Age-dependent associations between RSA reactivity, affective and cognitive regulation, and psychopathology risk in young children exposed to varying levels of socioeconomic disadvantage.

This study examined autonomic nervous system activity (respiratory sinus arrhythmia [RSA]) as a biomarker of psychopathology in an ethnically and socioeconomically diverse sample (N = 57) of young children ages 4-7 years. RSA was measured at baseline and across four standardized tasks designed to assess self-regulation in both affective (i.e., "hot") and cognitive (i.e., "cool") contexts during early childhood. Our findings reveal that age moderated RSA activity, such that reduced RSA suppression was associated with a heightened risk of externalizing problems among older children during "cool" and "hot" contexts; for younger children, only RSA suppression during "hot" contexts predicted externalizing risk. The influence of socioeconomic disadvantage did not moderate the relationship between RSA and the risk of psychopathology, and there were minimal associations between RSA suppression and internalizing symptoms at this age range. These results suggest that autonomic variability may be a more effective predictor of psychopathology risk in older children, perhaps as they transition into formal schooling and face increasingly complex cognitive and social demands. Findings have implications for the identification of psychopathology in early developmental periods when regulation over emotions becomes essential for academic and social success.

Changes in environmental exposures over decades may influence the genetic architecture of severe spermatogenic failure.

STUDY QUESTION: Do the genetic determinants of idiopathic severe spermatogenic failure (SPGF) differ between generations? SUMMARY ANSWER: Our data support that the genetic component of idiopathic SPGF is impacted by dynamic changes in environmental exposures over decades. WHAT IS KNOWN ALREADY: The idiopathic form of SPGF has a multifactorial etiology wherein an interaction between genetic, epigenetic, and environmental factors leads to the disease onset and progression. At the genetic level, genome-wide association studies (GWASs) allow the analysis of millions of genetic variants across the genome in a hypothesis-free manner, as a valuable tool for identifying susceptibility risk loci. However, little is known about the specific role of non-genetic factors and their influence on the genetic determinants in this type of conditions. STUDY DESIGN, SIZE, DURATION: Case-control genetic association analyses were performed including a total of 912 SPGF cases and 1360 unaffected controls. PARTICIPANTS/MATERIALS, SETTING, METHODS: All participants had European ancestry (Iberian and German). SPGF cases were diagnosed during the last decade either with idiopathic non-obstructive azoospermia (n = 547) or with idiopathic non-obstructive oligozoospermia (n = 365). Case-control genetic association analyses were performed by logistic regression models considering the generation as a covariate and by in silico functional characterization of the susceptibility genomic regions. MAIN RESULTS AND THE ROLE OF CHANCE: This analysis revealed 13 novel genetic association signals with SPGF, with eight of them being independent. The observed associations were mostly explained by the interaction between each lead variant and the age-group. Additionally, we established links between these loci and diverse non-genetic factors, such as toxic or dietary habits, respiratory disorders, and autoimmune diseases, which might potentially influence the genetic architecture of idiopathic SPGF. LARGE SCALE DATA: GWAS data are available from the authors upon reasonable request. LIMITATIONS, REASONS FOR CAUTION: Additional independent studies involving large cohorts in ethnically diverse populations are warranted to confirm our findings. WIDER IMPLICATIONS OF THE FINDINGS: Overall, this study proposes an innovative strategy to achieve a more precise understanding of conditions such as SPGF by considering the interactions between a variable exposome through different generations and genetic predisposition to complex diseases. STUDY FUNDING/COMPETING INTEREST(S): This work was supported by the "Plan Andaluz de Investigación, Desarrollo e Innovación (PAIDI 2020)" (ref. PY20_00212, P20_00583), the Spanish Ministry of Economy and Competitiveness through the Spanish National Plan for Scientific and Technical Research and Innovation (ref. PID2020-120157RB-I00 funded by MCIN/ AEI/10.13039/501100011033), and the 'Proyectos I+D+i del Programa Operativo FEDER 2020' (ref. B-CTS-584-UGR20). ToxOmics-Centre for Toxicogenomics and Human Health, Genetics, Oncology and Human Toxicology, is also partially supported by the Portuguese Foundation for Science and Technology (Projects: UIDB/00009/2020; UIDP/00009/2020). The authors declare no competing interests. TRIAL REGISTRATION NUMBER: N/A.

