CAMKK2 is upregulated in primary human osteoarthritis and its inhibition protects against chondrocyte apoptosis.

OBJECTIVE: To investigate the role of calcium/calmodulin-dependent protein kinase kinase 2 (CAMKK2) in human osteoarthritis. MATERIALS AND METHODS: Paired osteochondral plugs and articular chondrocytes were isolated from the relatively healthier (intact) and damaged portions of human femoral heads collected from patients undergoing total hip arthroplasty for primary osteoarthritis (OA). Cartilage from femoral plugs were either flash frozen for gene expression analysis or histology and immunohistochemistry. Chondrocyte apoptosis in the presence or absence of CAMKK2 inhibition was measured using flow cytometry. CAMKK2 overexpression and knockdown in articular chondrocytes were achieved via Lentivirus- and siRNA-mediated approaches respectively, and their effect on pro-apoptotic and cartilage catabolic mechanisms was assessed by immunoblotting. RESULTS: CAMKK2 mRNA and protein levels were elevated in articular chondrocytes from human OA cartilage compared to paired healthier intact samples. This increase was associated with elevated catabolic marker matrix metalloproteinase 13 (MMP-13), and diminished anabolic markers aggrecan (ACAN) and type II collagen (COL2A1) levels. OA chondrocytes displayed enhanced apoptosis, which was suppressed following pharmacological inhibition of CAMKK2. Levels of MMP13, pSTAT3, and the pro-apoptotic marker BAX became elevated when CAMKK2, but not its kinase-defective mutant was overexpressed, whereas knockdown of the kinase decreased the levels of these proteins. CONCLUSIONS: CAMKK2 is upregulated in human OA cartilage and is associated with elevated levels of pro-apoptotic and catabolic proteins. Inhibition or knockdown of CAMKK2 led to decreased chondrocyte apoptosis and catabolic protein levels, whereas its overexpression elevated them. CAMKK2 may be a therapeutic target to prevent or mitigate human OA.

Clinical and Demographic Patterns of Vulval Dermatoses and Their Impact on Quality of Life.

Background: Vulval dermatoses may present with varied manifestations ranging from asymptomatic to chronic disabling conditions. The multifactorial nature of symptoms and physical expression of the disease on the vulva complicate the evaluation and management of genital dermatoses, thereby severely impairing the quality of life of patients. Objectives: To study the clinical patterns and socio-demographic features of vulval dermatoses and their impact on the quality of life using the dermatology life quality index (DLQI) questionnaire. Materials and Methods: Female patients of all age groups who attended our outpatient department (OPD) from October 2019 to March 2021 with vulval lesions were included in the study after a detailed history and complete examination. Based on sites of involvement, the lesions were classified as genital lesions alone, genital and skin lesions, oro-genital lesions, and oro-genital and skin lesions. DLQI score was assessed using the DLQI questionnaire. Results: In total, 520 patients were recruited for the study after following the inclusion and exclusion criteria. The most common age group was 31-40 years (33.65%). The majority of the patients were married (91.92%), housewives (82.88%), and illiterate (49.61%) women. The most common presenting symptom was itching (43%). The most common vulval dermatoses were infections, seen in 401 (77.11%) patients, followed by inflammatory diseases in 78 (15%) patients, and immunobullous diseases (1.53%). Patients with genital, skin, and oral involvement showed statistically significant higher DLQI scores (P value < 0.05). Patients with immunobullous disorders had the highest mean DLQI scores. Limitations: As this study was a hospital-based study, the observations may not represent and reflect the general population. Conclusion: Patients with genital, skin, and oral lesions had the highest DLQI scores, indicating higher impact on the quality of life. Assessment of the disease's impact on the quality of life is essential because it not only aids in early management but also helps in minimizing the duration of the ailment.

Dermatoses Occurring after Parlor Procedures.

BACKGROUND: Cosmetic procedures are on the rise and practiced by all age groups, especially by teenagers. These procedures enhance the individual appearance and confidence levels, but they are not without side effects. AIMS AND OBJECTIVES: The aim of this study was to evaluate the side effects occurring after various parlor procedures such as facials, threading, waxing, and laser hair reduction. SETTING AND DESIGN: A prospective study for 12 months in a tertiary hospital. MATERIALS AND METHODS: Patients attending the department of dermatology at a tertiary care hospital for 12 months (July 2018-June 2019) were evaluated for any skin lesions, developed after one of the above parlor procedures. Detailed history, clinical examination, and correlation with the parlor procedure were noted. RESULTS: A total of 102 patients were found to have dermatoses after various parlor procedures during the 1-year study period (81 F and 21 M). Acneiform eruptions 26 (25.4%), followed by post-waxing folliculitis 17(16.7%), and hyperpigmentation of face 15 (14.7%) were the most common dermatoses. Molluscum contagiosum, verrucae plana, and tinea faciei were observed in 11, 6, and 3 patients, respectively. CONCLUSION: Side effects are not uncommon after parlor procedures. Awareness of these is necessary and educating the patients is extremely important to avoid these unwanted complications.

