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Objectives: This umbrella review aimed to review the effects of resistance training on patients with end-stage renal disease and assess the methodological quality of the available literature., Methods: An umbrella review and meta-meta-analysis was performed. A systematic search was conducted until May 2022. Article selection, quality assessment, and risk of bias assessment were performed by two independent reviewers. The meta-meta-analyses were performed with a random-effects model and the summary statistics were presented in the form of a forest plot with a weighted compilation of all standardized mean differences and corresponding 95% confidence interval. Twenty-four reviews were eventually included. The protocol was registered in the international registry PROSPERO (CRD42022321702)., Results: Resistance training showed positive effects on functional capacity (g = 0.614), aerobic capacity (g = 0.587), health-related quality of life (g = 0.429), and peak force (g = 0.621). Fifteen of the included studies (63%) presented low risk of bias, and the remaining studies (37%) showed unclear risk of bias., Conclusion: Resistance training in patients undergoing hemodialysis is an intervention that shows positive results regarding physical and functional outcomes. The quality level of the literature is inconclusive, but the included studies present low risk of bias., (© 2023. The Author(s).)

Purpose: To describe the proteomic profiles in semen samples and define the differences in sperm proteomic profiles among samples that ultimately achieved pregnancy (P) via intracytoplasmic sperm injection (ICSI) in an oocyte donation program and those that were unsuccessful (NP)., Methods: Prospective, analytical, observational nested case and control study evaluating the proteomic profile of spermatozoa from patients' ejaculates where pregnancies were (group pregnant (P), n= 4) or were not (group non-pregnant (NP), n=4) achieved after ICSI in an oocyte donation program aiming to standardize female factor. Proteins were separated and analyzed by means of SWATH-MS) and compared between P/NP groups to identify sperm biomarkers of fertility/infertility. Proteins are available via ProteomeXchange., Results: We identified and quantified 2228 proteins, with 37 significantly higher in the P group and 16 higher in NP. Enrichment analysis revealed that the increased proteins in P group sperm were related to motility, anaerobic metabolism, and protein biosynthesis functions, while the increased proteins in the NP group were involved in protein biosynthesis, protein folding, aerobic metabolism, and signal transduction, all of which are functions not previously described as influencing sperm success. Some proteins identified (e.g., SLC2A3, or CD81) are located in the cell membrane and thus may be employed to select spermatozoa by magnetic-activated cell sorting (MACS)., Conclusion(s): This work revealed differences in the proteomic profiles of sperm samples successful in achieving pregnancy and those that were not, expanding our understanding of sperm function and infertility-related molecular markers, and enabling the future development of male fertility diagnostic tools and therapies.

Carpal tunnel syndrome (CTS) is a common finding among patients with cardiac amyloidosis. We sought to determine the prevalence of cardiac amyloidosis in patients who had undergone CTS surgery. From 2005 to 2014, 308 patients ≥ 60 years underwent CTS surgery. Of these, 233 (76%) agreed to participate in the study and 101 (73 ± 8 years; 68% females) showed left ventricular hypertrophy (LVH) ≥ 12 mm and underwent additional studies to diagnose AL and ATTR amyloidosis. Based on complementary studies, three patients were diagnosed with cardiac amyloidosis (two wild-type ATTR and one AL). The three patients showed bilateral CTS with no occupational risk factors. Prevalence of cardiac amyloidosis in the overall cohort was only 1.2% (3/233), but among patients with LVH and bilateral CTS, the prevalence was 5.5% (3/55) and 13.6% (3/22) if cases with an occupational risk factor were excluded. Cardiac amyloidosis should be excluded in the presence of bilateral CTS and particularly if an occupational risk factor is absent.

