Localisation of citrullinated and carbamylated proteins in inflamed gingival tissues from rheumatoid arthritis patients.

OBJECTIVES: It has been proposed that citrullination and carbamylation occur in the inflamed periodontium and could be the plausible mechanisms for the generation of antigens involved in the development and progression of RA. The purpose of this study was to determine the presence and location of citrullinated and carbamylated proteins in the gingival tissues and compare their abundance in periodontitis (PD) patients with or without RA. MATERIALS AND METHODS: Gingival tissue samples of healthy (n = 5), PD with RA (n = 5) and PD without RA (n = 5) were collected. Specimens were formalin fixed, paraffin embedded and sectioned at 4 µm. The tissue sections were analysed for the presence of citrullinated and carbamylated proteins by immunohistochemistry. Semi-quantitative analysis was performed to quantify and compare the protein abundance between groups. RESULTS: The number of cells containing citrullinated and carbamylated proteins with higher intensity was markedly increased in gingival tissues from PD with or without RA in comparison with healthy controls. CONCLUSION: Inflamed gingival tissue is a potential source of citrullinated and carbamylated proteins other than synovial tissues. The extent to which the local accumulation of these proteins contributes to the pathogenesis of RA needs further elucidation. CLINICAL RELEVANCE: If PD is a potential source of post-translationally modified proteins, untreated PD should not be taken lightly in the context of RA. Hence, addressing gingival inflammation should be viewed as an important preventive measure in the general population not only for the progression of periodontal disease but also reducing the risk of developing extra-oral comorbidities.

Antibodies against citrullinated proteins in relation to periodontitis with or without rheumatoid arthritis: a cross-sectional study.

BACKGROUND: Previous studies have reported conflicting findings between serum anti-citrullinated protein antibodies (ACPA) levels in rheumatoid arthritis (RA) participants with and without periodontitis (Pd). This study aimed to analyse possible correlations between serum ACPA levels and clinical parameters in Pd and RA participants. METHODS: Full mouth periodontal examination (probing pocket depth, clinical attachment levels, gingival bleeding index, visual plaque index) was conducted and serum samples obtained from 80 participants comprising RA, Pd, both RA and Pd (RAPd) and healthy individuals (HC). Erythrocyte sedimentation rates (ESR) and periodontal inflamed surface area (PISA) were obtained. Serum samples were analysed for ACPA quantification using enzyme-linked immunosorbent assay (ELISA). RESULTS: Median levels (IU/mL) of ACPA (interquartile range, IQR) in RAPd, RA, Pd and HC groups were 118.58(274.51), 102.02(252.89), 78.48(132.6) and 51.67(91.31) respectively. ACPA levels were significantly higher in RAPd and RA as compared to HC group (p < 0.05). However, ACPA levels of any of the groups were not correlated with any clinical periodontal and RA parameters within the respective groups. CONCLUSIONS: At individual level, the amount of serum ACPA seem to have an increasing trend with the diseased condition in the order of RAPd > RA > Pd > HC. However, lack of any significant correlation between the serum ACPA levels with the clinical Pd and RA parameters warrants further studies to investigate the causal link between RA and Pd for such a trend. Further studies involving more inflammatory biomarkers might be useful to establish the causal link between Pd in the development and progression of RA or vice versa.

Isolation and identification of salt-tolerant plant-growth-promoting rhizobacteria and their application for rice cultivation under salt stress.

