Glutathione synthesis in the mouse liver supports lipid abundance through NRF2 repression.

Cells rely on antioxidants to survive. The most abundant antioxidant is glutathione (GSH). The synthesis of GSH is non-redundantly controlled by the glutamate-cysteine ligase catalytic subunit (GCLC). GSH imbalance is implicated in many diseases, but the requirement for GSH in adult tissues is unclear. To interrogate this, we have developed a series of in vivo models to induce Gclc deletion in adult animals. We find that GSH is essential to lipid abundance in vivo. GSH levels are highest in liver tissue, which is also a hub for lipid production. While the loss of GSH does not cause liver failure, it decreases lipogenic enzyme expression, circulating triglyceride levels, and fat stores. Mechanistically, we find that GSH promotes lipid abundance by repressing NRF2, a transcription factor induced by oxidative stress. These studies identify GSH as a fulcrum in the liver's balance of redox buffering and triglyceride production.

Rapid Whole-Genome Sequencing and Clinical Management in the PICU: A Multicenter Cohort, 2016-2023.

OBJECTIVES: Analysis of the clinical utility of rapid whole-genome sequencing (rWGS) outside of the neonatal period is lacking. We describe the use of rWGS in PICU and cardiovascular ICU (CICU) patients across four institutions. DESIGN: Ambidirectional multisite cohort study. SETTING: Four tertiary children's hospitals. PATIENTS: Children 0-18 years old in the PICU or CICU who underwent rWGS analysis, from May 2016 to June 2023. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: A total of 133 patients underwent clinical, phenotype-driven rWGS analysis, 36 prospectively. A molecular diagnosis was identified in 79 patients (59%). Median (interquartile range [IQR]) age was 6 months (IQR 1.2 mo-4.6 yr). Median time for return of preliminary results was 3 days (IQR 2-4). In 79 patients with a molecular diagnosis, there was a change in ICU management in 19 patients (24%); and some change in clinical management in 63 patients (80%). Nondiagnosis changed management in 5 of 54 patients (9%). The clinical specialty ordering rWGS did not affect diagnostic rate. Factors associated with greater odds ratio (OR [95% CI]; OR [95% CI]) of diagnosis included dysmorphic features (OR 10.9 [95% CI, 1.8-105]) and congenital heart disease (OR 4.2 [95% CI, 1.3-16.8]). Variables associated with greater odds of changes in management included obtaining a genetic diagnosis (OR 16.6 [95% CI, 5.5-62]) and a shorter time to genetic result (OR 0.8 [95% CI, 0.76-0.9]). Surveys of pediatric intensivists indicated that rWGS-enhanced clinical prognostication (p < 0.0001) and contributed to a decision to consult palliative care (p < 0.02). CONCLUSIONS: In this 2016-2023 multiple-PICU/CICU cohort, we have shown that timely genetic diagnosis is feasible across institutions. Application of rWGS had a 59% (95% CI, 51-67%) rate of diagnostic yield and was associated with changes in critical care management and long-term patient management.

Point of Care Ultrasound as a Key Tool in the Evaluation of a Woman with Syncope.

Using point of care ultrasound (POCUS) to evaluate patients with syncope in the emergency department facilitates the timely diagnosis of life-threatening pathologies. Case: A 56-year-old woman presented to the emergency department of a hospital in Bogotá, Colombia, for a syncopal episode. Vital signs, physical examination, electrocardiogram, and routine laboratory tests were normal. Cardiac POCUS was performed, which identified an echogenic mass located in the left atrium, measuring 35x28mm, which in left atrial systole appeared to occupy the entire chamber. She underwent surgical resection of the mass and histopathology revealed atrial myxoma. Conclusions: POCUS was useful in the rapid diagnosis of atrial myxoma in a woman presenting with syncope.

Penetrant-induced plasticization in microporous polymer membranes.

Penetrant-induced plasticization has prevented the industrial deployment of many polymers for membrane-based gas separations. With the advent of microporous polymers, new structural design features and unprecedented property sets are now accessible under controlled laboratory conditions, but property sets can often deteriorate due to plasticization. Therefore, a critical understanding of the origins of plasticization in microporous polymers and the development of strategies to mitigate this effect are needed to advance this area of research. Herein, an integrative discussion is provided on seminal plasticization theory and gas transport models, and these theories and models are compared to an exhaustive database of plasticization characteristics of microporous polymers. Correlations between specific polymer properties and plasticization behavior are presented, including analyses of plasticization pressures from pure-gas permeation tests and mixed-gas permeation tests for pure polymers and composite films. Finally, an evaluation of common and current state-of-the-art strategies to mitigate plasticization is provided along with suggestions for future directions of fundamental and applied research on the topic.

