to the varying case-fatality rates among different countries across the globe.


Cases of coronavirus disease-2019 in HIV-infected transgender women.


title: A phase 2a, randomized, crossover trial of gabapentin enacarbil for the treatment of postherpetic neuralgia in gabapentin inadequate responders.

text: OBJECTIVE To compare the efficacy of high-dose (3,600 mg/day) vs low-dose (1,200 mg/day) oral gabapentin enacarbil (GEn) on pain intensity in adults with postherpetic neuralgia (PHN) and a history of inadequate response to ≥1,800 mg/day gabapentin. DESIGN Multicenter, randomized, double-blind, crossover study (NCT00617461). SETTING Thirty-five outpatient centers in Germany and the United States. SUBJECTS Subjects aged ≥18 years with a diagnosis of PHN. METHODS During a 2-week baseline period, subjects received open-label treatment with 1,800 mg/day gabapentin. Subjects who had a mean 24-hour average pain intensity score ≥4 during the last 7 days of the baseline period were randomized to receive GEn (1,200 or 3,600 mg/day) for treatment period 1 (28 days), followed by GEn 2,400 mg/day (4 days), and the alternate GEn dose for treatment period 2 (28 days). RESULTS There was a modest but significant improvement in pain intensity scores with GEn 3,600 mg vs 1,200 mg (adjusted mean [90% confidence interval] treatment difference, -0.29 [-0.48 to -0.10]; P = 0.013). The difference in efficacy between doses was observed primarily in subjects who received the higher dose during treatment period 2; certain aspects of the study design may have contributed to this outcome. Plasma steady-state gabapentin exposure during GEn treatment was as expected and consistent between treatment periods. No new safety signals or adverse event trends relating to GEn exposure were identified. CONCLUSIONS While the overall results demonstrated efficacy in a PHN population, the differences between treatment periods confound the interpretation. These findings could provide insight into future trial designs.


title: Molecular testing for acute respiratory tract infections: clinical and diagnostic recommendations from the IDSA's Diagnostics Committee.

text: The clinical signs and symptoms of acute respiratory tract infections (RTIs) are not pathogen specific. Highly sensitive and specific nucleic acid amplification tests have become the diagnostic reference standard for viruses and translation of bacterial assays from basic research to routine clinical practice represents an exciting advance in respiratory medicine. Most recently, molecular diagnostics have played an essential role in the global health response to the novel coronavirus pandemic. How best to use newer molecular tests for RTI in combination with clinical judgment and traditional methods can be bewildering given the plethora of available assays and rapidly evolving technologies. Here, we summarize the current state of the art with respect to the diagnosis of viral and bacterial RTIs, provide a practical framework for diagnostic decision-making using selected patient-centered vignettes, and make recommendations for future studies to advance the field.


title: The factors predicting pneumonia in COVID-19 patients: preliminary results of a university hospital in Turkey.

text: BACKGROUND/AIM Pneumonia is the most serious clinical presentation of COVID-19. This study is aimed to determine the demographic, clinical, and laboratory findings that can properly predict COVID-19 pneumonia. MATERIALS AND METHODS This study was conducted in Gazi University hospital. All hospitalized patients with confirmed and suspected SARS-CoV-2 infection between 16 March 2020, and 30 April 2020, were analyzed retrospectively. COVID-19 patients were separated into two groups as pneumonia and non-pneumonia and compared to determine predicting factors for COVID-19 pneumonia. Variables with a p-value of less than 0.20 and not correlated with each other were included in the logistic regression model. RESULTS Of the 247 patients included in the study, the median age was 40, 58% was female. COVID-19 was confirmed in 70.9% of these patients. 21.4% of COVID-19 confirmed cases had pneumonia. In the multivariate analysis male sex (p = 0.028), hypertension (p = 0.022) and shortness of breath on hospital admission (p = 0.025) were significant factors predicting COVID-19 pneumonia Conclusion: Shortness of breath, male gender, and hypertension were significant for predicting COVID-19 pneumonia on admission. The patients with those factors should be evaluated more carefully for diagnostic procedures, such as thorax CT.


title: Risk stratification in patients undergoing nonoperating room anesthesia.

text: PURPOSE OF REVIEW A growing numerical and complexity of patients requiring nonoperating room anesthesia (NORA) necessitates a multidisciplinary approach of a highly experienced team in a highly technological setting of the cathlab or radiology suite. These requirements are even more magnified in the context of the coronavirus disease 2019 (COVID-19) pandemic. RECENT FINDINGS This review describes the aspects of risk stratification both in adults and children with respect to patient morphology, airway management, cardiorespiratory function and finally future developments, which could beneficially interfere with imminent management in NORA. Moreover, some particular features related to COVID-19 are also discussed. SUMMARY Apart from a thorough preoperative assessment, preventive strategies and well-chosen monitoring should be implemented to preclude inadvertent events in sometimes high-risk patients. Timely preventive measures and early recognition of complications could only be achieved by a multidisciplinary cooperating team. In addition, the implementation of safety measurements due to the infectious transmission to both the patients and care givers is crucial.


New Issues in Nursing Management During the COVID-19 Pandemic in Italy.


Pneumonia in China: lack of information raises concerns among Hong Kong health workers.


title: Impact assessment of leaf pigments in selected landscape plants exposed to roadside dust.

text: Continuous addition of undesired effluents to the environment affects foliar surface of leaf, changes their morphology, stomata, photosynthetic pigments, and biochemical constituents which result in massive damage due to persistent nature of the pollutant. In persistent hostile environment, plants fail to grow and develop, and the effects are often extensive. In current study, landscape plants were exposed to different levels of road dust to analyze the effect on various photosynthetic pigments. Dry roadside sediments were collected through a vacuum pump and passed through filters to get fine particles less than 100 μm and sprinkled on Euphorbia milii (EM), Gardenia jasminoides (GJ), and Hibiscus rosa-sinensis (HRs) by using a hand pump, twice daily at T1 (control), T2, T3, and T4 (0, 2, 4, and 6 g/plant, respectively) for a period of 3 months in green house. Road sediment significantly reduces leaf pigments in landscape plants population and the effects were more severe in high level of dust deposition. Individual response of EM, GJ, and HRs to different levels of road dust was variable; however, road sediment significantly reduces leaf pigments at high dose of roadside dust deposition. EM plants exposed to 2 g/plant roadside dust showed higher chlorophyll-a, chlorophyll-b, total chlorophyll, chlorophyllide-b, and polar carotenoid contents as compared to GJ and HRs. Leaf chlorophyll-a, chlorophyll-b, total chlorophyll, carotenoid, and polar carotenoid contents of EM were higher than GJ and HRs in T3 and T4 treatments. However HRs showed significantly higher protochlorophyllide, chlorophyllide-a, and pheophytin-b contents of leaf in T4 group. EM was found as tolerant landscape plant followed by HRs. GJ was most vulnerable to road dust stress. Present study concludes that the entire biosynthesis of leaf pigments is in chain and interlinked together where effect of road dust on one pigment influences other pigments and their derivatives. Salient features of the present study provide useful evidence to estimate roadside dust as a major risk factor for plant pigments, and plants in green belt along roadside suffer retarded growth and fail to establish and develop.


title: Correlation between the Spread of COVID-19 and the Interest in Personal Protective Measures in Poland and Portugal.

text: The pandemic of the coronavirus disease 2019 (COVID-19), has gained extensive coverage in public media and global news, generated international and national communication campaigns to educate the communities worldwide and raised the attention of everyone. The coronavirus has caused viral pneumonia in tens of thousands of people around the world, and the COVID-19 outbreak changed most countries' routines and concerns and transformed social behaviour. This study explores the potential use of Google Trends (GT) in monitoring interest in the COVID-19 outbreak and, specifically, in personal protective equipment and hand hygiene, since these have been promoted by official health care bodies as two of the most protective measures. GT was chosen as a source of reverse engineering data, given the interest in the topic and the novelty of the research. Current data on COVID-19 are retrieved from GT using keywords in two languages-Portuguese and Polish. The geographical settings for GT are two countries: Poland and Portugal. The period under analysis is 20 January 2020, when the first cases outside China were known, to 15 June 2020. The results show that there is a correlation between the spread of COVID-19 and the search for personal protective equipment and hand hygiene and that GT can help, to a certain extent, understand people's concerns, behaviour and reactions to sanitary problems and protection recommendations.


title: Acute Basilar Artery Occlusion with Underlying High-Grade Basilar Artery Stenosis: Multimodal Endovascular Therapy in a Series of Seven Patients.

text: PURPOSE Acute basilar artery occlusion is associated with high rates of major morbidity and mortality. In rare cases, the underlying pathology is a high-grade stenosis of the basilar artery. We report on a series of seven cases with occluded high-grade basilar artery stenosis who received endovascular therapy at our center. MATERIAL AND METHODS Our prospective database since October 2009 until September 2013 was screened for patients with acute basilar artery occlusion and underlying high-grade stenosis who underwent endovascular therapy. Case files were retrospectively reviewed for clinical, outcome, and technical data. RESULTS Seven patients were identified who suffered from an acute basilar artery occlusion based on a high-grade stenosis between October 2009 and September 2013. These patients were treated with an acute stenting of the basilar artery with or without a preceding mechanical thrombectomy. Median age was 75 (53-83) years; median prethrombectomy National Institute of Health Stroke scale score was 19 (7-28). A successful recanalization result defined as modified Thrombolysis In Cerebral Infarction grade 2b or higher was achieved in all cases. Two of the seven patients had a procedural complication consisting of a vessel dissection after angioplasty. A good clinical outcome according to the Solitaire flow restoration device versus the Merci Retriever in patients with acute ischaemic stroke (SWIFT) study criteria was achieved in three of the seven patients. One patient died during hospitalization in the acute phase. CONCLUSION Mechanical thrombectomy combined with acute stenting of the basilar artery is technically feasible and may be an effective therapeutic option in the rare case of an acutely occluded high-grade stenosis of the basilar artery in patients with an otherwise poor prognosis.


