The structure and matrix dynamics of bacterial biofilms as revealed by antimicrobial peptides' diffusion.

From the biological point of view, bacterial biofilms are communities of bacteria embedded in a self-produced gel matrix composed of polysaccharides, DNA, and proteins. Considering the biophysical point of view, the biofilm matrix is a highly dense, crowded medium that imposes constraints to solute diffusion, depending on the size, conformational dynamics, and net charge. From the pharmacological point of view, biofilms are additional difficulties to drug development as heterogeneity in oxygen and nutrient distribution, and consequently, heterogeneity in bacterial metabolic status leads to recalcitrance. For peptide scientists, biofilms are both a challenge and an opportunity. Biofilms can be intruded by peptides, revealing important biological, biophysical, and pharmacological insights. Peptides can be engineered for different sizes, flexibilities, and net charges, unravelling the determinants of diffusion; they kill bacteria by lysis, overcoming the hurdles of metabolic status heterogeneity, and they are able to kill bacteria in the biofilm core, leaving the matrix intact, that is, without causing bacterial biofilm dispersion as side effect. This concise review addresses the knowledge reached while interrogating bacterial biofilms with peptides and other reporter molecules, and the advances therefrom in biology, biophysics, and drug development.

Low-dimensionality carbon-based biosensors: the new era of emerging technologies in bioanalytical chemistry.

Since the last decade, carbon nanomaterials have had a notable impact on different fields such as bioimaging, drug delivery, artificial tissue engineering, and biosensors. This is due to their good compatibility toward a wide range of chemical to biological molecules, low toxicity, and tunable properties. Especially for biosensor technology, the characteristic features of each dimensionality of carbon-based materials may influence the performance and viability of their use. Surface area, porous network, hybridization, functionalization, synthesis route, the combination of dimensionalities, purity levels, and the mechanisms underlying carbon nanomaterial interactions influence their applications in bioanalytical chemistry. Efforts are being made to fully understand how nanomaterials can influence biological interactions, to develop commercially viable biosensors, and to gain knowledge on the biomolecular processes associated with carbon. Here, we present a comprehensive review highlighting the characteristic features of the dimensionality of carbon-based materials in biosensing.

Potential of pharmaceutical formulation based on Morinda citrifolia extract for the treatment of schistosomiasis.

Schistosomiasis is a parasitic disease that can be asymptomatic, but it can progress and cause serious damage, such as hospitalization and death. This work aimed to characterize and carry out the in vivo pharmacological test of the dry extract of Morinda citrifolia and obtain a pharmaceutical dosage form based on this extract for the treatment of schistosomiasis. The aqueous extract was characterized based on the evaluation of pH, dry residue and density. The aqueous extract was dried through the freeze-drying process. The obtained dry extract was characterized through phytochemical screening, rheological analysis, acute toxicity and in vivo pharmacology. Additionally, the pre-formulation development of a pharmaceutical dosage form was pursued with the dry extract. Through the HPLC chromatogram, characteristic rutin peaks were identified. The rheological behavior of the dry extract did not show good characteristics. Acute toxicity, at a dose of 2000 mg/kg, showed excitatory activity in the central and autonomous nervous system. The in vivo pharmacological test of the dry extract showed that, at a dose of 400 mg/kg, it was possible to reduce 67.5% of the total adult worms, 66% of female worms and 60% of the number of eggs. The pharmaceutical dosage form obtained was an oral solution that was clear, transparent, without the presence of lumps and precipitates, having a density of 1.1276 g mL-1 and pH of 5.92. The results obtained will provide parameters for the production of suitable pharmaceutical formulations, as well as for the quality control of products based on M. citrifolia, with promising schistosomicidal activity.

Resazurin Reduction-Based Assays Revisited: Guidelines for Accurate Reporting of Relative Differences on Metabolic Status.

