Load-velocity Relationship of the Bench Press Exercise is not Affected by Breast Cancer Surgery and Adjuvant Therapy.

We examined the effect of breast cancer surgery and adjuvant therapy on the relationship between bar velocity and relative intensity (load-velocity [L-V] relationship) of the bench press (BP) exercise. Twenty-two breast cancer survivors (age: 48.0±8.2 yr., relative strength: 0.40±0.08) completed a loading test up to the one-repetition maximum (1RM) in the BP using a lightweight carbon bar. General and individual relationships between relative intensity (%1RM) and mean propulsive velocity (MPV) were studied. Furthermore, the mean test velocity (MPVTest) and velocity attained to the 1RM (MPV1RM) were analyzed. These procedures and analyses were also conducted in 22 healthy women (age: 47.8±7.1 yr., relative strength: 0.41±0.09) to examine the differences in velocity parameters derived from these L-V relationships. Polynomial regressions showed very close relationships (R2≥0.965) and reduced estimation errors (≤4.9% 1RM) for both groups. Between-group differences in MPV attained to each %1RM were small (≤0.01 m·s-1) and not significant (p≥0.685). Similarly, the MPVTest (0.59±0.06 m·s-1) and MPV1RM (0.17±0.03 m·s-1) were identical for breast cancer survivors and healthy women. These results suggest that practitioners could use the same velocity parameters derived from the BP L-V relationship to prescribe this exercise in middle-aged women, regardless of whether they have suffered from breast cancer.

Entomological Survey and Leishmania (Leishmania) mexicana Prevalence in Sand Fly Species during an Outbreak of Cutaneous Leishmaniasis in Quintana Roo State, Mexico.

(1) Background: Localized cutaneous leishmaniasis is a neglected vector-borne disease that has become a serious public health problem in the Yucatan Peninsula. Although more than 60% of cases originate from the state of Quintana Roo, it is one of the least explored areas in terms of incriminating vectors of the Leishmania parasite. Additionally, cases of leishmaniasis have increased substantially in that region in recent years. For this reason, we explored and provided primary evidence of Leishmania DNA in sand fly species from four localities during outbreaks of leishmaniasis in Quintana Roo. We also contributed information on the regional genetic diversity of Leishmania parasites. (2) Methods: Sand flies were collected during several periods from November 2022 to April 2023 using Mosquito Light Circle and Shannon traps, as well as an active entomological search in refuges. For Leishmania detection, we amplified a fragment of 300-350 bp of the internal transcribed spacer subunit 1 (ITS-1). (3) Results: Of the 242 females collected, we detected Leishmania DNA in 25 specimens represented by Bichromomyia olmeca (1), Psathyromyia shannoni (17), Lutzomyia cruciata (4), Psathyromyia undulata (2), and Dampfomyia deleoni (1). The detection of Leishmania in these last two species represents new records for the Yucatan Peninsula and for Mexico. Leishmania (Leishmania) mexicana was the only species detected in the Phlebotominae species, with prevalence values that ranked between 7.41% and 33.33% from specimens collected in the sylvatic areas of Cozumel Island and Petcacab. (4) Conclusions: This study provides the first evidence of infection of Da. deleoni and Pa. undulata by L. (L.) Mexicana. In addition, the presence of three dominant haplotypes in all the evaluated localities was evidenced using the analysis of genetic diversity, and the locality of Petcacab was the one with the circulation of two new haplotypes not previously described in Mexico or neighboring countries. These results highlight the importance of intensive epidemiological surveillance due to the dynamics of transmission of Leishmania between different species.

DNA barcoding and new records of Ornithodoros yumatensis from Central Mexico.