title: Endovascular treatment of brain arteriovenous malformations using a liquid embolic agent: results of a prospective, multicentre study (BRAVO).

text: OBJECTIVES To evaluate the safety and efficacy of a new liquid embolic agent in brain arteriovenous malformation (bAVMs) embolisation. METHODS A prospective, multicentre series was conducted at 11 interventional centres in Europe to evaluate embolisation of bAVMs with the new liquid embolic agent. Technical conditions, complications, clinical outcome and anatomical results were independently analysed. RESULTS From December 2005 to December 2008, 117 patients (72 male; 45 female, aged 18-75 years) were included. Clinical presentation was mostly haemorrhage (34.2 %) and seizures (28.2 %). Most AVMs were located in the brain hemispheres (85.5 %). AVMs were <3 cm in 52.1 % of patients and ≥ 3 cm in 47.9 %. Morbidity was observed in 6/117 patients (5.1 %), related to haemorrhagic events in 2 cases and non-haemorrhagic complications in 4 cases. Five patients (4.3 %) died in relation to the treatment (bleeding in 4 patients and extensive venous thrombosis in 1). Complete occlusion of the AVM by embolisation alone was obtained in 23.5 % of patients. Complementary treatment was performed in 82.3 % of patients with partial AVM occlusion, mostly radiosurgery. CONCLUSIONS In this prospective, multicentre, European, observational series, the new liquid embolic agent proved to be suitable for BAVM embolisation, with acceptable morbidity and mortality and good efficacy. KEY POINTS • Numerous interventional techniques have been used to embolise brain arteriovenous malformations (AVMs). • This prospective multicentre study demonstrates the suitability of a liquid embolic agent. • The safety of treatment using Onyx is acceptable. • Such embolisation leads to complete AVM occlusion in 23.5 % of patients.


title: Extracellular high mobility group box-1 inhibits R5 and X4 HIV-1 strains replication in mononuclear phagocytes without induction of chemokines and cytokines.

text: OBJECTIVE High mobility group box-1 (HMGB1) is a nuclear chromatin protein. Furthermore, it induces chemotaxis and inflammation once released in the extracellular milieu, and it has been reported to upregulate, but also to inhibit HIV-1 replication in different cell types. We here investigated the potential role of extracellular HMGB1 in both R5 and X4 HIV-1 replication in primary human monocyte-derived macrophages (MDM) and U937 promonocytic cells, respectively. DESIGN MDM or U937 cells were infected with R5 and X4 HIV-1 strains, respectively, in the presence or absence of endotoxin-free recombinant (r) HMGB1 or necrotic cell supernatants either containing or depleted of endogenous HMGB1. METHODS HIV replication was measured by means of virion-associated reverse transcriptase activity in culture supernatants and cell-associated viral protein expression. Cytokine and chemokine production were measured by enzyme-linked immunosorbent assay; cell surface expression of CD4, CC chemokine receptor 5, receptor for advanced glycation end-products, Toll-like receptor-2 and Toll-like receptor-4 were analyzed by flow cytometry. RESULTS Both rHMGB1 and necrotic cell supernatant-associated HMGB1 inhibited replication of R5 HIV-1 in MDM. Surprisingly enough, no upregulation of CC chemokine receptor 5-binding chemokines or of other chemokines and cytokines was observed in rHMGB1-stimulated MDM. HMGB1 also induced chemotaxis and strongly inhibited the replication of X4 HIV-1 in the 'Minus' subset of U937 cell clones expressing high levels of putative HMGB1 receptors (receptor for advanced glycation end-products, Toll-like receptors 2 and 4). CONCLUSION Extracellular HMGB1 is a potent inhibitor of both R5 and X4 HIV-1 replication in mononuclear phagocytic cells without inducing the release of HIV-Modulatory chemokines or cytokines.


title: Contraindications for video capsule endoscopy.

text: Video capsule endoscopy (VCE) has been applied in the last 15 years in an increasing field of applications. Although many contraindications have been put into perspective, some precautions still have to be considered. Known stenosis of the gastrointestinal tract is a clear contraindication for VCE unless surgery is already scheduled or at least has been considered as an optional treatment modality. In patients with a higher incidence of stenosis, as in an established diagnosis of Crohn's disease, clinical signs of obstruction, prior radiation or surgical small bowel resection, a preceding test with the self-dissolving patency capsule can override this contraindication. Endoscopic placement of the capsule should be considered in patients with swallowing disorders to avoid aspiration. Esophageal or gastric motility disorders may require endoscopic capsule transport or application of prokinetics if the real-time viewer proofs delayed transit. In pregnant women, VCE should be restricted to urgent cases where diagnosis cannot be postponed after delivery, as data on safety are missing. There is theoretical and clinical evidence that patients with implanted cardiac devices such as a pacemaker, cardioverters or left heart assist devices, can safely undergo VCE in spite of still existing contraindication by manufacturers. Children from the age of 2 years have safely undergone VCE. Although video capsules are not proven safe with magnetic resonance imaging (MRI), first single cases of patients incidentally undergoing MRI with an incorporated capsule have been reported, showing susceptibility artifacts but no signs of clinical harm.


title: CRISPRai for simultaneous gene activation and inhibition to promote stem cell chondrogenesis and calvarial bone regeneration.

text: Calvarial bone healing remains difficult but may be improved by stimulating chondrogenesis of implanted stem cells. To simultaneously promote chondrogenesis and repress adipogenesis of stem cells, we built a CRISPRai system that comprised inactive Cas9 (dCas9), two fusion proteins as activation/repression complexes and two single guide RNA (sgRNA) as scaffolds for recruiting activator (sgRNAa) or inhibitor (sgRNAi). By plasmid transfection and co-expression in CHO cells, we validated that dCas9 coordinated with sgRNAa to recruit the activator for mCherry activation and also orchestrated with sgRNAi to recruit the repressor for d2EGFP inhibition, without cross interference. After changing the sgRNA sequence to target endogenous Sox9/PPAR-γ, we packaged the entire CRISPRai system into an all-in-one baculovirus for efficient delivery into rat bone marrow-derived mesenchymal stem cells (rBMSC) and verified simultaneous Sox9 activation and PPAR-γ repression. The activation/inhibition effects were further enhanced/prolonged by using the Cre/loxP-based hybrid baculovirus. The CRISPRai system delivered by the hybrid baculovirus stimulated chondrogenesis and repressed adipogenesis of rBMSC in 2D culture and promoted the formation of engineered cartilage in 3D culture. Importantly, implantation of the rBMSC engineered by the CRISPRai improved calvarial bone healing. This study paves a new avenue to translate the CRISPRai technology to regenerative medicine.


Laparoscopic colorectal anastomosis technique without ''dog ear'' formation using LigaSure for bowel transection.


title: Neutralizing anti-influenza virus monoclonal antibodies: therapeutics and tools for discovery.

text: The human antibody response to influenza virus infection plays a protective role against re-infection, yet little molecular detail is available regarding how human antibodies, when characterized at the monoclonal level, neutralize this important human pathogen. Recent studies, using a diverse array of strategies, have isolated and characterized human anti-virus neutralizing antibodies and shed light not only on the specificity and origin of these antibodies but on their potential for therapeutic use against influenza virus infection.


title: Bioabsorbable fixation: scientific, technical, and clinical concepts.

text: Bioabsorbable internal fixation has been clinically available for nearly 20 years and has been used for hard tissue and/or soft tissue fixation from the head to toe. During this time, there has been a rapid evolution in bioabsorbable polymers as well as in the implants and their clinical applications. There is a plethora of bioabsorbable polymers now available for clinical use, and although all are related chemically, seemingly small changes in formulation can have a dramatic effect on their biomechanical and physiological properties. This article summarizes much of the relevant scientific, technical, and clinical literature in a simple, straightforward manner to help surgeons better understand and appreciate the nuances of bioabsorbable fixation. This up-to-date review should also help researchers establish a baseline of knowledge that can provide a platform for further developments in this exciting field.