Cell viability and metabolic activity are ubiquitous parameters used in biochemistry, molecular biology, and biotechnological studies. Virtually all toxicology and pharmacological projects include at some point the evaluation of cell viability and/or metabolic activity. Among the methods used to address cell metabolic activity, resazurin reduction is probably the most common. At variance with resazurin, resorufin is intrinsically fluorescent, which simplifies its detection. Resazurin conversion to resorufin in the presence of cells is used as a reporter of metabolic activity of cells and can be detected by a simple fluorometric assay. UV-Vis absorbance is an alternative technique but is not as sensitive. In contrast to its wide empirical "black box" use, the chemical and cell biology fundamentals of the resazurin assay are underexplored. Resorufin is further converted to other species, which jeopardizes the linearity of the assays, and the interference of extracellular processes has to be accounted for when quantitative bioassays are aimed at. In this work, we revisit the fundamentals of metabolic activity assays based on the reduction of resazurin. Deviation to linearity both in calibration and kinetics, as well as the existence of competing reactions for resazurin and resorufin and their impact on the outcome of the assay, are addressed. In brief, fluorometric ratio assays using low resazurin concentrations obtained from data collected at short time intervals are proposed to ensure reliable conclusions.

Cathelicidin protects mice from Rhabdomyolysis-induced Acute Kidney Injury.

Background: Cathelicidins are ancient and well-conserved antimicrobial peptides (AMPs) with intriguing immunomodulatory properties in both infectious and non-infectious inflammatory diseases. In addition to direct antimicrobial activity, cathelicidins also participate in several signaling pathways inducing both pro-inflammatory and anti-inflammatory effects. Acute kidney injury (AKI) is common in critically ill patients and is associated with high mortality and morbidity. Rhabdomyolysis is a major trigger of AKI. Objectives: Here, we investigated the role of cathelicidins in non-infectious Acute kidney Injury (AKI). Method: Using an experimental model of rhabdomyolysis, we induced AKI in wild-type and cathelicidin-related AMP knockout (CRAMP-/-) mice. Results: We previously demonstrated that CRAMP-/- mice, as opposed wild-type mice, are protected from AKI during sepsis induced by cecal ligation and puncture. Conversely, in the current study, we show that CRAMP-/- mice are more susceptible to the rhabdomyolysis model of AKI. A more in-depth investigation of wild-type and CRAMP-/- mice revealed important differences in the levels of several inflammatory mediators. Conclusion: Cathelicidins can induce a varied and even opposing repertoire of immune-inflammatory responses depending on the subjacent disease and the cellular context.

Effect of silica coating and laser treatment on the flexural strength, surface characteristics, and bond strength of a dental zirconia.

This study investigated the effect of irradiation with an erbium-doped yttrium aluminium garnet (Er:YAG) laser and coating with silica on the surface characteristics, bond strength, and flexural strength of dental zirconia. Three hundred and forty-three standard zirconia specimens were created, and 49 were assigned to each of seven surface treatment groups: (i) no treatment; Er:YAG laser (80 mJ/2 Hz) with pulse widths of 50 µs (ii), 100 µs (iii), 300 µs (iv), or 600 µs (v); or tribochemical silica coating at the partially sintered stage (vi) or after sintering was complete (vii). All specimens were sintered after the surface treatments, except for the group in which specimens were sintered before treatment. The study outcomes were roughness, surface loss, microshear bond strength (µSBS), and biaxial flexural strength (BFS). Mean roughness and surface loss values were significantly higher in specimens from irradiated groups than in those from silica-coated groups. Regarding µSBS, after aging, specimens from all experimental groups presented very low and similar µSBS values, irrespective of the surface treatment. Silica coating after sintering yielded the highest BFS (1149.5 ± 167.6 MPa), while coating partially sintered specimens with silica resulted a BFS (826.9 ± 60.9 MPa) similar to that of the untreated control group (794.9 ± 101.7 MPa). Laser treatments, irrespective of pulse width used, significantly decreased the BFS. In the group treated with laser at 300 µs pulse width, specimens exhibited the lowest BFS value (514.1 ± 71.5 MPa). Adhesion to zirconia was not stable after aging, regardless of the surface treatment implemented.

Quality of recovery in patients under low- or standard-pressure pneumoperitoneum. A randomised controlled trial.

