Treatment of spinal cord injury with biomaterials and stem cell therapy in non-human primates and humans.

Spinal cord injury results in the loss of sensory, motor, and autonomic functions, which almost always produces permanent physical disability. Thus, in the search for more effective treatments than those already applied for years, which are not entirely efficient, researches have been able to demonstrate the potential of biological strategies using biomaterials to tissue manufacturing through bioengineering and stem cell therapy as a neuroregenerative approach, seeking to promote neuronal recovery after spinal cord injury. Each of these strategies has been developed and meticulously evaluated in several animal models with the aim of analyzing the potential of interventions for neuronal repair and, consequently, boosting functional recovery. Although the majority of experimental research has been conducted in rodents, there is increasing recognition of the importance, and need, of evaluating the safety and efficacy of these interventions in non-human primates before moving to clinical trials involving therapies potentially promising in humans. This article is a literature review from databases (PubMed, Science Direct, Elsevier, Scielo, Redalyc, Cochrane, and NCBI) from 10 years ago to date, using keywords (spinal cord injury, cell therapy, non-human primates, humans, and bioengineering in spinal cord injury). From 110 retrieved articles, after two selection rounds based on inclusion and exclusion criteria, 21 articles were analyzed. Thus, this review arises from the need to recognize the experimental therapeutic advances applied in non-human primates and even humans, aimed at deepening these strategies and identifying the advantages and influence of the results on extrapolation for clinical applicability in humans.

Human cystic echinococcosis: first molecular identification of Echinococcus canadensis G7 in Brazil.

Echinococcus granulosus sensu lato (s.l.) is a species complex with the potential to cause cystic echinococcosis (CE). Contact with the feces of domestic dogs (Canis familiaris) fed with raw viscera of intermediate livestock hosts is a risk factor for this infection in the southern region of Brazil. Although the region has been considered endemic to CE for many years, molecular data regarding the species of the complex causing CE in humans are scarce. This study aimed to perform a molecular analysis of the biological fluid from a human liver cyst to investigate the species responsible for CE. Genetic material obtained from the hydatid fluid of a hepatic cyst from a human with CE was subjected to PCR to amplify mitochondrial and nuclear DNA sequences. The phylogenetic analysis confirmed the human infection by Echinococcus canadensis G7 in the state of Paraná, Brazil. This is the first molecular record of E. canadensis G7 infecting a human in Brazil, and it is important to reiterate the risk of human CE caused by this species in South America, as reported by a previous study in Patagonia, Argentina. From the epidemiological point of view, this finding is of great relevance for the southern region of Brazil, since this parasite has previously only been detected in pigs in the state of Rio Grande do Sul, neighboring Paraná. The finding points to the importance of this identification in the molecular epidemiology of E. granulosus s.l., especially in South America.

Promising Effects of Casearins in Tumor-Bearing Mice and Antinociceptive Action against Oncologic Pain: Molecular Docking and In Vivo Findings.

Safer analgesic drugs remain a hard challenge because of cardiovascular and/or gastrointestinal toxicity, mainly. So, this study evaluated in vivo the antiproliferative actions of a fraction with casearins (FC) from Casearia sylvestris leaves against human colorectal carcinomas and antihyperalgesic effects on inflammatory- or opiate-based pain relief and oncologic pain in Sarcoma 180 (S180)-bearing mice. Moreover, docking investigations evaluated the binding among Casearin X and NMDA(N-methyl-D-aspartate)-type glutamate receptors. HCT-116 colorectal carcinoma-xenografted mice were treated with FC for 15 days. Antinociceptive assays included chemically induced algesia and investigated mechanisms by pharmacological blockade. Intraplantar region S180-bearing animals received a single dose of FC and were examined for mechanical allodynia and behavior alterations. AutoDock Vina determined molecular interactions among Cas X and NMDA receptor subunits. FC reduced tumor growth at i.p. (5 and 10 mg/kg) and oral (25 mg/kg/day) doses (31.12-39.27%). FC reduced abdominal pain, as confirmed by formalin and glutamate protocols, whose antinociception activity was blocked by naloxone and L-NAME (neurogenic phase) and naloxone, atropine, and flumazenil (inflammatory phase). Meanwhile, glibenclamide potentiated the FC analgesic effects. FC increased the paw withdrawal threshold without producing changes in exploratory parameters or motor coordination. Cas X generated a more stable complex with active sites of the NMDA receptor GluN2B subunits. FC is a promising antitumor agent against colorectal carcinomas, has peripheral analgesic effects by desensitizing secondary afferent neurons, and inhibits glutamate release from presynaptic neurons and/or their action on cognate receptors. These findings emphasize the use of clerodane diterpenes against cancer-related pain conditions.