Opportunities for Research for COVID-19 in the Mission of NIDDK.


title: Severity of gambling problems modulates autonomic reactions to near outcomes in gambling.

text: Outcomes in gambling games cannot only be classified based on their valence (wins and misses) but also based on their closeness (near and full outcomes). The present study investigated autonomic responses (phasic heart period changes and skin conductance responses) to near and full outcomes on a wheel of fortune in a sample of males with different degrees of gambling problems. Near relative to full outcomes elicited increased interbeat intervals shortly after outcome presentation. Furthermore, participants with more severe gambling problems showed increased skin conductance responses following near relative to full outcomes as well as relatively smaller interbeat interval responses to near relative to full misses. The findings confirm different processing of near compared to full outcomes and altered processing of gambling outcomes with increasing severity of gambling problems.


title: Age-related changes in mechanical properties of the Achilles tendon.

text: The stiffness of a tendon, which influences muscular force transfer to the skeleton and increases during childhood, is dependent on its material properties and dimensions, both of which are influenced by chronic loading. The aims of this study were to: (i) determine the independent contributions of body mass, force production capabilities and tendon dimensions to tendon stiffness during childhood; and (ii) descriptively document age-related changes in tendon mechanical properties and dimensions. Achilles tendon mechanical and material properties were determined in 52 children (5-12 years) and 19 adults. Tendon stiffness and Young's modulus (YM) were calculated as the slopes of the force-elongation and stress-strain curves, respectively. Relationships between stiffness vs. age, mass and force, and between YM vs. age, mass and stress were determined by means of polynomial fits and multiple regression analyses. Mass was found to be the best predictor of stiffness, whilst stress was best related to YM (< 75 and 51% explained variance, respectively). Combined, mass and force accounted for up to 78% of stiffness variation. Up to 61% of YM variability could be explained using a combination of mass, stress and age. These results demonstrate that age-related increases in tendon stiffness are largely attributable to increased tendon loading from weight-bearing tasks and increased plantarflexor force production, as well as tendon growth. Moreover, our results suggest that chronic increases in tendon loading during childhood result in microstructural changes which increase the tendon's YM. Regarding the second aim, peak stress increased from childhood to adulthood due to greater increases in strength than tendon cross-sectional area. Peak strain remained constant as a result of parallel increases in tendon length and peak elongation. The differences in Achilles tendon properties found between adults and children are likely to influence force production, and ultimately movement characteristics, which should be explicitly examined in future research.


title: Hospitalization Rates and Characteristics of Patients Hospitalized with Laboratory-Confirmed Coronavirus Disease 2019 - COVID-NET, 14 States, March 1-30, 2020.

text: Since SARS-CoV-2, the novel coronavirus that causes coronavirus disease 2019 (COVID-19), was first detected in December 2019 (1), approximately 1.3 million cases have been reported worldwide (2), including approximately 330,000 in the United States (3). To conduct population-based surveillance for laboratory-confirmed COVID-19-associated hospitalizations in the United States, the COVID-19-Associated Hospitalization Surveillance Network (COVID-NET) was created using the existing infrastructure of the Influenza Hospitalization Surveillance Network (FluSurv-NET) (4) and the Respiratory Syncytial Virus Hospitalization Surveillance Network (RSV-NET). This report presents age-stratified COVID-19-associated hospitalization rates for patients admitted during March 1-28, 2020, and clinical data on patients admitted during March 1-30, 2020, the first month of U.S. surveillance. Among 1,482 patients hospitalized with COVID-19, 74.5% were aged ≥50 years, and 54.4% were male. The hospitalization rate among patients identified through COVID-NET during this 4-week period was 4.6 per 100,000 population. Rates were highest (13.8) among adults aged ≥65 years. Among 178 (12%) adult patients with data on underlying conditions as of March 30, 2020, 89.3% had one or more underlying conditions; the most common were hypertension (49.7%), obesity (48.3%), chronic lung disease (34.6%), diabetes mellitus (28.3%), and cardiovascular disease (27.8%). These findings suggest that older adults have elevated rates of COVID-19-associated hospitalization and the majority of persons hospitalized with COVID-19 have underlying medical conditions. These findings underscore the importance of preventive measures (e.g., social distancing, respiratory hygiene, and wearing face coverings in public settings where social distancing measures are difficult to maintain)† to protect older adults and persons with underlying medical conditions, as well as the general public. In addition, older adults and persons with serious underlying medical conditions should avoid contact with persons who are ill and immediately contact their health care provider(s) if they have symptoms consistent with COVID-19 (https://www.cdc.gov/coronavirus/2019-ncov/symptoms-testing/symptoms.html) (5). Ongoing monitoring of hospitalization rates, clinical characteristics, and outcomes of hospitalized patients will be important to better understand the evolving epidemiology of COVID-19 in the United States and the clinical spectrum of disease, and to help guide planning and prioritization of health care system resources.


title: Velopharyngeal closure analysis using four-dimensional computed tomography: a pilot study of healthy volunteers and adult patients with cleft palate.

text: BACKGROUND Nasopharyngoscopy is a common method to evaluate velopharyngeal closure in patients with cleft palate. However, insertion of a fiberoptic nasopharyngoscope causes discomfort in patients. The aim of this study was to estimate the reliability of short-time exposure images obtained using 320-row area detector computed tomography (320-ADCT) as a novel evaluation method for the assessment of velopharyngeal function. METHODS We evaluated five healthy adult volunteers and five postoperative adult patients with cleft palate. During a 3.3-s imaging exposure, the participants were asked to perform two tasks: nasal inspiration and subsequent oral expiration through a catheter into a water-filled cup. The movement of the velopharyngeal structures was recorded during each examination, and the presence of velopharyngeal insufficiency (VPI) and velopharyngeal closure (VPC) patterns were estimated. If VPI was detected, the cross-sectional area was also calculated. Cohen's kappa and weighted kappa coefficients were used to evaluate the concordance of nasopharyngoscopy and 320-ADCT evaluation. RESULTS Speech pathology evaluation did not reveal hypernasality in any study participant. Micro-VPI was detected by nasopharyngoscopy in one healthy volunteer and two patients. 320-ADCT detected micro-VPI in two more patients. The cross-sectional area of the VPI in these subjects ranged from 2.53 to 16.28 mm2. Nasopharyngoscopy and 320-ADCT were concordant in detecting VPI in eight participants (κ = 0.6) and in assessing VPC patterns in nine (κ = 0.82). Moreover, images obtained using 320-ADCT allowed for reduced dead angle and, thus, easy detection of micro-VPI and Passavant's ridges. CONCLUSION Although the radiation exposure cannot be ignored, our novel evaluation method using 320-ADCT enables more detailed evaluation of VPC than nasopharyngoscopy. Future studies should investigate the relationship between 320-ADCT findings and speech pathology evaluations.


title: Abrupt deterioration and pulmonary embolism in COVID-19: a case report.

text: A case is presented highlighting pulmonary embolism as an important complication of COVID-19 and the abruptness with which deterioration and widespread pulmonary infiltrates can develop even after relatively normal initial investigations, illustrating the importance of follow-up. The role of CT scanning in COVID-19 is also discussed.


title: Effect of a retrievable inferior vena cava filter plus anticoagulation vs anticoagulation alone on risk of recurrent pulmonary embolism: a randomized clinical trial.

text: IMPORTANCE Although retrievable inferior vena cava filters are frequently used in addition to anticoagulation in patients with acute venous thromboembolism, their benefit-risk ratio is unclear. OBJECTIVE To evaluate the efficacy and safety of retrievable vena cava filters plus anticoagulation vs anticoagulation alone for preventing pulmonary embolism recurrence in patients presenting with acute pulmonary embolism and a high risk of recurrence. DESIGN, SETTING, AND PARTICIPANTS Randomized, open-label, blinded end point trial (PREPIC2) with 6-month follow-up conducted from August 2006 to January 2013. Hospitalized patients with acute, symptomatic pulmonary embolism associated with lower-limb vein thrombosis and at least 1 criterion for severity were assigned to retrievable inferior vena cava filter implantation plus anticoagulation (filter group; n = 200) or anticoagulation alone with no filter implantation (control group; n = 199). Initial hospitalization with ambulatory follow-up occurred in 17 French centers. INTERVENTIONS Full-dose anticoagulation for at least 6 months in all patients. Insertion of a retrievable inferior vena cava filter in patients randomized to the filter group. Filter retrieval was planned at 3 months from placement. MAIN OUTCOMES AND MEASURES Primary efficacy outcome was symptomatic recurrent pulmonary embolism at 3 months. Secondary outcomes were recurrent pulmonary embolism at 6 months, symptomatic deep vein thrombosis, major bleeding, death at 3 and 6 months, and filter complications. RESULTS In the filter group, the filter was successfully inserted in 193 patients and was retrieved as planned in 153 of the 164 patients in whom retrieval was attempted. By 3 months, recurrent pulmonary embolism had occurred in 6 patients (3.0%; all fatal) in the filter group and in 3 patients (1.5%; 2 fatal) in the control group (relative risk with filter, 2.00 [95% CI, 0.51-7.89]; P = .50). Results were similar at 6 months. No difference was observed between the 2 groups regarding the other outcomes. Filter thrombosis occurred in 3 patients. CONCLUSIONS AND RELEVANCE Among hospitalized patients with severe acute pulmonary embolism, the use of a retrievable inferior vena cava filter plus anticoagulation compared with anticoagulation alone did not reduce the risk of symptomatic recurrent pulmonary embolism at 3 months. These findings do not support the use of this type of filter in patients who can be treated with anticoagulation. TRIAL REGISTRATION clinicaltrials.gov Identifier: NCT00457158.


title: Systematic review of the influence of enhanced recovery pathways in elective lung resection.

text: OBJECTIVE Enhanced-recovery pathways aim to accelerate postoperative recovery and facilitate early hospital discharge. The aim of this systematic review was to summarize the evidence regarding the influence of this intervention in patients undergoing lung resection. METHODS The review was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Statement. Eight bibliographic databases (Medline, Embase, BIOSIS, CINAHL, Web of Science, Scopus, Cochrane Database of Systematic Reviews, and Cochrane Central Register of Controlled Trials) were searched for studies comparing postoperative outcomes in adult patients treated within an enhanced-recovery pathway or traditional care. Risk of bias was assessed using the Cochrane Collaboration risk of bias tool. RESULTS Six studies fulfilled our selection criteria (1 randomized and 5 nonrandomized studies). All the nonrandomized studies reported shorter length of stay in the intervention group (difference, 1.2-9.1 days), but the randomized study reported no differences. There were no differences between groups in readmissions, overall complications, and mortality rates. Two nonrandomized studies reported reduction in hospital costs in the intervention group. Risk of bias favoring enhanced recovery pathways was high. CONCLUSIONS A small number of low-quality comparative studies have evaluated the influence of enhanced-recovery pathways in patients undergoing lung resection. Some studies suggest that this intervention may reduce length of stay and hospital costs, but they should be interpreted in light of several methodologic limitations. This review highlights the need for well-designed trials to provide conclusive evidence about the role of enhanced-recovery pathways in this patient population.