Engineering the Polymer-MOF Interface in Microporous Composites to Address Complex Mixture Separations.

Poor interfacial compatibility remains a pressing challenge in the fabrication of high-performance polymer-MOF composites. In response, introducing compatible chemistries such as a carboxylic acid moiety has emerged as a compelling strategy to increase polymer-MOF interactions. In this work, we leveraged compatible functionalities in UiO-66-NH2 and a carboxylic acid-functionalized PIM-1 to fabricate mixed-matrix membranes (MMMs) with improved separation performance compared to PIM-1-based MMMs in industrially relevant conditions. Under pure-gas conditions, PIM-COOH-based MMMs retained selectivity with increasing MOF loading and showed increased permeability due to increased diffusion. The composites were further investigated under industrially relevant conditions, including CO2/N2, CO2/CH4, and H2S/CO2/CH4 mixtures, to elucidate the effects of competitive sorption and plasticization. Incorporation of UiO-66-NH2 in PIM-COOH and PIM-1 mitigated the effects of CO2- and H2S-induced plasticization typically observed in linear polymers. In CO2-based binary mixed-gas tests, all samples showed similar performance as that in pure-gas tests, with minimal competitive sorption contributions associated with the amine functional groups of the MOF. In ternary mixed-gas tests, improved plasticization resistance and interfacial compatibility resulted in PIM-COOH-based MMMs having the highest H2S/CH4 and CO2/CH4 selectivity combinations among the films tested in this study. These findings demonstrate that selecting MOFs and polymers with compatible functional groups is a useful strategy in developing high-performing microporous MMMs that require stability under complex and industrially relevant conditions.

Clinicopathologic and Survival After Cystectomy Outcomes in Squamous Cell Carcinoma of the Bladder.

BACKGROUND: Squamous cell carcinoma of the bladder (SqCC) is a rare disease with limited management data. Thus, we sought to characterize the clinicopathologic and survival outcomes amongst patients with SqCC and explore the association of squamous differentiation within urothelial carcinoma (UC w/Squam), as compared to muscle invasive pure UC. METHODS: We conducted a single-center retrospective cohort study of patients, stratified by histology, who underwent cystectomy for MIBC. Baseline clinicopathologic characteristics were compared, and overall survival was assessed using Kaplan-Meier method. RESULTS: We identified 1,034 patients; 37 (3.58%) with SqCC histology, 908 (87.81%) with UC histology, and 89 (8.61%) with UC w/ Squam histology. Among SqCC patients, a higher proportion were Black and similarly a higher proportion were women; amongst patients with UC w/ Squam a higher proportion had lower BMI; and amongst patients with UC a higher proportion had lower clinical (c) T, cN, pathological (p) T, and pN stages. Patients presenting with UC were more likely to receive intravesical therapy; patients presenting with SqCC were less likely to receive neoadjuvant chemotherapy (NAC). Adjuvant chemotherapy rates were similar. With post-hoc Bonferroni analysis, overall survival, cancer-specific survival, and recurrence-free survival were significantly worse for the UC w/ Squam cohort. CONCLUSIONS: UC w/ Squam histology was associated with worse survival outcomes after cystectomy for muscle invasive bladder cancer compared to UC. Our results suggest that UC w/ Squam is associated with more advanced disease compared to UC, warranting further prospective work on consideration of combination therapies for patients with this disease state.

Glutathione supports lipid abundance in vivo.

Cells rely on antioxidants to survive. The most abundant antioxidant is glutathione (GSH). The synthesis of GSH is non-redundantly controlled by the glutamate-cysteine ligase catalytic subunit (GCLC). GSH imbalance is implicated in many diseases, but the requirement for GSH in adult tissues is unclear. To interrogate this, we developed a series of in vivo models to induce Gclc deletion in adult animals. We find that GSH is essential to lipid abundance in vivo. GSH levels are reported to be highest in liver tissue, which is also a hub for lipid production. While the loss of GSH did not cause liver failure, it decreased lipogenic enzyme expression, circulating triglyceride levels, and fat stores. Mechanistically, we found that GSH promotes lipid abundance by repressing NRF2, a transcription factor induced by oxidative stress. These studies identify GSH as a fulcrum in the liver's balance of redox buffering and triglyceride production.

