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TMEM176B was recently described as a negative modulator of Nlrp3 inflammasome activation in mice. In the mouse model, the inhibition of TMEM176B leads to an increased anti-tumoral activity which is dependent on Nlrp3. Since we have recently shown that single nucleotide variants (SNPs) in inflammasome genes, including NLRP3, significantly affect colorectal cancer (CRC) prognosis, we proposed to investigate here the association between genetic variants in TMEM176B and CRC prognosis.

Considering that, up to now, no genetic study analyzing this gene in humans exists, we selected possible functional SNPs and genotyped them in a cohort of CRC patients submitted to surgery and followed up for more than 10years. Genotype-guided assays were realized to evaluate the effect of the variant on NLRP3 inflammasome activation. Gene expression from The Cancer Genome Atlas (TCGA) cohort was analyzed to valid possible prognostic and predictive features.

We identified the Ala134Thr variant (rs2072443) in TMEM176B as a protective factor for CRC prognosis. This SNP is associated with decreased gene expression and with an increased activation of NLRP3 inflammasome, at least in monocytes and dendritic cells. Furthermore, low TMEM176B expression is associated with higher overall survival.

Altogether, these findings supported the role of TMEM176B in NLRP3 inflammasome biology and for the first time demonstrated the genetic association between rs2072443 and CRC in humans.

Altogether, these findings supported the role of TMEM176B in NLRP3 inflammasome biology and for the first time demonstrated the genetic association between rs2072443 and CRC in humans.

The course of osteosarcoma patients primarily treated as such has been well described. Little, however, is known about patients who were primarily treated assuming a different tumor diagnosis.

The database of the Cooperative Osteosarcoma Study Group COSS was searched (4.435 primary high-grade central osteosarcomas registered prior to 01/01/21). A different tumor entity had to have been assumed for at least one month after the initial diagnostic procedure before the correct diagnosis of osteosarcoma was finally made. Identified patients were analyzed for demographic, tumor-, and treatment-related factors as well as for survival outcomes.

37 patients were identified. They were a median of 19.7 (2.7-60.4) years old at first presentation and were more likely to be females than males (2314). Bone cysts (n = 8), giant cell tumor of bone (n = 6), and osteoblastoma (n = 6) were the most frequent of 29/37 (78%) benign, chondrosarcoma and its variants (n = 6) the most frequent of 8/37 (22%) malignant original diacured if finally treated according to modern osteosarcoma standards.

Osteosarcoma may initially be misdiagnosed and hence subjected to inappropriate treatment including misguided surgery. Once diagnosed correctly, some of the affected patients may still be cured if finally treated according to modern osteosarcoma standards.

Autoimmune hemolytic anemias (AIHA) constitute a rare and heterogeneous group of diseases whose therapy differs according to the type of antibody involved in the genesis of the disease and the existence or not of an identified cause. With the aim of providing a practical guide for the therapy of AIHA, we summarize the emergency therapy and general measures habitually used in all forms of AIHA, as well as the specific treatment of the most frequent primary forms of AIHA primary warm AIHA and AIHA from cold agglutinin disease (AIHA from CAD). We discuss the dependence of the treatment of the secondary forms on their underlying causes and the changes in the treatment of the primary forms in recent years.

We examined the options available for the treatment of primary warm AIHA and AIHA from CAD.

We found many differences and only one similarity in their treatment.

The differences, particularly due to the non-responsiveness of AIHA from CAD to many treatments useful for primary warm AIHA, such as steroids, splenectomy and immunosuppressive agents, must be considered in the face of each, single case of AIHA. Preliminary identification of the type of antibody involved in the genesis of the disease and careful exclusion of a secondary form are particularly important. Rituximab plays a central role in the treatment of primary warm AIHA and AIHA from CAD.

The differences, particularly due to the non-responsiveness of AIHA from CAD to many treatments useful for primary warm AIHA, such as steroids, splenectomy and immunosuppressive agents, must be considered in the face of each, single case of AIHA. Preliminary identification of the type of antibody involved in the genesis of the disease and careful exclusion of a secondary form are particularly important. Rituximab plays a central role in the treatment of primary warm AIHA and AIHA from CAD.

Survivors of stroke often experience post-stroke sleep disorders (PSSDs), but pharmacotherapy risks adverse side effects. Transcranial magnetic stimulation (TMS) is potentially a nonpharmacotherapeutic option. This meta-analysis investigated the effects of rTMS to treat PSSD.

Databases were searched for randomized controlled trials (RCTs) of rTMS to treat PSSD, conducted in accordance with the PRISMA 2020 guidelines. Risk-of-bias assessments were performed using the Cochrane risk-of-bias tool. A meta-analysis of the following indexes was performed using RevMan 5.4 software Pittsburgh sleep quality index; effective rate of sleep improvement; Hamilton Anxiety Rating Scale (for mood); and National Institute of Health Stroke Scale (NIHSS, stroke severity). Tubastatin A Mean differences (MDs) and confidence intervals (CIs) were calculated.