Growth and productivity of rice are negatively affected by soil salinity. However, some salt-tolerant rhizosphere-inhabiting bacteria can improve salt resistance of plants, thereby augmenting plant growth and production. Here, we isolated a total of 53 plant-growth-promoting rhizobacteria (PGPR) from saline and non-saline areas in Bangladesh where electrical conductivity was measured as >7.45 and <1.80 dS/m, respectively. Bacteria isolated from saline areas were able to grow in a salt concentration of up to 2.60 mol/L, contrary to the isolates collected from non-saline areas that did not survive beyond 854 mmol/L. Among the salt-tolerant isolates, Bacillus aryabhattai, Achromobacter denitrificans, and Ochrobactrum intermedium, identified by comparing respective sequences of 16S rRNA using the NCBI GenBank, exhibited a higher amount of atmospheric nitrogen fixation, phosphate solubilization, and indoleacetic acid production at 200 mmol/L salt stress. Salt-tolerant isolates exhibited greater resistance to heavy metals and antibiotics, which could be due to the production of an exopolysaccharide layer outside the cell surface. Oryza sativa L. fertilized with B. aryabhattai MS3 and grown under 200 mmol/L salt stress was found to be favoured by enhanced expression of a set of at least four salt-responsive plant genes: BZ8, SOS1, GIG, and NHX1. Fertilization of rice with osmoprotectant-producing PGPR, therefore, could be a climate-change-preparedness strategy for coastal agriculture.

Impact of non-surgical periodontal therapy on serum Resistin and periodontal pathogen in periodontitis patients with obesity.

BACKGROUND: Non-surgical periodontal therapy (NSPT) known as gold standard treatment in managing periodontitis. The aim of this study was to investigate the response of NSPT in periodontitis subjects who were obese. Clinical parameters of periodontitis, changes in serum resistin and periodontal pathogens in subgingival plaque were compared before and after NSPT in periodontitis subjects who were obese and with normal weight. METHODS: A total of 48 periodontitis subjects (obese, n = 18; normal weight, n = 30) were recruited (hereafter will be referred as participants) to participate into a prospective, before and after clinical trial. Obesity status is defined by body mass index (BMI) criteria (obese: ≥30 kg/ m2; normal weight < 25 kg/m2). Visible Plaque Index (VPI), Gingival Bleeding Index (GBI), Probing Pocket Depth (PPD) and Clinical Attachment Loss (CAL) were recorded; and serum and plaque were collected at baseline and following 12 weeks post-NSPT. Serum resistin level was analyzed using enzyme-linked immune-sorbant assay (ELISA), while detection of periodontal pathogens in dental plaque were carried out using real time PCR (qPCR). RESULTS: Following NSPT, means VPI and GBI showed significant improvement between obese and normal weight groups (p <  0.05), but no difference in means PPD and CAL was observed between groups. Obesity remained as a predictor for VPI and GBI after adjusting for smoking habit. No significant difference was observed in serum resistin level and mean counts for P. gingivalis, T. forsythia, and P. intermedia between obese and normal weight groups following NSPT. CONCLUSIONS: Regardless of obesity status, NSPT has a significant impact on VPI and GBI in periodontitis subjects. However, the impact of NSPT towards serum resistin and periodontal pathogens was non-significant in those with periodontitis. TRIAL REGISTRATION: This study followed the Consolidation Standards of Reporting Trials Statement and retrospectively registered on 26/11/2015 at clinicaltrials.gov (No. NCT02618486).

Origin, Function, and Fate of Metallothionein in Human Blood.

Toxic heavy metals, toxic organic compounds, reactive oxygen species (ROS), infections, and temperature are well-known metallothionein (MT) inducers in human blood. The current review aims to summarize synthesis, function, and fate of human blood MT in response to the known MT inducers. Part of the MTs that are synthesized in different organs such as the liver, kidney, and spleen is transported and stored in different blood cells and in plasma. Cells of the circulatory system also synthesize MT. From the circulation, MT returns to the kidney where the metal-bound MTs are degraded to release the metal ion that in turn induces MT expression therein. The blood MTs play important roles in metal detoxification, transportation, and storage. By neutralizing ROS, MTs protect blood cells from oxidative stress-induced cytotoxicity and genotoxicity. Arguably, MTs are also involved in immune suppression. Given the permeating distribution of blood MT throughout the body as well as its diverse role in the protection against harmful environmental factors and in metal homeostasis, MT could be better recognized as a major public health protein.

Arsenic Induction of Metallothionein and Metallothionein Induction Against Arsenic Cytotoxicity.