Bats represent the second order of mammals with the highest number of species worldwide with over 1,616 species, and almost 10% of them are recorded in Mexico. These mammals have a great diversity of ectoparasites, in particular soft ticks of the genus Ornithodoros. Desmodus rotundus is one of the bat species that has scarcely been studied in terms of tick species richness in Mexico, with three tick species reported in five of the 32 Mexican states. For this reason, the aim of the present work was to identify ticks associated with D. rotundus from Central Mexico. Fieldwork was undertaken in the municipality El Marqués, Ejido Atongo A, Querétaro, Mexico. Bats were captured using mist nets and were visually inspected for tick presence. The ectoparasites were identified morphologically and molecularly with the use of mitochondrial markers 16SrDNA and cytochrome oxidase subunit I (COI). A total of 30 D. rotundus (1 female, 29 males) were captured, from which 20 larvae identified as Ornithodoros yumatensis were recovered. Molecular analysis confirmed the presence of this species with identity values of 99-100% with sequences of this species from the southwestern US, and the Yucatán Peninsula, Mexico. This is the first report of ticks associated with bats for the state of Querétaro, providing the first sequences of the COI gene from Mexican populations of O. yumatensis and shows an increase in the distribution of this soft tick across Central Mexico.

First-trimester plasma extracellular heat shock proteins levels and risk of preeclampsia.

Preeclampsia (PE) occurs annually in 8% of pregnancies. Patients without risk factors represent 10% of these. There are currently no first-trimester biochemical markers that accurately predict PE. An increase in serum 60- and 70-KDa extracellular heat shock proteins (eHsp) has been shown in patients who developed PE at 34 weeks. We sought to determine whether there is a relationship between first-trimester eHsp and the development of PE. This was a prospective cohort study performed at a third level hospital in Mexico City from 2019 to 2020. eHsp levels were measured during the first-trimester ultrasound in singleton pregnancies with no comorbidities. First-trimester eHsp levels and biochemical parameters of organ dysfunction were compared between patients who developed preeclampsia and those who did not. All statistical analyses and model of correlation (r) between eHsp and clinical parameter were performed using bootstrapping R-software. p-values <0.05 were considered significant. The final analysis included 41 patients. PE occurred in 11 cases. eHsp-60 and eHsp-70 were significantly higher at 12 weeks in patients who developed PE (p = 0.001), while eHsp-27 was significantly lower (p = 0.004). Significant differences in first-trimester eHsp concentration suggest that these are possible early biomarkers useful for the prediction of PE.

Children victims of drug abuser parents: Hair testing as a forensic tool to assess exposure-A cohort of 37 cases from Spain.

Hair testing is a useful tool to investigate suspected pediatric exposure to drugs of abuse. Newborns and young children are at high risk of exposure to drugs of abuse from parents or caregivers who consumed these substances, a fact prosecuted by Spanish authorities as child abuse. A retrospective study based on a cohort of 37 cases classified using several parameters, which involve children under 12 years old, were analyzed at the Drugs Laboratory of the National Institute of Toxicology and Forensic Sciences (Madrid, Spain) between 2009 and 2021. Hair samples were tested for the presence of opiates, cocaine, ketamine, amphetamines, methadone, and cannabis using a gas chromatography-mass spectrometry (GC-MS) method. A 59% of the studied children had ages in the range of 1-3 years old, and in 81% of cases, victims required hospitalization. In 81% of cases (n = 30), hair was submitted only or in combination with other samples, and these were classified in four categories according to analyzed samples: A (only hair), B (hair and blood), C (hair and urine), and D (hair, blood, and urine). The 93.3% of these cases (n = 28) showed a positive result of cannabinoids (THC and CBN in hair and THC-COOH in urine; 71.4% n = 20), cocaine and metabolites (benzoylecgonine and cocaethylene; 46.4% n = 13), opiates (morphine and 6-acetylmorphine), and amphetamines (MDMA and MDMA; 3.10% n = 1). Hair analysis matched positive results in cases where urine screening test was carried out previously (n = 24) and in those cases where blood and/or urine were also submitted (35.6% n = 11). As a conclusion, hair analysis was confirmed as a useful tool to detect previous exposure to acute poisoning events in children.

Bacillus thuringiensis Cyt Proteins as Enablers of Activity of Cry and Tpp Toxins against Aedes albopictus.