Plasma cell free next-generation sequencing detects an unusual pneumonia pathogen in an immunocompetent adolescent with acute respiratory distress syndrome.

This case details a rapid diagnosis of legionella pneumonia causing severe acute respiratory distress syndrome (ARDS) in an otherwise healthy adolescent through plasma microbial cell-free DNA next generation sequencing (mcfDNA-NGS). Diagnosis by mcfDNA-NGS of this unexpected pathogen led to narrowing of antimicrobials and the addition of glucocorticoids as adjunctive therapy for ARDS.

Rapid genome sequencing identifies novel variants in complement factor I.

Complement factor I deficiency (CFID; OMIM #610984) is a rare immunodeficiency caused by deficiencies in the serine protease complement factor I (CFI). CFID is characterized by predisposition to severe pneumococcal infection, often in infancy. We report a previously healthy adolescent male who presented with respiratory failure secondary to pneumococcal pneumonia and severe systemic inflammatory response. Rapid genome sequencing (rGS) identified compound heterozygous variants in CFI in the proband, with a novel maternally inherited likely pathogenic variant, a single nucleotide deletion resulting in premature stop (c.1646del; p.Asn549ThrfsTer25) and a paternally inherited novel likely pathogenic deletion (Chr 4:110685580-110692197del).

Adrenal pheochromocytoma in a patient with Lynch Syndrome.

Lynch Syndrome (LS), or hereditary non-polyposis colorectal cancer, is the most common cause of hereditary colorectal cancer. There are well described extra-colonic manifestations of LS, including gynecologic and upper urinary tract malignancies. Other extra-colonic manifestations of LS are less understood. Here we present an unusual case of a functional adrenal pheochromocytoma in a 31-year old man with LS.

Efectividad de las vacunas COVID-19 / Effectiveness of COVID-19 vaccines

La pandemia del SARS-CoV-2, ha generado que se realicen esfuerzos considerables en el desarrollo de las vacunas, para comprobar su efectividad se requiere que ensayos clínicos y emplearlos en la población a nivel mundial. Se realizó una revisión sistemática de literatura (RSL) del COVID-19 y su impacto en el desarrollo de las vacunas desde el 2019 hasta el 2022. La estrategia de búsqueda consiguió obtener 8 646 artículos, escogidos de las 6 fuentes de investigación (Wiley Online Library, Taylor & Francis, THE LANCET Infectious Diseases, National Library of Medicine, Nature Portfolio y Oxford Academic), luego se realizó un filtrado de 4 etapas con 2 criterios de exclusión cada una de ellas, quedando solo 78 artículos, los cuáles se utilizaron para responder tres preguntas de investigación planteadas. Se identificaron en los artículos científicos analizados, los laboratorios más referenciados que desarrollaron vacunas Pfizer/ BioNTech, Moderna, AstraZeneca, Sinovac, Sinopharm y Sputnik V, se identificó la utilización de nanotecnología en el diseño de las vacunas, principalmente utilizaron ARN mensajero, vector viral y subunidades proteicas, según el caso con coadyuvantes que potencia la inmunogenicidad. Los estudios demostraron buena efectivad, en los diferentes grupos priorizados y gracias a la dosificación de las inmunizaciones contra la COVID-19, se ha prevenido el número de casos graves y por ende la tasa de mortalidad. Sin embargo, se recomienda promoción y educación sanitaria a la población en general para incentivar la aceptación(AU)

The SARS-CoV-2 pandemic has generated considerable efforts in the development of vaccines, to verify their effectiveness, clinical trials are required and use them in the population worldwide. A systematic literature review (RSL) of COVID-19 and its impact on vaccine development was carried out from 2019 to 2022. The search strategy managed to obtain 8,646 articles, chosen from the 6 research sources (Wiley Online Library, Taylor & Francis, THE LANCET Infectious Diseases, National Library of Medicine, Nature Portfolio and Oxford Academic), then a 4-stage filter was performed with 2 exclusion criteria each, leaving only 78 articles, which were used to answer three research questions posed. In the scientific articles analyzed, the most referenced laboratories that developed Pfizer/BioNTech, Moderna, AstraZeneca, Sinovac, Sinopharm and Sputnik V vaccines were identified, the use of nanotechnology in the design of the vaccines was identified, mainly using messenger RNA, viral vector and protein subunits, depending on the case with adjuvants that enhance immunogenicity. The studies demonstrated good effectiveness, in the different prioritized groups and thanks to the dosage of the immunizations against COVID-19, the number of serious cases and therefore the mortality rate have been prevented. However, health promotion and education is recommended for the general population to encourage acceptance(AU)

