*2.2.1. History*

The first case of VL in Tunisia was reported by Laveran and Cathoire in 1904 [64] in the region of La Goulette, north of the country. Between 1904 and 1908, Charles Nicolle reported two new VL cases of children living in Tunis (north of the country). Since this date and till 1935, Charles Nicolle and collaborators reported 120 new VL cases mainly distributed in the north (Tunis, Bizerte, Zaghouan, Grombalia, Beja, and El Kef), the centre (Sousse and Kairouan) with one case in Tozeur (south of Tunisia) [65]. Some outbreaks of VL were reported in centre Tunisia mainly Kairouan where 247 cases were reported between 1984 and 1996 [66].

Since the description of VL in Tunisia, the annual incidence has increased progressively going from three cases in beginning of the twentieth century to 57 in the 1980s of the same century [66]. Currently, VL in Tunisia shows a stable incidence of about 100 cases per year [67, 68].


Histoplasmosis - A Comprehensive Study of Epidemiology, Pathogenesis, Diagnosis, and Treatment

*Edited by Elena Dantes and Elena Dumea*

Published in London, United Kingdom

Histoplasmosis - A Comprehensive Study of Epidemiology, Pathogenesis, Diagnosis, and Treatment http://dx.doi.org/10.5772/intechopen.104142 Edited by Elena Dantes and Elena Dumea

#### Contributors

Filipa Sousa, Domingos Ferreira, Salette Reis, Paulo Costa, Israel Kiiza Njovu, Pauline Petra Nalumaga, Kennedy Kasaaza, Edwin Nuwagira, Joel Bazira, Lucas Ampaire, Herbert Itabangi, Monica Marc, Diana Manolescu, Estera Boeriu, Ana Adriana Trusculescu, Milena Adina Man, Doina Adina Todea, Nicoleta Ștefania Motoc, Ruxandra-Mioara Rajnoveanu, Nela Daniela Efrim, Elena Dumea, Roxana Carmen Cernat, Elena Dantes, Roxana-Carmen Cernat

#### © The Editor(s) and the Author(s) 2023

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**5.2.1 Participants**

The study population comprised 474 families and their children attending preschools in the city of Braunschweig (Germany), a moderately sized city with 250,000 inhabitants. Families were recruited for universal and selective prevention efficacy studies of child behaviour problems. Study details for recruitment were described by Hahlweg et al. (2010) and Heinrichs (2006). Data reported here were collected at the first (pre) assessment point. The age of the parents ranged between 23 and 47 years (mothers: *M* = 34.5, *SD* = 5.3; fathers: *M* = 36.4, *SD* = 6.1). The families had between one and four children (*M* = 2.0, *SD* = 0.9). The average age of the target children was 4.5 years (*SD* = 1.0), and 53% (*n* = 253) were boys. Seventy-eight percent (*n* = 219) of the couples were married, and 27 % (*n* = 127) were single parents. 200 fathers (91 % participation rate) completed the questionnaire assessment at pre-test. Forty-two percent of mothers (51 % of fathers) had a higher-track school school leaving qualification (= 13 years of schooling), and 37 % (22 %) had completed medium-track school (= 10 years of schooling). The net family income was equivalent to the German average; 35 % of the families were receiving social security benefits, and 7 % of mothers (5 % of fathers) were immigrants.

### **5.2.2 Measures**

To assess psychopathology in children the German translation of the ASEBA Preschool Forms & Profiles (Achenbach & Rescorla, 2000) was used. The CBCL/1½-5 and the C-TRF are similarly constructed to cover an empirical range of behavioural, emotional and social function problems. Both forms comprise 99 items, and the respondent is requested to rate each item, based on the preceding two months, as 0 for *not true*, 1 for *somewhat or sometimes true* or 2 for *very true or often true*. The CBCL/1½-5 was completed by the mothers and fathers, whereas the kindergarten teachers completed the C-TRF.

