Transmission and secretion of signals via the choroid plexus (ChP) brain barrier can modulate brain states via regulation of cerebrospinal fluid (CSF) composition. Here, we developed a platform to ...analyze diurnal variations in male mouse ChP and CSF. Ribosome profiling of ChP epithelial cells revealed diurnal translatome differences in metabolic machinery, secreted proteins, and barrier components. Using ChP and CSF metabolomics and blood-CSF barrier analyses, we observed diurnal changes in metabolites and cellular junctions. We then focused on transthyretin (TTR), a diurnally regulated thyroid hormone chaperone secreted by the ChP. Diurnal variation in ChP TTR depended on Bmal1 clock gene expression. We achieved real-time tracking of CSF-TTR in awake Ttr
mice via multi-day intracerebroventricular fiber photometry. Diurnal changes in ChP and CSF TTR levels correlated with CSF thyroid hormone levels. These datasets highlight an integrated platform for investigating diurnal control of brain states by the ChP and CSF.
Purpose
This paper investigates the deterrence effect of development on crime against women in India. Specifically, the authors examine the deterrence effect of the composite development index, i.e. ...Human Development Index (HDI), along with other variables acting as development indicators such as women’s employment, the relative strength of women in the police force, urbanization, etc., on crimes against women.
Design/methodology/approach
This study adopts a fixed effect within-group (WG) panel regression model and pooled regression model on the data of 28 states over 20 years from 2000 to 2019. For checking the robustness of the results, the authors use the estimation from the system generalized method of moments.
Findings
The results confirm the deterrence effect of development as measured by the HDI and female labor force participation on various crimes against women. In addition, female feticide representing the socio-cultural attitude toward women turned out to be another significant determinant of almost all types of crime against women. Further, the study also finds the deterrence effect of variables such as police expenditure, the relative strength of women in the police force, urbanization and arrest rate on various crimes against women.
Originality/value
This research paper is unique because it tries to examine the deterrence hypothesis of development by taking a composite index of development, i.e. HDI and other variables at the state level in the Indian union.
Reissner's fiber (RF) is an extracellular polymer comprising the large monomeric protein SCO-spondin (SSPO) secreted by the subcommissural organ (SCO) that extends through cerebrospinal fluid ...(CSF)-filled ventricles into the central canal of the spinal cord. In zebrafish, RF and CSF-contacting neurons (CSF-cNs) form an axial sensory system that detects spinal curvature, instructs morphogenesis of the body axis, and enables proper alignment of the spine. In mammalian models, RF has been implicated in CSF circulation. However, challenges in manipulating Sspo, an exceptionally large gene of 15,719 nucleotides, with traditional approaches has limited progress. Here, we generated a Sspo knockout mouse model using CRISPR/Cas9-mediated genome-editing. Sspo knockout mice lacked RF-positive material in the SCO and fibrillar condensates in the brain ventricles. Remarkably, Sspo knockout brain ventricle sizes were reduced compared to littermate controls. Minor defects in thoracic spine curvature were detected in Sspo knockouts, which did not alter basic motor behaviors tested. Altogether, our work in mouse demonstrates that SSPO and RF regulate ventricle size during development but only moderately impact spine geometry.
A broad ligament pregnancy is an extremely rare condition. Diagnosis is often missed and finally made during laparotomy. We present a case which remained undiagnosed throughout her pregnancy till she ...reached term and unfortunately had intrauterine foetal demise when she reported to our hospital. On clinical suspicion, ultrasound and magnetic resonance imaging evaluation was done which picked up the diagnosis of abdominal pregnancy. On laparotomy a broad ligament pregnancy was found with a rent in the previous Cesarean scar towards the gestational sac in the broad ligament.
Funding bias in shoulder arthroplasty research Haislup, Brett D.; Gupta, Suhasini; Fleisher, Ilan ...
Journal of shoulder and elbow surgery,
08/2024, Letnik:
33, Številka:
8
Journal Article
Recenzirano
Prior research has shown that industry funding can impact the outcomes reported in medical literature. Limited data exist on the degree of bias that industry funding may have on shoulder arthroplasty ...literature outside of the Journal of Shoulder and Elbow Surgery. The purpose of this study is to characterize the type and frequency of funding for recently published shoulder arthroplasty studies and the impact of industry funding on reported outcomes. We hypothesized that studies with industry funding are more likely to report positive outcomes than those without.
We performed a retrospective study searching all articles with the term “shoulder arthroplasty,” “reverse shoulder arthroplasty,” “anatomic total shoulder arthroplasty,” or “total shoulder arthroplasty” on PubMed from the years January 2020 to December 2022. The primary outcome of studies was coded as either positive, negative, or neutral. A positive result was defined as one in which the null hypothesis was rejected. A negative result was defined as one in which the result did not favor the group in which the industry-funded implant was used. A neutral result was defined as one in which the null hypothesis was confirmed. Article funding type, subcategorized as National Institutes of Health funding or industry funding was recorded. Author disclosures were recorded to determine conflicts of interest. Statistical analysis was conducted using the χ2 test and Fisher exact test.
