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Fertilization failure (complete fertilization failure or low fertilization rotes) after intracytoplasmic sperm injection (ICSI) can occur in rare eases. In the majority of these cases, the unfertilized oocytes are inactivated. Assisted oocyte activation was applied as a treatment option for a case of low fertilization rate as a clinical trial. A patient with a low fertilization rate (ranging from 0% to 33.3%; mean = 17.0%) after eight previous ICSI cycles at another hospital, was diagnosed with fertilization failure. The most likely cause of fertilization failure was failure of oocyte activation. Therefore, artificial oocyte activation by strontium treatment was combined with ICSI to achieve viable fertilized oocytes. Oocytes were stimulated with strontium (10 mM SrCl2 60 min) approximately 30 min after ICSI. Six injected oocytes were stimulated and all were then successfully fertilized. Two blastocysts were transferred into the uterus, resulting in a pregnancy and birth. A second pregnancy was achieved following implantation of two cryopreserved embryos (one blastocyst and one morula). In conclusion, strontium treatment was found to be an effective method for artificial oocyte activation in a case with a low fertilization rate after ICSI. [ABSTRACT FROM AUTHOR]

Patients with infective endocarditis (IE) often have renal complications which may include infarcts, abscesses and glomerulonephritis (GN). Furthermore, it is generally accepted that there is an association between IE and anti-neutrophil cytoplasmic antibody (ANCA). Here, we report the case of a 24-year-old man who developed rapidly progressive GN in the course of IE due to infection with α-streptococcus. The initial clinical manifestation of the condition was severe sacroiliitis without fever. Sandwich ELISA showed that the patient was positive for PR3-ANCA at low titer, and the classical complement pathway was also activated. Renal biopsy demonstrated several lesions: focal embolic GN, GN with immune deposits and focal and segmental crescentic necrotizing GN. Treatment with antibiotics and steroids led to eradication of the infection, and resolution of the renal disease was accompanied by immediate disappearance of PR3-ANCA and hypocomplementemia. During a 4-year follow-up period, no recurrence was observed. There have only been 7 case reports of GN associated with IE and PR3-ANCA in which the renal pathology has been described, and the current report is the first to document renal pathology in a patient with isolated pulmonic valve IE and PR3-ANCA. Moreover, this report is the first to show a change in renal biopsy findings in response to treatment. A review of the 7 literature cases and that of our patient showed that none involved pauci-immune GN. Hence, further studies are needed to clarify the prevalence of pauci-immune GN in ANCA-positive IE patients. [ABSTRACT FROM AUTHOR]

We present the case of a 69-year-old man with nephrotic syndrome and renal insufficiency, who developed lobular glomerulonephritis. An electron microscopy examination of a renal biopsy showed micro-tubular structures of 24 nm in diameter in the subendothelial space and the paramesangial area. These deposits were PAS-positive and Congo red-negative, and revealed predominantly positive staining for κ light chain. There was no evidence of diseases with highly organized glomerular deposits, such as amyloidosis, cryoglobulinemia, systemic lupus erythematosus or paraproteinemia. Therefore, the patient was diagnosed to have immunotactoid glomerulopathy (ITG). During a seven-year course he has not developed any disease known to be associated with organized glomerular immune deposits. Hence, we believe ITO occurred as a primary glomerular disease in this case. We also highlight cases of ITG with microtubular deposits that have been reported in Japan, compare these cases to previous reports, and show that the characteristics of the Japanese cases are male predominance; a high incidence of membranoproliferative glomerulonephritis (MPGN); a low incidence of monoclonal gammopathy and hematological malignancies and a higher incidence of hypocomplementemia. [ABSTRACT FROM AUTHOR]

This review contains data on a wide class of microporous materials with frameworks belonging to the sodalite topological type. Various methods for the synthesis of these materials, their structural and crystal chemical features, as well as physical and chemical properties are discussed. Specific properties of sodalite-related materials make it possible to consider they as thermally stable ionic conductors, catalysts and catalyst carriers, sorbents, ion exchangers for water purification, matrices for the immobilization of radionuclides and heavy metals, hydrogen and methane storage, and stabilization of chromophores and phosphors. It has been shown that the diversity of properties of sodalite-type materials is associated with the chemical diversity of their frameworks and extra-framework components, as well as with the high elasticity of the framework. [ABSTRACT FROM AUTHOR]

