Sexual and reproductive health in military settings: A qualitative study.

Mission readiness is critical to the operational success of the United States (US) military and includes having a healthy and fit fighting force. Service members and their dependents have access to a wide range of sexual and reproductive health services with no out-of-pocket costs. Despite this access, negative outcomes such as sexually transmitted infections (STIs) and unintended pregnancy persist. Semi-structured, in-depth interviews were conducted with service members and stakeholders (e.g. medical providers). Interviews explored the individual, interpersonal, organizational, and institutional factors that inform sexual norms, behaviors, and healthcare experiences in the US military. Interview transcripts were coded manually; data were summarized for themes related to unique aspects of military culture and healthcare affecting sexual and reproductive health. Twenty-five (25) service members and 15 stakeholders completed interviews. Four themes emerged: 1) despite free access, both general and military-specific barriers to sexual and reproductive healthcare persist; 2) general and military-specific cultural norms apply to sexual behavior and care seeking; 3) sexual and reproductive health-related norms can be perceived as confusing and contradictory within the military; and 4) resources addressing sexual assault are ubiquitous in military settings, but resources addressing prevention of STIs and unintended pregnancy are limited. Both general and military-specific norms, behavior, and healthcare experiences need to be considered in clinical care, public health campaigns, and other efforts to promote sexual and reproductive health in military settings.

Personalised virtual gene panels reduce interpretation workload and maintain diagnostic rates of proband-only clinical exome sequencing for rare disorders.

PURPOSE: The increased adoption of genomic strategies in the clinic makes it imperative for diagnostic laboratories to improve the efficiency of variant interpretation. Clinical exome sequencing (CES) is becoming a valuable diagnostic tool, capable of meeting the diagnostic demand imposed by the vast array of different rare monogenic disorders. We have assessed a clinician-led and phenotype-based approach for virtual gene panel generation for analysis of targeted CES in patients with rare disease in a single institution. METHODS: Retrospective survey of 400 consecutive cases presumed by clinicians to have rare monogenic disorders, referred on singleton basis for targeted CES. We evaluated diagnostic yield and variant workload to characterise the usefulness of a clinician-led approach for generation of virtual gene panels that can incorporate up to three different phenotype-driven gene selection methods. RESULTS: Abnormalities of the nervous system (54.5%), including intellectual disability, head and neck (19%), skeletal system (16%), ear (15%) and eye (15%) were the most common clinical features reported in referrals. Combined phenotype-driven strategies for virtual gene panel generation were used in 57% of cases. On average, 7.3 variants (median=5) per case were retained for clinical interpretation. The overall diagnostic rate of proband-only CES using personalised phenotype-driven virtual gene panels was 24%. CONCLUSIONS: Our results show that personalised virtual gene panels are a cost-effective approach for variant analysis of CES, maintaining diagnostic yield and optimising the use of resources for clinical genomic sequencing in the clinic.

Effect of pulmonary hypertension on exercise capacity and gas exchange in patients with chronic obstructive pulmonary disease living at high altitude.

BACKGROUND: Pulmonary hypertension (PH) is associated with decreased exercise tolerance in chronic obstructive pulmonary disease (COPD) patients, but in the altitude the response to exercise in those patients is unknown. Our objective was to compare exercise capacity, gas exchange and ventilatory alterations between COPD patients with PH (COPD-PH) and without PH (COPD-nonPH) residents at high altitude (2640 m). METHODS: One hundred thirty-two COPD-nonPH, 82 COPD-PH, and 47 controls were included. Dyspnea by Borg scale, oxygen consumption (VO2), work rate (WR), ventilatory equivalents (VE/VCO2), dead space to tidal volume ratio (VD/VT), alveolar-arterial oxygen tension gradient (AaPO2), and arterial-end-tidal carbon dioxide pressure gradient (Pa-ETCO2) were measurement during a cardiopulmonary exercise test. For comparison of variables between groups, Kruskal-Wallis or one-way ANOVA tests were used, and stepwise regression analysis to test the association between PH and exercise capacity. RESULTS: All COPD patients had a lower exercise capacity and higher PaCO2, A-aPO2 and VD/VT than controls. The VO2 % predicted (61.3 ± 20.6 vs 75.3 ± 17.9; p < 0.001) and WR % predicted (65.3 ± 17.9 vs 75.3 ± 17.9; p < 0.001) were lower in COPD-PH than in COPD-nonPH. At peak exercise, dyspnea was higher in COPD-PH (p = 0.011). During exercise, in COPD-PH, the PaO2 was lower (p < 0.001), and AaPO2 (p < 0.001), Pa-ETCO2 (p = 0.033), VE/VCO2 (p = 0.019), and VD/VT (p = 0.007) were higher than in COPD-nonPH. In the multivariate analysis, PH was significantly associated with lower peak VO2 and WR (p < 0.001). CONCLUSION: In COPD patients residing at high altitude, the presence of PH was an independent factor related to the exercise capacity. Also, in COPD-PH patients there were more dyspnea and alterations in gas exchange during the exercise than in those without PH.