Human exposure to arsenic (As) can lead to oxidative stress that can become evident in organs such as the skin, liver, kidneys and lungs. Several intracellular antioxidant defense mechanisms including glutathione (GSH) and metallothionein (MT) have been shown to minimize As cytotoxicity. The current review summarizes the involvement of MT as an intracellular defense mechanism against As cytotoxicity, mostly in blood. Zinc (Zn) and selenium (Se) supplements are also proposed as a possible remediation of As cytotoxicity. In vivo and in vitro studies on As toxicity were reviewed to summarize cytotoxic mechanisms of As. Intracellular antioxidant defense mechanisms of MT are linked in relation to As cytotoxicity. Arsenic uses a different route, compared to major metal MT inducers such as Zn, to enter/exit blood cells. A number of in vivo and in vitro studies showed that upregulated MT biosynthesis in blood components are related to toxic levels of As. Despite the cysteine residues in MT that aid to bind As, MT is not the preferred binding protein for As. Nonetheless, intracellular oxidative stress due to As toxicity can be minimized, if not eliminated, by MT. Thus MT induction by essential metals such as Zn and Se supplementation could be beneficial to fight against As toxicity.

Molecular Mechanisms of Stress-Responsive Changes in Collagen and Elastin Networks in Skin.

Collagen and elastin networks make up the majority of the extracellular matrix in many organs, such as the skin. The mechanisms which are involved in the maintenance of homeostatic equilibrium of these networks are numerous, involving the regulation of genetic expression, growth factor secretion, signalling pathways, secondary messaging systems, and ion channel activity. However, many factors are capable of disrupting these pathways, which leads to an imbalance of homeostatic equilibrium. Ultimately, this leads to changes in the physical nature of skin, both functionally and cosmetically. Although various factors have been identified, including carcinogenesis, ultraviolet exposure, and mechanical stretching of skin, it was discovered that many of them affect similar components of regulatory pathways, such as fibroblasts, lysyl oxidase, and fibronectin. Additionally, it was discovered that the various regulatory pathways intersect with each other at various stages instead of working independently of each other. This review paper proposes a model which elucidates how these molecular pathways intersect with one another, and how various internal and external factors can disrupt these pathways, ultimately leading to a disruption in collagen and elastin networks.

Selenium added unripe carica papaya pulp extracts enhance wound repair through TGF-ß1 and VEGF-a signalling pathway.

BACKGROUND: Increased wound healing efficiency by Se(2+) added Carica papaya L. (Caricaceae) fruit extract was linked to increased antioxidant and anti-inflammatory responses during healing. We investigated the impact of Se(2+) or Zn(2+) added papaya water (WE) and phosphate-buffered saline (PE) extracts on cells recruitment and bio-molecular alterations on days 4 and 10 post wounding in an in vivo excision wound. METHODS: Excision wounds were created on the dorsum of Sprague Dawley rats and treated topically twice/day with 20 µL of PE and WE (5 mg extract/mL), 0.5 µgSe(2+) added PE and WE (PES and WES), or 100 µMZn(2+) added PE and WE (PEZ and WEZ). Deionised water (negative) and Solcoseryl (positive) were applied on the control groups. Histochemical and biochemical assays were used to evaluate cellular and bio-molecular changes in the wound. RESULTS: PES (PE + 0.5 µg Se(2+)) only increased significantly (p < 0.05) wound total protein content (95.14 ± 1.15 mg/g tissue vs positive control; 80.42 ± 0.86 mg/g tissue) on day 10 post wounding. PES increased significantly (p < 0.05) the number of fibroblasts/high power field (HPF) (75.60 ± 9.66) but decreased significantly (p < 0.05) the number of polymorphonuclear leukocytes/HPF (59.20 ± 12.64) in the wound compared to positive control (50.60 ± 12.58 fibroblasts/HPF, 101.00 ± 27.99 polymorphonuclear leukocytes/HPF) on day 4. Similar results were recorded for WES. PES demonstrated increased neovascularization, TGF-ß1 and VEGFA expressions at day 4 and increased collagen at day 10. CONCLUSION: Papaya extract improved wound repair by increasing fibroblasts recruitment and reducing polymorphonuclear leukocytes infiltration through early transient expressions of TGF-ß1 and VEGFA at the wound area. The processes were amplified with Se(2+) addition.

