**Fotini Botsou 1,\*, Aristomenis P. Karageorgis 2, Vasiliki Paraskevopoulou 1, Manos Dassenakis 1 and Michael Scoullos 1**

Received: 6 August 2019; Accepted: 2 September 2019; Published: 4 September 2019

**Abstract:** The Antinioti Lagoon is a karstified, rather pristine, and shallow coastal lagoon located in the northern part of Corfu Island in NW Greece. The present study examines the levels of metals (Al, Fe, Mn, Cd, Cu, Pb, and Zn) in the dissolved and particulate phase, as well as in surface and core sediments, and identifies the critical processes that define their behavior. The major transport pathway of dissolved Mn, Cd, and Pb, and particulate Mn, Cd, and Zn into the lagoon is through freshwater springs, whereas surface runo ff dominates the transport of particulate Al, Fe, and Cu. Interestingly, large particles (>8 μm) contain higher amounts of Al, Fe and Mn than the finer ones (<8 μm), due to flocculation of oxyhydroxides that, eventually, scavenge other metals, as well. Cadmium and Zn bound to the large particles were found to be less prone to desorption than the smaller ones and were effectively captured within the lagoon. In the sediments, diagenetic processes are responsible for post-depositional changes in the forms of metals (particularly Fe, Mn and Cd). Enrichment factors (EFs) based on local background showed that sediments are enriched in restricted areas in Cd and Pb by maximum factors 4.8 and 10, respectively. These metals were predominantly found in potentially labile forms. Thus, any interventions introducing changes in the physico-chemical conditions may result in the release of metals, with negative implications on the lagoon's ecological quality.

**Keywords:** coastal lagoon; dissolved and particulate metals; sediments; labile forms; enrichment factor; early diagenetic process; groundwater discharges


*3.1. Research Setting*

Participants were enrolled individually at the Harris Center for Precision Wellness (HC) and Institute for Next Generation Healthcare research offices within the Icahn School of Medicine at Mount Sinai. Monetary compensation in the form of a \$100 gift card was provided to study participants upon device return. During the enrollment visit, participants met with an authorized study team member in a private office to complete the consent process, onboarding, and baseline procedures. The remainder of the study activities took place remotely with limited participant-team interaction. The study team maintained remote contact with each research participant throughout his/her participation via phone or email to answer any questions and provide technical support. The study was approved by the Mount Sinai Program for the Protection of Human Subjects (IRB #15-01012).


**Contents**

#### **Peter. C. Taylor, Alejandro Balsa Criado, Anne-Barbara Mongey, Jerome Avouac, Hubert Marotte and Rudiger B. Mueller**

How to Get the Most from Methotrexate (MTX) Treatment for Your Rheumatoid Arthritis Patient?—MTX in the Treat-to-Target Strategy

Reprinted from: *J. Clin. Med.* **2019**, *8*, 515, doi:10.3390/jcm8040515 .................. **219**

## **About the Editor**

#### **R ¨udiger M ¨uller**

## **1. Personal Data:**

Date and Place of Birth: 21 February 1971, Munich, Germany

## **2. Clinical Career:**

	- 8/2000 Resident at the Dept. of Int. Med. III (Prof. Dr. Dr. Kalden and Prof. Dr. Grorg Schett) and postdoctoral fellow in the group of Prof. Dr. Schulze-Koops
	- 2/2002 Doctoral Degree, Mentor: Prof. Fleckenstein (Institute for clinical and molecular Virology/University of Erlangen). Title: Sequencing and comparison of the nef-gene of long-term-surviving HIVpos children
	- 03/2009 Degree Infectiology
	- 07/2012 Degree interventional pain therapy
	- 08/2015 Habilitation at the University of Munich (Prof. Dr. Schulze-Koops)
		- 09/18 Executive MBA University St. Gallen
		- 1/19 Deputy chief physician in Aarau