Aedes albopictus is a species of mosquito, originally from Southeast Asia, that belongs to the Culicidae family and the Dipteran insect order. The distribution of this vector has rapidly changed over the past decade, making most of the temperate territories in the world vulnerable to important human vector-borne diseases such as dengue, yellow fever, zika or chikungunya. Bacillus thuringiensis var. israeliensis (Bti)-based insecticides represent a realistic alternative to the most common synthetic insecticides for the control of mosquito larvae. However, several studies have revealed emerging resistances to the major Bti Crystal proteins such as Cry4Aa, Cry4Ba and Cry11Aa, making the finding of new toxins necessary to diminish the exposure to the same toxicity factors overtime. Here, we characterized the individual activity of Cyt1Aa, Cry4Aa, Cry4Ba and Cry11Aa against A. albopictus and found a new protein, Cyt1A-like, that increases the activity of Cry11Aa more than 20-fold. Additionally, we demonstrated that Cyt1A-like facilitates the activity three new Bti toxins: Cry53-like, Cry56A-like and Tpp36-like. All in all, these results provide alternatives to the currently available Bti products for the control of mosquito populations and position Cyt proteins as enablers of activity for otherwise non-active crystal proteins.

Intoxicación suicida por nitrito sódico: una peligrosa modalidad en Internet. A propósito de un caso / Suicidal poisoning by sodium nitrite: A dangerous mode from Internet. In regard of a case

Se reporta un caso de suicidio por ingesta de nitritos. Se trata de una joven que fue hallada muerta en un vehículo junto a una serie de objetos, entre ellos una bolsa de polvo blanco etiquetada como «nitrito sódico» y comprimidos de lorazepam, paracetamol y metoclopramida. La autopsia reveló signos compatibles con metahemoglobinemia. Se remitieron muestras de sangre, humor vítreo y contenido gástrico, así como la bolsa con el polvo, los comprimidos y otros objetos al Servicio de Drogas del Departamento de Madrid del Instituto Nacional de Toxicología y Ciencias Forenses. El polvo fue identificado como nitrito sódico, y se detectaron concentraciones de nitritos en las muestras biológicas similares a las de otras intoxicaciones letales. El porcentaje de metahemoglobina en sangre fue del 80%. La existencia de páginas en Internet donde el suicidio con nitritos y metoclopramida es detalladamente descrito, así como el aumento del reporte de este tipo de suicidios, alertan acerca de una posible tendencia. (AU)

A case of suicide by nitrites ingestion is reported: a young woman was found death into a car with various objetcs around her, such as a white powder bag labelled as «sodium nitrite» and pills of lorazepam, acetaminophen and metoclopramide. The autopsy revealed signs compatible with methemoglobinemia and samples of blood, vitreous and gastric content were submitted to the Drugs Service of the National Institute of Toxicology and Forensic Sciences in Madrid, as well as the powder bag, the pills and other objects. The white powder was identified as sodium nitrite, and nitrites concentrations similar to other fatalities were detected in biological samples. The methemoglobin level was 80%. The existence of websites where suicide with nitrites and metoclopramide is described step-by-step, joined to the increasement of reports about these fatalities, alert us to a possible trend. (AU)

Confirmation of the presence of Rickettsia felis infecting Ornithodoros puertoricensis in Mexico.

Soft ticks are neglected competent vectors of a wide range of pathogenic microorganisms, among which bacteria of the genera Rickettsia and Borrelia stand out. In Mexico, previous studies have shown the presence of a member of the Ornithodoros talaje complex in the Virginia opossum (Didelphis virginiana Didelphimorphia: Didelphidae Kerr) from southeastern Mexico. However, its specific identification has not been achieved. Two D. virginiana were treated in a private clinic during the period of April-May 2022. Tick larvae were manually removed, DNA extraction was performed, and some genes from various bacterial and parasitic pathogens were amplified and sequenced. A total of 96 larvae were recovered, which were morphologically identified as Ornithodoros puertoricensis (Ixodida: Argasidae Fox); the 16 S sequences showed a similarity of 96.79%-99.51% with sequences of O. puertoricensis from Panama and Colombia. The presence of Rickettsia felis (Rickettsiales: Rickettsiaceae Bouyer et al.) was detected in 15 specimens from one host. The soft tick O. puertoricensis is recorded for the first time as an ectoparasite of the Virginia opossum in America and represents the second report for this soft tick in Mexico since 1963. This represents the most northern record of this tick species in its geographic distribution and brings a new soft tick-Rickettsia association.

