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In our observational study, we aim to highlight the role of rehabilitation program in the control and maintaining of the clinical and functional status of people with primary knee osteoarthritis and co-morbidities. We established that the complete rehabilitation program (diet, symptomatic medication and herbal products, electrotherapy measures and kinetic exercises) will give the optimal healthcare for this type of patients.

Aim: Rheumatoid arthritis is an autoimmune disease affecting the joints. Antiarthritic drugs are given systemically, thereby exposing various healthy organs to these drugs, resulting in adverse reactions. Accordingly, there is an urgent need for targeted drug delivery methods for inflamed joints. Materials & methods: We developed a liposomal drug delivery system using a novel peptide ligand (CKPFDRALC) named ART-2, which homes to the inflamed joints when injected intravenously to rats with adjuvant-induced arthritis. Results: The ART-2-coated liposomes encapsulating an antiarthritic drug, dexamethasone (DEX), were more effective in inhibiting arthritis progression than control-DEX liposomes or free DEX, despite a comparable safety profile. Conclusion: Peptide-targeted therapy has advantages over conventional drug delivery and can be adapted for rheumatoid arthritis therapy.

Rheumatoid arthritis (RA) is an autoimmune disease characterized by chronic inflammation of the synovial joints. Inflammation, new blood vessel formation (angiogenesis) and bone resorption (osteoclastogenesis) are three key processes involved in the joint damage and deformities of arthritis. Various gut microbiota-derived metabolites are implicated in RA pathogenesis. However, there is barely any information about the impact of two such metabolites, indole-3-aldehyde (IAld) and indole-3-acetic acid (I3AA), on arthritis-related processes. We conducted a comparative analysis of IAld and I3AA using established cell-based models to understand how they might influence RA pathogenesis. Although structurally similar, the bioactivities of these two metabolites were profoundly different. IAld but not I3AA, inhibited the expression of pro-inflammatory cytokines (IL-1β and IL-6) in RAW 264.7 (RAW) cells stimulated with heat-killed M. tuberculosis sonicate (Mtb) and lipopolysaccharide (LPS). IAld also exhibited pro-angiogenic activity and pro-osteoclastogenic activity. In contrast, I3AA exhibited anti-angiogenic activity on endothelial cell tube formation but had no effect on osteoclastogenesis. Both IAld and I3AA have been proposed as aryl hydrocarbon receptor (AhR) agonists. Use of CH-223191, an inhibitor of the AhR, suppressed the anti-angiogenic activity of I3AA but failed to mitigate the effects of IAld. Further investigation of the anti-inflammatory activities of IAld and I3AA in LPS-treated RAW cells indicated that inhibition of MyD88-dependent activation of NF-κB and MAPK pathways was not likely involved. Our results suggest that the relative bioavailability of these indole derivatives may differentially impact RA progression and possibly other diseases that share similar cellular processes.