Evaluation of the Relationship Between Diabetic Macular Edema and Renal Function in a Latino Population.

INTRODUCTION: Diabetic macular edema (DME) is one of the leading causes of vision impairment. The relationship between DME and estimated glomerular filtration rate (eGFR) has not been clearly evaluated in Hispanic or Latino populations. The objective of this study was to evaluate the eGFR in a Latino population with DME. METHODS: A cross-sectional, observational, and descriptive study was carried out on the basis of a multicenter phase III clinical trial. RESULTS: A total of 82 subjects diagnosed with DME (36 women and 46 men) were included in the study. The mean age was 61.93 ± 6.71 years. Mean values of the blood chemistry parameters glycated hemoglobin and eGFR were 7.20 ± 0.95% and 74.42 ± 26.82 mL/min/1.73 m2, respectively. The time elapsed since diagnosis of diabetes mellitus was 15.30 ± 7.35 years, while the duration of DME was 1.41 ± 1.75 years. Mean values for central macular thickness (CMT) and total macular volume (TMV) were 440.99 ± 132.22 µm and 11.97 ± 2.11 mm3, respectively. DME duration had a negative correlation with TMV (Rho - 0.26, p < 0.05) and a positive correlation with mean arterial pressure (Rho 0.26, p < 0.05). CMT was correlated with TMV (Rho 0.43, p < 0.0001) and visual acuity (Rho 0.26, p < 0.05). No significant correlations were observed between eGFR and CMT, TMV, or any demographic variable (p > 0.05). Chronic kidney disease (CKD) was associated with hypertension (OR 9.32, p = 0.035), elevated intraocular pressure (IOP) (OR 0.03, p = 0.011), and advanced age (OR 0.45, p = 0.011). CMT was significantly associated with TMV (ß = 27.69, p < 0.0001). CONCLUSIONS: We did not find a correlation between eGFR and DME. Our findings suggest that the presence of hypertension is associated with a decrease in the GFR < 60 mL/min/1.73 m2, and CKD may be associated with advanced age and elevated IOP which may increase the risk for the development of glaucoma. TRIAL REGISTRATION: NCT05217680 (clinicaltrials.gov).

Delivering on sustainable development goals in wastewater reuse for agriculture: Initial prioritization of emerging pollutants in the Tula Valley, Mexico.

Wastewater reuse for agricultural irrigation is a widespread beneficial practice, in line with the sustainable development goals. However, contaminants of emerging concern (CECs) present in wastewater, such as pharmaceuticals, pose an environmental risk. The Tula Valley in Mexico is one of the world's largest agricultural areas reusing wastewater for agriculture. However, no untargeted CEC monitoring has been undertaken there, limiting the information available to prioritise local environmental risk assessment. Furthermore, CEC environmental presence in the Global South remains understudied, compared to the Global North. There is a risk that current research efforts focus on CECs predominantly found in the Global North, leading to strategies that may not be appropriate for the Global South where the pollution profile may be different. To address these knowledge gaps, a sampling campaign at five key sites in the Tula Valley was undertaken and samples analysed using multi-residue targeted and untargeted liquid chromatography mass spectrometry methods. Using the targeted data, ten CECs were found to be of environmental risk for at least one sampling site: 4­tert-octylphenol, acetaminophen, bezafibrate, diclofenac, erythromycin, levonorgestrel, simvastatin, sulfamethoxazole, trimethoprim and tramadol as well as total estrogenicity (combination of three steroid hormones). Six of these have not been previously quantified in the Tula Valley. Over one hundred pollutants never previously measured in the area were identified through untargeted analysis supported by library spectrum match. Examples include diclofenac and carbamazepine metabolites and area-specific pollutants such as the herbicide fomesafen. This research contributes to characterising the presence of CECs in the Global South, as well as providing site-specific data for the Tula Valley.

Immunotherapy for Cancer: Common Gastrointestinal, Liver, and Pancreatic Side Effects and Their Management.