title: Detection of respiratory viruses in sputum from adults by use of automated multiplex PCR.

text: Respiratory tract infections (RTI) frequently cause hospital admissions among adults. Diagnostic viral reverse transcriptase PCR (RT-PCR) of nose and throat swabs (NTS) is useful for patient care by informing antiviral use and appropriate isolation. However, automated RT-PCR systems are not amenable to utilizing sputum due to its viscosity. We evaluated a simple method of processing sputum samples in a fully automated respiratory viral panel RT-PCR assay (FilmArray). Archived sputum and NTS samples collected in 2008-2012 from hospitalized adults with RTI were evaluated. A subset of sputum samples positive for 10 common viruses by a uniplex RT-PCR was selected. A sterile cotton-tip swab was dunked in sputum, swirled in 700 μL of sterile water (dunk and swirl method) and tested by the FilmArray assay. Quantitative RT-PCR was performed on "dunked" sputum and NTS samples for influenza A (Flu A), respiratory syncytial virus (RSV), coronavirus OC43 (OC43), and human metapneumovirus (HMPV). Viruses were identified in 31% of 965 illnesses using a uniplex RT-PCR. The sputum sample was the only sample positive for 105 subjects, including 35% (22/64) of influenza cases and significantly increased the diagnostic yield of NTS alone (302/965 [31%] versus 197/965 [20%]; P = 0.0001). Of 108 sputum samples evaluated by the FilmArray assay using the dunk and swirl method, 99 (92%) were positive. Quantitative RT-PCR revealed higher mean viral loads in dunked sputum samples compared to NTS samples for Flu A, RSV, and HMPV (P = 0.0001, P = 0.006, and P = 0.011, respectively). The dunk and swirl method is a simple and practical method for reliably processing sputum samples in a fully automated PCR system. The higher viral loads in sputa may increase detection over NTS testing alone.


title: Subgenomic messenger RNA amplification in coronaviruses.

text: Coronaviruses possess the largest known RNA genome, a 27- to 32-kb (+)-strand molecule that replicates in the cytoplasm. During virus replication, a 3' coterminal nested set of five to eight subgenomic (sg) mRNAs are made that are also 5' coterminal with the genome, because they carry the genomic leader as the result of discontinuous transcription at intergenic donor signals during (-)-strand synthesis when templates for sgmRNA synthesis are made. An unanswered question is whether the sgmRNAs, which appear rapidly and abundantly, undergo posttranscriptional amplification. Here, using RT-PCR and sequence analyses of head-to-tail-ligated (-) strands, we show that after transfection of an in vitro-generated marked sgmRNA into virus-infected cells, the sgmRNA, like the genome, can function as a template for (-)-strand synthesis. Furthermore, when the transfected sgmRNA contains an internally placed RNA-dependent RNA polymerase template-switching donor signal, discontinuous transcription occurs at this site, and a shorter, 3' terminally nested leader-containing sgmRNA is made, as evidenced by its leader-body junction and by the expression of a GFP gene. Thus, in principle, the longer-nested sgmRNAs in a natural infection, all of which contain potential internal template-switching donor signals, can function to increase the number of the shorter 3'-nested sgmRNAs. One predicted advantage of this behavior for coronavirus survivability is an increased chance of maintaining genome fitness in the 3' one-third of the genome via a homologous recombination between the (now independently abundant) WT sgmRNA and a defective genome.


title: Metal composition of fine particulate air pollution and acute changes in cardiorespiratory physiology.

text: BACKGROUND Studying the physiologic effects of components of fine particulate mass (PM2.5) could contribute to a better understanding of the nature of toxicity of air pollution. OBJECTIVES We examined the relation between acute changes in cardiovascular and respiratory function, and PM2.5-associated-metals. METHODS Using generalized linear mixed models, daily changes in ambient PM2.5-associated metals were compared to daily changes in physiologic measures in 59 healthy subjects who spent 5-days near a steel plant and 5-days on a college campus. RESULTS Interquartile increases in calcium, cadmium, lead, strontium, tin, vanadium and zinc were associated with statistically significant increases in heart rate of 1-3 beats per minute, increases of 1-3 mmHg in blood pressure and/or lung function decreases of up to 4% for total lung capacity. CONCLUSION Metals contained in PM2.5 were found to be associated with acute changes in cardiovascular and respiratory physiology.


title: Strokes in the anterior circulation: comparison between bridging and intravenous thrombolysis.

text: BACKGROUND AND PURPOSE To compare safety and efficacy of bridging approach with intravenous (IV) thrombolysis in patients with acute anterior strokes and proximal occlusions. PATIENTS AND METHODS Consecutive patients with ischemic anterior strokes admitted within a 4 h 30 min window in two different centers were included. The first center performed IV therapy (alteplase 0.6 mg/kg) during 30 min and, in absence of clinical improvement, mechanical thrombectomy with flow restoration using a Solitaire stent (StS); the second carried out IV thrombolysis (alteplase 0.9 mg/kg) alone. Only T, M1 or M2 occlusions present on CT angiography were considered. Endpoints were clinical outcome and mortality at 3 months. RESULTS There were 63 patients in the bridging and 163 in the IV group. No significant differences regarding baseline characteristics were observed. At 3 months, 46% (n = 29) of the patients treated in the combined and 23% (n = 38) of those treated in the IV group had a modified Rankin scale (mRS) of 0-1 (P < 0.001). A statistical significant difference was observed for all sites of occlusion. In a logistic regression model, National Institute of Health Stroke Scale (NIHSS) and bridging therapy were independent predictors of good outcome (respectively, P = 0.001 and P = 0.0018). Symptomatic hemorrhage was documented in 6.3% vs 3.7% in the bridging and in the IV group, respectively (P = 0.32). There was no difference in mortality. CONCLUSIONS Our results suggest that patients treated with a bridging approach were more likely to have minimal or no deficit at all at 3 months as compared to the IV treated group.


title: Effect of treatment delay, age, and stroke severity on the effects of intravenous thrombolysis with alteplase for acute ischaemic stroke: a meta-analysis of individual patient data from randomised trials.

text: BACKGROUND Alteplase is effective for treatment of acute ischaemic stroke but debate continues about its use after longer times since stroke onset, in older patients, and among patients who have had the least or most severe strokes. We assessed the role of these factors in affecting good stroke outcome in patients given alteplase. METHODS We did a pre-specified meta-analysis of individual patient data from 6756 patients in nine randomised trials comparing alteplase with placebo or open control. We included all completed randomised phase 3 trials of intravenous alteplase for treatment of acute ischaemic stroke for which data were available. Retrospective checks confirmed that no eligible trials had been omitted. We defined a good stroke outcome as no significant disability at 3-6 months, defined by a modified Rankin Score of 0 or 1. Additional outcomes included symptomatic intracranial haemorrhage (defined by type 2 parenchymal haemorrhage within 7 days and, separately, by the SITS-MOST definition of parenchymal type 2 haemorrhage within 36 h), fatal intracranial haemorrhage within 7 days, and 90-day mortality. FINDINGS Alteplase increased the odds of a good stroke outcome, with earlier treatment associated with bigger proportional benefit. Treatment within 3·0 h resulted in a good outcome for 259 (32·9%) of 787 patients who received alteplase versus 176 (23·1%) of 762 who received control (OR 1·75, 95% CI 1·35-2·27); delay of greater than 3·0 h, up to 4·5 h, resulted in good outcome for 485 (35·3%) of 1375 versus 432 (30·1%) of 1437 (OR 1·26, 95% CI 1·05-1·51); and delay of more than 4·5 h resulted in good outcome for 401 (32·6%) of 1229 versus 357 (30·6%) of 1166 (OR 1·15, 95% CI 0·95-1·40). Proportional treatment benefits were similar irrespective of age or stroke severity. Alteplase significantly increased the odds of symptomatic intracranial haemorrhage (type 2 parenchymal haemorrhage definition 231 [6·8%] of 3391 vs 44 [1·3%] of 3365, OR 5·55, 95% CI 4·01-7·70, p<0·0001; SITS-MOST definition 124 [3·7%] vs 19 [0·6%], OR 6·67, 95% CI 4·11-10·84, p<0·0001) and of fatal intracranial haemorrhage within 7 days (91 [2·7%] vs 13 [0·4%]; OR 7·14, 95% CI 3·98-12·79, p<0·0001). The relative increase in fatal intracranial haemorrhage from alteplase was similar irrespective of treatment delay, age, or stroke severity, but the absolute excess risk attributable to alteplase was bigger among patients who had more severe strokes. There was no excess in other early causes of death and no significant effect on later causes of death. Consequently, mortality at 90 days was 608 (17·9%) in the alteplase group versus 556 (16·5%) in the control group (hazard ratio 1·11, 95% CI 0·99-1·25, p=0·07). Taken together, therefore, despite an average absolute increased risk of early death from intracranial haemorrhage of about 2%, by 3-6 months this risk was offset by an average absolute increase in disability-free survival of about 10% for patients treated within 3·0 h and about 5% for patients treated after 3·0 h, up to 4·5 h. INTERPRETATION Irrespective of age or stroke severity, and despite an increased risk of fatal intracranial haemorrhage during the first few days after treatment, alteplase significantly improves the overall odds of a good stroke outcome when delivered within 4·5 h of stroke onset, with earlier treatment associated with bigger proportional benefits. FUNDING UK Medical Research Council, British Heart Foundation, University of Glasgow, University of Edinburgh.