A recurrent missense variant in HARS2 results in variable sensorineural hearing loss in three unrelated families.

HARS2 encodes mitochondrial histidyl-tRNA synthetase (HARS2), which links histidine to its cognate tRNA in the mitochondrial matrix. Biallelic variants in HARS2 are associated with Perrault syndrome, a rare recessive condition characterized by sensorineural hearing loss in both sexes and primary ovarian insufficiency in 46,XX females. Some individuals with Perrault syndrome have a broader phenotypic spectrum with neurological features, including ataxia and peripheral neuropathy. Here, we report a recurrent variant in HARS2 in association with sensorineural hearing loss. In affected individuals from three unrelated families, the variant HARS2 c.1439G>A p.(Arg480His) is present as a heterozygous variant in trans to a putative pathogenic variant. The low prevalence of the allele HARS2 c.1439G>A p.(Arg480His) in the general population and its presence in three families with hearing loss, confirm the pathogenicity of this variant and illustrate the presentation of Perrault syndrome as nonsyndromic hearing loss in males and prepubertal females.

The use of GnRH-agonist trigger for the final maturation of oocytes in normal and low responders undergoing planned oocyte cryopreservation.

STUDY QUESTION: Does GnRH-agonist trigger offer similar maturity rate (MR) in low and normal responders compared to high responders in women undergoing planned oocyte cryopreservation, for whom even a small risk of ovarian hyperstimulation syndrome (OHSS) may not be acceptable? SUMMARY ANSWER: GnRH-agonist is an appropriate choice for final maturation of oocytes in planned oocyte cryopreservation, regardless of response to stimulation or risk of ovarian hyperstimulation syndrome. WHAT IS KNOWN ALREADY: Numerous studies have demonstrated the utility of GnRH-agonist trigger for the prevention of ovarian hyperstimulation in high-responder in vitro fertilization cycles. Limited data exist supporting its use in normal or low responders, or in non-infertile women undergoing planned oocyte cryopreservation. STUDY DESIGN, SIZE, DURATION: Retrospective cohort study of 1189 subjects including all planned oocyte cryopreservation cycles performed at a large, single center, oocyte cryopreservation program from April 2016 to December 2018. PARTICIPANTS/MATERIALS, SETTING, METHODS: A total of 1680 cycles were included in the study. A total of 57.1% (959/1680) utilized GnRH-agonist for trigger. Demographic and clinical data were collected from the medical record. Maturation rate was calculated for the entire cohort, and by trigger type, using the quotient of Metaphase II (MII) oocytes and retrieved oocytes. A sub-cohort of GnRH-agonist trigger cycles were categorized by peak estradiol (E2) levels and maturation rates compared between groups. Associations were made using Student's t test, ANOVA, Mann-Whitney U and Kruskal-Wallis, where appropriate. A sample size calculation for 90% power with a significance of 5% to detect non-inferiority of <0.05 from a 0.75 maturity rate between subjects with E2 > 3000 pg/mL and E2 < 3000 pg/mL demonstrated the need for at least 116 cycles per group. MAIN RESULTS AND THE ROLE OF CHANCE: Mean MR was 0.71 ± 0.19 overall, and 0.73 ± 0.18 in the sub-cohort of GnRH-agonist trigger cycles. A total of 611 cycles (63.7%) had peak E2 < 3000, and 331 (34.5%) had E2 > 3000. No significant difference in maturity rate was noted between cycles with E2 levels >3000 pg/mL and <3000 pg/mL (0.72 ± 0.19 vs. 0.74 ± 0.14, P = 0.18), confirming the non-inferiority of maturity rates with GnRH-agonist triggers in cycles with peak E2 < 3000 pg/mL. While lower mean oocytes retrieved and mean MII oocytes were associated with lower peak E2 levels, maturity rate did not significantly differ amongst E2 level groups. Cycles with E2 < 1000 pg/mL had lower MR irrespective of trigger type. LIMITATIONS, REASONS FOR CAUTION: The retrospective nature cannot entirely exclude selection biases, confounding factors or additional variables that could not be accounted for or were not collected by the electronic medical record. Given the nature of planned oocyte cryopreservation, studies of ongoing pregnancy rates and birth outcomes will naturally be delayed. Lastly, the study population was limited to women undergoing planned oocyte cryopreservation; therefore, the results may not be generalizable to women undergoing in vitro fertilization. WIDER IMPLICATIONS OF THE FINDINGS: This is the first study specifically comparing the efficacy of GnRH-agonist in patients at lower risk for OHSS to those at high risk, as well the first study evaluating GnRH-agonist's efficacy specifically in planned oocyte cryopreservation cycles. STUDY FUNDING/COMPETING INTEREST(S): Study support provided by departmental funds from the Center for Fertility Research and Education-Extend Fertility Medical Practice. BLM discloses personal fees from Ferring Pharmaceuticals and Merck KgAA, unrelated to the submitted work. C.S., M.G., L.R. and J.K. have nothing to disclose. TRIAL REGISTRATION NUMBER: N/A.