Cancer cells can block the activation of T lymphocytes by deploying inhibitory signals to cell surface receptors that downregulate the immune response. Immune checkpoint inhibitors (ICI) are monoclonal antibodies that regulate the immune response by acting on these receptors. The use of ICI has been successful for cancer types that do not respond well to conventional chemotherapy, showing clinical benefit in various advanced and metastatic cancers and supporting the promise of cancer immunotherapy. However, in some cases, these treatments are associated with immune-related adverse events, many of which affect the digestive system. The treatment of immune-related adverse events depends on the affected organ and the severity of symptoms. Here, we review the commonly used US FDA-approved ICI and briefly outline their mechanism of action. We also describe the resulting collateral effects on the gastrointestinal tract, liver, and pancreas and discuss their management and prognosis.

Randomized controlled trial of an internet-based self-guided hand exercise program to improve hand function in people with systemic sclerosis: the Scleroderma Patient-centered Intervention Network Hand Exercise Program (SPIN-HAND) trial.

BACKGROUND: Systemic sclerosis (scleroderma; SSc) is a rare autoimmune connective tissue disease. Functional impairment of hands is common. The Scleroderma Patient-centered Intervention Network (SPIN)-HAND trial compared effects of offering access to an online self-guided hand exercise program to usual care on hand function (primary) and functional health outcomes (secondary) in people with SSc with at least mild hand function limitations. METHODS: The pragmatic, two-arm, parallel-group cohort multiple randomized controlled trial was embedded in the SPIN Cohort. Cohort participants with Cochin Hand Function Scale (CHFS) scores ≥ 3 and who indicated interest in using the SPIN-HAND Program were randomized (3:2 ratio) to an offer of program access or to usual care (targeted N = 586). The SPIN-HAND program consists of 4 modules that address (1) thumb flexibility and strength; (2) finger bending; (3) finger extension; and (4) wrist flexibility and strength. The primary outcome analysis compared CHFS scores 3 months post-randomization between participants offered versus not offered the program. Secondary outcomes were CHFS scores 6 months post-randomization and functional health outcomes (Patient-Reported Outcomes Measurement Information System profile version 2.0 domain scores) 3 and 6 months post-randomization. RESULTS: In total, 466 participants were randomized to intervention offer (N = 280) or usual care (N = 186). Of 280 participants offered the intervention, 170 (61%) consented to access the program. Of these, 117 (69%) viewed at least one hand exercise instruction video and 77 (45%) logged into the program website at least 3 times. In intent-to-treat analyses, CHFS scores were 1.2 points lower (95% CI - 2.8 to 0.3) for intervention compared to usual care 3 months post-randomization and 0.1 points lower (95% CI - 1.8 to 1.6 points) 6 months post-randomization. There were no statistically significant differences in other outcomes. CONCLUSION: The offer to use the SPIN-HAND Program did not improve hand function. Low offer uptake, program access, and minimal usage among those who accessed the program limited our ability to determine if using the program would improve function. To improve engagement, the program could be tested in a group format or as a resource to support care provided by a physical or occupational therapist. TRIAL REGISTRATION: NCT03419208 . Registered on February 1, 2018.

Immune and spermatogenesis-related loci are involved in the development of extreme patterns of male infertility.

We conducted a genome-wide association study in a large population of infertile men due to unexplained spermatogenic failure (SPGF). More than seven million genetic variants were analysed in 1,274 SPGF cases and 1,951 unaffected controls from two independent European cohorts. Two genomic regions were associated with the most severe histological pattern of SPGF, defined by Sertoli cell-only (SCO) phenotype, namely the MHC class II gene HLA-DRB1 (rs1136759, P = 1.32E-08, OR = 1.80) and an upstream locus of VRK1 (rs115054029, P = 4.24E-08, OR = 3.14), which encodes a protein kinase involved in the regulation of spermatogenesis. The SCO-associated rs1136759 allele (G) determines a serine in the position 13 of the HLA-DRß1 molecule located in the antigen-binding pocket. Overall, our data support the notion of unexplained SPGF as a complex trait influenced by common variation in the genome, with the SCO phenotype likely representing an immune-mediated condition.

Effect of Low-Dose Radiotherapy on the Circulating Levels of Paraoxonase-1-Related Variables and Markers of Inflammation in Patients with COVID-19 Pneumonia.

