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The pig is an important translational model for studying intestinal physiology and disorders for its many homologies with humans, including the organization of the enteric nervous system (ENS), the major regulator of gastrointestinal functions. This study focused on the quantification and neurochemical characterization of substance P (SP) neurons in the pig ascending (AC) and descending colon (DC) in wholemount preparations of the inner submucosal plexus (ISP), outer submucosal plexus (OSP), and myenteric plexus (MP). We used antibodies for the pan-neuronal marker HuCD, and choline acetyltransferase (ChAT) and neuronal nitric oxide synthase (nNOS), markers for excitatory and inhibitory transmitters, for multiple labeling immunofluorescence and high-resolution confocal microscopy. The highest density of SP immunoreactive (IR) neurons was in the ISP (222/mm2 in the AC, 166/mm2 in the DC), where they make up about a third of HuCD-IR neurons, compared to the OSP and MP (19-22% and 13-17%, respectively, P

Abstract Background A few studies have suggested that light at night (LAN) exposure, i.e. lighting during night hours, may increase dementia risk. We evaluated such association in a cohort of subjects diagnosed with mild cognitive impairment (MCI). Methods We recruited study participants between 2008 and 2014 at the Cognitive Neurology Clinic of Modena Hospital, Northern Italy and followed them for conversion to dementia up to 2021. We collected their residential history and we assessed outdoor artificial LAN exposure at subjects’ residences using satellite imagery data available from the Visible Infrared Imaging Radiometer Suite (VIIRS) for the period 2014–2022. We assessed the relation between LAN exposure and cerebrospinal fluid biomarkers. We used a Cox-proportional hazards model to compute the hazard ratio (HR) of dementia with 95% confidence interval (CI) according to increasing LAN exposure through linear, categorical, and non-linear restricted-cubic spline models, adjusting by relevant confounders. Results Out of 53 recruited subjects, 34 converted to dementia of any type and 26 converted to Alzheimer’s dementia. Higher levels of LAN were positively associated with biomarkers of tau pathology, as well as with lower concentrations of amyloid β1−42 assessed at baseline. LAN exposure was positively associated with dementia conversion using linear regression model (HR 1.04, 95% CI 1.01–1.07 for 1-unit increase). Using as reference the lowest tertile, subjects at both intermediate and highest tertiles of LAN exposure showed increased risk of dementia conversion (HRs 2.53, 95% CI 0.99–6.50, and 3.61, 95% CI 1.34–9.74). In spline regression analysis, the risk linearly increased for conversion to both any dementia and Alzheimer’s dementia above 30 nW/cm2/sr of LAN exposure. Adding potential confounders including traffic-related particulate matter, smoking status, chronic diseases, and apolipoprotein E status to the multivariable model, or removing cases with dementia onset within the first year of follow-up did not substantially alter the results. Conclusion Our findings suggest that outdoor artificial LAN may increase dementia conversion, especially above 30 nW/cm2/sr, although the limited sample size suggests caution in the interpretation of the results, to be confirmed in larger investigations.

Abstract Systemic inflammation and neuroinflammation affect the natural course of the sporadic form of Alzheimer’s disease (AD), as supported by epidemiological and preclinical data, and several epidemiological studies indicate a higher prevalence of AD in patients with inflammatory bowel disease. In this study, we explored whether colitis induced by dextran sulfate sodium (DSS) in young, presymptomatic/preplaque mice worsens and/or anticipates age-dependent cognitive impairment in Tg2576, a widely used mouse model of AD. We demonstrated that DSS colitis induced in young Tg2576 mice anticipates the onset age of learning and memory deficit in the Morris water maze test. To explore potential mechanisms behind the acceleration of cognitive decline in Tg2576 mice by DSS colitis, we focused on gut microbiota, systemic inflammation and neuroinflammation markers. We observed a Firmicutes/Bacteroidetes ratio change in Tg2576 DSS animals comparable to that of elderly Tg2576 mice, suggesting accelerated microbiota aging in Tg2576 DSS mice, a change not observed in C57BL6 DSS mice. We also observed substantial differences between Tg2576 and WT mice in several inflammation and neuroinflammation-related parameters as early as 3 months of age, well before plaque deposition, a picture which evolved rapidly (between 3 and 5.5 months of age) in contrast to Tg2576 and WT littermates not treated with DSS. In detail, following induction of DSS colitis, WT and Tg2576 mice exhibited contrasting features in the expression level of inflammation-evoked astrocyte-associated genes in the hippocampus. No changes in microglial features occurred in the hippocampus between the experimental groups, whereas a reduced glial fibrillary acidic protein immunoreactivity was observed in Tg2576 vs. WT mice. This finding may reflect an atrophic, “loss-of-function” profile, further exacerbated by DSS where a decreased of GFAP mRNA expression level was detected. In conclusion, we suggest that as-yet unidentified peripheral mediators evoked by DSS colitis and involving the gut-brain axis emphasize an astrocyte “loss-of-function” profile present in young Tg2576 mice, leading to impaired synaptic morphological and functional integrity as a very early sign of AD.

