Low blood pressure syndrome: a myth or a reality? results of a patient\u27s survey at a teaching hospital in Karachi

Objective: To study patient’s knowledge, perceptions attitude and practice with regard to low blood pressure. Design: A Questionnaire-based survey. Settings: Family Practice Center, Aga Khan University Hospital, Karachi, Pakistan, in June 2004. Main outcome measures: Low blood pressure is a disease, causes and treatment of low blood pressure, patient ever suffered from low blood pressure, low blood pressure can be diagnosed with BP apparatus, without apparatus and stress can cause low blood pressure. Results: A 110 patients were interviewed. Majority of the subjects were educated young married men, well placed socio-economically. A majority (73%) of the respondents consider low blood pressure as a disease entity. Weakness, dizziness, low mood and headaches are reported as symptoms and use of salt (41%) and medications (20%) are considered treatments for low blood pressure. Conclusion: Further studies are recommended to ascertain the existence of low blood pressure syndrome in our population as a myth or a disease entity. Physician and patient education is also strongly recommended

The Dynamics of Central-Peripheral Stress Responses after Acute Psychosocial Stress: a Multimodal Perspective

An acute stress response is a complex interaction of central and peripheral psychophysiological systems with unique temporal characteristics. Interestingly, the interaction represents a unique temporal characteristic. Investigating the dynamics of both brain and body signals during and after an encounter with a stressor allows us to understand the underlying principle of the acute stress response, which has been shown to be atypical in various psychiatric disorders. However, a detailed understanding of stress response is rarely investigated. Therefore, this thesis investigates two major approaches for understanding the acute stress response dynamics using simultaneous electroencephalography (EEG)-photoplethysmographyfunctional magnetic resonance imaging experiments in 39 subjects before and after the ScanStress task. The EEG-derived vigilance indexes reveal a continuous decline at rest. Given the role of alertness in an efficient stress response, the effects of acute stress induction on EEG-derived vigilance metrics are of interest. Therefore, the first approach uses the dynamic analysis of psychophysiological stress responses after the acute psychosocial stress induction. The first study investigates the carry-over effect of acute psychosocial stress on vigilance and its modulation by the multicomponent over-thecounter drug neurexan, which has been shown to modulate the neuroendocrine stress response. By using dynamic analysis, six vigilance scores were calculated every two minutes before and after the stress induction during the resting state. The study revealed that stress delays the continuous decline of vigilance at rest. In addition, the stress-induced increase in mean vigilance levels at rest was correlated positively with the levels of perceived stress during the last month. In addition, the mean vigilance level exhibited a decrease after neurexan treatment compared to placebo intake. Heart rate variability (HRV) can be viewed as an indicator of how well the adaptive regulation system in the brain reacts the peripheral environment. However, the relationship between the HRV and functional connectivity patterns in the brain networks in stressful situations is rarely investigated. Therefore, the second approach uses the multimodal approach to examine the interaction between different stress response systems. The study investigated the temporal association between HRV and FC between the three core brain networks, namely the central executive network, salience network, and default mode network at baseline and after the psychosocial stress induction. In this study, the functional connectivity between three core brain networks and the HRV was examined by taking 60s window length. Furthermore, the temporal association between HRV and functional connectivity was investigated. A significant association was found between HRV and default mode network-central executive network functional connectivity at rest, which was significantly reduced after acute stress induction compared to baseline. These findings suggest that HRV cofluctuates with the core brain networks selectively depending on the stress conditions. In summary, acute psychological stress affects brain dynamics by exhibiting a delay in the continuously declining vigilance and keeping the brain in a more alert state even after the stressor disappears. Furthermore, the results suggest that EEG-derived vigilance metrics index not only stress-response but also the temporal dynamics of vigilance regulation. It can serve as a potential biomarker for the diagnosis and prognosis for stress-related disorders disrupting temporal characteristics of stress response dynamics and showing atypical stress response. In addition, the study revealed that stress affects the interactions among the core large-scale functional networks and physiological dynamics of the heart. The dynamic adaptation of the resources is crucial in a stressful situation; therefore, the stress alters the interaction between the brain and heart. The perturbation in this interaction may play an important role in developing and maintaining stress-related disorders. The thesis work provides novel insights and an understanding of the central and peripheral stress response dynamics, which show a huge potential for the diagnosis, prognosis, and therapeutic planning of individuals with neuropsychiatric disorders

