Efficacy of texture and color enhancement imaging for the visibility and diagnostic accuracy of non-polypoid colorectal lesions.

Objective: A newly launched endoscopy system (EVIS X1, CV-1500; Olympus) is equipped with texture and color enhancement imaging (TXI). We aimed to investigate the efficacy of TXI for the visibility and diagnostic accuracy of non-polypoid colorectal lesions. Methods: We examined 100 non-polypoid lesions in 42 patients from the same position, angle, and distance of the view in three modes: white light imaging (WLI), narrow-band imaging (NBI), and TXI. The primary outcome was to compare polyp visibility in the three modes using subjective polyp visibility score and objective color difference values. The secondary outcome was to compare the diagnostic accuracy without magnification. Results: Overall, the visibility score of TXI was significantly higher than that of WLI (3.7 ± 1.1 vs. 3.6 ± 1.1; p = 0.008) and lower than that of NBI (3.7 ± 1.1 vs. 3.8 ± 1.1; p = 0.013). Color difference values of TXI were higher than those of WLI (11.5 ± 6.9 vs. 9.1 ± 5.4; p < 0.001) and lower than those of NBI (11.5 ± 6.9 vs. 13.1 ± 7.7; p = 0.002). No significant differences in TXI and NBI (visibility score: 3.7 ± 1.0 vs. 3.8 ± 1.1; p = 0.833, color difference values: 11.6 ± 7.1 vs. 12.9 ± 8.3; p = 0.099) were observed for neoplastic lesions. Moreover, the diagnostic accuracy of TXI was significantly higher than that of NBI (65.5% vs. 57.6%, p = 0.012) for neoplastic lesions. Conclusions: TXI demonstrated higher visibility than that of WLI and lower than that of NBI. Further investigations are warranted to validate the performance of the TXI mode comprehensively.

BSE risk posed by ruminant collagen and gelatine derived from bones.

The European Commission requested an estimation of the BSE risk (C-, L- and H-BSE) from gelatine and collagen derived from ovine, caprine or bovine bones, and produced in accordance with Regulation (EC) No 853/2004, or Regulation (EC) No 1069/2009 and its implementing Regulation (EU) No 142/2011. A quantitative risk assessment was developed to estimate the BSE infectivity, measured in cattle oral infectious dose 50 (CoID50), in a small size batch of gelatine including one BSE-infected bovine or ovine animal at the clinical stage. The model was built on a scenario where all ruminant bones could be used for the production of gelatine and high-infectivity tissues remained attached to the skull (brain) and vertebral column (spinal cord). The risk and exposure pathways defined for humans and animals, respectively, were identified. Exposure routes other than oral via food and feed were considered and discussed but not assessed quantitatively. Other aspects were also considered as integrating evidence, like the epidemiological situation of the disease, the species barrier, the susceptibility of species to BSE and the assumption of an exponential dose-response relationship to determine the probability of BSE infection in ruminants. Exposure to infectivity in humans cannot be directly translated to risk of disease because the transmission barrier has not yet been quantified, although it is considered to be substantial, i.e. much greater amounts of infectivity would be needed to successfully infect a human and greater in the oral than in the parenteral route of exposure. The probability that no new case of BSE in the cattle or small ruminant population would be generated through oral exposure to gelatine made of ruminant bones is 99%-100% (almost certain) This conclusion is based on the current state of knowledge, the epidemiological situation of the disease and the current practices, and is also valid for collagen.

The effect of adding protein to a carbohydrate meal on postprandial glucose and insulin responses: a systematic review and meta-analysis of acute controlled feeding trials.