Background: Healthcare workers (HCWs),particularly from lower-middle income countries (LMIC), are at high risk of acquiring COVID-19. Limited data exist on the effectiveness of hydroxychloroquine as prophylaxis. Our trial evaluated the effectiveness of a 12-week regimen of hydroxychloroquine among HCWs on the risk of laboratory-confirmed COVID-19 in the 6 months after randomization Methods: We conducted a multicentre parallel-group open-label randomized controlled trial in 9 centres across India. HCWs serving in an environment with exposure to COVID-19 were eligible and randomized in a 1:1 ratio to hydroxychloroquine plus standard practice or to standard practice alone (role-appropriate personal protective equipment). In the intervention arm, participants received 2 doses of 400mg hydroxychloroquine at randomization followed by a weekly dose for 12 weeks. The primary outcome was the proportion of laboratory-confirmed COVID-19 in the 6 months after randomization using an intention-to-treat analysis. The trial was registered on Clinical Trials Registry of India(CTRI/2020/05/025067). Findings: From 29th June 2020 to 4th February 2021, 886 participants were screened and 416 were randomized (203-standard practice and 213- hydroxychloroquine plus standard practice). In the 6 months after randomization (primary analysis population=413), 11 participants assigned to the hydroxychloroquine group and 12 participants assigned to the standard practice group met the primary end point[ 5.1% vs 5.9%; OR 0.85, [95% CI 0.35-2.06] p=0.71]. There was no heterogeneity of treatment effect on the primary outcome in any of the pre-specified subgroups. There were no significant differences in any of the secondary outcomes. The adverse event rates were 9.9% and 6.9% in the hydroxychloroquine and standard practice arms respectively. There were no serious adverse events in either group. Interpretation: Hydroxychloroquine along with standard practice was not superior to standard practice alone on the proportion of lab-confirmed COVID-19. However, conclusions are limited by the premature trial cessation. Trial Registration: Clinical Trials Registry of India (CTRI/2020/05/025067). Funding: Wesley Medical Research, Australia Declaration of Interest: OJ reports being a member of the WHO R&D Blueprint Safety Monitoring Team, ACT Acclerator-R&D Digital Health working group and COVID-19 Clinical Research Coalition data sharing working group. Remaining authors have nothing to declare. Ethical Approval: Written informed consent was obtained from all participants. The trial was approved by the Ethics Committee at all participating sites (coordinating centre EC approval number: The George Institute Ethics Committee:08-2020)

The study was undertaken to see the variation of the suprascapular notch. The notch is present on the superior border of the scapula near the root of coracoid process. It is roofed by the superior transverse ligament and is converted into foramen for the passage of suprascapular nerve. The study was carried out on 121 scapulae in the department of Anatomy RMC Loni, Ahmednagar. The parameters included in the study were presence of notch, shape of notch, transvers length of notch, edge of notch, ossification of transverse ligament and other finding were also noted. The parameters were measured by Vernier calliper and appropriate statistical tests were applied. The supra-scapular notch was present in 82.64% of scapulae. U Deep shaped notch was most common shape followed by J shallow shaped notch. Round edge at the depth of the notch was more common. The knowledge of suprascapular notch variations is of great importance for surgeons performing suprascapular nerve decompression especially by means of endoscopic techniques. Our anatomical study helps the clinicians before planning a surgery.

Objective Nonalcoholic hepatic steatosis, also known as fatty liver, is a uniform response of the liver to hyperlipidic-hypercaloric diet intake. However, the post-ingestive signals and mechanistic processes driving hepatic steatosis are not well understood. Emerging data demonstrate that protein kinase C beta (PKCβ), a lipid-sensitive kinase, plays a critical role in energy metabolism and adaptation to environmental and nutritional stimuli. Despite its powerful effect on glucose and lipid metabolism, knowledge of the physiological roles of hepatic PKCβ in energy homeostasis is limited. Methods The floxed-PKCβ and hepatocyte-specific PKCβ-deficient mouse models were generated to study the in vivo role of hepatocyte PKCβ on diet-induced hepatic steatosis, lipid metabolism, and mitochondrial function. Results We report that hepatocyte-specific PKCβ deficiency protects mice from development of hepatic steatosis induced by high-fat diet, without affecting body weight gain. This protection is associated with attenuation of SREBP-1c transactivation and improved hepatic mitochondrial respiratory chain. Lipidomic analysis identified significant increases in the critical mitochondrial inner membrane lipid, cardiolipin, in PKCβ-deficient livers compared to control. Moreover, hepatocyte PKCβ deficiency had no significant effect on either hepatic or whole-body insulin sensitivity supporting dissociation between hepatic steatosis and insulin resistance. Conclusions The above data indicate that hepatocyte PKCβ is a key focus of dietary lipid perception and is essential for efficient storage of dietary lipids in liver largely through coordinating energy utilization and lipogenesis during post-prandial period. These results highlight the importance of hepatic PKCβ as a drug target for obesity-associated nonalcoholic hepatic steatosis., Highlights • Hepatocyte-specific PKCβ deficiency protects from diet-induced hepatic steatosis but not either obesity or insulin resistance. • The underlying mechanism involves modulation of mitochondrial function and lipogenesis. • Hepatocyte PKCβ does not regulate hepatic insulin signaling. • Our study provides a link between dietary lipid intake, hepatic protein kinase Cβ, modulation of hepatic lipid metabolism, and development of hepatic steatosis.

