Cell lineage-specific mitochondrial resilience during mammalian organogenesis.

Mitochondrial activity differs markedly between organs, but it is not known how and when this arises. Here we show that cell lineage-specific expression profiles involving essential mitochondrial genes emerge at an early stage in mouse development, including tissue-specific isoforms present before organ formation. However, the nuclear transcriptional signatures were not independent of organelle function. Genetically disrupting intra-mitochondrial protein synthesis with two different mtDNA mutations induced cell lineage-specific compensatory responses, including molecular pathways not previously implicated in organellar maintenance. We saw downregulation of genes whose expression is known to exacerbate the effects of exogenous mitochondrial toxins, indicating a transcriptional adaptation to mitochondrial dysfunction during embryonic development. The compensatory pathways were both tissue and mutation specific and under the control of transcription factors which promote organelle resilience. These are likely to contribute to the tissue specificity which characterizes human mitochondrial diseases and are potential targets for organ-directed treatments.

Hierarchical unimodal processing within the primary somatosensory cortex during a bimodal detection task.

Do sensory cortices process more than one sensory modality? To answer these questions, scientists have generated a wide variety of studies at distinct space-time scales in different animal models, and often shown contradictory conclusions. Some conclude that this process occurs in early sensory cortices, but others that this occurs in areas central to sensory cortices. Here, we sought to determine whether sensory neurons process and encode physical stimulus properties of different modalities (tactile and acoustic). For this, we designed a bimodal detection task where the senses of touch and hearing compete from trial to trial. Two Rhesus monkeys performed this novel task, while neural activity was recorded in areas 3b and 1 of the primary somatosensory cortex (S1). We analyzed neurons' coding properties and variability, organizing them by their receptive field's position relative to the stimulation zone. Our results indicate that neurons of areas 3b and 1 are unimodal, encoding only the tactile modality in both the firing rate and variability. Moreover, we found that neurons in area 3b carried more information about the periodic stimulus structure than those in area 1, possessed lower response and coding latencies, and had a lower intrinsic time scale. In sum, these differences reveal a hidden processing-based hierarchy. Finally, using a powerful nonlinear dimensionality reduction algorithm, we show that the activity from areas 3b and 1 can be separated, establishing a clear division in the functionality of these two subareas of S1.

Hyperammonemic encephalopathy after tyrosine kinase inhibitors: A literature review and a case example.

OBJECTIVE: To review the evidence of uncommon but fatal adverse event of hyperammonemic encephalopathy by tyrosine kinase inhibitors (TKI) and the possible mechanisms underlying this condition and to describe the case of a patient that developed drug-induced hyperammonemic encephalopathy related to TKI. DATA SOURCES: Literature search of different databases was performed for studies published from 1 January 1992 to 7 May 2023. The search terms utilized were hyperammonemic encephalopathy, TKI, apatinib, pazopanib, sunitinib, imatinib, sorafenib, regorafenib, trametinib, urea cycle regulation, sorafenib, carbamoyl-phosphate synthetase 1, ornithine transcarbamylase, argininosuccinate synthetase, argininosuccinate lyase, arginase 1, Mitogen activated protein kinases (MAPK) pathway and mTOR pathway, were used individually search or combined. DATA SUMMARY: Thirty-seven articles were included. The articles primarily focused in hyperammonemic encephalopathy case reports, management of hyperammonemic encephalopathy, urea cycle regulation, autophagy, mTOR and MAPK pathways, and TKI. CONCLUSION: Eighteen cases of hyperammonemic encephalopathy were reported in the literature from various multitargeted TKI. The mechanism of this event is not well-understood but some authors have hypothesized vascular causes since some of TKI are antiangiogenic, however our literature review shows a possible relationship between the urea cycle and the molecular inhibition exerted by TKI. More preclinical evidence is required to unveil the biochemical mechanisms responsible involved in this process and clinical studies are necessary to shed light on the prevalence, risk factors, management and prevention of this adverse event. It is important to monitor neurological symptoms and to measure ammonia levels when manifestations are detected.

The Omicron wave in Mexico: vaccine protection against progression to severe Covid-19 in SARS-CoV-2-infected workers.