Tratamiento farmacológico y no farmacológico y su impacto del estrés durante la pandemia de COVID-19 / Pharmacological and non-pharmacological treatment and its impact of stress during the COVID-19 pandemic

El COVID-19, ha generado estrés a nivel mundial ante la ausencia del desarrollo de los hábitos diarios, causando complicaciones físicas y psicológicas. Se realizó una revisión sistemática de literatura (RSL) del tratamiento farmacológico y no farmacológico y su impacto del estrés durante la pandemia de COVID-19 desde el 2019 hasta el 2021. La estrategia de búsqueda consiguió obtener 25.078 artículos, escogidos de las 6 fuentes de investigación (Taylor & Francis, Springer Link, Wiley Online Library, ARDI, Microsoft Academic y Nature Portfolio), luego se realizó un filtrado de 4 etapas con 2 criterios de exclusión cada una de ellas, quedando solo 78 artículos, los cuáles se utilizaron para responder 4 preguntas de investigación planteadas. Se precisó alteración del bienestar emocional de la población en general, con aumento alarmante de prevalencia de ansiedad, depresión e insomnio; el presente estudio brinda información necesaria sobre los tratamientos, ya sea farmacológico (teniendo como principal en un 31,11% a los antidepresivos y antupsicóticos); como no farmacológico (teniendo como principal en un 21,62% a la telemedicina), orientados a mejorar el estado psicológico, sobretodo de la población vulnerable, que demanda abordaje integral, ante la incertidumbre asociada con la infección por SARS-CoV-2, más el efecto el aislamiento físico, que repercute negativamente sobre la salud mental, incrementando pensamientos suicidas, alucinaciones, y trastornos psiquiátricos(AU)

COVID-19 has generated stress worldwide in the absence of the development of daily habits, causing physical and psychological complications. A systematic literature review (RSL) of pharmacological and non-pharmacological treatment and its impact on stress during the COVID-19 pandemic from 2019 to 2021 was carried out. The search strategy managed to obtain 25,078 articles, chosen from the 6 research sources (Taylor & Francis, Springer Link, Wiley Online Library, ARDI, Microsoft Academic and Nature Portfolio), then a 4-stage filter was carried out with 2 exclusion criteria, each of them, leaving only 78 articles, which were used to answer 4 research questions. Alteration of the emotional well-being of the general population was specified, with an alarming increase in the prevalence of anxiety, depression and insomnia; The present study provides necessary information on treatments, whether pharmacological (having antidepressants and anthropsychotics as the main one in 31.11%); as non-pharmacological (21.62% having telemedicine as the main one), aimed at improving the psychological state, especially of the vulnerable population, which demands a comprehensive approach, given the uncertainty associated with SARS-CoV-2 infection, plus the effect of physical isolation, which has a negative impact on mental health, increasing suicidal thoughts, hallucinations, and psychiatric disorders(AU)

Advanced Glycation End Products Associated With Cardiometabolic Biomarkers in Treated Human Immunodeficiency Virus Infection.