The aim of our study was to investigate the changes produced by low-dose radiotherapy (LDRT) in the circulating levels of the antioxidant enzyme paraoxonase-1 (PON1) and inflammatory markers in patients with COVID-19 pneumonia treated with LDRT and their interactions with clinical and radiological changes. Data were collected from the IPACOVID prospective clinical trial (NCT04380818). The study included 30 patients treated with a whole-lung dose of 0.5 Gy. Clinical follow-up, as well as PON1-related variables, cytokines, and radiological parameters were analyzed before LDRT, at 24 h, and 1 week after treatment. Twenty-five patients (83.3%) survived 1 week after LDRT. Respiratory function and radiological images improved in survivors. Twenty-four hours after LDRT, PON1 concentration significantly decreased, while transforming growth factor beta 1 (TGF-ß1) increased with respect to baseline. One week after LDRT, patients had increased PON1 activities and lower PON1 and TGF-ß1 concentrations compared with 24 h after LDRT, PON1 specific activity increased, lactate dehydrogenase (LDH), and C-reactive protein (CRP) decreased, and CD4+ and CD8+ cells increased after one week. Our results highlight the benefit of LDRT in patients with COVID-19 pneumonia and it might be mediated, at least in part, by an increase in serum PON1 activity at one week and an increase in TGF-ß1 concentrations at 24 h.

Common genetic variation in KATNAL1 non-coding regions is involved in the susceptibility to severe phenotypes of male infertility.

BACKGROUND: Previous studies in animal models evidenced that genetic mutations of KATNAL1, resulting in dysfunction of its encoded protein, lead to male infertility through disruption of microtubule remodelling and premature germ cell exfoliation. Subsequent studies in humans also suggested a possible role of KATNAL1 single-nucleotide polymorphisms in the development of male infertility as a consequence of severe spermatogenic failure. OBJECTIVES: The main objective of the present study is to evaluate the effect of the common genetic variation of KATNAL1 in a large and phenotypically well-characterised cohort of infertile men because of severe spermatogenic failure. MATERIALS AND METHODS: A total of 715 infertile men because of severe spermatogenic failure, including 210 severe oligospermia and 505 non-obstructive azoospermia patients, as well as 1058 unaffected controls were genotyped for three KATNAL1 single-nucleotide polymorphism taggers (rs2077011, rs7338931 and rs2149971). Case-control association analyses by logistic regression assuming different models and in silico functional characterisation of risk variants were conducted. RESULTS: Genetic associations were observed between the three analysed taggers and different severe spermatogenic failure groups. However, in all cases, the haplotype model (rs2077011*C | rs7338931*T | rs2149971*A) better explained the observed associations than the three risk alleles independently. This haplotype was associated with non-obstructive azoospermia (adjusted p = 4.96E-02, odds ratio = 2.97), Sertoli-cell only syndrome (adjusted p = 2.83E-02, odds ratio = 5.16) and testicular sperm extraction unsuccessful outcomes (adjusted p = 8.99E-04, odds ratio = 6.13). The in silico analyses indicated that the effect on severe spermatogenic failure predisposition could be because of an alteration of the KATNAL1 splicing pattern. CONCLUSIONS: Specific allelic combinations of KATNAL1 genetic polymorphisms may confer a risk of developing severe male infertility phenotypes by favouring the overrepresentation of a short non-functional transcript isoform in the testis.

Common Variation in the PIN1 Locus Increases the Genetic Risk to Suffer from Sertoli Cell-Only Syndrome.

We aimed to analyze the role of the common genetic variants located in the PIN1 locus, a relevant prolyl isomerase required to control the proliferation of spermatogonial stem cells and the integrity of the blood-testis barrier, in the genetic risk of developing male infertility due to a severe spermatogenic failure (SPGF). Genotyping was performed using TaqMan genotyping assays for three PIN1 taggers (rs2287839, rs2233678 and rs62105751). The study cohort included 715 males diagnosed with SPGF and classified as suffering from non-obstructive azoospermia (NOA, n = 505) or severe oligospermia (SO, n = 210), and 1058 controls from the Iberian Peninsula. The allelic frequency differences between cases and controls were analyzed by the means of logistic regression models. A subtype specific genetic association with the subset of NOA patients classified as suffering from the Sertoli cell-only (SCO) syndrome was observed with the minor alleles showing strong risk effects for this subset (ORaddrs2287839 = 1.85 (1.17-2.93), ORaddrs2233678 = 1.62 (1.11-2.36), ORaddrs62105751 = 1.43 (1.06-1.93)). The causal variants were predicted to affect the binding of key transcription factors and to produce an altered PIN1 gene expression and isoform balance. In conclusion, common non-coding single-nucleotide polymorphisms located in PIN1 increase the genetic risk to develop SCO.

