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This study estimated the effects of the COVID-19 pandemic on maternal mortality in Chile between 2020 and 2021. A natural experiment was conducted using official data on maternal deaths and live births (LBs) between 1997 and 2021. The effects of the SARS-CoV-2 outbreak were evaluated using interrupted time series (ITS) and an autoregressive integrated moving average (ARIMA) model to forecast the expected rates on MMR and 95% confidence intervals (95% CI). In Chile, following World Health Organization suggestions, maternal deaths aggravated by SARS-CoV-2 are assigned to code O98.5 (non-respiratory infectious indirect) accompanied by code U07.1 or U07.2, depending on confirmation of the presence or absence of the virus. ITS analysis revealed that the SARS-CoV-2 outbreak impacted the MMR due to indirect causes, with a greater increase in indirect nonrespiratory causes than respiratory causes. The ARIMA forecast was consistent with ITS, showing that the expected MMR for indirect causes (3.44 in 2020 and 1.55 in 2021) was substantially lower than the observed rates (9.65 in 2020 and 7.46/100.000 LBs in 2021). For nonrespiratory indirect causes, the observed values of the MMR for 2020 (8.77/100.000 LBs) and 2021 (7.46/100.000 LBs) were double the predicted values of 4.02 (95% CI: 0.44-7.61) and 3.83 (95% CI: -0.12-7.79), respectively. A lower effect was observed on direct obstetrical deaths. During 2020-2021, there was a rise in the MMR in Chile attributable to SARS-CoV-2. The pandemic contributed to an escalation in the MMR due to indirect causes, particularly nonrespiratory and infectious causes. MMR due to direct obstetric causes were less affected. This suggests that the pandemic disproportionately affected maternal health by exacerbating conditions unrelated to pregnancy, childbirth, or postpartum, more than those directly linked to obstetric complications.

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The emergence of hypervirulent Klebsiella pneumoniae (hvKP) strains poses a significant threat to public health due to high mortality rates and propensity to cause severe community-acquired infections in healthy individuals. The ability to form biofilms and produce a protective capsule contributes to its enhanced virulence and is a significant challenge to effective antibiotic treatment. Polyphosphate kinase 1 (PPK1) is an enzyme responsible for inorganic polyphosphate synthesis and plays a vital role in regulating various physiological processes in bacteria. In this study, we investigated the impact of polyP metabolism on the biofilm and capsule formation and virulence traits in hvKP using Dictyostelium discoideum amoeba as a model host. We found that the PPK1 null mutant was impaired in biofilm and capsule formation and showed attenuated virulence in D. discoideum compared to the wild-type strain. We performed a proteomic analysis to gain further insights into the underlying molecular mechanism. The results revealed that the PPK1 mutant had a differential expression of proteins involved in capsule synthesis (Wzi-Ugd), biofilm formation (MrkC-D-H), synthesis of the colibactin genotoxin precursor (ClbB), as well as proteins associated with the synthesis and modification of lipid A (ArnB-LpxC-PagP). These proteomic findings corroborate the phenotypic observations and indicate that the PPK1 mutation is associated with impaired biofilm and capsule formation and attenuated virulence in hvKP. Overall, our study highlights the importance of polyP synthesis in regulating extracellular biomolecules and virulence in K. pneumoniae and provides insights into potential therapeutic targets for treating K. pneumoniae infections.

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Introduction: Long-term pulmonary dysfunction (L-TPD) is one of the most critical manifestations of long-COVID. This lung affection has been associated with disease severity during the acute phase and the presence of previous comorbidities, however, the clinical manifestations, the concomitant consequences and the molecular pathways supporting this clinical condition remain unknown. The aim of this study was to identify and characterize L-TPD in patients with long-COVID and elucidate the main pathways and long-term consequences attributed to this condition by analyzing clinical parameters and functional tests supported by machine learning and serum proteome profiling. Methods: Patients with L-TPD were classified according to the results of their computer-tomography (CT) scan and diffusing capacity of the lungs for carbon monoxide adjusted for hemoglobin (DLCOc) tests at 4 and 12-months post-infection. Results: Regarding the acute phase, our data showed that L-TPD was favored in elderly patients with hypertension or insulin resistance, supported by pathways associated with vascular inflammation and chemotaxis of phagocytes, according to computer proteomics. Then, at 4-months post-infection, clinical and functional tests revealed that L-TPD patients exhibited a restrictive lung condition, impaired aerobic capacity and reduced muscular strength. At this time point, high circulating levels of platelets and CXCL9, and an inhibited FCgamma-receptor-mediated-phagocytosis due to reduced FcγRIII (CD16) expression in CD14+ monocytes was observed in patients with L-TPD. Finally, 1-year post infection, patients with L-TPD worsened metabolic syndrome and augmented body mass index in comparison with other patient groups. Discussion: Overall, our data demonstrated that CT scan and DLCOc identified patients with L-TPD after COVID-19. This condition was associated with vascular inflammation and impair phagocytosis of virus-antibody immune complexes by reduced FcγRIII expression. In addition, we conclude that COVID-19 survivors required a personalized follow-up and adequate intervention to reduce long-term sequelae and the appearance of further metabolic diseases.

