RLJ-NE-299A: a new plant based vaccine adjuvant

Alum has been in use since long as an adjuvant for vaccines. However, its use as a vaccine adjuvant offers limitation in supporting cell mediated response. Therefore, a new plant based product RLJ-NE-299A from Picrorhiza kurroa reported for its immunostimulatory activity, has been explored for its potential as an alternative adjuvant. In order to compare the adjuvant activity with alum, antigen-specific immune responses were evaluated following immunization with a formulation containing hepatitis B surface antigen (HBsAg) adjuvanted with RLJ-NE-299A and alum in mice. The adjuvant RLJ-NE-299A up-regulated remarkably the expression of Th1 cytokines IL-2, IL-12, IFN-gamma, TNF alpha and Th2 cytokine IL-4 in lymph node cell cultures after 2 weeks of primary immunization with HBsAg. Further, the levels of both immunoglobulins IgG2a (Th1) and IgG1 (Th2) subtypes increased profoundly in blood sera of mice immunized with HBsAg/RLJ-NE-299A. The results indicated that RLJ-NE-299A has strong potential to increase both cell mediated and humoral immune responses and is capable of sustaining the total antigen-specific antibody response. Besides, the RLJ-NE-299A provides a signal to gear up both CD4 helper cells (Th1 and Th2) and CD8 cells populations, which may have important implications for vaccination against hepatitis B virus. Variable doses of RLJ-NE-299A (0.312-40 microg) containing vaccine antigen (HBsAg) were well tolerated with optimum T cell response at 2.5 microg/ml. Not only this, the adjuvant was also able to induce cellular immune responses to HBsAg as evidenced by Th1 and Th2 cytokines upregulation, which enabled mice to overcome the unresponsiveness to antigen HBsAg encountered with alum-adjuvanted vaccine in otherwise non-responding mice population. The study presents evidence that the HPLC standardized fraction RLJ-NE-299A, is an adjuvant of choice over alum in improving and maintaining the improved immune status against HBsAg, and may also prove useful adjuvant candidate with other vaccine antigens, too.     

Distichiasis, congenital heart defects and mixed peripheral vascular anomalies

We report on a previously apparently unreported syndrome of distichiasis with congenital heart defects and with mixed peripheral vascular anomalies in a mother and her four children. The mother had a ventricular septal defect; both daughters had surgery for patent ductus arteriosus. Sinus bradycardia alone (elder son), with stress induced asystole (younger son), and with wandering atrial pacemaker (both daughters) are documented electrocardiographically. Three of the five have edema, two have visible varicosities, three have symptoms consistent with chronic venous disease of the legs, and the older daughter has complaints consistent with arterial disease in the legs. Doppler flow studies demonstrated post-phlebitic syndrome in all but the younger daughter, and vasospastic disease in the mother, older daughter, and second son.     

Childhood Gender Nonconformity and Recalled Perceived Parental and Peer Acceptance Thereof,Internalized Homophobia,and Psychological Well-Being Outcomes in Heterosexual and Gay Men from Poland

Archives of Sexual Behavior - The link between gender nonconformity and psychopathology may be due in part to negative childhood experiences resulting from other people’s reactions to gender...     

Association of serum level of chemerin with visceral fat obesity in type 2 diabetic patient

International Journal of Diabetes in Developing Countries - This study aimed to investigate whether circulating chemerin levels might be associated with visceral obesity and other metabolic...     

The rapid assessment for prostate imaging and diagnosis (RAPID) prostate cancer diagnostic pathway

Objective

To report outcomes within the Rapid Assessment for Prostate Imaging and Diagnosis (RAPID) diagnostic pathway, introduced to reduce patient and healthcare burdens and standardize delivery of pre-biopsy multiparametric magnetic resonance imaging (MRI) and transperineal biopsy.

Patients and Methods

A total of 2130 patients from three centres who completed the RAPID pathway (3 April 2017 to 31 March 2020) were consecutively entered as a prospective registry. These patients were also compared to a pre-RAPID cohort of 2435 patients. Patients on the RAPID pathway with an MRI score 4 or 5 and those with PSA density ≥0.12 and an MRI score 3 were advised to undergo a biopsy. Primary outcomes were rates of biopsy and cancer detection. Secondary outcomes included comparison of transperineal biopsy techniques, patient acceptability and changes in time to diagnosis before and after the introduction of RAPID.