BACKGROUND: Despite advances in antiretroviral therapy (ART), people living with human immunodeficiency virus (HIV) continue to be at increased risk of cardiometabolic complications compared to HIV-uninfected individuals. Advanced glycation end products (AGEs) are implicated in the development and progression of cardiometabolic complications in the general population. Their role in HIV remains unclear. METHODS: ACTG A5260s is a prospective open-label randomized trial in which ART-naive people living with HIV were randomized to tenofovir disoproxil fumarate /emtricitabine plus atazanavir/ritonavir, darunavir/ritonavir, or raltegravir over 96 weeks. Changes in circulating AGEs with ART initiation were assessed, and linear regression was used to examine the associations between serum AGEs with carotid intima-media thickness (cIMT), visceral and subcutaneous adipose tissue, total fat, lean mass, body mass index, insulin resistance, leptin, and adiponectin. RESULTS: Overall, 214 participants were included. Ninety percent were male, 48% were White, the median age was 36 years, median HIV-1 RNA was 4.58 log10 copies/mL, and median CD4 count was 338 cells/µL. Most AGEs remained relatively unchanged following 96 weeks of ART initiation, except for methylglyoxal-derived hydroimidazolone 1 (MG-H1), which increased following 96 weeks of ART (mean fold change, 1.15 [95% confidence interval, 1.02-1.30]). No differences were detected across ART regimens. Increases in AGE levels over time were associated with worsening body fat composition measures, insulin resistance, and cIMT, even after adjusting for clinically relevant factors. CONCLUSIONS: AGE levels did not decrease following ART initiation. Most AGE levels remained stable, except for MG-H1, which increased. In people with HIV on ART, the accumulation of circulating AGEs over time appears to be independently associated with worsening cardiometabolic biomarkers.Summary: Antiretroviral therapy (ART) does not appear to be effective in reducing advanced glycation end product (AGE) levels. On the contrary, AGE levels seem to increase following ART initiation. Accumulation of AGEs was found to be independently associated with cardiometabolic complications in treated people living with HIV.

Impact of pre-existing drug resistance on risk of virological failure in South Africa.

OBJECTIVES: There is conflicting evidence on the impact of pre-existing HIV drug resistance mutations (DRMs) in patients infected with non-B subtype virus. METHODS: We performed a case-cohort substudy of the AIDS Drug Resistance Surveillance Study, which enrolled South African patients initiating first-line efavirenz/emtricitabine/tenofovir. Pre-ART DRMs were detected by Illumina sequencing of HIV pol and DRMs present at <20% of the viral population were labelled as minority variants (MVs). Weighted Cox proportional hazards models estimated the association between pre-ART DRMs and risk of virological failure (VF), defined as confirmed HIV-1 RNA ≥1000 copies/mL after ≥5 months of ART. RESULTS: The evaluable population included 178 participants from a randomly selected subcohort (16 with VF, 162 without VF) and 83 additional participants with VF. In the subcohort, 16% of participants harboured ≥1 majority DRM. The presence of any majority DRM was associated with a 3-fold greater risk of VF (P = 0.002), which increased to 9.2-fold (P < 0.001) in those with <2 active drugs. Thirteen percent of participants harboured MV DRMs in the absence of majority DRMs. Presence of MVs alone had no significant impact on the risk of VF. Inclusion of pre-ART MVs with majority DRMs improved the sensitivity but reduced the specificity of predicting VF. CONCLUSIONS: In a South African cohort, the presence of majority DRMs increased the risk of VF, especially for participants receiving <2 active drugs. The detection of drug-resistant MVs alone did not predict an increased risk of VF, but their inclusion with majority DRMs affected the sensitivity/specificity of predicting VF.

A Curious Case of Croup: Laryngotracheitis Caused by COVID-19.

We describe a case of croup in a 14-month-old boy caused by severe acute respiratory syndrome coronavirus 2, the virus that causes coronavirus disease 2019. The patient presented with classic signs and symptoms consistent with croup. Workup was remarkable for a positive point-of-care test for severe acute respiratory syndrome coronavirus 2. This case represents recognition of a new clinical entity caused by coronavirus disease 2019.

Leveraging Free Volume Manipulation to Improve the Membrane Separation Performance of Amine-Functionalized PIM-1.

Gas-separation polymer membranes display a characteristic permeability-selectivity trade-off that has limited their industrial use. The most comprehensive approach to improving performance is to devise strategies that simultaneously increase fractional free volume, narrow free volume distribution, and enhance sorption selectivity, but generalizable methods for such approaches are exceedingly rare. Here, we present an in situ crosslinking and solid-state deprotection method to access previously inaccessible sorption and diffusion characteristics in amine-functionalized polymers of intrinsic microporosity. Free volume element (FVE) size can be increased while preserving a narrow FVE distribution, enabling below-upper bound polymers to surpass the H2 /N2 , H2 /CH4 , and O2 /N2 upper bounds and improving CO2 -based selectivities by 200 %. This approach can transform polymers into chemical analogues with improved performance, thereby overcoming traditional permeability-selectivity trade-offs.

Shift Work Sleep Disorder and Night Shift Work Significantly Impair Erectile Function.