Galectin-3 absence alters lymphocytes populations dynamics behavior and promotes functional recovery after spinal cord injury in mice.

Spinal cord injury (SCI) results from various mechanisms that damage the nervous tissue and the blood-brain barrier, leading to sensory and motor function loss below the injury site. Unfortunately, current therapeutic approaches for SCI have limited efficacy in improving patients outcomes. Galectin-3, a protein whose expression increases after SCI, influences the neuroinflammatory response by favoring pro-inflammatory M1 macrophages and microglia, while inhibiting pro-regenerative M2 macrophages and microglia, which are crucial for inflammation resolution and tissue regeneration. Previous studies with Galectin-3 knock-out mice demonstrated enhanced motor recovery after SCI. The M1/M2 balance is strongly influenced by the predominant lymphocytic profiles (Th1, Th2, T Reg, Th17) and cytokines and chemokines released at the lesion site. The present study aimed to investigate how the absence of galectin-3 impacts the adaptive immune system cell population dynamics in various lymphoid spaces following a low thoracic spinal cord compression injury (T9-T10) using a 30 g vascular clip for one minute. It also aimed to assess its influence on the functional outcome in wild-type (WT)and Galectin-3 knock-out (GALNEG) mice. Histological analysis with hematoxylin-eosin and Luxol Fast Blue staining revealed that WT and GALNEG animals exhibit similar spinal cord morphology. The absence of galectin-3 does not affect the common neuroanatomy shared between the groups prompting us to analyze outcomes between both groups. Following our crush model, both groups lost motor and sensory functions below the lesion level. During a 42-day period, GALNEG mice demonstrated superior locomotor recovery in the Basso Mouse Scale (BMS) gait analysis and enhanced motor coordination performance in the ladder rung walk test (LRW) compared to WT mice. GALNEG mice also exhibited better sensory recovery, and their electrophysiological parameters suggested a higher number of functional axons with faster nerve conduction. Seven days after injury, flow cytometry of thymus, spleen, and blood revealed an increased number of T Reg and Th2 cells, accompanied by a decrease in Th1 and Th17 cells in GALNEG mice. Immunohistochemistry conducted on the same day exhibited an increased number of Th2 and T Reg cells around the GALNEG's spinal cord lesion site. At 42-day dpi immunohistochemistry analyses displayed reduced astrogliosis and greater axon preservation in GALNEG's spinal cord seem as a reduction of GFAP immunostaining and an increase in NFH immunostaining, respectively. In conclusion, GALNEG mice exhibited better functional recovery attributed to the milder pro-inflammatory influence, compensated by a higher quantity of T Reg and Th2 cells. These findings suggest that galectin-3 plays a crucial role in the immune response after spinal cord injury and could be a potential target for clinical therapeutic interventions.

Loss of Fshr Prevents Testicular Maturation in Atlantic Salmon (Salmo salar L.).

