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A case study of a 4 year old child with hypospadias and cryptorchidism on the right side is presented. Combined analysis by Karyotype and FISH showed a mosaic pattern of 48, XYYY (73%); 47,XYY (7%); 46,XY (7%) and 45,X (13%). Apart from hypospadias and cryptorchidism there were no significant phenotypic changes observed. Inheritance of this clonal abnormality was ruled out as the karyotype patterns of the child's father and brother both showed a normal karyotype. For further management, genetic counseling, and the correction of hypospadias and the undescended testis were recommended.

Introduction: We aimed to assess complications and stone-free rate of flexible ureteroscopy (FU) reusing disposable scopes (RDS) after repeated sterilization. Methods: Data from adults from 11 centers were retrospectively reviewed (January 2020-December 2022). Inclusion criteria were proximal ureteral/renal stone(s). All cases were performed using an RDS to save costs for patients who come from economically challenged environments. Residual fragments (RFs) were defined as single fragment ≥4 mm or multiple fragments of any size within 3 months. Continuous variables are presented as median and interquartile range. Results: Two thousand one hundred and eighty-three patients were included, of whom 67.0 were male. Median age was 48.0 (36-59) years. The median stone diameter was 10.2 (9-14) mm. Flash sterilization was used in 90.2 (plasma in 60.5). Approximately, 88 had FU with an RDS used ≤2 times (12: 3-5 times). RDS needed to be changed intraoperatively in 3.9 of cases due to its malfunction. Commonly, defects in RDS function were reported in upward (1.6) and downward deflection (6.5) and image quality on white balancing (4.7). Fever >38C was seen in 13.7 of cases, and sepsis in 0.5. RFs were found in 31.4 of cases. Lower pole (odds ratio [OR] 5.63) or pelvis stone (OR 4.67), faulty scopes (OR 12.8), and total operation time (OR 1.05) were factors associated with higher odds of RFs. Stone size (OR 1.09), positive urine culture (OR 1.67), interpolar stone (OR 1.68), and prestenting (OR 1.37) were factors associated with higher odds of fever/sepsis. Conclusions: RDS was used as a cost-conscious approach with a low rate of serious infections but with a high rate of RFs., Author(s): Vineet Gauhar [1]; Olivier Traxer [2]; Ravindra B Sabnis [3]; Khi Yung Fong [4]; Parimalsinh Gharia [5]; Rishi Grover [5]; Deepak Ragoori [6]; Ee Jean Lim [7]; Yiloren Tanidir [...]

Objective: Diabetes management remains challenging despite advancements in therapeutics, with many subjects developing complications. Yoga has been shown to aid diabetes management. This study investigates the impact of yoga therapy on diabetes progression, utilizing proteomics and metabolomics analyses to explore underlying molecular mechanisms. Methodology: A 3-month longitudinal study involving healthy subjects with prediabetes and diabetes was conducted. Blood glucose, glycated hemoglobin (HbA1c), lipid profile, and malondialdehyde (MDA) levels were measured before and after the yoga intervention. Results and Conclusion: Healthy subjects showed no significant changes in blood glucose, lipid profile, HbA1c, or MDA levels. However, subjects with prediabetes and diabetes experienced positive changes, with decreases in HbA1c and MDA levels. Proteomics and metabolomics analyses provided insights into the molecular mechanisms by which yoga attenuates diabetes progression in subjects with prediabetes and diabetes. This study is a pioneering effort to understand the molecular basis of yoga’s beneficial effects on diabetes management.

Schwannomas are considered benign soft tissue tumors that originate from Schwann cells. Oral Schwannomas are rare and account for only 1% of all Schwannomas. Cellularschwannoma (CS) is a rare histological variant of schwannoma, characterized by high cellularity and cellular atypia. We present a case of localized growth of palatal mucosa that imitated the features of malignant peripheral nerve sheath tumor (MPNST) on histopathological examination; it was differentiated from MPNST by the correlation of clinical, histopathological, and immunohistochemical features.

