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Background: Some of those infected with SARS-CoV-2 suffer from post-COVID syndrome (PCS). However, an uniform definition of PCS is lacking, causing uncertainty about the prevalence and nature of this syndrome. We aimed to improve understanding of PCS by operationalizing different classifications and to explore clinical subtypes., Methods: We used data from Nivel Primary Care database from 2019-2020 which consists of electronic health records (EHR) from general practices (GPs) combined with sociodemographic data for n = 10,313 individuals infected with the SARS-CoV-2. In addition, data from n = 276 individuals who had been infected with the SARS-CoV-2 in 2021, collected via a longitudinal survey, was used. In the GP-EHR data, we operationalized two classifications of PCS (based on symptoms and diagnosis recorded in GP-EHR data and healthcare utilization 3-12 months after acute infection) to calculate frequency and characteristics and compared this to the survey results. In a subgroup of the EHR data we conducted community detection analyses to explore clinical subtypes of PCS., Results: The frequency of PCS was 15% with on average 4.6 symptoms for which the GP was consulted using the narrow definition and 32% with on average 6.8 symptoms for the broad definition. Across all methods and classifications, the mean age of individuals with PCS was around 53 years and they were more often female. There were small sex differences in the type of symptoms and overall symptoms were persistent for 6 months. The community detection analysis revealed three possible clinical subtypes., Discussion: We showed that frequency rates of PCS differ between methods and data sources, but characteristics of the affected individuals are relatively stable. Overall, PCS is a heterogeneous syndrome affecting a substantial group of individuals who need adequate care. Future studies should focus on care trajectories and qualitative measures such as quality of life of individuals living with PCS., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2025 Bos et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Mycoplasmosis is of concern for chelonian conservation. We detected a Mycoplasma sp. in confiscated radiated tortoises (Astrochelys radiata) and spider tortoises (Pyxis arachnoides). Sequence analysis of the 16S-23S ribosomal RNA intergenic spacer region was consistent with Mycoplasma agassizii. Mycoplasma spp. have not been previously reported in native tortoises in Madagascar., (© Wildlife Disease Association 2025.)

The BOOST-2 trial indicated that optimising brain oxygen (PbtO2) could be a viable therapeutic target for severe traumatic brain injury (sTBI). Previous studies have suggested the safety of airway pressure release ventilation (APRV) in sTBI patients, but its effect on PbtO2 has not been demonstrated. This study is aimed to show that APRV can improve PbtO2 in sTBI patients. In a retrospective case series, two sTBI patients with controlled intracranial pressures developed refractory hypoxemia and brain hypoxia, unresponsive to traditional therapies. Treated with APRV, both patients showed improved hypoxemia and increased PbtO2 levels above 20 mm Hg without adverse effects on intracranial pressure. They recovered from hypoxemia, transitioned to assist-controlled ventilation and were discharged to rehabilitation. These cases suggest that APRV can safely and effectively improve PbtO2 in sTBI patients when other treatments fail, warranting further exploration pending results from the ongoing BOOST-3 trial., Competing Interests: Competing interests: None declared., (© BMJ Publishing Group Limited 2024. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Hybrids are expected to show greater phenotypic variation than their parental species, yet how hybrid phenotype expression varies with genetic distances in closely-related parental species remains surprisingly understudied. Here, we investigate pelage and morphometric trait variation in anthropogenic hybrids between four species of Brazilian Callithrix marmosets, a relatively recent primate radiation. Marmoset species are distinguishable by pelage phenotype and morphological specializations for eating tree exudates. In this work, we (1) describe qualitative phenotypic pelage differences between parental species and hybrids; (2) test whether significant quantitative differences exist between parental and hybrid morphometric phenotypes; and (3) determine which hybrid morphometic traits show heterosis, dysgenesis, trangression, or intermediacy relative to the parental trait. We investigated cranial and post-cranial morphometric traits, as most hybrid morphological studies focus on the former instead of the latter. Finally, we estimate mitogenomic distances between marmoset species from previously published data., Results: Marmoset hybrid facial and overall body pelage variation reflected novel combinations of coloration and patterns present in parental species. In morphometric traits, C. jacchus and C. penicillata were the most similar, while C. aurita was the most distinct, and C. geoffroyi trait measures fell between these species. Only three traits in C. jacchus x C. penicillata hybrids showed heterosis. We observed heterosis and dysgenesis in several traits of C. penicillata x C. geoffroyi hybrids. Transgressive segregation was observed in hybrids of C. aurita and the other species. These hybrids were also C. aurita-like for a number of traits, including body length. Genetic distance was closest between C. jacchus and C. penicillata and farthest between C. aurita and the other species., Conclusion: We attributed significant morphometric differences between marmoset species to variable levels of morphological specialization for exudivory in these species. Our results suggest that intermediate or parental species-like hybrid traits relative to the parental trait values are more likely in crosses between species with relatively lesser genetic distance. More extreme phenotypic variation is more likely in parental species with greater genetic distance, with transgressive traits appearing in hybrids of the most genetically distant parental species. We further suggest that fewer developmental disturbances can be expected in hybrids of more recently diverged parental species, and that future studies of hybrid phenotypic variation should investigate selective pressures on Callithrix cranial and post-cranial morphological traits., (© 2024. The Author(s).)

Purpose: Body image affects health practices. With acculturation superimposed on globalization, 21st century body size preferences of African immigrants, one of the fasting growing populations in the United States, are unknown. Therefore, in African immigrants living in America we assessed: 1) body size preference; and 2) body size dissatisfaction., Methods: Participants chose two silhouettes from the Stunkard Figure Rating Scale: one for body size preference and one for perceived body size. Each silhouette corresponds to a BMI category: (a) Underweight: 1 and 2; (b) Normal weight: 3 and 4; (c) Overweight: 5, 6 and 7; (d) Obesity: 8 and 9. Dissatisfaction was defined as the difference between silhouette numbers for perceived and preferred body size., Results: Characteristics of the 412 participants were: women: 42% (174/412), age 40±11y (mean±SD), range 20-69 y, BMI 27.9±4.6, range 19.5-47.3 kg/m 2 . As a body size of preference, no one (0/412) chose obese silhouettes. Normal weight silhouettes were chosen as their body size of preference by 75% (131/174) of women and 60% (143/238) of men. Overweight silhouettes were chosen as their preferred body size by 11% (19/174) of women and 26% (62/238) of men. Combining normal and overweight silhouettes into one group, 86% (150/174) of women and 86% (205/238) of men preferred to be either normal or overweight. Underweight silhouettes were preferred by 14% (24/174) of women and 14% (33/238) of men. Dissatisfaction because body size was too large occurred in 78% (135/174) of women and 53% (126/238) of men. Dissatisfaction because body size was too small occurred in 6% (11/174) of women and 16% (38/238) of men., Conclusion: African immigrants prefer body sizes which are normal or overweight. However, and presumably attributable to the combined influence of globalization and acculturation, a worrisome fraction of African immigrants favor an underweight silhouette., Competing Interests: All authors state that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2024 Hurston et al.)

Background and Objectives: Persistent neuropathic pain after brachial plexus avulsion (BPA) is common and generally nonresponsive to medical management. Dorsal root entry zone (DREZ) lesioning is the last resort for pain management in patients with BPA. This study aims to investigate and compare the outcomes and complications of DREZ procedures., Methods: A systematic literature search was conducted to identify all related studies. Comparisons were based on the number of patients with preoperative pain vs postoperative pain, with the effect size calculated using the risk ratio. Mean visual analog scale (VAS) scores were extracted and analyzed between interventions. A meta-regression analysis was performed to identify risk factors for final outcomes. The rates of complications were also assessed and analyzed between interventions., Results: A total of 30 studies with 917 patients (90.0% male and 10.0% female, mean age: 42.9 ± 16.6) were included in this systematic review. Of the 917 patients who underwent surgery, 655 (71.4%) patients had significant pain reduction at the last follow-up ( P < .05). The weighted mean preoperative VAS score was 8.3 ± 1.3, compared with postoperative VAS scores (1.9 ± 2.2); a significant improvement was observed ( P < .05). The subgroup analysis showed that microsurgical DREZotomy (MDT) is associated with better outcomes in terms of VAS score improvements compared with radiofrequency (RF)-assisted DREZ lesioning ( P < .05). Meta-analysis showed that the relative risk of motor deficits was significantly lower in the MDT group, compared with the RF-assisted group ( P < .05). Meta-regression showed that older age is correlated with an elevated risk of postoperative motor deficits compared with the incidence of sensory loss., Conclusion: DREZ lesioning is effective for intractable pain alleviation after BPA. Compared with RF-assisted DREZ lesioning, MDT is associated with better VAS score improvements and a lower rate of postoperative motor weakness., (Copyright © Congress of Neurological Surgeons 2024. All rights reserved.)