The CBCL/1½-5 consists of three problem scales (Internalizing, Externalizing, and Total Problems) and seven syndrome subscales (Emotionally Reactive, Anxious/Depressed, Somatic Complaints, Withdrawn, Sleep Problems, Attention Problems, and Aggressive Behavior). The C-TRF consists also of three problem scales (Internalizing, Externalizing, and Total Problems) and six syndrome subscales (Emotionally Reactive, Anxious/Depressed, Somatic Complaints, Withdrawn, Attention Problems, and Aggressive Behavior). Studies on the German versions of the ASEBA Preschool Forms have supported the psychometric properties, showing good reliability and validity in both clinical and non-clinical populations (e.g. Plück et al., under review). Since there are no German norms available for the ASEBA Preschool Forms & Profiles, we used the norms provided by Achenbach and Rescorla (2000).

#### **5.2.3 Statistical analysis**

Prevalence rates of problem scales and syndrome subscales were calculated for mothers, fathers and caregivers based on the norms provided by Achenbach and Rescorla (2000). Prevalence rates were calculated as a proportion of children with *subclinical* behaviour (T = 60 - 63 for problem scales, T = 65 - 69 for syndrome subscales) and *clinically relevant* behaviour (T ≥ 64 for problem scales, T ≥ 70 for syndrome subscales). Associations between problem scale prevalence and demographic and socio-economic factors (e.g. child´s age and gender, single parenthood, parents' education, family income, migration status) were carried out with Chi square statistics, and the significance level was set at *p* < .01. To determine whether children who had deviant problem scores (T ≥ 60) were at higher risk of having a demographic (economic) factor, odds ratios (OR) and 95 % confidence intervals were calculated.


**1. Introduction**

Foodborne pathogens are an emerging global public health problem [1]. Even with increased awareness in food safety and quality control, there are still about 48 million cases of foodborne diseases in the United States every year [2,3]. *Salmonella*, *Escherichia coli O157:H7*, *Staphylococcus aureus*, *Listeria monocytogenes*, and *Bacillus cereus* are the most common foodborne pathogens [4,5]. Of these, *Listeria monocytogenes* (*L. monocytogenes*) is more likely to cause death and is associated with listeriosis. Aside from its high fatality rate (20–30%), listeriosis can cause many diseases such as sepsis and meningitis. It readily infects immunocompromised people and in particular neonates, pregnant women, and people over age 65 [6,7]. Meats, fruits, vegetables, seafood, milk, and dairy products are common foods associated with *Listeria monocytogenes* [8,9].

Culture and colony counting are most often used for bacterial identification, but these are time-consuming and laborious processes and require several steps (sample pre-enrichment, selective enrichment, and confirmation) [10,11]. To shorten the analysis time, various rapid detection methods have been presented, including enzyme-linked immunosorbent assay (ELISA) [12], polymerase chain reaction (PCR) [13], and surface plasmon resonance (SPR) [14]. These strategies offer good specificity and sensitivity but require expensive instruments, multiple steps, and well-trained technicians. For example, the high cost of antibodies and the multiple steps involved in manual applications limit immunoassays methods [15]. In some PCR-based assays, DNA extraction and false-positive results can lead to cross-contamination of samples. This is a major drawback of PCR [11]. Hence, a fast, real-time, and effective detection method is urgently needed for *L. monocytogenes* in food.

Molecular imprinting technology (MIT) is an attractive strategy for designing a matrix using customized materials with high selectivity for template molecules or which are related to analogous compounds. Through continuing development of this technology, molecularly imprinted polymers (MIPs) have wide potential application in the fields of biosensors [16], separation [17], drug delivery [18], and catalysis [19]. To date, the synthesis of MIPs of small organic molecules has been straightforward, but MIT for larger templates such as biomacromolecules (e.g., proteins) and bacteria remains highly challenging [20].

Pan et al. prepared MIPs via an inverse-phase suspension and bulk polymerization to detect *Staphylococcus aureus* using *S. aureus* protein A (SpA) as a template protein. However, because of the fragility and complexity of bacteria, it is difficult to generate cavities of a specific size and shape during the imprinting reaction. To address this problem, Shen et al. presented a novel Pickering emulsion polymerization strategy for the preparation of a series of small molecules and protein imprinted polymers [21,22] in which the dispersed liquid droplets are stabilized by solid particles instead of surfactants. Recently, they further proposed the synthesis of bacteria recognition polymers to detect *Escherichia coli* and *Micrococcus luteus* by exploiting the capability of bacteria to self-assemble at an oil–water interface [23].