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CD8+ and CD4+ T-cells play a key role in cellular immune responses against cancer by cytotoxic responses and effector lineages differentiation, respectively. These subsets have been found in different types of cancer; however, it is unclear whether tumor-infiltrating T-cell subsets exhibit similar transcriptome profiling across different types of cancer in comparison with healthy tissue-resident T-cells. Thus, we analyzed the single cell transcriptome of five tumor-infiltrating CD4-T, CD8-T and Treg cells obtained from different types of cancer to identify specific pathways for each subset in malignant environments. An in silico analysis was performed from single-cell RNA-sequencing data available in public repositories (Gene Expression Omnibus) including breast cancer, melanoma, colorectal cancer, lung cancer and head and neck cancer. After dimensionality reduction, clustering and selection of the different subpopulations from malignant and nonmalignant datasets, common genes across different types of cancer were identified and compared to nonmalignant genes for each T-cell subset to identify specific pathways. Exclusive pathways in CD4+ cells, CD8+ cells and Tregs, and common pathways for the tumor-infiltrating T-cell subsets were identified. Finally, the identified pathways were compared with RNAseq and proteomic data obtained from T-cell subsets cultured under malignant environments and we observed that cytokine signaling, especially Th2-type cytokine, was the top overrepresented pathway in Tregs from malignant samples.

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Background: Early-onset gastric cancers (EOGC) are poor prognosis hard-to treat malignancies that affect young individuals (<45 years old). Case Description: Herein we describe the case of a 26-year-old female EOGC patient that initially displayed stable disease after first-line CAPOX plus immunotherapy. However, patient eventually developed progressive disease and was consecutively switched to paclitaxel plus ramucirumab, and palliative irinotecan. In search for therapeutic alternatives a proteo-genomic analysis was performed in a tissue biopsy taken after the first progression. Our analyses found a total of 18 somatic mutations, including TP53 and PIK3R1, and a previously unreported germline alteration in the tumor suppressor SMAD4. Also, our proteomic analysis found 62 proteins previously documented as "enriched in stomach cancer" and AKT/mTOR and EGFR as pathways with therapeutic potential. Unfortunately, the clinical utility of AKT/mTOR inhibitors or EGFR targeted therapies could not be assessed. Conclusions: As explained above EOGC is a growing health concern that affects young individuals. Furthermore, the reported case displayed a poor response to standard therapy including checkpoint inhibitors and chemotherapy despite the presence of biomarkers that predict a favorable outcome. Future studies should adopt alternative approaches to find novel, more effective therapies.

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Background: Emerging pandemic viruses may have multiple deleterious effects on maternal health. This study examines the effects of a pandemic influenza virus on cause-specific maternal mortality time series, using Argentinian vital statistics. Methods: We conducted a population-based natural experiment from national vital records of maternal deaths between 1980 and 2017. Joinpoint regression models were used to model time series of the maternal mortality ratio (MMR). The sensitivity of the registry to detect the effects of the pandemic H1N1 2009 influenza virus on cause-specific MMR was analysed using a panel of parallel interrupted time series (ITS). Findings: Over this 38-year study, the MMR decreased by 58·6% (69·5 to 28·8 deaths/100,000 live births), transitioning from direct obstetric causes (67·0 to 21·1/100,000 live births; 68·4% decrease) to indirect causes (2·6 to 7·7/100,000 live births; 196·2% increase). The regression analysis showed an average reduction of -2·2%/year (95% CI: -2·9 to -1·4) with 2 join points in the total trend (1998 and 2009). Parallel ITS analyses revealed the pandemic H1N1 virus had an increasing effect on mortality from the respiratory system- and sepsis-related complications (level change 4·7 and 1·6/100,000 live births respectively), reversing after the outbreak. No effect was found on MMR from hypertensive disorders, haemorrhage, abortive outcomes, other direct obstetric causes, and indirect non-respiratory comorbidities. Interpretation: The Argentinian maternal death registry appears sensitive to detect different effects of emerging infectious epidemics on maternal health. In a population-based natural experiment, pandemic H1N1 virus impacted maternal mortality almost exclusively from the respiratory system- and sepsis-related complications. Funding: Supported by FISAR www.fisarchile.org.