Early puberty poses a significant challenge for male Atlantic salmon in aquaculture due to its negative impact on growth and welfare. The regulation of puberty in vertebrates involves 2 key reproductive hormones: follicle-stimulating hormone (FSH) and luteinizing hormone (LH) and their gonadal receptors. In male mice lacking FSH receptor, testes size is reduced, but fertility is maintained, while medaka and zebrafish with a disrupted fshr gene exhibit near normal testis size and fertility. In these fishes both Fsh and Lh are present during puberty and Lh may rescue fertility, while in salmonid fish only Fsh is present in the circulation during puberty. Using CRISPR-Cas9, we produced crispants with a high prevalence of fshr mutations at the target site, which remained fertile, although more than half showed a testis development deviating from wild-type (wt) males. Crossing out these F0 crispants to each other produced a viable F1 generation showing frameshift (fshr-/-) or in-frame mutations (fshrif/if). Nearly all wt males matured while all fshr-/- males remained immature with small testes containing A spermatogonia as the furthest developed germ cell type and prepubertal plasma androgen levels. Also, the pituitary transcript levels of gnrhr2bba and lhb, but not for fshb, were reduced in the fshr-/- males compared with maturing males. More than half of the fshrif/if mutant males showed no or a delayed maturation. In conclusion, Atlantic salmon show the unique characteristic that loss of Fshr function alone results in male infertility, offering new opportunities to control precocious puberty or fertility in salmon.

Focus of dental sleep medicine on obstructive sleep apnea in older adults: A narrative review.

PURPOSE: To review dental sleep medicine in older adults based on the literature. STUDY SELECTION: This narrative review focuses on sleep physiology, common sleep disorders, and obstructive sleep apnea (OSA) in older adults and their management. RESULTS: Sleep physiology differs between older and younger adults, with sleep disturbances occurring more frequently in older adults. The prevalence of insomnia increases in older adults due to age-related changes in sleep physiology. Insomnia, sleep-disordered breathing, periodic limb movement disorder, restless legs syndrome, and rapid eye movement (REM) sleep behavior disorder are common sleep disorders in older adults. OSA is more prevalent in older adults, and its effects on them are considered more substantial than those on younger adults. The treatment of older patients with mandibular advancement devices may be less effective and more complex owing to potential impairments in oral and dental health. Furthermore, the prevalence of edentulism in older adults is decreasing while life expectancy is increasing. CONCLUSIONS: As older adults have comorbidities that affect sleep quality, dentists should consider the effects of sleep physiology and sleep disorders in these patients. OSA may decrease the quality of life and increase the risk of developing other diseases. Therefore, dentists proposing treatment with mandibular advancement devices need to inform patients of their potential lack of efficacy and the requirement for careful follow-up owing to known and unknown side effects.

Management of Persistent, Post-adenotonsillectomy Obstructive Sleep Apnea in Children: An Official American Thoracic Society Clinical Practice Guideline.

Background: Obstructive sleep apnea (OSA) is the most common sleep-related breathing disorder. Although adenotonsillectomy is first-line management for pediatric OSA, up to 40% of children may have persistent OSA. This document provides an evidence-based clinical practice guideline on the management of children with persistent OSA. The target audience is clinicians, including physicians, dentists, and allied health professionals, caring for children with OSA. Methods: A multidisciplinary international panel of experts was convened to determine key unanswered questions regarding the management of persistent pediatric OSA. We conducted a systematic review of the relevant literature. The Grading of Recommendations, Assessment, Development, and Evaluation approach was used to rate the quality of evidence and the strength of the clinical recommendations. The panel members considered the strength of each recommendation and evaluated the benefits and risks of applying the intervention. In formulating the recommendations, the panel considered patient and caregiver values, the cost of care, and feasibility. Results: Recommendations were developed for six management options for persistent OSA. Conclusions: The panel developed recommendations for the management of persistent pediatric OSA based on limited evidence and expert opinion. Important areas for future research were identified for each recommendation.

Effect of thermo mechanical stimulation duringlocal anesthesia in pediatric dentistry: a pilot randomized clinical trial / Efeito de estimulação termomecânica durante anestesia local em odontopediatria: um ensaio clínico randomizado piloto

