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Four lytic mycobacteriophages, namely, SynergyX, Abinghost, Bananafish, and Delton, were isolated from soil in Washington, DC, using the bacterial host Mycobacterium smegmatis mc

Background Minimally invasive intratumoural administration of thermoresponsive hydrogels, that transition from liquid to gel in response to temperature, has been proposed as a potential treatment modality for solid tumours. The aim of this study was to assess the inherent cytotoxicity of a poloxamer-based thermoresponsive hydrogel in a murine xenograft model of lung cancer. Methods In vitro viability assessment was carried out in a lung cancer (A549) and non-cancerous (Balb/c 3T3 clone A31) cell line. Following intratumoural administration of saline or the thermoresponsive hydrogel to an A549 xenograft model in female Athymic Nude-Foxn1nu mice (n = 6/group), localisation was confirmed using IVIS imaging. Tumour volume was assessed using callipers measurements over 14 days. Blood serum was analysed for liver and kidney damage and ex vivo tissue samples were histologically assessed. Results The thermoresponsive hydrogel demonstrated a dose-dependent cancer cell-specific toxicity in vitro and was retained in situ for at least 14 days in the xenograft model. Tumour volume increase was statistically significantly lower than saline treated control at day 14 (n = 6, p = 0.0001), with no associated damage of hepatic or renal tissue observed. Conclusions Presented is a poloxamer-based thermoresponsive hydrogel, suitable for intratumoural administration and retention, which has demonstrated preliminary evidence of local tumour control, with minimal off-site toxicity.

Objective To provide updated American College of Rheumatology (ACR) recommendations on rheumatoid arthritis (RA) disease activity measurements to facilitate a treat-to-target approach in routine clinical care. Methods A working group conducted a systematic literature review from the time of the prior ACR recommendations literature search. Properties of disease activity measures were abstracted, and study quality was assessed using the Consensus-Based Standards for the selection of Health Measurement Instruments 4-point scoring method, allowing for overall level of evidence assessment. Measures that fulfilled a minimum standard were identified, and through a modified Delphi process preferred measures were selected for regular use in most clinic settings. Results The search identified 5,199 articles, of which 110 were included in the review. This search identified 46 RA disease activity measures that contained patient, provider, laboratory, and/or imaging data. Descriptions of the measures, properties, study quality, level of evidence, and feasibility were abstracted and scored. Following a modified Delphi process, 11 measures fulfilled a minimum standard for regular use in most clinic settings, and 5 measures were recommended: the Disease Activity Score in 28 Joints with Erythrocyte Sedimentation Rate or C-Reactive Protein Level, Clinical Disease Activity Index, Simplified Disease Activity Index, Routine Assessment of Patient Index Data 3, and Patient Activity Scale-II. Conclusion We have updated prior ACR recommendations for preferred RA disease activity measures, identifying 11 measures that met a minimum standard for regular use and 5 measures that were preferred for regular use in most clinic settings.

Two temperate mycobacteriophages, Dallas and Jonghyun, were isolated from soil in Washington, DC, using the bacterial host Mycobacterium smegmatis mc 2 155. Analysis of the genomes revealed that Dallas and Jonghyun belong to clusters J and G, respectively. The structures of the genomes are typical of their respective clusters.

The objective of this study is to describe the clinical features and outcomes of patients with the newly defined vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic (VEXAS) syndrome. Nine men with somatic mutations in the UBA1 gene were identified; the most frequent variant was p.Met41Thr (7 of 9, 78%). The median age at VEXAS diagnosis was 74 (67, 76.5) years, and patients had a median duration of symptoms for 4 years before diagnosis. Refractory constitutional symptoms (88%), ear and nose chondritis (55%), and inflammatory arthritis (55%) were common clinical features. Vasculitis was noted in 44%. All patients had significantly elevated inflammatory markers and macrocytic anemia. Thrombocytopenia was present in 66% at diagnosis of VEXAS. Eight patients had bone marrow biopsies performed. All bone marrows were hypercellular, and there was vacuolization of the erythroid (100%) or myeloid precursors (75%). Glucocorticoids attenuated symptoms at prednisone doses ≥20 mg per day, but no other immunosuppressive agent showed consistent long-term control of disease. One patient with coexisting plasma-cell myeloma received plasma-cell-directed therapy with improvement of the inflammatory response, which is a novel finding. In conclusion, VEXAS syndrome is a clinically heterogeneous, treatment-refractory inflammatory condition caused by somatic mutation of the UBA1 gene. Patients often present with overlapping rheumatologic manifestations and persistent hematologic abnormalities. As such, internists and subspecialists, including pathologists, should be aware of this condition to avert diagnostic delay, now that the etiology of this syndrome is known.