The Pickering emulsion is a solid particle-stabilized emulsion which is either oil-in-water (O/W) or water-in-oil (W/O) [24]. Versus traditional emulsion polymerization, dispersed liquid droplets are stabilized by solid particles instead of conventional surfactants [25]. Because of the lower toxicity, well controlled size, and high mechanical strength, Pickering emulsion polymerization has been widely applied to synthesize MIPs for the specific recognition of small molecules, such as bifenthrin, malachite green, and bisphenols [26–28]. However, the application of Pickering emulsion polymerization for bacteria-based MIPs is still relatively unexplored.

Quantum dots (QDs) are semiconductor nanocrystals with broad absorption spectra, narrow and tunable emission, and high photoluminescence [29]. Combining the unique optical ability of QDs and specific recognition of MIPs, the common applications of imprinted polymers in optical sensors have been reported for the detection of different molecules. For example, Wang et al. developed molecularly imprinted silica layers coated with QDs for diethylstilbestrol [30]. Feng et al. obtained molecularly imprinted sensor-coated QDs to determine tetrabromobisphenol-A (TBBPA) by sol-gel method [31]. Huang et al. have described a novel fluorescent sensing platform by employing inorganic perovskite quantum dots as a fluorescence signal for the detection of omethoate [32]. However, there have been no fluorescence-imprinted sensor studies used to detect *Listeria monocytogenes* in food samples.

The objective of this study was, therefore, to fabricate stable, rapid, low-cost, and convenient fluorescence-imprinted polymers for the visual qualitative identification of *L. monocytogenes* via a fluorescence microscope. The fluorescence MIPs were prepared by Pickering emulsion polymerization, in which whole *L. monocytogenes* were directly used as the template, and the bacteria-chitosan-QDs network stabilized the particles. In addition, a novel MIP-based sensor based on the response of fluorescence intensity was developed for the qualitative detection of *L. monocytogenes*.

#### **2. Materials and Methods**


**4. Conclusion**

In order to retrofit settlements and cities in which we live and make them more livable and sustainable, it is necessary that our point of view and approaches related to urban spatial arrangements should be retrofitted and be gained ecological dimension. Ecology should be the key issue in the spatial planning and design process at every scale.

This chapter proposed a theoretical framework on retrofitting process based on urban ecology for making cities, settlements, and the whole environment livable and sustainable. From planning to design and to production technologies of the building and landscaping materi‐ als, adoption of throughout process based on ecology and ecological principles is essential so that habitats for the next generation to live in the earth have not been destructed.

**Figure 5.** Ecology-based retro-fitting cycle in the framework.

With the guiding of the hierarchic succession on both creating and retro-fitting process urban environment shown in **Figure 3**, decisions, strategies, actions and studies conducted in every phase should consider the other phases' and should be integrated to each other. Thus, the framework emphasized in this chapter is an ecology-based cycle which contains integrated tools for ecological retro-fitting of urban environment (**Figure 5**).

Following this theoretical framework, it may not be remove ecological footprint of the human on the earth, but it would be reduced considering ecology from planning for human and making decisions for land uses in the urban areas to production processes of building and industrial materials. Thus, ecological and biological destruction on natural resources due to rapid urbanization would be stopped. With the sustainability of natural resources and ecologically balanced conservation-utilization strategies, livable and sustainable urban environment and cities can be realized.

consequences of productions and services have also become a significant theme for enter‐ prise management. Resent approach on enterprises' environmental precautions aims envi‐ ronmental performance of production process, especially, through eco-innovation [39]. In order to minimize environmental effects of a production and to realize its life cycle, design, and post-design processes should be organized in accordance with ecological principles.

In order to retrofit settlements and cities in which we live and make them more livable and sustainable, it is necessary that our point of view and approaches related to urban spatial arrangements should be retrofitted and be gained ecological dimension. Ecology should be

This chapter proposed a theoretical framework on retrofitting process based on urban ecology for making cities, settlements, and the whole environment livable and sustainable. From planning to design and to production technologies of the building and landscaping materi‐ als, adoption of throughout process based on ecology and ecological principles is essential so

With the guiding of the hierarchic succession on both creating and retro-fitting process urban environment shown in **Figure 3**, decisions, strategies, actions and studies conducted in every phase should consider the other phases' and should be integrated to each other. Thus, the framework emphasized in this chapter is an ecology-based cycle which contains integrated

Following this theoretical framework, it may not be remove ecological footprint of the human on the earth, but it would be reduced considering ecology from planning for human and making decisions for land uses in the urban areas to production processes of building and industrial materials. Thus, ecological and biological destruction on natural resources due to

that habitats for the next generation to live in the earth have not been destructed.

the key issue in the spatial planning and design process at every scale.

