Chiman Kumari

Traditionally, the human central nervous system (CNS) is described as having three meningeal layers, from outer to inner: dura mater, arachnoid mater, and pia mater. The arachnoid and pia mater are called the leptomeninges, and the space between them is filled with cerebrospinal fluid (CSF). Using gross dissection, light microscopy, and ultrastructural analysis of fresh postmortem and cadaveric CNS specimens spanning fetal to adult ages (N=61), we demonstrate a fibrocellular intermediate leptomeningeal layer (ILL) from the cortex to the caudal end of the spinal cord. The ILL divides the subarachnoid space (SAS) into two distinct structural compartments, through which vessels and nerves pass. The ILL shows unique structural features, such as dips into the brain’s sulci and fissures, as a double-fold membrane that bears intra-layer trabeculae, carries vessels, and forms the perivascular sheath. Moreover, throughout the CNS, it appears to be a non-sieved barrier, characterized by the presence of tight and adherens junctions. ILL, predominantly in the spinal cord, contains macrophage-like cells, indicating its layer-specific immune properties. The ILL warrants recognition as a distinct human meningeal layer with potential barrier and immune functions. Significance: An Intermediate Leptomeningeal Layer encloses the Central Nervous System in Humans: The integrated analysis of our macroscopic, microscopic, and ultrastructural study provides robust support for an intermediate leptomeningeal layer (ILL) in the subarachnoid space (SAS) of the human central nervous system (CNS) along the entire neural axis. The ILL is a fibrocellular macroscopic structure, with restricted permeability, that divides the cerebrospinal fluid (CSF)-filled SAS into two distinct structural compartments. Uniquely, ILL revealed the presence of cells with macrophage-like properties, suggesting a possible role in immune surveillance. The ILL may redefine the established concept of protective coverings of CNS, CSF circulation dynamics, and the role of leptomeninges in health and disease, including drug delivery.

Background: The Delta variant (B.1.617.2) was considered the most dangerous SARS-CoV-2 strain; however, in-depth studies on its impact based on demographic and clinical characteristics of COVID-19 are scarce. Objective: We aimed to investigate the shift in demographic and clinical characteristics of the COVID-19 pandemic with the emergence of the SARS-CoV-2 Delta variant compared with the wild-type (WT) strain (B.1). Methods: A cross-sectional study of COVID-19 cases in the Indian population caused by the WT strain (B.1) and Delta variant of SARS-CoV-2 was performed. The viral genomic sequence metadata containing demographic, vaccination, and patient status details (N=9500, NDelta=6238, NWT=3262) were statistically analyzed. Results: With the Delta variant, in comparison with the WT strain, a higher proportion of young individuals (<20 years) were infected (0-9 years: Delta: 281/6238, 4.5% vs B.1: 75/3262, 2.3%; 10-19 years: Delta: 562/6238, 9% vs B.1: 229/3262, 7%; P<.001). The proportion of women contracting infection increased (Delta: 2557/6238, 41% vs B.1: 1174/3262, 36%; P<.001). However, it decreased for men (Delta: 3681/6238, 59% vs B.1: 2088/3262, 64%; P<.001). An increased proportion of the young population developed symptomatic illness and were hospitalized (Delta: 27/262, 10.3% vs B.1: 5/130, 3.8%; P=.02). Moreover, an increased proportion of the women (albeit not men) from the young (Delta: 37/262, 14.1% vs B.1: 4/130, 3.1%; P<.001) and adult (Delta: 197/262, 75.2% vs B.1: 72/130, 55.4%; P<.001) groups developed symptomatic illness and were hospitalized. The mean age of men and women who contracted infection (Delta: men=37.9, SD 17.2 years; women=36.6, SD 17.6 years; P<.001; B.1: men=39.6, SD 16.9 years; women=40.1, SD 17.4 years; P<.001) as well as developing symptoms or being hospitalized (Delta: men=39.6, SD 17.4 years; women=35.6, SD 16.9 years, P<.001; B.1: men=47, SD 18 years; women=49.5, SD 20.9 years, P<.001) were considerably lower with the Delta variant than the B.1 strain. The total mortality was about 1.8 times higher with the Delta variant than with the WT strain. With the Delta variant, compared with B.1, mortality decreased for men (Delta: 58/85, 68% vs B.1: 15/20, 75%; P<.001); in contrast, it increased for women (Delta: 27/85, 32% vs B.1: 5/20, 25%; P<.001). The odds of death increased with age, irrespective of sex (odds ratio 3.034, 95% CI 1.7-5.2, P<.001). Frequent postvaccination infections (24/6238) occurred with the Delta variant following complete doses. Conclusions: The increased involvement of young people and women, the lower mean age for illness, higher mortality, and frequent postvaccination infections were significant epidemiological concerns with the Delta variant.

