Neuronal programming by microbiota regulates intestinal physiology.

Neural control of the function of visceral organs is essential for homeostasis and health. Intestinal peristalsis is critical for digestive physiology and host defence, and is often dysregulated in gastrointestinal disorders1. Luminal factors, such as diet and microbiota, regulate neurogenic programs of gut motility2-5, but the underlying molecular mechanisms remain unclear. Here we show that the transcription factor aryl hydrocarbon receptor (AHR) functions as a biosensor in intestinal neural circuits, linking their functional output to the microbial environment of the gut lumen. Using nuclear RNA sequencing of mouse enteric neurons that represent distinct intestinal segments and microbiota states, we demonstrate that the intrinsic neural networks of the colon exhibit unique transcriptional profiles that are controlled by the combined effects of host genetic programs and microbial colonization. Microbiota-induced expression of AHR in neurons of the distal gastrointestinal tract enables these neurons to respond to the luminal environment and to induce expression of neuron-specific effector mechanisms. Neuron-specific deletion of Ahr, or constitutive overexpression of its negative feedback regulator CYP1A1, results in reduced peristaltic activity of the colon, similar to that observed in microbiota-depleted mice. Finally, expression of Ahr in the enteric neurons of mice treated with antibiotics partially restores intestinal motility. Together, our experiments identify AHR signalling in enteric neurons as a regulatory node that integrates the luminal environment with the physiological output of intestinal neural circuits to maintain gut homeostasis and health.

Periprosthetic shoulder infection management: one-stage should be the way: a systematic review and meta-analysis.

BACKGROUND: There is still no consensus among surgeons on whether to perform a 1- or 2-stage surgical revision in infected shoulder arthroplasties. The aim of this systematic review and meta-analysis is to rigorously synthesize published studies evaluating the clinical outcomes, recurrence of infection, and other clinical complications in order to discuss which is the best strategy for treating periprosthetic joint infection after shoulder arthroplasty. METHODS: Upon research using the PubMed, Scopus, and Web of Science databases, in November 2022, studies that presented 1- or 2-stage surgical revision as a treatment for periprosthetic joint infection after shoulder arthroplasty and assessed the reinfection rate on these patients, as well as other clinical outcomes, with a minimum follow-up of 12 months, were included. Study quality was evaluated using the Methodological Index for Non-Randomized Studies (MINORS) score. Reinfection and complication rates were extracted, and pooled estimates were calculated using the random-effect model. RESULTS: After careful screening, 44 studies were included, 5 reporting on 1-stage and 30 on 2-stage revisions and 9 assessing both strategies. A total of 185 shoulders were reported in 1-stage revision studies, whereas 526 shoulders were reported in 2-stage revision studies. The overall pooled random-effects reinfection rate was 6.68% (95% confidence interval [CI]: 3.76-10.13), with low heterogeneity (I2 = 28%, P = .03). One-stage revision showed a reinfection rate of 1.14% (95% CI: 0.00-4.88), whereas 2-stage revision analysis revealed a reinfection rate of 8.81% (95% CI: 4.96-13.33). There were significant statistical differences between 1- and 2-stage reinfection rates (P = .04). The overall pooled rate for other clinical complications was 16.76% (95% CI: 9.49-25.15), with high heterogeneity (I2 = 70%, P < .01). One-stage revision had a complication rate of 6.11% (95% CI: 1.58-12.39), whereas the 2-stage revision complication rate was 21.26% (95% CI: 11.51-32.54). This difference was statistically significant (P = .03). CONCLUSIONS: This is the first systematic review and meta-analysis showing significant statistical differences between 1- and 2-stage surgical revision in infected shoulder arthroplasties. Provided the right conditions exist, 1-stage revision shows better results in infection control, with lower clinical complications and possible better clinical outcomes.

Gastroesophageal Reflux Disease Diagnosis by New Consensus in Clinical Practice: The Additional Value of Mean Basal Impedance.