Objetivo: Avaliar a eficácia de um dispositivo de estimulação termomecânica (Buzzy®) em relação à dor, medo e ansiedade durante anestesia local em crianças. Materiais e métodos: Estudo realizado no período de maio de 2018 a julho de 2019, com crianças de 7 a 11 anos, sem experiência prévia envolvendo anestesia nos últimos 2 anos e que necessitassem de tratamento odontológico (extração, restauração ou endodontia) sob anestesia local em molares decíduos. A amostra foi randomizada em grupo controle, que recebeu anestesia convencional, e grupo intervenção, que recebeu anestesia com Buzzy®. Os níveis de ansiedade, medo e percepção de dor de ambos os grupos foram verificados por meio de: Venham Modified Picture Test (VPTM); frequência cardíaca; Escala Comportamental Venham; Faces Pain Scale ­ Revised (FPS-R) e Face, Legs, Activity, Cry, Consolability (FLACC). Resultados: A maioria das crianças (55%) apresentou baixa ansiedade antes e depois do tratamento (P<0,05). A aceitabilidade das crianças ao Buzzy® foi de 100% e a maioria (90%) gostaria de usar novamente. Discussão: O aparelho testado é uma ferramenta interessante para complementar as técnicas de manejo durante as consultas, tendo em vista a excelente aceitabilidade e interesse por parte dos pacientes e familiares. Conclusão: Este estudo demonstrou que o uso da estimulação termomecânica é viável na clínica odontológica, devido ao seu fácil uso e boa aceitabilidade no meio clínico, além de não apresentar riscos em seu uso.

Aim: To evaluate the effectiveness of a thermo mechanical stimulation device (Buzzy®) in relation to pain, fear and anxiety during local anesthesia in children. Materials and methods: Study carried out from May 2018 to July 2019, with children aged 7 to 11 years, without previous experience involving anesthesia in the last 2 years and who needed dental treatment (extraction, restoration or endodontic) under local anesthesia in deciduous molars. The sample was randomized into a control group, which received conventional anesthesia, and an intervention group, which received anesthesia with Buzzy®. The levels of anxiety, fear and pain perception of both groups were verified using: Come Modified Picture Test (VPTM); heart rate; Behavioral Scale Come; Faces Pain Scale ­ Revised (FPS-R) and Face, Legs, Activity, Cry, Consolability (FLACC). Results: Most children (55%) had low anxiety before and after treatment (P<0.05). The acceptability of the children to Buzzy® was 100% and the majority (90%) would like to use it again. Discussion: The tested device is an interesting tool to complement management techniques during consultations, in view of the excellent acceptability and interest on the part of patients and family members. Conclusion: This study demonstrated that the use of thermo mechanical stimulation is feasible in the dental clinic, due to its easy use and good acceptability in the clinical environment, in addition to not presenting risks in its use.

Growth of breast muscles in European and Japanese quail raised in meat production system: a morphological analysis.

Growth curves have been described in the quail but with no attention to the muscle composing of the breast. The description of the characteristics of growth curves to body weight and to breast muscle was the aim of this study. Morphological development of Musculus supracoracoideus and Musculus pectoralis in European and Japanese quail was assessed from the final incubation of to 35 days. Gompertz models were adjusted with maximum growth rates to body weight, breast weight, and Musculus pectoralis and supracoracoideus weight at 17.6; 22.2; 23.5, and 21.4 days. The European quail had a higher body and breast weight at maturity. Musculus supracoracoideus developed faster in both subspecies but with larger Musculus pectoralis. Both musculus had a greater number of fibers type IIA and largest fibers IIB, with quadratically increasing in fiber diameter with age in both subspecies and muscles. At 35 days, results of meat quality indicated similarity between genders and subspecies, with darker and redness breast meat in Japanese quail. In conclusion, breast weight gain was a result of type IIA and IIB fiber hypertrophy in both muscles and, despite the difference in size and aptitude, Japanese and European quail showed similar body and muscle growth patterns.

Diversity of helminths with zoonotic potential and molecular characterization of Toxocara canis infecting domestic dogs from locations of Amazon and Atlantic Forest Brazilian biomes.

