The surged faradic stimulation to the pelvic floor muscles as an adjunct to the medical management in children with rectal prolapse

<p>Abstract</p> <p>Background</p> <p>To assess the role of the surged faradic stimulation to the pelvic floor muscles as an adjunct to the conservative management in the children of idiopathic rectal prolapse</p> <p>Methods</p> <p><it>Study design</it>: Prospective</p> <p><it>Setting</it>: Pediatric Surgery Department, Pt BD Sharma, Post Graduate Institute of Medical Sciences, Rohtak</p> <p><it>Subjects</it>: 47 consecutive children with idiopathic rectal prolapse attending the Pediatric Surgery out patient department from July 2005 to June 2006</p> <p><it>Methodology</it>: The information pertaining to duration and the extent of rectal prolapse, predisposing or associated medical conditions, results of local clinical examination were noted. Surged faradic stimulation using modified intraluminal rectal probe, was given on the alternate days. The conventional conservative medical management was also continued. The extent of relief and the number of the sittings of faradic stimulation required were noted at various stages of follow-ups</p> <p><it>Statistical Methods</it>: Mean values between those completely cured and others; poor responders and others were compared with t-test and proportions were compared with Chi square test. The p-value < 0.05 was considered statistically significant.</p> <p>Results</p> <p>The mean number of sittings in the completely cured group (n = <b>28</b>(64%)) was (12.4 ± 7.8) and was comparable with very poor responder (n = 6(13%). There was higher percentage of relief (76%) at the first follow up (at 15 days) in completely cured Vs other (37%) and also the poor responders showed (20%) Vs other (68%) and was statistically significant.</p> <p>Conclusion</p> <p>With use of faradic stimulation, even the long-standing rectal prolapse can be fully cured. The follow up visit at 2 weeks is very important to gauge the likely success of this modality in treatment of the patients with rectal prolapse. Those showing poor response at this stage may require alternative treatment or take a long time to get cured</p

Transglutaminase 2 Contributes to Apoptosis Induction in Jurkat T Cells by Modulating Ca(2+) Homeostasis via Cross-Linking RAP1GDS1

BACKGROUND: Transglutaminase 2 (TG2) is a protein cross-linking enzyme known to be associated with the in vivo apoptosis program of T cells. However, its role in the T cell apoptosis program was not investigated yet. RESULTS: Here we report that timed overexpression of both the wild type (wt) and the cross-linking mutant of TG2 induced apoptosis in Jurkat T cells, the wt being more effective. Part of TG2 colocalised with mitochondria. WtTG2-induced apoptosis was characterized by enhanced mitochondrial Ca(2+) uptake. Ca(2+)-activated wtTG2 cross-linked RAP1, GTP-GDP dissociation stimulator 1, an unusual guanine exchange factor acting on various small GTPases, to induce a yet uncharacterized signaling pathway that was able to promote the Ca(2+) release from the endoplasmic reticulum via both Ins3P and ryanodine sensitive receptors leading to a consequently enhanced mitochondrial Ca(2+)uptake. CONCLUSIONS: Our data indicate that TG2 might act as a Ca(2+) sensor to amplify endoplasmic reticulum-derived Ca(2+) signals to enhance mitochondria Ca(2+) uptake. Since enhanced mitochondrial Ca(2+) levels were previously shown to sensitize mitochondria for various apoptotic signals, our data demonstrate a novel mechanism through which TG2 can contribute to the induction of apoptosis in certain cell types. Since, as compared to knock out cells, physiological levels of TG2 affected Ca(2+) signals in mouse embryonic fibroblasts similar to Jurkat cells, our data might indicate a more general role of TG2 in the regulation of mitochondrial Ca(2+) homeostasis

Prognostic molecular markers in early breast cancer

A multitude of molecules involved in breast cancer biology have been studied as potential prognostic markers. In the present review we discuss the role of established molecular markers, as well as potential applications of emerging new technologies. Those molecules used routinely to make treatment decisions in patients with early-stage breast cancer include markers of proliferation (e.g. Ki-67), hormone receptors, and the human epidermal growth factor receptor 2. Tumor markers shown to have prognostic value but not used routinely include cyclin D(1 )and cyclin E, urokinase-like plasminogen activator/plasminogen activator inhibitor, and cathepsin D. The level of evidence for other molecular markers is lower, in part because most studies were retrospective and not adequately powered, making their findings unsuitable for choosing treatments for individual patients. Gene microarrays have been successfuly used to classify breast cancers into subtypes with specific gene expression profiles and to evaluate prognosis. RT-PCR has also been used to evaluate expression of multiple genes in archival tissue. Proteomics technologies are in development

Human embryonic stem cell-derived neurons as a tool for studying neuroprotection and neurodegeneration.

The capacity to generate myriad differentiated cell types, including neurons, from human embryonic stem cell (hESC) lines offers great potential for developing cell-based therapies and also for increasing our understanding of human developmental mechanisms. In addition, the emerging development of this technology as an experimental tool represents a potential opportunity for neuroscientists interested in mechanisms of neuroprotection and neurodegeneration. Potentially unlimited generation of well-defined functional neurons from hES and patient specific induced pluripotent (iPS) cells offers new systems to study disease mechanisms, signalling pathways and receptor pharmacology within a human cellular environment. Such systems may help in overcoming interspecies differences. Far from replacing rodent in vivo and primary culture systems, hES and iPS cell-derived neurons offer a complementary resource to overcome issues of interspecies differences, accelerate drug discovery, study of disease mechanism as well as provide basic insight into human neuronal physiology

Genomic reconstruction of the SARS-CoV-2 epidemic in England.

The evolution of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus leads to new variants that warrant timely epidemiological characterization. Here we use the dense genomic surveillance data generated by the COVID-19 Genomics UK Consortium to reconstruct the dynamics of 71 different lineages in each of 315 English local authorities between September 2020 and June 2021. This analysis reveals a series of subepidemics that peaked in early autumn 2020, followed by a jump in transmissibility of the B.1.1.7/Alpha lineage. The Alpha variant grew when other lineages declined during the second national lockdown and regionally tiered restrictions between November and December 2020. A third more stringent national lockdown suppressed the Alpha variant and eliminated nearly all other lineages in early 2021. Yet a series of variants (most of which contained the spike E484K mutation) defied these trends and persisted at moderately increasing proportions. However, by accounting for sustained introductions, we found that the transmissibility of these variants is unlikely to have exceeded the transmissibility of the Alpha variant. Finally, B.1.617.2/Delta was repeatedly introduced in England and grew rapidly in early summer 2021, constituting approximately 98% of sampled SARS-CoV-2 genomes on 26 June 2021