## **3. Scientific Training:**

	- 2/2002 Doctoral Degree, Mentor: Prof. Fleckenstein (Institute for clinical and molecular Virology/ University of Erlangen) and PD Dr. Baur. Title: Sequencing and comparison of the nef-gene of long-term-surviving HIVpos children
	- 2005–2008 Scientific work in the laboratory of Prof Dr. Herrmann at the Dept. of Int. Med. III of the University Erlangen-Nuremberg (Prof. Dr. Schett)
	- 8/7/2015 Venia legendi at LMU in Munich, Rheumatology, Prof. Dr. Schulze-Koops

21/8/2015 Habilitation at LMU in Munich, Rheumatology, Prof. Dr. Schulze-Koops

## **4. Clinical Focus:**

Rheumatoid arthritis Clinical trials and epidemiological research Apps: Rheum-Class, Acronym Finder Rheumatology, eDrugfinder Book: Clinical Trials in Rheumatology (Springer, ISBN 978-1-4471-2869-4 ISBN 978-1-4471-2870-0)

St. Gallen, 20/08/2020

Rudiger M ¨ uller MD ¨

## *Editorial* **Rheumatoid Arthritis from Pathogenesis to Therapeutic Strategies**

**Ruediger B. Mueller \* and Paul Hasler \***

Division of Rheumatology, Medical University Department, Kantonsspital Aarau, 5001 Aarau, Switzerland **\*** Correspondence<EMAIL_ADDRESS>(R.B.M<EMAIL_ADDRESS>(P.H.)

Received: 31 July 2020; Accepted: 1 August 2020; Published: 7 August 2020

Rheumatoid arthritis (RA) is a chronic inflammatory disease that leads to joint destruction. Various therapeutic agents have been showed to halt disease progression in clinical studies. In this special issue, we cover subjects from the periodontal condition of RA patients [1,2] to therapeutic strategies [3], and patient related outcomes [4,5], accompanied by the most extensive review ever on methotrexate (MTX) use in RA [6].

Eriksson et al. [1] describe that the subgingival plaque of RA patients with moderate/severe RA was enriched with abundant bacteria of di fferent bacterial strains typical for periodontitis. Interestingly, ACPA also positivity correlated with moderate to severe periodontitis. Rinaudo-Gaujous et al. [2] showed that MMP-3 (matrix metalloproteinase 3), a marker of periodontal disease and bone and cartilage degradation, decreases subsequent to newly introduced infliximab therapy together with a reduction of disease activity. The interesting question is whether periodontitis primarily improves due to the reduction of disease activity, or whether improved arthritis leads to less pain during dental brushing and improved dental care remains, so far, unsolved.

Köhler et al. [7] reviewed the available methods for treatment of RA, while Mueller et al. [3] discussed how combination of the whole therapeutic armamentarium (new onset biologic agent, intra-articular and oral glucocorticoids, and optimization of conventional synthetic DMARDs) leads to a vastly improved outcome in a randomized clinical study. ACR 20, 50, and 70 response rates were achieved in 90.5%, 76.2%, 71.4%, an outcome that has so far not been achieved in a clinical trial of RA. The same group also reports the most extensive real-life experience of RA patients treated with tofacitinib in this issue [8]

Taylor et al. [6] wrote the largest and most comprehensive review on MTX, covering the pharmacology, the flexibility and e fficacy and cost/benefit of the drug. Included among many other topics are the potential toxicities of MTX.

Hirter et al. [9] reviewed the literature on pseudo-erosions and came to three conclusions: (A) Pseudo-erosions may be related to normal anatomy or technical artefacts. (B) So-called calcified zones can be part of classical anatomical structures, such as subchondral, sub-tendinous or -ligamentous bone. (C) As a caveat, a real arthritic erosion can develop at the site of a pseudo-erosion.

In two post-hoc analyses of the RA BEAM Study Fautrel et al. [4] and Taylor et al. [5] demonstrated that in RA patients with moderately to severely active RA despite MTX treatment, the addition of baricitinib may be more e ffective in improving pain and physical function than placebo or addition of adalimumab.

In summary, in this special issue the disease of RA and its therapy is described from di fferent angles to provide a broad and profound insight into the disease.