BACKGROUND: protein influences acute postprandial-glucose and -insulin responses but the effects of dose, protein-type and health-status are unknown. OBJECTIVE: to determine the acute effect of adding protein to carbohydrate on postprandial responses and identify effect modifiers. METHODS: we searched MEDLINE, EMBASE and Cochrane databases through 30 July 2023 for acute, crossover trials comparing acute postprandial-responses elicited by carbohydrate-containing test-meals with vs without added protein in adults without-diabetes or with type-2 (T2DM) or type-1 (T1DM) diabetes. Group data were pooled separately using generic inverse-variance with random-effects models and expressed as ratio-of-means with [95% CIs]. Risk-of-bias and certainty-of-evidence (GRADE) were assessed. RESULTS: in 154 trial-comparisons of animal-, dairy- and plant-proteins (without-diabetes, n=22,67,32; T2DM, n=14,16,3), each gram-protein/gram-carbohydrate (g/g) reduced glucose-area-under-the-curve (AUC) less in T2DM than in those without-diabetes (-10% vs -50%, P<0.05) but increased insulin-AUC similarly (+76 vs +56%, respectively). In subjects without-diabetes, each g/g of dairy- and plant-proteins reduced glucose-AUC by 52 and 55% and increased insulin-AUC by 64 and 45% (all P<0.05). Animal-proteins significantly reduced glucose-AUC by 31% and increased insulin-AUC by 37% (pooled effects), but without a significant dose-response. In T2DM animal-protein reduced glucose-AUC by 13% and increased insulin-AUC by 105%, with no significant dose-response. Dairy-protein reduced glucose-AUC by 18% (no dose-response), but each g/g increased insulin-AUC by 34% (P<0.05). In T1DM protein increased glucose-AUC by 40% (P<0.05, n=5). Data-source (reported vs calculated) and study-methodology-quality significantly modified some outcomes and contributed to high between-study heterogeneity. CONCLUSIONS: in people without-diabetes, adding dairy- or plant-protein to a carbohydrate-containing meal elicits physiologically significant reductions in glucose-AUC and increases insulin-AUC. Animal-protein may slightly reduce glucose-AUC and may increase insulin-AUC. In T2DM, protein may not have such large and consistent effects. Further research is needed to determine if the effects of protein differ by health status and protein-source. REGISTRATION: PROSPERO CRD42022322090. FUNDING: General Mills.

Morphometric Characteristics and Species Identification of Bed Bugs (Hemiptera: Cimicidae) in Eastern Iran.

Background: The common bed bugs, Cimex lectularius, and tropical bed bugs, Cimex hemipterus are the primary species of public health importance in the family Cimicidae. This study aimed to determine the morphometric criteria and prevalent species of bed bugs in eastern Iran. Methods: Bed bugs were collected from March 2021 to June 2022 from infested residential buildings and apartments in eastern Iran, including North Khorasan, Khorasan Razavi, and Sistan and Baluchistan Provinces. The morphological and morphometrical characteristics were used to identify collected bed bugs at inter- and intra-specific levels. Results: A total of 34 isolates comprising 127 adult bed bugs were collected from Bojnord, Mashhad, Neishabur, Taibad, Sabzevar, Kashmer, Zahedan, Saravan, Rask, Pishin and Chabahar. Of these, 33 isolates (n=124) were found to be tropical bed bugs, C. hemipterus, and one population (n=3) was identified as C. lectularius. The index pronotal width/length ratio was calculated from 2.72 to 2.94 and 1.98 to 2.47 for C. lectularius and C. hemipterus, respectively. The length/width ratio of the hind femur was 3.365 in C. hemipterus and 4.267 in C. lectularius. The ratio of length/width of the third femur (F3 l/w) between populations of C. hemipterus was different, and this difference was statistically significant (P< 0.05). Conclusion: The results of this study indicated that C. hemipterus was the dominant bed bug species in the east of Iran and provided more morphometric criteria of C. hemipterus for researchers to identify the species and determine the intraspecific variations in the present and future.

A most aggressive bear: Safari videos document sloth bear defense against tiger predation.