© 2020 International Society of NephrologyThere is a huge gap between the number of patients worldwide requiring versus those actually receiving safe, sustainable, and equitable care for kidney failure. To address this, the International Society of Nephrology coordinated the development of a Strategic Plan for Integrated Care of Patients with Kidney Failure. Implementation of the plan will require engagement of the whole kidney community over the next 5–10 years.

Eczema is a complex chronic inflammatory skin disease impacted by environmental factors, infections, immune disorders, and deficiencies in skin barrier function. Shi Zhen Tea (SZT), derived from traditional Chinese medicine Xiao-Feng-San, has shown to be an effective integrative therapy for treating skin lesions, itching, and sleeping loss, and it facilitates reduction of topical steroid and antihistamine use in pediatric and adult patients with severe eczema. Yet, its active compounds and therapeutic mechanisms have not been elucidated. In this study, we sought to investigate the active compounds and molecular mechanisms of SZT in treating eczema using systems pharmacology and in silico docking analysis. SZT is composed of 4 medicinal herbs, Baizhu (Atractylodis macrocephalae rhizome), Jingjie (Schizonepetae herba), Kushen (Sophorae flavescentis radix), and Niubangzi (Arctii fructus). We first identified 51 active compounds from SZT and their 81 potential molecular targets by high-throughput computational analysis, from which we identified 4 major pathways including Th17 cell differentiation, metabolic pathways, pathways in cancer, and the PI3K-Akt signaling pathway. Through network analysis of the compound-target pathway, we identified hub molecular targets within these pathways including carbonic anhydrase II (CA2), peroxisome proliferator activated receptor γ (PPAR γ), retinoid X receptor α (RXRA), and vitamin D receptor (VDR). We further identified top 5 compounds including cynarine, stigmasterin, kushenol, β-sitosterol, and (24S)-24-propylcholesta-5-ene-3β-ol as putative key active compounds on the basis of their molecular docking scores with identified hub target proteins. Our study provides an insight into the therapeutic mechanism underlying multiscale benefits of SZT for eczema and paves the way for developing new and potentially more effective eczema therapies.

Various materials are used to improve the longevity of the dental implants. In our study, we assessed the marginal bone loss around dental implants after implantation with platelet-rich plasma.We conducted a prospective clinical study among 200 subjects who were grouped equally as those with and without the application of PRF in the implantation. The radiographic and clinical features for the marginal bone loss were assessed and compared keepingWe observed no significant variation between the groups for the mobility, bleeding on probing, plaque index, and marginal bone loss.We can conclude that the application of PRP concentrate did not significantly affect the marginal bone loss in the dental implantation.

Skin metastases are rarely found in lung cancer compared to other types of neoplasia. Of the types of lung cancer that can have skin metastases, the most common one is adenocarcinoma. Pulmonary cancer metastasizing to the skin has poor prognosis, usually the survival rate of the patients is 4-6 months. We present the case of a 59-year-old woman, smoker, high blood pressure, dyslipidemia, with two skin ertitemato-nodular lesions, incompletely delimited, with a diameter of 4-5cm, in the left arm (1/3 medio-external) and left latero-thoracic (near IV intercostal space) area, discovered during a regular medical examination at her family doctor’s practice. After multiple clinical and paraclinical investigations, almost 3 months after the initial presentation, the patient was diagnosed with stage IV pulmonary adenocarcinoma with supra and subdiaphragmatic lymph-node metastases, soft tissue metastases, liver metastases and breast metastases. Oncological treatment was initiated, but the patient's progression was unfavorable, her passing occurring 6 months after being diagnosed.