Likelihood of achieving a 50%, 60%, or 70% estimated live birth rate threshold with 1 or 2 cycles of planned oocyte cryopreservation.

PURPOSE: To characterize the likelihood of cryopreserving enough oocytes for 50%, 60%, or 70% estimated live birth rate (eLBR) with 1-2 planned oocyte cryopreservation (Pl-OC) cycles. METHODS: We performed a retrospective cohort study utilizing all patients completing ≥ 1 Pl-OC cycle from 2016 to 2018 at a large single-center OC program. Subjects were categorized by age at retrieval and number of cycles. We extrapolated age-based oocyte thresholds for 50%, 60%, or 70% eLBR from previously published data. We calculated the proportion of subjects overall, and for each age group, whose number of frozen oocytes was greater than or equal to their age-based threshold for a 50%, 60%, or 70% eLBR after 1 and 2 cycles. OR for 60% eLBR with one cycle was calculated for age and AMH cutoff values and corroborated with logistic regression. RESULTS: A total of 1241 subjects, completing 1799 Pl-OC cycles, were included. With one cycle, 66% (819/1241) achieved ≥ 50% eLBR and 51% (634/1241) achieved 70% eLBR. With two cycles, 79.6% (988/1241) attained ≥ 50% eLBR and 65.5% (813/1241) achieved 70% eLBR. Achieving 50%, 60%, or 70% eLBR with 1-2 cycles was significantly associated with both age (p < 0.001) and AMH (p < 0.001). Age < 37.5 and AMH > 1.995 were independently associated with attaining 60% eLBR with one cycle (age: OR 13.73; 95%CI 9.16-20.57, p < 0.001; AMH: OR 7.32; 95% CI 5.50-9.76, p < 0.001). CONCLUSIONS: Younger age and higher AMH were associated with achieving 50%, 60%, or 70% eLBR thresholds with Pl-OC. Nevertheless, almost all subjects were successfully able to preserve enough oocytes for ≥ 50% eLBR in 1-2 cycles.

Increasing Incidence of Gonorrhea at an Urban STI Clinic in the United States.

Medical record data was extracted from a sexually transmitted infection (STI) clinic in Providence, Rhode Island to characterize trends in Neisseria gonorrhoeae (GC) infection and explore risk factors. Of 16,601 clinical encounters, 6% (n=991) tested GC positive: 5.28 GC case rate (per 100 encounters) in the first two years of data collection (2015-2016) and 7.04 in the last two years (2020-2021). Analysis suggested a single linear trend line over time (p<.05). Overall, in more recent years, patients were older and more like to identify as male, Black, and Hispanic/Latino, as well as to have reported a previous STI, current symptoms, and specific risk behaviors. GC-positive patients in 2020-2021 were older and more like to identify as female and Black compared to 2015-2016. Lower rates of condom use were especially salient among female patients. These findings may reflect GC trends in the community.

Cytochrome P450 and Epoxide Hydrolase Metabolites in Aß and tau-induced Neurodegeneration: Insights from Caenorhabditis elegans.

This study aims to uncover potent cytochrome P450 (CYP) and epoxide hydrolase (EH) metabolites implicated in Aß and/or tau-induced neurodegeneration, independent of neuroinflammation, by utilizing Caenorhabditis elegans (C. elegans) as a model organism. Our research reveals that Aß and/or tau expression in C. elegans disrupts the oxylipin profile, and epoxide hydrolase inhibition alleviates the ensuing neurodegeneration, likely through elevating the epoxy-to-hydroxy ratio of various CYP-EH metabolites. In addition, our results indicated that the Aß and tau likely affect the CYP-EH metabolism of PUFA through different mechanism. These findings emphasize the intriguing relationship between lipid metabolites and neurodegenerations, in particular, those linked to Aß and/or tau aggregation. Furthermore, our investigation sheds light on the crucial and captivating role of CYP PUFA metabolites in C. elegans physiology, opening up possibilities for broader implications in mammalian and human contexts.