Towards the rational utilization of SARS-CoV-2 serological tests in clinical practice.


title: Ethics, pandemics, and the duty to treat.

text: Numerous grounds have been offered for the view that healthcare workers have a duty to treat, including expressed consent, implied consent, special training, reciprocity (also called the social contract view), and professional oaths and codes. Quite often, however, these grounds are simply asserted without being adequately defended or without the defenses being critically evaluated. This essay aims to help remedy that problem by providing a critical examination of the strengths and weaknesses of each of these five grounds for asserting that healthcare workers have a duty to treat, especially as that duty would arise in the context of an infectious disease pandemic. Ultimately, it argues that none of the defenses is currently sufficient to ground the kind of duty that would be needed in a pandemic. It concludes by sketching some practical recommendations in that regard.


title: A Randomized Controlled Trial Comparison of NeuroSENSE and Bispectral Brain Monitors During Propofol-Based Versus Sevoflurane-Based General Anesthesia.

text: BACKGROUND NeuroSENSE is a depth of anesthesia monitor that uses automated electroencephalogram quantification. The Wavelet-based Anesthetic Value for Central Nervous System (WAVCNS) index calculated by this monitor is based on wavelet analysis of a normalized electroencephalogram signal in the γ-frequency band. The aim of this study was to determine the extent of disagreement between the Bispectral Index (BIS) and the WAVCNS index during propofol-based and sevoflurane-based maintenance of general anesthesia in a routine surgical population. METHODS Patients undergoing elective surgery were enrolled in the study and randomly assigned to receive either propofol or sevoflurane for the maintenance of anesthesia and remifentanil in both groups. Anesthesiologists were blinded to monitors in both groups. Discordance between the 2 monitors was assessed by the count of discrepancy in recommendation (DR) (type 1 defined as one parameter <40 and the other >60, or type 2 defined as BIS and WAVCNS values on different sides of a threshold [40 or 60]) and also by the proportion of agreement (P0) between WAVCNS and BIS, obtained every 5 seconds, in 3 categories of index (<40, 40-60, and >60). RESULTS The analyzed data set consisted of 22 patients (36,872 data pairs) in the propofol group and 24 patients (32,826 data pairs) in the sevoflurane group. The type 1 DR rarely occurred in both the groups (<1%); however, the median (interquartile range) type 2 DR was significantly more frequent in the propofol group (20.6% [7.0-36.9] vs 4.5% [2.3-12.4]; P = 0.0005). The median difference in P0 was 11.53% (95% confidence interval, 0.57-21.32). Major disagreement between WAVCNS index and BIS was related to the weight of burst suppression pattern for the index calculation. CONCLUSIONS Disagreement between BIS and NeuroSENSE during the maintenance of general anesthesia was worse in the propofol group than that in the sevoflurane groups. The disagreement increases during deep anesthesia or in the occurrence of burst suppression.


title: Vitamin D to prevent exacerbations of COPD: systematic review and meta-analysis of individual participant data from randomised controlled trials.

text: BACKGROUND Randomised controlled trials (RCTs) of vitamin D to prevent COPD exacerbations have yielded conflicting results.Individual participant data meta-analysis could identify factors that explain this variation. METHODS PubMed, Embase, the Cochrane Central Register of Controlled Trials and Web of Science were searched from inception up to and including 5 October 2017 to identify RCTs of vitamin D supplementation in patients with COPD that reported incidence of acute exacerbations. Individual participant data meta-analysis was performed using fixed effects models adjusting for age, sex, Global Initiative for Chronic Obstructive Lung Disease spirometric grade and trial. RESULTS Four eligible RCTs (total 560 participants) were identified; individual participant data were obtained for 469/472 (99.4%) participants in three RCTs. Supplementation did not influence overall rate of moderate/severe COPD exacerbations (adjusted incidence rate ratio (aIRR) 0.94, 95% CI 0.78 to 1.13). Prespecified subgroup analysis revealed that protective effects were seen in participants with baseline 25-hydroxyvitamin D levels <25 nmol/L (aIRR 0.55, 95% CI 0.36 to 0.84) but not in those with baseline 25-hydroxyvitamin D levels ≥25 nmol/L (aIRR 1.04, 95% CI 0.85 to 1.27; p for interaction=0.015). Vitamin D did not influence the proportion of participants experiencing at least one serious adverse event (adjusted OR 1.16, 95% CI 0.76 to 1.75). CONCLUSIONS Vitamin D supplementation safely and substantially reduced the rate of moderate/severe COPD exacerbations in patients with baseline 25-hydroxyvitamin D levels <25 nmol/L but not in those with higher levels. TRIAL REGISTRATION NUMBER CRD42014013953.


title: Patient-generated health data and electronic health record integration: protocol for a scoping review.

text: INTRODUCTION The objective of this study is to determine the extent and describe the nature of patient-generated health data (PGHD) integration into electronic health records (EHRs) using systematic scoping methods to review the available literature. PGHD have the potential to enhance decision making by providing the valuable information that may not be ordinarily captured during a routine care visit. These data which are captured from mobile devices, such as smartphones, activity trackers and other sensors, should be integrated into clinical workflows to allow for optimal use by clinicians. METHODS AND ANALYSIS This study aims to conduct a rigorous scoping review to explore evidence related to the integration of PGHD into EHRs. Using the framework developed by Arksey and O'Malley, we will create a systematic search strategy, chart data from the relevant articles, and use a qualitative, thematic approach to analyse the data. This review will enable the identification of types of integration and describe challenges and barriers to integrating PGHD. ETHICS AND DISSEMINATION Database searches will be initiated in June 2019. The review is expected to be completed by October 2019. As the content of the full-text articles emerges, the authors will summarise the characteristics related to the integration of PGHD. The findings of this scoping review will identify research gaps and present implications for future research.


title: Successful endovascular treatment of a holo-hemispheric cerebral arteriovenous fistula in an infant.

text: A cerebral arteriovenous fistula (CAVF) is a rare abnormality representing only 4.7% of all cerebral arteriovenous malformations. In this report a unique case is presented of a giant holo-hemispheric CAVF in an infant who presented with congestive heart failure and was successfully treated endovascularly with transarterial and transvenous embolization. A 4-day-old girl presented with lethargy and poor feeding and was found to be in congestive heart failure secondary to a large left hemispheric vascular malformation. Embolization was performed via a transarterial route on days of life (DOL) 11 and 18, a transvenous route on DOL 54 and a final transarterial treatment on DOL 76. After all treatment the patient was discharged home on minimal cardiac medications. At 2-year follow-up the patient had moderate motor delays and mild speech delays, but she continued to meet milestones and her cardiac failure was completely resolved. This case demonstrates one of the largest CAVFs treated successfully in the neonatal population.


title: Effect of sevoflurane on systemic and cerebral circulation, cerebral autoregulation and CO2 reactivity.

text: BACKGROUND Sevoflurane is one of the most frequently used inhaled anesthetics for general anesthesia. Previously it has been reported that at clinically used doses of sevoflurane, cerebral vasoreactivity is maintained. However, there are no data how sevoflurane influences systemic and cerebral circulation in parallel. The aim of our study was to assess systemic and cerebral hemodynamic changes as well as cerebral CO2-reactivity during sevoflurane anesthesia. METHODS Twenty nine patients undergoing general anesthesia were enrolled. Anesthesia was maintained with 1 MAC sevoflurane in 40% oxygen. Ventilatory settings (respiratory rate and tidal volume) were adjusted to reach and maintain 40, 35 and 30 mmHg EtCO2 for 5 min respectively. At the end of each period, transcranial Doppler and hemodynamic parameters using applanation tonometry were recorded. RESULTS Systemic mean arterial pressure significantly decreased during anesthetic induction and remained unchanged during the entire study period. Central aortic and peripherial pulse pressure and augmentation index as markers of arterial stiffness significantly increased during the anesthetic induction and remained stable at the time points when target CO2 levels were reached. Both cerebral autoregulation and cerebral CO2-reactivity was maintained at 1 MAC sevoflurane. DISCUSSION Cerebral autoregulation and CO2-reactivity is preserved at 1 MAC sevoflurane. Cerebrovascular effects of anesthetic compounds have to be assessed together with systemic circulatory effects. TRIAL REGISTRATION The study was registered at http://www.clinicaltrials.gov , identifier: NCT02054143, retrospectively registered. Date of registration: February 4, 2014.


title: [Comparison of two epidemic patterns of COVID-19 and evaluation of prevention and control effectiveness: an analysis based on Guangzhou and Wenzhou].