Background Depression is associated with insulin resistance (IR). However, the potential beneficial effect, on antidepressant treatment response, of adjunctive therapy with insulin sensitivity-enhancing lifestyle and dietary interventions (exercise; supplementation with: vitamin D, magnesium, zinc, probiotics or omega-3 fatty acids) has not been systematically explored. Aims To determine the effect of the above stated adjuncts on antidepressant treatment response in clinically depressed patients via a systematic review and meta-analysis. Methods RCTs which assessed the effect, on antidepressant treatment response of adjunctive therapy with any of the interventions in comparison with treatment as usual were included. Results The interventions had a significant antidepressant effect, with SMD for follow-up (end of study) scores and change (from baseline) scores being -0.88, [95% CI: -1.19 to -0.57; P < 0.001] and -1.98 [95% CI -2.86 to -1.10; P < 0.001], respectively. The odds ratio (OR) for remission was 2.28 (95% CI 1.42 to 3.66; P < 0.001). The number-needed-to-treat (NNT) for remission was 6. Subgroup analysis of the follow-up scores revealed age effect: SMD significant in those with mean age ≤50 (-1.02 SMD; 95% CI: -1.40 to -0.64; p < 0.001) and insignificant in those with mean age >50 (-0.38 SMD (95% CI: -0.82 to 0.05; P = 0.08)). Also, the interventions were more beneficial among outpatients- SMD: -0.97 (95% CI: -1.32 to -0.62; P < 0.001) compared to inpatients- SMD: -0.34 (95% CI: -0.88 to 0.20; P = 0.22). Sensitivity analysis did not change the results. Conclusion The finding that antidepressant treatment response may be improved using insulin sensitivity-enhancing lifestyle and dietary adjuncts is worthy of further exploration., Psychiatry; Biological Psychiatry; Depression; Pharmacology; Endocrinology; Endocrine System; depression; Adjuncts; Insulin sensitivity; Lifestyle; Dietary Supplements; Antidepressants; systematic review.

ObjectivePrevious prevalence estimates of POtentially Serious Alcohol–Medication INteractions in Older adults (POSAMINO) are based on in-home inventories of medications; however, this method is associated with under-reporting of medications when compared with dispensing records. This study aims to estimate the prevalence of POSAMINO among community-dwelling older adults using drug dispensing data from the community pharmacy setting.DesignCross-sectional study.SettingIrish Community Pharmacy.Participants1599 consecutive older adults presenting with a prescription to 1 of 120 community pharmacies nationwide; community-dwelling, aged ≥65 years, able to speak and understand English, with no evidence of cognitive impairment. The mean age of sample was 75.5 years (SD 6.5); 55% (n=884) female.Measures38 POSAMINO criteria were identified using participants’ pharmacy dispensing records linked to self-reported alcohol consumption (beverage-specific quantity and frequency measures) over the last 12 months.ResultsThe overall prevalence of POSAMINO in the study population was 28%, with 10% at risk of at least one POSAMINO criteria and 18% at risk of two or more. Exposure to POSAMINO most commonly involved cardiovascular agents (19%) and central nervous system agents (15%). Exposure to a higher number of POSAMINO criteria was associated with younger age (adjusted incident rate ratio (AIRR): 0.97; 95% CI: 0.95 to 0.98), male sex (AIRR: 0.55; 95% CI: 0.45 to 0.67) and a higher number of comorbidities (AIRR: 1.05; 95% CI: 1.01 to 1.13).ConclusionThis study adds to the growing body of evidence, which suggests that older adults are vulnerable to potentially serious alcohol–medication interactions, particularly those involving cardiovascular and central nervous system agents, increasing their risk of orthostatic hypotension, gastrointestinal bleeds and increased sedation. Application of the POSAMINO criteria at the point of prescribing may facilitate the risk stratification of older adults and prioritise alcohol screening and brief alcohol interventions in those at greatest risk of harm.