Background and Purpose: Aiming to achieve light sedation via intranasal administration, this study showed that propofol (PPF) did not permeate across the rabbit nasal mucosa ex vivo from its marketed emulsion for injection. Experimental approach: Dilution of the emulsion with methyl-b-cyclodextrin in saline solution increased propofol solubility in water and diffusion across the nasal epithelium. Key results and conclusion: Despite these positive effects of the cyclodextrin, the amount of PPF permeated was minimal in 3 h, exceeding the formulation residence time in the nose. These results highlight the key role of formulation and the need for innovation in solubility and transmucosal transport enhancement techniques to optimize drug delivery and therapeutic efficacy.

Abstract Background Pediatric chronic intestinal pseudo-obstruction (PIPO) is a rare disease characterized by symptoms and radiological signs suggestive of intestinal obstruction, in the absence of lumen-occluding lesions. It results from an extremely severe impairment of propulsive motility. The intestinal endocrine system (IES) jointly with the enteric nervous system (ENS) regulates secreto-motor functions via different hormones and bioactive messengers/neurotransmitters. The neurotransmitter 5-hydroxytryptamine (5-HT) (or serotonin) is linked to intestinal peristalsis and secretory reflexes. Gut microbiota and its interplay with ENS affect 5-HT synthesis, release, and the subsequent serotonin receptor activation. To date, the interplay between 5-HT and gut microbiota in PIPO remains largely unclear. This study aimed to assess correlations between mucosa associated microbiota (MAM), intestinal serotonin-related genes expression in PIPO. To this purpose, biopsies of the colon, ileum and duodenum have been collected from 7 PIPO patients, and 7 age-/sex-matched healthy controls. After DNA extraction, the MAM was assessed by next generation sequencing (NGS) of the V3-V4 region of the bacterial RNA 16 S, on an Illumina Miseq platform. The expression of genes implicated in serotoninergic pathway (TPH1, SLC6A4, 5-HTR3 and 5-HTR4) was established by qPCR, and correlations with MAM and clinical parameters of PIPO have been evaluated. Results Our results revealed that PIPO patients exhibit a MAM with a different composition and with dysbiosis, i.e. with a lower biodiversity and fewer less connected species with a greater number of non-synergistic relationships, compared to controls. qPCR results revealed modifications in the expression of serotonin-related intestinal genes in PIPO patients, when compared to controls. Correlation analysis do not reveal any kind of connection. Conclusions For the first time, we report in PIPO patients a specific MAM associated to underlying pathology and an altered intestinal serotonin pathway. A possible dysfunction of the serotonin pathway, possibly related to or triggered by an altered microbiota, may contribute to dysmotility in PIPO patients. The results of our pilot study provide the basis for new biomarkers and innovative therapies targeting the microbiota or serotonin pathways in PIPO patients.

Background & Aims: Although chronic diarrhea and constipation are common, the treatment is symptomatic because their pathophysiology is poorly understood. Accumulating evidence suggests that the microbiota modulates gut function, but the underlying mechanisms are unknown. We therefore investigated the pathways by which microbiota modulates gastrointestinal motility in different sections of the alimentary tract. Methods: Gastric emptying, intestinal transit, muscle contractility, acetylcholine release, gene expression, and vasoactive intestinal polypeptide (VIP) immunoreactivity were assessed in wild-type and Myd88-/-Trif-/- mice in germ-free, gnotobiotic, and specific pathogen-free conditions. Effects of transient colonization and antimicrobials as well as immune cell blockade were investigated. VIP levels were assessed in human full-thickness biopsies by Western blot. Results: Germ-free mice had similar gastric emptying but slower intestinal transit compared with specific pathogen-free mice or mice monocolonized with Lactobacillus rhamnosus or Escherichia coli, the latter having stronger effects. Although muscle contractility was unaffected, its neural control was modulated by microbiota by up-regulating jejunal VIP, which co-localized with and controlled cholinergic nerve function. This process was responsive to changes in the microbial composition and load and mediated through toll-like receptor signaling, with enteric glia cells playing a key role. Jejunal VIP was lower in patients with chronic intestinal pseudo-obstruction compared with control subjects. Conclusions: Microbial control of gastrointestinal motility is both region- and bacteria-specific; it reacts to environmental changes and is mediated by innate immunity-neural system interactions. By regulating cholinergic nerves, small intestinal VIP plays a key role in this process, thus providing a new therapeutic target for patients with motility disorders.

