Notes

"The Device or perhaps the Pin for Exceptional Vena Cava syndrome"?
Although a number of new immunosuppressive agents and biologics have been approved for treating various autoimmune inflammatory rheumatic diseases, there remains a substantial number of patients who have no clinical response or limited clinical response to these available treatments. Use of cellular therapies is a novel approach for the treatment of autoimmune inflammatory rheumatic diseases, with perhaps enhanced efficacy and less toxicity than current therapies. Autologous hematopoietic stem cell transplants were the first foray into cellular therapies, with proven efficacy in scleroderma and multiple sclerosis. Newer, yet unproven, cellular therapies include allogeneic mesenchymal stromal cells, which have been shown to be effective in graft-versus-host disease and in healing Crohn's fistulas. Chimeric antigen receptor T cells are effective in various malignancies, with possible application in rheumatic diseases, as shown in preclinical studies in murine lupus and recently in human lupus. Treg cells are one of the master controllers of the immune response and are decreased in number and/or effectiveness in specific autoimmune diseases. Expansion of autologous Treg cells is an attractive approach to controlling autoimmunity. There are a number of other regulatory cells in the immune system, including Breg cells, dendritic cells, macrophages, and other T cell types, that are in early stages of development as treatments. In this review, the current evidence for the efficacy and mechanisms of actions of cellular therapies already in use or in clinical trials in human autoimmune diseases will be discussed, including the limitations of these therapies and potential side effects.Pandemics are large-scale outbreaks of infectious disease that can greatly increase morbidity and mortality all the globe. Since past 1990 till twentieth century, these infectious diseases have been major threat all over the globe associated with poor hygiene and sanitation. In light of these epidemics, researches have gained enormous rise in the developing the potential therapeutic treatment. Thus, revolutionized antibiotics have led to the near eradication of such ailments. Around 50 million prescription of antibiotics written in US per year according to center for disease control and prevention (CDC) report. There is a wide range of antibiotics available which differ in their usage and their mechanism of action. Among these quinoline and quinolone class of antibiotics get attention as they show tremendous potential in fighting the epidemics. Quinoline and quinolone comprise of two rings along with substitutions at different positions which is synthetically obtained by structural modifications of quinine. Qompounds are helpful in the treatment of numerous epidemics as a chief and combination therapy. These quinoline and quinolone pharmacophore fascinate the interest of researchers as they inhibit the entry of virus in host cell and cease its replication by blocking the host receptor glycosylation and proteolytic processing. They act as immune modulator by inhibiting autophagy and reduction of both lysosomal activity and production of cytokine. Therefore, quinoline and quinolone derivatives attain significance in area of research and treatment of various life-threatening epidemics such as SARS, Zika virus, Ebola virus, dengue, and COVID-19 (currently). In this chapter, the research and advancements of quinoline- and quinolone-based antibiotics in epidemic management are briefly discussed.
We aimed to develop and validate a new risk scoring tool for predicting in-hospital mortality after lung cancer surgery.

We retrospectively identified patients admitted for lung cancer surgery from a nationwide administrative database in Japan and randomly divided them into derivation and validation cohorts. In the derivation cohort, we performed logistic regression analysis to determine predictive variables and developed a risk scoring tool by proportionally weighting the regression coefficients and assigning points to each variable. In both cohorts, we evaluated the predictive performance of the score using the c-index and showed the in-hospital mortality at each risk score.

In total, 64 175 patients (32 170 and 32 005 patients in the derivation and validation cohort, respectively) were enrolled, including 115 (0.4%) and 119 (0.4%) in-hospital patient deaths in the derivation and validation cohorts, respectively. Following the multivariate regression analysis, we selected six variables to create the SABCIP score, a risk scoring tool named after the parameters on which it is based, namely male sex, age ≥ 75 years, body mass index <18.5, clinical stage ≥3, interstitial lung disease, and procedure type (sleeve resection, chest wall resection, or pneumonectomy). The c-index of the score was 0.82 and 0.80 in the derivation and validation cohorts, respectively, which represents a better or equal discrimination performance compared with previous scoring tools. In-hospital mortality increased as the score increased in both cohorts.

The SABCIP score is a simple and useful predictor of in-hospital mortality in patients after lung cancer surgery.
The SABCIP score is a simple and useful predictor of in-hospital mortality in patients after lung cancer surgery.The first non-directed dehydrogenative phenone coupling method of methylarenes with aromatic C-H bonds, displaying a large substrate scope, is herein reported. This reaction represents a far more direct atom- and step-efficient alternative to the classical Friedel-Crafts or Suzuki-Miyaura derived acylation reactions. The method can be carried out on a gram scale and was successfully applied to the synthesis of several Ketoprofen drug analogues.
Fidgeting, a type of spontaneous physical activity (SPA), has substantial thermogenic potential. This research aims to examine secular trends in SPA and energy expenditure (EE) inside a respiratory chamber.