Sloth bears are non-carnivorous yet they attack more people than any other bear. They often stand up and charge explosively if a person mistakenly gets too close. Here, we argue that their aggression toward humans is an extension of their behavior toward tigers, which are their only natural predator. Interactions between sloth bears and tigers have not previously been studied because scientists have rarely observed such events. We collected and examined 43 videos or photo documentations of sloth bear-tiger interactions posted on the internet or social media from 2011 to 2023, mainly by tourists visiting tiger parks in India. We observed that sloth bears were most likely to stand up and charge if they first became aware of the tiger at close range (<3 m away). This aggressive-defensive strategy, intended to dissuade the tiger from attacking, appeared to be successful, in that 86% of interactions ended with no contact, whereas four (9%) culminated in the bear's death. We propose that a myrmecophagous diet led to this species' aggressive behavior: (1) their long, blunt front claws, well adapted for digging termites and ants, hamper their ability to climb trees for escape, and (2) they walk with their head down focused on scents underground, and make considerable noise digging and blowing soil, enabling tigers to approach quite closely without being detected. Sloth bears have coexisted with tigers or other (now extinct) large felid predators for their entire evolutionary history. Whereas their aggressive behavior has served them well for millions of years, more recently, people's fear of and retaliation against sloth bears represents a major threat to their survival. Understanding how sloth bears react to tigers provides guidance for reducing attacks on humans, thereby contributing to sloth bear conservation. Our investigation was made possible by passive citizen scientists, who unknowingly collected valuable data.

Indomethacin Does Not Reduce Post-ERCP Pancreatitis in High-Risk Patients Receiving Pancreatic Stenting.

BACKGROUND: Rectal indomethacin reduces pancreatitis following endoscopic retrograde cholangiopancreatography (ERCP). However, there is insufficient evidence regarding its added benefits in patients already receiving prophylactic pancreatic stenting. Our goal was to evaluate the impact of indomethacin in high-risk patients undergoing pancreatic stenting. METHODS: A cohort study was conducted on all patients who underwent the rescue cannulation technique for challenging bile duct cannulation (selected high-risk patients). Patients were split into two groups based on the prophylaxis method for post-ERCP pancreatitis (PEP): one receiving a combination of indomethacin and pancreatic stenting, while the other received pancreatic stenting alone. Comparative analyses were carried out on PEP, hyperamylasemia, gastrointestinal bleeding, and postoperative hospital stay among post-ERCP pancreatitis patients. RESULTS: Between November 2017 and May 2023, a total of 607 patients with native papillae were enrolled, with 140 grouped into the indomethacin plus stent group and 467 into the stent alone group. The overall PEP rate was 4.4% in the entire cohort, with no statistical differences observed between the groups in terms of PEP rates (P = 0.407), mild PEP (P = 0.340), moderate to severe PEP (P = 1.000), hyperamylasemia (P = 0.543), gastrointestinal bleeding (P = 0.392), and postoperative hospital stay (P = 0.521). Furthermore, sensitivity analysis using multivariable analysis also validated these findings. CONCLUSIONS: Indomethacin did not reduce the incidence or severity of PEP in high-risk patients who routinely received prophylactic pancreatic stent placement. Therefore, the additional administration of rectal indomethacin to further mitigate PEP appears to be not necessary.

Effect of Nitrate Supplementation on Oxygen Saturation Levels for Acute Mountain Sickness Prevention: A Systematic Review and Meta-Analysis.

PURPOSE: This study aimed to systematically review the effect of nitrate supplementation on blood oxygen saturation. METHODS: We searched PubMed, Scopus, and Cochrane Library databases from their inception up to October 2022. Two reviewers independently conducted two stages of the screening process to include a randomized controlled trial with nitrate supplementation versus placebo intervention assessing oxygen saturation among lowlanders going to either real or simulated high altitude environments. We used the Cochrane Risk of Bias 2.0 tool to assess the risk of bias in the included studies. Fixed-effect model meta-analyses were conducted for laboratory-based studies. Random-effect meta-analyses were conducted for real-world studies. RESULTS: We found 7 trials that met the eligibility criteria. A meta-analysis of studies with some bias concerns showed an increase of 1.26% in the SpO2 with 44% I2 during submaximal exercise at simulated high altitudes (GRADE: low). On the contrary, a meta-analysis of studies without heterogeneity showed that nitrate supplementation aggravated oxygen saturation decline (-2.64%, p=0.03, GRADE: high) during rest in real high-altitude environments. A meta-analysis also showed that nitrate supplementation did not affect Acute Mountain Sickness (AMS) symptoms (GRADE: high). CONCLUSION: Our results suggest that nitrate supplementation did not provide benefits for AMS prevention during rest at high altitudes. The low-quality evidence showing small beneficial effects of nitrate supplementation during exercise calls for further studies.

Effectiveness of digital health interventions for telemedicine/telehealth for managing blood pressure in adults: a systematic review and meta-analysis.