Although assisted reproduction techniques involve the use of semen samples, there is little scientific methodology applied when selecting sperm. To select the most appropriate spermatozoa, first we need to define the optimal molecular characteristics. Sperm lipids may contribute to sperm function, thus our aim was to compare the lipidic profiles of sperm samples used in intracytoplasmic sperm injection cycles that ultimately led to a pregnancy with those that did not.Spermatozoa from infertile patients after intracytoplasmic sperm injection (group non-pregnant, n = 16; vs. group pregnant, n = 22) were analyzed for lipid composition using ultra-high performance liquid chromatography coupled to mass spectrometry, by means two platforms for measuring fatty acyls, bile-acids, lysoglycerophospholipids, glycerolipids, cholesteryl-esters, sphingolipids, and glycerophospholipids. Lipid levels were compared using a univariate test and multivariate analyses after logarithmic transformation.We detected 151 different lipids in the sperm samples, 10 of which were significantly increased in sperm samples from the NP group, ranging from 1.10- to 1.30-fold change. These were primarily ceramides, sphingomyelins and three glycerophospholipids, a lysophosphatidylcholine, and two plasmalogen species. Additionally, 2-Monoacylglycerophosphocholine were also found in higher levels in non-pregnant group.Our results describe the composition of sperm lipids linked to optimal sperm function, opening new possibilities for the development of male fertility diagnostic tools and culture media formulations to improve sperm quality and enhance reproductive results. Given that lipids compose the majority of the sperm plasma membrane, this information is also useful in designing new sperm selection tools that will allow for the selection of the best spermatozoa.

Purpose: It has been reported that stromal cell features may affect the clinical outcome of breast cancer patients. Cancer associated fibroblasts (CAFs) represent one of the most abundant cell types within the breast cancer stroma. Here, we aimed to explore the influence of CAFs on breast cancer gene expression, as well as on invasion and angiogenesis., Methods: qRT-PCR was used to evaluate the expression of several cancer progression related genes (S100A4, TGFβ, FGF2, FGF7, PDGFA, PDGFB, VEGFA, IL-6, IL-8, uPA, MMP2, MMP9, MMP11 and TIMP1) in the human breast cancer-derived cell lines MCF-7 and MDA-MB-231, before and after co-culture with CAFs. Stromal mononuclear inflammatory cell (MIC) MMP11 expression was used to stratify primary tumors. In addition, we assessed the in vitro effects of CAFs on both MDA-MB-231 breast cancer cell invasion and endothelial cell (HUVEC) tube formation., Results: We found that the expression levels of most of the genes tested were significantly increased in both breast cancer-derived cell lines after co-culture with CAFs from either MMP11+ or MMP11- MIC tumors. IL-6 and IL-8 showed an increased expression in both cancer-derived cell lines after co-culture with CAFs from MMP11+ MIC tumors. We also found that the invasive and angiogenic capacities of, respectively, MDA-MB-231 and HUVEC cells were increased after co-culture with CAFs, especially those from MMP11+ MIC tumors., Conclusions: Our data indicate that tumor-derived CAFs can induce up-regulation of genes involved in breast cancer progression. Our data additionally indicate that CAFs, especially those derived from MMP11+ MIC tumors, can promote breast cancer cell invasion and angiogenesis.

This study sought to determine the usefulness of genetic testing to predict evolution in hypertrophic cardiomyopathy (HCM) and to assess the role of genetic testing in clinical practice. Genetic results of 100 HCM patients tested for mutations in ≥10 HCM-causing genes were evaluated. Patients were classified as with poor (group A) or favourable (group B) clinical course. Forty-five pathogenic mutations (PM) were identified in 28 patients (56 %) from group A and in 23 (46 %) from group B (p = 0.317). Only 40 patients (40 %) exhibited PM that had been previously reported and only 15 (15 %) had PM reported in ≥10 individuals. PM associated with poor prognosis were identified in just five patients from group A (10 %). Genetic findings are not useful to predict prognosis in most HCM patients. By contrast, real-world data reinforce the usefulness of genetic testing to provide genetic counselling and to enable cascade genetic screening.

Relatively little is known about the proteome/secretome of the human preimplantation embryo, in particular the protein composition/secretion of the blastocyst just before implantation. Given the legal and ethical guidelines, new approaches are needed to study the human embryo proteome. At present, morphological assessment is the primary method used to determine embryo viability during assisted reproductive technologies cycles, but technological advances in translational research have made the use of noninvasive methods possible to determine the proteomic and metabolic status of the human embryo. We have investigated the protein secretion and consumption profile of the human blastocyst (secretome) and the implanted blastocyst (implantome) to develop new noninvasive models of blastocyst selection. In short, we herein review the information available on the human proteome using different approaches and techniques.