IntroductionThe accurate distinction between periprosthetic joint infections (PJI) and aseptic failures (AF) is of paramount importance due to differences in treatment. However, this could be challenging by using the current criteria. Various synovial fluid biomarkers are being assessed to improve the diagnostic accuracy. Myeloperoxidase (MPO), an enzyme contained in the granules of neutrophils, may be a promising biomarker for PJI.MethodsSynovial fluids of 99 patients (n = 65 PJI according to EBJIS criteria; n = 34 AF) were collected in two specialized orthopedic centers. PJI were divided into acute (n = 33) and low-grade (n = 32) according to previously published classification. An activity assay specific for active MPO was performed in each sample. Ability of MPO to correctly discriminate patients with PJI from AF was determined by ROC analysis. The best discriminating cut-off value was determined by calculating the J Youden index. For all analyses, a P value < 0.05 was considered statistically significant.ResultsActive MPO was higher in PJI than AF (P < 0.0001). The ROC analysis revealed a significant area under the curve (AUC: 0.86; 95% CI: 0.78–0.93, P < 0.0001). A cut-off value of 561.9 U/mL, with good sensitivity (0.69) and specificity (0.88), discriminated between AF and PJI (accuracy 75.76%, 95% CI: 66.11–83.81%, positive likelihood ratio 5.88, 95% CI: 2.31–14.98 and negative likelihood ratio 0.35, 95%CI: 0.24–0.51). No difference in MPO levels was found between acute and chronic low-grade PJI.ConclusionThe proposed assay appears to be a reliable and affordable tool for detecting the active MPO in synovial fluid, with promising characteristics of sensitivity and specificity in discriminating both acute and low-grade PJI from AF. Further studies are needed to confirm MPO diagnostic cut-off values and validate their use in the routine clinical practice.

Urban surfaces play a crucial role in shaping the Urban Heat Island (UHI) effect by absorbing and retaining significant solar radiation. This paper explores the potential of high-resolution satellite imagery as an alternative method for characterizing urban surfaces to support UHI mitigation strategies in urban redevelopment plans. We utilized Landsat images spanning the past 40 years to analyze trends in Land Surface Temperature (LST). Additionally, WorldView-3 (WV3) imagery was acquired for surface characterization, and the results were compared with ground truth measurements using the ASD FieldSpec 4 spectroradiometer. Our findings revealed a strong correlation between satellite-derived surface reflectance and ground truth measurements across various urban surfaces, with Root Mean Square Error (RMSE) values ranging from 0.01 to 0.14. Optimal characterization was observed for surfaces such as bituminous membranes and parking with cobblestones (RMSE < 0.03), although higher RMSE values were noted for tiled roofs, likely due to aging effects. Regarding surface albedo, the differences between satellite-derived data and ground measurements consistently remained below 12% for all surfaces, with the lowest values observed in high heat-absorbing surfaces like bituminous membranes. Despite challenges on certain surfaces, our study highlights the reliability of satellite-derived data for urban surface characterization, thus providing valuable support for UHI mitigation efforts.

Sex and gender are fundamental health determinants and their role as modifiers of treatment response is increasingly recognized. Norepinephrine is a cornerstone of septic shock management and its use is based on the highest level of evidence compared to dopamine. The related 2021 Surviving Sepsis Campaign (SCC) recommendation is presumably applicable to both females and males; however, a sex- and gender-based analysis is lacking, thus not allowing generalizable conclusions. This paper was aimed at exploring whether sex- and gender-disaggregated data are available in the evidence supporting this recommendation. For all the studies underpinning it, four pairs of authors, including a woman and a man, extracted data concerning sex and gender, according to the Sex and Gender Equity in Research guidelines. Nine manuscripts were included with an overall population of 2126 patients, of which 43.2% were females. No sex analysis was performed and gender was never reported. In conclusion, the present manuscript highlighted that the clinical studies underlying the SCC recommendation of NE administration in septic shock have neglected the likely role of sex and gender as modifiers of treatment response, thus missing the opportunity of sex- and gender-specific guidelines.