We describe our efforts to access a compound with an Al=P double bond by reaction of Al(Nacnac) towards [H 2 CN(Dipp)] 2 P(PCO) (Nacnac=HC[C(Me)N(Dipp)] 2 ; Dipp=2,6- i Pr 2 C 6 H 3 ). Our observations are consistent with the formation of a transient phosphanyl-phosphaalumene at low temperatures (-70 °C), however this species was found to readily undergo intramolecular C-H activation of the β-diketiminato ligand upon warming to room temperature. The reactivity of the transient complex toward small molecules including dihydrogen, carbon dioxide, phosphaketenes, amines and silanes could be explored at low temperatures, showcasing that the target compound can react as both a frustrated Lewis pair (via the pendant phosphanyl moiety) or in hydroelementation reactions of the Al=P bond. The elusive target molecule could be trapped by addition of a Lewis base (tetrahydrofuran) affording an isolable molecular species that reacts in an analogous fashion to the base-free compound., (© 2024 The Authors. Chemistry - A European Journal published by Wiley-VCH GmbH.)

This paper proposes a bidimensional modeling framework for Wolbachia invasion, assuming imperfect maternal transmission, incomplete cytoplasmic incompatibility, and direct infection loss due to thermal stress. Our model adapts to various Wolbachia strains and retains all properties of higher-dimensional models. The conditions for the durable coexistence of Wolbachia-carrying and wild mosquitoes are expressed using the model's parameters in a compact closed form. When the Wolbachia bacterium is locally established, the size of the remanent wild population can be assessed by a direct formula derived from the model. The model was tested for four Wolbachia strains undergoing laboratory and field trials to control mosquito-borne diseases: wMel, wMelPop, wAlbB, and wAu. As all these bacterial strains affect the individual fitness of mosquito hosts differently and exhibit different levels of resistance to temperature variations, the model helped to conclude that: (1) the wMel strain spreads faster in wild mosquito populations; (2) the wMelPop exhibits lower resilience but also guarantees the smallest size of the remanent wild population; (3) the wAlbB strain performs better at higher ambient temperatures than others; (4) the wAu strain is not sustainable and cannot persist in the wild mosquito population despite its resistance to high temperatures., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: The authors declare no conflict of interest., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

The use, misuse, and overuse of antimicrobials is one of the main public health threats of the 21st century. We investigated the risk factor of the presence of extended-spectrum, cephalosporin-resistant Enterobacterales in feces of non-domestic and domestic birds and other domestic animals in Piauí State, northeast Brazil. We collected a total of 387 cloacal and rectal swab samples of free-living birds, domestic birds, and domestic mammals in five municipalities: Amarante, Água Branca, Lagoa Alegre, Parnaíba, and Teresina. A total of 59/387 (15.2%) of these samples harbored extended spectrum beta-lactamase (ESBL)-producing Enterobacterales. Using the MALDI-TOF technique, we identified fifty-seven samples as Escherichia coli and two samples as Klebsiella pneumoniae . Teresina and Parnaíba had the highest prevalence of animals with resistant bacteria (32.1% and 27.1%, respectively) and highest exposure risk factor (OR of 16.06 and 8.58, respectively, and p < 0.001 for all). Multidrug-resistant, ESBL-producing Enterobacterales were observed in 72.8% of the samples (43/59). For the free-living birds, the positive samples belonged to a great kiskadee ( Pitangus sulphuratus ) and a semipalmated sandpiper ( Calidris pusilla ) in migratory and resident species, respectively. For domestic animals, the swine samples showed the highest prevalence of antimicrobial resistance. The lack of access to veterinary care and information regarding antimicrobial therapy, along with the easy access to antimicrobials without medical prescription, favors the inadequate use of antimicrobials in Piauí.

Here we studied the entire Atlantic Forest hotspot to investigate whether the effect of different environmental predictors depends on the phylogenetic extension and the biogeographical history of different Atlantic Forest sectors. We used occurrence data of 3,183 plant species with arboreal or arborescent habits. We reconstructed climatic stability across 120,000 years using the Random Forest method. Then, we compared the effect of biogeographical history, topographic, and climatic variables on species richness and phylogenetic diversity using Geographically Weighted Regression (GWR) models. Niche conservatism drives the strength and direction of environmental correlates with tree diversity, interacting with the biogeographical and phylogenetic extension considered. Low current climate seasonalities were the main drivers of species richness and phylogenetic diversity variation across the Atlantic Forest. Whereas in higher phylogenetic extension, topographic heterogeneity increased the number of tree species independent of the sector, deep-past climate stability favored phylogenetic diversity by increasing relict lineages of distant clades in all forests, but with anomalies in the southern sector. This investigation yields substantial evidence that the response of the northern and southern sectors of the Atlantic Forest to identical environmental conditions diverges significantly, providing compelling support for the imprint of phylogenetic heritage in generating non-linear diversity patterns.

Tail docking in lambs is associated with an acute inflammatory and ischemic response correlated to pain. The present study sought to quantify these responses by utilizing infrared thermographic imaging (IRT) after tail docking lambs. Images were taken for each lamb before tail docking (T0), within a minute after the band was placed (T1), at 5 minutes (T5), and 15 minutes (T15) respectively and analyzed for pixel intensity in areas on the lamb's rump, tail base, and two locations below the docking band. The pixel intensity at 2 cm below the docking band did significantly decrease ( p  < 0.05) over the course of the study at 15 minutes, indicating the presence of ischemia, and a significant decrease in the pixel intensity of the rump and tail base was observed. The closest location to the rubber ring showed the presence of inflammation as an indirect indicator of acute pain . IRT is a valuable tool in the detection of inflammation and ischemic areas and has the potential to be used to quantify and measure the experience of inflammation and pain after tail docking.

This systematic literature review of the clinical characteristics of radiation-induced brachial plexopathy and outcomes after intervention includes 30 trials with 611 patients. The mean radiation dose to the brachial plexus was 56 Gy, and the mean duration of radiation was 4 weeks. The mean time from radiation to the onset of symptoms was 35 months. The most commonly reported symptom was sensory loss ( n  = 323, 62%), followed by motor deficits ( n  = 294, 56%) and neuropathic pain ( n  = 284, 54%). In total, 65 (56%) patients had panplexus involvement and 51 (44%) patients had partial plexus involvement. The most common surgical procedure was neurolysis with flap coverage ( n  = 108, 6%), followed by neurolysis alone ( n  = 71, 30%). Of the 237 patients who underwent surgery, 125 (53%) reported an improvement in pain. Motor and sensory deficits were improved in 46 (19%) and 39 (16%) patients, respectively, suggesting that surgery is beneficial in relieving pain, but not as beneficial in restoring motor and sensory function., Competing Interests: Declaration of conflicting interestsThe authors declare no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: A cardiac rehabilitation programme is a medically supervised intervention to assist patients in recovery after heart surgeries and to prevent potential complications. Nurses should have the knowledge, a positive attitudes, and good practices to improve patient quality of life during the recovery process., Aim: This study aimed to describe the knowledge, attitudes, and practices of the nurses regarding cardiac rehabilitation for patients after heart valve surgery., Setting: The study setting was Windhoek Central Hospital, Cardiac Unit, in Windhoek, Namibia., Methods: A quantitative and descriptive research design was used for convenient non-probability sampling of ( N = 23) nurses who consented to participate in the study. Data were collected through self-administered questionnaires and analyzed using SPSS Version 26. Descriptive statistics were used and Fischer's Exact test for associations of variables was performed., Results: The study results showed a high level of knowledge, good attitudes, and poor to fair practices toward cardiac rehabilitation. However, the respondents demonstrate a lack of knowledge about the indications, and benefits of cardiac rehabilitation, negative attitudes regarding counselling of patients on sexual activities, and poor practice regarding exercises and counseling of patients and caregivers on cardiac rehabilitation. Furthermore, there is a positive relationship between the respondents' older age, senior rank, and having been trained I cardiac conditions and their knowledge, attitudes and practices regarding some core components of cardiac rehabilitation with P-value < 0.050., Conclusion: There is a need for a cardiac rehabilitation programme to improve nurses' attitudes and practices toward cardiac rehabilitation., Contribution: Understanding the gap in knowledge, attitudes, and practices among the nurses regarding cardiac rehabilitation would guide the Ministry of Health and Social Services (MoHSS) in the implementation of the cardiac rehabilitation for patients after heart valve surgery., Competing Interests: The authors have declared that no competing interest exists., (© 2024. The Authors.)

Background: Disease suppressiveness of soils to fungal root pathogens is typically induced in the field by repeated infections of the host plant and concomitant changes in the taxonomic composition and functional traits of the rhizosphere microbiome. Here, we studied this remarkable phenomenon for Bipolaris sorokiniana in two wheat cultivars differing in resistance to this fungal root pathogen., Results: The results showed that repeated exposure of the susceptible wheat cultivar to the pathogen led to a significant reduction in disease severity after five successive growth cycles. Surprisingly, the resistant wheat cultivar, initially included as a control, showed the opposite pattern with an increase in disease severity after repeated pathogen exposure. Amplicon analyses revealed that the bacterial families Chitinophagaceae, Anaerolineaceae and Nitrosomonadaceae were associated with disease suppressiveness in the susceptible wheat cultivar; disease suppressiveness in the resistant wheat cultivar was also associated with Chitinophagaceae and a higher abundance of Comamonadaceae. Metagenome analysis led to the selection of 604 Biosynthetic Gene Clusters (BGCs), out of a total of 2,571 identified by AntiSMASH analysis, that were overrepresented when the soil entered the disease suppressive state. These BGCs are involved in the biosynthesis of terpenes, non-ribosomal peptides, polyketides, aryl polyenes and post-translationally modified peptides., Conclusion: Combining taxonomic and functional profiling we identified key changes in the rhizosphere microbiome during disease suppression. This illustrates how the host plant relies on the rhizosphere microbiome as the first line of defense to fight soil-borne pathogens. Microbial taxa and functions identified here can be used in novel strategies to control soil-borne fungal pathogens., (© 2023. The Author(s).)