text: Objective: To compare the epidemiological characteristics of COVID-19 in Guangzhou and Wenzhou, and evaluate the effectiveness of their prevention and control measures. Methods: Data of COVID-19 cases reported in Guangzhou and Wenzhou as of 29 February, 2020 were collected. The incidence curves of COVID-19 in two cities were constructed. The real time reproduction number (R(t)) of COVID-19 in two cities was calculated respectively. Results: A total of 346 and 465 confirmed COVID-19 cases were analysed in Guangzhou and Wenzhou, respectively. In two cities, most cases were aged 30-59 years (Guangzhou: 54.9%; Wenzhou: 70.3%). The incidence curve peaked on 27 January, 2020 in Guangzhou and on 26 January, 2020 in Wenzhou, then began to decline in both cities. The peaks of imported COVID-19 cases from Hubei occurred earlier than the peak of COVID-19 incidences in two cities, and the peak of imported cases from Hubei occurred earlier in Wenzhou than in Guangzhou. In early epidemic phase, imported cases were predominant in both cities, then the number of local cases increased and gradually took the dominance in Wenzhou. In Guangzhou, the imported cases was still predominant. Despite the different epidemic pattern, the R(t) and the number of COVID-19 cases declined after strict prevention and control measures were taken in Guangzhou and in Wenzhou. Conclusion: The time and scale specific differences of imported COVID-19 resulted in different epidemic patterns in two cities, but the spread of the disease were effectively controlled after taking strict prevention and control measures.


title: The need for a systematic approach to disaster psychosocial response: a suggested competency framework.

text: Competency models attempt to define what makes expert performers "experts." Successful disaster psychosocial planning and the institutionalizing of psychosocial response within emergency management require clearly-defined skill sets. This necessitates anticipating both the short- and long-term psychosocial implications of a disaster or health emergency (ie, pandemic) by developing effective and sustained working relationships among psychosocial providers, programs, and other planning partners. The following article outlines recommended competencies for psychosocial responders to enable communities and organizations to prepare for and effectively manage a disaster response. Competency-based models are founded on observable performance or behavioral indicators, attitudes, traits, or personalities related to effective performance in a specific role or job. After analyzing the literature regarding competency-based frameworks, a proposed competency framework that details 13 competency domains is suggested. Each domain describes a series of competencies and suggests behavioral indicators for each competency and, where relevant, associated training expectations. These domains have been organized under three distinct categories or types of competencies: general competency domains; disaster psychosocial intervention competency domains; and disaster psychosocial program leadership and coordination competency domains. Competencies do not replace job descriptions nor should they be confused with performance assessments. What they can do is update and revise job descriptions; orient existing and new employees to their disaster/emergency roles and responsibilities; target training needs; provide the basis for ongoing self-assessment by agencies and individuals as they evaluate their readiness to respond; and provide a job- or role-relevant basis for performance appraisal dimensions or standards and review discussions. Using a modular approach to psychosocial planning, service providers can improve their response capacity by utilizing differences in levels of expertise and training. The competencies outlined in this paper can thus be used to standardize expectations about levels of psychosocial support interventions. In addition this approach provides an adaptable framework that can be adjusted for various contexts.


title: Oncologic outcomes for complete robot-assisted laparoscopic management of upper-tract transitional cell carcinoma.

text: BACKGROUND AND PURPOSE The gold standard for treatment of upper-tract transitional cell carcinoma (TCC) is nephroureterectomy. For distal ureteral TCC, distal ureterectomy with ureteral reimplantation represents a treatment option. Multiple minimally invasive techniques have been introduced with the goal of replicating these open procedures. Currently, there is a paucity of literature for the use of robot-assisted laparoscopic (RAL) management of upper-tract TCC. We evaluated our experience with RAL management of upper-tract TCC. PATIENTS AND METHODS A retrospective chart review was performed on all patients who underwent complete RAL nephroureterectomy or distal ureterectomy with ureteral reimplantation at our institution. RESULTS Eleven patients with a mean age of 67.4 years underwent RAL nephroureterectomy. Mean operative time was 326 minutes (range 243-470 minutes), estimated blood loss 200 mL (range 100-400 mL), and mean length of hospital stay was 4.7 days. With a mean follow-up of 15.2 months (range 2-31 months), four patients experienced recurrence, and two ultimately died from metastatic disease. Four patients with a mean age of 73.5 years underwent RAL distal ureterectomy with ureteral reimplantation for distal ureteral TCC. Mean operative time was 311 minutes (range 225-446 minutes), estimated blood loss 200 mL (range 100-350 mL), and mean length of hospital stay was 4.7 days. With a mean follow-up of 30.5 months (range 12-48 months), only one patient, whose pathology exhibited carcinoma in situ within periureteral tissue, required adjuvant treatment for recurrent disease. CONCLUSIONS RAL nephroureterectomy and distal ureterectomy with ureteral reimplantation are feasible options for patients with upper-tract TCC with promising short-term oncologic outcomes.


title: Metformin attenuates blood-brain barrier disruption in mice following middle cerebral artery occlusion.

text: BACKGROUND Metformin, a widely used hypoglycemic drug, reduces stroke incidence and alleviates chronic inflammation in clinical trials. However, the effect of metformin in ischemic stroke is unclear. Here, we investigated the effect of metformin on ischemic stroke in mice and further explored the possible underlying mechanisms. METHODS Ninety-eight adult male CD-1 mice underwent 90-minute transient middle cerebral artery occlusion (tMCAO). Metformin (200 mg/kg) was administrated for up to 14 days. Neurobehavioral outcomes, brain infarct volume, inflammatory factors, blood-brain barrier (BBB) permeability and AMPK signaling pathways were evaluated following tMCAO. Oxygen glucose deprivation was performed on bEND.3 cells to explore the mechanisms of metformin in inhibiting inflammatory signaling pathways. RESULTS Infarct volume was reduced in metformin-treated mice compared to the control group following tMCAO (P < 0.05). Neurobehavioral outcomes were greatly improved in metformin-treated mice (P < 0.05). MPO+ cells, Gr1+ cells, MPO activity and BBB permeability were decreased after metformin administration (P < 0.05). In addition, metformin activated AMPK phosphorylation, inhibited NF-κB activation, down-regulated cytokine (IL-1β, IL-6, TNF-α) and ICAM-1 expression following tMCAO (P < 0.05). Furthermore, metformin activated AMPK signaling pathway and alleviated oxygen-glucose deprivation-induced ICAM-1 expression in bEND.3 cells (P < 0.05). Compound C, a selective AMPK inhibitor, eliminated this promotional effect. CONCLUSIONS Metformin down-regulated ICAM-1 in an AMPK-dependent manner, which could effectively prevent ischemia-induced brain injury by alleviating neutrophil infiltration, suggesting that metformin is a promising therapeutic agent in stroke therapy.


title: Analysis of outcomes for single-incision laparoscopic surgery (SILS) right colectomy reveals a minimal learning curve.

text: BACKGROUND Single-incision right colectomy has emerged as a safe and feasible alternative to standard laparoscopic resection. As with any new surgical approach, definition of the number of procedures required to optimize the technique is an important goal. Data on this learning curve for single-incision right colectomy are lacking; therefore, we report the outcomes of consecutive single-incision right colectomies to identify the procedural learning curve. METHODS We retrospectively reviewed consecutive single-incision right colectomies performed by a single surgeon from May 2010 to May 2013. Patients were evaluated in groups of ten to minimize individual patient variability and selection bias. Demographics and peri-operative outcomes among groups were evaluated using ANOVA or Kruskal-Wallis. Statistical improvement was assessed between groups using Student T tests or Mann-Whitney U tests. RESULTS Seventy consecutive single-incision right colectomies were performed during the study period. There were no differences in patient demographics over the course of the experiences, suggesting that the selection bias did not influence the outcomes. There was a statistical improvement in operative time after the first 10 cases (103 vs. 130 min, p = 0.01). A second statistical improvement in operative time occurred after 40 cases (97 vs. 114 min, p = 0.03). There was no statistical improvement in estimated blood loss, lymph node harvest, conversion rate, length of stay, or post-operative morbidity throughout the experience. CONCLUSIONS Analysis of our large series of consecutive cases indicates that for a surgeon trained in advanced laparoscopic techniques and given adequate case volume, the outcomes from the procedure are quickly optimized with a minimal learning curve. Operative time is optimized following 40 procedures. Identification of the learning curve is critical for surgeons wishing to implement a single-incision approach and to ensure that the outcomes are optimized prior to thorough comparison with standard laparoscopic or open approaches.


title: Novel in vitro model for assessing susceptibility of synthetic hernia repair meshes to Staphylococcus aureus infection using green fluorescent protein-labeled bacteria and modern imaging techniques.

text: BACKGROUND Mesh infection complicating hernia repair is a major cause of patient morbidity and results in substantial healthcare expenditures. The various constructs of prosthetic mesh may alter the ability of bacteria to attach and form a biofilm. Few data exist evaluating biofilm formation. Using the Maestro in-Vivo Imaging System (CRi, Inc., Woburn, MA) to detect green fluorescent protein (GFP)-expressing Staphylococcus aureus, we studied the ability of synthetic mesh to withstand bacterial biofilm formation in an in vitro model. METHODS We included four meshes: Polypropylene (PP), polypropylene/expanded PTFE (PX), compressed PTFE (cPTFE), and polyester/polyethylene glycol and collagen hydrogel (PE). Five samples of each mesh were exposed to GFP-expressing S. aureus for 18 h at 37°C. Next, green fluorescence was measured using the Maestro Imaging System, with the results expressed in relative fluorescence units (RFU), subtracting the fluorescence of uninfected mesh (control). Each mesh subsequently underwent sonication and quantitative culture of the released bacteria, with the results expressed in colony-forming units (CFU). Analysis of variance was performed to compare the mean values for the different meshes. RESULTS There was a statistically significant difference in bacterial fluorescence for the four meshes: PE (49.9 ± 25.5 [standard deviation] RFU), PX (30.8 ± 9.4 RFU), cPTFE (10.1 ± 4.0 RFU), and PP (5.8 ± 7.5 RFU)(p = 0.001). Bacterial counts also were significantly different: PE (2.2 × 10(8) CFU), PX (8.6 × 10(7) CFU), cPTFE (3.7 × 10(7) CFU), and PP (9.1 × 10(7) CFU)(p < 0.001). CONCLUSION Using novel imaging technology, this study documented significantly different amounts of S. aureus biofilm formation and proliferation on different mesh constructs, with good agreement between imaging and culture results. A multifilament woven mesh (PE) had the highest degree of biofilm formation. These findings are being evaluated in a clinical infection model.


