Probiotics in septic acute kidney injury, a double blind, randomized control trial.

INTRODUCTION: During acute kidney injury (AKI) due to sepsis, the intestinal microbiota changes to dysbiosis, which affects the kidney function recovery (KFR) and amplifies the injury. Therefore, the administration of probiotics could improve dysbiosis and thereby increase the probability of KFR. METHODS: In this double-blind clinical trial, patients with AKI associated with sepsis were randomized (1:1) to receive probiotics or placebo for 7 consecutive days, with the objectives of evaluate the effect on KFR, mortality, kidney replacement therapy (KRT), urea, urine volume, serum electrolytes and adverse events at day 7. RESULTS: From February 2019 to March 2022, a total of 92 patients were randomized, 48 to the Probiotic and 44 to Placebo group. When comparing with placebo, those in the Probiotics did not observe a higher KFR (HR 0.93, 0.52-1.68, p = 0.81), nor was there a benefit in mortality at 6 months (95% CI 0.32-1.04, p = 0.06). With probiotics, urea values decreased significantly, an event not observed with placebo (from 154 to 80 mg/dl, p = 0.04 and from 130 to 109 mg/dl, p = 0.09, respectively). Urinary volume, need for KRT, electrolyte abnormalities, and adverse events were similar between groups. (ClinicalTrial.gov NCT03877081) (registered 03/15/2019). CONCLUSION: In AKI related to sepsis, probiotics for 7 consecutive days did not increase the probability of KFR, nor did other variables related to clinical improvement, although they were safe.

Fetal Alcohol-Related Postnatal Growth Restriction Is Independent of Infant Feeding Practices and Postnatal Alcohol Exposure in a Prospective South African Birth Cohort.

Prenatal alcohol exposure (PAE) causes growth restriction that worsens in the first year of life. However, the roles of postnatal nutrition in fetal alcohol growth restriction and the impact of postnatal alcohol exposure via breastmilk on growth remain unknown. We aimed to compare infant feeding practices during the first 6.5 months of life between heavy drinkers and abstainers/light drinkers, to examine whether these practices play confounding roles in fetal alcohol growth restriction, and to determine the impact of postnatal alcohol exposure via breastmilk on growth. Eighty-seven heavy-drinking pregnant women and 71 abstainers/light drinkers (controls) were recruited prenatally from antenatal clinics in Cape Town, South Africa. Demographic background and alcohol, cigarette, marijuana, and methamphetamine use during pregnancy were assessed pre- and postnatally. Infant feeding practices were assessed at 6.5 months postpartum using the USDA Infant Feeding Questionnaire. Infant weight, length, and head circumference were measured at 2 weeks, 6.5 and 12 months, and 5 years. Neither prenatal nor postnatal alcohol consumption was related to the duration of breastfeeding, exclusive breastfeeding, exclusive formula, or mixed feeding. Complementary feeding practices were remarkably similar between exposure groups. PAE was related to all postnatal anthropometry measures at all age points, independent of infant feeding practices. Postnatal alcohol exposure via breastmilk was unrelated to any anthropometry outcome after control for PAE. In conclusion, fetal alcohol-related postnatal growth restriction was not attributable to differences in postnatal infant feeding practices or postnatal alcohol exposure and is thus likely a direct teratogenic effect of PAE.

Yeast Mitochondria Import Aqueous FeII and, When Activated for Iron-Sulfur Cluster Assembly, Export or Release Low-Molecular-Mass Iron and Also Export Iron That Incorporates into Cytosolic Proteins.