BACKGROUND: The use of low-pressure pneumoperitoneum seems to be capable of reducing complications such as post-operative pain. However, the quality of evidence supporting this conclusion is low. Both the lack of investigator blinding to both intra-abdominal pressure and to method of neuromuscular blockade represent key sources of bias. Hence, this prospective, randomised, and double-blind study aimed to compare the quality of recovery (Questionnaire QoR-40) of patients undergoing laparoscopic cholecystectomy under low-pressure and standard-pressure pneumoperitoneum. We tested the hypothesis that low pneumoperitoneum pressure enhances the quality of recovery following LC. METHODS: Eighty patients who underwent elective laparoscopic cholecystectomy were randomly divided into two groups, a low-pressure (10 mm Hg) pneumoperitoneum group and a standard-pressure (14 mm Hg) pneumoperitoneum group. For all participants, the value of the insufflation pressure was kept hidden and only the nurse responsible for the operating room was aware of it. Deep neuromuscular blockade was induced for all cases [train-of-four (TOF) = 0; post-tetanic count (PTC) > 0]. The quality of recovery was assessed on the morning of first post-operative day. RESULTS: No difference was found in either total score or in its different dimensions according to the QoR-40 questionnaire. The patients in the low-pressure pneumoperitoneum group experienced more pain during forced coughing measured at 4 hours (median difference [95% CI], 1 [0-2]; P = .030), 8 hours (1 [0-2]; P = .030) and 12 hours (0 [0-1] P = .025) after discharge from the post-anaesthesia care unit, when compared with those in the standard-pressure pneumoperitoneum group. CONCLUSION: We thus conclude that the use of low-pressure pneumoperitoneum during elective laparoscopic cholecystectomy does not improve the quality of recovery.

Patient safety culture in primary and home care services.

BACKGROUND: Safety culture is still a poorly studied subject in primary care and home care, although these settings are considered gateways to access to healthcare. This study aims to evaluate safety culture in primary and home care settings. METHODS: An observational cross-sectional study was carried out with 147 professionals from nine districts covered by one home care program and six primary healthcare centres. The Safety Attitudes Questionnaire (SAQ) was used to evaluate the safety culture, in which scores ≥75 are indicative of a positive safety culture. RESULTS: A total of 56 (86,1%) questionnaires returned from the home care professionals and 91 (86,6%) from the primary care professionals. The Job satisfaction domain was the best evaluated, achieving a score of 88.8 in home care and 75.1 in primary care. The achievement of high scores on Safety Climate, Job Satisfaction, Teamwork Climate, and Total SAQ was related to male gender, and time of professional experience of three to 4 years. Perception of management and Working conditions had the lowest scores, and this result was related with long time of experience. CONCLUSIONS: It is concluded that professionals working in home care gave higher scores for safety culture in their workplace than the primary care workers.

Effect of erosive and abrasive challenges on the glaze layer applied to ceramic materials.

PURPOSE: This study aims to evaluate the effect of erosive, abrasive, and erosive/abrasive challenges on the glaze layer of ceramic materials. METHODS: Ninety-five samples of monolithic zirconia (MZ) (LuxaCam Zircon HT-Plus) and lithium disilicate (LD) (IPS e.max CAD) were divided according to the response variables: Surface roughness and surface loss (n = 10), evaluated with optical profilometry; surface topography, with scanning electron microscopy SEM (n = 3); and biofilm deposition, with microbiological assay (n = 5). The evaluations were performed in three different time evaluations: (a) Sintered, (b) Glaze, and (c) Challenge (Erosion, Abrasion, and Erosion/Abrasion). Erosion consisted in immersing specimens in HCl solution, abrasion was performed with brushing machine, and erosion/abrasion consisted of a combination of the two previous protocols. Data were analyzed with parametric tests (P < 0.05). RESULTS: MZ glaze layer presented significantly higher surface roughness (P = 0.00), surface loss (P = 0.03), and biofilm deposition (P = 0.00) than LD. Abrasion and erosion/abrasion showed similar outcomes, generating significantly higher surface roughness (P = 0.00), surface loss (P = 0.00), and biofilm deposition (P = 0.01) than erosion. CONCLUSIONS: Glaze layer properties were altered by the challenges, with abrasion and erosion/abrasion generating higher surface roughness, surface loss, and biofilm deposition than erosion. A significant correlation was found between the surface roughness and biofilm deposition. CLINICAL SIGNIFICANCE: The glaze layer is susceptible to challenges, especially to abrasion and erosion/abrasion, which generated greater surface roughness and surface loss than erosion. The greater surface roughness lead to a greater biofilm deposition on the glaze layer.

An international cluster-randomized quality improvement trial to increase the adherence to evidence-based therapies for acute ischemic stroke and transient ischemic attack patients: Rationale and design of the BRIDGE STROKE Trial.