Background: Road safety improvement is a governmental priority due to driver-caused accidents. Driving style variation affects safety, with emotional regulation being pivotal. However, functional near-infrared spectroscopy (fNIRS) studies show inconsistent prefrontal cortex activity during emotion processing. This study examines prefrontal cortex response to negative emotional stimuli, particularly traffic accident images, across drivers diverse in age and gender. Method: The study involved 118 healthy males (44.38 ± 12.98 years) and 84 females (38.89 ± 10.60 years). The Multidimensional Driving Style Inventory (MDSI) was used to assess driving behavior alongside fNIRS recordings. Participants viewed traffic accident and neutral images while prefrontal oxygenation was monitored. Results: Women rated traffic accidents (t-test = 2.43; p < 0.016) and neutral images (t-test = 2.19; p < 0.030) lower in valence than men. Arousal differences were significant for traffic accident images (t-test = −3.06; p < 0.002). correlational analysis found an inverse relationship between Dissociative scale scores and oxygenation (all p-values ≤ 0.013). Greater prefrontal oxygenation occurred with neutral images compared to traffic accidents. Left hemisphere differences (t-test = 3.23; p < 0.001) exceeded right hemisphere differences (t-test = 2.46; p < 0.015). Subgroup analysis showed male participants to be driving these disparities. Among adaptive drivers, significant oxygenation differences between neutral and accident images were evident in both hemispheres (left: t-test = 2.72, p < 0.009; right: t-test = 2.22, p < 0.030). Conclusions: Male drivers with maladaptive driving styles, particularly dissociative ones, exhibit reduced prefrontal oxygenation when exposed to neutral and traffic accident images. This response was absent in female drivers, with no notable age-related differences. [ABSTRACT FROM AUTHOR]

For those affected, infertility is linked to impaired overall health and reduced life expectancy. In particular, infertile individuals bear an increased risk for cardiovascular disease (CVD) and different types of cancer, partially due to lifestyle differences and to genetic alterations that cause both infertility and an increased cancer risk. Genetic variants causing an increased CVD risk are more commonly found in infertile individuals, but their link to infertility remains unclear. Offspring of infertile couples, conceived via medically assisted reproduction, are as likely as their parents to exhibit or develop adiposity, hormonal alterations such as insulin resistance, and infertility. The effects on health of subsequent generations are completely unclear. [ABSTRACT FROM AUTHOR]

Chronic immunosuppressive therapy is currently the only effective method to prevent acute rejection of a transplanted organ. Unfortunately, the expected effect of treatment brings a number of grave side effects, one of the most serious being cardiovascular complications. In our study, we wanted to investigate how treatment with commonly used immunosuppressive drugs affects the occurrence of programmed cardiac cell death. For this purpose, five groups of rats were treated with different triple immunosuppressive regimens. Cardiac tissue fragments were subjected to the TUNEL assay to visualize apoptotic cells. The expression of Bcl-2 protein, Bax protein, caspase 3 and caspase 9 was also assessed. This study indicates that all immunosuppressive protocols used chronically at therapeutic doses result in an increased percentage of cells undergoing apoptosis in rat heart tissue. The greatest changes were recorded in the TMG (rats treated with tacrolimus, mycophenolate mofetil and glucocorticosteroids) and CMG (rats treated with cyclosporin A, mycophenolate mofetil and glucocorticosteroids) groups. The TRG (rats treated with rapamycin, tacrolimus and glucocorticosteroids) group showed the lowest percentage of apoptotic cells. The internal apoptosis pathway was confirmed only in the TMG group; in the remaining groups, the results indicate programmed cell death via the receptor pathway. [ABSTRACT FROM AUTHOR]

BACKGROUND: We previously investigated the factors involved in uraemic neuropathy in patients undergoing regular haemodialysis and found a significant relationship between the severity of vibration sensation impairment and the patients' smoking habits. The administration of methylcobalamin markedly improved the severity of uraemic neuropathy in terms of vibration perception thresholds. We presumed that abnormal cyanide metabolism is involved in the development of uraemic neuropathy. METHODS: Serum levels of thiocyanate (SCN-), the detoxication product of cyanide, were determined in 12 patients with preterminal chronic renal failure (PCRF), 30 patients undergoing regular haemodialysis (HD patients), and 13 healthy volunteers as a control group. Nine of the 30 HD patients were smokers. In addition, in 10 HD patients without smoking habits and 10 non-smoking healthy volunteers, the proportion of each vitamin B12 analogue in total vitamin B12 was estimated. RESULTS: The mean serum SCN- level of the 12 PCRF patients (5.1 +/- 1.5 micrograms/ml) was significantly higher than that of the control (2.8 +/- 0.9 micrograms/ml) (P < 0.01). The mean SCN- level before haemodialysis in the 21 non-smoking HD patients was identical to that in the PCRF group, whereas the level in the nine smoking HD patients (7.2 +/- 1.8 micrograms/ml) significantly higher than that in the non-smoking subgroup (P < 0.01). In 16 HD patients with methylcobalamin treatment, serum SCN- levels were lower than in those without methylcobalamin treatment (4.5 +/- 0.5 micrograms/ml in non-smoking subgroup, P < 0.05). And in the methylcobalamin-treated subgroup (n = 5), the proportion of each vitamin B12 analogue in total vitamin B12 was normal. In the untreated subgroup (n = 5), the proportion of cyanocobalamin fraction (10.5 +/- 2.6%) was as high as the level in Leber's disease patients, while the proportion of methylcobalamin fraction was low. And the serum cyanocobalamin level was higher in the treated subgroup. CONCLUSION: In uraemic patients, cyanide detoxication capability is impaired because of a reduced SCN- clearance, and increased cyanocobalamin synthesis indicates elevation of cyanide pool, which would be related to the development of uraemic neuropathy. Methylcobalamin was considered to be utilized in cyanide detoxication process via cyanocobalamin synthesis. [ABSTRACT FROM PUBLISHER]