Background: Dementia is a neurological syndrome characterized by severe cognitive impairment with functional impact on everyday life. It can be classified as young onset dementia (EOD) in case of symptom onset before 65, and late onset dementia (LOD). The purpose of this study is to assess the risk of dementia due to light pollution, and specifically outdoor artificial light at night (LAN). Methods: Using a case-control design, we enrolled dementia patients newly-diagnosed in the province of Modena in the period 2017–2019 and a referent population from their caregivers. We geo-referenced the address of residence on the date of recruitment, provided it was stable for the previous five years. We assessed LAN exposure through 2015 nighttime luminance satellite images from the Visible Infrared Imaging Radiometer Suite (VIIRS). Using a logistic regression model adjusted for age, sex, and education, we calculated the risk of dementia associated with increasing LAN exposure, namely using

Background: Allergic Rhinitis (AR) is an atopic disease affecting the upper airways of predisposed subjects exposed to aeroallergens. This study evaluates the effects of a mix of specific probiotics (L. acidophilus PBS066, L. rhamnosus LRH020, B. breve BB077, and B. longum subsp. longum BLG240) on symptoms and fecal microbiota modulation in subjects with AR. Methods: Probiotic effects were evaluated at the beginning (T0), at four and eight weeks of treatment (T1 and T2, respectively), and after four weeks of follow-up from the end of treatment (T3) (n = 19) compared to the placebo group (n = 22). AR symptoms and quality of life were evaluated by the mini rhinitis quality of life questionnaire (MiniRQLQ) at each time point. Allergic immune response and fecal microbiota compositions were assessed at T0, T2, and T3. The study was registered on Clinical-Trial.gov (NCT05344352). Results: The probiotic group showed significant improvement in the MiniRQLQ score at T1, T2, and T3 vs. T0 (p < 0.01, p < 0.05, p < 0.01, respectively). At T2, the probiotic group showed an increase in Dorea, which can be negatively associated with allergic diseases, and Fusicatenibacter, an intestinal bacterial genus with anti-inflammatory properties (p-value FDR-corrected = 0.0074 and 0.013, respectively). Conversely, at T3 the placebo group showed an increase in Bacteroides and Ruminococcaceae unassigned, (p-value FDR-corrected = 0.033 and 0.023, respectively) which can be associated with allergies, while the probiotic group showed a significative increase in the Prevotella/Bacteroides ratio (p-value FDR-corrected = 0.023). Conclusions: This probiotic formulation improves symptoms and quality of life in subjects with AR, promoting a shift towards anti-inflammatory and anti-allergic bacterial species in the intestinal microbiota. [ABSTRACT FROM AUTHOR]

Global warming has become a critical environmental, social, and economic threat, with increasing frequency and intensity of extreme weather events. This study aims to analyse temperature trends and climate indices in the Po Valley, a significant economic and agricultural region in Italy, by examining data from two historical stations: the urban Modena Observatory and the rural Mount Cimone Observatory. The analysis extends previous studies to 2018, assessing the magnitude of climate changes since the 1950s and isolating the Urban Heat Island (UHI) effect in Modena. Significant warming trends were confirmed at both sites, with in maximum (TX) and minimum (TN) temperatures trends nearly doubling from 1981 to 2018 compared to 1951–2018. For example, TX trends reached 0.84°C·decade−1 in Modena and 0.62°C·decade−1 at Mount Cimone, while TN trends were 0.77 and 0.80°C·decade−1, respectively. Extreme climate indices showed a substantial increase in warm days and nights (TX90p and TN90p, respectively). Particularly we found TX90p of 27.5 days·decade−1 in Modena and 15 days·decade−1 at Mount Cimone while TN90p of 29.5 days·decade−1 in Modena, 22 days·decade−1 at Mount Cimone. The UHI effect significantly impacts Modena's temperature trends. Urbanization contributes up to 65% of the rise in warm nights. Specifically, frost days decreased by 1.88 days·decade−1 (37% of Urban Contribute, UC), tropical nights increased by 5.16 days·decade−1 (57% UC), warm nights increased by 12.7 days·decade−1 (65% UC), and cool nights decreased by 3.19 days·decade−1 (39% UC). Overall, the study underscores the importance of considering both global and local factors in regional climate trend analysis. [ABSTRACT FROM AUTHOR]