Implications of the ‘War on Terror’ for Muslim women in Britain; Narratives of resistance and resilience

This thesis troubles the deafening silence, surrounding South Asian Muslim women’s (SAMW) experience, of the collateral damage from the ‘War on Terror’ as prolonged adversity and harm. It identifies forms of adversity to which SAMW are exposed and their resilience responses in the ‘War on Terror’. This thesis offers a radical critique, of adversity, resistance, and resilience through the frames of temporality and hegemony. It exposes interrelated tensions inherent in resilience as survival/ coping, or as transformation/ adaptation. Hegemony brings power and resistance, to the centre of the concept in new ways; problematizing accepted notions of resilience as the capacity to ‘bounce back’ to a former state of equilibrium. It identifies the past in the present; in this frame the ‘War on Terror’, is a present day manifestation of past patterns of ideological struggle with roots in empire. Ethnographic research was undertaken with SAMW, in a neighbourhood in the north of England, to gather information on SAMW’s experience of adversity, resistance, and resilience to the effects of the ‘War on Terror’. The research identified mechanisms in community, neighbourhood, and through state institutions, that support SAMW’s resilience. The findings, unequivocally identified links between SAMW’s fear of assault/adversity and the ‘War on Terror’; as signified in 9/11. SAMW had little, if any, recourse to material resources as insulators from adversity, and, civil and civic institutions failed to offer SAMW adequate support. Social capital, generated in relationships and social networks, insulated SAMW, and enabled them to build hybrid ‘resistant identities’. This thesis identifies new ways of thinking about the ‘War on Terror’, adversity and resilience; it presents new knowledge to highlight the urgency for further investigation into adversity and resilience in conditions of prolonged trauma. The imperative is to address dislocations between SAMW and local and national state institutio

Genomic investigations of unexplained acute hepatitis in children

Since its first identification in Scotland, over 1,000 cases of unexplained paediatric hepatitis in children have been reported worldwide, including 278 cases in the UK1. Here we report an investigation of 38 cases, 66 age-matched immunocompetent controls and 21 immunocompromised comparator participants, using a combination of genomic, transcriptomic, proteomic and immunohistochemical methods. We detected high levels of adeno-associated virus 2 (AAV2) DNA in the liver, blood, plasma or stool from 27 of 28 cases. We found low levels of adenovirus (HAdV) and human herpesvirus 6B (HHV-6B) in 23 of 31 and 16 of 23, respectively, of the cases tested. By contrast, AAV2 was infrequently detected and at low titre in the blood or the liver from control children with HAdV, even when profoundly immunosuppressed. AAV2, HAdV and HHV-6 phylogeny excluded the emergence of novel strains in cases. Histological analyses of explanted livers showed enrichment for T cells and B lineage cells. Proteomic comparison of liver tissue from cases and healthy controls identified increased expression of HLA class 2, immunoglobulin variable regions and complement proteins. HAdV and AAV2 proteins were not detected in the livers. Instead, we identified AAV2 DNA complexes reflecting both HAdV-mediated and HHV-6B-mediated replication. We hypothesize that high levels of abnormal AAV2 replication products aided by HAdV and, in severe cases, HHV-6B may have triggered immune-mediated hepatic disease in genetically and immunologically predisposed children

Investigation of hospital discharge cases and SARS-CoV-2 introduction into Lothian care homes

Background The first epidemic wave of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) in Scotland resulted in high case numbers and mortality in care homes. In Lothian, over one-third of care homes reported an outbreak, while there was limited testing of hospital patients discharged to care homes. Aim To investigate patients discharged from hospitals as a source of SARS-CoV-2 introduction into care homes during the first epidemic wave. Methods A clinical review was performed for all patients discharges from hospitals to care homes from 1st March 2020 to 31st May 2020. Episodes were ruled out based on coronavirus disease 2019 (COVID-19) test history, clinical assessment at discharge, whole-genome sequencing (WGS) data and an infectious period of 14 days. Clinical samples were processed for WGS, and consensus genomes generated were used for analysis using Cluster Investigation and Virus Epidemiological Tool software. Patient timelines were obtained using electronic hospital records. Findings In total, 787 patients discharged from hospitals to care homes were identified. Of these, 776 (99%) were ruled out for subsequent introduction of SARS-CoV-2 into care homes. However, for 10 episodes, the results were inconclusive as there was low genomic diversity in consensus genomes or no sequencing data were available. Only one discharge episode had a genomic, time and location link to positive cases during hospital admission, leading to 10 positive cases in their care home. Conclusion The majority of patients discharged from hospitals were ruled out for introduction of SARS-CoV-2 into care homes, highlighting the importance of screening all new admissions when faced with a novel emerging virus and no available vaccine