BACKGROUND: Recently, Lyon consensus and ROME IV were published as there was a need to create a more objective evaluation for gastroesophageal reflux disease (GERD) in order to better predict treatment outcomes. However, with classical pH-impedance measures, some patients would still have diagnostic uncertainty, and new metrics, such as mean nocturnal basal impedance (MNBI), have emerged to corroborate with GERD diagnosis. The aim of the present study was to describe the prevalence of GERD, functional heartburn (FH), reflux hypersensitivity (RH), and undetermined diagnosis using current consensuses and to evaluate if MNBI could be considered a supportive measure for the diagnosis of GERD. METHODS: Patients who underwent pH-multichannel intraluminal impedance (MII-pH) for suspected GERD between 2013 and 2018 were included. Subjects with previous diagnosis of GERD (e.g., esophagitis grade C or D according to Los Angeles classification, Barrett's esophagus, or peptic stricture), atypical symptoms, major esophageal motor disorder, eosinophilic esophagitis, or under proton pump inhibitor were excluded from the analysis. RESULTS: We included 75 patients. The prevalence of GERD, FH, RH and undetermined diagnosis was 44%, 14.7%, 12%, and 29.3%, respectively. MNBI was lower in patients with GERD (GERD: 1,307.5 ± 817.9 Ω vs. FH: 3,039.6 ± 1,040.8 Ω, RH: 2,617.1 ± 1,342.2 Ω, undetermined: 2,351.9 ± 1,018.2, p < 0.001), although it was similar between patients with FH and RH (p = 0.44) or between undetermined diagnosis and FH/RH (p = 0.15). More patients with a GERD diagnosis had a MNBI under 2,292 Ω (GERD: 93.9% vs. non-GERD: 31.7%, p < 0.001). CONCLUSION: In our study, using MII-pH criteria, less than half of the patients had a GERD diagnosis. MNBI showed additional value as another metric for the diagnosis of GERD.

Gynecological history to diagnosis and pregnancy outcomes in diagnosed Wilson's disease patients under therapy - A bicentric matched-control cohort study.

INTRODUCTION: most studies narrowly focus on pregnancy outcome comparisons between Wilson's disease (WD) patients on and off treatment. We aimed to identify menses irregularities in untreated WD, and to evaluate pregnancy outcomes in treated WD patients as compared to matched controls (with and without liver disease). METHODS: females with WD, hepatitis C (liver disease controls), and other gastrointestinal conditions (controls without liver disease) were identified at two tertiary hospital gastroenterology departments. Gynecological and obstetric data were retrospectively collected. A comparison of gynecological and obstetric outcomes was performed between the groups, and regression models were used to further assess obstetric outcomes. RESULTS: a total of 18 females with WD were identified, comprising 19 pregnancies under treatment in 11 patients, and 20 females were included in each control group. Age and liver disease stage were adjusted between groups. The incidence of menses irregularities was higher for WD (late menarche, 83 % vs. 10 % vs. 10 %, p < 0.01; irregular cycles, 100 % vs. 20 % vs. 20 %, p < 0.01; amenorrhea, 67 % vs. 10 % vs. 5 %, p < 0.01). Logistic regression models identified WD as a predictor of miscarriage and low birth weight (OR: 6.0; CI: 1.1-33.3; p < 0.05) but not of birth defects. Neither therapies (D-penicillamine 300 mg or zinc acetate 150 mg) nor disease presentation (hepatic and/or neurological) were associated with obstetric complications in WD subjects. CONCLUSION: there was a higher incidence of menses irregularities in untreated females with WD. In addition, our data suggest that treated WD still carries a higher risk of spontaneous abortion and low birth weight when compared to matched control groups with and without liver disease.

Adapting to a New Country During an Expatriate Mission: The Vital Role of Events and Emotions.