OBJECTIVES: Here we examine the association between shift work sleep disorder (SWSD) and erectile dysfunction (ED) in shift workers. METHODS: Men presenting to a single andrology clinic between January 2014 and July 2017 completed validated questionnaires: International Index of Erectile Function (IIEF), Patient Health Questionnaire-9 (PHQ-9), and the nonvalidated SWSD Questionnaire. Men were also asked about shift work schedule, comorbidities, phosphodiesterase 5 (PDE5) inhibitor use, and testosterone use. Serum total testosterone values were determined for each visit. Linear regression was performed controlling for testosterone use, testosterone levels, PDE5 inhibitor use, age, and comorbidities to determine the effect of SWSD on ED as assessed using the IIEF. RESULTS: Of the 754 men completing questionnaires, 204 reported nonstandard shift work (begins before 7 am or after 6 pm, regularly extends out of that frame, or rotates frequently) and 48 were found to have SWSD using a screening questionnaire. Nonstandard shift work alone did not result in worse IIEF-EF scores (P = .31), but those who worked nonstandard shifts and had SWSD demonstrated IIEF-EF scores 2.8 points lower than men without SWSD (P < .01). When assessing for the type of shift work performed, men who worked night shifts had IIEF-EF scores 7.6 points lower than men who worked during the day or evening (P < .01). Testosterone use improved IIEF-EF scores for men with SWSD by 2.9 points, ameliorating the effect of SWSD on ED. However, baseline testosterone levels were not associated with worse erectile function in this cohort. CONCLUSION: Men with SWSD have worse erectile function, with men who work night shifts having even poorer erectile function. These findings suggest that circadian rhythm disturbance may significantly impact erectile function. While testosterone therapy may partly reverse the effects of SWSD, shift work is a potential risk factor for ED and should be assessed for as part of the evaluation of men with ED. Rodriguez KM, Kohn TP, Kohn JR, et al. Shift Work Sleep Disorder and Night Shift Work Significantly Impair Erectile Function. J Sex Med 2020;17:1687-1693.

MOF-Based Membranes for Gas Separations.

Metal-organic frameworks (MOFs) represent the largest known class of porous crystalline materials ever synthesized. Their narrow pore windows and nearly unlimited structural and chemical features have made these materials of significant interest for membrane-based gas separations. In this comprehensive review, we discuss opportunities and challenges related to the formation of pure MOF films and mixed-matrix membranes (MMMs). Common and emerging separation applications are identified, and membrane transport theory for MOFs is described and contextualized relative to the governing principles that describe transport in polymers. Additionally, cross-cutting research opportunities using advanced metrologies and computational techniques are reviewed. To quantify membrane performance, we introduce a simple membrane performance score that has been tabulated for all of the literature data compiled in this review. These data are reported on upper bound plots, revealing classes of MOF materials that consistently demonstrate promising separation performance. Recommendations are provided with the intent of identifying the most promising materials and directions for the field in terms of fundamental science and eventual deployment of MOF materials for commercial membrane-based gas separations.

Varicocele Repair Prior to Assisted Reproductive Technology: Patient Selection and Special Considerations.

Clinical varicoceles are one of the most commonly identified physical exam abnormalities in men presenting with infertility. Clinical varicoceles can cause impaired spermatogenesis and surgical correction can improve semen parameters in select men. Increasingly, andrologists are performing varicocele repairs prior to intrauterine insemination (IUI), in vitro fertilization (IVF), and intracytoplasmic sperm injection (ICSI) to boost male fertility potential. In this review, we evaluated the available literature 1) to determine if varicocelectomy prior to IUI or assisted reproductive technologies proved to improve sperm production or pregnancy outcomes; and 2) to identify who may be the ideal candidate for pre-IUI/ART varicocelectomy. Overall, few studies have explored this topic and little can be concluded about the impact of varicocelectomy prior to IUI. The evidence, however, does support that correcting a clinical varicocele can increase pregnancy outcomes in couples who plan to pursue IVF or ICSI. When selecting patients for varicocelectomy prior to IUI or ART, clinicians should evaluate female age as improvement in semen parameters can take 6 months after varicocelectomy and this duration of time may be deleterious in cases of advanced maternal age when each cycle becomes increasingly important. Overall, the currently limited literature regarding clinical varicoceles correction demonstrates that pregnancy rates can be increased when comparing patients who have undergone varicocelectomy prior to ART with those who had clinical varicocele but did not undergo surgery.