Iron-sulfur cluster (ISC) assembly occurs in both mitochondria and cytosol. Mitochondria are thought to export a low-molecular-mass (LMM) iron and/or sulfur species which is used as a substrate for cytosolic ISC assembly. This species, called X-S or (Fe-S)int, has not been directly detected. Here, an assay was developed in which mitochondria were isolated from 57Fe-enriched cells and incubated in various buffers. Thereafter, mitochondria were separated from the supernatant, and both fractions were investigated by ICP-MS-detected size exclusion liquid chromatography. Aqueous 54FeII in the buffer declined upon exposure to intact 57Fe-enriched mitochondria. Some 54Fe was probably surface-absorbed but some was incorporated into mitochondrial iron-containing proteins when mitochondria were activated for ISC biosynthesis. When activated, mitochondria exported/released two LMM nonproteinaceous iron complexes. One species, which comigrated with an Fe-ATP complex, developed faster than the other Fe species, which also comigrated with phosphorus. Both were enriched in 54Fe and 57Fe, suggesting that the added 54Fe entered a pre-existing pool of 57Fe, which was also the source of the exported species. When 54Fe-loaded 57Fe-enriched mitochondria were mixed with isolated cytosol and activated, multiple cytosolic proteins became enriched with Fe. No incorporation was observed when 54Fe was added directly to the cytosol in the absence of mitochondria. This suggests that a different Fe source in mitochondria, the one enriched mainly with 57Fe, was used to export a species that was ultimately incorporated into cytosolic proteins. Iron from buffer was imported into mitochondria fastest, followed by mitochondrial ISC assembly, LMM iron export, and cytosolic ISC assembly.

Spinal cords: Symphonies of interneurons across species.

Vertebrate movement is orchestrated by spinal inter- and motor neurons that, together with sensory and cognitive input, produce dynamic motor behaviors. These behaviors vary from the simple undulatory swimming of fish and larval aquatic species to the highly coordinated running, reaching and grasping of mice, humans and other mammals. This variation raises the fundamental question of how spinal circuits have changed in register with motor behavior. In simple, undulatory fish, exemplified by the lamprey, two broad classes of interneurons shape motor neuron output: ipsilateral-projecting excitatory neurons, and commissural-projecting inhibitory neurons. An additional class of ipsilateral inhibitory neurons is required to generate escape swim behavior in larval zebrafish and tadpoles. In limbed vertebrates, a more complex spinal neuron composition is observed. In this review, we provide evidence that movement elaboration correlates with an increase and specialization of these three basic interneuron types into molecularly, anatomically, and functionally distinct subpopulations. We summarize recent work linking neuron types to movement-pattern generation across fish, amphibians, reptiles, birds and mammals.

Labile Iron Pool of Isolated Escherichia coli Cytosol Likely Includes Fe-ATP and Fe-Citrate but not Fe-Glutathione or Aqueous Fe.

The existence of labile iron pools (LFePs) in biological systems has been recognized for decades, but their chemical composition remains uncertain. Here, the LFeP in cytosol from Escherichia coli was investigated. Mössbauer spectra of whole vs lysed cells indicated significant degradation of iron-sulfur clusters (ISCs), even using an unusually gentle lysis procedure; this demonstrated the fragility of ISCs. Moreover, the released iron contributed to the non-heme high-spin Fe(II) species in the cell, which likely included the LFeP. Cytosol batches isolated from cells grown with different levels of iron supplementation were passed through a 3 kDa cutoff membrane, and resulting flow-through-solutions (FTSs) were subjected to SEC-ICP-MS. Mössbauer spectroscopy was used to evaluate the oxidation states of standards. FTSs exhibited iron-detected peaks likely due to different forms of Fe-citrate and Fe-nucleotide triphosphate complexes. Fe-Glutathione (GSH) complexes were not detected using physiological concentrations of GSH mixed with either Fe(II) or Fe(III); Fe(II)-GSH was concluded not to be a significant component of the LFeP in E. coli under physiological conditions. Aqueous iron was also not present in significant concentrations in isolated cytosol and is unlikely a major component of the pool. Fe appeared to bind ATP more tightly than citrate, but ATP also hydrolyzed on the timescale of tens of hours. Isolated cytosol contained excess ligands that coordinated the added Fe(II) and Fe(III). The LFeP in healthy metabolically active cells is undoubtedly dominated by the Fe(II) state, but the LFeP is redox-active such that a fraction might be present as stable and soluble Fe(III) complexes especially under oxidatively stressed cellular conditions.

Fathers' Heightened Stress Responses to Recounting their NICU Experiences Months after Discharge: A Mixed Methods Pilot Study.