Meta-analysis and machine learning to explore soil-water partitioning of common pharmaceuticals.

The first meta-analysis and modelling from batch-sorption literature studies of the soil/water partitioning of pharmaceuticals is presented. Analysis of the experimental conditions reported in the literature demonstrated that though batch-sorption studies have value, they are limited in evaluating partitioning under environmentally-relevant conditions. Recommendations are made to utilise environmental relevant pharmaceutical concentrations, perform batch-sorption studies at temperatures other than 4, 20 and 25 °C to better reflect climate diversity, and utilise the Guideline 106 methodology as a benchmark to enable comparison between future studies (and support modelling and prediction). The meta-dataset comprised 82 data points, which were modelled using multivariate analysis; where Kd (soil/water partitioning coefficient) was the independent variable. The dependent variables fit into three categories: 1) pharmaceutical studied (including physical-chemical properties), 2) soil characteristics and 3) experimental conditions. The pharmaceutical solubility, the soil/liquid equilibration time (prior to adding the pharmaceutical), the soil organic carbon, the soil sterilisation method and the liquid phase were found to be significantly important variables for predicting Kd.

Translating wastewater reuse for irrigation from OECD Guidelines: Tramadol sorption and desorption in soil-water matrices.

Treated and untreated wastewater is often used for agricultural irrigation and, despite the many benefits of this practice, it poses the risk of biologically active chemical pollutants (such as pharmaceuticals, like tramadol) entering the environment. The partitioning of tramadol between soil/water at environmentally relevant concentrations is important to understand its environmental toxicity. Kinetics and isotherm sorption studies based on the Organisation for Economic Cooperation and Development (OECD) 106 Guideline were undertaken, ensuring comparability to previous studies. Studies were undertaken in three soils of different characteristics using aqueous concentrations of tramadol from 500 ng L-1 (environmentally relevant) to 100 µg L-1 (comparable to previous studies). Two of the soils presented a significantly (p < 0.05) higher sorption at a lower initial tramadol concentration (5000 ng L-1), compared to 20,000 ng L-1. Hysteresis was observed in all studied soils, indicating the accumulation of tramadol. Higher sorption to soils correlated with higher clay content, with soil/water partitioning coefficients (Kd) of 5.5 ± 13.3, 2.5 ± 3.8 and 0.9 ± 3.0 L kg1 for soils with clay contents of 41.9%, 24.5% and 7.4%, respectively. Cation exchange was proposed as the main sorption mechanism for tramadol to soils when the pH was below tramadol's pKa values (9.41 and 13.08). A comparative kinetics study between tramadol in soil/calcium chloride buffer and soil/wastewater effluent demonstrated significantly higher (p < 0.05) tramadol sorption to soil from wastewater effluent. This has the environmental implication that clay soils will be able to retain tramadol from irrigation water, despite the organic content of the irrigation water. Therefore, our studies show that tramadol soil sorption is likely to be higher in agricultural environments reusing wastewater than that predicted from experiments using the OECD 106 Guideline calcium chloride buffer.

Acute Attack of Glaucoma after Scleral Melting and Iris Blockage of the Surgical Ostium: A Case Report of a Complication Derived from a Mitomycin C Supplemented Trabeculectomy.