OBJECTIVE: To assess the effectiveness of seven Covid-19 vaccines in preventing disease progression (DP) using data from national private sector workers during the Omicron wave in Mexico from January 2 to March 5, 2022. MATERIALS AND METHODS: This study employed an administrative retrospective cohort design, analyzing DP (hospitalization or death due to respiratory disease) among workers who filed a respiratory short-term disability claim and tested positive for SARS-CoV-2. Risk ratios (RRadj) were estimated using Poisson regression models adjusted for various factors. RESULTS: Vaccinated individuals had a lower risk of hospitalization and death compared with unvaccinated individuals. The overall RRadj for hospitalization and death were 0.36 (95%CI 0.32, 0.41) and 0.24 (0.17, 0.33), respectively. When evaluating vaccines individually, the RRadj for hospitalization were as follows Pfizer BioNTech 0.27 (95%CI 0.22, 0.33), Moderna 0.29 (95%CI 0.15, 0.57), Sinovac 0.32 (95%CI 0.25, 0.41), AstraZeneca 0.39 (95%CI 0.34, 0.46), Sputnik 0.39 (95%CI 0.28, 0.53), CanSino 0.41 (95%CI 0.24, 0.7), and Janssen 0.53 (95%CI 0.39, 0.72). The RRadj for death were as follows: Pfizer BioNTech 0.12 (95%CI 0.07, 0.19), Sputnik 0.15 (95%CI 0.06, 0.38), Sinovac 0.29 (95%CI 0.16, 0.53), AstraZeneca 0.30 (95%CI 0.20, 0.44), CanSino 0.38 (95%CI 0.1, 1.4), and Janssen 0.50 (95%CI 0.26, 0.97). CONCLUSION: Covid-19 vaccines significantly reduced the risk of severe disease during the Omicron wave in Mexico.

SARS-CoV-2 seroprevalence and respiratory disease disability claims in Mexico City Metropolitan Area.

OBJECTIVE: To characterize the impact of SARS-CoV-2 infection in workers from an essential large-scale company in the Greater Mexico City Metropolitan Area using point prevalence of acute infection, point prevalence of past infection through serum antibodies and respiratory disease short-term disability claims (RD-STDC). MATERIALS AND METHODS: Four randomized surveys, three during 2020 before and one after (December 2021) vaccines' availability. OUTCOMES: point prevalence of acute infection through saliva PCR (polymerase chain reaction) testing, point prevalence of past infection through serum antibodies against Covid-19, RD-STDC and prevalence of symptoms during the previous six months. RESULTS: Prevalence of SARS-CoV-2 cases was 1.29-4.88%, on average, a quarter of participants pre-vaccination were seropositive; over half of participants with a RD-STDC had antibodies. The odds of having antibodies were 6-7 times more among workers with an RD-STDC. CONCLUSIONS: High antibody levels against Covid-19 in this study population reflects that coverage is high among workers in this industry. STDCs are a useful tool to track workplace epidemics.

Use of Private Sector Workforce Respiratory Disease Short-Term Disability Claims to Assess SARS-CoV-2, Mexico, 2020.

We examined respiratory disease short-term disability claims submitted to the Mexican Social Security Institute during 2020. A total of 1,631,587 claims were submitted by 19.1 million insured workers. Cumulative incidence (8.5%) was 3.6 times higher than that for January 2015‒December-2019. Workers in healthcare, social assistance, self-service, and retail stores were disproportionately affected.

Carglumic acid in methylmalonic acidemia: Use of breast milk as an alternative vehicle to water.

WHAT IS KNOWN AND OBJECTIVE: Carbaglu® or N-carbamylglutamate (NCG) is not recommended for administration in a vehicle other than water. We aim to report the use of breast milk (BM) as an alternative vehicle in a neonate rejecting NCG diluted in water. CASE SUMMARY: A neonate diagnosed with methylmalonic acidemia presented symptomatology of acidemia and hyperammonemia. After the patient refused oral NCG administration, a dissolution test was conducted in BM showing correct dissolution. The NCG-BM solution was tolerated and plasma ammonium concentrations remained within range in subsequent analytical controls. WHAT IS NEW AND CONCLUSION: BM as a vehicle for NCG is a safe and effective option for patients who refuse suspension in water and could lead to better treatment compliance in paediatric patients.