OBJECTIVE: The acute and traumatic events associated with having a newborn who requires admission to the neonatal intensive care unit (NICU) may elicit long-term concerns for parents postdischarge. Cognitive processing of taxing events influences recurring stress responses, which can be inferred via biomarkers such as salivary cortisol (sCort) and skin conductance (SC). In addition, personal narratives provide an important insight into individual perceptions and coping strategies. The current pilot study aimed to (1) test the hypotheses that fathers' sCort and SC would peak in response to stress induction and decrease during recovery, (2) examine associations among stress biomarkers and stress perceptions, (3) explore fathers' narratives using thematic analysis, and (4) integrate fathers' narrative themes with their stress responsivity. STUDY DESIGN: Using a convergent mixed methods approach, we enrolled 10 fathers of infants formerly cared for in NICU who underwent a Trier Social Stress Test including recounting their NICU experience months postdischarge. Stress responsivity was measured via sCort and SC, while stress perceptions were identified by using the Perceived Stress Scale and Distress Thermometer-Parent. Personal narratives were explored by using thematic analysis. RESULTS: The significant rise in fathers' sCort and SC in response to stress induction was reflected in narrative themes including loss, worry, and role strain. Subsequently, fathers' sCort and SC returned to baseline, which was illustrated by themes such as role strength, coping, and medical staff interactions. Fathers' stress measured by PSS was lower than that required for mental health referral, and did not correlate with stress biomarkers. CONCLUSION: Salivary cortisol and skin conductance are useful biomarkers of paternal stress responsivity and recovery. Thematic analysis identified fathers' NICU stressors and coping strategies that mirrored their stress responsivity patterns. Further studies are needed to more broadly examine the sociodemographic variables that influence stress reactivity and perceptions in parents of infants formerly cared for in NICU. KEY POINTS: · Stress associated with NICU stay is impactful on fathers and may have long-term implications.. · Salivary cortisol and skin conductance are useful noninvasive stress biomarkers.. · Fathers' coping strategies included infant bonding, partner relationship, and trust building..

Characterization of the complete mitochondrial genome of Thyonella gemmata (Echinodermata: Cucumariidae).

Thyonella gemmata , also known as the Green sea cucumber, is a biomedically and ecologically important species. In this study, the complete mitogenome of T. gemmata (Echinodermata: Holothuroidea) collected from the Florida Panhandle, USA is reported. The mitochondrial genome of T. gemmata consisted of 15,696 base pairs, and was composed of 36.10% A, 28.27% T, 23.18% C, and 12.45% G. There were 13 protein coding genes, 22 tRNA genes, and 2 rRNA genes within the mitogenome of T. gemmata. Mapping out the complete mitochondrial genome of T. gemmata, will help aid in future evolutionary studies and can be applied to future phylogenetic research of holothurians and related species.

Health, disability, and consumption of psychoactive substances among people in a homeless situation in León (Nicaragua).

Nicaragua is one of the countries in Latin America with lowest levels of development. In Nicaragua, people in a homeless situation are one of the most socially excluded groups, and there is a lack of data regarding their characteristics, circumstances, and needs. This study examines the state of health, disability, and substance use among people living homeless (n = 68) in the city of León (Nicaragua). Sixty percent of the homeless people contacted responded to a questionnaire which was administered with the respondents by means of an interview. The findings showed that people living homeless in León had very negative states of health and disability, worse than those observed in other socially excluded groups in the same city and homeless people in more developed countries. The interviewees also presented a high level of substance abuse - mainly of alcohol and inhaled glue.

Prenatal opioid exposure heightens sympathetic arousal and facial expressions of pain/distress in term neonates at 24-48 hours post birth.