From 1985 to 2005, healthy adults (n=678; mean age 28.8 years; men 60%; 522 Indigenous American, 129 White, and 27 Black) had a 24-hour stay in the respiratory chamber equipped with radar sensors. Body composition, glucose tolerance, fasting insulin, insulin action (hyperinsulinemic-euglycemic clamp), and insulin secretion (intravenous glucose tolerance test) were measured as covariates.

SPA, adjusted for age, sex, race, and body composition, declined (r=-0.30, p<0.0001), with a concomitant rise in the energy cost of SPA (r=0.30, p<0.0001). learn more The 24-hour EE adjusted for covariates increased (r=0.31, p<0.0001), which was reflected in increases in EE during sleep (r=0.18, p<0.0001) and during the awake, fed condition (r=0.28, p<0.0001). The secular trends in SPA or 24-hour EE were unchanged with adjustment for measures related to glucose metabolism.

Secular trend analyses showed a decline in fidgeting. However, this decline in SPA was partially counterbalanced by an increase in energy cost of this activity and a rise in EE. Nevertheless, our results support public health efforts to promote small but sustained changes in these behaviors.
Secular trend analyses showed a decline in fidgeting. However, this decline in SPA was partially counterbalanced by an increase in energy cost of this activity and a rise in EE. Nevertheless, our results support public health efforts to promote small but sustained changes in these behaviors.The document ICH E9 (R1) has brought much attention to the concept of estimand in the clinical trials community. ICH stands for International Conference for Harmonization. In this article, we draw attention to one facet of estimand that is not discussed in that document but is crucial in the context of observational studies, namely weighting for covariate balance. How weighting schemes are connected to estimand, or more specifically to one of its five attributes identified in ICH E9 (R1), the attribute of population, is illustrated using the Rubin Causal Model. Three estimands are examined from both theoretical and practical perspectives. Factors that may be considered in choosing among these estimands are discussed.Multiple myeloma (MM) is a clonal plasma cell malignancy that remains incurable to date. Thus, the aims of this study were to evaluate the involvement of the NF-κB and PI3K/Akt/mTOR pathways in the cytotoxicity of stypoldione, an o-quinone isolated from the brown algae Stypopodium zonale, in MM cells (MM1.S). The cytotoxic effect was evaluated in MM1.S cells and peripheral blood mononuclear cells (PBMCs) by MTT assay. The stypoldione reduced the cell viability of MM1.S cells in a concentration and time-dependent manner (IC50 in MM.1S from 2.55 to 5.38 μM). However, it was also cytotoxic to PBMCs, but at a lower range. Additionally, no significant hemolysis was observed even at concentration up to 10 times the IC50 . Apoptotic cell death was confirmed by cell morphology and Annexin V-FITC assay. Stypoldione induced intrinsic and extrinsic apoptosis by increasing FasR expression and reactive oxygen species (ROS) production, inverting the Bax/Bcl-2 ratio, and inducing ΔΨm loss, which resulted in AIF release and caspase-3 activation. It also increased Ki-67 and survivin expression and inhibited the NF-κB and PI3K/Akt/mTOR pathways. These results suggest that stypoldione is a good candidate for the development of new drugs for MM treatment.The coronavirus disease 2019 (COVID-19) pandemic has brought about many changes in the relationships between high-income countries and partner organisations in low- or low-middle-income countries, such as predominate in sub-Saharan Africa. Medicine, surgery and in particular urology is no exception to the changes that COVID-19 has demanded. Urolink represents the British Association of Urological Surgeons (BAUS) on the global urology stage and has been deleteriously impacted by the pandemic. Education, one of the pillars of Urolink's founding philosophies, has conventionally been delivered by face-to face teaching, training, or mentoring by UK urologists at their host's site outside of the UK. As a consequence of the inability to travel due to the pandemic, BAUS Urolink has evolved a virtual on-line webinar package evolved by, and delivered between, urologists in Lusaka, Zambia, and various centres in the UK. The aim was to deliver curricular-based educational topics to trainees in both countries. This programme has generated a number of live webinars and archived recordings during the pandemic that has proven accessible and educationally acceptable to trainees in the UK and Zambia. This webinar series has also generated relationships between young urologists on different continents, given each a different view of healthcare delivery outside of their country of origin at no appreciable cost, and would appear to be an educational mechanism that is durable for, and applicable to, a wider participation in the post-pandemic world.The genomic region surrounding the Tenascin-XB gene (TNXB) is a complex and duplicated region, with several pseudogenes that predispose to high rates of homologous recombination. Classical-like Ehlers-Danlos syndrome (clEDS) is the result of tenascin-X deficiency due to biallelic loss of function variants in the TNXB gene. Here we present a patient with clEDS and spontaneous pneumothorax, a feature not previously reported to be associated with this condition. Two inherited pathogenic/likely pathogenic variants were identified; a previously reported deletion resulting in a TNXA/TNXB chimeric gene and a novel frameshift variant. The Tenascin-XB gene is well described in the literature to be associated with collagen metabolism, stabilization of the fibrillar-collagen matrix and is expressed abundantly in the extracellular matrix. We propose that tenascin-X deficiency is directly related to pneumothorax predisposition. This case expands the phenotypic spectrum of clEDS and highlights the challenges with molecular analysis and diagnosis.
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