Context: Despite recent medical advances, the number of patients beginning dialysis annually is increasing in both the United States and Japan. The ethnically homogeneous population of Japan presents an opportunity to study the presence of factors other than race/ethnicity that might contribute to incidence of end-stage renal disease (ESRD).Objective: To determine if and where regional differences exist in ESRD in Japan.Design, Setting, and Subjects: Analysis of data reported by the Japanese Society for Dialysis Therapy based on the annual number of patients with ESRD beginning maintenance dialysis therapy in all 47 prefectures of Japan from 1982 to 1998.Main Outcome Measures: Mean annual ESRD incidence and increasing rate of ESRD in each of 11 predefined areas making up the entire country.Results: Incidence of ESRD increased approximately 3-fold in Japan during the study years, from 81.3 per 1 million in 1982 to 237.6 per 1 million in 1998. Significant regional differences were found in both measures. The mean (SEM) annual ESRD incidence (P<.01) and increasing rate of ESRD (P<.01), respectively, were significantly different across Japan. Koshinetsu (140 [11] per 1 million and 9.1 [0.6] per 1 million/y) and Hokuriku (141 [12] per 1 million and 9.7 [0.5] per 1 million/y) were the areas with the lowest incidence and increasing rate of incidence, while Okinawa (188 [17] per 1 million and 13.4 [0.6] per 1 million/y) and Kyushu (179 [15] per 1 million and 12.0 [0.6] per 1 million/y) were the areas with the highest incidence and increasing rate of incidence.Conclusions: We found definite and significant regional differences in incidence and increasing rate of incidence of ESRD in Japan. Further analyses are needed to identify factors that contribute to these regional differences and thereby improve strategies for treatment of renal disease. JAMA. 2000;284:2622-2624. [ABSTRACT FROM AUTHOR]

Intracytoplasmic sperm injection (ICSI) is clinically used to treat obstructive/nonobstructive azoospermia. This study compared the efficacy of ICSI with cauda epididymal and testicular sperm in Wistar (WI) and Brown- Norway (BN) rats. The transfer of ICSI oocytes with cryopreserved epididymal and testicular WI sperm resulted in offspring production of 26.2% and 3.7%-4.7%, respectively (P < 0.05). Treatments for artificial oocyte activation (AOA) and acrosome removal improved pronuclear formation in BN-ICSI oocytes; however, only AOA treatment was effective in producing offspring (3.7%-6.5%). In the case of ICSI with testicular sperm (TESE-ICSI), one offspring (0.6%) was derived from the BN-TESE-ICSI oocytes. The application of AOA or a hypo-osmotic sperm suspension did not improve the production of TESE-ICSI offspring. Thus, outbred WI rat offspring can be produced by using ICSI and less efficiently by using TESE-ICSI. Challenges in producing offspring by using ICSI/TESE-ICSI in inbred BN strain require further investigation. [ABSTRACT FROM AUTHOR]

Simple Summary: First-line treatment options for patients with hormone-sensitive metastatic prostate cancer (mHSPC) have evolved in recent years with treatment intensification strategies used to improve survival and delay disease progression. This study reviews the evolution of treatment intensification in these patients, as well as ongoing trials that will provide us with answers to different questions that we ask in routine clinical practice. The treatment landscape for metastatic hormone-sensitive prostate cancer continues to evolve, with systemic treatment being the mainstay of current treatment. Prognostic and predictive factors such as tumour volume and disease presentation have been studied to assess responses to different treatments. Intensification and de-escalation strategies arouse great interest, so several trials are being developed to further personalize the therapy in these populations. Is there an optimal sequence and a possible option to de-intensify treatment in selected patients with a favourable profile? This and other goals will be the subject of this review. [ABSTRACT FROM AUTHOR]

Background/Aim: This study investigated the follow-up rate of living kidney donors and explored the factors related to continuous follow-up and remnant renal function, enabling the optimal management of living kidney donors. Patients and Methods: We retrospectively evaluated 180 living kidney donors who underwent donor nephrectomies at our institute. Clinical information was obtained from medical charts, and remnant renal function was defined as the estimated glomerular filtration rate 12 months after donor nephrectomy. Results: Overall, 6/180 donors (3.3%) were lost to follow-up within a year, and the follow-up rate gradually declined yearly. Independent risk factors for loss to follow-up included a follow-up period <60 months and graft survival of the recipient (p=0.002 and p=0.043, respectively). Recipient survival was correlated with loss to follow-up; however, this was not significant (p=0.051). Regarding remnant renal function, age ≥60 years, preoperative estimated glomerular filtration rate <74 ml/min/1.73 m², and a Δsingle-kidney estimated glomerular filtration rate <9.3 ml/min/1.73m² were independent risk factors for poorly preserved remnant renal function (p=0.036, p<0.0001, and p<0.0001, respectively). Using propensity score matching to adjust for preoperative factors, a Δsingle-kidney estimated glomerular filtration rate <9.3 ml/min/1.73 m2 was the only significant postoperative factor for poorly preserved remnant renal function (p=0.023). Conclusion: An increased 5-year follow-up rate could lead to an increase in long-term follow-up, and recipient prognosis may be correlated with the living kidney donor follow-up status. Furthermore, Δsingle-kidney estimated glomerular filtration rate was identified as a factor for establishing the optimal precision follow-up management of living kidney donors. [ABSTRACT FROM AUTHOR]

