Hospital padrino: a collaborative strategy model to tackle maternal mortality: a mixed methods study in a middle-income region.

Background: Reducing maternal mortality ratio (MMR) remains a paramount goal for low- and middle-income countries (LMICs), especially after COVID-19's devastating impact on maternal health indicators. We describe our experience implementing the Hospital Padrino Strategy (HPS), a collaborative model between a high-complexity hospital (Fundación Valle del Lili) and 43 medium- and low-complexity hospitals in one Colombian department (an administrative and territorial division) from 2021 to 2022, to sustain the trend towards reducing MMR. The study aimed to assess the effects of implementing HPS on both hospital performance and maternal health indicators in Valle del Cauca department (VCD). Methods: A mixed-methods study was conducted, comprising two phases. In the first phase, we investigated a cohort of hospitals through prospective follow-up to assess the outcomes of HPS implementation on hospital performance and maternal health indicators in VCD. In the second phase, qualitative data were collected through focus groups with 131 health workers from 33 hospitals to explore the implications of the HPS implementation on healthcare personnel. All data were obtained from records within the HPS implementation and from the Health Secretary of VCD. Findings: Evidence shows that in the context of HPS, 51 workshops involved 980 healthcare workers, covering the entire territory. Substantial improvements were observed in hospital conditions and healthcare personnel's technical competencies when providing obstetric care. Seven hundred eighty-five pregnant women with obstetric or perinatal emergencies received care through telehealth systems, with a progressive increase in technology adoption. Nine percent required Intensive Care Unit (ICU) admission, and none died. The MMR decreased from 78.8 in 2021 to 12.0 cases per 100,000 live births by 2022. Improvements in indicators and conducted training sessions instilled confidence and empowerment among the healthcare teams in the sponsored hospitals, as evidenced in focus groups derived from a sample of 131 healthcare workers from 33 hospitals. Interpretation: Implementing the Hospital Padrino Strategy led to a significant MMR reduction, and consolidated a model of social healthcare innovation replicable in LMICs. Funding: The Hospital Padrino Strategy was funded by the Fundación Valle del Lili and the Health Secretary of Valle del Cauca. Furthermore, this study received funding from a general grant for research from Tecnoquimicas S.A.

Tau reduction with artificial microRNAs modulates neuronal physiology and improves tauopathy phenotypes in mice.

Abnormal tau accumulation is the hallmark of several neurodegenerative diseases, named tauopathies. Strategies aimed at reducing tau in the brain are promising therapeutic interventions, yet more precise therapies would require targeting specific nuclei and neuronal subpopulations affected by disease while avoiding global reduction of physiological tau. Here, we developed artificial microRNAs directed against the human MAPT mRNA to dwindle tau protein by engaging the endogenous RNA interference pathway. In human differentiated neurons in culture, microRNA-mediated tau reduction diminished neuronal firing without affecting neuronal morphology or impairing axonal transport. In the htau mouse model of tauopathy, we locally expressed artificial microRNAs in the prefrontal cortex (PFC), an area particularly vulnerable to initiating tau pathology in this model. Tau knockdown prevented the accumulation of insoluble and hyperphosphorylated tau, modulated firing activity of putative pyramidal neurons, and improved glucose uptake in the PFC. Moreover, such tau reduction prevented cognitive decline in aged htau mice. Our results suggest target engagement of designed tau-microRNAs to effectively reduce tau pathology, providing a proof of concept for a potential therapeutic approach based on local tau knockdown to rescue tauopathy-related phenotypes.

Factors Predicting Prolonged Mechanical Ventilation in Guillain-Barré Syndrome.