Carica papaya induces in vitro thrombopoietic cytokines secretion by mesenchymal stem cells and haematopoietic cells.

BACKGROUND: Use of Carica papaya leaf extracts, reported to improve thrombocyte counts in dengue patients, demands further analysis on the underlying mechanism of its thrombopoietic cytokines induction METHODS: In vitro cultures of peripheral blood leukocytes (PBL) and stem cells from human exfoliated deciduous teeth (SHED) were treated with unripe papaya pulp juice (UPJ) to evaluate its potential to induce thrombopoietic cytokines (IL-6 and SCF) RESULTS: In vitro scratch gap closure was significantly faster (p < .05) in SHED culture treated with UPJ. IL-6 concentration was significantly increased (p < .05) in SHED and PBL culture supernatant when treated with UPJ. SCF synthesis in SHED culture was also significantly increased (p < .05) when treated with UPJ CONCLUSION: In vitro upregulated synthesis of IL -6 and SCF both in PBL and SHED reveals the potential mechanism of unripe papaya to induce thrombopoietic cytokines synthesis in cells of hematopoietic and mesenchymal origin.

Anti-inflammatory and antioxidant properties of unripe papaya extract in an excision wound model.

CONTEXT: Carica papaya L. (Caricaceae) fruit was shown to exhibit wound healing properties. OBJECTIVES: We investigated anti-inflammatory and antioxidant potential of papaya fruit phosphate-buffered saline extract (PE) during wound healing and enhancement of the potentials due to trace ions addition. MATERIALS AND METHODS: Rat excision wounds were topically treated twice/day with 20 µL of PE (5 mg extract/mL), 0.5 µg Se(2+) added PE (PES), or 100 µM Zn(2+) added PE (PEZ). Control groups were treated with deionized water (negative) and deproteinized calf blood extract ointment (Solcoseryl®, positive). Lipid peroxidation (LPX), antioxidant, proinflammatory, and arginine metabolic enzymes were estimated in the wound excised on days 4 and 10 post wounding. RESULTS: PE (5 mg/mL; 9.80 ± 0.33 d) and PES (PE + 0.5 µg Se(2+); 8.90 ± 0.23 d) significantly (p < 0.05) reduced the average time for complete wound closure compared with the negative (13.00 ± 0.37 d) and positive (9.80 ± 0.33 d) controls, respectively. Biochemical evaluations of LPX product (malondialdehyde), antioxidant (catalase, superoxide dismutase (SOD), and glutathione peroxidase (GPx)), and pro-inflammatory (cyclooxygenase-2 and myeloperoxidase (MPO)) enzyme activities and metabolites (nitrite and urea), on days 4 and 10 post wounding, confirmed the anti-inflammatory and antioxidant properties of PE and PES in this study. DISCUSSION AND CONCLUSION: Treatment of excision wounds with papaya extract, especially with the addition of selenium for 10 d, reduced inflammation associated oxidative damage apparently via cyclooxygenase specific inhibition, arginine metabolism, and up-regulation of antioxidant enzymes.

Hypoxic culture conditions as a solution for mesenchymal stem cell based regenerative therapy.

Cell-based regenerative therapies, based on in vitro propagation of stem cells, offer tremendous hope to many individuals suffering from degenerative diseases that were previously deemed untreatable. Due to the self-renewal capacity, multilineage potential, and immunosuppressive property, mesenchymal stem cells (MSCs) are considered as an attractive source of stem cells for regenerative therapies. However, poor growth kinetics, early senescence, and genetic instability during in vitro expansion and poor engraftment after transplantation are considered to be among the major disadvantages of MSC-based regenerative therapies. A number of complex inter- and intracellular interactive signaling systems control growth, multiplication, and differentiation of MSCs in their niche. Common laboratory conditions for stem cell culture involve ambient O2 concentration (20%) in contrast to their niche where they usually reside in 2-9% O2. Notably, O2 plays an important role in maintaining stem cell fate in terms of proliferation and differentiation, by regulating hypoxia-inducible factor-1 (HIF-1) mediated expression of different genes. This paper aims to describe and compare the role of normoxia (20% O2) and hypoxia (2-9% O2) on the biology of MSCs. Finally it is concluded that a hypoxic environment can greatly improve growth kinetics, genetic stability, and expression of chemokine receptors during in vitro expansion and eventually can increase efficiency of MSC-based regenerative therapies.