Background: Various treatment options have been introduced for the management of primary tumors of the brachial plexus (BP), ranging from conservative therapy to wide local excision with/without postoperative chemoradiotherapy. However, no consensus exists regarding optimal treatment strategies based on collated and published data., Objective: The aim of this study was to investigate the clinicopathological characteristics and outcome of patients with primary tumors of the BP who underwent surgical treatment., Data Sources: A systematic search of the four main online databases, including Web of Science (WOS), PubMed, Scopus, and Google Scholar, was conducted., Study Selection: All related articles addressing the clinical outcome and role of surgical interventions for management of primary tumors of the BP., Intervention: Optimal surgical and radiotherapeutic interventions for benign and malignant lesions based on the pathologic characteristics and location of primary BP tumors., Results: A total of 687 patients (693 tumors) with a mean age of 41.7±8.7 years old were evaluated. In total, 629 (90.8%) tumors were benign, and 64 (9.2%) were malignant, with a mean tumor size of 5.4±3.1 cm. The location of the tumor was reported for 639 patients. For these tumors, 444 (69.5%) originated from the supraclavicular region, and 195 (30.5%) were infraclavicular. The trunks were the most common location for tumor involvement, followed by the roots, cords, and terminal branches. Gross total resection was achieved in 432 patients and subtotal resection (STR) was performed in 109 patients. With neurofibromas, STR still resulted in good outcomes. The outcomes following treatment of malignant peripheral nerve sheath tumors were poor regardless of the type of resection. In general, symptoms related to pain and sensory issues resolved rapidly postoperatively. However, the resolution of motor deficits was often incomplete. Local tumor recurrence occurred in 15 (2.2%), patients and distant metastasis was observed in only eight (1.2%) cases. The overall mortality was 21 (3.1%) patients among the study population., Limitations: The main limitation was the lack of level I and II evidence., Conclusions: The ideal management strategy for primary BP tumors is complete surgical resection. However, in some cases, particularly for neurofibromas, STR may be preferable to preserve maximal neurological function. The degree of surgical excision (total or subtotal) mainly depends on the pathological characteristics and primary location of the tumor., (Copyright © 2023 the Author(s). Published by Wolters Kluwer Health, Inc.)

This paper aims to evaluate and discuss the digital competence of academics at universities, to identify challenges and define recommendations for policy. This study was conducted through collaboration between the Joint Research Centre (JRC) of the European Commission and Metared of the Universia Foundation, surveying 30,407 participants who present the perceptions of their own digital competence levels. These self-reflections took place in universities in seven countries, namely Argentina, Brazil, Colombia, Chile, Peru, Mexico and Portugal, and used the Check-In tool, which consists of 22 questions based on the European Framework for the Digital Competence of Educators-or 'DigCompEdu' framework. A descriptive statistical analysis was performed, followed by a qualitative evaluation. Almost 70% of the academics have an average intermediate level of competence when the data is aggregated, with results varying in each DigCompEdu area according to the specific question asked. There is no significant difference between young and senior academics, as well as between men and women. The results present a discussion of whether the age and gender of educators and their work environment have an impact on their digital competence level, and at the same time highlights the areas in which educators perceive themselves to be most and least competent. It shows how the amount of institutional support that is offered affects the academics' perceptions of their level of digital competence. On the basis of the results, recommendations are presented for higher-education institutions, with the aim of supporting the professional development of their academics., Competing Interests: Competing interestsThe authors declare that they have no competing interests., (© The Author(s) 2023.)

Abnormal-glucose tolerance (Abnl-GT) is due to an imbalance between β-cell function and insulin resistance (IR) and is a major risk factor in cardiovascular disease (CVD). In sub-Saharan Africa, β-cell failure is emerging as an important cause of Abnl-GT (Abnl-GT-β-cell-failure). Visceral adipose tissue (VAT) volume and hyperlipidemia are major contributors to CVD risk when Abnl-GT is due to IR (Abnl-GT-IR). Yet, the CVD profile associated with Abnl-GT-β-cell failure is unknown. Therefore, our goals in 450 African-born Blacks (Male: 65%; Age: 39 ± 10 years; BMI 28 ± 5 kg/m 2 ), living in America were to: (1) determine Abnl-GT prevalence and etiology; (2) assess by Abnl-GT etiology, associations between four understudied subclinical CVD risk factors in Africans: (a) subclinical myocardial damage (high-sensitivity troponin T (hs-cTnT)); (b) neurohormonal regulation (N-terminal pro-Brain-natriuretic peptide (NT-proBNP)); (c) coagulability (fibrinogen); (d) inflammation (high-sensitivity C-reactive protein (hsCRP)), as well as HbA 1c , Cholesterol/HDL ratio and VAT. Glucose tolerance status was determined by the OGTT. IR was defined by the threshold at the lowest quartile for the Matsuda Index (≤ 2.97). Abnl-GT-IR required both Abnl-GT and IR. Abnl-GT-β-cell-failure was defined as Abnl-GT without IR. VAT was assessed by CT-scan. For both the Abnl-GT-β-cell-failure and Abnl-GT-IR groups, four multiple regression models were performed for hs-cTnT; NT-proBNP; fibrinogen and hsCRP, as dependent variables, with the remaining three biomarkers and HbA 1c , Cholesterol/HDL and VAT as independent variables. Abnl-GT occurred in 38% (170/450). In the Abnl-GT group, β-cell failure occurred in 58% (98/170) and IR in 42% (72/170). VAT and Cholesterol/HDL were significantly lower in Abnl-GT-β-cell-failure group vs the Abnl-GT-IR group (both P < 0.001). In the Abnl-GT-β-cell-failure group: significant associations existed between hscTnT, fibrinogen, hs-CRP, and HbA 1c (all P < 0.05), and none with Cholesterol/HDL or VAT. In Abnl-GT-IR: hs-cTnT, fibrinogen and hsCRP significantly associated with Cholesterol/HDL (all P < 0.05) and NT-proBNP inversely related to fibrinogen, hsCRP, HbA 1c , Cholesterol/HDL, and VAT (all P < 0.05). The subclinical CVD risk profile differed between Abnl-GT-β-cell failure and Abnl-GT-IR. In Abnl-GT-β-cell failure subclinical CVD risk involved subclinical-myocardial damage, hypercoagulability and increased inflammation, but not hyperlipidemia or visceral adiposity. For Abnl-GT-IR, subclinical CVD risk related to subclinical myocardial damage, neurohormonal dysregulation, inflammation associated with hyperlipidemia and visceral adiposity. ClinicalTrials.gov Identifier: NCT00001853., (© 2022. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)

Gossypium hirsutum L. represents the best cotton species for fiber production, thus computing the largest cultivated area worldwide. Meloidogyne incognita is a root-knot nematode (RKN) and one of the most important species of Meloidogyne genus, which has a wide host range, including cotton plants. Phytonematode infestations can only be partially controlled by conventional agricultural methods, therefore, more effective strategies to improve cotton resistance to M. incognita disease are highly desirable. The present study employed functional genomics to validate the involvement of two previously identified candidate genes, encoding dirigent protein 4- GhDIR4 and peroxiredoxin-2- GhPRXIIB , in cotton defense against M. incognita . Transgenic A. thaliana plant lines overexpressing GhDIR4 and GhPRXIIB genes were generated and displayed significantly improved resistance against M. incognita infection in terms of female nematode abundance in the roots when compared to wild-type control plants. For our best target-gene GhDIR4 , an in-silico functional analysis, including multiple sequence alignment, phylogenetic relationship, and search for specific protein motifs unveiled potential orthologs in other relevant crop plants, including monocots and dicots. Our findings provide valuable information for further understanding the roles of GhDIR and GhPRXIIB genes in cotton defense response against RKN nematode., Supplementary Information: The online version contains supplementary material available at 10.1007/s13205-022-03282-4., Competing Interests: Conflict of interestsThe authors declare that the research was conducted in the absence of any commercial or financial competing interest., (© King Abdulaziz City for Science and Technology 2022, Springer Nature or its licensor holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.)

Human-wildlife cooperation occurs when humans and free-living wild animals actively coordinate their behavior to achieve a mutually beneficial outcome. These interactions provide important benefits to both the human and wildlife communities involved, have wider impacts on the local ecosystem, and represent a unique intersection of human and animal cultures. The remaining active forms are human-honeyguide and human-dolphin cooperation, but these are at risk of joining several inactive forms (including human-wolf and human-orca cooperation). Human-wildlife cooperation faces a unique set of conservation challenges, as it requires multiple components-a motivated human and wildlife partner, a suitable environment, and compatible interspecies knowledge-which face threats from ecological and cultural changes. To safeguard human-wildlife cooperation, we recommend: (i) establishing ethically sound conservation strategies together with the participating human communities; (ii) conserving opportunities for human and wildlife participation; (iii) protecting suitable environments; (iv) facilitating cultural transmission of traditional knowledge; (v) accessibly archiving Indigenous and scientific knowledge; and (vi) conducting long-term empirical studies to better understand these interactions and identify threats. Tailored safeguarding plans are therefore necessary to protect these diverse and irreplaceable interactions. Broadly, our review highlights that efforts to conserve biological and cultural diversity should carefully consider interactions between human and animal cultures. Please see AfricanHoneyguides.com/abstract-translations for Kiswahili and Portuguese translations of the abstract., Competing Interests: The authors declare no conflict of interest., (© 2022 The Authors. Conservation Letters published by Wiley Periodicals LLC.)