BACKGROUND: Up to 30% of patients with Guillain-Barré syndrome require mechanical ventilation and 5% die due to acute complications of mechanical ventilation. There is a considerable group of patients that will need prolonged mechanical ventilation (considered as >14 days) and should be considered for early tracheostomy. The objective of this study is to identify risk factors for prolonged mechanical ventilation. METHODS: We prospectively analyzed patients with Guillain-Barré diagnosis with versus without prolonged mechanical ventilation. We considered clinical and electrophysiological characteristics and analyzed factors associated with prolonged mechanical ventilation. RESULTS: Three hundred and three patients were included; 29% required mechanical ventilation. When comparing the groups, patients with prolonged invasive mechanical ventilation (IMV) have a lower score on the Medical Research Council score (19.5 ± 16.2 vs 27.4 ± 17.5, p = 0.03) and a higher frequency of dysautonomia (42.3% vs 19.4%, p = 0.037), as well as lower amplitudes of the distal compound muscle action potential (CMAP) of the median nerve [0.37 (RIQ 0.07-2.25) vs. 3.9 (RIQ1.2-6.4), p = <0.001] and ulnar nerve [0.37 (RIQ0.0-3.72) vs 1.5 (RIQ0.3-6.6), p = <0.001], and higher frequency of severe axonal damage in these nerves (distal CMAP ≤ 1.0 mV). Through binary logistic regression, severe axonal degeneration of the median nerve is an independent risk factor for prolonged IMV OR 4.9 (95%CI 1.1-21.5) p = 0.03, AUC of 0.774, (95%CI 0.66-0.88), p = < 0.001. CONCLUSIONS: Severe median nerve damage is an independent risk factor for prolonged mechanical ventilation.

Relationship between the hemodynamic profile and resistant hypertension in pregnant patients with hypertensive crisis.

OBJECTIVE: Reducing maternal morbidity and mortality has been a challenge for low and middle-income countries, especially in the setting of hypertensive disorders of pregnancy. Improved strategies for treating obstetric patients with resistant hypertension are needed. We sought to explore whether hemodynamic parameters may be used to identify patients that develop resistant hypertension in pregnancy. METHODS: Retrospective cohort study among pregnant patients with gestational hypertension or preeclampsia that experienced severe blood pressure elevations. Hemodynamic variables were evaluated, including cardiac output (CO), and total peripheral resistance (TPR). The primary endpoint was resistant hypertension. An exploratory logistic regression was performed to evaluate the association between the hemodynamic profile and the development of resistant hypertension. Adverse maternal and fetal outcomes were additionally described according to the presence of resistant hypertension. RESULTS: Fifty-seven patients with severe pregnancy hypertension were included, of whom 34 developed resistant hypertension (59.7%). The resistant hypertension group, in comparison to those without resistant hypertension, presented with a hypodynamic profile characterized by reduced CO < 5 L/min (41.2% vs. 8.7%, p: 0.007), and increased TPR > 1400 dyn-s/cm5 (64.7% vs. 39.1%, p: 0.057). Logistic regression analysis revealed an association between a hypodynamic profile and resistant hypertension (OR 3.252, 95% CI 1.079-9.804; p = 0.035). Newborns of the resistant hypertension group had more frequent low birth weight (<2500 g), low Apgar scores, ICU admissions, and acute respiratory distress syndrome. CONCLUSION: Patients experiencing hypertensive crisis during pregnancy and exhibiting a hypodynamic profile (TPR ≥1400 dyn·s/cm5 and CO ≤ 5 L/min) developed higher rates of resistant hypertension.

Universal Screening for SARS-CoV-2 in Obstetric Care: Clinical Characteristics and Maternofetal Outcomes in a Latin American High-Complexity Unit.

The asymptomatic population's role in COVID-19 transmission poses challenges for control efforts. Pregnant women are susceptible to severe manifestations, increasing maternal and perinatal morbidity and mortality. This study describes the clinical characteristics, maternal and fetal outcomes, and our experience in universal severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) screening of pregnant women admitted to a high-complexity obstetric unit in Latin America. Of 568 pregnant women tested for SARS-CoV-2, 23 obtained a positive result. Among these patients, 17% had symptoms at admission, and 0.2% reported an epidemiological link. Pregnant women with positive were associated with an increased risk of eclampsia (16.7% vs 4.9%, P = .014) and acute respiratory distress (16.7% vs 4.9%, P = .014). In this group, 4 patients developed maternal near misses, and no maternal deaths were noted. Two early perinatal deaths occurred in the positive SARS-CoV-2 test group (2, 9.5% vs 17, 4.1%, P = .235). The high prevalence of asymptomatic pregnant women with SARS-CoV-2 and the adverse outcomes for those infected during pregnancy highlights the importance of universal screening upon hospital admission. This approach streamlines risk management, and enhances service structure, resource allocation, care pathways, patient management, follow-up, and overall outcomes.