The aim of this study was to identify the most relevant positive and negative events, and their consequent emotional experiences, occurring during the adaptation to a new country in an expatriate mission. We opted to train an artificial neural network to explore the relation between events and emotions since there is increasing evidence of the nonlinear patterns characterizing the adaptation to a new country as well as regarding the superior performance of nonlinear methods for understanding the experience of emotions. We surveyed 99 expatriate workers who reported a total of 221 events and 2,467 associated emotions. Three judges categorized the events, reducing them into 11 categories. The neural network architecture grouped the events into 3 hidden layers, two of them leading to positive emotions and the other one leading exclusively to negative emotions. We found that events related to self-realization and recognition and to overall well-being were the most relevant to the experience of positive emotions while those related to security were the most important predictors of negative emotions. This study addresses a major gap in the expatriates' literature by relating specific occurrences with the phenomenological emotional experience. Practical implications are further discussed.

Inhalational anaesthetics, ozone depletion, and greenhouse warming: the basics and status of our efforts in environmental mitigation.

PURPOSE OF REVIEW: Following their use for medicinal purposes, volatile inhalational anaesthetic agents are expelled into the atmosphere where they contribute to anthropogenic climate change. We describe recent evidence examining the benefits and harms associated with their use. RECENT FINDINGS: The environmental harms associated with desflurane and nitrous oxide likely outweigh any purported clinical benefits. Life cycle analyses are beginning to address the many gaps in our understanding, and informing choices made on all aspects of anaesthetic care. There is, however, an urgent need to move beyond the debate about anaesthetic technique A vs. B and focus also on areas such as sustainable procurement, waste management, pharmacological stewardship and joined-up solutions. SUMMARY: There is now compelling evidence that anaesthetists, departments and hospitals should avoid desflurane completely, and limit nitrous oxide use to settings where there is no viable alternative, as their environmental harms outweigh any perceived clinical benefit. Life cycle analyses seem supportive of total intravenous and/or regional anaesthesia. There are many other areas where choices can be made by individual anaesthetists that contribute towards reducing the environmental burden of healthcare, such as prioritising the reduction of inappropriate resource use and over-treatment. However, this all requires joined up solutions where all parts of an organisation engage.

Synthesis of Iron(II)-N-Heterocyclic Carbene Complexes: Paving the Way for a New Class of Antibiotics.

The synthesis and structural modulation of five pro-ligand salts was achieved using alternative sustainable synthetic strategies, the use of microwaves being the method of choice, with an 81% yield and an E factor of 43 for 3d. After complexation with Fe3(CO)12 by direct reaction with the appropriate pro-ligands at 130 °C, a set of iron(II) N-heterocyclic carbene (NHC) complexes were isolated and fully characterized (via 1H and 13C NMR and IR spectroscopy and elemental analysis). The antibacterial activities of the iron(II)-NHC complexes were tested against standard World Health Organization priority bacterial strains: Staphylococcus aureus ATCC 29213 and Escherichia coli ATCC 25922. The results showed a significant effect of the Fe(II)-NHC side-chain on the antibacterial activity against both Gram-negative and Gram-positive bacteria. Among all compounds, the most lipophilic iron complex, 3b, was found to be the most active one, with a minimum inhibitory concentration of 8 µg/mL. Pioneering mechanistic studies suggested an alternative mechanism of action (OH· formation), which opens the way for the development of a new class of antibiotics.

Fermentation at non-conventional conditions in food- and bio-sciences by the application of advanced processing technologies.

The interest in improving the yield and productivity values of relevant microbial fermentations is an increasingly important issue for the scientific community. Therefore, several strategies have been tested for the stimulation of microbial growth and manipulation of their metabolic behavior. One promising approach involves the performance of fermentative processes during non-conventional conditions, which includes high pressure (HP), electric fields (EF) and ultrasound (US). These advanced technologies are usually applied for microbial inactivation in the context of food processing. However, the approach described in this study focuses on the use of these technologies at sub-lethal levels, since the aim is microbial growth and fermentation under these stress conditions. During these sub-lethal conditions, microbial strains develop specific genetic, physiologic and metabolic stress responses, possibly leading to fermentation products and processes with novel characteristics. In some cases, these modifications can represent considerable improvements, such as increased yields, productivities and fermentation rates, lower accumulation of by-products and/or production of different compounds. Although several studies report the successful application of these technologies during the fermentation processes, information on this subject is still scarce and poorly understood. For that reason, the present review paper intends to assemble and discuss the main findings reported in the literature to date, and aims to stimulate interest and encourage further developments in this field.