Purpose: The rising issue of opioid use during pregnancy poses an increased risk of fetal exposure to opioids in-utero and the development of neonatal abstinence syndrome (NAS). The cessation of exposure to opioids upon birth causes elevated levels of norepinephrine in the circulation enhancing sympathetic arousal. Skin conductance (SC) detects sympathetic-mediated sweating while the Neonatal Facial Coding System (NFCS) depicts facial expressions of stress and pain. We hypothesize that there will be a direct correlation between SC and NFCS scores, such that neonates with prenatal opioid exposure will have higher SC and facial responses to pain/stress as compared with healthy neonates without prenatal opioid exposure.Objective: This study evaluates the utility of SC and the NFCS in the objective assessment of early postnatal pain response in opioid-exposed and non-opioid exposed neonates.Methods: This prospective, single-center, pilot study enrolled opioid-exposed term neonates (>37 weeks) and healthy controls. Subjects were observed within 24-48 hours post-birth (and prior to opioid withdrawal) for pain at baseline, during, and post-heel lance/squeeze (HLS) with simultaneously measured SC and videotaped facial expressions. SC data included electro-dermal responses over time (EDR/second) and the average amplitude of responses (mean of peaks [MP]). Video data were scored using the NFCS by two trained coders with inter-rater agreement >85%.Results: SC and NFCS scores were significantly associated with both groups. The opioid-exposed neonates had significantly higher skin conductance indices, EDR/sec for the HLS phase, and MP for HLS and post phases as compared with controls (p < .05). Opioid-exposed neonates demonstrated higher NFCS at baseline (p = .003).Conclusions: Prenatal opioid exposure was associated with heightened sympathetic arousal during both pain and recovery phases and higher facial expressions of pain/distress at baseline only. A multimodal system of assessment may be useful in understanding the complexity and severity of opioid withdrawal associated with NAS.

Chronic kidney disease of unknown cause in Mexico: The case of Poncitlan, Jalisco.

Chronic kidney disease of unknown cause (CKDu) is relatively common in low- and middle-income countries. A high prevalence of CKDu has been reported among the inhabitants of Poncitlan, Mexico. We did a cross-sectional study to compare the characteristics of residents in Poncitlan, a very poor municipality, with those from other municipalities in Jalisco state. We also estimated the prevalence of renal replacement therapy (RRT) in this region. We assessed 51,789 individuals in Jalisco: 16,351 (32.1%) were men, mean age 51.8 ± 15.3 years; 650 (1.3%) were aged < 18 years. Overall the prevalence of CKD (10.5%) and proteinuria (11.5%), were similar to the overall Mexican population. There were 283 adult and 144 child participants who resided in Poncitlan: adults were more likely to be female (78.0 vs. 67.9%, p = 0.000) but were of similar age as compared to those from other municipalities; children were younger (8.78 ± 3.97 vs. 15.03 ± 2.57 years, p = 0.000) but had a similar proportion of females compared to children from other municipalities. In Poncitlan, the prevalence of CKD and proteinuria were both higher in adults compared to those from other municipalities (CKD: 20.1 vs. 10.4%, p = 0.002; proteinuria: 36.1 vs. 11.0%, p = 0.000), and the prevalence of proteinuria in children was also higher (44.4 vs. 4.8%, p = 0.000). However, the prevalence of diabetes mellitus and obesity were lower in Poncitlan than elsewhere. The prevalence of RRT in Poncitlan was 2,228 pmp, twice as high as the prevalence for Jalisco state as a whole. In conclusion, CKD and proteinuria were detected frequently in residents of the Poncitlan community. Future studies should consider the possibility that CKDu is due to multifactorial causes, especially in poor communities.
.

Homeless people in León (Nicaragua): Conceptualizing and measuring homelessness in a developing country.

Homelessness is a global phenomenon that affects groups in situations of poverty and social exclusion, in both developed and developing nations. However, the scientific literature on homeless people in developing countries is scant. This work shows the difficulties defining homelessness and examines the necessary criteria for who will be deemed a homeless person in a developing country. Furthermore, the results of the Point-In-Time (PIT) count of homeless people-a measure of the number of homeless people on a specific day-done in the city of León, Nicaragua (population: 185,000). Throughout the PIT count, 82 unduplicated people living in homelessness were tallied (76% male, 23% female), of which 47 answered a questionnaire. Most of the homeless people in León are male, mestizo, of Nicaraguan nationality, with a primary level education or less, and in a situation of chronic homelessness. Results showed a mean age of 47 years for these individuals. Most of the homeless people showed a bad physical appearance, had poor personal hygiene, and wore dirty clothing. Around half of the homeless observed seemed to have problems related to mental health, alcohol, and/or drugs. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

Retraction of Complaints Among Female Victims of Intimate Partner Violence Living in Poverty in Nicaragua.