Going to the Source: Discussions With Early and Mid-Career Faculty From Groups Underrepresented in Biomedical Research to Develop and Enhance CFAR Services.

BACKGROUND: To include, sustain, and retain HIV-focused early career faculty from groups historically excluded from biomedical research, the Providence/Boston Center for AIDS Research (CFAR) conducted focus groups and individual interviews with early and mid-career faculty to discern their needs. METHODS: We conducted focus groups and interviews with 15 faculty at institutions affiliated with Providence/Boston CFAR from groups underrepresented in biomedical research. The discussion was guided using the domains of an Asset Bundle Model encompassing scientific human capital, social capital, and financial capital. RESULT: Participants' identities, including their race, ethnicity, gender, sexual orientation, and being a parent affected their vision of themselves as scientists. Participants reported confusion or limited training on or access to resources for professional development, hiring staff, meeting NIH reporting requirements, international research, support for working parents, sabbaticals, and addressing workplace conflict or unsupportive work environments. Some described feeling like they were a burden on their mentors who seemed overextended. They identified attributes of effective mentors, such as believing in and investing in the mentee; having the requisite content area expertise and self-confidence; being able to identify mentees needs and meet them where they are; and being consistent, communicative, respectful, and kind. They described a need for additional education and support preresearch and postresearch grant award management. CONCLUSIONS: To learn how to equitably serve all interested in HIV research, CFARs should engage and include perspectives from scientists who have historically been excluded from biomedical research. Our future work will test, implement, and disseminate the ideas generated by these focus group discussions.

Performance of a deep learning based neural network in the selection of human blastocysts for implantation.

Deep learning in in vitro fertilization is currently being evaluated in the development of assistive tools for the determination of transfer order and implantation potential using time-lapse data collected through expensive imaging hardware. Assistive tools and algorithms that can work with static images, however, can help in improving the access to care by enabling their use with images acquired from traditional microscopes that are available to virtually all fertility centers. Here, we evaluated the use of a deep convolutional neural network (CNN), trained using single timepoint images of embryos collected at 113 hr post-insemination, in embryo selection amongst 97 clinical patient cohorts (742 embryos) and observed an accuracy of 90% in choosing the highest quality embryo available. Furthermore, a CNN trained to assess an embryo's implantation potential directly using a set of 97 euploid embryos capable of implantation outperformed 15 trained embryologists (75.26% vs. 67.35%, p<0.0001) from five different fertility centers.

Around one in seven couples have trouble conceiving, which means there is a high demand for solutions such as in vitro fertilization, also known as IVF. This process involves fertilizing and developing embryos in the laboratory and then selecting a few to implant into the womb of the patient. IVF, however, only has a 30% success rate, is expensive and can be both mentally and physically taxing for patients. Selecting the right embryos to implant is therefore extremely important, as this increases the chance of success, minimizes complications and ensures the baby will be healthy. Currently the tools available for making this decision are limited, highly subjective, time-consuming, and often extremely expensive. As a result, embryologists often rely on their experience and observational skills when choosing which embryos to implant, which can lead to a lot of variability. An automated system based on artificial intelligence (AI) could therefore improve IVF success rates by assisting embryologists with this decision and ensuring more consistent results. The AI system could learn how embryos develop over time and then uses this information to select the best embryos to implant from just a single image. This would offer a cheaper alternative to current analysis tools that are only available at the most expensive IVF clinics. Now, Bormann, Kanakasabapathy, Thirumalaraj et al. have developed an AI system for IVF based on thousands of images of embryos. Using individual images, the system selected embryos of a comparable quality to those selected by a human specialist. It also showed a greater ability to identify embryos that will lead to successful implantation. Indeed, the software outperformed 15 embryologists from five different centers across the United States in detecting which embryos were most likely to implant out of a group of high-quality embryos with few visible differences. Artificial intelligence has many potential applications to support expert clinical decision-making. Systems like these could improve success, reduce errors and lead to faster, cheaper and more accessible results. Beyond immediate IVF applications, this system could also be used in research and industry to help understand differences in embryo quality.

Establishing Genotype-phenotype Correlation in USH2A-related Disorders to Personalize Audiological Surveillance and Rehabilitation.