Human herpesvirus-6 (HHV-6) may cause serious diseases in immunocompromised individuals. SARS-CoV-2/HHV-6 coinfection has been emphasized in previous works, mostly case reports, small series, or epidemiological studies, but few are known about its real clinical outcomes. Here we present a real-world pilot study aiming to understand the frequency and the clinical impact of HHV-6 coinfection in moderate to critically ill patients hospitalized due to COVID-19. SARS-CoV-2 and HHV-6 were evaluated in nasopharyngeal samples at the hospital admission of suspected COVID-19 patients. From 173 consecutive cases, 60 were SARS-CoV-2 positive and 13/60 (21.7%) were HHV-6 positive after identified as the HHV-6B species by a Sanger sequencing. The SARS-CoV-2+/HHV-6+ group was younger but not significant for cardiovascular diseases, diabetes, obesity, and cancer, but significant among therapeutic immunosuppressed patients (as systemic lupus erythematosus and kidney transplant patients). In the medical records, only sparse data on cutaneous or neurological manifestations were found. Biochemical and hematological data showed only a trend towards hyperferritinemic status and lymphopenia. In conclusion, despite the impressive high frequency of HHV-6 coinfection in SARS-CoV-2 positive cases, it did not impact general mortality. We suggest larger future prospective studies to better elucidate the influence of HHV-6 reactivation in cases of COVID-19, designed to specific assessment of clinical outcomes and viral reactivation mechanisms., (© 2021 Wiley Periodicals LLC.)

Nicotinamide adenine dinucleotide (NAD) metabolism plays an important role in the regulation of immune function. However, a complete picture of how NAD, its metabolites, precursors, and metabolizing enzymes work together in regulating immune function and inflammatory diseases is still not fully understood. Surprisingly, few studies have compared the effect of different forms of vitamin B3 on cellular functions. Therefore, we investigated the role of NAD boosting in the regulation of macrophage activation and function using different NAD precursors supplementation. We compared nicotinamide mononucleotide (NMN), nicotinamide riboside (NR), and nicotinamide (NAM) supplementation, with the recently described potent NAD precursor NRH. Our results show that only NRH supplementation strongly increased NAD + levels in both bone marrow-derived and THP-1 macrophages. Importantly, NRH supplementation activated a pro-inflammatory phenotype in resting macrophages, inducing gene expression of several cytokines, chemokines, and enzymes. NRH also potentiated the effect of lipopolysaccharide (LPS) on macrophage activation and cytokine gene expression, suggesting that potent NAD + precursors can promote inflammation in macrophages. The effect of NRH in NAD + boosting and gene expression was blocked by inhibitors of adenosine kinase, equilibrative nucleoside transporters (ENT), and IκB kinase (IKK). Interestingly, the IKK inhibitor, BMS-345541, blocked the mRNA expression of several enzymes and transporters involved in the NAD boosting effect of NRH, indicating that IKK is also a regulator of NAD metabolism. In conclusion, NAD precursors such as NRH may be important tools to understand the role of NAD and NADH metabolism in the inflammatory process of other immune cells, and to reprogram immune cells to a pro-inflammatory phenotype, such as the M2 to M1 switch in macrophage reprogramming, in the cancer microenvironment., Competing Interests: EC holds a patent on the use of CD38 inhibitors for metabolic diseases that is licensed by Elysium health. EC is a consultant for TeneoBio, Calico, Mitobridge and Cytokinetics. EC is on the advisory board of Eolo Pharma (Santa Fe, Argentina). The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Chini, Peclat, Gomez, Zeidler, Warner, Kashyap, Mazdeh, Hayat, Migaud, Paulus, Chanan-Khan and Chini.)

To identify determinants of daily life stress in Africans in America, 156 African-born Blacks (Age: 40 ± 10 years (mean ± SD), range 22-65 years) who came to the United States as adults (age ≥ 18 years) were asked about stress, sleep, behavior and socioeconomic status. Daily life stress and sleep quality were assessed with the Perceived Stress Scale (PSS) and Pittsburgh Sleep Quality Index (PSQI), respectively. High-stress was defined by the threshold of the upper quartile of population distribution of PSS (≥16) and low-stress as PSS < 16. Poor sleep quality required PSQI > 5. Low income was defined as <40 k yearly. In the high and low-stress groups, PSS were: 21 ± 4 versus 9 ± 4, p < 0.001 and PSQI were: 6 ± 3 versus 4 ± 3, p < 0.001, respectively. PSS and PSQI were correlated (r = 0.38, p < 0.001). The odds of high-stress were higher among those with poor sleep quality (OR 5.11, 95% CI: 2.07, 12.62), low income (OR 5.03, 95% CI: 1.75, 14.47), and no health insurance (OR 3.01, 95% CI: 1.19, 8.56). Overall, in African-born Blacks living in America, daily life stress appears to be linked to poor quality sleep and exacerbated by low income and lack of health insurance.

Neglected tropical diseases are a diverse group of communicable diseases that are endemic in low- or low-to-middle-income countries located in tropical and subtropical zones. The number and availability of drugs for treating these diseases are low, the administration route is inconvenient in some cases, and most of them have safety, efficacy, or adverse/toxic reaction issues. The need for developing new drugs to deal with these issues is clear, but one of the most drastic consequences of this negligence is the lack of interest in the research and development of new therapeutic options among major pharmaceutical companies. Positive changes have been achieved over the last few years, although the overall situation remains alarming. After more than one decade since the original work reviewing antiprotozoal agents came to light, now it is time to question ourselves: How has the scenario for the treatment of protozoal diseases such as malaria, leishmaniasis, human African trypanosomiasis, and American trypanosomiasis changed? This review covers the last decade in terms of the drugs currently available for the treatment of these diseases as well as the clinical candidates being currently investigated., (© 2021 Deutsche Pharmazeutische Gesellschaft.)

Aim: COVID-19, the novel coronavirus, has been characterized as a pandemic, as it spreads all over the world and has so far infected more than 20 million worldwide. In Palestine, the first seven cases were documented on March 5 2020, followed by the declaration of the state of emergency. This study aimed to assess knowledge, attitudes and practices toward COVID-19 among Birzeit University students., Subject and Methods: A cross-sectional study was carried out; a questionnaire was developed based on the WHO, CDC, and ECDC recommendations. The questionnaire was distributed online and filled out by Birzeit University students. Chi-square testing was performed to check for significant association between KAP (knowledge, attitude, and practices) and different socio-demographic variables. Binary logistic regression was performed to identify and control the confounding factors. Data were analyzed using SPSS (version 22)., Results: A total of 665 students have completed the online questionnaire. The mean age was 20.55 ± 3.069 years. Multivariate analysis revealed that males, students from health professions and scientific faculties, and those with highly educated parents had manifested a good knowledge level (GKL) about COVID-19. With regard to students' practices, fewer negative practices were displayed by students from health professions faculty and the students living at the middle governorate of Palestine, compared to north, south, and Jerusalem dwellers. With regard to the practices, the vast majority of the participants showed a positive and very cautious practice in relation to the COVID-19 epidemic., Conclusion: Our results revealed that students had variable knowledge about COVID-19, and the vast majority depended on the official media briefs in Palestine as a source of information. With regard to practices, positive and cautious practices with regard to the COVID- 19 epidemic were carried out by the vast majority of participants., Competing Interests: Conflict of interestThe authors state that they do not present any conflict of interests in the present research., (© The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature 2021.)