This systematic review and meta-analysis included randomized controlled trials or observational studies that compare digital health interventions (DHIs) for telemedicine/telehealth versus usual care for managing blood pressure (BP) in adults. We searched PubMed, Cochrane CENTRAL, and IchuShi-Web, and used a random-effects meta-analysis of the weighted mean difference (MD) between the comparison groups to pool data from the included studies. The outcome included the pooled MD of office BP from baseline to each follow-up period. This meta-analysis considered 117 studies with 68677 participants as eligible. The 3-month intervention period reduced office systolic BP (SBP) compared with usual care in 38 studies (MD: -3.21 mmHg [95% confidence interval: -4.51 to -1.90]), with evidence of heterogeneity. Office SBP across intervention periods demonstrated comparable effects (3-, 6- [54 studies], 12- [43 studies], and >12-month periods [9 studies]). The benefits for office diastolic BP were similar to those for office SBP. Additionally, the interventions significantly reduced the office SBP compared with the control, regardless of the mode of intervention delivery (smartphone apps [38 studies], text messages [35 studies], and websites [34 studies]) or type of facility (medical [74 studies] vs. non-medical [33 studies]). The interventions were more effective in 41 hypertension cohorts compared with 66 non-hypertension cohorts (-4.81 mmHg [-6.33, -3.29] vs. -2.17 mmHg [-3.15, -1.19], P = 0.006 for heterogeneity). In conclusion, DHIs for telemedicine/telehealth improved BP management compared with usual care. The effectiveness with heterogeneity should be considered, as prudent for implementing evidence-based medicine. This meta-analysis considered 117 studies with 68677 participants eligible. The DHIs for telemedicine/telehealth reduced office BP compared with usual care, regardless of intervention duration, intervention delivery mode, facility type, and cohort type. Additionally, the DHIs reduced the risk of uncontrolled BP compared with usual care, regardless of intervention duration, intervention delivery mode, and facility type. BP blood pressure, DHI digital health intervention, MD mean difference, RR risk ratio, SBP systolic blood pressure.

Childhood PFAS exposure and immunotoxicity: a systematic review and meta-analysis of human studies.

BACKGROUND: Exposure to poly- and perfluoroalkyl substances (PFAS) may affect infant and childhood health through immunosuppression. However, the findings of epidemiological literature examining relationships between prenatal/childhood PFAS exposure and vaccine response and infection in humans are still inconclusive. The aim of this review was to examine the effects of PFAS exposure on vaccine antibody response and infection in humans. METHODS: The MEDLINE/Pubmed database was searched for publications until 1 February 2023 to identify human studies on PFAS exposure and human health. Eligible for inclusion studies had to have an epidemiological study design and must have performed logistic regression analyses of gestational or childhood exposure to PFAS against either antibody levels for pediatric vaccines or the occurrence of children's infectious diseases. Information on baseline exposure to PFAS (in ng/mL), the age of PFAS exposure (gestational or in years), and the outcome was measured, potentially leading to multiple exposure-outcome comparisons within each study was collected. Percentage change and standard errors of antibody titers and occurrence of infectious diseases per doubling of PFAS exposure were calculated, and a quality assessment of each study was performed. RESULTS: Seventeen articles were identified matching the inclusion criteria and were included in the meta-analysis. In general, a small decrease in antibody response and some associations between PFAS exposure and childhood infections were observed. CONCLUSIONS: This meta-analysis summarizes the findings of PFAS effects on infant and childhood immune health. The immunosuppression findings for infections yielded suggestive evidence related to PFAS exposure, particularly PFOS, PFOA, PFHxS, and PFNA but moderate to no evidence regarding antibody titer reduction. SYSTEMATIC REVIEW REGISTRATION: The research protocol of this systematic review is registered and accessible at the Open Science Framework ( https://doi.org/10.17605/OSF.IO/5M2VU ).

Systematic review: Global host range, case fatality and detection rates of Mycobacterium ulcerans in humans and potential environmental sources.