Factores relacionados a mortalidad por Covid 19, hospital la portada, La Paz - Bolivia, 2020 / Factors related to Covid 19 mortality, hospital la portada, La Paz - Bolivia, 2020

INTRODUCCIÓN: la reciente aparición del COVID-19 implica comprender de los patrones de transmisión, la gravedad, las características clínicas y los factores de riesgo de infección, ya sea entre la población general, entre el personal médico o en el entorno familiar. Los estudios para evaluar las características epidemiológicas y clínicas de los casos en diferentes contextos resultan esenciales para profundizar y comprender mejor este virus y la enfermedad asociada. MATERIAL Y MÉTODOS: el propósito del estudio fue determinar los factores de riesgo relacionados a mortalidad por COVID-19 en pacientes internados en el Hospital de la Portada durante el periodo de la gestión 2020 mediante un estudio transversal analítico. Se incluyó a todos los pacientes internados, desde abril a agosto del 2020, utilizando las fichas epidemiológicas RESULTADOS: las categorías asociadas, fueron el sexo masculino (p = 0,000) duplicando la posibilidad de muerte respecto a las mujeres (OR =2,46) y la eritrocitosis, (p = 0,002), triplicando la posibilidad de muerte respecto a no padecerla (OR = 3,11). La probabilidad de fallecer por COVID 19 con el antecedente de padecer eritrocitosis fue de 55,17%. Los casos de mortalidad más frecuentes fue en población adulta y tercera edad, del sexo masculino. Los antecedentes patológicos más frecuentes fue la hipertensión arterial. Se dejaron de vivir 2179,5 años. La tasa de mortalidad alcanzo a 8,3 muertes por cada 100.000 habitantes. CONCLUSIÓN: es importante considerar el sexo y la eritrocitosis acompañadas de otras patologías de base como factor fundamental, a la mortalidad por COVID 19.

INTRODUCTION: the recent emergence of COVID-19 implies an understanding of transmission patterns, severity, clinical features, and risk factors for infection, whether among the general population, among medical personnel, or in the family setting. Studies to assess the epidemiological and clinical characteristics of cases in different settings are essential to deepen and better understand this virus and the associated disease. MATERIAL AND METHODS: the purpose of the study was to determine the risk factors related to COVID-19 mortality in patients hospitalized at the Hospital de la Portada during the period of the 2020 administration by means of an analytical cross-sectional study. All hospitalized patients were included, from April to August 2020, using epidemiological records. RESULTS: the associated categories were male sex (p = 0.000), doubling the possibility of death with respect to women (OR = 2.46) and erythrocytosis (p = 0.002), tripling the possibility of death with respect to not having it (OR = 3.11). The probability of dying from COVID 19 with a history of erythrocytosis was 55.17%. The most frequent cases of mortality were in the adult and elderly male population. The most frequent pathological history was arterial hypertension. A total of 2179.5 years of life were lost. The mortality rate was 8.3 deaths per 100,000 inhabitants. CONCLUSION: it is important to consider sex and erythrocytosis accompanied by other underlying pathologies as a fundamental factor in mortality due to COVID 19.

Multifunctional Properties of a Bacillus thuringiensis Strain (BST-122): Beyond the Parasporal Crystal.

Chemical products still represent the most common form of controlling crop pests and diseases. However, their extensive use has led to the selection of resistances. This makes the finding of new solutions paramount to countering the economic losses that pests and diseases represent in modern agriculture. Bacillus thuringiensis (Bt) is one of the most reliable alternatives to chemical-based solutions. In this study, we aimed to further expand the global applicability of Bt strains beyond their spores and crystals. To this end, we selected a new Bt strain (BST-122) with relevant toxicity factors and tested its activity against species belonging to different phyla. The spore and crystal mixture showed toxicity to coleopterans. Additionally, a novel Cry5-like protein proved active against the two-spotted spider mite. In vivo and plant assays revealed significant control of the parasitic nematode, Meloidogyne incognita. Surprisingly, our data indicated that the nematocidal determinants may be secreted. When evaluated against phytopathogenic fungi, the strain seemed to decelerate their growth. Overall, our research has highlighted the potential of Bt strains, expanding their use beyond the confinements of spores and crystals. However, further studies are required to pinpoint the factors responsible for the wide host range properties of the BST-122 strain.