Clinical outcomes after preimplantation genetic diagnosis of patients with Corino de Andrade disease (familial amyloid polyneuropathy).

The aim of this study was to determine whether patients with transthyretin-related hereditary amyloidosis (V30M), after transplantation or under tafamidis treatment, have normal gamete reproductive capacity. A retrospective analysis was carried out of all preimplantation genetic diagnosis (PGD) cycles performed in patients with the V30M mutation. The groups analysed were: total cases with V30M, female cases with V30M and male cases with V30M. Detailed demographic, stimulation, embryological, clinical and newborn outcomes were evaluated. Comparisons revealed that patients have a high likelihood of achieving a live birth per PGD treatment cycle (48%). This is the first large report on patients with the V30M mutation treated with PGD. The high rate of live birth obtained should represent a strong stimulus for patients to use PGD as it proved to be effective and safe. As a neurodegenerative disease that leads to death, it is of maximum importance that it could be eradicated using PGD in order to definitively avoid the transmission of the disease.

Application of High Pressure with Homogenization, Temperature, Carbon Dioxide, and Cold Plasma for the Inactivation of Bacterial Spores: A Review.

Formation of highly resistant spores is a concern for the safety of low-acid foods as they are a perfect vehicle for food spoilage and/or human infection. For spore inactivation, the strategy usually applied in the food industry is the intensification of traditional preservation methods to sterilization levels, which is often accompanied by decreases of nutritional and sensory properties. In order to overcome these unwanted side effects in food products, novel and emerging sterilization technologies are being developed, such as pressure-assisted thermal sterilization, high-pressure carbon dioxide, high-pressure homogenization, and cold plasma. In this review, the application of these emergent technologies is discussed, in order to understand the effects on bacterial spores and their inactivation and thus ensure food safety of low-acid foods. In general, the application of these novel technologies for inactivating spores is showing promising results. However, it is important to note that each technique has specific features that can be more suitable for a particular type of product. Thus, the most appropriate sterilization method for each product (and target microorganisms) should be assessed and carefully selected.

Emotions as Proximal Causes of Word of Mouth: A Nonlinear Approach.

Service research tends to operationalize word of mouth (WOM) behavior as one of the many responses to service satisfaction. In this sense, little is known about its antecedents or moderators. The objective of this study was to investigate the role of customers' emotions during service experiences on WOM, applying nonlinear techniques and exploring the moderating role of customers' propensity for emotional contagion. Using the critical incidents technique, 122 customers recalled significant service experiences and the emotions they aroused, and reported if they shared said experiences with other individuals. We found that, whereas linear methods presented non-significant results in the emotions-WOM relationship, nonlinear ones (artificial neural networks) explained 46% of variance. Negative emotions were stronger predictors of WOM and the importance of emotions for WOM was significantly higher for individuals with high propensity for emotional contagion (R^2 = .79) than for those with lower levels (R^2 = .48). Theoretical and practical implications are discussed.

Lhx8 regulates primordial follicle activation and postnatal folliculogenesis.

BACKGROUND: The early stages of ovarian follicle formation-beginning with the breakdown of germ cell cysts and continuing with the formation of primordial follicles and transition to primary and secondary follicles-are critical in determining reproductive life span and fertility. Previously, we discovered that global knockouts of germ cell-specific transcriptional co-regulators Sohlh1, Sohlh2, Lhx8, and Nobox, cause rapid oocyte loss and ovarian failure. Also factors such as Nobox and Sohlh1 are associated with human premature ovarian failure. In this study, we developed a conditional knockout of Lhx8 to study oocyte-specific pathways in postnatal folliculogenesis. RESULTS: The conditional deficiency of Lhx8 in the oocytes of primordial follicles leads to massive primordial oocyte activation, in part, by indirectly interacting with the PI3K-AKT pathway, as shown by synergistic effects on FOXO3 nucleocytoplasmic translocation and rpS6 activation. However, LHX8 does not directly regulate members of the PI3K-AKT pathway; instead, we show that LHX8 represses Lin28a expression, a known regulator of mammalian metabolism and of the AKT/mTOR pathway. LHX8 can bind to the Lin28a promoter, and the depletion of Lin28a in Lhx8-deficient oocytes partially suppresses primordial oocyte activation. Moreover, unlike the PI3K-AKT pathway, LHX8 is critical beyond primordial follicle activation, and blocks the primary to secondary follicle transition. CONCLUSIONS: Our results indicate that the LHX8-LIN28A pathway is essential in the earliest stages of primordial follicle activation, and LHX8 is an important oocyte-specific transcription factor in the ovary for regulating postnatal folliculogenesis.