Social-spatial network structures among young urban and suburban persons who inject drugs in a large metropolitan area.

BACKGROUND: Recent studies underscore the significance of adopting a syndemics approach to study opioid misuse, overdose, hepatitis C (HCV) and HIV infections, within the broader context of social and environmental contexts in already marginalized communities. Social interactions and spatial contexts are crucial structural factors that remain relatively underexplored. This study examines the intersections of social interactions and spatial contexts around injection drug use. More specifically, we investigate the experiences of different residential groups among young (aged 18-30) people who inject drugs (PWID) regarding their social interactions, travel behaviors, and locations connected to their risk behaviors. By doing so, we aim to achieve a more comprehensive understanding of the multidimensional risk environment, thereby facilitating the development of informed policies. METHODS: We collected and examined data regarding young PWID's egocentric injection network and geographic activity spaces (i.e., where they reside, inject drugs, purchase drugs, and meet sex partners). Participants were stratified based on the location of all place(s) of residence in the past year i.e., urban, suburban, and transient (both urban and suburban) to i) elucidate geospatial concentration of risk activities within multidimensional risk environments based on kernel density estimates; and ii) examine spatialized social networks for each residential group. RESULTS: Participants were mostly non-Hispanic white (59%); 42% were urban residents, 28% suburban, and 30% transient. We identified a spatial area with concentrated risky activities for each residential group on the West side of Chicago in Illinois where a large outdoor drug market area is located. The urban group (80%) reported a smaller concentrated area (14 census tracts) compared to the transient (93%) and suburban (91%) with 30 and 51 tracts, respectively. Compared to other areas in Chicago, the identified area had significantly higher neighborhood disadvantages. Significant differences were observed in social network structures and travel behaviors: suburban participants had the most homogenous network in terms of age and residence, transient participants had the largest network (degree) and more non-redundant connections, while the urban group had the shortest travel distance for all types of risk activities. CONCLUSION: Distinct residential groups exhibit varying patterns of network interaction, travel behaviors, and geographical contexts related to their risk behaviors. Nonetheless, these groups share common concentrated risk activity spaces in a large outdoor urban drug market area, underscoring the significance of accounting for risk spaces and social networks in addressing syndemics within PWID populations.

The Nß motif of NaTrxh directs secretion as an endoplasmic reticulum transit peptide and variations might result in different cellular targeting.

Soluble secretory proteins with a signal peptide reach the extracellular space through the endoplasmic reticulum-Golgi conventional pathway. During translation, the signal peptide is recognised by the signal recognition particle and results in a co-translational translocation to the endoplasmic reticulum to continue the secretory pathway. However, soluble secretory proteins lacking a signal peptide are also abundant, and several unconventional (endoplasmic reticulum/Golgi independent) pathways have been proposed and some demonstrated. This work describes new features of the secretion signal called Nß, originally identified in NaTrxh, a plant extracellular thioredoxin, that does not possess an orthodox signal peptide. We provide evidence that other proteins, including thioredoxins type h, with similar sequences are also signal peptide-lacking secretory proteins. To be a secretion signal, positions 5, 8 and 9 must contain neutral residues in plant proteins-a negative residue in position 8 is suggested in animal proteins-to maintain the Nß motif negatively charged and a hydrophilic profile. Moreover, our results suggest that the NaTrxh translocation to the endoplasmic reticulum occurs as a post-translational event. Finally, the Nß motif sequence at the N- or C-terminus could be a feature that may help to predict protein localisation, mainly in plant and animal proteins.

Diagnoses and key for the larvae of Progomphus Selys, 1854 from Argentina (Anisoptera: Gomphidae), with first larval descriptions for P. aberrans Belle, 1973 and P. kimminsi Belle, 1973.

Ten species of Progomphus Selys, 1854 are known to occur in Argentina. The larval stages of only four of them are described. We here add the larval descriptions of two species: P. aberrans Belle, 1973 and P. kimminsi Belle, 1973, and diagnose and illustrate important characters for the remaining species known at the larval stage in Argentina: P. complicatus Selys, 1854, P. joergenseni Ris, 1908, P. lepidus Ris, 1911 and P. phyllochromus Ris, 1918. New geographical records for these species are presented, including new records for P. kimminsi in Bolivia, and new provincial records in Argentina: P. aberrans and P. joergenseni in San Luis, and P. kimminsi in Santiago del Estero. A key to distinguish the larval stage of Argentinean species is proposed.