**Figure 5.** Ecology-based retro-fitting cycle in the framework.

tools for ecological retro-fitting of urban environment (**Figure 5**).

**4. Conclusion**

262 Sustainable Urbanization

As a summary ofthe retro-fitting framework based on ecology, the following checklist of which some items suggested by author [5], can be used for a guide to sustainability of natural and ecological resources for sustainable cities:

From spatial planning and design point of view, eco-cities, eco-tech cities, smart cities, which are final phase of hierarchic succession of integrated retro-fitting tools, are ecology based settlements in which natural resources are not exhausted, technology is used for ecology (both human ecology and urban ecology), and there is a sustainable balance between econo‐ my and ecology.

Eco-tech has great influence on the construction of environment. The utilization of eco-tech is the necessary means of architecture to the aim of sustainable development [40]. Ecological and

technological design of new comfortable, healthy, environment-friendly, minimum carbon consuming, self-efficient settlements contribute to urban sustainability [41]. From design point of view, eco-technology can be identified as the design of human society with its natural environment for the benefit of both. Eco-tech planning/design for eco-cities considers energy, environment and ecology for human wellbeing.

The principles of eco-tech city can be explained as the following: "Eco-tech city, when planned in collaboration with local investor, local management and technical team, can decrease ecological footprint of that city by using high performance ecological building and city technologies" [42].

Among the various types of "eco-city" initiatives currently underway across different parts of the world, this tension is arguably particularly pronounced in the case of entirely new, largescale cities. According to a recent global survey, of the 80 or so recent eco-city initiatives-which include the retro-fitting of existing cities and urban expansion through variously sized "ecodistricts" and "eco-towns"—there are a dozen or so brand new cities in the process of being realized [43].


# **Life in the Time of a Pandemic Social, Economic, Health and Environmental Impacts of COVID-19—Systems Approach Study**

Edited by Oz Sahin and Russell Richards Printed Edition of the Special Issue Published in *Systems*

www.mdpi.com/journal/systems


**2.3. Drought**

**Genotypes Tolerance to iron chlorosis**

Calamondin 108 USDA 1 Tuzcu Cleopatra mandarin 2 Volkameriana CRC 01 3 Volkameriana CRC 02 3 Macrophylla 4 Rangpur lime 3 Volkameriana 3 *Citrus ichangensis* CRC 3 *Citrus sulcata* 2 *Severinia buxifolia* SRA 2 Alanya Dilimli sweet orange 5 Gou Tou sour orange SRA 506 5 Smooth Seville sour orange 3 Taiwanica 2 Tuzcu 31-31 sour orange 5 Tuzcu 891 sour orange 4

538 Abiotic and Biotic Stress in Plants - Recent Advances and Future Perspectives

\*1: very sensitive, 2: sensitive, 3: acceptable, 4: tolerant, 5: very tolerant

crossing [44].

moderately tolerant.

**Table 2.** Classification of the rootstocks in collection of Çukurova University in terms of tolerance of iron deficiency.

Although trifoliate orange has many advantages in terms of tolerance to abiotic and biotic stresses, it is susceptible to calcareous soil conditions. However, there are some superior genotypes to improve the tolerance to high pH of present rootstocks by hybridization and

Several rootstock breeding programs have been carried out by different countries leading in citriculture. Forner et al. [62] reported two new citrus rootstocks named F-A 5 and F-A 13, released in Spain. These rootstocks are hybrids of Cleopatra mandarin × Rubidoux trifoliate crosses with a high level of tolerance to lime-induced iron chlorosis. Besides, Bowman and Rouse [63] mentioned a new citrus rootstock named as US-812 which is a hybrid obtained by a cross between Sunki mandarin (*Citrus reticulata*) and Benecke trifoliate orange in USDA Indio Research Station, California. They have reported that using Valencia trees budded on to US-812 resulted in some tolerance to high alkalinity under pH conditions 8.1– 8.3. Moreover, Federici et al. [64] indicated that three citrus rootstocks released in August 2009 by the University of California named as "Bitters," "Carpenter," and "Furr" trifoliate hybrids, tested as C22, C54, and C57, respectively, by crossing Sunki mandarin × Swingle trifoliate orange. Bitters were found to be very tolerant to calcareous soil, whereas Carpenter and Furr were found to be