The coproparasitological examination of dogs (n=278) from two Brazilian biomes (Amazon [AZ] and Atlantic Forest [AF]) by centrifugal flotation demonstrated positivity values of 54.2% (AF) and 48.5% (AZ). The most prevalent parasites in AF were hookworms (81.0% - 47/58), Toxocara sp. (17.3% - 10/58) and Trichuris vulpis (12.1% - 7/58); while in AZ they were hookworms (86.7% - 72/83), Toxocara sp. (18.1% - 15/83), Dipylidium caninum (13.3% - 11/83) and T. vulpis (10.8% - 9/83). PCR was performed using the partial mitochondrial genes cytochrome c oxidase subunit 1 (pcox1) and NADH dehydrogenase 1 (pnad1) in 25 fecal samples positive for Toxocara sp. eggs and found one sample positive for pcox1 and six positives for pnad1. The sequencing of these samples was unsuccessful due to the difficulties inherent in copro-PCR+sequencing. The sequencing of 14 samples of T. canis adult helminths retrieved 11 sequences of 414 bp for pcox1 and nine sequences of 358 bp for pnad1. The phylogenetic trees of these sequences confirmed the species T. canis. Intraspecific genetic variation was only observed for pnad1. This is the second study involving molecular analysis of T. canis in dogs from Brazil and adds new information through the use of pnad1.

Craniofacial features of adult obese obstructive sleep apnoea patients in relation to the obesity onset - A pilot study.

INTRODUCTION: Obesity and craniofacial structures are aetiologies of obstructive sleep apnoea (OSA). The effect of obesity onset on the craniofacial development and growth of obese OSA subjects has been suggested, but supporting data were lacking. This study aimed to assess the craniofacial features of adult obese OSA patients in relation to their obesity onset. MATERIALS AND METHODS: A total of 62 adult OSA patients were included in the study, consisting of 12 early-onset (i.e. before puberty), 21 late-onset (i.e. after puberty) and 29 non-obese. All participants underwent a sleep study and cephalometric radiograph. Cephalometric analysis was conducted to measure the craniofacial features among the groups. RESULTS: The early obesity onset group (n = 12) showed a more prognathic mandible, longer lower facial height, protrusive incisors, a more caudal position of the hyoid bone and a wider lower airway. The late-onset group (n = 21) had more proclined and protrusive upper incisors, a shallower overbite, a more inferiorly positioned hyoid bone and an obtuse craniocervical angle. The overall obese group showed a combination of the findings above, plus a shorter soft palate and shorter airway length. There was no significant difference between early and late obesity onset groups. However, the early group showed a tendency for a shallower or decreased mandibular plane angle and deeper overbite. CONCLUSIONS: The current pilot study had many limitations but holds important information as a hypothesis generator. Craniofacial features of OSA patients with different obesity onset showed discrepancies and were distinguished from non-obese controls. Adult OSA patients with an early obesity onset showed a tendency for a more hypodivergent growth pattern than those with a late obesity onset.

T Cell Response in Tuberculosis-Infected Patients Vaccinated against COVID-19.

Many studies have focused on SARS-CoV-2 and Mycobacterium tuberculosis (Mtb) co-infection consequences. However, after a vaccination plan against COVID-19, the cases of severe disease and death are consistently controlled, although cases of asymptomatic and mild COVID-19 still happen together with tuberculosis (TB) cases. Thus, in this context, we sought to compare the T cell response of COVID-19-non-vaccinated and -vaccinated patients with active tuberculosis exposed to SARS-CoV-2 antigens. Flow cytometry was used to analyze activation markers (i.e., CD69 and CD137) and cytokines (IFN-γ, TNFα, IL-17, and IL-10) levels in CD4+ and CD8+ T cells upon exposure to SARS-CoV-2 peptides. The data obtained showed that CD8+ T cells from non-vaccinated TB patients present a high frequency of CD69 and TNF-α after viral challenge compared to vaccinated TB donors. Conversely, CD4+ T cells from vaccinated TB patients show a high frequency of IL-10 after spike peptide stimulus compared to non-vaccinated patients. No differences were observed in the other parameters analyzed. The results suggest that this reduced immune balance in coinfected individuals may have consequences for pathogen control, necessitating further research to understand its impact on clinical outcomes after COVID-19 vaccination in those with concurrent SARS-CoV-2 and Mtb infections.

Maternal chronic caffeine intake impairs fertility, placental vascularization and fetal development in mice.