title: Statins for the primary prevention of cardiovascular disease: an overview of systematic reviews.

text: OBJECTIVE To synthesise evidence from exclusively primary prevention data on the effectiveness of statins for prevention of cardiovascular disease (CVD), including stroke, and outcomes stratified by baseline risk and gender. DESIGN Overview of systematic reviews (SRs) using Revised-AMSTAR approach to assess quality. DATA SOURCES Cochrane Database of Systematic Reviews, MEDLINE, Embase, PubMed, Scopus and PROSPERO to June 2017. ELIGIBILITY CRITERIA FOR SELECTING STUDIES SRs of randomised control trials (RCTs) or individual patient data (IPD) from RCTs, examining the effectiveness of statins versus placebo or no treatment on all-cause mortality, coronary heart disease, CVD (including stroke) and composite endpoints, with stratification by baseline risk and gender. DATA EXTRACTION AND SYNTHESIS Two independent reviewers extracted data and assessed methodological quality. A narrative synthesis was conducted. RESULTS Three SRs were included. Quality of included SRs was mixed, and none reported on the risk of bias of included trials.We found trends towards reduced all-cause mortality in all SRs (RR 0.91 [95% CI 0.85 to 0.97]), (RR 0.91 [95% CI 0.83 to 1.01]) and (RR 0.78 [95% CI 0.53 to 1.15]) though it was not statistically significant in two SRs. When stratified by baseline risk, the effect on all-cause mortality was no longer statistically significant except in one medium risk category. One review reported significant reductions (RR 0.85 [95% CI 0.77 to 0.95]) in vascular deaths and non-significant reductions in non-vascular deaths (RR 0.97 [95% CI 0.88 to 1.07]). There were significant reductions in composite outcomes overall, but mixed results were reported in these when stratified by baseline risk. These reviews included studies with participants considered risk equivalent to those with established CVD. CONCLUSIONS There is limited evidence on the effectiveness of statins for primary prevention with mixed findings from studies including participants with widely ranging baseline risks. Decision making for the use of statins should consider individual baseline risk, absolute risk reduction and whether risk reduction justifies potential harms and taking a daily medicine for life. TRIAL REGISTRATION NUMBER CRD42017064761.


The hand-sewn gastrojejunostomy: braided suture or monofilament suture?


title: Morbidity and mortality after closure of loop ileostomy.

text: BACKGROUND A temporary loop ileostomy is commonly used to protect low pelvic anastomoses. Closure is associated with morbidity and mortality. This study investigated patterns of complications after loop ileostomy closure and factors associated with morbidity and mortality. METHOD A review was performed of patients who underwent loop ileostomy closure between 1999 and 2005. RESULTS Three hundred and twenty-five patients underwent closure of loop ileostomy. Reasons for primary surgery were: anterior resection for cancer (n = 160, 49%), ileal pouch-anal anastomosis (n = 114, 35%), diverticular disease (n = 25, 8%), Crohn's colitis (n = 4, 1%) and other conditions (n = 22, 7%). Overall mortality was 2.5% (n = 8) and morbidity was 22.8% (n = 74). Thirty-two patients (10%) developed small bowel obstruction, of whom seven required operative intervention. Overall, the re-operation rate in this series was 28 patients (8.6%). Thirteen (4%) patients had an anastomotic leak of whom 12 patients had re-operation. Preoperative anaemia was significantly associated with leakage (Hb < 11 g/dl; n = 65, P = 0.033). The leakage rate was lower after a stapled anastomosis than a hand-sutured anastomosis (4/203 vs 9/122; P = 0.039). Hypo-albuminaemia (albumin < 34 g/l) was significantly associated with mortality (n = 46, P < 0.001). CONCLUSIONS Loop ileostomy closure is associated with morbidity and mortality. Anaemia and hypo-albuminaemia may be associated with poor outcome.


title: Respiratory performance offered by N95 respirators and surgical masks: human subject evaluation with NaCl aerosol representing bacterial and viral particle size range.

text: OBJECTIVES This study aimed at determining the protection factors (PFs) provided by N95 filtering facepiece respirators and surgical masks against particles representing bacterial and viral size ranges (aerodynamic size: 0.04-1.3 mum). METHODS The protection levels of N95 filtering facepiece respirators (four models) and surgical masks (three models) were investigated while they were donned by 12 subjects performing the OSHA (US Occupational Safety and Health Administration) fit-testing exercises in a test chamber. RESULTS About 29% of N95 respirators and approximately 100% of surgical masks had PFs <10, which is the assigned PF designated for this type of respirator by the OSHA. On average, the PFs of N95 respirators were 8-12 times greater than those of surgical masks. The minimum PFs were observed in the size range of 0.04-0.2 mum. No significant difference in PF results was found between N95 respirators with and without an exhalation valve. CONCLUSIONS The study indicates that N95 filtering facepiece respirators may not achieve the expected protection level against bacteria and viruses. An exhalation valve on the N95 respirator does not affect the respiratory protection; it appears to be an appropriate alternative to reduce the breathing resistance.


Concerns and needs of patients with systemic lupus erythematosus regarding hydroxychloroquine supplies during the COVID-19 pandemic: results from a patient-centred survey.


title: Short self-interacting N-terminal region of rubella virus capsid protein is essential for cooperative actions of capsid and nonstructural p150 proteins.

text: UNLABELLED Nucleocapsid formation is a primary function of the rubella virus capsid protein, which also promotes viral RNA synthesis via an unknown mechanism. The present study demonstrates that in infected cells, the capsid protein is associated with the nonstructural p150 protein via the short self-interacting N-terminal region of the capsid protein. Mutational analyses indicated that hydrophobic amino acids in this N-terminal region are essential for its N-terminal self-interaction, which is critical for the capsid-p150 association. An analysis based on a subgenomic replicon system demonstrated that the self-interacting N-terminal region of the capsid protein plays a key role in promoting viral gene expression. Analyses using a virus-like particle (VLP) system also showed that the self-interacting N-terminal region of the capsid protein is not essential for VLP production but is critical for VLP infectivity. These results demonstrate that the close cooperative actions of the capsid protein and p150 require the short self-interacting N-terminal region of the capsid protein during the life cycle of the rubella virus. IMPORTANCE The capsid protein of rubella virus promotes viral RNA replication via an unknown mechanism. This protein interacts with the nonstructural protein p150, but the importance of this interaction is unclear. In this study, we demonstrate that the short N-terminal region of the capsid protein forms a homo-oligomer that is critical for the capsid-p150 interaction. These interactions are required for the viral-gene-expression-promoting activity of the capsid protein, allowing efficient viral growth. These findings provide information about the mechanisms underlying the regulation of rubella virus RNA replication via the cooperative actions of the capsid protein and p150.


title: Testicular perfusion after standing laparoscopic peritoneal flap hernioplasty in stallions.

text: Acquired inguinal herniation is a very common condition in stallions, usually leading to unilateral or bilateral castration to prevent future recurrence. Recently, several surgical techniques such as the standing laparoscopic peritoneal flap hernioplasty (SLPFH) have been developed to avoid herniation recurrence and also preserve the breeding activity of high economic value stallions. However, studies on SLPFH lack more comprehensive and systematic data about reproductive-related adverse effects and outcomes. The aim of this study was to evaluate whether SLPFH of the internal inguinal rings produces changes in the testicular blood flow in a 1-year follow-up. For that purpose, six healthy stallions were used and testicular blood flow was assessed before, 3, 6, and 12 months (T0, T3, T6, and T12) after the procedure. Blood flow was evaluated ultrasonographically, using the pulsed-wave color Doppler mode. Peak systolic velocity, end-diastolic velocity, the time-averaged maximum velocity, and the derived indexes (resistive index) and pulsatility index) of the testicular artery were measured in two localizations: in the spermatic cord and on the caudal epididymal edge of the testicle. On the spermatic cord, the peak systolic velocity of the testicular artery increased significantly at T12. However, on the epididymal edge location of the artery, the pulsatility and resistive indexes were decreased at T12 (P < 0.05). This pattern of blood flow was related to a hyperemic process. Furthermore, SLPFH might have compressed the spermatic cord, causing a slight occlusion of the testicular artery and triggering a compensatory hyperemia to compensate the deficit of blood flow that supplies the testes. The SLPFH of the internal inguinal ring affected the testicular perfusion in stallions in a 1 year follow-up, although there was no effect on sperm production during this time. The spectral Doppler ultrasound is a useful tool to asses the testicular perfusion after reproductive surgical procedure and provides information which anticipates vascular supply compromise of the stallion testicles.


title: Successful closed suction drain management of a canine elbow hygroma.

text: A 1-year-old castrated male St. Bernard dog presented to Angell Animal Medical Center with bilateral elbow hygromas which had been present for several weeks. The largest hygroma involving the left elbow was managed with a closed suction (active) drain system to continuously collapse the hygroma pocket over a 3-week period. Soft bedding was used to protect the elbows from further impact trauma to the olecranon areas. Following drain removal, there was no evidence of hygroma recurrence based on periodic examinations over an 18-month period. The smaller non-operated right elbow hygroma had slightly enlarged during this period. Closed suction drain management of the hygroma proved to be a simple and economical method of collapsing the left elbow hygroma. This closed drainage system eliminated the need for the postoperative bandage care required with the use of the Penrose (passive) drain method of managing elbow hygromas. The external drain tube should be adequately secured in order to minimise the risk of its inadvertent displacement.