Mediterranean region has a subtropical climate and is an important region for citriculture. A significant amount of high-quality citrus fruits is produced in Mediterranean countries such as Spain, Turkey, Italy, Greece, Egypt, Morocco, and Tunisia. Fruit yield and quality are affected by genetic traits together with environmental factors. Fruit crops are frequently exposed to environmental stresses spontaneously or by conventional agronomic conditions. Some of these conditions such as high temperature may last only for a short period of time, whereas lack of water in soil may last for longer periods. Global warming is a type of green‐ house effect which is defined as the increase of Earth's average surface temperature due to the effect of greenhouse gases, such as carbon dioxide emissions from burning fossil fuels or from deforestation, which trap heat that would otherwise escape from Earth.

Yaacoubi et al. [65] indicated that Mediterranean fruit tree production is facing major changes that have environmental and socioeconomic consequences. Climatic changes related to temperature warming have been reported worldwide.

Drought stress, as one of the most ominous abiotic factors limiting the productivity of horticultural crops, is increasingly growing in dimension of severity in many regions of the world [66]. In general, the mechanism of drought resistance in plants can be explained as drought escape, drought avoidance, and drought tolerance. These traits consist of osmotic adjustments, cell membrane stability, epicuticular wax, partitioning and stem reserve mobili‐ zation, manipulation and stability of flowering processes, and seedling drought traits.

Drought tolerance is a complex trait that is important at different growth stages and involves multiple adaptations. Fundamental to this is the ability to maximize the extraction of water from the soil while minimizing loss from the leaves. Morphological adaptations include the development of deep roots and alterations in leaf morphology and cuticle structure, while physiological adaptations involve changes in stomatal density to maximize water uptake and retention [67, 68, 69].

Drought stress effects on the plant may range from slight suppression of growth and yield to temporary wilting, in which leaves flag but recover after transpiration demands decrease, to permanent wilting in which the plant suffers injury and death [70]. A plant responds to a lack of water by halting growth and reducing photosynthesis and other plant processes in order to reduce water use. As water loss progresses, leaves of some species may appear to change color, usually to blue-green. Foliage begins to wilt and, if the plant is not irrigated, leaves will fall off and the plant will eventually die. Drought lowers the water potential of a plant's root and upon extended exposure, abscisic acid is accumulated, and as a result stomatal closure occurs. This reduces a plant's leaf relative water content. The time required for drought stress to occur depends on the water-holding capacity of the soil, environmental conditions, stage of plant growth, and plant species [71]. Plants growing in sandy soils with low water-holding capacity are more susceptible to drought stress than plants growing in clay soils. A limited root system will accelerate the rate at which drought stress develops. A plant with a large mass of leaves in relation to the root system is prone to drought stress because the leaves may lose water faster than the roots can supply it. The root system has a great importance when the plant faces drought. For instance, Rough lemon rootstocks are very drought tolerant because of their extensive, deep root systems. Newly installed plants and poorly established plants may be especially susceptible to drought stress because of the limited root system or the large mass of stems and leaves in comparison to roots.

Citrus, a perennial crop with a long orchard life, is likewise a globally important fruit crop responsible for world trade and often exposed to the vagaries of soil and atmospheric drought stress [72]. Drought stress is known to restrict the vegetative growth and yield of citrus, in addition to adversely affecting fruit quality and incurring huge economic loss to the citrus growers [73]. Therefore, screening and selection of germplasm are of great importance in terms of drought tolerance.

Pedrosoa et al. [74] reported that citrus rootstocks have differential capacities for supplying shoot tissues with water and carbon, improving the resistance to biotic and abiotic stresses and affecting plant water status and photosynthesis. Water relations have been well studied in citrus trees, showing that rootstocks alter the physiological performance under water deficit through variations in plant hydraulic conductance, leaf water potential, and stomatal conduc‐ tance [75, 76, 77]. In addition, several studies have found that citrus rootstocks showed different performances when they are exposed to drought [13, 73].

