Effect of telmisartan on sub-acute model of inflammation in male Wistar rats - an experimental study

Background: Cardiovascular diseases remain the major cause of death and premature disability in developed societies.Current predictions estimate that by the year 2020 cardiovascular diseases, notably atherosclerosis and hypertension will become leading global causes of total disease burden. The objective of the study was to investigate the influence of telmisartan on sub-acute model of inflammation in adult male Wistar rats.Methods: After obtaining ethical clearance from Institutional Animal Ethics Committee, animals were allotted to the three groups i.e. control, aspirin and telmisartan (n=6 animals in each group). The effect of telmisartan on inflammation was studied using sub-acute (Cotton pellet granuloma and histopathologic examination of grass piths) models. Experiment was conducted according to the Committee for the purpose of Control and Supervision of Experiments on Animals (CPCSEA) guidelines. Analysis was done using one way ANOVA followed by post hoc tests of Dunnett’s and Bonferroni’s. P<0.05 was considered as statistically significant.Results: In the present study telmisartan showed significant anti-inflammatory activity in sub-acute models of inflammation.Conclusions: In view of role of inflammation in the pathogenesis of atherosclerosis and their complications, treatment by telmisartan can reduce complications by virtue of its anti-inflammatory activity, in addition to its antihypertensive effect. Also this study may help to open new avenues for therapeutic indications of telmisartan.

Influence of Tinospora cordifolia on wound healing in wistar rats

Background: T.cordifolia is widely used in veterinary folk medicine ayurvedic system of medicine. It is known to possess various properties. In a study T.cordifolia promoted wound healing in diabetic patients. However, one study showed that octacosanol content in T.cordifolia possessed anti-angiogenic activity which can hinder wound healing. Therefore, effect of T.cordifolia on wound healing appears to be controversial and there is scarcity of information regarding its effect on wound healing in animal models.Methods: Excision wound, resutured incision wound and dead space wounds were inflicted under light thiopentone anesthesia in male wistar rats (n=6 in each group). Methanol extract of T.cordifolia stem in the dose of 250 mg/kg was administered orally once a day for 10 days in resutured incision (assessed by wound breaking strength), dead space (granuloma dry weight and histopathology of granulation tissue) excision wounds was monitored by planimetry. Data was expressed as mean±SEM and analyzed by student’s t-test. p <0.05 was considered as significant.Results: The results of the present study revealed that T.cordifolia significantly promotes wound healing in all the three models viz. enhanced wound contraction and decreased days for complete epithelization in excision wound; increased breaking strength in resutured incision wound; increased granuloma dry weight and cellular infiltration in granulation tissue.Conclusions: T.cordifolia significantly (p<0.05) promoted wound healing in all the three models of wound in male wistar rats

Global uncertainty in the diagnosis of neurological complications of SARS-CoV-2 infection by both neurologists and non-neurologists: An international inter-observer variability study

Introduction: Uniform case definitions are required to ensure harmonised reporting of neurological syndromes associated with SARS-CoV-2. Moreover, it is unclear how clinicians perceive the relative importance of SARS-CoV-2 in neurological syndromes, which risks under- or over-reporting. Methods: We invited clinicians through global networks, including the World Federation of Neurology, to assess ten anonymised vignettes of SARS-CoV-2 neurological syndromes. Using standardised case definitions, clinicians assigned a diagnosis and ranked association with SARS-CoV-2. We compared diagnostic accuracy and assigned association ranks between different settings and specialties and calculated inter-rater agreement for case definitions as “poor” (κ ≤ 0.4), “moderate” or “good” (κ > 0.6). Results: 1265 diagnoses were assigned by 146 participants from 45 countries on six continents. The highest correct proportion were cerebral venous sinus thrombosis (CVST, 95.8%), Guillain-Barré syndrome (GBS, 92.4%) and headache (91.6%) and the lowest encephalitis (72.8%), psychosis (53.8%) and encephalopathy (43.2%). Diagnostic accuracy was similar between neurologists and non-neurologists (median score 8 vs. 7/10, p = 0.1). Good inter-rater agreement was observed for five diagnoses: cranial neuropathy, headache, myelitis, CVST, and GBS and poor agreement for encephalopathy. In 13% of vignettes, clinicians incorrectly assigned lowest association ranks, regardless of setting and specialty. Conclusion: The case definitions can help with reporting of neurological complications of SARS-CoV-2, also in settings with few neurologists. However, encephalopathy, encephalitis, and psychosis were often misdiagnosed, and clinicians underestimated the association with SARS-CoV-2. Future work should refine the case definitions and provide training if global reporting of neurological syndromes associated with SARS-CoV-2 is to be robust