Introduction: Uncertainties exist on whether the main determinant of abnormal glucose tolerance (Abnl-GT) in Africans is β-cell failure or insulin resistance (IR). Therefore, we determined the prevalence, phenotype and characteristics of Abnl-GT due to β-cell failure versus IR in 486 African-born blacks (male: 64%, age: 38±10 years (mean±SD)) living in America., Research Design and Methods: Oral glucose tolerance test were performed. Abnl-GT is a term which includes both diabetes and prediabetes and was defined as fasting plasma glucose (FPG) ≥5.6 mmol/L and/or 2-hour glucose ≥7.8 mmol/L. IR was defined by the lowest quartile of the Matsuda Index (≤2.98) and retested using the upper quartile of homeostatic model assessment of insulin resistance (HOMA-IR) (≥2.07). Abnl-GT-IR required both Abnl-GT and IR. Abnl-GT-β-cell failure was defined as Abnl-GT without IR. Beta-cell compensation was assessed by the Disposition Index (DI). Fasting lipids were measured. Visceral adipose tissue (VAT) volume was obtained with abdominal CT scan., Results: The prevalence of Abnl-GT was 37% (182/486). For participants with Abnl-GT, IR occurred in 38% (69/182) and β-cell failure in 62% (113/182). Compared with Africans with Abnl-GT-IR, Africans with Abnl-GT-β-cell failure had lower body mass index (BMI) (30.8±4.3 vs 27.4±4.0 kg/m 2 ), a lower prevalence of obesity (52% vs 19%), less VAT (163±72 vs 107±63 cm 2 ), lower triglyceride (1.21±0.60 vs 0.85±0.42 mmol/L) and lower FPG (5.9±1.4 vs 5.3±0.6 mmol/L) and 2-hour glucose concentrations (10.0±3.1 vs 9.0±1.9 mmol/L) (all p<0.001) and higher DI, high-density lipoprotein (HDL), low-density lipoprotein particle size and HDL particle size (all p<0.01). Analyses with Matsuda Index and HOMA-IR yielded similar results. Potential confounders such as income, education, alcohol and fiber intake did not differ by group., Conclusions: Beta-cell failure occurred in two-thirds of participants with Abnl-GT and may be a more frequent determinant of Abnl-GT in Africans than IR. As BMI category, degree of glycemia and lipid profile appeared more favorable when Abnl-GT was due to β-cell failure rather than IR, the clinical course and optimal interventions may differ., Trial Registration Number: NCT00001853., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Leishmania , an intracellular parasite species, causes lesions on the skin and in the mucosa and internal organs. The dissemination of infected host cells containing Leishmania is crucial to parasite survival and the establishment of infection. Migratory phenomena and the mechanisms underlying the dissemination of Leishmania -infected human dendritic cells (hDCs) remain poorly understood. The present study aimed to investigate differences among factors involved in hDC migration by comparing infection with visceral leishmaniasis (VL) induced by Leishmania infantum with diverse clinical forms of tegumentary leishmaniasis (TL) induced by Leishmania braziliensis or Leishmania amazonensis . Following the infection of hDCs by isolates obtained from patients with different clinical forms of Leishmania , the formation of adhesion complexes, actin polymerization, and CCR7 expression were evaluated. We observed increased hDC migration following infection with isolates of L. infantum (VL), as well as disseminated (DL) and diffuse (DCL) forms of cutaneous leishmaniasis (CL) caused by L. braziliensis and L. amazonensis , respectively. Increased expression of proteins involved in adhesion complex formation and actin polymerization, as well as higher CCR7 expression, were seen in hDCs infected with L. infantum , DL and DCL isolates. Together, our results suggest that hDCs play an important role in the dissemination of Leishmania parasites in the vertebrate host.

Landscape change is one of the foremost drivers of the emergence of infectious diseases. Exploring demographic, household and environmental conditions under which infectious diseases occur may inform strategies to prevent disease emergence in human populations. We collected blood samples from 523 humans and explore factors for arbovirus emergence in Bahia, Brazil. The overall arbovirus seroprevalence was 65.2%, with the genus Flavivirus most prevalent (64.4%). Based on monotypic reactions, the population had contact with five arbovirus: Dengue 3, Ilheus, Oropouche, Caraparu and Eastern equine encephalitis virus. To our knowledge, this is the first study reporting exposure to Oropouche, Caraparu and Eastern equine encephalitis virus in human populations in Bahia, Northeast of Brazil. The best model fit demonstrated that household and environmental variables were more predictive of the risk of arbovirus exposure than demographic variables. The presence of forest and free-living monkeys in the areas close to the communities had a protective effect for the human population (i.e. lower seroprevalence). The dilution effect is considered as one explanation for this finding. These results highlight the important ecological role of wildlife-friendly agriculture., (© 2021 Wiley-VCH GmbH.)

Whether an OGTT reproducibly detects either type 2 diabetes (T2D) or prediabetes in Africans in unknown. Therefore, 131 Africans had two OGTT. Diagnostic reproducibility for T2D was excellent (κ = 0.84), but only moderate for prediabetes (κ = 0.51). A single OGTT positive for T2D may be sufficient to guide clinical care and inform epidemiologic study design. ClinicalTrials.gov Identifier: NCT00001853., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Decreased NAD + levels have been shown to contribute to metabolic dysfunction during aging. NAD + decline can be partially prevented by knockout of the enzyme CD38. However, it is not known how CD38 is regulated during aging, and how its ecto-enzymatic activity impacts NAD + homeostasis. Here we show that an increase in CD38 in white adipose tissue (WAT) and the liver during aging is mediated by accumulation of CD38 + immune cells. Inflammation increases CD38 and decreases NAD + . In addition, senescent cells and their secreted signals promote accumulation of CD38 + cells in WAT, and ablation of senescent cells or their secretory phenotype decreases CD38, partially reversing NAD + decline. Finally, blocking the ecto-enzymatic activity of CD38 can increase NAD + through a nicotinamide mononucleotide (NMN)-dependent process. Our findings demonstrate that senescence-induced inflammation promotes accumulation of CD38 in immune cells that, through its ecto-enzymatic activity, decreases levels of NMN and NAD + .

Objective: In African-born Blacks living in America, we determined by BMI category 1 ) prevalence of abnormal glucose tolerance (Abnl-GT) and 2 ) diagnostic value and reproducibility of hemoglobin A 1c (HbA 1c ), fructosamine, and glycated albumin (GA)., Research Design and Methods: Participants ( n = 416; male, 66%; BMI 27.7 ± 4.5 kg/m 2 [mean ± SD]) had an oral glucose tolerance test with HbA 1c , GA, and fructosamine assayed. These glycemic markers were repeated 11 ± 7 days later. Abnl-GT diagnosis required 0 h ≥5.6 mmol/L (≥100 mg/dL) and/or 2 h ≥7.8 mmol/L (≥140 mg/dL). Thresholds for HbA 1c , GA, and fructosamine were the values at the 75th percentile for the population (39 mmol/mol [5.7%], 14.2%, and 234 μmol/L, respectively)., Results: Abnl-GT prevalence in the nonobese was 34% versus 42% in the obese ( P = 0.124). Reproducibility was excellent for HbA 1c and GA (both κ ≥ 0.8), but moderate for fructosamine (κ = 0.6). Focusing on HbA 1c and GA in the nonobese, we found as single tests the sensitivities of HbA 1c and GA were 36% versus 37% ( P = 0.529). Combining HbA 1c and GA, sensitivity increased to 58% because GA identified 37% of Africans with Abnl-GT not detected by HbA 1c ( P value for both tests vs. HbA 1c alone was <0.001). For the obese, sensitivities for HbA 1c , GA, and the combined tests were 60%, 27%, and 67%, respectively. Combined test sensitivity did not differ from HbA 1c alone ( P = 0.25) because GA detected only 10% of obese Africans with Abnl-GT not detected by HbA 1c ., Conclusions: Adding GA to HbA 1c improves detection of Abnl-GT in nonobese Africans., (© 2020 by the American Diabetes Association.)

Aims/hypothesis: Metformin is the only approved oral agent for youth with type 2 diabetes but its mechanism of action remains controversial. Recent data in adults suggest a primary role for the enteroinsular pathway, but there are no data in youth, in whom metformin efficacy is only ~50%. Our objectives were to compare incretin concentrations and rates of glucose production and gluconeogenesis in youth with type 2 diabetes before and after short-term metformin therapy compared with peers with normal glucose tolerance (NGT)., Methods: This is a case-control observational study in youth with type 2 diabetes who were not on metformin (n = 18) compared with youth with NGT (n = 10) who were evaluated with a 2 day protocol. A 75 g OGTT was administered to measure intact glucagon-like 1 peptide (iGLP-1), gastric inhibitory polypeptide (GIP) and peptide YY (PYY). Insulinogenic index (IGI) and whole-body insulin sensitivity were calculated using glucose and insulin levels from the OGTT. Basal rates of gluconeogenesis ( 2 H 2 O), glucose production ([6,6- 2 H 2 ]glucose) and whole-body lipolysis ([ 2 H 5 ]glycerol) were measured after an overnight fast on study day 2. Youth with type 2 diabetes (n = 9) were subsequently evaluated with an identical 2 day protocol after 3 months on the metformin study., Results: Compared with individuals with NGT, those with type 2 diabetes had higher fasting (7.8 ± 2.5 vs 5.1 ± 0.3 mmol/l, mean ± SD p = 0.002) and 2 h glucose concentrations (13.8 ± 4.5 vs 5.9 ± 0.9 mmol/l, p = 0.001), higher rates of absolute gluconeogenesis (10.0 ± 1.7 vs 7.2 ± 1.1 μmol [kg fat-free mass (FFM)] -1  min -1 , p < 0.001) and whole-body lipolysis (5.2 ± 0.9 vs 4.0 ± 1.4 μmol kg FFM -1  min -1 , p < 0.01), but lower fasting iGLP-1 concentrations (0.5 ± 0.5 vs 1.3 ± 0.7 pmol/l, p < 0.01). Metformin decreased 2 h glucose (pre metformin 11.4 ± 2.8 vs post metformin 9.9 ± 1.9 mmol/l, p = 0.04) and was associated with ~20-50% increase in IGI (median [25th-75th percentile] pre 1.39 [0.89-1.47] vs post 1.43 [0.88-2.70], p = 0.04), fasting iGLP-1 (pre 0.3 ± 0.2 vs post 1.0 ± 0.7 pmol/l, p = 0.02), 2 h iGLP (pre 0.4 ± 0.2 vs post 1.2 ± 0.9 pmol/l, p = 0.06), fasting PYY (pre 6.3 ± 2.2 vs post 10.5 ± 4.3 pmol/l, p < 0.01) and 2 h PYY (pre 6.6 ± 2.9 vs post 9.0 ± 4.0 pmol/l, p < 0.01). There was no change in BMI, insulin sensitivity or GIP concentrations pre vs post metformin. There were no differences pre vs post metformin in rates of glucose production (15.0 ± 3.9 vs 14.9 ± 2.2 μmol kg FFM -1  min -1 , p = 0.84), absolute gluconeogenesis (9.9 ± 1.8 vs 9.7 ± 1.7 μmol kg FFM -1  min -1 , p = 0.76) or whole-body lipolysis (5.0 ± 0.7 vs 5.3 ± 1.3 μmol kg FFM -1  min -1 , p = 0.20). Post metformin iGLP-1 and PYY concentrations in youth with type 2 diabetes were comparable to levels in youth with NGT., Conclusions/interpretation: Overall, the improved postprandial blood glucose levels and increase in incretins observed in the absence of changes in insulin sensitivity and gluconeogenesis, support an enteroinsular mechanistic pathway in youth with type 2 diabetes treated with short-term metformin.