Fundamental aspects of the epidemiology and ecology of Mycobacterium ulcerans (MU) infections including disease burden, host range, reservoir, intermediate hosts, vector and mode of transmission are poorly understood. Understanding the global distribution and burden of MU infections is a paramount to fight against Buruli ulcer (BU). Four databases were queried from inception through December 2023. After critical review of published resources on BU, 155 articles (645 records) published between 1987 and 2023 from 16 countries were selected for this review. Investigating BU in from old endemic and new emerging foci has allowed detection of MU in humans, animals, plants and various environmental samples with prevalence from 0 % up to 100 % depending of the study design. A case fatality rate between 0.0 % and 50 % was described from BU patients and deaths occurred in Central African Republic, Gabon, Democratic Republic of the Congo, Burkina Faso and Australia. The prevalence of MU in humans was higher in Africa. Nucleic Acid Amplification Tests (NAAT) and non-NAAT were performed in > 38 animal species. MU has been recovered in culture from possum faeces, aquatic bugs and koala. More than 7 plant species and several environmental samples have been tested positive for MU. This review provided a comprehensive set of data on the updates of geographic distribution, the burden of MU infections in humans, and the host range of MU in non-human organisms. Although MU have been found in a wide range of environmental samples, only few of these have revealed the viability of the mycobacterium and the replicative non-human reservoirs of MU remain to be explored. These findings should serve as a foundation for further research on the reservoirs, intermediate hosts and transmission routes of MU.

Molecular Detection of Tick-Borne Pathogens in Kumasi: With a First Report of Zoonotic Pathogens in Abattoir Workers.

Tick-borne pathogens continue to infect humans and animals worldwide. By adapting to the movement of livestock, ticks facilitate the spread of these infectious pathogens. Humans in close contact with animals that could be amplifying hosts are especially at risk of being infected with tick-borne pathogens. This study involved the collection of dry blood spots (DBSs) to determine tick-borne pathogens occurring in slaughtered livestock and abattoir workers in Kumasi. This study employed the use of conventional PCR, RT-PCR, and Sanger sequencing to detect and identify the tick-borne pathogens. The resulting data was analysed using Stata version 13. A total of 175 DBSs were collected from goats (76), cattle (54), and sheep (45) in the Kumasi abattoir (130, 74.29%) and Akwatia Line slaughter slab (45, 25.71%). The pathogens identified were mostly bacterial including Anaplasma capra (9.71%), Anaplasma phagocytophilum (1.14%), and Rickettsia aeschlimannii (0.57.%). The only parasite identified was Theileria ovis (9.14%). A significant association was seen between A. capra (p < 0.001) infection and female sheep sampled from the Akwatia Line slaughter slab. Again, there was a significant association between T. ovis (p < 0.001) infections and female sheep from the Kumasi abattoir. From the human DBS (63) screened, the pathogens identified were all bacterial including Coxiella burnetii (1.89%), Rickettsia africae (1.89%), and R. aeschlimannii (1.89%). This study reports the first detection of R. aeschlimannii in livestock as well as the occurrence of the above-mentioned pathogens in humans in Ghana. Animals can serve as amplifying hosts for infectious pathogens; hence, there is an increased risk of infections among the abattoir workers. Continuous surveillance effort is essential, and abattoir workers need to protect themselves from tick bites and infectious tick-borne pathogens.

Fundamental dermatology education of medical doctors at a regional hospital in Johannesburg, South Africa.

Introduction: dermatology is a prevalent field of global health and dermatological conditions are amongst the most frequent complaints affecting communities, yet dermatology has become an overlooked aspect of the medical school curricula and many medical schools have failed to provide doctors with training to manage these conditions confidently and adequately. This study aimed to determine the baseline dermatological knowledge of medical doctors and determine the influence of fundamental dermatology education on hospital medical staff at a regional hospital in Johannesburg, South Africa. Methods: the knowledge and confidence of 33 medical doctors were tested using a pre-test and post-test quasi-experimental design. Participants completed an online questionnaire followed by an image-based test consisting of 20 questions to determine their level of confidence in diagnosing and managing common dermatological conditions. The participants then attended a sixty-minute educational session based on common dermatological conditions. Following this, their level of confidence and knowledge on the subject was re-assessed using the same online test. Pre and post-intervention confidence and test scores were compared. Results: the pre-intervention test mean score was 67.11%. The post-intervention mean score was 92.50%. The difference between means (post-intervention - pre-intervention) ± SEM was 25.39 ± 4.81. The intervention significantly improved overall test scores (p-value < 0.0001). Many participants felt that their undergraduate training was insufficient in preparing them for the management of common dermatological conditions. Conclusion: the baseline knowledge and confidence of medical doctors in managing common dermatological conditions was poor and such educational interventions have significant value in improving the ability of medical doctors in managing common dermatological conditions. More time should be dedicated to dermatology training at an undergraduate level.