Results

The median patient age and PSA level were 66 years and 6.6 ng/mL, respectively. Biopsy could be omitted in 43% of patients (920/2130). A further 7.9% of patients (168/2130) declined a recommendation for biopsy. The percentage of biopsies avoided among sites varied (45% vs 36% vs 51%; P < 0.001). In all, 30% (221/742) had a local anaesthetic (grid and stepper) transperineal biopsy. Clinically significant cancer detection (any Gleason score ≥3 + 4) was 26% (560/2130) and detection of Gleason score 3 + 3 alone constituted 5.8% (124/2130); detection of Gleason score 3 + 3 did not significantly vary among sites (P = 0.7). Among participants who received a transperineal targeted biopsy, there was no difference in cancer detection rates among local anaesthetic, sedation and general anaesthetic groups. In the 2435 patients from the pre-RAPID cohor, time to diagnosis was 32.1 days (95% confidence interval [CI] 29.3–34.9) compared to 15.9 days (95% CI 12.9–34.9) in the RAPID group. A total of 141 consecutive patient satisfaction surveys indicated a high satisfaction rate with the pathway; 50% indicated a preference for having all tests on a single day.

Conclusions

The RAPID prostate cancer diagnostic pathway allows 43% of men to avoid a biopsy while preserving good detection of clinically significant cancers and low detection of insignificant cancers, although there were some centre-level variations.     

Real life data on the biopsychosocial effects of Adalimumab in the management of hidradenitis suppurativa: A multicenter cross sectional analysis and consideration of a multisystem monitoring approach to follow up

Hidradenitis suppurativa (HS) is a chronic relapsing, remitting disease which results in the formation of inflammatory nodules and pustules in intertriginous areas. HS is a complex disease with known psychosocial impact. Adalimumab is a biologic, used for treatment resistant HS, which working by inactivating TNF‐alpha. Our primary objective was to determine the effects of adalimumab on HS‐PGA and DLQI scores in patients with HS that had been on the treatment for at least 6 months. Our secondary objective was to note and assess the significance of adverse effects and impacts on wider health, namely occupational and social. A retrospective cross‐sectional study was performed using clinic notes from routine follow ups in biologic clinics in three specialist HS centers. About 77% (n = 78/101) patients demonstrated improvements in their HS‐PGA scores. Significant improvements in the DLQI scores of the patient cohort (P = .0001, 95% CI ?12.8 to ?5.9) have also been demonstrated. A total of 31.7% (32/101) patients experienced adverse effects spanning multiple organ systems, with 27.7% (28/101) requiring treatment cessation. Three of these patients stopped due to the worsening of preexisting mental health symptoms. Adalimumab is effective in reducing HS‐PGA and DLQI scores, but patients still complain of systemic effects necessitating drug cessation in some instances. A holistic and multisystemic approach to follow up is required, and there is scope for further studies examining temporal causality in the context of adalimumab and its multisystemic physical and psychological effects.     

Evolution of efficacious pangenotypic hepatitis C virus therapies

Hepatitis C compromises the quality of life of more than 350 million individuals worldwide. Over the last decade, therapeutic regimens for treating hepatitis C virus (HCV) infections have undergone rapid advancements. Initially, structure-based drug design was used to develop molecules that inhibit viral enzymes. Subsequently, establishment of cell-based replicon systems enabled investigations into various stages of HCV life cycle including its entry, replication, translation, and assembly, as well as role of host proteins. Collectively, these approaches have facilitated identification of important molecules that are deemed essential for HCV life cycle. The expanded set of putative virus and host-encoded targets has brought us one step closer to developing robust strategies for efficacious, pangenotypic, and well-tolerated medicines against HCV. Herein, we provide an overview of the development of various classes of virus and host-directed therapies that are currently in use along with others that are undergoing clinical evaluation.