Plataforma CLIMSS como herramienta de alfabetización en salud durante la crisis sanitaria de Covid-19.

OBJETIVO: Describir a la plataforma Cursos en Línea Masivos del IMSS (CLIMSS) como herramienta de alfabetización en salud, a través de la evaluación de la eficiencia terminal, la ganancia de competencias y satisfacción de los usuarios de cursos en línea masivos en el tema de Covid-19. Material y métodos. Se analizaron datos de 20 cursos ofertados entre marzo y octubre de 2020. Se evaluaron las calificaciones pre y pos, el número total de registros, el total de cursos terminados y la satisfacción del usuario. RESULTADOS: Se registraron un total de 4.9 millones de usuarios y 10 millo-nes de inscripciones, en todos los estados de la República mexicana, con una eficiencia terminal de 85%, una ganancia de competencias de 30% y una satisfacción de 9.34 (10). CONCLUSIONES: La plataforma CLIMSS ha mostrado ser una herramienta para la alfabetización en salud con un alcance de millones de mexicanos en temas relacionados con la crisis sanitaria Covid-19.

Comportamiento epidemiológico de SARS-CoV-2 en población trabajadora afiliada al Instituto Mexicano del Seguro Social.

Objetivo. Describir el comportamiento de la epidemia de SARS-CoV-2 entre los trabajadores afiliados al Instituto Mexicano del Seguro Social (IMSS). Material y métodos. Se analizaron las incapacidades temporales para el trabajo por enfermedades respiratorias (ITT-ER), las hospitalizaciones y defunciones asociadas durante el periodo del 1 marzo al 31 diciembre 2020. Se estimó la tasa de ataque (TA) por SARS-CoV-2, así como los riesgos relativos (RR) de ITT-ER, hos-pitalización y defunción. Resultados. De los trabajadores afiliados al IMSS, 8.8% (n=1 730 334) recibió al menos una ITT-ER. La TA fue mayor en mujeres y en ambos sexos fue menor en el grupo de >60 años. Los RR de hospitalización y defunción fueron mayores en hombres y aumentaron con la edad. Comparado con las ITT-ER de 2015-2019, Durango, Tamaulipas y Nuevo León tuvieron un RR mayor de ITT-ER que el resto del país. Conclusiones. La epidemia de SARS-CoV-2 tuvo repercusiones importantes en los trabajadores afiliados al IMSS; se observó un exceso de ITT-ER de 4.6 veces respecto a la frecuencia esperada y cerca de un millón de casos de SARS-CoV-2. Los datos sugieren que el sistema de ITT-ER puede ser utilizado como elemento adicional para la vigilancia epidemiológica de enfermedades emergentes.

Intradialytic Hypertension / Hypotension and Mortality in San Juan, Puerto Rico.

End Stage Renal Disease patients undergo profound hemodynamic changes during hemodialysis treatments which are now recognized as a marker for increased risk of morbidity and mortality. Development of intradialytic hypotension or hypertension are a common clinical problem in this population with an incidence of up to 20%. We performed a retrospective review of 49 Hispanic patients receiving ambulatory hemodialysis during a period of 6 months to ascertain the development of aforementioned intradialytic events. Clinical data examined the association of these events to mortality and their relationship to antihypertensive medications and cardiomegaly. The prevalence of intradialytic hypotension was 38.78%, hypertension 16.33% individually and both taking place 16.33%. Taken together, the prevalence of these intradialytic events was 71.43% in our Hispanic population. A significant association was found between mortality and Beta blockers (BB)(P=0.044), Calcium channel blockers (CCB) (P=0.023), cardiomegaly (P=0.044), and intradialytic events (P=0.035). Odds ratio of multiple variables dis- closed that dependent variable death decreased in probability with the use of BB by an estimate of 73% and with the use of CCB by 74.8%. On the other hand, odds of developing the dependent variable death increased by 74.5% if the patients developed intradialytic events. Similarly, the odds of developing cardiomegaly in the living group increased by 70%. A logistic regression of multiple variables found that the probability of developing the dependent condition of death increases by almost 2.896 times if intradialytic events are present and that there is a 58.9% inferred causality. It is concluded that intradialytic hyper- tension and hypotension are major risk factors for mortality in dialysis patients. The use of BB and CCB may be protetive to avoid the risk of mortality in these patients.