Calidad de vida percibida en dos redes de salud, El Alto y La Paz, 2019 / Perceived quality of life in two health networks, El Alto and La Paz, 2019

INTRODUCCIÓN: para evaluar la calidad de vida se toma en cuenta su multidimensionalidad; de ahí que la calidad de vida se conceptualiza de acuerdo con un sistema de valores, estándares o perspectivas que varían de persona a persona, de grupo a grupo y de lugar a lugar. OBJETIVO: describir la percepción de calidad de vida de la población adulta en dos redes de salud Red de salud Corea El Alto y Red Norte Central N° 3 La Paz, 2019. MATERIAL Y METODOS: diseño transversal, realizado en una red de El Alto y otra de La Paz, con 1671 unidades de estudio. Se utilizó el WHOQOL-BREF (26 ítems), con opciones de respuesta tipo Likert y estructuradas en 4 dimensiones: Salud física, Salud psicológica. Relaciones sociales y Ambiente. RESULTADOS: la catalogación de bien fue la calificación más frecuente en la autopercepción de la calidad de vida, la dimensión con la frecuencia más alta fue lo normal con el 53,4%. Respecto a la satisfacción de salud 41,5% lo normal. Referente a la salud física la categoría bastante fue la más frecuente con 51,5%. En relación a la salud psicológica, la frecuencia más alta correspondió a la categoría bastante con el 50,6% de los casos; en las relaciones sociales de igual manera la CONCLUSIÓN: hubo una autopercepción de calidad de vida catalogada como bien en la mayoría de los casos. categoría relevante fue bastante con 47,1%. Finalmente, en la valoración del ambiente la población asegura estar bastante satisfecho, en el 54% de los casos.

INTRODUCTION: in order to evaluate quality of life, its multidimensionality is taken into account; hence, quality of life is conceptualized according to a system of values, standards or perspectives that vary from person to person, from group to group and from place to place. OBJECTIVE: to describe the perception of quality of life of the adult population in two health networks Red de salud Corea El Alto and Red Norte Central N° 3 La Paz, 2019. MATERIAL AND METHODS: cross sectional design, carried out in one network in El Alto and another in La Paz, with 1671 study units. The WHOQOL- BREF (26 items) was used, with Likert-type response options and structured in 4 dimensions: physical health, psychological health. Social relationships and environment. RESULTS: the categorization of good was the most frequent qualification in the self-perception of quality of life, the dimension with the highest frequency was normal with 53.4%, regarding health satisfaction 41.5% normal. Regarding physical health, the category quite was the most frequent with 51.5%. In relation to psychological health, the highest frequency corresponded to the category quite a lot with 50.6% of the cases; in social relations in the same way the relevant category was quite a lot with 47.1%. Finally, in the evaluation of the environment, the population assures to be quite satisfied in 54% of the cases. CONCLUSION: the self-perception of quality of life was classified as good in most cases

Retinal pigment epithelium atrophy after epiretinal membrane and internal limiting membrane peeling: case reports.

Objective: To describe the development of retinal pigment epithelium (RPE) atrophy after uncomplicated pars plana vitrectomy (PPV) with epiretinal membrane (ERM) and/or internal limiting membrane (ILM) peeling in 2 patients. Cases description: Case 1: A 79-years-old female with diagnosis of a full-thickness macular hole in her right eye (OD) with best corrected visual acuity (BCVA) of: 20/100 and left eye (OS): 20/70. After surgery she developed large RPE hyperplasia and presented hand movement that did not improve with pinhole. Case 2: A 69-years-old female patient who had ERM in her OS with BCVA of 20/30 in both eyes (OU). PPV was assisted with brilliant blue (BB) to better visualize the ILM. During follow-up visits we evidenced RPE atrophy in the zone where peeling was done. In the last control after 2-years, her visual acuity was 20/40 that did not improve with pinhole. Discussion: There are three possible mechanisms to explain this complication: toxic damage, mechanical trauma during the membrane removal with forceps, or a combination of both. In our cases, a combination of them is probably the cause of the presence of RPE atrophy. Conclusion: Vitrectomy with membrane removal is successful in most cases with low rate of complications. Because RPE atrophy is infrequent, our suggestion is to continue performing this technique and if possible, it should be done without dye staining to minimize risks. Abbreviations: ERM = epiretinal membrane, ILM = internal limiting membrane, MH = macular hole, RPE = Retinal pigment epithelium, OD = right eye, BCVA = Best corrected visual acuity, OS = left eye, OU = both eyes, IOL = intraocular lens, OCT = Optical coherence tomography, BB = Brilliant blue, TB = Trypan blue, ICG = indocyanine green.