Inflammatory Responses in Periodontitis with or Without Rheumatoid Arthritis Alter Salivary Metallothionein and Zinc.

Periodontitis (PD) and rheumatoid arthritis (RA) are causally linked by their common inflammatory responses, yet it is largely unknown if these inflammatory responses might have an impact on salivary metallothionein (MT), zinc (Zn), and calcium (Ca) content. In this study, we analysed salivary concentrations of pro-inflammatory (IFN-γ, IL-6, and IL-17) and anti-inflammatory (IL-4 and IL-10) cytokines, as well as MT, Zn, and Ca in four groups of participants, namely control (without PD or RA, n = 21), PD (n = 21), RA (n = 21), or RAPD (n = 19). As expected, an increased amount of salivary pro-inflammatory cytokines were observed in the PD, RA, and RAPD groups. While Ca concentration was not significantly different between the groups, Zn concentration was lower in the PD, RA, and RAPD groups compared to the control group (p < 0.05). These groups also expressed higher MT/Zn ratios compared to the control group (p < 0.05). Unlike the control group, concentrations of inflammatory cytokines, MT, Zn, and Ca correlated with each other in the PD, RA, and RAPD groups (p < 0.05). Additionally, comorbidity of PD and RA appears to have a cumulative immuno-pathological impact that warrants further investigation. This study suggests that, in addition to inflammatory cytokines, salivary MT and Zn could reflect the severity of PD with or without RA, hence providing an important biomarker for diagnosis.

Beneficial effects of ginger (Zingiber officinale) on carbohydrate metabolism in streptozotocin-induced diabetic rats.

Zingiber officinale (ZO), commonly known as ginger, has been traditionally used in the treatment of diabetes mellitus. Several studies have reported the hypoglycaemic properties of ginger in animal models. The present study evaluated the antihyperglycaemic effect of its aqueous extract administered orally (daily) in three different doses (100, 300, 500 mg/kg body weight) for a period of 30 d to streptozotocin (STZ)-induced diabetic rats. A dose-dependent antihyperglycaemic effect revealed a decrease of plasma glucose levels by 38 and 68 % on the 15th and 30th day, respectively, after the rats were given 500 mg/kg. The 500 mg/kg ZO significantly (P<0·05) decreased kidney weight (% body weight) in ZO-treated diabetic rats v. control rats, although the decrease in liver weight (% body weight) was not statistically significant. Kidney glycogen content increased significantly (P<0·05) while liver and skeletal muscle glycogen content decreased significantly (P<0·05) in diabetic controls v. normal controls. ZO (500 mg/kg) also significantly decreased kidney glycogen (P<0·05) and increased liver and skeletal muscle glycogen in STZ-diabetic rats when compared to diabetic controls. Activities of glucokinase, phosphofructokinase and pyruvate kinase in diabetic controls were decreased by 94, 53 and 61 %, respectively, when compared to normal controls; and ZO significantly increased (P<0·05) those enzymes' activities in STZ-diabetic rats. Therefore, the present study showed that ginger is a potential phytomedicine for the treatment of diabetes through its effects on the activities of glycolytic enzymes.

Real Time PCR-based diagnosis of human visceral leishmaniasis using urine samples.