BACKGROUND: Translating evidence into clinical practice in the management of acute ischemic stroke (AIS) and transient ischemic attack (TIA) is challenging especially in low- and middle-income countries. OBJECTIVES: The aim of this study is to assess the effect of a multifaceted quality improvement intervention on adherence to evidence-based therapies for AIS and TIA patients care. DESIGN: We designed a pragmatic, 2-arm cluster-randomized trial involving 36 clusters and 1624 patients from Brazil, Argentina, and Peru. Hospitals are randomized to receive a multifaceted quality improvement intervention (intervention group) or to routine care (control group). The BRIDGE Stroke multifaceted quality improvement intervention includes case management, reminders, health care providers' educational materials (including treatment algorithms), interactive workshops, and audit and feedback reports. Primary outcome is a composite adherence score to AIS and TIA performance measures. Secondary outcomes include an "all or none" composite end point to performance measures, the individual components of the composite end points, and clinical outcomes at 90 days following admission (stroke recurrence, death, and disability measured by the modified Rankin scale). SUMMARY: The BRIDGE Stroke Trial is an international pragmatic evaluation of a multifaceted quality improvement intervention. If effective, this intervention could be potentially extended widely to improve the quality of care and outcomes of patients with AIS or TIA.

Influence of Er:YAG laser pulse duration on the long-term stability of organic matrix and resin-dentin interface.

The purpose of this study was to explore the influence of Er:YAG laser irradiation with different pulse durations on the organic matrix, micromorphology of the hybrid layer (HL), and bond strength over time. Sixty caries-free human molars were cut to obtain flat dentin surfaces which were randomly divided into 4 groups: control (not irradiated-G1) and laser groups (80 mJ/2 Hz) with pulse duration ranging between 50 (G2), 300 (G3), and 600 µs (G4). A self-etch adhesive system (Universal 3M ESPE) was applied on pre-treated dentin surfaces and cylinders of resin composite were built up and stressed in a universal testing machine (µSBS) at 24 h and after12 months (n = 12). In addition, 3 other dentin-bonded specimens were prepared as previously described for each group with the adhesive doped with 0.1 wt% Rhodamine B to analyze hybrid layer morphology under Confocal Laser Microscope Scanning (CLMS). Organic matrix and collagen fibrils were analyzed by second harmonic generation (SGH). Two-way ANOVA and Tukey's test detected significantly higher µSBS values for the control group, whereas the lower values were observed in all laser groups at 24 h (p < 0.05). Storage in artificial saliva did not reduce µSBS in all groups. The low signal emitted by SHG images below the irradiated area demonstrated thermal damage of the collagen matrix. CLMS images of laser groups exhibited thicker and irregular resin-dentin interfaces than the control group. Regardless of the pulse duration, Er:YAG laser pre-treatment altered the organic matrix and HL formation which resulted in low µSBS values at 24 h. The alterations on dentin's organic structure did not jeopardize the µSBS after 1 year of saliva storage.

Species Distribution, Virulence Factors, and Antifungal Susceptibility Among Candida parapsilosis Complex Isolates Recovered from Clinical Specimens.

The Candida parapsilosis complex has emerged as an important fungal pathogen. In spite of this, relatively little is known about its characteristics. Thus, the purposes of this study were (1) to determine by BanI-RFLP-assay the occurrence of C. parapsilosis complex species among 81 clinical isolates primarily identified as C. parapsilosis; (2) to evaluate their in vitro production of virulence factors; and (3) to compare their susceptibility profiles, grown as planktonic cells and biofilms, against amphotericin B, fluconazole, voriconazole, and caspofungin by following the Clinical and Laboratory Standards Institute (CLSI) guidelines. Seventy-seven isolates (95%) were identified as C. parapsilosis sensu stricto, 2 (2.5%) as C. orthopsilosis, and 2 (2.5%) as C. metapsilosis. Protease activity was detected in 29 (37.7%) isolates of C. parapsilosis sensu stricto, whereas only 7 (9.1%) exhibited phospholipase activity. None of the C. metapsilosis or C. orthopsilosis was able to produce protease or phospholipase. Biofilm production was detected in 35 (43.2%) isolates, among which 33 were C. parapsilosis sensu stricto and 2 were C. orthopsilosis. Antifungal resistance was uncommon; only one C. metapsilosis was fluconazole resistant. However, biofilm-producing isolates showed a marked resistance to all antifungal agents tested, particularly to voriconazole. This knowledge could be of clinical relevance for guiding therapeutic decisions.