C3 glomerulopathy is a rare disease, characterized by an abnormal activation of the complement's alternative pathway that leads to the accumulation of the C3 component in the kidney. The disease recurs in more than half of kidney transplant recipients, with a significant impact on graft survival. Recurrence of the primary disease represents the second cause of graft loss after organ rejection. In C3 glomerulopathy, there are several risk factors which can promote a recurrence during transplantation, such as delayed graft function, infection and monoclonal gammopathy. All these events can trigger the alternative complement pathway. In this review, we summarize the impact of C3 glomerulopathy on kidney grafts and present the latest treatment options. The most widely used treatments for the disease include corticosteroids and mycophenolate mofetil, which are already used chronically by kidney transplant recipients; thus, additional treatments for C3 glomerulopathy are required. Currently, several studies using anti-complement drugs (i.e., eculizumab, Ravalizumab, avacopan) for C3 glomerulopathy in kidney transplant patients are ongoing with encouraging results. [ABSTRACT FROM AUTHOR]

The development of resistance to tyrosine kinase inhibitors (TKIs) is a major cause of treatment failure in metastatic renal cell carcinoma (mRCC). A deeper understanding of the metabolic mechanisms associated with TKI resistance is critical for refining therapeutic strategies. In this study, we established resistance to sunitinib and pazopanib by exposing a parental Caki-1 cell line to increasing concentrations of sunitinib and pazopanib. The intracellular and extracellular metabolome of sunitinib- and pazopanib-resistant mRCC cells were investigated using a nuclear magnetic resonance (NMR)-based metabolomics approach. Data analysis included multivariate and univariate methods, as well as pathway and network analyses. Distinct metabolic signatures in sunitinib- and pazopanib-resistant RCC cells were found for the first time in this study. A common metabolic reprogramming pattern was observed in amino acid, glycerophospholipid, and nicotinate and nicotinamide metabolism. Sunitinib-resistant cells exhibited marked alterations in metabolites involved in antioxidant defence mechanisms, while pazopanib-resistant cells showed alterations in metabolites associated with energy pathways. Sunitinib-resistant RCC cells demonstrated an increased ability to proliferate, whereas pazopanib-resistant cells appeared to restructure their energy metabolism and undergo alterations in pathways associated with cell death. These findings provide potential targets for novel therapeutic strategies to overcome TKI resistance in mRCC through metabolic regulation. [ABSTRACT FROM AUTHOR]

Background: An increased chance of developing chronic kidney disease (CKD), which has higher morbidity and mortality, exists among patients with Type 2 diabetes (T2D). Aims and Objectives: Our goal was to determine and classify the anthropometric, physiological, and demographic risk factors for CKD in individuals with T2D. Materials and Methods: A cross-sectional research study was conducted at a tertiary care hospital involving 218 participants. Data were collected on various parameters including age, gender, education level, employment status, height, weight, blood pressure, hemoglobin levels, and estimated glomerular filtration rates (eGFRs). Participants were selected based on specific inclusion and exclusion criteria, and rigorous statistical analyses were applied to the collected data. Using the SPSS program, we analyzed the data, and when the P<0.05, we declared the results statistically significant. Results: There were 218 people in the research, 58.3% of whom were male and 41.7% of whom were female. The mean age group was between 51 and 60 at 36.2%. The age group distribution among the patients showed significant value (P<0.0001). About 87.6% of the patients had normal weight. 49.5% were recorded in Stage 1 CKD. Fasting blood sugar has a negative correlation (-182) with glomerular filtration rate (GFR) and shows a significant result. The post-prandial blood sugar value is also statistically significant and negatively relates to GFR. In addition, random blood sugar and glycated hemoglobin also reported statistically significant values. Conclusion: In individuals with T2D, it was determined that significant risk factors for the onset of CKD include eGFR, age, and the duration of diabetes. Males had a considerably greater incidence of CAD, peripheral neuropathy, and diabetic foot. [ABSTRACT FROM AUTHOR]

Fly ash was used as raw material to prepare zeolites through silicate gels, assisted by the hydrothermal method. The silicate gels could be effectively formed in a few minutes in a molten alkali environment. The zeolites could be prepared by using these silicate gels through the hydrothermal method, which realizes the transformation from useless materials to highly valuable materials. The obtained zeolites were applied to the removal of ammonium in water, achieving the highvalue utilization of fly ash. The synthesized zeolites were characterized by X-ray diffraction (XRD), scanning electron microscopy (SEM), energy dispersive spectrum (EDS), thermogravimetric (TG), and Fourier transform infrared (FTIR) spectroscopy. The study on the adsorption and removal of ammonium in water shows that the adsorption of ammonium is more in line with pseudo first-order kinetics, and the adsorption mainly occurs in the first 20 min. The adsorption can reach equilibrium in 30 min, and the maximum adsorption capacity can reach 49.1 mg/g. The adsorption capacity of ammonium has the best performance at pH = 5. Furthermore, within a certain range, an increase in temperature is beneficial for the removal of ammonium. [ABSTRACT FROM AUTHOR]