Aim: To describe a case of an acute attack of glaucoma due to scleral melting in the area where a trabeculectomy was previously done. This condition resulted from the blockage of the surgical opening due to an iris prolapse in an eye that was previously supplemented with mitomycin C (MMC) during a filtering surgery and bleb needling revision. Case description: A 74-year-old Mexican female with a prior glaucoma diagnosis who assisted to an appointment presenting an acute ocular hypertensive crisis after several months of adequately controlled intraocular pressure (IOP). Ocular hypertension had been regulated after undergoing a trabeculectomy and bleb needling revision; both supplemented with MMC. The severe IOP increase occurred due to uveal tissue blockage in the filtering site, related to melting of the sclera in the same area. The patient was successfully treated through the use of a scleral patch graft and the implantation of an Ahmed valve. Conclusion: An acute attack of glaucoma associated with scleromalacia after trabeculectomy and needling has not been previously reported and is currently attributed to MMC supplementation. Nevertheless, the use of a scleral patch graft and further glaucoma surgery seems to be an efficient way to treat this condition. Clinical significance: Even though this complication was appropriately managed with this patient, we want to prevent further cases like this through the judicious and careful use of MMC. How to cite this article: Paczka JA, Ponce-Horta AM, Tornero-Jimenez A. Acute Attack of Glaucoma after Scleral Melting and Iris Blockage of the Surgical Ostium: A Case Report of a Complication derived from a Mitomycin C Supplemented Trabeculectomy. J Curr Glaucoma Pract 2022;16(3):199-204.

Contribution of TEX15 genetic variants to the risk of developing severe non-obstructive oligozoospermia.

Background: Severe spermatogenic failure (SPGF) represents one of the most relevant causes of male infertility. This pathological condition can lead to extreme abnormalities in the seminal sperm count, such as severe oligozoospermia (SO) or non-obstructive azoospermia (NOA). Most cases of SPGF have an unknown aetiology, and it is known that this idiopathic form of male infertility represents a complex condition. In this study, we aimed to evaluate whether common genetic variation in TEX15, which encodes a key player in spermatogenesis, is involved in the susceptibility to idiopathic SPGF. Materials and Methods: We designed a genetic association study comprising a total of 727 SPGF cases (including 527 NOA and 200 SO) and 1,058 unaffected men from the Iberian Peninsula. Following a tagging strategy, three tag single-nucleotide polymorphisms (SNPs) of TEX15 (rs1362912, rs323342, and rs323346) were selected for genotyping using TaqMan probes. Case-control association tests were then performed by logistic regression models. In silico analyses were also carried out to shed light into the putative functional implications of the studied variants. Results: A significant increase in TEX15-rs1362912 minor allele frequency (MAF) was observed in the group of SO patients (MAF = 0.0842) compared to either the control cohort (MAF = 0.0468, OR = 1.90, p = 7.47E-03) or the NOA group (MAF = 0.0472, OR = 1.83, p = 1.23E-02). The genotype distribution of the SO population was also different from those of both control (p = 1.14E-02) and NOA groups (p = 4.33-02). The analysis of functional annotations of the human genome suggested that the effect of the SO-associated TEX15 variants is likely exerted by alteration of the binding affinity of crucial transcription factors for spermatogenesis. Conclusion: Our results suggest that common variation in TEX15 is involved in the genetic predisposition to SO, thus supporting the notion of idiopathic SPGF as a complex trait.

Intensity of care and perceived burden among informal caregivers to persons with chronic medical conditions: a systematic review and meta-analysis.

PURPOSE: Informal caregivers provide ongoing assistance to a loved one with a health condition. No studies have compared caregiving intensity and perception of burden across chronic medical conditions. MATERIALS AND METHODS: Databases were searched from inception through 11 September 2020 to identify studies that included the Level of Care Index or the Zarit Burden Inventory (ZBI) among caregivers for people with chronic diseases. Pooled mean ZBI scores and 95% confidence intervals by medical condition were calculated using a random effects model and heterogeneity with I2. RESULTS: Ninety-seven included articles reported on 98 unique samples across 21 chronic diseases. No study used the Level of Care Index. Among 12 disease groups with more than one study, heterogeneity was too high (I2 range: 0-99.6%, ≥76.5% in 11 groups) to confidently estimate burden. The percent of studies rated high risk of bias ranged from 0% to 98%, but all external validity items were rated as high-risk in >50% of studies. CONCLUSIONS: Findings highlight the need for studies on caregiver burden to improve sampling techniques; better report sampling procedures and caregiver and care recipient characteristics; and develop a standard set of outcomes, including a measure of caregiving intensity. Systematic Review Registration: CRD42017080962IMPLICATIONS FOR REHABILITATIONThe amount of burden reported by caregivers to loved ones is associated with reduced physical and mental health.We found considerable heterogeneity in perceived burden reported by informal caregivers across different studies within disease groups, which is likely related to methodological issues, including sampling techniques.Health care providers who use research on caregiver burden should assess how representative study samples may be and exercise caution in drawing conclusions.