Declining liver graft quality threatens the future of liver transplantation in the United States.

National liver transplantation (LT) volume has declined since 2006, in part because of worsening donor organ quality. Trends that degrade organ quality are expected to continue over the next 2 decades. We used the United Network for Organ Sharing (UNOS) database to inform a 20-year discrete event simulation estimating LT volume from 2010 to 2030. Data to inform the model were obtained from deceased organ donors between 2000 and 2009. If donor liver utilization practices remain constant, utilization will fall from 78% to 44% by 2030, resulting in 2230 fewer LTs. If transplant centers increase their risk tolerance for marginal grafts, utilization would decrease to 48%. The institution of "opt-out" organ donation policies to increase the donor pool would still result in 1380 to 1866 fewer transplants. Ex vivo perfusion techniques that increase the use of marginal donor livers may stabilize LT volume. Otherwise, the number of LTs in the United States will decrease substantially over the next 15 years. In conclusion, the transplant community will need to accept inferior grafts and potentially worse posttransplant outcomes and/or develop new strategies for increasing organ donation and utilization in order to maintain the number of LTs at the current level.

Interventional nephrology in Puerto Rico: a four year experience.

Puerto Rico is one of the most prevalent areas covered by Medicare in need of renal replacement therapy for which interventional procedures are performed. A cumulative analysis of this management is reported in patients during the period between June 2007 and August 2010. Experience accumulated with 3755 surgical patients revealed that 58% had intravascular catheters, 28% had arteriovenous fistulas, 15% had arteriovenous grafts, and 2% without vascular access. Procedures performed in these patients were: catheter introduction in 1990 cases (33%), angioplasty in 751 cases (20%), angiography in 450 cases (12%), thrombectomy in 413 cases (11%) and venous mapping in 151 cases (4%). The success rates of these procedures were evaluated by analysis of the Society of Interventional Radiology (SIR) criteria for Lifeline Vascular Access. Using SIR definition of success rate for at least one session that includes "declots", placement of catheters and angioplasty, our results revealed an average of 98.2% overall success rate greater than the standard value KDOQI/SIR (> 85% ). This study has documented for four years the success rate of Vascular Interventional Nephrology Center at Auxilio Mutuo Hospital. In order to maintain this success rate is necessary to further evaluate its effectiveness and, most importantly, the development of an educational program for vascular access in patients with chronic kidney disease prior to placement in dialysis units.

"Deeply woven roots": health initiatives and community social services of faith-based organizations of the Hidalgo County, Texas.

Faith-based organizations (FBO) continue to play a significant role in the lives of individuals and communities in the United States. This study focused on the contributions of FBO to the health and well-being of residents of Rio Grande Valley, South Texas. Specifically, this study examined two main areas of involvement of FBO in Hidalgo County, Texas: health initiatives and community social services. Despite their influential and historical involvement, FBO partnership in the delivery of health and social services is not well accounted for. This study explores the characteristics of the clergy, parishioners, and FBO that are associated with community health initiatives and social services. Analyses revealed that FBO deliver a remarkably wide range of services. On a weekly basis, one in six or 17% of Hidalgo County residents were reported as receiving some form of health assistance or social services from county FBO. Variations exist depending on the characteristics of the clergy and the FBO. Policy and practice recommendations include engaging in additional networking, organizing resources, and strengthening FBO health initiatives.

Anemia management among hemodyalisis patients at the University Hospital in Puerto Rico.

End-stage renal disease is frequently complicated with anemia. Iron deficiency anemia occurs in most hemodialysis patients secondary to increased iron demand driven by the accelerated erythropoiesis that occurs when stimulating agents are administered as treatment of the anemia. The purpose of this study was to determine the prevalence of anemia and iron stores in patients undergoing hemodialysis at our unit; identify their treatment and effectiveness. Medical records of fifty-three patients undergoing ambulatory hemodialysis were evaluated for three months. Patient's hemoglobin, ferritin, iron, total iron binding capacity and percent transferrin saturation were recorded. 91% patients had arterial hypertension and 62% were diabetic. The prevalence of anemia was 34%, 57% and 47% during the three-month period respectively. Only 21% of the population had transferrin saturation less than 20% and none had ferritin below 200 ng/ml. Throughout the study, the majority of patients were managed with combination of iron and erythropoietin stimulating agents (ESAs). The prevalence of anemia remained elevated despite treatment with iron and ESAs. However, 56% of anemic patients throughout the three months showed an increase in hemoglobin levels by the end of the observation period. 53% of patients were treated with iron alone or with ESAs for the three consecutive month periods and only two had transferrin saturation less than 20%. In our population, ESAs low responsiveness is not related to iron deficiency but to the morbidity of their disease.

