articles epidemiology several identified from the literature (21-23). These protocols varied by anatomical site, posture, respiratory phase, and time since last meal. Methods and Procedures study design and settingA cross-sectional study was conducted from September 2005 to April 2006 at the All India Institute of Medical Sciences, New Delhi, a tertiary care hospital in North India. study populationHealthy volunteers (N = 123; males = 48, females = 75), mostly residents of New Delhi, of age >16 years were recruited by using local posters and advertisements. We excluded subjects with any systemic illness, pregnancy, ascites, intestinal obstruction tumor, or any other abdominal pathology. Anthropometric measurements were done after an overnight fast at the Metabolic Research Center. Appropriate informed consent was given by all volunteers before participation.The study protocol was approved by institutional review board on human research. Also, we certify that all applicable institutional regulations concerning the ethical conduct of research with human volunteers were followed during this research. anthropometric measurementsParticipants relaxed for 15 min before the measurements were taken. Body weight (to nearest 0.1 kg) and height (to nearest 0.01 m) were measured while subjects were dressed in light clothing and stood barefoot, erect with eyes directed straight ahead. Hip circumference (measured at the largest posterior extension of the buttocks) and WC were measured using a heavy-duty inelastic tape, kept in contact with skin without pressing it. WC measurements (to the nearest 0.001 m) varying by anatomical site, phases of respiration, and time since last meal were recorded. Special attention was given to keep the tape perpendicular to the long axis of the subject's body with the help of another observer. Volunteers were asked to eat a routine meal and then report back within 10 min for postmeal measures. WC was measured at two anatomical locations as follows: suprailiac (just lateral and above the iliac crest) in midaxillary line (according to NIH protocol (20)) and midabdomen (midpoint between subcostal and suprailiac landmarks) (according to World Health Organization (WHO) protocol (1)). Normal posture was defined as standing barefoot in a comfortable position with eyes directed straight ahead, while erect posture refers to standing barefoot on both feet with heels, buttocks, and occiput in contact with a straight wall; both arms hanging loosely by the side of body; and eyes directed straight ahead. Normal breathing was defined as breathing at a regular pace with tidal volume, and the measure was taken irrespective of the respiratory phase. Other phases of respiration, like normal end-expiration and end-inspiration, were demonstrated to the subjects and defined as described in Table 1. Similarly, forced end-inspiration and end-expiration were demonstrated and WC measured while the subjected inhaled to maximum lung capacity and then exhaled as hard and as completely as possible.Two repeat measurements of ...

QacA is a drug:H + antiporter with 14 transmembrane helices that confers antibacterial resistance to methicillin-resistant Staphylococcus aureus strains, with homologs in other pathogenic organisms. It is a highly promiscuous antiporter, capable of H +-driven efflux of a wide array of cationic antibacterial compounds and dyes. Our study, using a homology model of QacA, reveals a group of six protonatable residues in its vestibule. Systematic mutagenesis resulted in the identification of D34 (TM1), and a cluster of acidic residues in TM13 including E407 and D411 and D323 in TM10, as being crucial for substrate recognition and transport of monovalent and divalent cationic antibacterial compounds. The transport and binding properties of QacA and its mutants were explored using whole cells, inside-out vesicles, substrate-induced H + release and microscale thermophoresis-based assays. The activity of purified QacA was also observed using proteoliposome-based substrate-induced H + transport assay. Our results identify two sites, D34 and D411 as vital players in substrate recognition, while E407 facilitates substrate efflux as a protonation site. We also observe that E407 plays an additional role as a substrate recognition site for the transport of dequalinium, a divalent quaternary ammonium compound. These observations rationalize the promiscuity of QacA for diverse substrates. The study unravels the role of acidic residues in QacA with implications for substrate recognition, promiscuity and processive transport in multidrug efflux transporters, related to QacA.