Abstract High-throughput screening techniques are pivotal to unlocking the mysteries of biology. Yet, the promise of droplet microfluidics in enabling single-cell resolution, ultra-high-throughput screening remains largely unfulfilled. Droplet sorting errors caused by polydisperse droplet sizes that are often inevitable in multi-step assays have severely limited the effectiveness and utility of this technique, especially when screening large libraries. Even a relatively low 1% sorting error results in 10,000 false calls in a 1,000,000 droplet screen, imposing an unreasonably large burden on downstream validation. Here, we present NOVAsort (Next-generation Opto-Volume-based Accurate droplet sorter), a device capable of discerning droplets based on both size and fluorescence intensity. With a 1000- and 10,000-fold reduction in false positives and false negatives, respectively. NOVAsort addresses the challenges of conventional droplet sorting approaches and sets standards for accuracy and throughput in droplet microfluidic assays.

Introduction: We aim to share the experience of a single center in the management of eight cases of renal primitive neuroectodermal tumor (PNET) which are uncommon, aggressive tumors. The objectives were to study the presentation of the disease, the treatment offered and its outcomes, and the comparison of the treatment with published literature. Methods: The single-center renal PNET data of all patients were retrospectively reviewed from 2011 to 2022. Renal PNET was seen in eight patients. Minimum follow-up period of 1 year was required. Results: Male-to-female ratio was 7:1. The mean age was 26.5 years. All were locally advanced tumors on presentation. One patient had an inferior vena cava thrombus, one patient had metastases on presentation, and two patients had tumor extending to paranephric space. The diagnosis was made by histopathology supported by immunohistochemistry showing CD99 positivity. All patients were treated with radical nephrectomy, followed by chemotherapy in all and radiotherapy in three patients. Two patients expired at 3½ and 6 years after surgery, the remaining six are alive at a median follow-up period of 34.5 months. Conclusion: Renal PNET is an uncommon renal tumor which is aggressive and requires multimodal therapy for prolonged survival., Author(s): Niramya J. Pathak (corresponding author) [1]; Abhishek G. Singh [1]; Pavan J. Surwase [1]; Sahil A. Agrawal [1]; Arvind P. Ganpule [1]; Ravindra B. Sabnis [1]; Mahesh R. Desai [...]

Introduction We aimed to assess complications and stone-free rate of flexible ureteroscopy (FU) reusing disposable scopes (RDS) after repeated sterilization. Methods Data from adults from 11 centers were retrospectively reviewed (January 2020–December 2022). Inclusion criteria were proximal ureteral/renal stone(s). All cases were performed using an RDS to save costs for patients who come from economically challenged environments. Residual fragments (RFs) were defined as single fragment ≥4 mm or multiple fragments of any size within 3 months. Continuous variables are presented as median and interquartile range. Results Two thousand one hundred and eighty-three patients were included, of whom 67.0% were male. Median age was 48.0 (36–59) years. The median stone diameter was 10.2 (9–14) mm. Flash sterilization was used in 90.2% (plasma in 60.5%). Approximately, 88% had FU with an RDS used ≤2 times (12%: 3–5 times). RDS needed to be changed intraoperatively in 3.9% of cases due to its malfunction. Commonly, defects in RDS function were reported in upward (1.6%) and downward deflection (6.5%) and image quality on white balancing (4.7%). Fever >38C was seen in 13.7% of cases, and sepsis in 0.5%. RFs were found in 31.4% of cases. Lower pole (odds ratio [OR] 5.63) or pelvis stone (OR 4.67), faulty scopes (OR 12.8), and total operation time (OR 1.05) were factors associated with higher odds of RFs. Stone size (OR 1.09), positive urine culture (OR 1.67), interpolar stone (OR 1.68), and prestenting (OR 1.37) were factors associated with higher odds of fever/sepsis. Conclusions RDS was used as a cost-conscious approach with a low rate of serious infections but with a high rate of RFs.