Thalamocortical interactions shape hierarchical neural variability during stimulus perception.

The brain is organized hierarchically to process sensory signals. But, how do functional connections within and across areas contribute to this hierarchical order? We addressed this problem in the thalamocortical network, while monkeys detected vibrotactile stimulus. During this task, we quantified neural variability and directed functional connectivity in simultaneously recorded neurons sharing the cutaneous receptive field within and across VPL and areas 3b and 1. Before stimulus onset, VPL and area 3b exhibited similar fast dynamics while area 1 showed slower timescales. During the stimulus presence, inter-trial neural variability increased along the network VPL-3b-1 while VPL established two main feedforward pathways with areas 3b and 1 to process the stimulus. This lower variability of VPL and area 3b was found to regulate feedforward thalamocortical pathways. Instead, intra-cortical interactions were only anticipated by higher intrinsic timescales in area 1. Overall, our results provide evidence of hierarchical functional roles along the thalamocortical network.

Management of heparin-induced thrombocytopenia during extracorporeal membrane oxygenation support: a case of neutropenia caused by argatroban anticoagulation.

We present the case of a man in his 70s admitted to the intensive care unit (ICU) after mitral valve replacement and coronary artery bypass graft surgery requiring extracorporeal membrane oxygenation support due to haemodynamic instability. He received anticoagulation therapy with heparin sodium and, after 5 days, the patient presented with thrombocytopenia and deep venous thrombosis. Heparin-induced thrombocytopenia was suspected based on a positive 4T score and confirmed by antiplatelet factor 4/heparin antibodies, so argatroban was initiated as an alternative anticoagulation therapy. In the following days the patient developed severe neutropenia requiring discontinuation of argatroban and the administration of granulocyte colony-stimulating factor. According to the Naranjo Adverse Drug Reaction Probability Scale, this event would be classified as a 'probable' argatroban-related adverse event. Argatroban should be conisdered as a possible cause of neutropenia and appropriate interventions need to be implemented due to the gravity of this adverse event in the ICU.

Influenza burden averted with a cell-based quadrivalent seasonal influenza vaccine compared with egg-based quadrivalent seasonal influenza vaccine.

BACKGROUND: Cell-based quadrivalent inactivated influenza vaccines (IIV4c) avoid egg-adaptive mutations found in egg-based production, improving vaccine effectiveness (VE). Studies demonstrate improved VE for IIV4c relative to egg-based quadrivalent inactivated influenza vaccines (IIV4). RESEARCH DESIGN AND METHODS: We built on a static compartmental model developed by the CDC to estimate the influenza burden in persons 0-64 years that would be additionally averted by vaccination with IIV4c vs. IIV4. Model inputs were based on published data from 2017-2018, 2018-2019, and 2019-2020 Northern Hemisphere influenza seasons for the US. RESULTS: Over 3 influenza seasons, relative to IIV4, IIV4c would avert 31-39% more symptomatic cases, 29-40% more outpatient visits, 29-38% more hospitalizations and ICU admissions, and 34-49% more deaths vs. IIV4. In a deterministic sensitivity analysis, the main drivers were the relative VE of IIV4c vs. IIV4 in the 2017-2018 season and influenza burden estimates for the 2018-2019 and 2019-2020 seasons. Probabilistic sensitivity analysis showed that the interquartile range of symptomatic cases was ± 13% of baseline in 2017-2018, ±8% in 2018-2019, and ± 7% in 2019-2020. CONCLUSIONS: IIV4c prevented significantly more symptomatic cases, outpatient visits, hospitalizations, and deaths than IIV4 in persons aged 0-64 years over 3 influenza seasons.