The meta-analysis included 17 RCTs, with 1411 patients overall. The indexes indicated that rTMS could improve the sleep quality, mood, and stroke severity of patients with PSSD Pittsburgh sleep quality index (12 studies; MD =  - 2.51, 95% CI [- 3.24, - 1.79], P < 0.00001); effective rate of sleep improvement (7 studies; MD = 4.03, 95% CI [2.43, 6.68], P < 0.0001); Hamilton Anxiety Rating Scale (2 studies; MD =  - 4.05, 95% CI [- 4.77, - 3.32], P < 0.00001); and NIHSS (2 studies; MD = -2.71, 95% CI [- 3.36, - 2.06], P < 0.00001).

The results suggest that rTMS may have positive effects on the sleep quality, mood, and stroke severity of patients with PSSD.

The results suggest that rTMS may have positive effects on the sleep quality, mood, and stroke severity of patients with PSSD.A zirconium-cobalt metal-organic framework (ZrCo-MOF) was prepared and used as sensing material to fabricate an aptasensor for trace detection of carcinoembryonic antigen (CEA). The ZrCo-MOF integrates the 3D porous structure and abundant defects of the MOF framework, the catalytic activity and inherent redox behavior of Co, and high stability of Zr-MOF, providing abundant active sites to effectively anchor aptamers. As a result, the ZrCo-MOF-based aptasensor shows high sensitivity to detect CEA via specific recognition between aptamer and CEA, as well as the formation of aptamer-CEA complex. A detection limit of 0.35 fg·mL-1 was deduced from the electrochemical impedance spectroscopy within a wide linear range of 0.001-100 pg·mL-1 for CEA, which was substantially lower than those of most reported CEA biosensors. The ZrCo-MOF-based aptasensor also shows good selectivity, reproducibility, regenerability, stability, and applicability for human serum sample. Therefore, the developed ZrCo-MOF-based aptasensor will be promising for ultrasensitive detection of biomarkers and the early diagnosis of cancer. This work presents a novel electrochemical aptasensor for the trace detection of carcinoembryonic antigen (CEA) based on a zirconium-cobalt metal-organic framework (ZrCo-MOF), which shows low detection limit of 0.35 fg·mL-1, high selectivity as well as good reproducibility, regenerability, stability, and applicability. The result provides a promising approach to detect the cancer biomarkers in an early age.The definitions and conceptualizations of health, and the management of healthcare have been challenged by the current global scenarios (e.g., new diseases, new geographical distribution of diseases, effects of climate change on health, etc.) and by the ongoing scholarship in humanities and science. In this paper we question the mainstream definition of health adopted by the WHO-'a state of complete physical, mental and social well-being and not merely the absence of disease or infirmity' (WHO in Preamble to the constitution of the World Health Organization as adopted by the international health conference, The World Health Organization, 1948)-and its role in providing tools to understand what health is in the contemporary context. More specifically, we argue that this context requires to take into account the role of the environment both in medical theory and in the healthcare practice. To do so, we analyse WHO documents dated 1984 and 1986 which define health as 'coping with the environment'. We develop the idea of 'coping with the environment', by focusing on two cardinal concepts adaptation in public health and adaptivity in philosophy of biology. We argue that the notions of adaptation and adaptivity can be of major benefit for the characterization of health, and have practical implications. We explore some of these implications by discussing two recent case studies of adaptivity in public health, which can be valuable to further develop adaptive strategies in the current pandemic scenario community-centred care and microbiologically healthier buildings.Statistical optimization of aeration conditions viz. aerobic, microaerobic and anaerobic, was performed using response surface methodology (RSM) utilizing soybean meal as medium to enhance the production of laccase from Rheinheimera sp. Maximum laccase yield (18.48 × 105 U/L) was obtained under microaerobic (static) conditions sustained for 12 h in tandem with 26 h aerobically (150 rpm) grown culture, which was 17.03-fold higher than laccase production in the starting M162 medium under aerobic conditions (150 rpm). The reduction in incubation time from 72 to 38 h and utilization of cost-effective soybean meal as medium, which is easily available from local market, have provided a promising, eco-friendly method of laccase enzyme production. Enhanced expression of laccase gene under microaerobic conditions corresponded to the increased expression of fnr (fumarate nitrate reductase) gene, the oxygen sensing global regulator. The putative FNR-binding site upstream of laccase transcription initiation site was predicted to play an imperative role in Rheinheimera sp. adaptation from aerobic to microaerobic conditions and for enhanced laccase production.Two key amino acids of isomultiflorenol synthase, Y125 and M254, were first proposed. They could be associated with the production of isomultiflorenol. Oxidosqualene cyclases (OSCs) are the first committed enzymes in the triterpenoid biosynthesis by converting 2,3-oxidosqualene to specific triterpenoid backbones. Thus, these enzymes are potential targets for developing plant-active compounds through the study of triterpenoid biosynthesis. We applied transcriptome information and metabolite profiling from Trichosanthes cucumerina L. to define the diversity of triterpenoids in this plant through OSCs. Isomultiflorenol synthase and cucurbitadienol synthase were previously identified in this plant. Here, three new OSCs, TcBAS, TcLAS, and TcCAS, were cloned and functionally characterized as β-amyrin synthase, lanosterol synthase, and cycloartenol synthase activities, respectively. We also took advantage of the multiple sequence alignment and molecular docking of OSCs exhibiting in this plant and other plant OSCs to identify key residues associated with isomultiflorenol synthase specificity.