Phase Angle in Head and Neck Cancer: A Sex-Differential Analysis from Biological and Clinical Behavior to Health-Related Quality of Life.

Head and neck cancer (H&NC) is a diverse category of tumors related to malignancies in the common aerodigestive pathway, with high metabolic rate, poor nutritional and treatment outcomes, and elevated mortality despite the best standard treatment. Herein, we focus on determining how the phase angle (PA) differs across sex as a predictor of poor prognosis, low quality-of-life (QoL) scores, and mortality in patients with head and neck cancer. This follow-up study presents a sex-differential analysis in a prospective cohort of 139 head and neck cancer patients categorized by sex as male (n = 107) and female (n = 32). Patients were compared in terms of nutritional, biochemical, and quality-of-life indicators between low and normal PA in women (<3.9° (n = 14, 43.75%) and ≥3.9°) and men (<4.5° (n = 62, 57.9%) and ≥4.5°). Our results show that most patients were in locally advanced clinical stages (women: n = 21 (65.7%); men: n = 67 (62.6%)) and that patients with low PA had a lower punctuation in parameters such as handgrip strength, four-meter walking speed, albumin, C-reactive protein (CRP), and CRP/albumin ratio (CAR), as well as the worst QoL scores in functional and symptomatic scales in both the male and female groups. A comparison between sexes revealed significant disparities; malnourishment and tumor cachexia related to an inflammatory state was more evident in the women's group.

Escala de Percepción de Reforzamiento Medioambiental (EROS): evidencias de validez en una muestra colombiana

Introducción: El objetivo de esta investigación fue confirmar la estructura interna de la Environmental Reward Observation Scale (EROS) y recoger evidencias de su relación con otros constructos en una muestra colombiana de 902 adultos que consintieron participar voluntariamente. Método: Se realizaron análisis psicométricos con Teoría Clásica de los Test y el modelo de Rasch. Se recolectaron evidencias de validez de la estructura interna y de la relación de las puntuaciones con otras variables. Resultados: Se obtuvieron buenos índices en los coeficientes alfa y omega de McDonald, nueve de los 10 ítems tuvieron buenos ajustes en los índices infit y outfit, y el ítem ocho presentó DIF en el nivel educativo. Se confirmó la estructura unidimensional de la EROS y fue invariante respecto al sexo y nivel educativo. Los puntajes tuvieron correlaciones de magnitud alta con sintomatología emocional y variables afines a la Activación Conductual. Conclusiones: La EROS presentó altas calidades psicométricas para su uso en población colombiana; sin embargo, se recomienda su uso solo para evaluación de tamizaje, porque los niveles de información están centrados en un área reducida a lo largo de la métrica logit.

Introduction: The aim of this research was to confirm the internal structure of the Environmental Reward Observation Scale (EROS) and to collect evidence of its relationship with other constructs in a Colombian sample of 902 adults who voluntarily consented to participate. Method: Psychometric analyses were performed using Classical Test Theory and the Rasch model. Evidence of validity based on internal structure and relations of scores with other variables was collected. Results: Good indexes were obtained in McDonald's Alpha and Omega coefficients, 9 of the 10 items had good adjustments in the Infit and Outfit indexes, and item 8 presented DIF in the educational level. The unidimensional structure of the EROS was confirmed and was invariant with respect to sex and educational level. Scores had high magnitude correlations with emotional symptomatology and variables related to Behavioral Activation. Conclusions: The EROS presented high psychometric qualities for its use in the Colombian population; however, its use is recommended only for screening assessment because the levels of information are centered in a reduced area along the Logit scaling.

Pregnancy-specific responses to COVID-19 revealed by high-throughput proteomics of human plasma.