Determination of high-intensity sweeteners in bakery products marketed in Brazil and dietary exposure assessment.

Bakery products, including biscuits, cakes and breads, generally present a high content of simple sugars of rapid absorption, high fat content and low amount of dietary fiber, which make them highly caloric foods. Although sucrose is a very important ingredient in bakery products for its preservation characteristics and a significant source of energy, there is a growing interest in replacing this sugar with alternative substances, such as high-intensity sweeteners (HIS) that provide sweetness with no or low calories. In Brazil, there is no data on the use of HIS in this class of food. Therefore, the objective of this study was to evaluate the presence of HIS in baked food commercially available in the country and estimate the dietary exposure to these food additives. For that, an analytical method was established for the simultaneous determination of nine HIS in bakery products using ultra-high performance liquid chromatography coupled to tandem mass spectrometry (UHPLC-MS/MS). Sample preparation steps were required based on mechanical kneading for homogenization, hexane extraction of fats, dilution in mobile phase and vortex homogenization, prior to injection into the system. The results obtained during validation showed that coefficients of variation (CV%) for precision were lower than 13.8% and the accuracy was between 91.6% and 109.1%. Aspartame, acesulfame potassium, sodium cyclamate, saccharin, sucralose and steviol glycosides were found in the samples, used alone or in combinations of up five substances. Steviol glycosides were the most found HIS in biscuit samples, while sucralose was the most common sweetener in cake and bread samples. Analysis of product labels revealed only three different claims, .i.e. 'no sugar', 'no added sugar' and 'zero sugar', with the latter being found in 70% of the samples. Exposure to HIS through the consumption of bakery products estimated per eating occasion showed no concerns regarding toxicological risk.

Nonpharmacological Interventions for Treating Breastfeeding Nipple Pain: Systematic Review and Meta-Analysis.

Objective: To evaluate the efficacy and safety of nonpharmacological topical interventions for treating breastfeeding nipple pain. Methods: Randomized clinical trials (RCTs) assessing lactating women suffering from breastfeeding painful nipples were included. Primary outcomes were pain, healing process, and adverse events. A comprehensive search was conducted on June 02, 2023, without date or language restrictions. Methodological quality was assessed using the Cochrane risk of bias tool and the certainty of the evidence, the GRADE approach. Results: Nineteen RCTs with unclear to high risk of bias were included. There was uncertain evidence regarding the effects of photobiomodulation versus placebo on pain reduction (mean difference [MD] -0.15; 95% confidence interval [95% CI] -1 0.49 to 1.19; 139 participants, 2 RCTs). There are uncertainties concerning the effects of lanolin versus breast milk on pain (MD -1.80; 95% CI -2.43 to -1.17; 1 RCT; 180 participants), wound healing (MD 0.10; 95% CI -0.26 to -0.46; 1 RCT; 180 participants), and any adverse events (zero events in both groups). Similar effects were observed by the other interventions assessed. Conclusion: The evidence of nonpharmacological topical interventions for painful nipples is imprecise, and future RCTs with higher methodological quality are needed to support recommendations. Considering the accessibility and low cost of these alternative treatments, the findings of this evidence synthesis could support clinical decision-making and guide future research. PROSPERO CRD42020170320.

Reduction of peripersonal comfort space correlate with eating disorder symptoms in young adolescents: a network analysis approach.

Background: Peripersonal Space (PS) is represented as the immediate area surrounding an individual. The extent of PS changes in relation to several factors, including emotional states, type of relationship or psychopathology. Attachment anxiety has an impact on the social adaptability of peripersonal space and anxiety and fear are associated with an expansion of peripersonal space, possibly serving as a mechanism of self-protection. Peripersonal space appears to be intricately linked to various psychiatric conditions like anxiety disorders and converging evidence suggests that social maladjustment may predict or exacerbate eating disorder symptoms expression. Methods: Fifty-eight healthy adolescents (38F, 20M) performed a comfort distance estimation task to assess peripersonal space. The Adolescent/Adult Sensory Profile (AASP) was used to assess sensory profiles and the SAFA protocol to investigate psychopathological aspects. Data was analysed using Network Analysis, estimating a Gaussian Graphical Models with a Bayesian approach. Results: We found that the task related to comfort estimation distance demonstrated a correlation with the visual scale of the Adolescent/Adult Sensory Profile (AASP). Additionally, a correlation was observed with the Eating Disorder scale of the SAFA protocol. The touch scale also was negatively correlated with Eating disorder symptoms but not with the comfort estimation task. Conclusion: Our results demonstrate a relation between peripersonal space and eating disorder symptoms in healthy adolescents in line with previous findings in adults with eating disorders diagnosis. These findings suggest that socio-emotional difficulties may be possible precursors or reinforce for the development of an eating disorder symptoms.