Despite the wide application of carvacrol (CAR) in different biological and medical areas, there is still insufficient electrophysiological data on the mechanisms of action of CAR, particularly in the pregnant uterine function. The aim of this study was to evaluate the in vitro tocolytic effect of CAR on the contractility of isolated pregnant rat uterus in the presence of a calcium channel antagonist (nifedipine) and a cyclooxygenase inhibitor (indomethacin). The uteri were isolated from pregnant Wistar rats at 16-18 days of pregnancy and suspended in an isolated organ bath chamber containing a Ringer's physiological solution and aerated with 95% O 2 and 5% CO 2 . Samples were used in functional tests to evaluate the inhibitory effect of CAR at increasing concentrations on the rhythmic spontaneous, oxytocin-induced phasic, K + -induced tonic, and Ca 2+ -induced contractions. The differences in inhibitory concentration-50 and E max among the compounds were determined using the one-way ANOVA followed by a post hoc Student-Newman-Keuls or Bonferroni test, in all casesP < 0.05 was considered statistically significant. Nifedipine was used as positive controls where required. CAR caused a significant concentration-dependent inhibition of the uterine contractions induced by the pharmaco- and electro-mechanic stimuli. We showed that the inhibitory effects of CAR depends on the type of muscle contraction stimuli, and that it acts stronger in spontaneous rhythmic activity and in contractions of isolated rat uterus induced by Ca 2+ . Nifedipine was more potent than CAR and indomethacin on the uterine contractility (P < 0.05), but none of them was more effective than nifedipine. Therefore, the tocolytic effect induced by CAR was associated with the blockade of the calcium channels in the pregnant rat uterus. This property placed CAR as a potentially safe and effective adjuvant agent in cases of preterm labor, an area of pharmacological treatment that requires urgent improvement., Competing Interests: None

Stress leads to physiologic dysfunction and cardiometabolic disease. Allostatic load score (ALS) measures stress-induced cardiovascular, metabolic, and inflammatory biomarkers. We estimated the odds of high ALS by reason for and age at immigration, duration of American residence, number of children, and socioeconomic status in 193 African immigrants (male: 65%, age 41 ± 10 y (mean ± Standard Deviation (SD)), range 22-65 y). ALS was calculated with High-ALS defined as ALS ≥ 3.0 and Low-ALS defined as ALS < 3.0. Oral glucose tolerance tests (OGTT) were performed, the cardiovascular disease (CVD) risk estimated, and TNF-α, an inflammatory cytokine, measured. Logistic regression was used to estimate odds of High-ALS. In the High- and Low-ALS groups, ALS were 4.0 ± 1.2 vs. 1.3 ± 0.7, diabetes prevalence: 14% vs. 4%, CVD risk: 23% vs. 8%, TNF-α levels: 15 ± 9 vs. 11 ± 6 pg/mL, respectively (all p ≤ 0.01). Immigrants were more likely to be in the High-ALS group if their reason for immigration was work or asylum/refugee (OR 2.18, p = 0.013), their age at immigration was ≥30 y (OR 3.28, p < 0.001), their duration of residence in United States was ≥10 y (OR 3.16, p = 0.001), or their number of children was ≥3 (OR 2.67, p = 0.019). Education, income, health insurance, marital status, and gender did not affect High-ALS odds. Factors adversely influencing allostatic load and cardiometabolic health in African immigrants were age at and reason for immigration, duration of residence in America, and number of children.

Individual behavioral differences may influence how animals cope with altered environments. Depending on their behavioral traits, individuals may thus vary in how their health is affected by environmental conditions. We investigated the relationship between individual behavior of free-living golden-headed lion tamarins (Leontopithecus chrysomelas) responding to a novel object (to assess exploration-avoidance), and their habitat use and health status (endoparasitism; clinical measures: biometric data, heart rate, respiratory frequency, and temperature; fecal glucocorticoid metabolites). As parasite transmission can be affected by individual variation in social contact and social grooming, we also evaluated whether more sociable individuals show higher endoparasite loads compared with less sociable animals. Four groups living in landscapes with different levels of human disturbance were investigated: two in degraded forest fragments in an agricultural matrix (DFAM-higher disturbance), and two in a cocoa agroforestry system (cabruca-lower disturbance) in the Atlantic forest of South Bahia, Brazil. Using a subjective ratings approach, highly correlated adjective descriptors were combined to produce z-score ratings of one derived variable ("confidence"), which was selected to characterize the tamarins' exploration/avoidance responses during a novel object test. The higher the confidence score, the longer female tamarins spent foraging for prey independent of landscape, and the greater their body mass independent of sex and landscape. Only DFAM individuals showed intestinal parasite infection. Endoparasite loads were positively correlated with the number of grooming partners, suggesting an association between social grooming and transmission (more groomers = more endoparasites). Individual behavior, including in a test situation, may thus have some predictive value for behavior in a free-living context, and for its health consequences., (© 2020 Wiley Periodicals, Inc.)

Introduction: Risk of insulin resistance, dyslipidemia, diabetes and cardiac death is increased in Asians and Europeans with normal glucose tolerance (NGT) and 1-hour glucose ≥8.6 mmol/L. As African descent populations often have insulin resistance but a normal lipid profile, the implications for Africans with NGT and glucose ≥8.6 mmol/L (NGT-1-hour-high) are unknown., Objective: We performed oral glucose tolerance tests (OGTTs) in 434 African born-blacks living in Washington, DC (male: 66%, age 38±10 years (mean±SD)) and determined in the NGT group if either glucometabolic or lipid profiles varied according to a 1-hour-glucose threshold of 8.6 mmol/L., Methods: Glucose tolerance category was defined by OGTT criteria. NGT was subdivided into NGT-1-hour-high (glucose ≥8.6 mmol/L) and NGT-1-hour-normal (glucose <8.6 mmol/L). Second OGTT were performed in 27% (119/434) of participants 10±7 days after the first. Matsuda Index and Oral Disposition Index measured insulin resistance and beta-cell function, respectively. Lipid profiles were obtained. Comparisons were by one-way analysis of variance with Bonferonni corrections for multiple comparisons. Duplicate tests were assessed by к-statistic., Results: One-hour-glucose ≥8.6 mmol/L occurred in 17% (47/272) with NGT, 72% (97/134) with pre-diabetes and in 96% (27/28) with diabetes. Both insulin resistance and beta-cell function were worse in NGT-1-hour-high than in NGT-1-hour-normal. Dyslipidemia occurred in both the diabetes and pre-diabetes groups but not in either NGT group. One-hour glucose concentration ≥8.6 mmol/L showed substantial agreement for the two OGTTs (к=0.628)., Conclusions: Although dyslipidemia did not occur in either NGT group, insulin resistance and beta-cell compromise were worse in NGT-1 hour-high. Subdividing the NGT group at a 1-hour glucose threshold of 8.6 mmol/L may stratify risk for diabetes in Africans., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Introduction: To improve detection of undiagnosed diabetes in Africa, there is movement to replace the OGTT with A1C. The performance of A1C in the absence of hemoglobin-related micronutrient deficiencies, anemia and heterozygous hemoglobinopathies is unknown. Therefore, we determined in 441 African-born blacks living in America [male: 65% (281/441), age: 38 ± 10 y (mean ± SD), BMI: 27.5 ± 4.4 kg/m 2 ] (1) nutritional and hematologic profiles and (2) glucose tolerance categorization by OGTT and A1C. Methods: Hematologic and nutritional status were assessed. Hemoglobin <11 g/dL occurred in 3% (11/441) of patients and led to exclusion. A1C and OGTT were performed in the remaining 430 participants. ADA thresholds for A1C and OGTT were used. Diagnosis by A1C required meeting either A1C-alone or A1C&OGTT criteria. Diagnosis by OGTT-alone required detection by OGTT and not A1C. Results: Hemoglobin, mean corpuscular volume and red blood cell distribution width were 14.0 ± 1.3 g/dL, 85.5 ± 5.3 fL, and 13.2 ± 1.2% respectively. B12, folate, and iron deficiency occurred in 1% (5/430), 0% (0/430), and 4% (12/310), respectively. Heterozygous hemoglobinopathy prevalence was 18% (78/430). Overall, diabetes prevalence was 7% (32/430). A1C detected diabetes in 32% (10/32) but OGTT-alone detected 68% (22/32). Overall prediabetes prevalence was 41% (178/430). A1C detected 57% (102/178) but OGTT-alone identified 43% (76/178). After excluding individuals with heterozygous hemoglobinopathies, the rate of missed diagnosis by A1C of abnormal glucose tolerance did not change (OR: 0.99, 95% CI: 0.61, 1.62). Conclusions: In nutritionally replete Africans without anemia or heterozygous hemoglobinopathy, if only A1C is used, ~60% with diabetes and ~40% with prediabetes would be undiagnosed. Clinical Trial Registration: : www.ClinicalTrials.gov, Identifier: NCT00001853.