Objective: Emerging evidence suggests a direct involvement of the gastrointestinal tract in COVID-19. Although the specific immune response is of paramount importance in the SARS-CoV-2 virus elimination process, aberrant immune activity could lead to severe disease and late inflammatory forms. In this context, the intestinal microbiota plays a primary role in the maturation and maintenance of the immune system. This study investigates whether the SARS-CoV-2 infection can be associated with alterations in the gut microbiome composition and if such variations could correlate with the severity of symptoms and disease outcomes. Patients and Methods: We performed shotgun metagenomic sequencing of stool samples of 45 patients, aged between 30 and 95 years, hospitalized with COVID-19. Patients were grouped by clinical severity (i.e., non-critical or critical), type of hospitalization (non-intensive care or intensive therapy unit) and outcome (survival or deceased) to explore the impact of the gut microbiome changes on patients’ health. Results: COVID-19 severity is associated with alterations in the intestinal microbiome, reduced microbial biodiversity and increased Escherichia and Bacteroides genera. No statistical significance was found between the extent of dysbiosis and clinical severity. We found an enrichment of micro-eukaryotic species, e.g., Candida albicans, Candida tropicalis, Saccharomyces cerevisiae and bacterial species previously associated with diseases as well as unhealthy cardiometabolic markers, e.g., Escherichia coli, Bacteroides fragilis, Clostridium bolteae, Clostridium innocuum, Clostridium symbiosum, Eggerthella lenta, Enterococcus faecium, and Flavonifractor plautii. Conclusions: Our findings suggest a trend of correlation between the degree of intestinal dysbiosis and the severity of the disease, likely depending on the depletion of some microorganisms with immunomodulatory effect. Furthermore, gut dysbiosis could explain the inflammatory outcome, which persists after viral negativization and might justify possible future complications.

The aim of this study was to investigate whether the presence of Staphylococcus aureus (SA) producing the Panton–Valentine leukocidin (PVL) affects the outcome of Prosthetic Joint Infection (PJI). Patients with acute and chronic PJI sustained by SA were prospectively enrolled at the orthopedic unit of “Casa di Cura Santa Maria Maddalena”, from January 2019 to October 2021. PJI diagnosis was reached according to the diagnostic criteria of the International Consensus Meeting on PJI of Philadelphia. Synovial fluid obtained via joint aspirations was collected in order to isolate SA. The detection of PVL was performed via real-time quantitative PCR (RT-qPCR). The outcome assessment was performed using the criteria of the Delphi-based International Multidisciplinary Consensus. Twelve cases of PJI caused by SA were included. Nine (75%) cases were acute PJI treated using debridement, antibiotic and implant retention (DAIR); the remaining three (25%) were chronic PJI treated using two-stage (n = 2) and one-stage revision (n = 1), respectively. The SA strains that tested positive for PVL genes were 5/12 (41.6%,). Treatment failure was documented in three cases of acute PJI treated using DAIR, all supported by SA–PVL strains (p < 0.045). The remaining two cases were chronic PJI treated with a revision arthroplasty (one and two stage, respectively), with a 100% eradication rate in a medium follow-up of 24 months. Although a small case series, our study showed a 100% failure rate in acute PJI, probably caused by SA PVL-producing strains treated conservatively (p < 0.04). In this setting, toxin research should guide radical surgical treatment and targeted antibiotic therapy.

Background: Celiac disease (CD) is an autoimmune disorder triggered by gluten ingestion. Herein, we assessed clinical, serological and histopathological findings of a single-center, large cohort of CD patients diagnosed and followed-up over forty years. Methods: From January 1980 to December 2020, 1547 CD patients (1170 females; age range: 8–81 years; F:M ratio = 3.1:1) were diagnosed in an Italian tertiary referral center. Comorbidities and complications were recorded at diagnosis and during follow-up. Results: CD diagnoses quadrupled after 2000. The most frequent phenotype was the non-classical CD (63.3%), and the most prevalent histotype was Marsh 3C (44.7%). Gastrointestinal manifestations, detectable in 51% of patients, were diarrhea (24.3%), bloating (28%) and aphthous stomatitis (19.7%). The most common CD-associated disorder was osteopenia (59.9%), predominant in females (64.3%); extraintestinal manifestations included anemia (35.8% iron-deficiency; 87% folic acid malabsorption), cryptogenic hypertransaminasemia (27.9%), and recurrent miscarriages (11.5%). Thyroiditis (26.9%), type 1 diabetes mellitus (2.9%), and dermatitis herpetiformis (1.4%) were the most common CD-related autoimmune disorders. Six patients had inflammatory bowel disease. Complications and mortality rate occurred in 1.8% and 1.9%, respectively. Conclusions: This single-center, large cohort analysis confirmed that CD presentation changed over the years, with an increase of non-classical and subclinical clinical phenotypes. [ABSTRACT FROM AUTHOR]