Microbial community sequencing analysis of the calf eye microbiota and relationship to infectious bovine keratoconjunctivitis.

Infectious bovine keratoconjunctivitis (IBK) is an important production limiting disease in cattle. Moraxella bovis has historically been considered the primary causal agent; however, vaccines have not been consistently shown as effective in controlling disease incidence. The purpose of this study was to examine the bacterial community of calf eyes prior to disease onset using high-throughput sequencing of 16S ribosomal RNA and determine if it was associated with IBK occurrence. The study was designed as a case-control nested within a randomized controlled trial (RCT). Eye swabs were collected from all spring-born calves without clinical signs of IBK (t0 swabs) on a research farm with a previous history of IBK disease outbreaks. At follow-up or weaning, calves were diagnosed as IBK positive or negative. The lag time between enrollment swabs (t0) and IBK diagnosis ranged from approximately one to three months. Cases were randomly selected from IBK positive calves and controls were selected from IBK negative calves (i.e. calves that did not exhibit clinical signs of IBK throughout the course of the RCT). Analysis of the fold-change differences between cases and controls did not reveal large-scale distinctions in bacterial composition. However, principal component analysis suggested bacterial composition differences between calf management groups, which were based on dam parity. Moraxella was found to be among the top ten most abundant genera in our population; however, the difference in abundance was not significant between the cases and controls. No large-scale differences in the bacterial communities of calves that did or did not develop IBK were observed in our population. Nevertheless, it remains unclear whether the "natural" bacterial population of the calf might ultimately impact disease status. Further study is warranted to examine bacterial taxa that were observed to be significantly more abundant in the cases or controls as potential vaccines/therapeutic targets.

Diagnostic value of coagulation factor and intracranial pressure monitoring in acute liver failure from heat stroke: case report and review of the literature.

BACKGROUND: Exertional heat stroke (HS) with resultant acute liver failure (ALF) is a rare condition with high mortality. Diagnosis of ALF in the context of HS is confounded by numerous laboratory abnormalities related to multisystem organ dysfunction. CASE REPORT: We present the case of a 20-year-old male athlete with exertional HS who developed ALF and was treated successfully with orthotopic liver transplantation. He remained well after 1 year with normal liver function and no permanent neurologic impairment. Diagnosis and treatment was guided by serial monitoring of coagulation factors and intracranial pressure (ICP). CONCLUSIONS: Currently, there are no well validated prognostic tools that predict the need for or survival with orthotopic liver transplantation for HS. We propose that serial monitoring of coagulation factors and, when safe and feasible, ICP monitoring may help to guide clinical decision making in this context.

Characterization of HCV-specific CD4+Th17 immunity in recurrent hepatitis C-induced liver allograft fibrosis.

Hepatitis C virus (HCV) recurrence with accelerated fibrosis following orthotopic liver transplantation (OLT) is a universal phenomenon. To evaluate mechanisms contributing to HCV induced allograft fibrosis/cirrhosis, we investigated HCV-specific CD4+Th17 cells and their induction in OLT recipients with recurrence utilizing 51 HCV+ OLT recipients, 15 healthy controls and 9 HCV- OLT recipients. Frequency of HCV specific CD4+ Tcells secreting IFN-γ, IL-17 and IL-10 was analyzed by ELISpot. Serum cytokines and chemokines were analyzed by LUMINEX. Recipients with recurrent HCV induced allograft inflammation and fibrosis/cirrhosis demonstrated a significant increase in frequency of HCV specific CD4+Th17 cells. Increased pro-inflammatory mediators (IL-17, IL-1ß, IL-6, IL-8 and MCP-1), decreased IFN-γ, and increased IL-4, IL-5 and IL-10 levels were identified. OLT recipients with allograft inflammation and fibrosis/cirrhosis demonstrated increased frequency of Foxp3+ regulatory T cells (Tregs) that inhibited HCV specific CD4+Th1 but not Th17 cells. This suggests that recurrent HCV infection in OLT recipients induces an inflammatory milieu characterized by increased IL-6, IL-1ß and decreased IFN-γ which facilitates induction of HCV specific CD4+Th17 cells. These cells are resistant to suppression by Tregs and may mediate an inflammatory cascade leading to cirrhosis in OLT recipients following HCV recurrence.