A Collaborative Approach for Scoping Ecosystem Services with Stakeholders: The Case of Arrábida Natural Park.

This paper presents an innovative approach for conducting collaborative scoping processes aiming to elicit multiple values of ecosystem services. The proposed methodology rests on three steps combining different participatory tools that promote a comprehensive examination of the perceptions hold by relevant stakeholder groups. The first step consists of an institutional and stakeholder analysis developed in the study area. The second includes a participatory workshop, where a sequence of scoping exercises is conducted with the active collaboration of the invited stakeholders. The final step aims to validate scoping results and develop dependency networks between organizations and the identified ecosystem services. The approach was tested in the Arrábida Natural Park, a marine and coastal protected area in Portugal. Invited participants were able to identify an extensive list of ecosystem services in the natural area, establish linkages between those services and human wellbeing, identify drivers of change and perform a preliminary screening of the associated ecological, social, and economic values. The case study evaluation provided positive feedback on the usefulness of the approach, which advances the existing set of methods for participatory identification of ecosystem services and sets the scene for involvement of stakeholder groups in assessment and management processes.

Transcription factor LIM homeobox 7 (Lhx7) maintains subtype identity of cholinergic interneurons in the mammalian striatum.

The generation and maintenance of a plethora of neuronal subtypes is essential for normal brain function. Nevertheless, little is known about the molecular mechanisms that maintain the defining characteristics of neurons following their initial postmitotic specification. Using conditional gene ablation in mice, we demonstrate here that the homeodomain protein LIM homeobox (Lhx)7 is essential for maintaining the morphological and molecular characteristics of cholinergic interneurons of the striatum. Lhx7-depleted cholinergic interneurons extinguish expression of several subtype-specific markers, including choline acetyl transferase and Isl1, and are respecified into Lhx6-expressing mature GABAergic interneurons. Additional expression studies support a model where Lhx7 controls the choice between cholinergic or GABAergic identity by gating a cross inhibitory regulation between Isl1 and Lhx6. By demonstrating that the switch between alternative striatal interneuron fates depends on persistent activity of a single transcription factor, we provide evidence that the intrinsic plasticity of mammalian forebrain neuronal subtypes is maintained after the initial specification and lineage commitment and possibly throughout life.

Healthy Variability in Organizational Behavior: Empirical Evidence and New Steps for Future Research.

The healthy variability thesis suggests that healthy systems function in a complex manner over time. This thesis is well-established in fields like physiology. In the field of organizational behavior, however, this relation is only starting to be explored. The objective of this article is threefold: First, we aim to provide a comprehensive review of the healthy variability thesis including some of the most important findings across different fields, with a focus on evidences from organizational research in work motivation and performance. Second, we discuss an opposite pattern, unhealthy stability, i.e., the relationship between unhealthy behaviors and lower variability. Again, we provide evidence from diverse areas, from affective processes to disruptive organizational comportments like mobbing. Third, we provide a critical evaluation of current methodological trends and highlight what we believe to be the main factors that are stopping organizational research from advancing in the field. Theoretical, methodological and epistemological implications are discussed. To conclude, we draw a compilation of the lessons learned, which hopefully provide insights for prolific research avenues. Our main purpose is to raise awareness of the healthy variability thesis and to enthuse organizational researchers to consider it in order to advance existing knowledge, revisit old theories and create new ones.