The existence of a previously unrecognized subarachnoid lymphatic‐like membrane (SLYM) was reported in a recent study. SLYM is described as an intermediate leptomeningeal layer between the arachnoid and pia mater in mouse and human brains, which divides the subarachnoid space (SAS) into two functional compartments. Being a macroscopic structure, having missed detection in previous studies is surprising. We systematically reviewed the published reports in animals and humans to explore whether prior descriptions of this meningeal layer were reported in some way. A comprehensive search was conducted in PubMed/Medline, EMBASE, Google Scholar, Science Direct, and Web of Science databases using combinations of MeSH terms and keywords with Boolean operators from inception until 31 December 2023. We found at least eight studies that provided structural evidence of an intermediate leptomeningeal layer in the brain or spinal cord. However, unequivocal descriptions for this layer all along the central nervous system were scarce. Obscure names like the epipial, intermediate meningeal, outer pial layers, or intermediate lamella were used to describe it. Its microscopic/ultrastructural details closely resemble the recently reported SLYM. We further examined the counterarguments in current literature that are skeptical of the existence of this layer. The potential physiological and clinical implications of this new meningeal layer are significant, underscoring the urgent need for further exploration of its structural and functional details.

Background: There is an urgent need to review the status of COVID-19 vaccine immunization in pregnant women globally so that the adverse outcomes may be prevented. Objective: To evaluate the probable outcome of COVID-19 vaccination in pregnant women. Search strategy: An electronic search was conducted over the period of 3 months (June 15-August 15, 2021). Selection criteria: The original studies evaluating safety concerns in pregnant women for COVID-19 vaccination were included. Data collection and analysis: Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2009 guidelines were used for the collection of the data and reporting of the findings. The inclusion and exclusion criteria for the studies were determined based on ‘PICO principle’ (Population, Intervention, Comparator, and Outcome, Study design. Risk of bias assessment was done using National Institute of Health (NIH) tool for systematic reviews. Main results: COVID-19 vaccination in pregnant women was not associated with increased adverse effects or complications to the mother as well as developing fetus or newborn compared to non-vaccinated pregnant women. Vaccinated pregnant women showed a robust immune response against COVID-19 infection. Conclusions: COVID-19 vaccination during pregnancy causes no significant health risks for the mother or developing fetus or newborn.

Journal of Clinical and Diagnostic Research aims to publish findings of doctors at grass root level and post graduate students, so that all unique medical experiences are recorded in literature.

BACKGROUND The Delta variant (B.1.617.2) was considered the most dangerous SARS-CoV-2 strain; however, in-depth studies on its impact based on demographic and clinical characteristics of COVID-19 are scarce. OBJECTIVE We aimed to investigate the shift in demographic and clinical characteristics of the COVID-19 pandemic with the emergence of the SARS-CoV-2 Delta variant compared with the wild-type (WT) strain (B.1). METHODS A cross-sectional study of COVID-19 cases in the Indian population caused by the WT strain (B.1) and Delta variant of SARS-CoV-2 was performed. The viral genomic sequence metadata containing demographic, vaccination, and patient status details (N=9500, NDelta=6238, NWT=3262) were statistically analyzed. RESULTS With the Delta variant, in comparison with the WT strain, a higher proportion of young individuals (<20 years) were infected (0-9 years: Delta: 281/6238, 4.5% vs B.1: 75/3262, 2.3%; 10-19 years: Delta: 562/6238, 9% vs B.1: 229/3262, 7%; P<.001). The proportion of women contracting infection increased (Delta: 2557/6238, 41% vs B.1: 1174/3262, 36%; P<.001). However, it decreased for men (Delta: 3681/6238, 59% vs B.1: 2088/3262, 64%; P<.001). An increased proportion of the young population developed symptomatic illness and were hospitalized (Delta: 27/262, 10.3% vs B.1: 5/130, 3.8%; P=.02). Moreover, an increased proportion of the women (albeit not men) from the young (Delta: 37/262, 14.1% vs B.1: 4/130, 3.1%; P<.001) and adult (Delta: 197/262, 75.2% vs B.1: 72/130, 55.4%; P<.001) groups developed symptomatic illness and were hospitalized. The mean age of men and women who contracted infection (Delta: men=37.9, SD 17.2 years; women=36.6, SD 17.6 years; P<.001; B.1: men=39.6, SD 16.9 years; women=40.1, SD 17.4 years; P<.001) as well as developing symptoms or being hospitalized (Delta: men=39.6, SD 17.4 years; women=35.6, SD 16.9 years, P<.001; B.1: men=47, SD 18 years; women=49.5, SD 20.9 years, P<.001) were considerably lower with the Delta variant than the B.1 strain. The total mortality was about 1.8 times higher with the Delta variant than with the WT strain. With the Delta variant, compared with B.1, mortality decreased for men (Delta: 58/85, 68% vs B.1: 15/20, 75%; P<.001); in contrast, it increased for women (Delta: 27/85, 32% vs B.1: 5/20, 25%; P<.001). The odds of death increased with age, irrespective of sex (odds ratio 3.034, 95% CI 1.7-5.2, P<.001). Frequent postvaccination infections (24/6238) occurred with the Delta variant following complete doses. CONCLUSIONS The increased involvement of young people and women, the lower mean age for illness, higher mortality, and frequent postvaccination infections were significant epidemiological concerns with the Delta variant.