Background: High-risk patients undergoing prophylactic mastectomy (PM) may have unsuspected cancers identified on pathology. The optimum way to identify and manage them is controversial. Magnetic resonance imaging (MRI) may identify occult cancer preoperatively. Sentinel lymph node biopsy (SLNB) allows intraoperative staging and axillary dissection during the same operation. We determined the efficacy and cost of MRI and/or SLNB in managing high-risk PM patients., Methods: We reviewed 192 PMs in 173 patients from 1999 to 2005. Costs were estimated for MRI and SLNB during PM by the 2005 Medicare Resource-Based Relative Value Scale. We also estimated costs and procedures for the four strategies in a larger hypothetical cohort., Results: A total of 19 (10%) of 192 PMs contained occult cancers, 14 ductal carcinoma-in-situ (DCIS) and 5 invasive ductal carcinoma (IDC). In 59 patients, MRI detected an IDC but missed two DCIS and an IDC. Positive MRIs generated an additional average cost of $1,207 per patient. In 56 PMs with SLNB, 6 occult cancers were found, 5 DCIS and 1 IDC, all with negative SLNBs. Adding a SLNB costs an additional average of $644. A theoretical analysis demonstrated that PM alone costs $808 per patient, PM with SLNB costs $1,420, PM with MRI and selective SLNB costs $1,774, and PM with routine MRI and SLNB costs $2,379., Conclusions: MRI adds great cost and misses most occult cancers in PMs. SLNB allows the rare patient with occult IDC to avoid axillary dissection but adds cost. Given the low rate of unsuspected invasive cancers and the costs of MRI and SLNB, neither is recommended as standard practice for PM patients.

Recent evidences indicate new roles for the glycolytic protein glyceraldehyde-3-phosphate dehydrogenase (GAPDH) in essential mammalian cell processes, such as apoptosis and proliferation. To clarify the involvement of this protein in growth and programmed cell death in the liver, cell models of hepatocytes in culture were used to study GAPDH expression, localization and enzymatic activity in hepatocyte proliferation and apoptosis. GAPDH expression in cell compartments was studied by Western blot. Nuclear expression of GAPDH increased in apoptosis, and cytoplasmic expression was elevated in apoptosis and proliferation. Subcellular localization was determined by GAPDH immunostaining and confocal microscopic analysis. Quiescent and proliferating hepatocytes showed cytoplasmic GAPDH, while apoptotic cells showed cytoplasmic but also some nuclear staining. The glycolytic activity of GAPDH was studied in nuclear and cytoplasmic cell compartments. GAPDH enzymatic activity increased in the nucleus of apoptotic cells and in cytoplasms of apoptotic and proliferating hepatocytes. Our observations indicate that during hepatocyte apoptosis GAPDH translocates to the nucleus, maintaining in part its dehydrogenase activity, and suggest that this translocation may play a role in programmed hepatocyte death. GAPDH over-expression and the increased enzymatic activity in proliferating cells, with preservation of its cytoplasmic localization, would occur in response to the elevated energy requirements of dividing hepatocytes. In conclusion, GAPDH plays different roles or biological activities in proliferating and apoptotic hepatocytes, according to its subcellular localization.

Prothymosin alpha is an acidic protein, reported to be involved in cell proliferation and apoptosis, although its precise function in both processes are still unknown. Due to the importance of these processes in the pathogenesis of hepatic diseases and the need to understand the molecular mechanisms underlying these diseases we aimed to investigate the behavior of this protein in liver growth and apoptosis, in two models of hepatocytes in culture. Prothymosin alpha expression varied throughout the hepatocyte cell cycle, according to its progression. Proliferating hepatocytes showed increased expression of the protein, while apoptotic ones showed decreased levels. The subcellular location of prothymosin alpha differed according to the different phases of the cell cycle. Thus, it appeared with a stippled and widely dispersed pattern throughout the nucleus in quiescent and proliferating hepatocytes, while it became cytoplasmic in mitotic and late apoptotic cells. These results are in agreement with the idea that high levels of prothymosin alpha need to be present in the nucleus for proliferation, and programmed cell death requires low levels of prothymosin alpha outside of the nucleus. The differences in prothymosin alpha expression and localization during hepatocyte proliferation and apoptosis suggest that this protein may have a pleiotropic function that depends not only on its availability but also on its various localizations in different subcellular compartments.