Prevalence of mandibular asymmetries in the pediatric population of Jazan: A radiographic analytical study.

Background: Facial asymmetry results from variation in mandibular linear and angular dimensions on the right and left sides of the face. Mandibular asymmetry is of great significance to oral surgeons and orthodontists as it directly impacts the facial profile of an individual. Aim: The present study aimed to measure the prevalence of mandibular asymmetry and its fluctuations during the mixed dentition growth phase in healthy children aged 6-8 years in the Jazan region of Saudi Arabia. Method: This retrospective observational study was conducted by measuring linear asymmetrical measurements of mandible on orthopantomograms of 390 healthy children (182 boys and 208 girls, aged 6-8 years) with mixed dentition. Linear measurements from orthopantomograms were obtained using a standardized digitizer. Two sets of mandibular measurements were recorded, alongside subjective assessments of mandibular first molar development. An independent t-test was employed to assess the significance between measurements on both sides, while one-way ANOVA was used to demonstrate facial asymmetry significance among different age groups. Result: The result of this study revealed a significant statistical difference (p-value≤ 0.05) for both sides of the mandible across two dimensions: condylar and ramus height (p value = 0.03) and mandibular length (p value = 0.04). The asymmetry index resulted in no asymmetry among most of the included subjects. However, compared to the other three linear measurements, many seven-year-old participants possess mandibular asymmetry on condylar height (54.5 %). Conclusion: Within the limitation it could be concluded that children in growing age have a significant mandibular asymmetry (mainly 7 years), which, however, is only seldom clinically significant. Hence, treatment plan should be cautiously planned.

Prevalence and Variation of Medical Comorbidities in Oral Surgery Patients: A Retrospective Study at Jazan University.

BACKGROUND An aged population is susceptible to chronic diseases, which impacts oral surgery treatment procedures. This retrospective study aimed to evaluate the incidence of medical comorbidities in 640 oral surgery patients treated at the College of Dentistry, Jazan University. MATERIAL AND METHODS This single-center observational study investigated medical records of outpatients who visited Jazan University Dental College Hospital in a 1-year period (2018-2019). Patients’ clinical and radiographic archives were screened to obtain relevant data. Categorical and continuous variables were expressed in terms of frequency and mean values, respectively. Differences in variables were statistically analyzed using the chi-square goodness of fit and proportional test, with a probability value P≤0.05 considered significant. RESULTS Analysis of 640 patient records included records of 300 men and 340 women who underwent oral surgery, of whom 176 patients (27.5%), including 97 men and 79 women, had medical comorbidities. The most common comorbidities were endocrine disease (7.03%), cardiovascular disease (6.71%), respiratory disease (4.53%), and hematological disorders (3.43%). Individual diseases that showed higher prevalence were diabetes mellitus (4.68%), hypertension (3.43%), bronchial asthma (2.65%), and anemia (1.4%). Differences by sex were observed in many individual disorders. CONCLUSIONS Outpatients in oral surgery clinics presented a significant variance in the incidence of medical comorbidities, among which diabetes and hypertension were most common. A proper case history is the best preventive measure that helps a surgeon avert medical emergencies and post-surgical complications.

Comparison of the effects of two different styles of orally prescribing prednisolone on postoperative sequelae of surgical extraction of an impacted mandibular third molar: a single-blind randomized study.

Objectives: Surgical intervention for removal of an impacted third molar can lead to significant pain and swelling. Corticosteroids show promise for mitigating postoperative sequelae across various surgical contexts. The use of corticosteroids following minor oral surgery, though controversial, has already been proven effective. However, little research has explored peroral prescription of corticosteroids despite its convenience for outpatients and for non-surgeons like implantologists and periodontists and others who don't have access to needle injections. The aim of this study was to address a void in the literature by comparing the effects of two styles of preoral administration of prednisolone after surgical removal of the mandibular third molar and to determine which style minimizes postoperative sequelae. Materials and Methods: A randomized, split-mouth clinical study was conducted to investigate the efficacy of two different styles of preoral prednisolone in mitigating postoperative sequelae following surgical extraction of impacted mandibular third molars. Fifteen participants were enrolled in the study. Random selection was used to determine the prescription style for the right and left mandibular arch. Group A included those who received a single dose of prednisolone 25 mg, while group B received prednisolone 5 mg postoperatively for a period of three days (5 mg three times/day on the first postoperative day, 5 mg twice/day on the second postoperative day; 5 mg once/day on the third postoperative day). Results: There was a significant difference in the distance between the corner of the mouth and tragus, which decreased with the time interval with respect to group B when compared to group A. Conclusion: The present study showed that a three-day tapered dose of prednisolone postoperatively was more effective in reducing post-extraction sequelae than a single-dose regimen.

Real-world analysis of integration of sacubitril/valsartan into clinical practice in Saudi Arabia.