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Mortality by abortion has continuously decreased over the past fifty years in Chile. In fact, maternal death as a result of an induced abortion has become an exceptionally rare phenomenon in epidemiological terms (a risk of 1 in 4 million pregnant women of fertile age or 0.4 per 100,000 life births for abortion of any type, excluding ectopic pregnancy). After abortion became illegal in 1989, deaths related to abortion continued to decrease from 10.8 to 0.39 per 100,000 live births. This scientific fact challenges the common notion that less permissive abortion laws lead to greater mortality associated with abortion.

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OBJECTIVE: To test whether there is an association between abortion legislation and maternal mortality outcomes after controlling for other factors thought to influence maternal health. DESIGN: Population-based natural experiment. SETTING AND DATA SOURCES: Official maternal mortality data from 32 federal states of Mexico between 2002 and 2011. MAIN OUTCOMES: Maternal mortality ratio (MMR), MMR with any abortive outcome (MMRAO) and induced abortion mortality ratio (iAMR). INDEPENDENT VARIABLES: Abortion legislation grouped as less (n=18) or more permissive (n=14); constitutional amendment protecting the unborn (n=17); skilled attendance at birth; all-abortion hospitalisation ratio; low birth weight rate; contraceptive use; total fertility rates (TFR); clean water; sanitation; female literacy rate and intimate-partner violence. MAIN RESULTS: Over the 10-year period, states with less permissive abortion legislation exhibited lower MMR (38.3 vs 49.6; p<0.001), MMRAO (2.7 vs 3.7; p<0.001) and iAMR (0.9 vs 1.7; p<0.001) than more permissive states. Multivariate regression models estimating effect sizes (ß-coefficients) for mortality outcomes showed independent associations (p values between 0.001 and 0.055) with female literacy (ß=-0.061 to -1.100), skilled attendance at birth (ß=-0.032 to -0.427), low birth weight (ß=0.149 to 2.166), all-abortion hospitalisation ratio (ß=-0.566 to -0.962), clean water (ß=-0.048 to -0.730), sanitation (ß=-0.052 to -0.758) and intimate-partner violence (ß=0.085 to 0.755). TFR showed an inverse association with MMR (ß=-14.329) and MMRAO (ß=-1.750) and a direct association with iAMR (ß=1.383). Altogether, these factors accounted for (R(2)) 51-88% of the variance among states in overall mortality rates. No statistically independent effect was observed for abortion legislation, constitutional amendment or other covariates. CONCLUSIONS: Although less permissive states exhibited consistently lower maternal mortality rates, this finding was not explained by abortion legislation itself. Rather, these differences were explained by other independent factors, which appeared to have a more favourable distribution in these states.

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Background: Inadequate blood pressure control in hypertensive patients remains a persistent health problem in Chile and worldwide. Poor adherence to antihypertensive drug therapy is one of the frequently cited factors. Objectives: To determine the influence of psychosocial factors in the adherence to drug therapy in hypertensive patients followed through a Cardiovascular Health Program (CHP) that provides free access to primary care centers located in the Metropolitan Region of Santiago, Chile. Methods: Cross sectional study. A randomized sample of 513 hypertensive patients (30 to 68 years) was obtained from a universe of 1.484 patients. Adherence to treatment was determined by the Morisky-Green-Levine test. Demographic, socioeconomic and average values of blood pressure were recorded. Validated questionnaires were utilized to assess the patient-physician relationship, awareness of being hypertensive, patient perception of social support, family cohesion, patient self-health assessment and symptoms of emotional stress and depression. Results: The drug therapy adherence was 36.6%, higher in women (38.4% vs 28.9%; p < 0.001). After multivariate analysis, absence of adherence was associated with male gender (OR: 1.76 [95% CI 1.21-2.56]), low education (OR: 1.72 [95% CI 1.18 to 2.53]), inadequate patient-physician relationship (OR: 1.56 [95% CI 1.13 to 2.27]), and high level of emotional stress and depression (OR: 1.93 [95% CI 1.27 to 2.94]). Conclusions: Our study highlights the influence of inadequate patient-physician relation, high level of emotional stress and depression, low education level and income and male gender in the lack of adherence to antihypertensive drug therapy in hypertensive patients followed throughout the CHP.

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