Severe gut motility disorders are characterized by the ineffective propulsion of intestinal contents. As a result, the patients develop disabling/distressful symptoms, such as nausea and vomiting along with altered bowel habits up to radiologically demonstrable intestinal sub-obstructive episodes. Chronic intestinal pseudo-obstruction (CIPO) is a typical clinical phenotype of severe gut dysmotility. This syndrome occurs due to changes altering the morpho-functional integrity of the intrinsic (enteric) innervation and extrinsic nerve supply (hence neuropathy), the interstitial cells of Cajal (ICC) (mesenchymopathy), and smooth muscle cells (myopathy). In the last years, several genes have been identified in different subsets of CIPO patients. The focus of this review is to cover the most recent update on enteric dysmotility related to CIPO, highlighting (a) forms with predominant underlying neuropathy, (b) forms with predominant myopathy, and (c) mitochondrial disorders with a clear gut dysfunction as part of their clinical phenotype. We will provide a thorough description of the genes that have been proven through recent evidence to cause neuro-(ICC)-myopathies leading to abnormal gut contractility patterns in CIPO. The discovery of susceptibility genes for this severe condition may pave the way for developing target therapies for enteric neuro-(ICC)-myopathies underlying CIPO and other forms of gut dysmotility.

Introduction: The accurate distinction between periprosthetic joint infections (PJI) and aseptic failures (AF) is of paramount importance due to differences in treatment. However, this could be challenging by using the current criteria. Various synovial fluid biomarkers are being assessed to improve the diagnostic accuracy. Myeloperoxidase (MPO), an enzyme contained in the granules of neutrophils, may be a promising biomarker for PJI. Methods: Synovial fluids of 99 patients (n = 65 PJI according to EBJIS criteria; n = 34 AF) were collected in two specialized orthopedic centers. PJI were divided into acute (n = 33) and low-grade (n = 32) according to previously published classification. An activity assay specific for active MPO was performed in each sample. Ability of MPO to correctly discriminate patients with PJI from AF was determined by ROC analysis. The best discriminating cut-off value was determined by calculating the J Youden index. For all analyses, a P value < 0.05 was considered statistically significant. Results: Active MPO was higher in PJI than AF (P < 0.0001). The ROC analysis revealed a significant area under the curve (AUC: 0.86; 95% CI: 0.78–0.93, P < 0.0001). A cut-off value of 561.9 U/mL, with good sensitivity (0.69) and specificity (0.88), discriminated between AF and PJI (accuracy 75.76%, 95% CI: 66.11–83.81%, positive likelihood ratio 5.88, 95% CI: 2.31–14.98 and negative likelihood ratio 0.35, 95%CI: 0.24–0.51). No difference in MPO levels was found between acute and chronic low-grade PJI. Conclusion: The proposed assay appears to be a reliable and affordable tool for detecting the active MPO in synovial fluid, with promising characteristics of sensitivity and specificity in discriminating both acute and low-grade PJI from AF. Further studies are needed to confirm MPO diagnostic cut-off values and validate their use in the routine clinical practice. [ABSTRACT FROM AUTHOR]

Sex and gender are fundamental health determinants and their role as modifiers of treatment response is increasingly recognized. Norepinephrine is a cornerstone of septic shock management and its use is based on the highest level of evidence compared to dopamine. The related 2021 Surviving Sepsis Campaign (SCC) recommendation is presumably applicable to both females and males; however, a sex- and gender-based analysis is lacking, thus not allowing generalizable conclusions. This paper was aimed at exploring whether sex- and gender-disaggregated data are available in the evidence supporting this recommendation. For all the studies underpinning it, four pairs of authors, including a woman and a man, extracted data concerning sex and gender, according to the Sex and Gender Equity in Research guidelines. Nine manuscripts were included with an overall population of 2126 patients, of which 43.2% were females. No sex analysis was performed and gender was never reported. In conclusion, the present manuscript highlighted that the clinical studies underlying the SCC recommendation of NE administration in septic shock have neglected the likely role of sex and gender as modifiers of treatment response, thus missing the opportunity of sex- and gender-specific guidelines. [ABSTRACT FROM AUTHOR]