Comparative study of subcutaneous versus intravenous IgG replacement therapy in pediatric patients with primary immunodeficiency diseases: a multicenter study in Argentina.

PURPOSE: Several studies have shown that subcutaneous immunoglobulin (SCIG) infusions demonstrate similar efficacy to intravenous Ig (IVIG) in preventing infections in patients with primary immunodeficiency diseases (PID), and are safe and well tolerated in this population. This open, prospective/retrospective, multicenter study was designed to compare the effectiveness, safety and tolerability of a 16 % liquid human IgG preparation (Beriglobina P), administered SC, with previous IVIG treatment in PID pediatric patients in Argentina. METHODS: Fifteen subjects were enrolled in the study, and a total of 13 subjects (aged 6-18 years) completed the 36-week SCIG treatment period. All children had previously received IVIG treatment. The dose of SCIG equaled the previous IVIG dose and subjects received an average weekly dose of 139 mg/kg (range 105-181) during the SCIG period. RESULTS: Significantly higher serum IgG trough levels were recorded on SCIG treatment at 16, 24, and 36 weeks, when compared with previous IgG trough levels on steady-state IVIG treatment. The annualized infection rate was 1.4 infections/subject/year during the IVIG administration period compared with 0.4 infections/subject/year during the SCIG period. All subjects who completed the study chose to continue administering SCIG at home after the study had ended. CONCLUSIONS: These data confirm that self-administered SCIG therapy is a well-tolerated and effective alternative to IVIG therapy for children with PID.

Empowering Latino church leaders to deal with the HIV-AIDS crisis: a strengths-oriented service model.

Ideology and attitudes of Latino church leaders in the United States toward HIV/AIDS are explored. A qualitative approach utilized with emergent categories including: a desire within the Latino church for greater acceptance of HIV/AIDS sufferers, the supposed contaminating influence of HIV/AIDS individuals over other church members, and the feelings of helplessness many church members experience in relation to the HIV/AIDS crisis. Understanding ideological resistance that prevents engagement is here identified and a strategy of empowerment of church leaders is recommended to overcome it including: adopting a strengths-oriented service model that focuses on resources religious denominations already have, as opposed to a financially driven, medically oriented service model that highlights what churches often do not have; church leaders educating health care agencies on how to use religious beliefs to motivate church members to work on behalf of HIV/AIDS patients; the power of doctrinal ideology in affecting church and civil society's response to HIV/AIDS.

Additional Burden Averted in the United States From Use of MF59-Adjuvanted Seasonal Influenza Vaccine Compared With Standard Seasonal Influenza Vaccine Among Adults ≥65 Years.

Background: The MF59-adjuvanted trivalent inactivated influenza vaccine (aIIV3) is designed to overcome immunosenescence and enhance vaccine responses in older adults. We expanded on the Centers for Disease Control and Prevention (CDC) modeling method to estimate the number of additional influenza-related outcomes averted with aIIV3 versus generic quadrivalent inactivated influenza vaccine (IIV4) in adults ≥65 years over 3 influenza seasons (2017-2018 to 2019-2020) in the United States. Methods: A static compartmental model was developed based on an existing CDC model with 2 previously recommended calculation methods that increased the accuracy of the model in providing estimates of burden averted. Model inputs included vaccine effectiveness, vaccine coverage, population counts, and disease burden estimates. Additional burden averted (symptomatic cases, outpatient visits, hospitalizations, intensive care unit [ICU] admissions, and deaths) was expressed as total incremental cases averted between the vaccines. Sensitivity analyses tested the resilience of the model results to uncertainties in model inputs. Results: The model estimated that vaccination with aIIV3 versus IIV4 would avert 2.24 times as many symptomatic cases, outpatient visits, hospitalizations, ICU stays, and deaths during 2017-2018; the burden averted in 2018-2019 and 2019-2020 with aIIV3 would be 3.44 and 1.72 times that averted with IIV4, respectively. Disease burden estimates and relative vaccine effectiveness of aIIV3 had the greatest impact on model estimates. Conclusions: Over 3 influenza seasons, the model estimated that aIIV3 was more effective than IIV4 in averting influenza-related outcomes, preventing 1.72 to 3.44 times as many influenza illnesses with proportionate decreases in related healthcare use and complications.