A total of 750 articles reported on either conflict of interest or funding source and were included in the study. Of the total number of industry-funded studies, the majority were found to have a positive primary endpoint (58.1%, 104 of 179), as compared to a negative (7.8%, 14 of 179) or neutral endpoint (33.5%, 60 of 179) (P = .004). Overall, 363 articles reported an author conflict of interest, and the majority of these studies had positive primary endpoint (55.6%, 202 of 363) as compared to negative (9.1%, 33 of 363) or neutral endpoints (34.4%, 125 of 363) (P = .002).
The results of this study suggest that there is a significant relationship between conflicts of interest and the primary outcome of shoulder arthroplasty studies, beyond the overall positive publication bias. Studies with industry funding and author conflicts of interest both report positive outcomes more frequently than negative outcomes. Shoulder surgeons should be aware of this potential bias when choosing to base clinical practice on published data.
Post-hemorrhagic hydrocephalus (PHH) refers to a life-threatening accumulation of cerebrospinal fluid (CSF) that occurs following intraventricular hemorrhage (IVH). An incomplete understanding of ...this variably progressive condition has hampered the development of new therapies beyond serial neurosurgical interventions. Here, we show a key role for the bidirectional Na-K-Cl cotransporter, NKCC1, in the choroid plexus (ChP) to mitigate PHH. Mimicking IVH with intraventricular blood led to increased CSF K+ and triggered cytosolic calcium activity in ChP epithelial cells, which was followed by NKCC1 activation. ChP-targeted adeno-associated viral (AAV)-NKCC1 prevented blood-induced ventriculomegaly and led to persistently increased CSF clearance capacity. These data demonstrate that intraventricular blood triggered a trans-choroidal, NKCC1-dependent CSF clearance mechanism. Inactive, phosphodeficient AAV-NKCC1-NT51 failed to mitigate ventriculomegaly. Excessive CSF K+ fluctuations correlated with permanent shunting outcome in humans following hemorrhagic stroke, suggesting targeted gene therapy as a potential treatment to mitigate intracranial fluid accumulation following hemorrhage.
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•CSF K+ increases sharply in pediatric and adult post-hemorrhagic hydrocephalus model•Blood triggers ChP calcium activity and NKCC1 expression/activation•ChP-NKCC1 overexpression prevents ventriculomegaly and enhances CSF clearance•Hemorrhagic stroke patient CSF samples revealed dysregulated CSF K+ levels
Intraventricular blood leads to increased CSF K+, choroid plexus (ChP) calcium activity, and increased NKCC1 expression/activation. Elevated CSF K+ reverses ChP-NKCC1 transport direction. In turn, ChP-NKCC1 overexpression reduces CSF K+, enhances CSF clearance, and prevents ventriculomegaly. Thus, ChP-targeted NKCC1 gene therapy prevents key neurological sequelae of post-hemorrhagic hydrocephalus modeled in mouse.
The choroid plexus (ChP) produces cerebrospinal fluid and forms an essential brain barrier. ChP tissues form in each brain ventricle, each one adopting a distinct shape, but remarkably little is ...known about the mechanisms underlying ChP development. Here, we show that epithelial WNT5A is crucial for determining fourth ventricle (4V) ChP morphogenesis and size in mouse. Systemic Wnt5a knockout, or forced Wnt5a overexpression beginning at embryonic day 10.5, profoundly reduced ChP size and development. However, Wnt5a expression was enriched in Foxj1-positive epithelial cells of 4V ChP plexus, and its conditional deletion in these cells affected the branched, villous morphology of the 4V ChP. We found that WNT5A was enriched in epithelial cells localized to the distal tips of 4V ChP villi, where WNT5A acted locally to activate non-canonical WNT signaling via ROR1 and ROR2 receptors. During 4V ChP development, MEIS1 bound to the proximal Wnt5a promoter, and gain- and loss-of-function approaches demonstrated that MEIS1 regulated Wnt5a expression. Collectively, our findings demonstrate a dual function of WNT5A in ChP development and identify MEIS transcription factors as upstream regulators of Wnt5a in the 4V ChP epithelium.
A broad ligament pregnancy is an extremely rare condition. Diagnosis is often missed and finally made during laparotomy. We present a case which remained undiagnosed throughout her pregnancy till she ...reached term and unfortunately had intrauterine foetal demise when she reported to our hospital. On clinical suspicion, ultrasound and magnetic resonance imaging evaluation was done which picked up the diagnosis of abdominal pregnancy. On laparotomy a broad ligament pregnancy was found with a rent in the previous Cesarean scar towards the gestational sac in the broad ligament.
Full-term broad ligament pregnancy Rudra, Samar; Gupta, Suhasini; Taneja, Bal Krishan ...
BMJ case reports,
08/2013, Letnik:
2013
Journal Article
Recenzirano
Odprti dostop
A broad ligament pregnancy is an extremely rare condition. The eventuality of such pregnancies reaching full term is even rarer. A full-term broad ligament pregnancy occurring through a rent in a ...previous lower segment caesarean scar has only been mentioned in literature but not reported. Our patient is an unbooked case, reported to us at 39 weeks of pregnancy. On clinical examination, an ultrasound and an MRI, a diagnosis of abdominal pregnancy was made. Ultimately the final diagnosis was made only on laparotomy. A broad ligament pregnancy was found with a rent in the previous caesarean scar communicating the fetal sac.
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