The purpose of the current study is to investigate the qualitative characterization of nine different pure vegetable oil samples using dielectric spectroscopy which is a vastly resourceful and reasoned technique in the temperature range 0 ℃ to 25 ℃. Time-domain reflectometry technique is applied up to the microwave frequencies of 50 GHz for the first time for qualitative characterization of the selected vegetable oil samples with a special focus on the variances of dielectric properties like dielectric permittivity (ε′), dielectric loss (ε″), relaxation time concerning temperature and other physiochemical properties of the vegetable oil specimens.The experimental methodology involves the use of time-domain reflectometry (TDR) measurements up to the scale of 50 GHz done to analyse the aspects like lower and higher scales of values towards the static dielectric permittivity (εs) and relaxation time (τ) (ps) to further meaningfully compare and correlate this values with the fatty acid profiles of each of the nine vegetable oil samples to reason and draw comparative inferences about the quality aspects of vegetable oils. Microwave TDR studies provide an effective, alternate, simple, rapid, and viable way to exercise quality control and actuate data regarding the quality status of vegetable oils. Variances of dielectric permittivity (ε′) concerning dielectric loss (ε″) are graphically interpreted using the Cole Davidson model. The static dielectric permittivity (εs) was further recertified and measured accurately by using a precision LCR meter. Thermodynamic properties of all the nine vegetable oil samples like enthalpy (ΔH) (kJ/mol) and entropy of activation (ΔS) (J/mol ∙ K) are also calculated to further insight the dependence of dielectric properties of these oil samples concerning temperature.This dielectric spectroscopic study affirms the association of the quality aspects of these nine vegetable oil samples with their dielectric properties by providing meaningful correlations, comparatives and concurrencies of dielectric properties concerning the physiochemical properties which are a part of fatty acid profiles of these samples, which is a novel aspect of this study. The Cole-Cole plot underlines the tendency of realignment of dipoles as per the applied field. The complex permittivity spectra indicate the dwindling nature of molecular alignment including a slow decline to average coinciding values depending on the molecular bonding pattern of vegetable oil samples. The activation energy (ΔH) in (kJ/mol) is calculated for all the samples which are indicative of endothermic nature which experimentally proves that high energy is required for rotation of unsaturated oil sample molecules with low relaxation times.The highlight of the current dielectric spectroscopic study is that it conclusively divides the nine vegetable oil samples into two groups based on the dielectric property of relaxation time. The vegetable oil samples with higher relaxation times were measured in ps [soyabean oil (398.5), groundnut oil (412.5), flaxseed oil (318.4), and castor oil (305.3)] and the oil samples with lower relaxation times [safflower oil (37.91), sunflower oil (30.6), walnut oil (22.4) and sesame oil (38.4)] and correlate this dielectric aspect with the aspect extent of the presence of oleic acid: C18H34O2, linoleic acid: C18H32O2, linolenic acid: C18H30O2 and ricinoleic acid C18H34O3 alongside the percentage of unsaturation present in the fatty acid profile of each sample. Saturated fatty profile of coconut oil (percentage of saturation 82.5) with low relaxation time (41.8) ps and its concurrency concerning the extent of percentage presence of lauric acid C12H24O2 (52 ps) myristic acid: C14H28O2 (21 ps) is also correlated. The current dielectric spectroscopic study further highlights and compares the variances of dielectric permittivity of the nine vegetable oils samples with the percentage of unsaturation /saturation to infer upon the correlation with the fatty acid profile of these oil samples.

Radical cure of Plasmodium vivax malaria must include elimination of quiescent "hypnozoite" forms in the liver; however, the only FDA-approved treatments are contraindicated in many vulnerable populations. To identify new drugs and drug targets, we screened the Repurposing, Focused Rescue, and Accelerated Medchem library against P. vivax liver stages and identified the DNA methyltransferase inhibitors hydralazine and cadralazine as active against hypnozoites. We then used bisulfite sequencing and immunostaining to identify cytosine modifications in the infectious stage (sporozoites) and liver stages, respectively. A subsequent screen of epigenetic inhibitors revealed hypnozoites are broadly sensitive to histone acetyltransferase and methyltransferase inhibitors, indicating that several epigenetic mechanisms are likely modulating hypnozoite persistence. Our data present an avenue for the discovery and development of improved radical cure antimalarials.

Introduction: We aim to share the experience of a single center in the management of eight cases of renal primitive neuroectodermal tumor (PNET) which are uncommon, aggressive tumors. The objectives were to study the presentation of the disease, the treatment offered and its outcomes, and the comparison of the treatment with published literature. Methods: The single-center renal PNET data of all patients were retrospectively reviewed from 2011 to 2022. Renal PNET was seen in eight patients. Minimum follow-up period of 1 year was required. Results: Male-to-female ratio was 7:1. The mean age was 26.5 years. All were locally advanced tumors on presentation. One patient had an inferior vena cava thrombus, one patient had metastases on presentation, and two patients had tumor extending to paranephric space. The diagnosis was made by histopathology supported by immunohistochemistry showing CD99 positivity. All patients were treated with radical nephrectomy, followed by chemotherapy in all and radiotherapy in three patients. Two patients expired at 3½ and 6 years after surgery, the remaining six are alive at a median follow-up period of 34.5 months. Conclusion: Renal PNET is an uncommon renal tumor which is aggressive and requires multimodal therapy for prolonged survival.