Diagnosis of visceral leishmaniasis (VL) through the detection of its causative agents namely Leishmania donovani and L. infantum is traditionally based on immunochromatographic tests, microscopy of bone marrow, spleen aspirates, liver or lymph node and differential diagnosis. While the first process has low specificity, the later one carries the risk of fatal hemorrhage. Over the last decade, multiple Polymerase Chain Reaction (PCR) based diagnosis has been developed using blood and urine sample with a varying degree of sensitivity and specificity, an issue worth improving for precision diagnosis. Earlier, we reported a PCR-based diagnosis of L. donovani in peripheral blood using a novel set of PCR primers with absolute specificity. Using the same set of primers and PCR conditions, here we describe diagnosis of L. donovani from urine, for a non-invasive, rapid and safe diagnosis. Diagnosis of VL was carried out using urine samples collected from clinically diagnosed VL patients (n = 23) of Bangladesh in Real Time PCR. Test results were validated by comparing blood samples from the same set of patients. Sensitivity and specificity of this diagnosis was analyzed using retrospective bone marrow samples, collected earlier from confirmed VL patients (n = 19). The method showed 100% sensitivity in detecting L. donovani in urine and corresponding blood and retrospective bone marrow samples, as well as 100% specificity in control groups. A Real Time PCR-based molecular detection system using urine sample is hereafter presented what could be a, non-invasive approach for VL detection with precision and perfection.

Time-based changes in authorship trend in research-intensive universities in Malaysia.

Considering the fact that publications serve as an important criterion to evaluate the scientific accomplishments of an individual within respective fields in academia, there has been an increasing trend to publish scientific articles whereby multiple authors are defined as primary, co-, or corresponding authors according to the roles performed. This article analyzes the authorship pattern in 4,561 papers (including 60 single-authored papers) from 1990 till 2020 of 94 academics who hold a position as professors and are affiliated with the Faculty of Medicine at three different research universities in Malaysia. Only 708 papers (15.5% of 4,561 papers) were authored by less than three authors. In 3,080 papers (67.5% of 4,561 papers), those academics appeared as coauthors. Using different years as cutoff periods, it was observed that the appearance as coauthor in the papers had steeply risen around the years: 2006, 2007, 2008 and onwards. The increased number of authors in the multi-author papers and the appearance of the selected academics as coauthors reflect the extent of boosting of collaborative research in that period which corresponds to the adoption of the "publish or perish policy" by the Ministry of Higher Education in Malaysia.

Dysregulation of metallothionein and zinc aggravates periodontal diseases.

BACKGROUND: Periodontitis (PD) is a multifaceted inflammatory disease connected to bacterial infection that results in the destruction of tooth supporting structures and eventually tooth loss. Given their involvement in infection and inflammation, both metallothionein (MT) and zinc (Zn) might play vital roles in the development and progression of PD. More specifically, both MT and Zn are heavily involved in regulating immune functions, controlling bacterial infection, balancing inflammatory responses, and reducing oxidative stress, all of which are associated with the pathogenesis of PD. OBJECTIVE: This review paper will explore the physiological functions of MT and Zn and hypothesise how dysregulation could negatively affect periodontal health, leading to PD. FINDINGS: Bacterial lipopolysaccharide (LPS) derived from periodontal pathogens, namely P. gingivalis initiates the acute phase response, thus upregulating the expression of MT which leads to the subsequent deficiency of Zn, a hallmark of periodontal disease. This deficiency leads to ineffective NETosis, increases the permeability of the gingival epithelium, and disrupts the humoral immune response, collectively contributing to PD. In addition, the presence of LPS in Zn deficient conditions favours M1 macrophage polarisation and maturation of dendritic cells, and also inhibits the anti-inflammatory activity of regulatory T cells. Collectively, these observations could theoretically give rise to the chronic inflammation seen in PD. CONCLUSION: A disrupted MT and Zn homeostasis is expected to exert an adverse impact on periodontal health and contribute to the development and progression of PD.

Can Zn Be a Critical Element in COVID-19 Treatment?

The current COVID-19 pandemic caused by SARS-CoV-2 has prompted investigators worldwide to search for an effective anti-viral treatment. A number of anti-viral drugs such as ribavirin, remdesivir, lopinavir/ritonavir, antibiotics such as azithromycin and doxycycline, and anti-parasite such as ivermectin have been recommended for COVID-19 treatment. In addition, sufficient pre-clinical rationale and evidence have been presented to use chloroquine for the treatment of COVID-19. Furthermore, Zn has the ability to enhance innate and adaptive immunity in the course of a viral infection. Besides, Zn supplement can favour COVID-19 treatment using those suggested and/or recommended drugs. Again, the effectiveness of Zn can be enhanced by using chloroquine as an ionophore while Zn inside the infected cell can stop SARS-CoV-2 replication. Given those benefits, this perspective paper describes how and why Zn could be given due consideration as a complement to the prescribed treatment of COVID-19.