Staphylococcus aureus ftnA 3'-Untranslated Region Modulates Ferritin Production Facilitating Growth Under Iron Starvation Conditions.

Iron acquisition and modulation of its intracellular concentration are critical for the development of all living organisms. So far, several proteins have been described to be involved in iron homeostasis. Among them, ferritins act as the major iron storage proteins, sequestering internalized iron and modulating its concentration inside bacterial cells. We previously described that the deletion of the 3'-untranslated region (3'UTR) of the ftnA gene, which codes for ferritin in Staphylococcus aureus, increased the ftnA mRNA and ferritin levels. Here, we show that the ferritin levels are affected by RNase III and PNPase, which target the ftnA 3'UTR. Rifampicin mRNA stability experiments revealed that the half-life of the ftnA mRNA is affected by both RNase III and the ftnA 3'UTR. A transcriptional fusion of the ftnA 3'UTR to the gfp reporter gene decreased green fluorescent protein (GFP) expression, indicating that the ftnA 3'UTR could work as an independent module. Additionally, a chromosomal deletion of the ftnA 3'UTR impaired S. aureus growth under conditions of iron starvation. Overall, this work highlights the biological relevance of the ftnA 3'UTR for iron homeostasis in S. aureus.

Uncommon Causes of Acute Kidney Injury.

Acute kidney injury (AKI) is one of the most important complications of critical illness and a significant public health concern. AKI is commonly associated with sepsis, cardiac dysfunction, and exposure to nephrotoxic medication; however, less common causes of AKI can lead to devastating patient outcomes when the underlying diagnosis is missed or delayed. These uncommon causes of AKI fall into 3 large categories: structural, immune mediated, and microvascular, including various types of thrombotic microangiopathy. Kidney imaging, urine studies, and serum hemolytic studies should be a routine part of the evaluation of AKI among critically ill patients.

Intoxicación letal por opio por el consumo de ejemplares silvestres de Papaver somniferum / Fatal intoxication by opium from wild specimens of Papaver somniferum

Se reporta un caso de muerte por consumo de opio y se destaca la contribución de la toxicología forense en el esclarecimiento de la misma. La víctima fue un varón de 20 años quien tras recoger cápsulas de adormidera (Papaver somniferum L) pertenecientes a ejemplares que crecían de manera silvestre en un campo de la provincia de Toledo, y consumir el contenido de las mismas, falleció al día siguiente tras presentar dificultades respiratorias. La autopsia reveló pulmones edematosos, y las muestras de sangre y humor vítreo fueron remitidas al Servicio de Drogas del Instituto Nacional de Toxicología y Ciencias Forenses en Madrid, así como un fragmento de la sustancia vegetal que resultó resina de hachís. Alcaloides del opio (morfina, codeína, noscapina y tebaína), anfetaminas y cannabinoides fueron hallados en los análisis químico-toxicológicos. Se dictaminó que fue una muerte violenta de etiología accidental por policonsumo de drogas, con un rol preponderante del consumo de opio. (AU)

A new fatality due to opium consumption is reported here and the importance of Forensic Toxicology in clarifying this death is highlighted. The deceased was a 20-year-old male who, after collecting opium poppy capsules (Papaver somniferum L) which grew wild in a field near Toledo and consuming his latex (opium), died the next day after presenting respiratory difficulties. The Autopsy revealed congestive lungs and blood and vitreous humor samples were submitted to the Drugs service of the National Institute of Toxicology and Forensic Sciences in Madrid, as well as a piece of vegetal substance, which was identified as hashis. Cannabinoids, amphetamine and opium alkaloids (morphine, codeine, noscapine and tebaine) were found in the toxicologycal analysis. As conclusion, a violent death of accidental etiology due to mixed drug intoxication is here presented. In our opinion, the opium consumption had a preponderant toxic role in this fatality. (AU)

Association of Metformin Use During Hospitalization and Mortality in Critically Ill Adults With Type 2 Diabetes Mellitus and Sepsis.