Abstract Diabetic kidney disease (DKD) is a devastating kidney disease and lacks effective therapeutic interventions. The present study was aimed to determine whether reconstituted high‐density lipoprotein (rHDL) ameliorated renal injury in eNOS−/− dbdb mice, a mouse model of DKD. Three groups of mice, wild type C57BLKS/J (non‐diabetes), eNOS−/− dbdb (diabetes), and eNOS−/− dbdb treated with rHDL (diabetes+rHDL) with both males and females were used. The rHDL nanoparticles were administered to eNOS−/− dbdb mice at Week 16 at 5 μg/g body weight in ~100 μL of saline solution twice per week for 4 weeks via retroorbital injection. We found that rHDL treatment significantly blunted progression of albuminuria and GFR decline observed in DKD mice. Histological examinations showed that the rHDLs significantly alleviated glomerular injury and renal fibrosis, and inhibited podocyte loss. Western blots and immunohistochemical examinations showed that increased protein abundances of fibronectin and collagen IV in the renal cortex of eNOS−/− dbdb mice were significantly reduced by the rHDLs. Taken together, the present study suggests a renoprotective effect of rHDLs on DKD.

Oncogenic FOXO1 gene fusions drive a subset of rhabdomyosarcoma (RMS) with poor survival; to date, these cancer drivers are therapeutically intractable. To identify new therapies for this disease, we undertook an isogenic CRISPR-interference screen to define PAX3-FOXO1-specific genetic dependencies and identified genes in the GATOR2 complex. GATOR2 loss in RMS abrogated aa-induced lysosomal localization of mTORC1 and consequent downstream signaling, slowing G1-S cell cycle transition. In vivo suppression of GATOR2 impaired the growth of tumor xenografts and favored the outgrowth of cells lacking PAX3-FOXO1. Loss of a subset of GATOR2 members can be compensated by direct genetic activation of mTORC1. RAS mutations are also sufficient to decouple mTORC1 activation from GATOR2, and indeed, fusion-negative RMS harboring such mutations exhibit aa-independent mTORC1 activity. A bisteric, mTORC1-selective small molecule induced tumor regressions in fusion-positive patient-derived tumor xenografts. These findings highlight a vulnerability in FOXO1 fusion-positive RMS and provide rationale for the clinical evaluation of bisteric mTORC1 inhibitors, currently in phase I testing, to treat this disease. Isogenic genetic screens can, thus, identify potentially exploitable vulnerabilities in fusion-driven pediatric cancers that otherwise remain mostly undruggable.

Background: There is a need to reliably render urolithiasis patients completely stone free with minimal morbidity. We report on the initial safety and feasibility with steerable ureteroscopic renal evacuation (SURE) in a prospective study using basket extraction as a comparison. Materials and Methods: A pilot randomized controlled study was conducted comparing SURE with basket extraction postlaser lithotripsy. SURE is performed using the CVAC™ Aspiration System, a steerable catheter (with introducer). The safety and feasibility of steering CVAC throughout the collecting system under fluoroscopy and aspirating stone fragments as it was designed to do were evaluated. Fluoroscopy time, change in hemoglobin, adverse events through 30 days, total and proportion of stone volume removed at 1 day, intraoperative stone removal rate, and stone-free rate (SFR) at 30 days through CT were compared. Results: Seventeen patients were treated (n = 9 SURE, n = 8 Basket). Baseline demographics and stone parameters were not significantly different between groups. One adverse event occurred in each group (self-limiting ileus for SURE and urinary tract infection for Basket). No mucosal injury and no contrast extravasation were observed in either group. The CVAC catheter was steered throughout the collecting system and aspirated fragments. There was no significant difference in fluoroscopy time, procedure time, change in hemoglobin, or stone removal rate between groups. SURE removed more and a greater proportion of stone volume at day 1 vs baskets (202 mm3 vs 91 mm3, p