Avian influenza overview March-June 2024.

Between 16 March and 14 June 2024, 42 highly pathogenic avian influenza (HPAI) A(H5) virus detections were reported in domestic (15) and wild (27) birds across 13 countries in Europe. Although the overall number of detections in Europe has not been this low since the 2019-2020 epidemiological year, HPAI viruses continue to circulate at a very low level. Most detections in poultry were due to indirect contact with wild birds, but there was also secondary spread. Outside Europe, the HPAI situation intensified particularly in the USA, where a new A(H5N1) virus genotype (B3.13) has been identified in >130 dairy herds in 12 states. Infection in cattle appears to be centred on the udder, with milk from infected animals showing high viral loads and representing a new vehicle of transmission. Apart from cattle, HPAI viruses were identified in two other mammal species (alpaca and walrus) for the first time. Between 13 March and 20 June 2024, 14 new human cases with avian influenza virus infection were reported from Vietnam (one A(H5N1), one A(H9N2)), Australia (with travel history to India, one A(H5N1)), USA (three A(H5N1)), China (two A(H5N6), three A(H9N2), one A(H10N3)), India (one A(H9N2)), and Mexico (one fatal A(H5N2) case). The latter case was the first laboratory-confirmed human infection with avian influenza virus subtype A(H5N2). Most of the human cases had reported exposure to poultry, live poultry markets, or dairy cattle prior to avian influenza virus detection or onset of illness. Human infections with avian influenza viruses remain rare and no human-to-human transmission has been observed. The risk of infection with currently circulating avian A(H5) influenza viruses of clade 2.3.4.4b in Europe remains low for the general public in the EU/EEA. The risk of infection remains low-to-moderate for those occupationally or otherwise exposed to infected animals or contaminated environments.

Interhospital Transfer for Endovascular Stroke Treatment in Canada: Results From the OPTIMISE Registry.

BACKGROUND: Interhospital transfer for patients with stroke due to large vessel occlusion for endovascular thrombectomy (EVT) has been associated with treatment delays. METHODS: We analyzed data from Optimizing Patient Treatment in Major Ischemic Stroke With EVT, a quality improvement registry to support EVT implementation in Canada. We assessed for unadjusted differences in baseline characteristics, time metrics, and procedural outcomes between patients with large vessel occlusion transferred for EVT and those directly admitted to an EVT-capable center. RESULTS: Between January 1, 2018, and December 31, 2021, a total of 6803 patients received EVT at 20 participating centers (median age, 73 years; 50% women; and 50% treated with intravenous thrombolysis). Patients transferred for EVT (n=3376) had lower rates of M2 occlusion (22% versus 27%) and higher rates of basilar occlusion (9% versus 5%) compared with those patients presenting directly at an EVT-capable center (n=3373). Door-to-needle times were shorter in patients receiving intravenous thrombolysis before transfer compared with those presenting directly to an EVT center (32 versus 36 minutes). Patients transferred for EVT had shorter door-to-arterial access times (37 versus 87 minutes) but longer last seen normal-to-arterial access times (322 versus 181 minutes) compared with those presenting directly to an EVT-capable center. No differences in arterial access-to-reperfusion times, successful reperfusion rates (85% versus 86%), or adverse periprocedural events were found between the 2 groups. Patients transferred to EVT centers had a similar likelihood for good functional outcome (modified Rankin Scale score, 0-2; 41% versus 43%; risk ratio, 0.95 [95% CI, 0.88-1.01]; adjusted risk ratio, 0.98 [95% CI, 0.91-1.05]) and a higher risk for all-cause mortality at 90 days (29% versus 25%; risk ratio, 1.15 [95% CI, 1.05-1.27]; adjusted risk ratio, 1.14 [95% CI, 1.03-1.28]) compared with patients presenting directly to an EVT center. CONCLUSIONS: Patients transferred for EVT experience significant delays from the time they were last seen normal to the initiation of EVT.