Simple Summary: We investigated financial toxicity in Japanese patients with metastatic renal cell carcinoma using the COST tool. Despite universal coverage, patients in Japan had similar levels of financial toxicity as in other countries. There was a positive correlation between the FACT-G total score and the COST score. Age < 65 years and not having private health insurance were associated with higher financial toxicity. Information on the financial toxicity experienced by Japanese patients with metastatic renal cell carcinoma (mRCC) is lacking, even though Japan has its own unique public health insurance system. Thus, a web-based survey was conducted to evaluate the financial toxicity experienced by Japanese mRCC patients using the COmprehensive Score for financial Toxicity (COST) tool. This study enrolled Japanese patients who underwent, or were undergoing, systemic therapy for mRCC. The outcomes evaluated were the distribution of COST scores, the correlation between COST and quality of life (QOL) assessed by the Functional Assessment of Cancer Therapy-General (FACT-G) scale, and demographic factors associated with financial toxicity. The median (range) COST score was 19.0 (3.0–36.0). The Pearson correlation coefficient for COST and FACT-G total scores was 0.40. Univariate analysis revealed that not having private health insurance and lower household income per year were significantly associated with lower COST scores. Multivariate analyses showed that age < 65 years and not having private health insurance were significantly associated with lower COST scores. This study revealed that Japanese mRCC patients experience adverse financial impacts even under the universal health insurance coverage system available in Japan, and financial toxicity negatively affects their QOL. [ABSTRACT FROM AUTHOR]

Background: The intracytoplasmic sperm injection (ICSI) technique has low efficiency in cattle. This has mainly been attributed to the oocyte activation failure due to oocyte and/or sperm factors. Aim: Our aim was to evaluate the effect of conventional ICSI and Piezo-ICSI with bull or human sperm on bovine oocyte activation and embryo development and to assess its relationship with the phospholipase C zeta (PLCɀ) activity of both species. Methods: In vitro matured bovine oocytes were randomly divided into five groups and were fertilized as follows: conventional ICSI using bovine sperm with chemical activation (control), conventional ICSI using bovine sperm, Piezo-ICSI using bovine sperm, conventional ICSI using human sperm, and Piezo-ICSI using human sperm. PLCɀ activity was determined in bull and human sperm samples. Results: Within the groups using bull sperm, the oocytes fertilized by conventional ICSI had the lowest values of 2 pronuclei (PN) formation and cleavage, Piezo-ICSI increased both percentages and ICSI + chemical activation presented the highest 2 PN, cleavage, and blastocyst rates (p < 0.05). Within the groups using human sperm, the oocytes fertilized by Piezo-ICSI presented higher 2 PN and cleavage rates than those activated by conventional ICSI (p < 0.05). Piezo-ICSI with human sperm increased bovine oocyte activation as much as conventional ICSI + chemical activation with bovine sperm (p < 0.05). Higher values of PLCɀ activity were found in human sperm compared with bovine sperm (p < 0.05). Conclusion: Our results suggest that the higher stability of the bovine sperm in combination with its relatively low content of PLCɀ impairs bovine oocyte activation after ICSI. [ABSTRACT FROM AUTHOR]

Isolated splenic vein thrombosis (ISVT) is a very rare venous thromboembolism in the absence of pancreatic diseases, which can cause acute abdominal pain and chronic left-side portal hypertension. Herein, we reported a 40-year-old female patient who developed ISVT after taking oral contraceptives. Anticoagulation with oral rivaroxaban was the first-line choice of therapy in this case. Since then, abdominal pain alleviated, but she did not achieve vessel recanalization. Thus, a 7-day systemic thrombolysis with urokinase was given. Abdominal pain disappeared, but ISVT was not significantly improved. During follow-up period, long-term anticoagulation with oral rivaroxaban was given. Collectively, this case indicates the possibility of oral contraceptives as a risk factor of ISVT as well as anticoagulation combined with systemic thrombolysis as a choice of treatment for ISVT. Certainly, long-term follow-up is necessary in this case. [ABSTRACT FROM AUTHOR]

Although myofascial release techniques (MRTs) are commonly used to improve athletes' range of motion (ROM), the effectiveness of MRTs may vary depending on the specific method performed. This systematic review and meta-analysis aimed to evaluate the effects of MRTs on the ROM performance of athletes. (2) Methods: The electronic databases of Cochrane Library, PubMed, Scopus, and Web of Science were searched to identify relevant articles published up to June 2023. This study utilized the PRISMA guidelines, and four databases were searched. The methodological quality of the studies was assessed using the PEDro scale, and the certainty of evidence was reported using the GRADE scale. The overall effect size was calculated using the robust variance estimator, and subgroup analyses were conducted using the Hotelling Zhang test. (3) Ten studies met the inclusion criteria. The overall effect size results indicated that the myofascial release intervention had a moderate effect on ROM performance in athletes when compared to the active or passive control groups. (4) Conclusions: Alternative MRTs, such as myofascial trigger point therapy, can further improve the ROM performance of athletes. Gender, duration of intervention, and joint type may have a moderating effect on the effectiveness of MRTs. [ABSTRACT FROM AUTHOR]