Caffeine is commonly consumed by pregnant women to avoid fatigue or as a habit. However, it is not clearly determined its side effects to the conceptuses. This study evaluated placental morphofunctional alterations after maternal chronic caffeine intake and the effects on fetal growth. Female Swiss mice received, via gavage, caffeine doses (either 60, 120 or 240 mg/kg/day) seven days before mating until gestational days-(GD) 11.5 or 17.5. Fetal biometrical parameters were assessed, and placentae were either submitted to histomorphometrical or molecular evaluation of angiogenesis (placental growth factor-1[PlGF-1]), apoptosis (Caspase-3) and proliferation (Ki-67) markers (evaluated in Swiss dams) and to intravital microscopy (evaluated in C57BL/6 dams). Caffeine exposed fetuses exhibited intrauterine growth restriction in a sex-dependent manner, with greater commitment of female fetuses (P < 0.05). In addition, placentae from dams that received 120 mg/kg/day showed less irrigation by maternal blood and greater development of fetal vasculature, characterized by higher number of larger vessels (P < 0.05). Although no effects on apoptosis (Caspase-3) and angiogenesis (PlGF-1) were observed, dams treated with 60 mg/kg/day showed greater placental cell proliferation (Ki-67 staining) at GD 11.5 (P < 0.05). The group treated with 240 mg/kg/day exhibited only one pregnant dam for each gestational age, suggesting that this high caffeine consumption may compromise fertility. Taken together, even in the doses currently ingested by many pregnant women, caffeine has detrimental effects on placental vasculature and fetal development in mice. Therefore, our results strongly suggest that caffeine consumption in human pregnancies greater than the recommended doses should be avoided.

Mycobacterium tuberculosis in a Trap: The Role of Neutrophil Extracellular Traps in Tuberculosis.

Mycobacterium tuberculosis complex causes tuberculosis (TB), a disease that causes pulmonary inflammation but can also affect other tissues. Despite macrophages having a defined role in TB immunopathogenesis, other innate immune cells, such as neutrophils, are involved in this process. These cells have high phagocytic ability and a microbial-killing machine comprised of enzymes, antimicrobial peptides, and reactive oxygen species. In the last two decades, a new neutrophil immune response, the neutrophil extracellular traps (NETs), has been intensely researched. NETs comprise DNA associated with histones, enzymes, and antimicrobial peptides. These structures are related to antimicrobial immune response and some immuno-pathogenesis mechanisms. This mini review highlights the role of NETs in tuberculosis and how they can be helpful as a diagnostic tool and/or therapeutic target.

Orthodontic and Facial Characteristics of Craniofacial Syndromic Children with Obstructive Sleep Apnea.

Introduction: Obstructive sleep apnea (OSA) is a disorder in which ventilation becomes disrupted due to a complete or partial upper airway obstruction Altered craniofacial morphology is one of the most important anatomical factors associated with obstructive sleep apnea (OSA). Studies have assessed craniofacial features in the non-syndromic pediatric population. The aim of this study was to analyze the orthodontic and facial characteristic of craniofacial syndromic children referred for polysomnography (PSG) and to assess the correlation with the apnea-hypopnea index (AHI). Methods: In the current cross-sectional study, consecutive syndromic patients referred for PSG were invited to participate. A systematic clinical examination including extra- and intra-oral orthodontic examination was performed by calibrated orthodontists. Standardized frontal and profile photographs with reference points were taken and analyzed using ImageJ® software to study the craniofacial morphology. PSG data were analyzed for correlation with craniofacial features. STROBE guidelines were strictly adopted during the research presentation. Results: The sample included 52 syndromic patients (50% females, mean age 9.38 ± 3.36 years) diagnosed with 17 different syndromes, of which 24 patients had craniofacial photography analysis carried out. Most of the sample (40%) had severe OSA, while only 5.8% had no OSA. Down's syndrome (DS) was the most common syndrome (40%) followed by Goldenhar syndrome (5%), Pierre Robin Sequence (5%), and other syndromes. The severity of AHI was significantly correlated with decreased midfacial height. increased thyromental angle and cervicomental angle, decreased mandibular angle, and decreased upper facial height. All patients with DS were diagnosed with OSA (57% severe OSA), and their ODI was significantly correlated with increased intercanthal distance. Obesity was not correlated to the severity of AHI for syndromic patients. Conclusions: Decreased midfacial height and obtuse thyromental angle were correlated with increased AHI for syndromic patients. Increased intercanthal distance of DS patients could be a major predictor of OSA severity. Obesity does not seem to play a major role in the severity of OSA for syndromic patients. Further studies with larger samples are necessary to confirm these findings.