BACKGROUND: Pregnant women are at greater risk of adverse outcomes, including mortality, as well as obstetrical complications resulting from COVID-19. However, pregnancy-specific changes that underlie such worsened outcomes remain unclear. METHODS: Plasma samples were collected from pregnant women and non-pregnant individuals (male and female) with (n = 72 pregnant, 52 non-pregnant) and without (n = 29 pregnant, 41 non-pregnant) COVID-19. COVID-19 patients were grouped as asymptomatic, mild, moderate, severe, or critically ill according to NIH classifications. Proteomic profiling of 7,288 analytes corresponding to 6,596 unique protein targets was performed using the SOMAmer platform. RESULTS: Herein, we profile the plasma proteome of pregnant and non-pregnant COVID-19 patients and controls and show alterations that display a dose-response relationship with disease severity; yet, such proteomic perturbations are dampened during pregnancy. In both pregnant and non-pregnant state, the proteome response induced by COVID-19 shows enrichment of mediators implicated in cytokine storm, endothelial dysfunction, and angiogenesis. Shared and pregnancy-specific proteomic changes are identified: pregnant women display a tailored response that may protect the conceptus from heightened inflammation, while non-pregnant individuals display a stronger response to repel infection. Furthermore, the plasma proteome can accurately identify COVID-19 patients, even when asymptomatic or with mild symptoms. CONCLUSION: This study represents the most comprehensive characterization of the plasma proteome of pregnant and non-pregnant COVID-19 patients. Our findings emphasize the distinct immune modulation between the non-pregnant and pregnant states, providing insight into the pathogenesis of COVID-19 as well as a potential explanation for the more severe outcomes observed in pregnant women.

Pregnant COVID-19 patients are at increased risk of experiencing complications and severe outcomes compared to the general population. However, the reasons for this heightened risk are still unclear. We measured the proteins present in the blood of pregnant and non-pregnant patients with COVID-19 and compared these to healthy individuals. We found that some COVID-19-associated proteins were present at lower levels in pregnant women, which could help to protect the fetus from harmful inflammation, the body's natural response to infection. While some proteins affected by COVID-19 are shared between pregnant and non-pregnant patients, others were distinctly affected only in pregnant women, providing a potential explanation for the more severe outcomes in this group.

Social-spatial network structures among young urban and suburban persons who inject drugs in a large metropolitan area.

Background: It is estimated that there are 1.5% US adult population who inject drugs in 2018, with young adults aged 18-39 showing the highest prevalence. PWID are at a high risk of many blood-borne infections. Recent studies have highlight the importance of employing the syndemic approach to study opioid misuse, overdose, HCV and HIV, along with the social and environmental contexts where these interrelated epidemics occur in already marginalized communities. Social interactions and spatial contexts are important structural factors that are understudied. Methods: Egocentric injection network and geographic activity spaces for young (aged 18-30) PWID and their injection, sexual, and social support network members (i.e., where reside, inject drugs, purchase drugs, and meet sex partners) were examined using baseline data from an ongoing longitudinal study (n=258). Participants were stratified based on the location of all place(s) of residence in the past year i.e., urban, suburban, and transient (both urban and suburban) to i) elucidate geospatial concentration of risk activities within multi-dimensional risk environments based on kernel density estimates; and ii) examine spatialized social networks for each residential group. Results: Participants were mostly non-Hispanic white (59%); 42% were urban residents, 28% suburban, and 30% transient. We identified a spatial area with concentrated risky activities for each residence group on the West side of Chicago where a large outdoor drug market area is located. The urban group (80%) reported a smaller concentrated area (14 census tracts) compared to the transient (93%) and suburban (91%) with 30 and 51 tracts, respectively. Compared to other areas in Chicago, the identified area had significantly higher neighborhood disadvantages (e.g., higher poverty rate, p <0.001). Significant ( p <0.01 for all) differences were observed in social network structures: suburban had the most homogenous network in terms of age and residence, transient participants had the largest network (degree) and more non-redundant connections. Conclusion: We identified concentrated risk activity spaces among PWID from urban, suburban, and transient groups in a large outdoor urban drug market area, which highlights the need for considering the role of risk spaces and social networks in addressing the syndemics in PWID populations.

Critical access medication for opioid use disorder (MOUD) treatment facilities in the continental United States.