C4d, a split product of C4 activation in classical and lectin pathways of the complement system activation, has been regarded as a footprint of tissue damage in antibody-mediated rejection in transplantology. The introduction of C4d staining into daily clinical practice aroused an ever-increasing interest in the role of antibody-mediated mechanisms in kidney allograft rejection. However, this marker of complement activation is also important in other various kidney glomerular pathologies such as immunoglobulin A nephropathy, membranoproliferative glomerulonephritis, lupus nephritis, and others. In routine histopathological practice, C4d staining can be done by two his tological methods, specifically by immunofluorescence on frozen tissue using monoclonal antibody to C4d (with the downside of unsteady availability of frozen tissue) or by immunohistochemistry using C4d antibodies on formalin-fixed and paraffin-embedded renal tissue. The aim of this narrative review is to summarize recent knowled ge about the complement fragment C4d and its significance in differe nt kidney pathologies, focusing on its immunohistochemical detection in renal tissue biopsies. We have supplemented this review with our experience with our proprietary methodology of preparation and practical use of antibodies such as anti-C4d, on a small national level. Immunohistochemical staining for C4d has revolutionized the field of renal histopathology. Despite being a simple diagnostic test, its utility can be of utmost importance, especially in a resource-poor setting where immunofluorescence and frozen tissue may not be available [ABSTRACT FROM AUTHOR]

Objective: The objective of this study is to provide a description of a group of retrospective cohort outcomes in patients with systemic lupus erythematosus (SLE) complicated with immune thrombocytopenia (ITP) receiving belimumab. Methods: This study reports on the treatment of 10 female patients (mean age 34.3 ± 14.0 years, mean weight 58.7 ± 18.2 kg) with both SLE and ITP who received belimumab in addition to basic drug therapy. The belimumab treatment regimen consisted of a dosage of 10 mg/kg, with an initial infusion every 2 weeks for the first 3 doses, followed by an infusion every 4 weeks. Results: Ten patients were included in the study. The overall response rate of thrombocytopenia was 90% after treatment. The parameters such as platelet count, lymphocyte count, erythrocyte count, hemoglobin, dsDNA, C3, and C4 were significantly improved (p <.05). The SLE Disease Activity Index (SLEDAI), British Islet lupus Assessment Group 2004 (BILAG-2004), and Physician Global assessment (PGA) scores were significantly decreased (p <.05). There were no significant differences in glutamic pyruvic transaminase (ALT), glutamic oxaloacetic transaminase (AST), and serum creatinine (Scr) before and after treatment (p >.05). Conclusion: Belimumab shows promising clinical outcomes in the treatment on patients with both SLE and ITP. Further studies are needed to validate these findings in larger patient populations and compare the efficacy of belimumab with other treatments for SLE complicated with ITP. Long-term response rates and adverse events associated with belimumab treatment also warrant further investigation. [ABSTRACT FROM AUTHOR]

Horike K, Takeda A, Yamaguchi Y, Ogiyama Y, Yamauchi Y, Murata M, Kawaguchi T, Suzuki T, Otsuka Y, Inaguma D, Goto N, Watarai Y, Uchida K, Morozumi K. Is arteriolar vacuolization a predictor of calcineurin inhibitor nephrotoxicity? Clin Transplant 2011: 25 (Suppl. 23): 23-27. © 2011 John Wiley & Sons A/S. Calcineurin inhibitors (CNI) have been commonly used as pivotal immunosuppressive agents to renal transplant recipients and have contributed significantly to improving short-term allograft survival. However, long-term administration of CNI may cause an adverse effect on kidney function, known as chronic nephrotoxicity. Chronic CNI nephrotoxicity (CNI-NT) shows characteristic histopathological findings that involve arteriolar hyalinosis. Recently, the term alternative arteriolar hyalinosis (aah) is used to discriminate CNI-specific arteriolar hyaline deposition from non-specific arteriolar hyalinosis. We studied whether arteriolar vacuolization represents an early lesion of aah as a predictor of CNI-NT. We retrospectively studied the 79 patients under treatment with a CNI immunosuppressant, who underwent living-related renal transplantation (RTx) from January 2007 to March 2009. We examined serial protocol graft biopsies at one h, one, six, and 12 months after RTx. We classified histological findings into two groups on the basis of aah lesion (with or without aah) in serial biopsies for 12 months. Arteriolar vacuolization was more frequently observed in the aah group than in the non-aah group with a significant difference. Arteriolar vacuolization was found even in the one-h biopsy specimens, indicating a non-specific histopathological finding. But in the aah group, arteriolar vacuolization tended to be more frequently observed later on. Aah can be a predictor of CNI-NT. [ABSTRACT FROM AUTHOR]