The role of oral appliance therapy in obstructive sleep apnoea.

There is now widespread recognition within the world of sleep medicine of the increasing importance of dental sleep medicine and, in particular, the role of oral appliance therapy (OAT) in the management of adults with obstructive sleep apnoea (OSA). For the purpose of this review, the term OAT refers to a custom-made intra-oral appliance, which acts to posture the mandible in a forward and downward direction, away from its natural resting position. Whilst nasally applied continuous positive airway pressure remains the "gold standard" in nonsurgical OSA management, OAT remains the recognised alternative treatment.This review of OAT aims to provide an evidence-based update on our current understanding of their mode of action, exploring the potential anatomical and physiological impact of their use in preventing collapse of the upper airway; the current clinical practice guidelines, including the recently published National Institute of Clinical Excellence 2021 guidance, in conjunction with the American Academy of Sleep Medicine and American Academy of Dental Sleep Medicine; optimal design features, comparing the role of custom-made versus noncustom OAT devices and the importance of titration in achieving a dose-dependent effect; patient predictors, preference and adherence to OAT; its impact on a range of both patient- and clinician-centred health outcomes, with a comparison with CPAP; the limitations and side-effects of providing OAT; and, finally, a look at future considerations to help optimise the delivery and outcomes of OAT.

Control of Tongue Position in Patients with Obstructive Sleep Apnea: Concept and Protocol for a Randomized Controlled Crossover Trial.

We hypothesize that the control of tongue position using a newly developed tongue position retainer, where the tongue is held in a protruded position (i.e., intervention A) or in its resting position (i.e., intervention B), is effective for maintaining upper airway patency in obstructive sleep apnea (OSA) compared with no control of tongue position. This is a randomized, controlled, non-blinded, crossover, and two-armed trial (i.e., sequence AB/BA) in 26 male participants (i.e., sample size) who are scheduled to undergo a dental operation under intravenous sedation with OSA (10 ≤ respiratory event index < 30/h). Participants will be randomly allocated into either sequence by a permuted block method, stratified by body mass index. Under intravenous sedation, participants will undergo two interventions, separated by a washout period after receiving intervention A or intervention B using a tongue position retainer after baseline evaluation, before each intervention is provided. The primary outcome is the abnormal breathing index of apnea as determined by the frequency of apnea per hour. We expect that, compared with no control of tongue position, both intervention A and intervention B will improve the abnormal breathing events with superior effects achieved by the former, offering a therapeutic option for OSA.

Leishmaniasis: Immune Cells Crosstalk in Macrophage Polarization.

Leishmaniasis is a complex infectious parasitic disease caused by protozoa of the genus Leishmania, belonging to a group of neglected tropical diseases. It establishes significant global health challenges, particularly in socio-economically disadvantaged regions. Macrophages, as innate immune cells, play a crucial role in initiating the inflammatory response against the pathogens responsible for this disease. Macrophage polarization, the process of differentiating macrophages into pro-inflammatory (M1) or anti-inflammatory (M2) phenotypes, is essential for the immune response in leishmaniasis. The M1 phenotype is associated with resistance to Leishmania infection, while the M2 phenotype is predominant in susceptible environments. Notably, various immune cells, including T cells, play a significant role in modulating macrophage polarization by releasing cytokines that influence macrophage maturation and function. Furthermore, other immune cells can also impact macrophage polarization in a T-cell-independent manner. Therefore, this review comprehensively examines macrophage polarization's role in leishmaniasis and other immune cells' potential involvement in this intricate process.