Background: The lack of formal instruments to measure Burden in primary caregivers of Children in a hospital context is limited because mostly of published instruments are related to cancer survivors, ambulatory environment or general context for children with chronic conditions, but none of them adapted property to prolonged hospitalization context. This leaves the rising population of hospitalized chronic children's caregivers without a proper assessment. The aim of this study was to develop a version of the Revised Impact on Family Scale adapted to primary caregivers of chronic hospitalized children. A cross-sectional study with two main stages was conducted. The first one describes the linguistic and contextual adaptation process of the instrument, and the second refers to the psychometric testing and analysis.., Results: Less than 15% of the participants expressed problems with some adapted items in the scale. Eighty-six caregivers were evaluated at Josefina Martinez Hospital, mostly female (34.2 ± 11.6 years old). Majority of participants were graduated from high school, salaried employee and mothers of the chronic child. The scale exhibits a high level of internal consistency (Cronbach's alpha 0.73), excellent intra-observer reliability (Intraclass Correlation Coefficient 0.9), acceptable empirical evaluation of content validity and low and negative construct validity (Pearson's correlation coefficient - 0.23)., Conclusions: This adapted version of the Revised Impact on Family Scale to the hospital context is a reliable, valid, self-administered and simple instrument to implement in order to assess the burden of primary caregivers with chronic hospitalized children.

Background: Patch testing of contact allergens to diagnose allergic contact dermatitis (ACD) is a traditional, useful tool. The most important decision is the distinction between allergic and irritant reactions, as this has direct implications on diagnosis and management. Our objective was to evaluate a new method of non-contact infrared reading of patch tests. Secondary objectives included a possible correlation between the intensity of the patch test reaction and temperature change., Methods: 420 positive reactions from patients were included in our study. An independent patch test reader assessed the positive reactions and classified them as allergic (of intensity + to +++) or irritant (IR). At the same time, a forward-looking infrared (FLIR) camera attachment for an iPhone was used to acquire infrared thermal images of the patch tests, and images were analyzed using the FLIR ONE app., Results: Allergic patch test reactions were characterized by temperature increases of 0.72 ± 0.67 °C compared to surrounding skin. Irritant reactions only resulted in 0.17 ± 0.31 °C temperature increase. The mean temperature difference between the two groups was highly significant (p < 0.0001) and therefore was used to predict the type of contact dermatitis., Conclusions: Thermography is a reliable and effective way to distinguish between allergic and irritant contact dermatitis., (Copyright © 2018 Japanese Society of Allergology. Production and hosting by Elsevier B.V. All rights reserved.)

Determining the electronic properties of nanoscopic, low-dimensional materials free of external influences is key to the discovery and understanding of new physical phenomena. An example is the suspension of graphene, which has allowed access to their intrinsic charge transport properties. Furthermore, suspending thin films enables their application as membranes, sensors, or resonators, as has been explored extensively. While the suspension of covalently bound, electronically active thin films is well established, semiconducting thin films composed of functional molecules only held together by van der Waals interactions could only be studied supported by a substrate. In the present work, it is shown that by utilizing a surface-crystallization method, electron conductive films with thicknesses of down to 6 nm and planar chiral optical activity can be freely suspended across several hundreds of nanometers. The suspended membranes exhibit a Young's modulus of 2-13 GPa and are electronically decoupled from the environment, as established by temperature-dependent field-effect transistor measurements., (© 2019 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Context: Postprandial hyperinsulinemia might be an important cardiometabolic risk determinant in black compared with white women. However, the contributions of insulin clearance and β-cell function to racial differences in postprandial insulin response are unknown., Objective: To compare, by race and menopause, early insulin response to oral and intravenous glucose and to measure postprandial intact glucagon-like peptide 1 (GLP-1) concentrations, insulin clearance, and β-cell function., Design and Participants: 119 federally employed women without diabetes [87 premenopausal (52 black, 35 white) and 32 postmenopausal (19 black, 13 white)] underwent an oral glucose tolerance test, insulin-modified frequently sampled intravenous glucose test (IM-FSIGT), and mixed meal tolerance test (MMTT)., Outcome Measures: Early insulin response was measured as follows: (i) insulinogenic index (oral glucose tolerance test); (ii) acute insulin response to glucose (IM-FSIGT); and (iii) ratio of incremental insulin/glucose area under the curve in the first 30 minutes of the MMTT. Insulin clearance was assessed during the IM-FSIGT and MMTT. During the MMTT, intact GLP-1 was measured and β-cell function assessed using the insulin secretion rate and β-cell responsivity indexes., Results: Black pre-menopausal and postmenopausal women had a greater insulin response and lower insulin clearance and greater dynamic β-cell responsivity (P ≤ 0.05 for all). No differences were found in the total insulin secretion rates or intact GLP-1 concentrations., Conclusions: Greater postprandial hyperinsulinemia in black pre-menopausal and postmenopausal women was associated with lower hepatic insulin clearance and heightened β-cell capacity to rapid changes in glucose, but not to higher insulin secretion. The relationship of increased β-cell secretory capacity, reduced insulin clearance, and ambient hyperinsulinemia to the development of cardiometabolic disease requires further investigation.

Background: More epidemiological data about lentigo maligna melanoma (LMM) are required to define follow-up guidelines. The study focused on recurrence, progression, and overall survival of LMM managed with primary wide local excision., Methods: In a 23-year retrospective study (1994 to 2016), a cohort of patients with LMM was evaluated by collecting data about the tumor location, the Breslow depth, the presence of ulceration, and patients' age and sex. Local recurrences, locoregional and distant metastases, and disease-free and overall survival were additionally assessed., Results: Overall, 150 cases (84 male, 66 female, mean age 71.3 ± 11.3 years) of single, localized, primary LMM with a mean follow-up of 6.6 ± 4.4 years were included. A total of 33 (22.2%) patients underwent sentinel lymph node biopsy (SLNB) during surgical excision. However, positive SLNB was detected in none of them. The multivariable Cox analysis indicated that age of diagnosis and male gender significantly influenced the overall survival, while a shorter disease-free survival could be correlated with a greater Breslow thickness. The metastatic potential turned out to be low, entailing 7 deaths in the context of the LMM., Conclusion: Male gender, age over 70 at diagnosis, and a Breslow thickness greater than 0.75 mm were associated with a statistically significant decrease in overall disease-free survival in the current study. The results of the study confirm the favorable outcome of LMM. However, diagnosed patients should undertake regular follow-ups. The intensity of follow-up in these patients can be individualized based on the probability of recurrence/metastasis and overall survival. Furthermore, the study showed that SLNB might not be a necessary staging procedure in patients with LMM., (© 2019 S. Karger AG, Basel.)

There have been several important outbreaks of mosquito-borne diseases in the Neotropics in recent years, particularly in Brazil. Some taxa are also considered to be indicators of environmental health. Despite the importance of understanding insect abundance and distribution to the understanding of disease dynamics and design strategies to manage them, very little is known about their ecology in many tropical regions. We studied the abundance and diversity of mosquitoes and sand flies in the Bahia State of Brazil, a point of origin for arbovirus outbreaks, including Zika and Chikungunya fever. During 2009-2014, 51 mosquito taxa were identified, belonging to three dipteran families, Ceratopogonidae, Culicidae, and Psychodidae. The family Culicidae, including the Sabethini tribe, were the most abundant (81.5%) and most taxa-rich (n=45). While season (winter and summer) was a strong factor determinant of the occurrence of the most abundant taxa, the stratification level in the forest (ground or tree level) had a strong effect and the dominant taxa at ground level were completely different from the dominant species collected at tree level. We suggest that sites with a mix of forest and agroforestry systems support the highest biodiversity of hematophagous insects as compared to highly disturbed landscapes., (© 2018 The Society for Vector Ecology.)