Treeby et al. [78] investigated irrigation management and rootstock effects on navel orange and reported that irrigation management is far more critical for external fruit quality for trees on sweet orange and, to a lesser extent, trees on the citranges compared to trees on trifoliate orange and Cleopatra mandarin.

Some studies also indicate that using tetraploid rootstocks increases the drought tolerance in comparison to their diploid clones in citrus. Allario et al. [79] reported that polyploidy is common in many plant species and often leads to better adaptation to adverse environmental conditions. The authors examined the drought tolerance in diploid (2x) and autotetraploid (4x) clones of Rangpur lime (*Citrus limonia*) rootstocks grafted with 2x Valencia Delta sweet orange (*Citrus sinensis*) scions, named V/2xRL and V/4xRL, respectively. The results of the authors showed that using tetraploid clones of Rangpur lime had increased the drought tolerance in grafted sweet orange.


*Article* **A Cyclical Phenomenon among Stock & Commodity Markets**

**Hector O. Zapata \*, Junior E. Betanco, Maria Bampasidou and Michael Deliberto**

Department of Agricultural Economics & Agribusiness, Louisiana State University, LSU Agricultural Center, Baton Rouge, LA 70803, USA<EMAIL_ADDRESS>(J.E.B<EMAIL_ADDRESS>(M.B<EMAIL_ADDRESS>(M.D.)

**\*** Correspondence<EMAIL_ADDRESS>
**Abstract:** Considerable studies have examined the relationship between commodity markets and stock markets. This paper studies the cyclical relationship between commodity markets and stock markets with implications for investing based on index relationships. Stock markets are represented by the U.S. S&P 500 index and aggregate commodity markets by the U.S. producer price index (PPI). Tradeable market indexes readily available to investors, namely the S&P GSCI Index and the Bloomberg Commodity Index (BCOM), are also studied. An optimal bandpass filter is used to estimate the cyclical component using a pricing-performance measure of the S&P 500 relative to the PPI, based on annual data from 1871 to 2022. The S&P GSCI and the BCOM indexes are also used to test the robustness of the findings. The impacts of the financial crisis of 2008 and the coronavirus pandemic are also assessed. The overriding conclusion of the study is that a cyclical relationship exists between stock markets and commodity markets for both aggregate and tradeable indexes which can last, from peak to peak, approximately 31 years. Measuring returns and risks in a manner consistent with these cycles can shed new light on the usefulness of commodity investing via tradeable indexes in seeking efficient portfolios.

**Keywords:** commodity; stock; markets; cycles; investing; risk; returns

**Citation:** Zapata, Hector O., Junior E. Betanco, Maria Bampasidou, and Michael Deliberto. 2023. A Cyclical Phenomenon among Stock & Commodity Markets. *Journal of Risk and Financial Management* 16: 320. https://doi.org/10.3390/ jrfm16070320

Academic Editor: Kentaro Iwatsubo

Received: 31 May 2023 Revised: 30 June 2023 Accepted: 1 July 2023 Published: 4 July 2023

**Copyright:** © 2023 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https:// creativecommons.org/licenses/by/ 4.0/).


**4.1 Pharmacological approach**

The selection of appropriate treatments should be based on the results of a wound culture once an infection is suspected. For accurate results during wound culture, it is ideal to harness tissue from the base of the ulcer after debridement rather than taken from a superficial wound [131, 132]. If deep tissue infections are suspected, specimens obtained aseptically during surgery provide optimal results. Chronic or previously treated wounds most often show polymicrobial growth, including Gram-positive cocci, Gram-negative rods or anaerobes and fungi in some cases [133]. Antibiotic-resistant organisms such as vancomycin-resistant *S. aureus* and methicillin-resistant *S. aureus* are frequently found in patients previously treated with antibiotic therapy or patients with a recent history of hospitalization or residence in a long-term care facility [134, 135]. The selection of appropriate antimicrobial therapy, including the agent, route of administration, and need for inpatient or outpatient treatment will be determined in part by the severity of the infection. In-patient admissions should be offered to individuals with systemic signs of severe infection with the provision of supportive care and intravenous antibiotic therapy based on result obtained from wound culture [136, 137]. Common classes of pharmacological agents used include lincosamides, fluoroquinolones, β-lactams/βlactamase inhibitors [138, 139], and exogenous sources of agents such as nitric oxide that stimulate angiogenesis and vasodilation.