OBJECTIVE: USH2A-related disorders are characterised by genetic and phenotypic heterogeneity, and are associated with a spectrum of sensory deficits, ranging from deaf blindness to blindness with normal hearing. It has been previously proposed that the presence of specific USH2A alleles can be predictive of unaffected hearing. This study reports the clinical and genetic findings in a group of patients with USH2A-related disease and evaluates the validity of the allelic hierarchy model. PATIENTS AND INTERVENTION: USH2A variants from 27 adults with syndromic and nonsyndromic USH2A-related disease were analyzed according to a previously reported model of allelic hierarchy. The analysis was replicated on genotype-phenotype correlation information from 197 individuals previously reported in 2 external datasets. MAIN OUTCOME MEASURE: Genotype-phenotype correlations in USH2A-related disease. RESULTS: A valid allelic hierarchy model was observed in 93% of individuals with nonsyndromic USH2A-retinopathy (n = 14/15) and in 100% of patients with classic Usher syndrome type IIa (n = 8/8). Furthermore, when two large external cohorts of cases were combined, the allelic hierarchy model was valid across 85.7% (n = 78/91) of individuals with nonsyndromic USH2A-retinopathy and 95% (n = 123/129) of individuals with classic Usher syndrome type II (p = 0.012, χ test). Notably, analysis of all three patient datasets revealed that USH2A protein truncating variants were reported most frequently in individuals with hearing loss. CONCLUSION: Genetic testing results in individuals suspected to have an USH2A-related disorder have the potential to facilitate personalized audiological surveillance and rehabilitation pathways.

Siniestralidad y apnea obstructiva del sueño. Revisión de la literatura y evaluación de la situación en 3 países latinoamericanos / Accident Rate and Obstructive Sleep Apnea: Literature Review and Assessment of the Situation in Three Latin American Countries

La apnea obstructiva del sueño (AOS) es una condición común en adultos en edad laboral. Incluso, en la actualidad, vemos cómo la edad de retiro se ha ido prolongando de tal manera que adultos mayores, quienes tienen mayor prevalencia de AOS, continúan trabajando incluso en situaciones de alto riesgo de siniestralidad. Uno de los principales síntomas de la AOS es la somnolencia diurna que puede contri- buir de manera directa al riesgo de accidentabilidad, compromiso cognitivo y desem- peño laboral. También se ha demostrado cómo la reducción de la materia gris a nivel cerebral y cerebelar provoca alteraciones en coordinación y capacidad de conducción. El tratamiento con dispositivos de presión positiva mejora el desempeño laboral y redu- ce la incidencia de accidentes de tránsito, pero algunos déficits cognitivos pueden per- sistir incluso después de meses de tratamiento. La evaluación del riesgo de accidentabilidad en conductores es un desafío y los cues- tionarios actuales no son adecuados para el cribado. Los simuladores de conducción y las pruebas de alerta son más prometedores. El futuro de la investigación se centra en estandarizar los resultados de los simulado- res, determinar los mejores predictores de eventos reales y utilizar la inteligencia arti- ficial y los automóviles autónomos para reducir los riesgos relacionados con la somno - lencia al volante. Es necesario que la posición de los entes gubernamentales de nuestros países latinoa- mericanos sea proactiva y orientada a la protección de la salud y la seguridad de la po- blación.

Obstructive sleep apnea (OSA) is a common condition among working-age adults. In today's context, we observe that the retirement age has been extended, with older adults, who have a higher prevalence of OSA, continuing to work even in high-risk situations. One of the main symptoms of OSA is daytime sleepiness, which can directly contribu- te to the risk of accidents, cognitive impairment and reduced work performance. It has also been demonstrated that the reduction of gray matter in the brain, especially in the cerebellum, can lead to coordination and driving capacity impairments. Treatment with positive pressure devices improves work performance and reduces the incidence of traffic accidents, but some cognitive deficits may persist even after months of treatment. Assessing the risk of accidents in drivers is a challenge, and current questionnaires are not suitable for screening. Driving simulators and alertness tests show more promise. The future of research is focused on standardizing simulator outcomes, identifying the best predictors of real-world events, and utilizing artificial intelligence and autonomous vehicles to mitigate risks associated with driver drowsiness. It is imperative that the stance of government entities in our Latin American countries is proactive and aimed at safeguarding the health and safety of the population.

