Autonomic function test during the COVID-19 pandemic: the Stanford experience

Clinical Autonomic Research -     

Towards more evidenced-based therapies for postural tachycardia syndrome and other updates on recent autonomic research

Clinical Autonomic Research -     

MALDI mass sequencing and biochemical characterization of Setaria cervi protein tyrosine phosphatase

A 30-kDa acid phosphatase with protein tyrosine phosphatase activity was identified in Setaria cervi (ScPTP). The enzyme was purified to homogeneity using three-step column chromatography. Matrix-assisted laser desorption/ionization-time of flight (MALDI-TOF) analysis of purified ScPTP yielded a total of eight peptides matching most closely to phosphoprotein phosphatase of Ricinus communis (RcPP). A hydrophilicity plot of RcPP revealed the presence of these peptides in the hydrophilic region, suggesting their antigenic nature. The substrate specificity of ScPTP with ortho-phospho-l-tyrosine and inhibition with sodium orthovanadate and ammonium molybdate affirmed it as a protein tyrosine phosphatase. ScPTP was also found to be tartrate resistant. The Km and Vmax were 6.60 mM and 83.3 μM/ml/min, respectively, with pNPP and 8.0 mM and 111 μM/ml/min, respectively, with ortho-phospho-l-tyrosine as the substrate. The Ki value with sodium orthovanadate was calculated to be 16.10 mM. Active site modification with DEPC, EDAC and pHMB suggested the presence of histidine, cysteine and aspartate at its active site. Thus, on the basis of MALDI-TOF and biochemical studies, it was confirmed that purified acid phosphatase is a PTP.     

The Citrus yellow mosaic badnavirus ORFI functions as a RNA-silencing suppressor

Virus Genes - Citrus yellow mosaic badnavirus (CMBV) causes mosaic disease in all economically important citrus cultivars of India, with losses reaching up to 70%. CMBV belongs to the genus...     

Associations of 25‐Hydroxyvitamin D and 1,25‐Dihydroxyvitamin D With Bone Mineral Density,Bone Mineral Density Change,and Incident Nonvertebral Fracture

Relationships between 1,25‐dihydroxyvitamin D (1,25(OH)₂D) and skeletal outcomes are uncertain. We examined the associations of 1,25(OH)₂D with bone mineral density (BMD), BMD change, and incident non‐vertebral fractures in a cohort of older men and compared them with those of 25‐hydroxyvitamin D (25OHD). The study population included 1000 men (aged 74.6 ± 6.2 years) in the Osteoporotic Fractures in Men (MrOS) study, of which 537 men had longitudinal dual‐energy X‐ray absorptiometry (DXA) data (4.5 years of follow‐up). A case‐cohort design and Cox proportional hazards models were used to test the association between vitamin D metabolite levels and incident nonvertebral and hip fractures. Linear regression models were used to estimate the association between vitamin D measures and baseline BMD and BMD change. Interactions between 25OHD and 1,25(OH)₂D were tested for each outcome. Over an average follow‐up of 5.1 years, 432 men experienced incident nonvertebral fractures, including 81 hip fractures. Higher 25OHD was associated with higher baseline BMD, slower BMD loss, and lower hip fracture risk. Conversely, men with higher 1,25(OH)₂D had lower baseline BMD. 1,25(OH)₂D was not associated with BMD loss or nonvertebral fracture. Compared with higher levels of calcitriol, the risk of hip fracture was higher in men with the lowest 1,25(OH)₂D levels (8.70 to 51.60 pg/mL) after adjustment for baseline hip BMD (hazard ratio [HR] = 1.99, 95% confidence interval [CI] 1.19–3.33). Adjustment of 1,25(OH)₂D data for 25OHD (and vice versa) had little effect on the associations observed but did attenuate the hip fracture association of both vitamin D metabolites. In older men, higher 1,25(OH)₂D was associated with lower baseline BMD but was not related to the rate of bone loss or nonvertebral fracture risk. However, with BMD adjustment, a protective association for hip fracture was found with higher 1,25(OH)₂D. The associations of 25OHD with skeletal outcomes were generally stronger than those for 1,25(OH)₂D. These results do not support the hypothesis that measures of 1,25(OH)₂D improve the ability to predict adverse skeletal outcomes when 25OHD measures are available. © 2015 American Society for Bone and Mineral Research.     

Increase in minimum inhibitory concentration to quinolones and ceftriaxone in salmonellae causing enteric fever

Multidrug resistance among Salmonella typhi is well known. Reports of treatment failure in enteric fever with Ciprofloxacin made us undertake this study to determine the antibiotic susceptibility pattern of S. typhi and S. paratyphi A isolated from typhoid bacteremia cases, by disc diffusion and MIC by broth dilution method. A total of 50 strains were tested, 48 of Salmonella typhi and 2 of S. paratyphi A. The disc diffusion method was done using ampicillin, chloramphenicol, cotrimoxazole, tetracycline, ciprofloxacin, ofloxacin, cefuroxime and ceftriaxone as antibiotics. The MIC was performed using ciproloxacin, ofloxacin and ceftriaxone based on standard procedure. ACCOT resistance as determined by disc diffusion method was seen in 68% of isolates. All the strains remained susceptible to flouroquinolones cephalosporins and aminoglycosides. The MIC of ciprofloxacin, ofloxacin and ceftriaxone were in the recommended range of susceptibility as given by NCCLS, 14 (28%) strains had MIC of ciprofloxacin greater than 0.5 ug/ml with 4 strains having an MIC of 1.56 ug/ml; 25 (50%) strains had MIC of ofloxacin greater than 0.5 ug/ml and 20 (40%) strains had MIC of ceftriaxone greater than 0.5 ug/ml. The high levels of MIC of ciprofloxacin may account for treatment failure cases. The rising levels of MIC of ofloxacin and ceftriaxone in S. typhi and S. paratyphi is also of concern. We document here the emergence of high levels of MIC not only to ciprofloxacin, but also ofloxacin and ceftriaxone in S. typhi and S. paratyphi A. We recommend that MIC levels of ofloxacin and ceftriaxone should be monitored along with ciprofloxacin in treatment failure cases of enteric fever.     

Indian tick typhus presenting as Purpura fulminans

Seriously ill patients presenting with purpura fulminans, sepsis and multi-organ failure often require extensive diagnostic workup for proper diagnosis and management. Host of common infections prevalent in the tropics, e.g. malaria, dengue; other septicemic infections e.g. meningococcemia, typhoid, leptospirosis, toxic shock syndrome, scarlet fever, viral exanthems like measles, infectious mononucleosis, collagen vascular diseases (Kawasaki disease, other vasculitis) diseases, and adverse drug reactions are often kept in mind, and the index of suspicion for rickettsial illness is quite low. We present a case of Indian tick typhus presenting with purpura fulminans (retiform purpura all over the body), sepsis and multiorgan failure without lymphadenopathy and eschar, successfully treated with doxycycline and discharged home. Hence, a high index clinical suspicion and prompt administration of a simple therapy has led to successful recovery of the patient.