Effects of Oral Butyrate on Blood Pressure in Patients With Hypertension: A Randomized, Placebo-Controlled Trial.

BACKGROUND: The microbiota-derived short chain fatty acid butyrate has been shown to lower blood pressure (BP) in rodent studies. Nonetheless, the net effect of butyrate on hypertension in humans remains uncovered. In this study, for the first time, we aimed to determine the effect of oral butyrate on BP in patients with hypertension. METHODS: We performed a double-blind randomized placebo-controlled trial including 23 patients with hypertension. Antihypertensive medication was discontinued for the duration of the study with a washout period of 4 weeks before starting the intervention. Participants received daily oral capsules containing either sodium butyrate or placebo with an equivalent dosage of sodium chloride for 4 weeks. The primary outcome was daytime 24-hour systolic BP. Differences between groups over time were assessed using linear mixed models (group-by-time interaction). RESULTS: Study participants (59.0±3.7 years; 56.5% female) had an average baseline office systolic BP of 143.5±14.6 mm Hg and diastolic BP of 93.0±8.3 mm Hg. Daytime 24-hour systolic and diastolic BP significantly increased over the intervention period in the butyrate compared with the placebo group, with an increase of +9.63 (95% CI, 2.02-17.20) mm Hg in daytime 24-hour systolic BP and +5.08 (95% CI, 1.34-8.78) mm Hg in diastolic BP over 4 weeks. Butyrate levels significantly increased in plasma, but not in feces, upon butyrate intake, underscoring its absorption. CONCLUSIONS: Four-week treatment with oral butyrate increased daytime systolic and diastolic BP in subjects with hypertension. Our findings implicate that butyrate does not have beneficial effects on human hypertension, which warrants caution in future butyrate intervention studies. REGISTRATION: URL: https://clinicaltrialregister.nl/nl/trial/22936; Unique identifier: NL8924.

Novel Role of 5-Methyl-(6S)-Tetrahydrofolate in Mediating Endothelial Cell Tetrahydrobiopterin in Pregnancy and Implications for Gestational Hypertension.

BACKGROUND: Folate intake during pregnancy is essential for fetal development and maternal health. However, the specific effects of folic acid (FA) and 5-methyl-(6S)-tetrahydrofolate (5-MTHF) on the prevention and treatment of hypertensive disorders of pregnancy remain unclear. We investigated whether FA and 5-MTHF have different effects on endothelial cell tetrahydrobiopterin (BH4) metabolism in pregnancy and the possible consequences for endothelial NO generation, maternal blood pressure, and fetal growth. METHODS: We analyzed the maternal blood pressure in pregnant wild-type (Gch1fl/fl) and Gch1fl/fl Tie2cre mice treated with either FA or 5-MTHF starting before pregnancy, mid-pregnancy or late pregnancy. BH4, superoxide, and NO bioavailability were determined in mouse and human models of endothelial cell BH4 deficiency by high-performance liquid chromatography. RESULTS: In vitro studies in mouse and human endothelial cells showed that treatment with 5-MTHF, but not FA, elevated BH4 levels, reduced superoxide production, and increased NO synthase activity. In primary endothelial cells isolated from women with hypertensive pregnancies, exposure to 5-MTHF, but not FA, restored the reduction in BH4 levels and NO synthase activity. In vivo studies in mice revealed that oral treatment with 5-MTHF, but not FA, prevented and treated hypertension in pregnancy when administered either before or during pregnancy, respectively, and normalized placental and fetal growth restriction if administered from mid-gestation onward. CONCLUSIONS: Collectively, these studies identify a critical role for 5-MTHF in endothelial cell function in pregnancy, related to endothelial cell BH4 availability and NO synthase activity. Thus, 5-MTHF represents a novel therapeutic agent that may potentially improve endothelial function in hypertensive disorders of pregnancy by targeting endothelial cell BH4.

Selective enzymatic debridement and modified Meek technique in the treatment of extensive burns: Preliminary observations.