Managing hyperemesis gravidarum: a multimodal challenge

Up to 90% of pregnant women experience nausea and vomiting. When prolonged or severe, this is known as hyperemesis gravidarum (HG), which can, in individual cases, be life threatening. In this article the aetiology, diagnosis and treatment strategies will be presented based on a selective literature review. Treatment strategies range from outpatient dietary advice and antiemetic drugs to hospitalization and intravenous (IV) fluid replacement in persistent or severe cases. Alternative methods, such as acupuncture, are not yet evidence based but sometimes have a therapeutic effect

Bi-allelic Loss-of-Function CACNA1B Mutations in Progressive Epilepsy-Dyskinesia.

The occurrence of non-epileptic hyperkinetic movements in the context of developmental epileptic encephalopathies is an increasingly recognized phenomenon. Identification of causative mutations provides an important insight into common pathogenic mechanisms that cause both seizures and abnormal motor control. We report bi-allelic loss-of-function CACNA1B variants in six children from three unrelated families whose affected members present with a complex and progressive neurological syndrome. All affected individuals presented with epileptic encephalopathy, severe neurodevelopmental delay (often with regression), and a hyperkinetic movement disorder. Additional neurological features included postnatal microcephaly and hypotonia. Five children died in childhood or adolescence (mean age of death: 9 years), mainly as a result of secondary respiratory complications. CACNA1B encodes the pore-forming subunit of the pre-synaptic neuronal voltage-gated calcium channel Cav2.2/N-type, crucial for SNARE-mediated neurotransmission, particularly in the early postnatal period. Bi-allelic loss-of-function variants in CACNA1B are predicted to cause disruption of Ca2+ influx, leading to impaired synaptic neurotransmission. The resultant effect on neuronal function is likely to be important in the development of involuntary movements and epilepsy. Overall, our findings provide further evidence for the key role of Cav2.2 in normal human neurodevelopment.MAK is funded by an NIHR Research Professorship and receives funding from the Wellcome Trust, Great Ormond Street Children's Hospital Charity, and Rosetrees Trust. E.M. received funding from the Rosetrees Trust (CD-A53) and Great Ormond Street Hospital Children's Charity. K.G. received funding from Temple Street Foundation. A.M. is funded by Great Ormond Street Hospital, the National Institute for Health Research (NIHR), and Biomedical Research Centre. F.L.R. and D.G. are funded by Cambridge Biomedical Research Centre. K.C. and A.S.J. are funded by NIHR Bioresource for Rare Diseases. The DDD Study presents independent research commissioned by the Health Innovation Challenge Fund (grant number HICF-1009-003), a parallel funding partnership between the Wellcome Trust and the Department of Health, and the Wellcome Trust Sanger Institute (grant number WT098051). We acknowledge support from the UK Department of Health via the NIHR comprehensive Biomedical Research Centre award to Guy's and St. Thomas' National Health Service (NHS) Foundation Trust in partnership with King's College London. This research was also supported by the NIHR Great Ormond Street Hospital Biomedical Research Centre. J.H.C. is in receipt of an NIHR Senior Investigator Award. The research team acknowledges the support of the NIHR through the Comprehensive Clinical Research Network. The views expressed are those of the author(s) and not necessarily those of the NHS, the NIHR, Department of Health, or Wellcome Trust. E.R.M. acknowledges support from NIHR Cambridge Biomedical Research Centre, an NIHR Senior Investigator Award, and the University of Cambridge has received salary support in respect of E.R.M. from the NHS in the East of England through the Clinical Academic Reserve. I.E.S. is supported by the National Health and Medical Research Council of Australia (Program Grant and Practitioner Fellowship)