The immunosuppression administered to renal transplant recipients to safeguard renal function elevates their susceptibility to renal cancer, which is estimated to be 15 times higher than in the general population. The current study aimed to analyze various aspects of native kidney renal cell carcinoma (RCC) in renal transplant recipients. This study involved a retrospective analysis of 11 patients who underwent nephrectomy for RCC in native kidneys among renal transplant recipients at our institution since 1992. Our institutional incidence was 0.4%. Median age at presentation was 57 (49–60) years. The ratio of male: female was 10:1. Most patients were asymptomatic at presentation and native kidney disease before transplantation was undetermined. In our study, the median time interval between diagnosis of RCC and transplant was 9.1 (8.4–11.2) years. All patients underwent native kidney nephrectomy. Clear cell type was more common than papillary type, 3.5 (2.5–4.2). Ten patients were diagnosed with stage I disease and one patient had stage IV disease. Fuhrman nuclear grading revealed low grades in nine patients and three patients had Grade 3. Immunosuppressive therapy modification was done in nine patients. Meticulous follow-up of renal transplant patients is essential for earlier diagnosis and appropriate treatment of native kidney RCC in transplant recipients. Authors recommend every year follow-up in transplant recipients with special emphasis on ultrasound of native kidney.

BACKGROUND: Rhabdomyosarcoma (RMS) is the most common soft-tissue sarcoma of childhood, but occurs infrequently in infants (

Abstract Acute myeloid leukemia (AML) microenvironment exhibits cellular and molecular differences among various subtypes. Here, we utilize single-cell RNA sequencing (scRNA-seq) to analyze pediatric AML bone marrow (BM) samples from diagnosis (Dx), end of induction (EOI), and relapse timepoints. Analysis of Dx, EOI scRNA-seq, and TARGET AML RNA-seq datasets reveals an AML blasts-associated 7-gene signature (CLEC11A, PRAME, AZU1, NREP, ARMH1, C1QBP, TRH), which we validate on independent datasets. The analysis reveals distinct clusters of Dx relapse- and continuous complete remission (CCR)-associated AML-blasts with differential expression of genes associated with survival. At Dx, relapse-associated samples have more exhausted T cells while CCR-associated samples have more inflammatory M1 macrophages. Post-therapy EOI residual blasts overexpress fatty acid oxidation, tumor growth, and stemness genes. Also, a post-therapy T-cell cluster associated with relapse samples exhibits downregulation of MHC Class I and T-cell regulatory genes. Altogether, this study deeply characterizes pediatric AML relapse- and CCR-associated samples to provide insights into the BM microenvironment landscape.

This single-center, prospective, observational study was conducted at a tertiary-care center over a span of two years. Patients presenting with acute Anterior-Wall STEMI were included as a study population. The subgroups included qRBBB pattern on ECG and non-qRBBB group. Among 1128 patients included in the study, 100 (11.28 %) patients presented with qRBBB pattern. Increased risk of cardiogenic shock, increased hospital-stay, a higher Killip class on presentation, high incidence of recanalized IRA, remarkably depressed LVEF were significantly associated with qRBBB-MI, which is a menacing form of ACS that leads not only to a high mortality but also to a long-term morbidity.

The targeting and conversion of the immunosuppressive (M2) tumor-associated macrophages (TAMs) to an immunostimulatory (M1) phenotype can induce tumor regression in advanced melanoma. We have previously characterized and reported the ability of reconstituted high-density lipoprotein nanoparticles (rHDL NPs) functionalized with DSPE-PEG-mannose (DPM) to deliver payload to macrophages. Herein, we investigate the modulation of macrophage phenotype and payload delivery mechanisms of the rHDL-DPM NPs in RAW 264.7 murine macrophages exposed to the conditioned medium (CM) from murine B16-F10 melanoma cells. The rHDL-DPM NPs loaded with the Stimulator of Interferon genes agonist, DMXAA, reduced protein levels of M2 markers. Through the mannose moiety, the rHDL-DPM-DMXAA NPs enhanced the production of interferon β and CXCL10 compared to the free DMXAA in the B16-F10 CM-educated RAW 264.7 macrophages. Compared to their non-mannosylated counterpart, the rHDL-DPM NPs delivered their payload more efficiently to the B16-F10 CM-educated RAW 264.7 macrophages. Mechanistically, both the scavenger receptor type B class 1 (SR-B1) and the mannose receptor (CD206) facilitated payload delivery to the macrophages via endocytic and non-endocytic mechanisms. Finally, the CM from rHDL-DPM-DMXAA NPs -treated macrophages enhanced paclitaxel (paclitaxel)-mediated cytotoxicity in B16-F10 cells. Together, these in vitro findings demonstrate the potential of the mannose-functionalized rHDL NPs in improving the targeting of M2-like TAMs and treatment outcomes when combined with immunotherapy or PTX in B16-F10 melanoma in vivo models.