A renal cell carcinoma tumorgraft platform to advance precision medicine.

Renal cell carcinoma (RCC) encompasses a heterogenous group of tumors, but representative preclinical models are lacking. We previously showed that patient-derived tumorgraft (TG) models recapitulate the biology and treatment responsiveness. Through systematic orthotopic implantation of tumor samples from 926 ethnically diverse individuals into non-obese diabetic (NOD)/severe combined immunodeficiency (SCID) mice, we generate a resource comprising 172 independently derived, stably engrafted TG lines from 148 individuals. TG lines are characterized histologically and genomically (whole-exome [n = 97] and RNA [n = 102] sequencing). The platform features a variety of histological and oncogenotypes, including TCGA clades further corroborated through orthogonal metabolomic analyses. We illustrate how it enables a deeper understanding of RCC biology; enables the development of tissue- and imaging-based molecular probes; and supports advances in drug development.

Anisakidosis diagnosticada tras la expulsión de vermes en deposiciones: forma poco frecuente de diagnóstico en humanos / Anisakidosis diagnosed after expulsion of worms in stools: a rare form of diagnosis in humans

Resumen La anisakidosis es una zoonosis parasitaria accidental y cosmopolita de los seres humanos, siendo su hospedero definitivo los mamíferos marinos como lobos de mar, focas y delfines, entre otros. El ser humano se infecta por el consumo en estado larvario del nemátodo de la familia Anisakidae presentes en pescados y mariscos crudos como la merluza o el congrio. Los helmintos se ubican preferentemente en el tubo digestivo alto, observándose la regurgitación del parásito a la boca o evidenciándose durante la realización de una endoscopía digestiva alta. En forma infrecuente las larvas pueden migrar al peritoneo o seguir su paso por el intestino delgado y colon, siendo inhabitual la expulsión por las deposiciones. Presentamos el caso de una expulsión dos larvas L3 de la familia Anisakidae en deposiciones.

Abstract Anisakidosis is an accidental and cosmopolitan parasitic zoonosis of human beings, its definitive host being marine mammals such as sea lions, seals and dolphins, among others. Humans are infested by consumption in the larval stage of the nematode of Anisakis present in raw fish and shellfish such as hake or conger eel. The infestation is preferably located in the upper digestive tract, observing the regurgitation of the parasite to the mouth or becoming evident during an upper gastrointestinal endoscopy. In rare cases, the larvae can migrate to the peritoneum or continue their passage through the small intestine and colon, with expulsion in stools being unusual. We present a case of expulsion of two larvae of the Anisakidae family in feces.

Acute liver failure due to herpes simplex virus: diagnostic clues and potential role of plasmapheresis: A case report.

INTRODUCTION: Acute liver failure (ALF) is a life-threatening condition that remains challenging for physicians despite several advances in supportive care. Etiologies vary worldwide, with herpes simplex virus (HSV) hepatitis representing less than 1% of cases. Despite its low incidence, ALF is a lethal cause of acute necrotizing hepatitis and has a high mortality. Early antiviral treatment is beneficial for survival and decreased liver transplantation necessity. However, plasmapheresis, despite its theoretical potential benefit, is scarcely reported. PATIENT CONCERNS: A 25-year-old woman with no known disease presented with painful pharynx ulcers, increased transaminases and impaired liver function. DIAGNOSIS: ALF due to a disseminated HSV-2 primary infection was diagnosed with a positive polymerase chain reaction for HSV-2 in the biopsied liver tissue and blood. INTERVENTIONS: Empiric antiviral treatment was initiated. After clinical deterioration, plasmapheresis was also initiated. OUTCOMES: After 6 cycles of plasmapheresis and supportive care, the patient's condition improved without undergoing liver transplantation. CONCLUSIONS: ALF is a life-threatening condition, and HSV as an etiology must be suspected based on background, clinical manifestation, and laboratory information. The potential role of plasmapheresis in HSV hepatitis should be considered.