Influence of Tinospora cordifolia on wound healing in wistar rats

Background: T.cordifolia is widely used in veterinary folk medicine ayurvedic system of medicine. It is known to possess various properties. In a study T.cordifolia promoted wound healing in diabetic patients. However, one study showed that octacosanol content in T.cordifolia possessed anti-angiogenic activity which can hinder wound healing. Therefore, effect of T.cordifolia on wound healing appears to be controversial and there is scarcity of information regarding its effect on wound healing in animal models.Methods: Excision wound, resutured incision wound and dead space wounds were inflicted under light thiopentone anesthesia in male wistar rats (n=6 in each group). Methanol extract of T.cordifolia stem in the dose of 250 mg/kg was administered orally once a day for 10 days in resutured incision (assessed by wound breaking strength), dead space (granuloma dry weight and histopathology of granulation tissue) excision wounds was monitored by planimetry. Data was expressed as mean±SEM and analyzed by student’s t-test. p &lt;0.05 was considered as significant.Results: The results of the present study revealed that T.cordifolia significantly promotes wound healing in all the three models viz. enhanced wound contraction and decreased days for complete epithelization in excision wound; increased breaking strength in resutured incision wound; increased granuloma dry weight and cellular infiltration in granulation tissue.Conclusions: T.cordifolia significantly (p&lt;0.05) promoted wound healing in all the three models of wound in male wistar rats

Global uncertainty in the diagnosis of neurological complications of SARS-CoV-2 infection by both neurologists and non-neurologists: An international inter-observer variability study.

IntroductionUniform case definitions are required to ensure harmonised reporting of neurological syndromes associated with SARS-CoV-2. Moreover, it is unclear how clinicians perceive the relative importance of SARS-CoV-2 in neurological syndromes, which risks under- or over-reporting.MethodsWe invited clinicians through global networks, including the World Federation of Neurology, to assess ten anonymised vignettes of SARS-CoV-2 neurological syndromes. Using standardised case definitions, clinicians assigned a diagnosis and ranked association with SARS-CoV-2. We compared diagnostic accuracy and assigned association ranks between different settings and specialties and calculated inter-rater agreement for case definitions as "poor" (κ ≤ 0.4), "moderate" or "good" (κ > 0.6).Results1265 diagnoses were assigned by 146 participants from 45 countries on six continents. The highest correct proportion were cerebral venous sinus thrombosis (CVST, 95.8%), Guillain-Barré syndrome (GBS, 92.4%) and headache (91.6%) and the lowest encephalitis (72.8%), psychosis (53.8%) and encephalopathy (43.2%). Diagnostic accuracy was similar between neurologists and non-neurologists (median score 8 vs. 7/10, p = 0.1). Good inter-rater agreement was observed for five diagnoses: cranial neuropathy, headache, myelitis, CVST, and GBS and poor agreement for encephalopathy. In 13% of vignettes, clinicians incorrectly assigned lowest association ranks, regardless of setting and specialty.ConclusionThe case definitions can help with reporting of neurological complications of SARS-CoV-2, also in settings with few neurologists. However, encephalopathy, encephalitis, and psychosis were often misdiagnosed, and clinicians underestimated the association with SARS-CoV-2. Future work should refine the case definitions and provide training if global reporting of neurological syndromes associated with SARS-CoV-2 is to be robust

Genetic testing for clinically suspected spinocerebellar ataxias: report from a tertiary referral centre in India

Spinocerebellar ataxias (SCAs) are a heterogeneous group of neurodegenerative syndromes, characterized by a wide range of muscular weakness and motor deficits, caused due to cerebellar degeneration. The prevalence of the syndromes of SCA varies across the world and is known to be linked to the instability of trinucleotide repeats within the high-end normal alleles, along with susceptible haplotype. We estimated sizes of the CAG or GAA repeat expansions at the SCA1, SCA2, SCA3, SCA12 and frataxin loci among 864 referrals of subjects to genetic counselling and testing (GCAT) clinic, National Institute of Mental Health and Neurosciences, Bengaluru, India, with suspected SCA. The most frequent mutations detected were SCA1 (n = 100 (11.6%)) and SCA2 (n = 98 (11.3%)) followed by SCA3 (n = 40 (4.6%)), FRDA (n = 20 (2.3%)) and SCA12 (n = 8 (0.9%))