Cobertura para el diagnóstico y tratamiento de la apnea obstructiva del sueño en Latinoamérica: reporte del Foro Latinoamericano de Sociedades Respiratorias / Coverage for the Diagnosis and Treatment of Obstructive Sleep Apnea in Latin America: Report from the Latin American Forum of Respiratory Societies

Introducción: La Apnea Obstructiva del Sueño (AOS) es un problema de salud pública en Latinoamérica; una región que es heterogénea, con recursos diferentes y sistemas de salud diversos. El objetivo fue describir la información recabada por el Foro Latino-americano de Sociedades Respiratorias sobre el acceso y cobertura para los estudios diagnósticos y tratamiento con CPAP de los pacientes con AOS. Material y Métodos: A través de la Asociación Latinoamericana de Tórax (ALAT), se envió una encuesta a todas las sociedades miembros con preguntas sobre el acceso a diagnóstico, tratamiento y cobertura de seguros privados. Resultados: El foro contó con 15 países. Se reportó la existencia de 396 unidades formales de sueño, 82% privadas y 18% públicas; en 12 países el sistema de salud público (SSP) contrata unidades privadas para otorgar servicios. En todos los países se realiza tanto polisomnografía como poligrafía respiratoria para el diagnóstico. En 8 (53%) países, el SSP cubre el tratamiento con CPAP de la AOS (en Argentina, Guatemala y México esta cobertura es parcial); los seguros privados cubren AOS en 7/15 países. Conclusiones: En Latinoamérica, existen pocas unidades formales de sueño y la mayoría son privadas. Cerca de la mitad de los sistemas de salud pública no cubren su tratamiento y, en la mayoría de los casos, los seguros privados no ofrecen cobertura. Esto deja a nuestra población vulnerable a las complicaciones de la AOS, con un concomitante aumento de la morbimortalidad y costos en salud.

Introduction: Obstructive Sleep Apnea (OSA) is a public health problem in Latin America, which is a heterogeneous region, with different resources and diverse health systems. The objective was to describe the information collected by the Latin American Forum of Respiratory Societies on access and coverage for diagnostic studies and CPAP treatment of patients with OSA. Methods: Through the Latin American Thorax Association (ALAT, Spanish acronym), a survey was sent to all member societies with questions about access to diagnosis, treatment, and private insurance coverage. Results: The forum included 15 countries. The existence of 396 sleep medicine units was reported, 82% private and 18% public; in 12/15 countries the public health system (PHS) contracts private units to provide services. In all countries, both polysomnography and respiratory polygraphy are performed to make the diagnosis. In only 8 (53%) countries the PHS covers the treatment of OSA (in Argentina, Guatemala and Mexico this coverage is partial); private insurance coverage is in 7/15 countries.Conclusions: In Latin America there are few formal sleep units and most are private. About half of public health systems do not cover their treatment and, in most cases, private insurance does not offer coverage. This leaves our population vulnerable to the complications of OSA, with a concomitant increase in morbidity, mortality and health costs.

Diagnosing and Preventing Hearing Loss in the Genomic Age.

Over the past two decades, significant technological advances have facilitated the identification of hundreds of genes associated with hearing loss. Variants in many of these genes result in severe congenital hearing loss with profound implications for the affected individual and their family. This review collates these advances, summarizing the current state of genomic knowledge in childhood hearing loss. We consider how current and emerging genetic technologies have the potential to alter our approach to the management and diagnosis of hearing loss. We review approaches being taken to ensure that these discoveries are used in clinical practice to detect genetic hearing loss as soon as possible to reduce unnecessary investigations, provide information about reproductive risks, and facilitate regular follow-up and early treatment. We also highlight how rapid sequencing technology has the potential to identify children susceptible to antibiotic-induced hearing loss and how this adverse reaction can be avoided.

A new theory of depression based on the serotonin/kynurenine relationship and the hypothalamicpituitary- adrenal axis

The serotonergic and immunological hypothesis of depression proposes that certain types of excessive stress distort the relationship between the activities of the innate immune and central nervous systems, so that the stress caused by an infection, or excessive psychological stress, activate toll-like receptors such as the TLR-4, the transcription factor NF-kB, the inflammasome NLRP3, as well as the secretion of interleukin-1 beta (IL-1ß), interleukin-6 (IL-6) and other factors of the innate immune response, causing first, the general symptoms of the disease which appear with any infection, but also those characteristic of depressive illness such as dysphoria and anhedonia. The evidence indicates that, if the stimulus persists or recurs within 24 hours, the indole-2, 3-dioxygenase enzyme (IDO) of the kynurenine metabolic pathway, which increases the synthesis of quinolinic acid, is activated with an associated reduction of serotonin synthesis. Quinolinic acid activates NMDA receptors in the central nervous system and stimulates the secretion of interleukins IL-6 and 1L-1ß, among others, promoting hyper-activity of the HPA axis and reinforcing a bias of the tryptophan metabolism to produce quinolinic acid, and interleukins by the innate immune system, further reducing the synthesis of serotonin and consolidating the depressive process. We discuss the evidence showing that this process can be initiated by either interleukin stimulated by an infection or some vaccines or excessive psychological stress that activates the HPA axis together with said innate immune response, causing a process of aseptic inflammation in the central nervous system.