Background Patients with systemic lupus erythematosus (SLE) are at risk of developing COVID-19 due to underlying immune abnormalities and regular use of immunosuppressant medications. We aimed to evaluate the presence of SARS-CoV-2 IgG antibodies in patients with SLE with or without previous COVID-19-related symptoms or RT-PCR-confirmed SARS-CoV-2 infection. Methods For this analysis, we included patients with SLE from two cohorts based in New York City: the Web-based Assessment of Autoimmune, Immune-Mediated and Rheumatic Patients during the COVID-19 pandemic (WARCOV) study; and the NYU Lupus Cohort (a prospective registry of patients at NYU Langone Health and NYC Health + Hospitals/Bellevue). Patients in both cohorts were tested for SARS-CoV-2 IgG antibodies via commercially available immunoassays, processed through hospital or outpatient laboratories. Patients recruited from the NYU Lupus Cohort, referred from affiliated providers, or admitted to hospital with COVID-19 were tested for SARS-CoV-2 IgG antibodies as part of routine surveillance during follow-up clinical visits. Findings 329 patients with SLE were included in this analysis, 146 from the WARCOV study and 183 from the NYU Lupus Cohort, and were tested for SARS-CoV-2 antibodies between April 29, 2020, and Feb 9, 2021. 309 (94%) were women and 91 (28%) were of Hispanic ethnicity. 51 (16%) of 329 patients had a positive SARS-CoV-2 IgG antibody test. Seropositive patients were more likely than seronegative patients to be Hispanic (24 [47%] of 51 vs 67 [24%] of 278). Other demographic variables, SLE-specific factors, and immunosuppressant use were not associated with SARS-CoV-2 positivity. Of the 29 patients with COVID-19 previously confirmed by RT-PCR, 18 (62%) were on immunosuppressants; 24 (83%) of 29 patients tested positive for SARS-CoV-2 IgG antibodies. Of 17 patients who had symptoms of COVID-19 but negative concurrent RT-PCR testing, one (6%) developed an antibody response. Of 26 patients who had COVID-19-related symptoms but did not undergo RT-PCR testing, six (23%) developed an antibody response. Of 83 patients who had no symptoms of COVID-19 and no RT-PCR testing, four (5%) developed an antibody response. Among 36 patients who were initially SARS-CoV-2 IgG positive, the majority maintained reactivity serially (88% up to 10 weeks, 83% up to 20 weeks, and 80% up to 30 weeks). Seven (70%) of ten patients with confirmed COVID-19 had antibody positivity beyond 30 weeks from disease onset.Interpretation Most patients with SLE and confirmed COVID-19 were able to produce and maintain a serological response despite the use of a variety of immunosuppressants, providing reassurance about the efficacy and durability of humoral immunity and possible protection against re-infection with SARS-CoV-2.

In phase I and II trials taxane chemotherapeutic agents reported side effects, including myelosuppression, peripheral edema, and fluid retention. With further use of these agents, studies in the late 1980s and early 1990s began to report peripheral neuropathy and proximal muscle weakness as common complaints, the later with unexplained pathophysiology. We report a 65-year-old Hispanic woman with estrogen receptor (ER) and progesterone receptor (PR) positive invasive ductal breast carcinoma who presented with right thigh pain and swelling eight days after her third infusion of docetaxel (a taxane chemotherapeutic) and cyclophosphamide. Laboratory findings were notable for elevation in creatine phosphokinase (CPK), aldolase, and erythrocyte sedimentation rate (ESR); a magnetic resonance imaging (MRI) of her lower extremities showed evidence of bilateral muscle edema involving the anterior compartment muscles of the thighs. A workup to rule out other causes of myositis was negative. Docetaxel was not reintroduced and the patient improved with corticosteroids. Since 2005 this is, to our knowledge, the fifth reported case of docetaxel related inflammatory myositis. Taxanes have been noted to cause disabling but transient arthralgias and myalgias; it is important to consider the possibility of inflammatory myopathy as a possible complication in patients undergoing treatment with these agents.