Changes in the sleep-wake cycle are frequent and may impair quality of life in individuals with cerebral palsy (CP). To investigate if a lack of a day/night variation of melatonin content could be related with sleep disorders (SD), the SD were evaluated with a Sleep Questionnaire and the melatonin content using ELISA in 33 individuals with CP and 24 controls. The indicative of SD were present in 47% of CP group, and the most frequent was the indicative of sleep breathing disorder. The CP group showed higher diurnal and lower nocturnal melatonin content than controls. Individuals with CP that had indicative of SD showed lower nocturnal content of melatonin than those without SD. These results showed that the lack of the day/night variation of melatonin was related to SD in individuals with CP., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Background: To lower the risk of diabetes and heart disease in Africa, identification of African-centred thresholds for inexpensive biomarkers of insulin resistance (IR) is essential. The waist circumference (WC) thresholds that predicts IR in African men and women have not been established, but investigations recently conducted in Africa using indirect measures of IR suggest IR is predicted by WC of 80-95 cm in men and 90-99 cm in women. These WC cannot be used for guidelines until validated by direct measurements of IR and visceral adipose tissue (VAT). Therefore, we determined in a group of African-born black people living in America (A) the WC, which predicts IR and (B) the influence of abdominal fat distribution on IR., Methods: The 375 participants (age 38±10  years (mean±SD), 67% men) had IR determined by HOMA-IR and Matsuda index. VAT and subcutaneous adipose tissue (SAT) were measured by abdominal CT scans. Optimal WC for the prediction of IR was determined in sex-specific analyses by area under the receiver operating characteristic (AUC-ROC) and Youden index., Results: Women had more SAT (203±114 vs 128±74  cm 2 ) and less VAT than men (63±48 vs 117±72  cm 2 , p<0.001). Optimal WC for prediction of IR in men and women were: 91 cm (AUC-ROC: 0.80±0.03 (mean±SE)) and 96 cm (AUC-ROC: 0.81±0.08), respectively. Regression analyses revealed a significant sex-VAT interaction (p<0.001). Therefore, for every unit increase in VAT, women had a 0.94 higher unit increase in SAT and 0.07 higher unit increase in WC than men., Conclusion: Working with a group of African-born black people living in America, we accessed technology, which validated observations made in Africa. Higher SAT at every level of VAT explained why the WC that predicted IR was higher in women (96 cm) than men (91 cm). For Africans to benefit from WC measurements, convening a panel of experts to develop evidence-based African-centred WC guidelines may be the way forward., Competing Interests: Competing interests: None declared.

Cancer vaccines may be harnessed to incite immunity against poorly immunogenic tumors, however they have failed in therapeutic settings. Poor antigenicity coupled with systemic and intratumoral immune suppression have been significant drawbacks. RNA encoding for tumor associated or specific epitopes can serve as a more immunogenic and expeditious trigger of anti-tumor immunity. RNA stimulates innate immunity through toll like receptor stimulation producing type I interferon, and it mediates potent adaptive responses. Since RNA is inherently unstable, delivery systems have been developed to protect and deliver it to intended targets in vivo. In this review, we discuss liposomes as RNA delivery vehicles and their role as cancer vaccines.

Black women, compared with White women, have high rates of whole-body insulin resistance but a lower prevalence of fasting hyperglycemia and hepatic steatosis. This dissociation of whole-body insulin resistance from fasting hyperglycemia may be explained by racial differences in gluconeogenesis, hepatic fat, or tissue-specific insulin sensitivity. Two groups of premenopausal federally employed women, without diabetes were studied. Using stable isotope tracers, [2H2O] and [6,62-H2]glucose, basal glucose production was partitioned into its components (gluconeogenesis and glycogenolysis) and basal whole-body lipolysis ([2H5]glycerol) was measured. Indices of insulin sensitivity, whole-body (SI), hepatic (HISIGPR), and adipose tissue, were calculated. Hepatic fat was measured by proton magnetic resonance spectroscopy. Black women had less hepatic fat and lower fractional and absolute gluconeogenesis. Whole-body SI, HISIGPR, and adipose tissue sensitivity were similar by race, but at any given level of whole-body SI, Black women had higher HISIGPR. Therefore, fasting hyperglycemia may be a less common early pathological feature of prediabetes in Black women compared with White women, because gluconeogenesis remains lower despite similar whole-body SI.

Lactobacilli are the dominant bacteria of the vaginal tract of healthy women and they play a major role in the maintenance of mucosal homeostasis, preventing genital infections, such as bacterial vaginosis (BV) and vulvovaginal candidiasis (VVC). It is now known that one mechanism of this protection is the influence that lactobacilli can exert on host immune responses. In this context, we evaluated two Lactobacillus strains (L. plantarum 59 and L. fermentum 137) for their immunomodulatory properties in response to Gardnerella vaginalis (BV) or Candida albicans (VVC) infections in a HeLa cell infection model. G. vaginalis and C. albicans triggered the secretion of pro-inflammatory cytokines (TNF-α, IL-1β, IL-6 and IL-8) and the activation of NF-κB in HeLa cells, in contrast to L. plantarum 59 and L. fermentum 137. Treatments with the Lactobacillus strains or their cell-free supernatants before (pre-treatment) or after (post-treatment) the challenge with the pathogens resulted in decreased secretion of pro-inflammatory cytokines and decreased activation of NF-κB. The treatments with Lactobacillus strains not only decreased the secretion of IL-8, but also its expression, as confirmed by gene reporter luciferase assay, suggesting transcription-level control by lactobacilli. In conclusion, L. plantarum 59 and L. fermentum 137 were confirmed to have an anti-inflammatory effect against G. vaginalis and C. albicans and they were able to influence signalling in NF-κB pathway, making them interesting candidates as probiotics for the prevention or treatment of BV and VVC.

l-carnitine is an antioxidant and β-oxidation stimulator substance commonly used to improve metabolic performance of oocytes and embryos in in vitro systems. However, few studies have evaluated its beneficial effects in embryos produced in vivo. This study aimed to evaluate the effect of l-carnitine supplementation into vitrification or warming solutions on the post-warming character of day 6-7 in vivo-produced ovine embryos. l-carnitine (3.72 mM) was added to vitrification (Experiment 1) or warming solutions (Experiment 2). In experiments 1 and 2, the embryos were vitrified using straw and cryo-tip protocols, respectively. In vitro culture (IVC) of warmed embryos was performed for 72 h in order to evaluate survival rates, reactive oxygen species (ROS) levels, total cell number (TCN), number of apoptotic cells, apoptotic index evaluation, and gene expression analysis of carnitine palmitoyltransferase I and 2 (CPT1 and CPT2), carnitine O-acetyltransferase (CrAT), and peroxiredoxin-1 (PRDX1). In experiment 1, survival rate, ROS levels after 24 h of IVC, total cell number at 24 h and 72 h, apoptotic cells and apoptotic index at 72 h of IVC were similar in embryos vitrified in medium supplemented with LC or not. Gene expression analysis showed no differences in CPT1 and CPT2 mRNA relative abundance in embryos of both experiments compared to fresh embryos (FE); however, CrAT was downregulated (p < 0.05) in C1, and PRDX1 was downregulated (p < 0.05) in both the control (C1) and l-carnitine (LC1) groups, compared to FE. Moreover, CrAT and PRDX1 were upregulated (p < 0.05) in C2, and CrAT was downregulated (p < 0.05) in LC2, in relation to FE. Although the short-term LC supplementation at 3.72 mM did not improve survival, and quality parameters of in vivo-produced ovine embryos, it could affect their quality at a molecular level. In conclusion, further investigations with different concentrations of LC and tools are needed for improvement of the efficiency of these strategies., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Food additives are compounds used in order to improve food palatability, texture, and shelf life. Despite a significant effort to assure safety of use, toxicological analysis of these substances, generally, rely on their direct toxicity to target organs (liver and kidney) or their genotoxic effects. Much less attention is paid to the effects of these compounds on cells of the immune system. This is of relevance given that metabolic dysregulation and obesity have a strong immune-mediated component. Obese individuals present a state of chronic low-grade inflammation that contributes to the establishment of insulin resistance and other metabolic abnormalities known as the metabolic syndrome. Obesity and metabolic syndrome are currently recognized as worldwide epidemics that pose a profound socioeconomic impact and represent a concern to public health. Cells of the immune system contribute to both the maintenance of "lean homeostasis" and the metabolic dysregulation observed in obese individuals. Although much attention has been drawn in the past decades to obesity and metabolic syndrome as a result of ingesting highly processed food containing large amounts of fat and simple sugars, mounting evidence suggest that food additives may also be important contributors to metabolic derangement. Herein, we review pieces of evidence from the literature showing that food additives have relevant effects on cells of the immune system that could contribute to immune-mediated metabolic dysregulation. Considering their potential to predispose individuals to develop obesity and metabolic syndrome, their use should be taken with caution or maybe revisited.

Objective: To evaluate speech in adults treated for unilateral cleft lip and palate with one-stage or two-stage palate closure and compare the speech of the patients with that of a noncleft control group., Design: Cross-sectional study with long-term follow-up., Participants/setting: All unilateral cleft lip and palate patients born from 1960 to 1987 and treated at Uppsala University Hospital, Sweden, were invited (n = 109). Participation rate was 67% (n = 73) at a mean of 35 years after primary surgery. Forty-seven had been treated according to one-stage palate closure and 26 according to two-stage palate closure. Pharyngeal flap surgery had been performed in 11 of the 73 patients (15%). The noncleft control group consisted of 63 age-matched volunteers., Main Outcome Measure(s): Speech-language pathologists rated perceptual speech characteristics from blinded audio recordings., Results: Among patients, seven (10%) presented with hypernasality, 12 (16%) had audible nasal emission and/or nasal turbulence, five (7%) had consonant production errors, one (2%) had glottal reinforcements/substitutions, and one (2%) had reduced intelligibility. Controls had no audible signs of velopharyngeal insufficiency and no quantifiable problems with the other speech production variables. No significant differences were identified between patients treated with one-stage and two-stage palate closure for any of the variables., Conclusions: The prevalence of speech outcome indicative of velopharyngeal insufficiency among adult patients treated for unilateral cleft lip and palate was low but higher compared with individuals without cleft. Whether palatal closure is performed in one or two stages does not seem to affect the speech outcome at a mean age of 35 years.