title: Quantitative proteomics identifies host factors modulated during acute hepatitis E virus infection in the swine model.

text: UNLABELLED Hepatitis E virus (HEV) causes acute enterically transmitted hepatitis. In industrialized countries, it is a zoonotic disease, with swine being the major reservoir of human HEV contamination. The occurrence and severity of the disease are variable, with clinical symptoms ranging from asymptomatic to self-limiting acute hepatitis, chronic infection, or fulminant hepatitis. In the absence of a robust cell culture system or small-animal models, the HEV life cycle and pathological process remain unclear. To characterize HEV pathogenesis and virulence mechanisms, a quantitative proteomic analysis was carried out to identify cellular factors and pathways modulated during acute infection of swine. Three groups of pigs were inoculated with three different strains of swine HEV to evaluate the possible role of viral determinants in pathogenesis. Liver samples were analyzed by a differential proteomic approach, two-dimensional difference in gel electrophoresis, and 61 modulated proteins were identified by mass spectroscopy. The results obtained show that the three HEV strains replicate similarly in swine and that they modulate several cellular pathways, suggesting that HEV impairs several cellular processes, which can account for the various types of disease expression. Several proteins, such as heterogeneous nuclear ribonucleoprotein K, apolipoprotein E, and prohibitin, known to be involved in other viral life cycles, were upregulated in HEV-infected livers. Some differences were observed between the three strains, suggesting that HEV's genetic variability may induce variations in pathogenesis. This comparative analysis of the liver proteome modulated during infection with three different strains of HEV genotype 3 provides an important basis for further investigations on the factors involved in HEV replication and the mechanism of HEV pathogenesis. IMPORTANCE Hepatitis E virus (HEV) is responsible for acute hepatitis, with clinical symptoms ranging from asymptomatic to self-limiting acute hepatitis, chronic infection, or fulminant hepatitis. In industrialized countries, HEV is considered an emerging zoonotic disease, with swine being the principal reservoir for human contamination. The viral and cellular factors involved in the replication and/or pathogenesis of HEV are still not fully known. Here we report that several cellular pathways involved in cholesterol and lipid metabolism or cell survival were modulated during HEV infection in the swine model. Moreover, we observed a difference between the different swine strains, suggesting that HEV's genetic variability could play a role in pathogenesis. We also identified some proteins known to be involved in other viral cycles. Our study provides insight into the mechanisms modulated during HEV infection and constitutes a useful reference for future work on HEV pathogenesis and virulence.


title: Modified esophagogastrostomy in laparoscopy-assisted proximal gastrectomy: A reverse-Tornado anastomosis.

text: INTRODUCTION The aim of this study was to introduce and examine a modified mechanical end-to-side esophagogastrostomy method ("reverse-Tornado" anastomosis) in laparoscopy-assisted proximal gastrectomy. METHODS Five patients with gastric cancer who underwent laparoscopy-assisted proximal gastrectomy were analyzed retrospectively. Esophagogastrostomy in the anterior wall was performed in three patients, and esophagogastrostomy in the posterior wall was performed in two patients. Clinicopathological features, operative outcomes (operative time, operative blood loss), and postoperative outcomes (complications, postoperative hospital stay, reflux esophagitis) were evaluated. RESULTS Operative time was normal (278 min). There was no marked operative blood loss, postoperative complications, prolonged hospital stay, or reflux esophagitis. CONCLUSION Esophagogastrostomy was completed in a normal time with reverse-Tornado anastomosis. This method can be safe and can enable good postoperative quality of life.


title: Ophthalmology and SARS-CoV-2: Blind toward those who fight blindness?

text: SARS-CoV-2 infection recently reached pandemic proportions, with high risk of death for the worldwide population. In this dramatic scenario, all the resources are addressed to the intensive care units for the assessment of the emergency. However, more attention should be paid with respect to the risk of viral diffusion among asymptomatic people. Italy is the second most involved country in the world, and we needed to gain a lot of experience in a very limited time. At least 1 m of distance among people is recommended; however, some clinical practices cannot allow this distance. In this context, we believe that the careful safety assessment of clinical settings, like ophthalmologic ones, may have a remarkable impact on the fight against SARS-CoV-2 spread.


title: Partially Uncleaved Alphavirus Replicase Forms Spherule Structures in the Presence and Absence of RNA Template.

text: Alphaviruses are positive-strand RNA viruses expressing their replicase as a polyprotein, P1234, which is cleaved to four final products, nonstructural proteins nsP1 to nsP4. The replicase proteins together with viral RNA and host factors form membrane invaginations termed spherules, which act as the replication complexes producing progeny RNAs. We have previously shown that the wild-type alphavirus replicase requires a functional RNA template and active polymerase to generate spherule structures. However, we now find that specific partially processed forms of the replicase proteins alone can give rise to membrane invaginations in the absence of RNA or replication. The minimal requirement for spherule formation was the expression of properly cleaved nsP4, together with either uncleaved P123 or with the combination of nsP1 and uncleaved P23. These inactive spherules were morphologically less regular than replication-induced spherules. In the presence of template, nsP1 plus uncleaved P23 plus nsP4 could efficiently assemble active replication spherules producing both negative-sense and positive-sense RNA strands. P23 alone did not have membrane affinity, but could be recruited to membrane sites in the presence of nsP1 and nsP4. These results define the set of viral components required for alphavirus replication complex assembly and suggest the possibility that it could be reconstituted from separately expressed nonstructural proteins.IMPORTANCE All positive-strand RNA viruses extensively modify host cell membranes to serve as efficient platforms for viral RNA replication. Alphaviruses and several other groups induce protective membrane invaginations (spherules) as their genome factories. Most positive-strand viruses produce their replicase as a polyprotein precursor, which is further processed through precise and regulated cleavages. We show here that specific cleavage intermediates of the alphavirus replicase can give rise to spherule structures in the absence of viral RNA. In the presence of template RNA, the same intermediates yield active replication complexes. Thus, partially cleaved replicase proteins play key roles that connect replication complex assembly, membrane deformation, and the different stages of RNA synthesis.


title: Transcatheter or Surgical Aortic Valve Replacement in Patients With Prior Coronary Artery Bypass Grafting.

text: BACKGROUND Transcatheter aortic valve replacement (TAVR) and surgical aortic valve replacement (SAVR) are treatment options for aortic stenosis in patients with prior coronary artery bypass graft surgery. We assessed the major clinical outcomes of such patients enrolled in the CoreValve High Risk (CHR) study. METHODS Of the 795 CHR study patients, 226 had prior coronary artery bypass graft surgery; 115 underwent TAVR and 111 underwent SAVR. The primary endpoint was a comparison of all-cause mortality at 1 year. Important secondary clinical endpoints were assessed. RESULTS At 1 year, all-cause mortality was 9.6% for TAVR versus 18.1% for SAVR (p = 0.06); cardiovascular mortality was 7.0% for TAVR versus 13.8% for SAVR (p = 0.09). A combination of The Society of Thoracic Surgeons risk score greater than 7 and age greater than 80 years was a significant predictor of mortality, with TAVR demonstrating a survival advantage (p = 0.03). No differences were seen for stroke. The SAVR group had longer intensive care unit and hospital stays, increased incidence of acute kidney injury, life-threatening or disabling bleeding, and major adverse cardiac and cerebrovascular events (p < 0.05). Pacemaker implantation and paravalvular regurgitation were greater with TAVR at all timepoints. CONCLUSIONS For patients with prior coronary artery bypass graft surgery and aortic stenosis, TAVR offers a significant morbidity advantage and a strong trend toward improved survival over SAVR at 1 year.


title: Tele-Neuro-Ophthalmology: Vision for 20/20 and Beyond.

text: BACKGROUND Telehealth provides health care to a patient from a provider at a distant location. Prior to the COVID-19 pandemic adoption of telehealth modalities was increasing slowly but steadily. During the public health emergency rapid widespread telehealth implementation has been encouraged to promote patient and provider safety and preserve access to health care. EVIDENCE ACQUISITION Evidence was acquired from English language Internet-searches of medical and business literature and following breaking news on the COVID-19 pandemic and responses from health care stakeholders including policy makers, payers, physicians and health care organizations, and patients. We also had extensive discussions with colleagues who are developing telehealth techniques relevant to neuro-ophthalmology. RESULTS Regulatory, legal, reimbursement and cultural barriers impeded the widespread adoption of telehealth prior to the COVID-19 pandemic. With the increased use of telehealth in response to the public health emergency, we are rapidly accumulating experience and an evidence base identifying opportunities and challenges related to the widespread adoption of tele-neuro-ophthalmology. One of the major challenges is the current inability to adequately perform funduscopy remotely. CONCLUSIONS Telehealth is an increasingly recognized means of healthcare delivery. Tele-neuro-ophthalmology adoption is necessary for the sake of our patients, the survival of our subspecialty, and the education of our trainees and students. Telehealth does not supplant but supplements and complements in-person neuro-ophthalmologic care. Innovations in digital optical fundus photography, mobile vision testing applications, artificial intelligence and principles of channel management will facilitate further adoption of tele-neuro-ophthalmology and bring the specialty to the leading edge of healthcare delivery.