Possible Benefits of Zinc supplement in CVD and COVID-19 Comorbidity.

As far as comorbidity is concerned, cardiovascular diseases (CVD) appear to be accounted for the highest prevalence, severity, and fatality among COVID 19 patients. A wide array of causal links connecting CVD and COVID-19 baffle the overall prognosis as well as the efficacy of the given therapeutic interventions. At the centre of this puzzle lies ACE2 that works as a receptor for the SARS-CoV-2, and functional expression of which is also needed to minimize vasoconstriction otherwise would lead to high blood pressure. Furthermore, SARS-CoV-2 infection seems to reduce the functional expression of ACE2. Given these circumstances, it might be advisable to consider a treatment plan for COVID-19 patients with CVD in an approach that would neither aggravate the vasodeleterious arm of the renin-angiotensinogen-aldosterone system (RAAS) nor compromise the vasoprotective arm of RAAS but is effective to minimize or if possible, inhibit the viral replication. Given the immune modulatory role of Zn in both CVD and COVID-19 pathogenesis, zinc supplement to the selective treatment plan for CVD and COVID-19 comorbid conditions, to be decided by the clinicians depending on the cardiovascular conditions of the patients, might greatly improve the therapeutic outcome. Notably, ACE2 is a zinc metalloenzyme and zinc is also known to inhibit viral replication.

Contribution based author categorization to calculate author performance index.

Despite the widely used author contribution criteria, unethical authorship practices such as guest, ghost, and honorary authorship remain largely unsolved. We have identified six major reasons by analyzing 78 published papers addressing unethical authorship practice. Those are lack of: (i) awareness about and (ii) compliance with authorship criteria, (iii) universal definition and scope for determining authorship, (iv) common mechanisms for positioning an author in the list, (v) quantitative measures of intellectual contribution; and (vi) pressure to publish. As a  measure to control unethical practice, we have evaluated the possibility to adopt an author categorization scheme - proposed according to the common understanding of how first-, co-, principal-, or corresponding- author is perceived. Based on an online opinion survey, the scheme was supported by ~80% of the respondents (n=370). The impact of the proposed categorization was then evaluated using a novel mathematical tool to measure "Author Performance Index (API)" that can be higher for those who might have authored more papers as primary and/or principal authors than those as coauthors. Hence, if adopted, the proposed author categorization scheme together with the API would provide a better way to evaluate the credit of an individual as a primary and principal author.

Biomechanical Effects of Unidirectional Expansion Using Anisotropic Expanders in Horse Skin Tissue.

The use of a self-inflating tissue expander is a technique to stretch cutaneous tissues for potential use in reconstructive skin surgeries. This study investigates the mechanical properties of horse skin stretched by the subcutaneous implantation of anisotropic tissue expanders at the forehead, right shoulder, and dorsomedial part of the cannon region of the right forelimb in six (n = 6) horses. After 14 days of skin expansion, expanded and normal (control) skin samples were harvested and their mechanical properties of elastic modulus (EM), maximum force (MF), maximum stress (MSs) and maximum strain (MSr) were evaluated using uniaxial tension test. The expanded skin from shoulder area has higher EM, MSs, MSr and MF than the normal skin when compared to the forehead and lower forelimb. Statistically, there was a significant (P= .02) mean difference for MSs between the expanded shoulder and lower forelimb skin, but the pairwise comparison of EM, MSr and MF showed no significant difference between the locations. The overall effect of locations on EM and MSs was statistically significant (P < .05), however, there was no overall effect of horse factor, treatment factor (normal and expanded skin) and location interaction on the EM, MSS, MF and MSr. In conclusion, the expanded skin from the frontal head and the distal limb are less elastic (stiffer) compared to that of the expanded skin of the shoulder, thus anatomical location of the skin has some degree of effect on EM and MSs.