Severe sleep apnea, Cheyne-Stokes respiration and desaturation in patients with decompensated heart failure at high altitude.

OBJECTIVES: To determine the sleep-disordered breathing in patients with decompensated HF (DHF) at an altitude of 2640m. METHODS: Polysomnogram during the first 48 hours of admission in patients hospitalized for DHF. Sleep apnea (SA) was defined as an apnea hypopnea index (AHI) > 5/hour and central sleep apnea (CSA) as central apnea index (CAI) ≥ 50% of the AHI. RESULTS: Sixteen participants, LVEF 24.2±9.9%. All patients had SA, severe in 12 (75%), CSA in 8 (50%) and 7 (43.8%) presented Cheyne-Stokes respiration (CSR). Out of the eight patients with obstructive SA, five had a central component (CAI ≥ 5/h). The SpO2 decreased during sleep to 80.6±5.5% and in patients with CSR to 77.6±6.9%. CONCLUSIONS: At an altitude of 2640m all patients with DHF presented sleep apnea, most were severe, with CSA and a significant percentage of CSR that was associated with higher oxygen desaturation.

Radiological and histological characteristics of patients with interstitial lung disease undergoing lung biopsy in a reference institution from eastern Colombia / Características radiológicas e histológicas de pacientes con enfermedad pulmonar intersticial llevados a biopsia pulmonar en una institución del oriente colombiano

Abstract Introduction: Interstitial lung disease (ILD) diagnosis requires a mukidisciplinary approach and, in some cases, lung biopsy. Objective: To describe the sociodemographic and clinical characteristics, as well as the radiological and histological findings, of patients with ILD who required lung biopsy after a mukidisciplinary board (pneumology, radiology, and pathology) of a reference center for respiratory diseases in Bucaramanga, Colombia, failed to reach the ILD diagnosis. Materials and methods: Cross-sectional study. The medical records of 56 patients treated at the Instituto Neumológico del Oriente who underwent lung biopsy between 2015 and 2019 were reviewed. Measures of central tendency and dispersion were calculated for demographic and clinical variables, respectively, to characterize them. A bivariate analysis was performed using Fisher's exact test to determine whether there were differences in the distribution of the sociodemographic and clinical variables according to the radiological patterns and the final histological diagnosis. Results: Participants' median age was 67 years (IQR: 59-72) and 55.35% were men. 43 patients had a radiological pattern inconsistent with usual interstitial pneumonia (UIP); 4 had a pattern consistent with possible UIP; and 9 had a pattern consistent with UIP. The most common histologic diagnoses were hypersensitivity pneumonitis (HP) (32.14%), nonspecific interstitial pneumonia (NSIP) (17.86%), and UIP (19.64%). Conclusion: In the study population, the primary reason for performing a lung biopsy was the presence of a radiologic pattern inconsistent with UIP, with HP being the predominant histopathological diagnosis. This is the first study to characterize patients with ILD who underwent lung biopsy in eastern Colombia, making a significant contribution to our understanding of the disease's epidemiology in the country.

Resumen Introducción. El diagnóstico de la enfermedad pulmonar intersticial (EPI) requiere un enfoque multidisciplinar y, en ocasiones, de una biopsia pulmonar. Objetivo. Describir las características sociodemográficas y clínicas, y los hallazgos radiológicos e histológicos de pacientes con EPI que requirieron biopsia pulmonar luego de no lograrse un diagnóstico de esta enfermedad por la junta médica multidisciplinar (neumología, radiología y patología) de un centro de referencia en enfermedades respiratorias de Bucaramanga, Colombia. Materiales y métodos. Estudio transversal. Se revisaron las historias clínicas de 56 pacientes atendidos en el Instituto Neumológico del Oriente y que fueron remitidos a biopsia pulmonar entre 2015 y 2019. Se analizaron variables demográficas y clínicas, calculando medidas de tendencia central y de dispersión para su respectiva caracterización. Se realizó un análisis bivariado mediante test exacto de Fisher para determinar si existían diferencias en la distribución de las variables sociodemográficas y clínicas de acuerdo con los patrones radiológicos y el diagnóstico histológico definitivo. Resultados. La mediana de edad fue 67 años (RIC: 59-72), 55.35% fueron hombres. 43 pacientes presentaron patrón radiológico inconsistente con neumonía intersticial usual (NIU); 4, patrón de posible NIU y, 9, patrón de NIU. Los diagnósticos histológicos más frecuentes fueron neumonitis por hipersensibilidad (NH) (32.14%), neumonía intersticial no específica (17.86%) y NIU (19.64%). Conclusión. La principal razón para realizar biopsia pulmonar en la población de estudio fue la presencia de un patrón radiológico inconsistente con NIU, siendo la NH el principal diagnóstico histopatológico. Este es el primer trabajo que caracteriza a pacientes con EPI del oriente colombiano llevados a biopsia pulmonar, lo que representa un importante aporte al conocimiento de la epidemiología de esta enfermedad en Colombia.