Glycolysis-related metabolic reprogramming is a central hallmark of human cancers, especially in renal cell carcinoma. However, the regulatory function of glycolytic signature in papillary RCC has not been well elucidated. In the present study, the glycolysis-immune predictive signature was constructed and validated using WGCNA, glycolysis-immune clustering analysis. PPI network of DEGs was constructed and visualized. Functional enrichments and patients' overall survival were analyzed. QRT-PCR experiments were performed to detect hub genes' expression and distribution, siRNA technology was used to silence targeted genes; cell proliferation and migration assays were applied to evaluate the biological function. Glucose concentration, lactate secretion, and ATP production were measured. Glycolysis-Immune Related Prognostic Index (GIRPI) was constructed and combined analyzed with single-cell RNA-seq. High-GIRPI signature predicted significantly poorer outcomes and relevant clinical features of pRCC patients. Moreover, GIRPI also participated in several pathways, which affected tumor immune microenvironment and provided potential therapeutic strategy. As a key glycolysis regulator, PFKFB3 could promote renal cancer cell proliferation and migration in vitro. Blocking of PFKFB3 by selective inhibitor PFK-015 or glycolytic inhibitor 2-DG significantly restrained renal cancer cells' neoplastic potential. PFK-015 and sunitinib could synergistically inhibit pRCC cells proliferation. Glycolysis-Immune Risk Signature is closely associated with pRCC prognosis, progression, immune infiltration, and therapeutic response. PFKFB3 may serve as a pivotal glycolysis regulator and mediates Sunitinib resistance in pRCC patients. [ABSTRACT FROM AUTHOR]

Glycosphingolipids (GSLs), mainly located in the cell membrane, play various roles in cancer cell function. GSLs have potential as renal cell carcinoma (RCC) biomarkers; however, their analysis in body fluids is challenging because of the complexity of numerous glycans and ceramides. Therefore, we applied wide-targeted lipidomics using liquid chromatography–tandem mass spectrometry (LC–MS/MS) with selected reaction monitoring (SRM) based on theoretical mass to perform a comprehensive measurement of GSLs and evaluate their potency as urinary biomarkers. In semi-quantitative lipidomics, 240 SRM transitions were set based on the reported/speculated structures. We verified the feasibility of measuring GSLs in cells and medium and found that disialosyl globopentaosylceramide (DSGb5 (d18:1/16:0)) increased GSL in the ACHN medium. LC–MS/MS analysis of urine samples from clear cell RCC (ccRCC) patients and healthy controls showed a significant increase in the peak intensity of urinary DSGb5 (d18:1/16:0) in the ccRCC group compared with that in the control group. Receiver operating characteristic analysis indicated that urinary DSGb5 could serve as a sensitive and specific marker for RCC screening, with an AUC of 0.89. This study demonstrated the possibility of urinary screening using DSGb5 (d18:1/16:0). In conclusion, urinary DSGb5 (d18:1/16:0) was a potential biomarker for cancer screening, which could contribute to the treatment of RCC patients. [ABSTRACT FROM AUTHOR]

Simple Summary: Quadriceps contracture is a condition that can be observed in young dogs, such as a congenital disability or complication following a hindlimb fracture. Although surgical treatments have been reported, it is difficult to restore normal limb function when the disease is advanced in stage. Rehabilitation early in the course of the disease may effectively improve progress. Using a rat model, we investigated the effectiveness of therapeutic ultrasound and neuromuscular electrical stimulation (NMES) for quadriceps contracture treatment. Quadriceps contracture was induced by immobilizing both hindlimbs for 14 days. Then, we compared the effectiveness of four rehabilitation programs, including spontaneous recovery, therapeutic ultrasound, NMES, and a therapeutic ultrasound and NMES combination on quadriceps contracture for 28 days. After completing 28 days of rehabilitation, the range of joint motion (ROM), muscle histopathology, and levels of fibrosis and anti-fibrosis-associated mRNA expression were measured. The results showed that the therapeutic ultrasound and NMES combination inhibited sarcomere length shortening, muscle atrophy, and muscle fibrosis in quadriceps contracture. Quadriceps contracture is a condition where the muscle–tendon unit is abnormally shortened. The treatment prognosis is guarded to poor depending on the progress of the disease. To improve the prognosis, we investigated the effectiveness of therapeutic ultrasound and NMES in treating quadriceps contracture in an immobilized rat model. Thirty-six Wistar rats were randomized into control, immobilization alone, immobilization and spontaneous recovery, immobilization and therapeutic ultrasound, immobilization and NMES, and immobilization and therapeutic ultrasound and NMES combination groups. The continuous therapeutic ultrasound (frequency, 3 MHz, intensity 1 W/cm2) and NMES (TENS mode, frequency 50 Hz; intensity 5.0 ± 0.8 mA) were performed on the quadriceps muscle. On Day 15, immobilization-induced quadriceps contracture resulted in a decreased ROM of the stifle joint, reduction in the sarcomere length, muscle atrophy, and muscle fibrosis. On Day 43, therapeutic ultrasound, NMES, and combining both methods improved muscle atrophy and shortening and decreased collagen type I and III and α-SMA protein. The combination of therapeutic ultrasound and NMES significantly reduced the mRNA expression of IL-1β, TGF-β1, and HIF-1α and increased TGF-β3. Therefore, the combination of therapeutic ultrasound and NMES is the most potent rehabilitation program for treating quadriceps contracture. [ABSTRACT FROM AUTHOR]