OBJECTIVES: Whether metformin exposure is associated with improved outcomes in patients with type 2 diabetes mellitus and sepsis. DESIGN: Retrospective cohort study. SETTING: Patients admitted to ICUs in 16 hospitals in Pennsylvania from October 2008 to December 2014. PATIENTS: Adult critical ill patients with type 2 diabetes mellitus and sepsis. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We conducted a retrospective cohort study to compare 90-day mortality in diabetic patients with sepsis with and without exposure to metformin during hospitalization. Data were obtained from the electronic health record of a large healthcare system in Pennsylvania from October 2008 to December 2014, on patients admitted to the ICU at any of the 16 hospitals within the system. The primary outcome was mortality at 90 days. The absolute and adjusted odds ratio (OR) with 95% CI were calculated in a propensity score-matched cohort. Among 14,847 patients with type 2 diabetes mellitus and sepsis, 682 patients (4.6%) were exposed to metformin during hospitalization and 14,165 (95.4%) were not. Within a total of 2,691 patients subjected to propensity score-matching at a 1:4 ratio, exposure to metformin (n = 599) was associated with decreased 90-day mortality (71/599, 11.9% vs 475/2,092, 22.7%; OR, 0.46; 95% CI, 0.35-0.60), reduced severe acute kidney injury (50% vs 57%; OR, 0.75; 95% CI, 0.62-0.90), less Major Adverse Kidney Events at 1 year (OR, 0.27; 95% CI, 0.22-0.68), and increased renal recovery (95% vs 86%; OR, 6.43; 95% CI, 3.42-12.1). CONCLUSIONS: Metformin exposure during hospitalization is associated with a decrease in 90-day mortality in patients with type 2 diabetes mellitus and sepsis.

Regulation of Heterogenous LexA Expression in Staphylococcus aureus by an Antisense RNA Originating from Transcriptional Read-Through upon Natural Mispairings in the sbrB Intrinsic Terminator.

Bacterial genomes are pervasively transcribed, generating a wide variety of antisense RNAs (asRNAs). Many of them originate from transcriptional read-through events (TREs) during the transcription termination process. Previous transcriptome analyses revealed that the lexA gene from Staphylococcus aureus, which encodes the main SOS response regulator, is affected by the presence of an asRNA. Here, we show that the lexA antisense RNA (lexA-asRNA) is generated by a TRE on the intrinsic terminator (TTsbrB) of the sbrB gene, which is located downstream of lexA, in the opposite strand. Transcriptional read-through occurs by a natural mutation that destabilizes the TTsbrB structure and modifies the efficiency of the intrinsic terminator. Restoring the mispairing mutation in the hairpin of TTsbrB prevented lexA-asRNA transcription. The level of lexA-asRNA directly correlated with cellular stress since the expressions of sbrB and lexA-asRNA depend on the stress transcription factor SigB. Comparative analyses revealed strain-specific nucleotide polymorphisms within TTsbrB, suggesting that this TT could be prone to accumulating natural mutations. A genome-wide analysis of TREs suggested that mispairings in TT hairpins might provide wider transcriptional connections with downstream genes and, ultimately, transcriptomic variability among S. aureus strains.

Metabolic Reprogramming and Host Tolerance: A Novel Concept to Understand Sepsis-Associated AKI.

Acute kidney injury (AKI) is a frequent complication of sepsis that increases mortality and the risk of progression to chronic kidney disease. However, the mechanisms leading to sepsis-associated AKI are still poorly understood. The recognition that sepsis induces organ dysfunction in the absence of overt necrosis or apoptosis has led to the consideration that tubular epithelial cells (TEC) may deploy defense mechanisms to survive the insult. This concept dovetails well with the notion that the defense against infection does not only depend on the capacity of the immune system to limit the microbial load (known as resistance), but also on the capacity of cells and tissues to limit tissue injury (known as tolerance). In this review, we discuss the importance of TEC metabolic reprogramming as a defense strategy during sepsis, and how this cellular response is likely to operate through a tolerance mechanism. We discuss the fundamental role of specific regulatory nodes and of mitochondria in orchestrating this response, and how this opens avenues for the exploration of targeted therapeutic strategies to prevent or treat sepsis-associated AKI.