Renal cell carcinoma classically presents as a triad of hematuria, loin pain, and a palpable mass. Sometimes it may present as an incidental finding, whereas spontaneous renal hemorrhage or Wunderlich syndrome is a rare presentation of renal cell carcinoma. We present a clinical case of 51 years old gentleman who presented with right flank pain with no other significant history. Computed tomography scan showed right perirenal hemorrhage with no abnormality in the kidney. A drain was placed and the hematoma was evacuated. The patient was discharged. On follow-up at 6 months, he was asymptomatic but found to have a renal lesion on ultrasound, which was evaluated with computed tomography scan and partial nephrectomy was done and histopathology was suggestive of papillary renal cell carcinoma. Renal cell carcinoma being an aggressive tumor, any spontaneous perirenal hemorrhage with unknown etiology mandates a strict follow-up with prompt imaging for concerns of impending renal cell carcinoma.

A 21-year-old man underwent a joint-preserving posterior acetabular resection of metastatic osteosarcoma using a three-dimensional (3D) printed model and intraoperative navigation. The combined application of these advanced technologies can allow for surgical planning of osteotomies involving complex anatomy and help guide resections intraoperatively. They can maximise the achievement of negative oncological margins, preservation of native hip stability and critical neurovascular structures, and optimal postoperative function in an effort to resect all clinically evident disease. For this particular patient, with secondary bony metastases, they allowed for a safe and well-tolerated procedure that ultimately afforded him palliative benefit, improved quality of life and, conceivably, prolonged survival in the setting of a devastating prognosis. Although he, sadly, has since passed away, he survived for over 2 years after initial metastasis with preserved hip stability and the ability to graduate college, stay active and maintain a quality of life that addressed his goals of care.

Phosphatase and tensin homolog deleted on chromosome 10 (PTEN) is a tumor suppressor and bi-functional lipid and protein phosphatase. We report that the metabolic regulator pyruvate dehydrogenase kinase1 (PDHK1) is a synthetic-essential gene in PTEN-deficient cancer and normal cells. The PTEN protein phosphatase dephosphorylates nuclear factor κB (NF-κB)-activating protein (NKAP) and limits NFκB activation to suppress expression of PDHK1, a NF-κB target gene. Loss of the PTEN protein phosphatase upregulates PDHK1 to induce aerobic glycolysis and PDHK1 cellular dependence. PTEN-deficient human tumors harbor increased PDHK1, a biomarker of decreased patient survival. This study uncovers a PTEN-regulated signaling pathway and reveals PDHK1 as a potential target in PTEN-deficient cancers.

Identification of the genomic drivers of cancer has led to the clinical development of targeted therapies that strike at the heart of many malignancies. Nonetheless, many cancers outsmart such precision-medicine efforts, and thus therapeutic resistance contributes significantly to cancer mortality. Attempts to understand the basis for resistance in patient samples and laboratory models has yielded two major benefits: one, more effective chemical inhibitors and rational combination therapies are now employed to prevent or circumvent resistance pathways; and two, our understanding of how oncogenic mutations drive cancer cell survival and oncogene addiction is deeper and broader, highlighting downstream or parallel cellular programs that shape these phenotypes. This review discusses emerging principles of resistance to therapies targeted against key oncogenic drivers.

OBJECTIVE:To classify NICU interventions for parental distress and quantify their effectiveness.STUDY DESIGN:We systematically reviewed controlled studies published before 2017 measuring NICU parental distress, defined broad intervention categories, and used random-effects meta-analysis to quantify treatment effectiveness.RESULTS:Among 1643 unique records, 58 eligible trials predominantly studied mothers of preterm infants. Interventions tested in 22 randomized trials decreased parental distress (p