Giant Intrathoracic Desmoid Tumor - a Case Report.

Desmoid tumors are soft tissue neoplasms arising from fascial and muscle-aponeurotic structure. These tumors are locally aggressive and have a high recurrence rate, even after complete resection. We present the case of a female with a giant intrathoracic desmoid tumor. She underwent complete surgical resection with no disease recurrence. Desmoid tumors' natural history is not well defined and is often enigmatic, making these tumors difficult to manage. Currently, for intrathoracic desmoid tumors, medical treatment is the recommended approach, nevertheless, surgery can be considered in selected patients.

IgG4-related disease: Case report and 6-year follow-up of an elusive diagnosis mimicking malignancy.

Key Clinical Message: IgG4-related disease is a rare and emerging pathology, characterized by the appearance of pseudotumors. Due to the ability to mimic other pathologies, it is essential to consider it as a differential diagnosis in multisystemic processes. The diagnosis is challenging, requiring a multidisciplinary approach, to minimize the associated morbidity and mortality. Abstract: IgG4-related disease (IgG4-RD) is a rare, emerging, systemic and chronic pathology, characterized by the appearance of pseudotumors resulting from tissue infiltration by IgG4-positive plasma cells that promote eosinophilic inflammation of the tissue with subsequent fibrosis. We present the case of a male, 45-year-old patient, with marked weight loss and skin pallor detected by his family doctor during a child health consultation of his daughter. When questioned, the patient referred complaints of postprandial discomfort in the left hypochondrium with a feeling of fullness, weight loss, chronic fatigue and hyperhidrosis that had lasted for a month. On physical examination, he was pale, and had pain at palpation of the left hypochondrium. Laboratory data showed increased inflammation markers, abdominal ultrasound and CT demonstrated numerous enlarged lymph nodes in the upper quadrants, raising concern for a malignant lymphoproliferative process. Serological, imaging, clinical and laparoscopic excisional biopsy revealed features of IgG4-related disease and excluded malignant lymphoproliferative disease. The immediate response to treatment with oral prednisolone 30 mg/day also contributed for diagnosis confirmation. Due to refractory disease after gradual prednisolone reduction, second-line therapy with rituximab was initiated. Over the 6 years of follow-up, the patient presented multiple exacerbations characterized by the emergence of systemic symptoms, being maintained under close clinical and imaging follow-up by reumathology, infectious diseases, and family medicine specialists.

A Symbiotic Meal Containing Extruded Sorghum and Probiotic (Bifidobacterium longum) Ameliorated Intestinal Health Markers in Individuals with Chronic Kidney Disease: A Secondary Analysis of a Subsample from a Previous Randomized and Controlled Clinical Trial.

BACKGROUND: Chronic kidney disease increases uremic toxins concentrations, which have been associated with intestinal dysbiosis. Sorghum bicolor L. Moench has dietary fiber and bioactive compounds, while Bifidobacterium longum can promote beneficial health effects. METHODS: It is a controlled, randomized, and single-blind clinical trial. Thirty-nine subjects were randomly separated into two groups: symbiotic group (SG), which received 100 mL of unfermented probiotic milk with Bifidobacterium longum strain and 40 g of extruded sorghum flakes; and the control group (CG), which received 100 mL of pasteurized milk and 40 g of extruded corn flakes for seven weeks. RESULTS: The uremic toxins decreased, and gastrointestinal symptoms improved intragroup in the SG group. The acetic, propionic, and butyric acid production increased intragroup in the SG group. Regarding α-diversity, the Chao1 index was enhanced in the SG intragroup. The KEGG analysis revealed that symbiotic meal increased the intragroup energy and amino sugar metabolism, in addition to enabling essential amino acid production and metabolism, sucrose degradation, and the biosynthesis of ribonucleotide metabolic pathways. CONCLUSIONS: The consumption of symbiotic meal reduced BMI, improved short-chain fatty acid (SCFA) synthesis and gastrointestinal symptoms, increased diversity according to the Chao1 index, and reduced uremic toxins in chronic kidney disease patients.