SARS-CoV-2 Omicron is an immune escape variant with an altered cell entry pathway

Vaccines based on the spike protein of SARS-CoV-2 are a cornerstone of the public health response to COVID-19. The emergence of hypermutated, increasingly transmissible variants of concern (VOCs) threaten this strategy. Omicron (B.1.1.529), the fifth VOC to be described, harbours multiple amino acid mutations in spike, half of which lie within the receptor-binding domain. Here we demonstrate substantial evasion of neutralization by Omicron BA.1 and BA.2 variants in vitro using sera from individuals vaccinated with ChAdOx1, BNT162b2 and mRNA-1273. These data were mirrored by a substantial reduction in real-world vaccine effectiveness that was partially restored by booster vaccination. The Omicron variants BA.1 and BA.2 did not induce cell syncytia in vitro and favoured a TMPRSS2-independent endosomal entry pathway, these phenotypes mapping to distinct regions of the spike protein. Impaired cell fusion was determined by the receptor-binding domain, while endosomal entry mapped to the S2 domain. Such marked changes in antigenicity and replicative biology may underlie the rapid global spread and altered pathogenicity of the Omicron variant

Association of karyomegalic interstitial nephritis with focal segmental glomerulosclerosis

Karyomegalic interstitial nephritis (KIN), first described in 1974, is a rare form of chronic tubulointerstitial nephritis. It is defined by the presence of markedly enlarged, hyperchromatic nuclei with prominent nucleoli, mainly involving tubular epithelial cells of the kidney, accompanied by marked interstitial fibrosis. The disease presents as asymptomatic proteinuria, gradually progresses to chronic kidney disease and eventually leads to end-stage renal disease by 30-40 years. The etiology of the disease remains unclear; however, genetic risk factors and possible association with HLA (B27/35) is proposed by some. It has also been linked to FAN1 (FANCD2/FANC1- associated nuclease 1) mutation. Case Report: We present two cases of KIN with associated focal segmental glomerulosclerosis. Both patients presented with nephrotic range proteinuria. The biopsies demonstrated marked enlargement of tubular nuclei (3-5x larger than the uninvolved tubular nuclei, a metric used by some authors in previous studies) in some tubules, meeting the diagnostic criteria of KIN.. Interestingly, case one had a prior biopsy that showed minimal change disease. In the biopsies done at our institution, H&E sections showed patchy tubular attenuation with readily recognizable tubular cell mitotic figures, indicating concurrent acute tubular injury. Electron microscopy showed diffuse podocyte foot process effacement, along with microvillous transformation, podocyte hypertrophy, and cytoplasmic vacuoles, suggesting podocyte injury. This cytoplasmic vacuolization was also observed in the tubular epithelial cells. In both cases, the injury factor appeared to target both podocytes and tubular cells

Utilizing electronic resources to promote your residency program

As the COVID-19 pandemic spread to the United States, it was followed by unprecedented changes. These changes did not spare undergraduate and graduate medical students. Specifically, medical students applying for residency programs were faced with a novel challenge. In March 2020, as the pandemic became increasingly severe, the Association of American Medical Colleges (AAMC) recommended pulling medical students from in-person clinical rotations. By May 2020, the AAMC recommended that all residency interviews be conducted online for the 2020-2021 residency application cycle. These unprecedented modifications to the interview season required programs to quickly adapt and find ways to utilize online tools to convey what their program offered to applicants. In this paper, we will outline the adaptations, tools, and resources that residencies and applicants have used to navigate through the 2020/2021 interview cycle