Better understanding of the surgical anatomy of the triangle of doom and the triangle of pain with fixed bony landmarks like the anterior superior iliac spine (ASIS) and the pubic symphysis (PS) can help in defining a safe location for trocar placement during laparoscopic surgeries and minimize neurovascular complications. Ten cadavers were dissected bilaterally to explore the surgical anatomy of both the triangles. ASIS and PS were evaluated in relation to the deep inguinal ring, external iliac artery, femoral nerve, and inferior epigastric artery. The deep inguinal ring was located at a depth of ~3 cm, about 4.9 ± 0.56 cm along the y‐axis and 6.2 ± 0.94 cm along the x‐axis, from the ASIS. The external iliac artery was located ~4.33 ± 0.6 cm along the y‐axis and 7.29 ± 0.76 along the x‐axis from the ASIS. The inferior epigastric artery was at ~4.31 ± 0.38 cm from the midline at the level of ASIS. This knowledge can help in the surface localization of both the triangles and prevent injury to the various neurovascular structures in relation to these triangles. In the current study, cranial to the ASIS lying at a distance of >5 cm from the midline was observed to be a safe zone for accessory trocar placement. The umbilical port has been observed to be safe for trocar placement. The mean angle between ductus deferens and testicular vessels was observed to be 43.5° ± 4.79°, which could help in determining their relative locations during various surgical procedures.

COVID-19 has prominent neurological manifestations including psychiatric symptoms, indicating significant synaptic pathology. Surprisingly, existing evidence suggests negligible expression of the key SARS-CoV-2 host cell entry mediators ACE2 and TMPRSS2 in human brain, which complicates understanding of the pathomechanisms of the neuropsychiatric manifestations in COVID-19. Recent studies suggested that an alternative host-cell entry receptor, NRP1 , can mediate entry of furin cleaved SARS-CoV-2 spike proteins into the host cells. However, the role of NRP1 and furin in mediating SARS-CoV-2 entry in human brain cells has been least explored and remains a lacuna in the literature. We performed an in silico analysis of the transcriptomic and proteomic expressions of SARS-CoV-2 host-cell entry receptors and associated tissue proteases in human brain tissue, using the publically available databases. Based on the expression analysis, SARS-CoV-2 entry in human brain cells is likely to be mediated through NRP1 and furin . Graphical

Young age, female sex, absence of comorbidities, and prior infection or vaccination are known epidemiological barriers for contracting the new infection and/or increased disease severity. Demographic trends from the recent coronavirus disease 2019 waves, which are believed to be driven by newer severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) variants, indicate that the aforementioned epidemiological barriers are being breached and a larger number of younger and healthy individuals are developing severe disease. The new SARS‐CoV‐2 variants have key mutations that can induce significant changes in the virus‐host interactions. Recent studies report that, some of these mutations, singly or in a group, enhance key mechanisms, such as binding of the receptor‐binding domain (RBD) of the viral spike protein with the angiotensin‐converting enzyme 2 (ACE2) receptor in the host‐cells, increase the glycosylation of spike protein at the antigenic sites, and enhance the proteolytic cleavage of the spike protein, thus leading to improved host‐cell entry and the replication of the virus. The putative changes in the virus–host interactions imparted by the mutations in the RBD sequence can potentially be the reason behind the breach of the observed epidemiological barriers. Susceptibility for contracting SARS‐CoV‐2 infection and the disease outcomes are known to be influenced by host‐cell expressions of ACE2 and other proteases. The new variants can act more efficiently, and even with the lesser availability of the viral entry‐receptor and the associated proteases, can have more efficient host‐cell entry and greater replication resulting in high viral loads and prolonged viral shedding, widespread tissue‐injury, and severe inflammation leading to increased transmissibility and lethality. Furthermore, the accumulating evidence shows that multiple new variants have reduced neutralization by both, natural and vaccine‐acquired antibodies, indicating that repeated and vaccine breakthrough infections may arise as serious health concerns in the ongoing pandemic.