Novel polymorphisms in the octopamine receptor gene of amitraz resistant population of Rhipicephalus sanguineus sensu lato, in south India.

The brown dog tick or Rhipicephalus sanguineus sensu lato is an ixodid tick, responsible for the dissemination of pathogens that cause canine infectious diseases besides inflicting the direct effects of tick bite. The hot humid climate of Kerala, a south Indian state, is favorable for propagation of tick vectors and acaricides are the main stay of tick control. Though the resistance against synthetic pyrethroids is reported among these species, the status of amitraz resistance in R. sanguineus s. l. in the country is uncertain due to the lack of molecular characterisation data and scarce literature reports. Hence the present study was focused on the phenotypic detection and preliminary genotypic characterisation of amitraz resistance in the R. sanguineus s. l. A modified larval packet test (LPT) on a susceptible isolate was performed to determine the discriminating dose (DD). Further LPT-DD on 35 tick isolates was carried out to detect amitraz resistance robustly, along with that full dose response bioassays on the resistant isolates were performed. The results indicated that amitraz resistance is prevalent with 49 per cent of the samples being resistant. Amplification of exon 3 of octopamine receptor gene from both the susceptible and resistant larval isolates was carried out. Amplicons of ten pooled amitraz susceptible and ten pooled amitraz resistant representative samples were sequenced and analysed, unveiling a total of three novel non-synonymous mutations in the partial coding region at positions V32A, N41D and V58I in phenotypically resistant larval DNA samples. In silico analysis by homology modelling and molecular docking of the mutated and unmutated receptors showed that these mutations had reduced the binding affinity to amitraz. However, lack of mutations in the octopamine receptor gene in three of the pooled low order resistant R. sanguineus s. l. larval samples could be suggestive of other mechanisms associated with amitraz resistance in the region. Hence, further association studies should be carried out to confirm the association of these mutations with target insensitivity in R. sanguineus s. l. ticks, along with exploring the status of metabolic resistance and other mechanisms of resistance.

Bilateral orbital myositis in a patient with rheumatoid arthritis on treatment with tofacitinib: a report and review of literature.

Orbital myositis is a rare inflammatory condition affecting the extraocular muscles of the eyes. It has also been linked to systemic autoimmune diseases. We present a case of orbital myositis in a 57-year-old male undergoing treatment for rheumatoid arthritis (RA) with tofacitinib, a Janus kinase inhibitor (JAK). Prompt administration of intravenous steroids led to rapid symptom improvement. To date, only six published cases have documented the association between RA and orbital myositis. This is the first description of orbital myositis occurring during treatment with the anti-inflammatory drug tofacitinib, an increasingly used disease-modifying anti-rheumatic drug (DMARD). We review the literature and emphasize the importance of ongoing vigilance regarding adverse events linked to tofacitinib.

Effects of almond consumption compared with the consumption of traditional isocaloric cereal/pulse-based snacks on glycaemic control and gut health in adults with pre-diabetes in rural India: protocol for a 16-week, parallel-arm, cluster randomised controlled trial.

INTRODUCTION: Almonds have prebiotic potential to maintain gut health and regulate glycaemia. Western studies have shown their positive effects on preventing non-communicable diseases like diabetes and cardiovascular diseases. However, there is a lack of research involving Asian Indians, who have a higher predisposition to diabetes due to their unique 'Asian phenotype'. Therefore, this study aims to evaluate the impact of almond supplementation on glycaemic control and gut health in adults with pre-diabetes in rural India through a randomised clinical trial. METHODS AND ANALYSIS: A parallel cluster randomised controlled trial with 178 participants with pre-diabetes (assigned 1:1) aged 20-50 years, of both genders, with a body mass index of 18.9-25 kg/m2, will be conducted in rural areas of Chikkaballapur, Kolar and Rural Bangalore districts in India. The intervention group will receive 56 g of almonds as mid-morning snacks for 16 weeks, while the control group will receive cereal/pulse-based traditional isocaloric snacks under the closed supervision of the study investigators. The primary outcome of the study is HbA1c measured at the 16th week. The secondary outcomes-anthropometry, clinical and other biochemical parameters-will be measured at 0th, 8th and 16th weeks, and a subgroup of 120 participants will undergo gut health analysis. Glucagon-like peptide 1 analysis will be conducted on 30 participants at 0th and 16th weeks. Statistical analysis will be performed using SPSS for Windows V.27.0, and both intention-to-treat and per-protocol analyses will be conducted. ETHICS AND DISSEMINATION: Ethics approval was obtained from the Institutional Ethics Committee at Ramaiah Medical College, Bangalore, Karnataka, India (DRPEFP7672021). We will obtain the informed written consent of the participants prior to screening and enrolling them in the study. Results from this trial will be disseminated through publication in peer-reviewed journals and scientific gatherings. TRIAL REGISTRATION NUMBER: Clinical Trial Registry of India (CTRI/2023/03/050421).

Mathematical study of the contamination phenomenon in the culture of tubercle bacilli

This paper demonstrates that when 'spot' specimens of sputum are cultured for tubercle bacilli on Lowenstein-Jensen medium, bacterial contamination occurs at random and follows a Poisson distribution. Over a period of 14 years, contamination rates with overnight 'collection' specimens (4.5 to 10.2%) were substantially higher than with spot specimens (1.3 to 4.0%), but the correlation between the two was very high (r = 0.98). In contrast to spot specimens, the incidence of contamination with collection specimens was significantly higher for females than for males, and significant variation was also found between patients of the same sex. In consequence, the Poisson distribution, which assumes a constant contamination rate for all patients, did not provide a satisfactory fit to the data on collection specimens. However, a negative binomial distribution, which incorporates individual variability in contamination rate, provided a good fit. The reasons for individual variability are discussed.