Psychological dimensions in alcohol use disorder: comparing active drinkers and abstinent patients.

Background: Alcohol use disorder (AUD) is a major public health concern due to its various physical, psychological, and social consequences. Despite regulatory differences, abstinence remains the primary treatment objective. Addressing the multifaceted nature of alcohol use disorder requires a comprehensive approach. Methods: 150 AUD patients (66%male) with a mean age of 54.10 ± 11.3 years were recruited for the study. Depression, impulsivity, alexithymia, and hopelessness were assessed to determine if there were significant differences in these dimensions between abstinent (N=72) and active drinkers (N=78). Results: The study found significant differences in the psychological dimensions scores, active drinkers exhibited higher levels of depression, impulsivity, alexithymia, and hopelessness compared to abstinent patients. Conclusion: Treatment outcomes for patients with AUD vary between regulatory agencies, but abstinence remains the safest and most preferred objective in managing AUD. Prioritizing abstinence-oriented interventions is crucial for achieving long term recovery and minimizing relapse risk. These results emphasize the intricate relationship between AUD and mental health issues, highlighting the need for comprehensive interventions addressing both alcohol consumption and associated psychological distress. Promoting abstinence (or at least reducing alcohol consumption) not only preserves mental health but also prevents life-threatening consequences such as suicide.

Association between Leukemic Evolution and Uncommon Chromosomal Alterations in Pediatric Myelodysplastic Syndrome.

Background: Pediatric myelodysplastic syndrome (pMDS) is a group of rare clonal neoplasms with a difficult diagnosis and risk of progression to acute myeloid leukemia (AML). The early stratification in risk groups is essential to choose the treatment and indication for allogeneic hematopoietic stem cell transplantation (HSCT). According to the Revised International Prognostic Scoring System, cytogenetic analysis has demonstrated an essential role in diagnosis and prognosis. In pMDS, abnormal karyotypes are present in 30-50% of the cases. Monosomy 7 is the most common chromosomal alteration associated with poor prognosis. However, the rarity of specific cytogenetic alterations makes its prognosis uncertain. Thus, this study aimed to describe uncommon cytogenetic alterations in a cohort of 200 pMDS patients and their association with evolution to AML. Methods: The cytogenetic analysis was performed in 200 pMDS patients by G-banding and fluorescence in situ hybridization between 2000 to 2022. Results: Rare chromosome alterations were observed in 7.5% (15/200) of the cases. These chromosome alterations were divided into four cytogenetic groups: hyperdiploidy, biclonal chromosomal alterations, translocations, and uncommon deletions representing 33.3%, 33.3%, 20%, and 13.3%, respectively. Most of these patients (10/15) were classified with advanced MDS (MDS-EB and MDS/AML) and the initial subtype was present in five patients (RCC). The leukemic evolution was observed in 66.66% (10/15) of the patients. Most patients had poor clinical outcomes and they were indicated for HSCT. Conclusion: The study of uncommon cytogenetic alterations in pMDS is important to improve the prognosis and guide early indication of HSCT.

Maternal exposure to tributyltin alters the breast milk, hormonal profile, and thyroid morphology of dams and induces sex-specific changes in neonate rat offspring.