Background: Immunosuppressive agents represent a broad group of drugs, such as calcineurin inhibitors, mTOR inhibitors, and glucocorticosteroids, among others. These drugs are widely used in a number of conditions, but lifelong therapy is crucial in the case of organ recipients to prevent rejection. To further increase the safety and efficacy of these agents, their off-target mechanisms of action, as well as processes underlying the pathogenesis of adverse effects, need to be thoroughly investigated. The aim of this study was to examine the impact of various combinations of cyclosporine/tacrolimus/mycophenolate with rapamycin and steroids (CRG, TRG, MRG), on the morphology and morphometry of rats' cardiomyocytes, together with the presence of cardiac collagen and the immunoexpression of MMPs and TIMPs. Methods: Twenty-four rats were divided into four groups receiving different immunosuppressive regiments. After six months of treatment, the hearts were collected and analyzed. Results: Cardiomyocytes from the CRG cohorts demonstrated the most pronounced morphological alterations. In addition, chronic immunosuppression reduced the width and length of cardiac cells. However, immunosuppressive therapy did not alter the presence of cardiac collagen fibers. Nevertheless, we observed significant alterations regarding MMP/TIMP homeostasis. Conclusions: Chronic immunosuppression seems to disturb the MMP/TIMP balance in aspects of immunolocalization in the hearts of rats. Further studies are required to analyze other mechanisms and pathways affected by the use of immunosuppressants. [ABSTRACT FROM AUTHOR]

Background: An inflammatory disorder known as trigger finger (TF) results in pain in the proximal and distal palm and digit, as well as restricted movement and diminished function. Physiotherapists use a specific treatment called dry needling (DN) to reduce musculoskeletal pain and assist patients with mobility restriction. Objectives: This study aimed to examine the effectiveness of DN on quality of life in patients suffering from trigger finger. Methods: Forty patients, ranging in age from 45 to 75, were randomized into one of two groups in this Prospective pre and post-test, single-blind parallel group randomized controlled trial. Twenty patients were assigned to the intervention group, which included traditional physiotherapy splinting and ultrasound (ultrasonic dosage was 3MHz, the intensity of 0.5 W/cm2, and the duty cycle 50%. Duration: 5 minutes) as well as to DN upon a nodule at the proximal end of the 1st annular (A1) pulley as well as the discrepancy that existed between the flexor tendon's diameter along with its sheath at the metacarpal head. Twenty patients were assigned to the control group, which consisted of traditional treatment alone, twice weekly, for a total of ten sessions over five weeks. The trial evaluated the quality of life, severity of pain, and hand grip strength using the World Health Organization Quality-of-Life Scale (WHOQOL-BREF), visual analogue scale, and Camry dynamometer respectively two times, beforetreatment and after 10 treatment sessions. Results: Within-group analysis using MANOVA demonstrated a significant decline in VAS (p = 0.001) and a significant improvement in quality of life (p = 0.001) and hand grip strength (p = 0.001). Regarding between group comparison using MANOVA there was significant improvement in favor of the DN intervention (p = 0.001) for all measured variables. Conclusions: A 5-week dry needling approach with a traditional physiotherapy program was effective in improving in quality of life, pain intensity, and hand grip strength in patients with trigger finger, emphasizing it as the better option. Trial registration: Clinical Trial. Gov, NCT05671523. Registered 14 December 2022. [ABSTRACT FROM AUTHOR]

Intracytoplasmic sperm injection (ICSI) is the most effective procedure to resolve male infertility, enhancing overall fertilization and pregnancy outcomes. However, it is important to note that fertilization failure (FF) can still occur in a few cases after ICSI. This study aims to introduce a specialized technique of aggressive sperm immobilization for ICSI and evaluate its impact on reproductive outcomes in cases involving prior fertilization failure. All infertile couples with male partners having suboptimal semen samples and previous ICSI fertilization failure were evaluated using retrospective data from National Taiwan tertiary university hospital (NTUH) between January 2016 and February 2022. Fertilization failure in our study was defined as less than 30% fertilization rate (FR, the number of normally fertilized oocytes divided by the total number of injected mature oocytes). Data involving both standard (routine procedure) and aggressive sperm immobilization (SI) techniques during different ICSI cycles were included in this study. Standard and aggressive SI methods were performed by compressing the distal half tail of the spermatozoa ≦ 5 and 15 times prior to ICSI respectively. Generalized estimating equations analysis were applied to compare the clinical outcomes between two procedures. Overall, data from 23 infertile couples who had undergone 65 ICSI cycles (31 standard SI with low fertilization rate and 34 aggressive SI) were included in the study. The average FR in the ICSI cycles with standard SI and aggressive SI were 23.6 ± 23.1% and 49.5 ± 31.8 respectively (P = 0.0002). The majority of embryos were transferred at the day 3 stage, with an average number transferred of 2.6 ± 0.9 in the aggressive SI group and 1.9 ± 0.9 in the standard group. The number of embryos transferred per transfer cycle was higher in the aggressive SI (P = 0.015), whereas the number of good-quality embryos was similar between the two procedures (P = 0.44). There were one and seven live births from the standard SI cycles and aggressive SI cycles respectively. In conclusion, aggressive SI was associated with a significantly higher FR, resulting in more available embryos for transfer without compromising embryo quality. Therefore, this specialized technique improved pregnancy outcome among infertile couples with a previous ICSI–FF. It can be a safe, economic, and effective method to improve the assisted reproductive technologies outcomes for infertile patients affected by previous ICSI–FF. [ABSTRACT FROM AUTHOR]