Background: Selective bromelain-based enzymatic debridement (BED) has emerged as a valid alternative for the treatment of extensive burns, with Total Body Surface Area (TBSA) > 20%. Autologous skin grafting represents the procedure of choice but the scarcity of donor sites remains the main reconstructive challenge. The modified Meek micro-grafting technique may represent a valid strategy to optimize the final outcome. Methods: A single-cohort retrospective analysis was performed, involving nine burn patients (TBSA > 20%) who underwent both BED and subsequently modified Meek technique. Demographic and clinical data (mechanism of injury, surgical treatment, complications, necessity of re-grafting, further surgery and esthetic outcome) were collected. Results: All patients had large burns of mixed and deep dermal thickness (first, second, and third degree). All burns were enzymatically debrided postadmission and covered by the modified Meek technique. Local infection due to poor general conditions was the main complication for all patients. All but two patients survived. The selectiveness of the enzymatic debridement and dermal preservation seemed to improve the quality of scars resulting from micro-grafting. Evaluations performed at 12 ± 2 months postburn showed superior scar quality compared to areas treated with traditional (sheet/mesh) grafts. Conclusion: Combined BED and Meek techniques may provide an effective synergic combination for the treatment of extensive burns.

Effects of Lacticaseibacillus rhamnosus HA-114 probiotic supplementation on circulating IGFBP-2 levels during a calorie-restricted diet in overweight humans.

Background and aim: Gut microbiota influences energy homeostasis in part through circulating hormones. Insulin-like growth factor-binding protein (IGFBP)-2 is a biomarker whose increase in systemic circulation is associated with positive effects on body weight and metabolism. In a recent clinical trial, probiotic Lacticaseibacillus rhamnosus HA-114 supplementation showed positive effects on eating behaviors and insulin resistance in overweight participants undergoing a weight-loss intervention. In this context, this ancillary study aimed at assessing the impact of L. rhamnosus HA-114 supplementation on plasma IGFBP-2 levels in these individuals, and whether this modulation correlated with changes in fat mass, energy metabolism, and eating behaviors. Methods: Fasting plasma IGFBP-2 concentrations were quantified in 100 overweight or obese men and women enrolled in a 12-week diet-based weight reduction program (-500 kcal/day), in combination with probiotic L. rhamnosus HA-114 or placebo supplementation. Baseline and changes in circulating IGFBP-2 concentrations were correlated with anthropometric parameter, glucose and lipid metabolism, cardiorespiratory function and eating behaviors. Results: On average, the intervention reduced BMI by 4.6 % and increased IGFBP-2 by 13 %, regardless of supplementation group. Individuals who presented an increase in IGFBP-2 levels had significantly greater reductions in BMI. Changes in IGFBP-2 levels were correlated with loss in fat mass (r = 0.2, p < 0.001) in the probiotic-supplemented group, but not with other metabolic parameters or eating behaviors. Baseline IGFBP-2 levels were not associated with weight loss or improvements in cardiometabolic parameters. Conclusion: Probiotic supplementation with L. rhamnosus HA-114 did not modulate plasma IGFBP-2 levels. Changes in IGFBP-2 levels were correlated with greater reductions in BMI, but not with other metabolic parameters or eating behaviors, indicating that the benefits of HA-114 on eating behaviors are likely independent of IGFBP-2. Additional changes in microbiota might be required to modulate IGFBP-2 and observe its associations with eating behaviors and cardiometabolic improvements.

Handedness in Animals and Plants.

Structural and functional asymmetries are traceable in every form of life, and some lateralities are homologous. Functionally speaking, the division of labour between the two halves of the brain is a basic characteristic of the nervous system that arose even before the appearance of vertebrates. The most well-known expression of this specialisation in humans is hand dominance, also known as handedness. Even if hand/limb/paw dominance is far more commonly associated with the presence of a nervous system, it is also observed in its own form in aneural organisms, such as plants. To date, little is known regarding the possible functional significance of this dominance in plants, and many questions remain open (among them, whether it reflects a generalised behavioural asymmetry). Here, we propose a comparative approach to the study of handedness, including plants, by taking advantage of the experimental models and paradigms already used to study laterality in humans and various animal species. By taking this approach, we aim to enrich our knowledge of the concept of handedness across natural kingdoms.