Tributyltin (TBT) is the chemical substance commonly used worldwide to prevent biofouling of vessels. Due to its ability to bioaccumulate and biomagnify, even after being banned, significant concentrations of TBT can be detected in sediment, affecting marine and human life. Although studies have shown that direct exposure to TBT alters physiological parameters in mammals, the relationship between exposure to TBT during pregnancy and lactation, considered critical windows for metabolic programming, has not been fully elucidated. Our hypothesis is that offspring whose mothers were exposed to TBT during critical stages of development may exhibit dysfunctions in endocrine-metabolic parameters. We used pregnant Wistar rats that were divided into groups and received the following treatments from gestational day 7 until the end of lactation by intragastric gavage: vehicle (ethanol 0.01%; Control), low TBT dose (100 ng/kg of body weight (bw)/day; TBT100ng) and high TBT dose (1000 ng/kg bw/day; TBT1000ng). Dams and offspring at birth and weaning (21 days old) were studied. Maternal exposure to TBT promoted dose-dependent changes in dams. The findings for adiposity, milk composition and lipid profile were more pronounced in TBT100 ng dam; however, thyroid morphology was altered in TBT1000 ng dam. Female offspring were differentially affected by the dose of exposure. At birth, females in the TBT100ng group had low body weight, lower naso-anal length (NAL), and higher plasma T4, and at weaning, females in the TBT100ng group had lower insulin and leptin levels. Females in the TBT1000ng group had lower NAL at birth and lower leptinemia and weight of white adipose tissue at weaning. Male offspring from TBT groups showed high T3 at birth, without biometric alterations at birth or weaning. Despite these findings, both sexes exhibited dose-dependent morphological changes in the thyroid gland. Thus, maternal exposure to TBT constitutes an important route of contamination for both dams and offspring.

T-cell immunophenotype correlations with cortical thickness and white matter microstructure in bipolar disorder.

BACKGROUND: Inflammation and immunological alterations, such as T-cell and cytokine changes, are implicated in bipolar disorder (BD), with some evidence linking them to brain structural changes (e.g., cortical thickness (CT), gray matter (GM) volume and white matter (WM) microstructure). However, the connection between specific peripheral cell types, such as T-cells, and neuroimaging in BD remains scarcely investigated. AIMS OF THE STUDY: This study aims to explore the link between T-cell immunophenotype and neuroradiological findings in BD. METHODS: Our study investigated 43 type I BD subjects (22 depressive, 21 manic) and 26 healthy controls (HC), analyzing T lymphocyte immunophenotype and employing neuroimaging to assess CT for GM and fractional anisotropy (FA) for WM. RESULTS: In lymphocyte populations, BD patients exhibited elevated CD4+ and CD4+ central memory (TCM) cells frequencies, but lower CD8+ effector memory (TEM) and terminal effector memory (TTEM) cells. Neuroimaging analysis revealed reduced CT in multiple brain regions in BD patients; and significant negative correlations between CD4 + TCM levels and CT of precuneus and fusiform gyrus. Tract-based spatial statistics (TBSS) analysis showed widespread alteration in WM microstructure in BD patients, with negative and positive correlations respectively between FA and radial diffusivity (RD) and CD4 + TCM. Additionally, positive and negative correlations were found respectively between FA and RD and the CD8 + TEM and CD8 + TTEM subsets. CONCLUSIONS: Our research revealed distinct T lymphocyte changes and brain structure alterations in BD, underscoring possible immune-brain interactions, warranting further study and therapeutic exploration.

Maternal low-dose caffeine intake during the perinatal period promotes short- and long-term sex-dependent hormonal and behavior changes in the offspring.

AIM: Maternal caffeine crosses the placenta and mammary barriers, reaching the baby and, because his/her caffeine metabolism is immature, our hypothesis is that even a low caffeine intake (250 mg/day), lower than the dose limit recommended by the World Health Organization, can promote caffeine overexposure in the offspring, leading to short- and long-term changes. MAIN METHODS: Pregnant Wistar rats received intragastric caffeine (CAF) (25 mg/Kg/day) or vehicle during the gestation and lactation periods. We evaluated morphometrical, metabolic, hormonal, and behavioral parameters of male and female offspring at different ages. KEY FINDINGS: Even a low caffeine intake promoted lower maternal body mass and adiposity, higher plasma cholesterol and lower plasma T3, without changes in plasma corticosterone. Female CAF offspring exhibited lower birth weight, body mass gain and food intake throughout life, and hyperinsulinemia at weaning, while male CAF offspring showed reduced food intake and lower plasma T3 at weaning. At puberty and adulthood, male CAF showed higher preference for palatable food, aversion to caffeine intake and higher locomotor activity, while female CAF only showed lower preference for high fat diet (HFD) and lower anxiety-like behavior. At adulthood, both male and female offspring showed higher plasma T3. Male CAF showed hypertestosteronemia, while female CAF showed hypoinsulinemia without effect on glucose tolerance. SIGNIFICANCE: A low caffeine intake during the perinatal period affects rat's offspring development, promoting sex-dependent hormonal and behavior changes. Current data suggest the need to review caffeine recommendations during the perinatal period.