The urban heat island (UHI) is an increasingly widespread phenomenon of concern to the wellbeing and the health of populations living in urban environments. The SUHI (Surface UHI) is directly related to UHI and influences its extension and intensity. Satellite images in the thermal infrared spectral region can be used to identify and study the SUHI. In this work, Landsat 8 TIR images were acquired to study the SUHI of a medium-sized municipality of the Po valley in the northern part of Italy. An additional Worldview 3 satellite image was used to classify the study area and retrieve the surface albedo of building roofs. Using the Local Climate Zone approach, existing roof materials were virtually replaced by solar reflective materials, and the mitigation potential of the SUHI and the UHI was quantified. This virtual scenario shows a decrease in the overheating of building roofs with respect to the ambient temperature of up to 33% compared to the current situation in the industrial areas. Focusing on UHI intensity, the air temperature decrease could be up to 0.5 °C.

Background Chronic constipation (CC) is a severe symptom in Parkinson's disease (PD), with an unclear pathogenesis. Abnormalities of the enteric nervous system (ENS) and/or intestinal epithelial barrier (IEB) may be pathophysiologically relevant in PD patients with CC. We investigated possible molecular changes of the IEB in PD/CCs compared with CCs and controls. Methods Twelve PD/CCs (2 female, age range 51-80 years), 20 CCs (15 female, age range 27-78 years), and 23 controls (11 female, age range 32-74 years) were enrolled. Ten PD/CCs and 10 CCs were functionally characterized by anorectal manometry (AM) and transit time (TT). Colon biopsies were obtained and assessed for gene and protein expression, and localization of IEB tight junction markers claudin-4 (CLDN4), occludin-1 (OCCL-1), and zonula occludens-1 (ZO-1) by RT-qPCR, immunoblot and immunofluorescence labeling. Results PD/CCs were clustered in 2 functional categories: patients with delayed TT and altered AM (60%), and a second group showing only modifications in AM pattern (40%). Gene expression of CLDN4, OCCL-1 and ZO-1 was higher in PD/CCs than controls (P<0.05). Conversely, PD/CCs showed a trend to decrease (P>0.05) in CLDN4 and OCCL-1 protein levels than controls, whereas ZO-1 protein was comparable. In PD/CCs compared with controls, decreasing tendency of vasoactive intestinal polypeptide mRNA, protein and immunoreactive fiber density were observed, although the difference was not statistically significant. Conclusion Transit and anorectal dysfunctions in PD/CCs are associated with difference in ZO-1, OCCL-1 and CLDN4 expression, thus supporting the role of an altered IEB as a contributory mechanism to possible neuronal abnormalities. [ABSTRACT FROM AUTHOR]

Cancer cells overexpress IF1, the endogenous protein that inhibits the hydrolytic activity of ATP synthase when mitochondrial membrane potential (ΔμH+) falls, as in ischemia. Other roles have been ascribed to IF1, but the associated molecular mechanisms are still under debate. We investigated the ability of IF1 to promote survival and proliferation in osteosarcoma and colon carcinoma cells exposed to conditions mimicking ischemia and reperfusion, as occurs in vivo, particularly in solid tumors. IF1-silenced and parental cells were exposed to the FCCP uncoupler to collapse ΔμH+ and the bioenergetics of cell models were validated. All the uncoupled cells preserved mitochondrial mass, but the implemented mechanisms differed in IF1-expressing and IF1-silenced cells. Indeed, the membrane potential collapse and the energy charge preservation allowed an increase in both mitophagy and mitochondrial biogenesis in IF1-expressing cells only. Interestingly, the presence of IF1 also conferred a proliferative advantage to cells highly dependent on oxidative phosphorylation when the uncoupler was washed out, mimicking cell re-oxygenation. Overall, our results indicate that IF1, by allowing energy preservation and promoting mitochondrial renewal, can favor proliferation of anoxic cells and tumor growth. Therefore, hindering the action of IF1 may be promising for the therapy of tumors that rely on oxidative phosphorylation for energy production. [ABSTRACT FROM AUTHOR]