Research objective: Medication opioid use disorder (MOUD) treatment is the first-line approach to the treatment of opioid use disorder (OUD). This analysis seeks to identify "critical access" MOUD facilities that ensure geographic access for MOUD patients. Using public-source data and spatial analysis, we identify the top 100 "critical access" MOUD units across the continental U.S. Study design: We use locational data from SAMHSA's Behavioral Health Treatment Services Locator and DATA 2000 waiver buprenorphine providers. We identify the closest MOUDs to each ZIP Code Tabulation Area (ZCTA)'s geographic centroid. We then construct a difference-in-distance metric by computing the difference in this distance measure between closest and second-closest MOUD, multiplied by ZCTA population, ranking MOUDs by difference-distance scores. Population studied: All listed MOUD treatment facilities and all listed ZCTA's across the continental U.S., and all listed MOUD providers proximate to these areas. Principal findings: We identified the top 100 critical access MOUD units in the continental United States. Many critical providers were in rural areas in the central United States, as well as a band extending east from Texas to Georgia. Twenty-three of the top 100 critical access providers were identified as providing naltrexone. Seventy-seven were identified as providing buprenorphine. Three were identified as providing methadone. Conclusions: Significant areas of the United States are dependent on a single critical access MOUD provider. Implications for policy or practice: Place-based supports may be warranted to support MOUD treatment access in areas dependent upon critical access providers.

Sural nerve involvement in Guillain-Barré syndrome: Clinical and prognostic implications. A prospective cohort.

BACKGROUND: Sural sparing is common in Guillain-Barré syndrome (GBS). However, one third of patients have sural nerve compromise. Its clinical implications associated factors and short-term prognosis are still unknown. The objective of this study is to identify if sural nerve compromise is associated with a worse prognosis and to describe clinical and electrophysiological characteristics in Guillain-Barré syndrome. MATERIALS AND METHODS: We prospectively analyzed patients with Guillain-Barré diagnosis with vs without sural nerve compromise. All patients underwent nerve conduction studies within the first 3 days of hospital admission. Clinical and electrophysiological characteristics were compared between groups. RESULTS: 174 patients were included in this study. Acute inflammatory demyelinating polyneuropathy was the predominant variant (43.7 %). Thirty percent of patients had sural nerve involvement. In the comparative analysis between affected vs unaffected sural groups, age ≥50 years and Guillain-Barré disability score ≥3 demonstrated a statistically significant difference. Regarding short-term recovery period for independent walking, there was no significant difference. In the multivariate analysis, age ≥50 years was identified as independent factors for sural nerve compromise on admission. CONCLUSION: sural nerve compromise occurs in 30 % of patients with GBS and is not associated with a worse functional prognosis. Age ≥50 years was identified as an independent factor for sural nerve compromise.

The uncharacterized Pseudomonas aeruginosa PA4189 is a novel and efficient aminoacetaldehyde dehydrogenase.

Neither the Pseudomonas aeruginosa aldehyde dehydrogenase encoded by the PA4189 gene nor its ortholog proteins have been biochemically or structurally characterized and their physiological function is unknown. We cloned the PA4189 gene, obtained the PA4189 recombinant protein, and studied its structure-function relationships. PA4189 is an NAD+-dependent aminoaldehyde dehydrogenase highly efficient with protonated aminoacetaldehyde and 3-aminopropionaldehyde, which are much more preferred to the non-protonated species as indicated by pH studies. Based on the higher activity with aminoacetaldehyde than with 3-aminopropionaldehyde, we propose that aminoacetaldehyde might be the PA4189 physiological substrate. Even though at the physiological pH of P. aeruginosa cells the non-protonated aminoacetaldehyde species will be predominant, and despite the competition of these species with the protonated ones, PA4189 would very efficiently oxidize ACTAL in vivo, producing glycine. To our knowledge, PA4189 is the first reported enzyme that might metabolize ACTAL, which is considered a dead-end metabolite because its consuming reactions are unknown. The PA4189 crystal structure reported here suggested that the charge and size of the active-site residue Glu457, which narrows the aldehyde-entrance tunnel, greatly define the specificity for small positively charged aldehydes, as confirmed by the kinetics of the E457G and E457Q variants. Glu457 and the residues that determine Glu457 conformation inside the active site are conserved in the PA4189 orthologs, which we only found in proteobacteria species. Also is conserved the PA4189 genomic neighborhood, which suggests that PA4189 participates in an uncharacterized metabolic pathway. Our results open the door to future efforts to characterize this pathway.