Impacto clínico de un grupo de discusión multidisciplinaria en el diagnóstico de fibrosis pulmonar idiopática en Colombia / Clinical impact of a multidisciplinary discussion group on the diagnosis of idiopathic pulmonary fibrosis in Colombia

Resumen Introducción: la fibrosis pulmonar idiopática (FPI) es una enfermedad pulmonar intersticial (EPID) de mal pronóstico, considerada huérfana en Colombia. Un diagnóstico correcto tiene implicaciones para el paciente y los costos de atención. Los grupos de discusión multidisciplinaria (GDM) se consideran el estándar de oro en el diagnóstico. No hay estudios previos en Colombia de la experiencia de un GDM. Objetivos: evaluar el impacto de un GDM en una institución de cuarto nivel en Bogotá en cambio de diagnóstico de pacientes con EPID y la concordancia entre el diagnóstico inicial y final de FPI. Material y métodos: pacientes con EPID evaluados entre 2015-2018 por el GDM conformado por neumólogos, radiólogo, patólogo y reumatólogos. Criterios ATS/ERS/JRS/ALAT de diagnóstico de FPI. Descripción del cambio en el diagnóstico y concordancia entre el diagnóstico inicial y del GDM en FPI. Resultados: de 165 pacientes con EPID se cambió el diagnóstico en 35.2%. En 77.3% pacientes con diagnóstico inicial de FPI y en 6.7% con diagnóstico inicial diferente a FPI el GDM confirmó FPI. Al descartar FPI, los principales diagnósticos fueron neumonitis de hipersensibilidad en fase crónica (29.4%) y neumonía intersticial no específica (23.5%). El índice kappa entre el diagnóstico inicial y final de FPI fue 0.71 (0.60-0.82). Conclusiones: el GDM en EPID tuvo un importante impacto clínico demostrado por un alto porcentaje de cambió del diagnóstico de remisión. Se descartó el diagnóstico inicial de FPI en un porcentaje significativo de pacientes y se ratificó en un grupo menor sin esta sospecha clínica inicial. (Acta Med Colomb 2022; 47. DOI:https://doi.org/10.36104/amc.2022.2017).

Abstract Introduction: idiopathic pulmonary fibrosis (IPF) is an interstitial lung disease (ILD) with a poor prognosis, considered an orphan disease in Colombia. An accurate diagnosis has implications for the patient and healthcare costs. Multidisciplinary discussion groups (MDGs) are considered the gold standard for diagnosis. There are no prior studies in Colombia on the experience of an MDG. Objectives: to evaluate the impact of an MDG in a quaternary care institution in Bogotá on the change in the diagnosis of patients with ILD and the concordance between the initial and final diagnosis of IPF. Materials and methods: patents with ILD evaluated from 2015-2018 by the MDG made up of pulmonologists, a radiologist, a pathologist and rheumatologists. The ATS/ERS/JRS/ALAT diagnostic criteria for IPF. A description of changes in the diagnosis and the agreement between the initial diagnosis and the MDG diagnosis of IPF. Results: out of 165 patients with ILD, the diagnosis was changed in 32.5%. The MDG confirmed IPF in 77.3% of patients with an initial diagnosis of ILD and 6.7% of those with a different initial diagnosis. When IPF was ruled out, the main diagnoses were chronic hypersensitivity pneumonitis (24.8%) and nonspecific interstitial pneumonia (23.5%). The Kappa index between the initial and final IPF diagnoses was 0.71 (0.60-0.82). Conclusions: the MDG on ILD had a significant clinical impact evidenced by a high percentage of change in the referral diagnosis. The initial diagnosis of IPF was ruled out in a significant percentage of patients and confirmed in a smaller group which did not have this initial clinical suspicion. (Acta Med Colomb 2022; 47. DOI:https://doi.org/10.36104/amc.2022.2017).