Retraction among female victims of intimate partner violence (IPV) who report their abuser is a major problem in all societies. This article describes a study of 136 female victims of physical IPV living in poverty in Nicaragua, one of the countries with the lowest levels of development in Central America. This article analyses the aspects that differentiate women living in poverty who retracted after reporting IPV from those who did not. The results show that retraction is widespread among female victims of IPV living in poverty in León (Nicaragua). Although it is difficult to predict the retraction behaviour of the respondents, some differences between the women who retracted their complaint and those who did not were observed. A combination of five variables (including personal circumstances and beliefs about the intimate partner relationship and family) was the best alternative for discriminating between women who had retracted and those who had not.

Maternal emotional availability at bedtime and infant cortisol at 1 and 3 months.

BACKGROUND: Previous work has shown that early experience influences infant cortisol secretion. Few studies, however, have examined associations between parenting quality and cortisol levels and patterning in very young infants. AIMS: This study examined linkages between maternal emotional availability (EA) during a routine caregiving task, bedtime, and infant cortisol in the first 3 months of life. Concurrent and longitudinal associations between maternal EA and infant cortisol were examined. STUDY DESIGN: Families were visited when their infants were 1 and 3 months old. Video equipment was set up in order to record the infant's bedtime routine. Parents were provided with materials with which to take saliva samples from their infants at late afternoon, bedtime, and the following morning. SUBJECTS: At 1 month, participants were 96 mothers and infants living in a rural U.S. state. Data were available for 88 mothers and infants at 3 months. OUTCOME MEASURES: Maternal EA was scored from videotapes of bedtime at each age point. Infant cortisol was assessed from the saliva samples taken by parents. RESULTS: Regression analyses indicated that at 1 and 3 months of age, infants of more emotionally available mothers showed lower levels of cortisol secretion across the night than infants of less emotionally available mothers. Additionally, multilevel model analyses indicated that infants of more emotionally available mothers showed greater evidence of a decline in their cortisol levels across the evening, followed by an increase across the nighttime into the morning in their cortisol at 3 months. CONCLUSIONS: Findings suggest that maternal care in the context of a routine caregiving task is associated with lower stress reactivity and with earlier circadian patterning in very young infants.

YGLF motif in the Kaposi sarcoma herpes virus G-protein-coupled receptor adjusts NF-κB activation and paracrine actions.

Kaposi sarcoma (KS) and primary effusion lymphoma (PEL) are two pathologies associated with KS herpes virus (KSHV/HHV-8) infection. KSHV genome contains several oncogenes, among which, the viral G-protein-coupled receptor (vGPCR open reading frame 74) has emerged as a major factor in KS pathogenicity. Indeed, vGPCR is a constitutively active receptor, whose expression is sufficient to drive cell transformation in vitro and tumour development in mice. However, neither the role of vGPCR in KSHV-infected B-lymphocytes nor the molecular basis for its constitutive activation is well understood. Here, we show that vGPCR expression contributes to nuclear factor-κB (NF-κB)-dependent cellular survival in both PEL cells and primary B cells from HIV-negative KS patients. We further identified within vGPCR an AP2 consensus binding motif, Y326GLF, that directs its localization between the plasma membrane and clathrin-coated vesicles. The introduction of a mutation in this site (Y326A) increased NF-κB activity and proinflammatory cytokines production. This correlated with exacerbated morphological rearrangement, migration and proliferation of non-infected monocytes. Collectively, our work raises the possibility that KSHV-infected B-lymphocytes use vGPCR to impact ultimately the immune response and communication within the tumour microenvironment in KSHV-associated pathologies.