Despite the demonstrated advantages of angiotensin receptor/neprilysin inhibitors in the management of heart failure, the pivotal Angiotensin-Neprilysin Inhibition versus Enalapril in Heart Failure (PARADIGM-HF) trial, which explored this class of medications, did not include individuals from Saudi Arabia. Recognizing that different nations and ethnic groups may exhibit unique characteristics, this study aimed to compare the demographics and outcomes of patients in Saudi Arabia who received sacubitril/valsartan (Sac/Val) with those enrolled in the PARADIGM-HF trial. In this retrospective, multicenter cohort study, we included all adult patients diagnosed with heart failure with reduced ejection fraction (HFrEF) within a tertiary healthcare system in Saudi Arabia between January 2018 and December 2021 and were initiated on Sac/Val. The primary objective was to compare the patient characteristics of those initiating Sac/Val treatment with the participants in the PARADIGM-HF trial. The secondary endpoints included the initiation setting, dose initiation, and titration, as well as alterations in B-type natriuretic peptide and ejection fraction at the 6-month mark. Furthermore, we reported the hospitalization and mortality event rates at the 12-month time point. The study included 400 patients with HFrEF receiving Sac/Val. Compared with the PARADIGM-HF trial, the cohort had a younger mean age and a higher prevalence of diabetes mellitus. SAC/VAL was prescribed as the initial therapy for 34% of the patients, while the remaining participants were initially treated with either an angiotensin-converting enzyme inhibitor or an angiotensin receptor blocker before transitioning to Sac/Val. Approximately 75% of patients were initiated on 100 mg Sac/Val twice daily, and 90% initiated therapy in the inpatient setting. The mean ejection fraction significantly improved from 26.5 ±â€…8.4% to 30.5 ±â€…6.4% at 6 months (P < .001), while the median B-type natriuretic peptide level change was not significant (P = .39). Our study revealed notable disparities in the baseline characteristics of patients with HFrEF compared with those in the PARADIGM-HF trial. These findings offer valuable real-world insights into the prescription patterns and outcomes of Sac/Val in patients with HFrEF in Saudi Arabia, an aspect not previously represented in the PARADIGM-HF study.

Oral administration of naringenin and a mixture of coconut water and Arabic gum attenuate oxidative stress and lipid peroxidation in gentamicin-induced nephrotoxicity in rats.

OBJECTIVE: This study aimed to investigate the effect of oral administration of naringenin in combination with an aqueous mixture of coconut water (CW) and Arabic gum (AG) on renal function, lipid profile, antioxidant activity, and morphology in gentamicin-induced kidney injury in rats. MATERIALS AND METHODS: Forty adult male Wistar rats were equally divided into four groups. 1-Negative control group, 2-positive control group (Gentamicin), 3-Naringenin+AG+CW, 4-Gentamicin+Naringenin+AG+CW: groups 2 and 4 were treated with gentamicin. After six weeks, the rats were anesthetized with diethyl ether, and blood was collected by cardiac puncture and dissected to collect the kidneys. Biochemical studies were performed to determine the levels of urea, creatinine, lipids, total antioxidant capacity, and lipid peroxide, antioxidant enzyme activity in the kidney, total phenolic content (TPC), radical-scavenging activity, calcium, magnesium, and potassium in AG, CW, and their mixture. Also, kidney histopathology was performed. RESULTS: Renal injury manifests as elevated serum urea and creatinine levels. A significant increase in total cholesterol, triglycerides (TG), low-density lipoprotein cholesterol (LDL-C), and malondialdehyde (MDA) was also noted. The activities of antioxidant capacity (TAC) and reduced glutathione (GSH) significantly decreased in the serum. There was a reduction in the activities of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px), and catalase (CAT) activities in kidney homogenates. Gentamicin administration induces morphological changes in the kidneys. Oral administration of naringenin+AG+CW significantly overturned all of the above-mentioned abnormalities. CONCLUSIONS: These results show that the naringenin+AG+CW combination exhibited an additive effect against renal dysfunction and structural damage through antioxidant and anti-inflammatory mechanisms, as well as replenishing and balancing intracellular and extracellular electrolytes. Therefore, oral administration of these three ingredients could potentially provide better protection and serve as a unique therapeutic tool against nephrotoxicity caused by gentamicin.

Does treatment modality affect measures of arterial stiffness in women with gestational diabetes?

OBJECTIVE: To investigate whether arterial stiffness (AS) differs between healthy women and women with gestational diabetes mellitus (GDM) managed by different treatment modalities. METHODS: This was a prospective longitudinal cohort study comparing AS in pregnancies complicated by GDM and low-risk controls. AS was assessed by recording aortic pulse-wave velocity (AoPWV), brachial augmentation index (BrAIx) and aortic augmentation index (AoAIx) using the Arteriograph® at four gestational-age windows: 24 + 0 to 27 + 6 weeks (W1); 28 + 0 to 31 + 6 weeks (W2); 32 + 0 to 35 + 6 weeks (W3) and ≥ 36 + 0 weeks (W4). Women with GDM were considered both as a single group and as subgroups stratified by treatment modality. Data were analyzed using a linear mixed model on each AS variable (log-transformed) with group, gestational-age window, maternal age, ethnicity, parity, body mass index, mean arterial pressure and heart rate as fixed effects and individual as a random effect. We compared the group means including relevant contrasts and adjusted the P-values using Bonferroni correction. RESULTS: The study population comprised 155 low-risk controls and 127 women with GDM, of whom 59 were treated with dietary intervention, 47 were treated with metformin only and 21 were treated with metformin + insulin. The two-way interaction term of study group and gestational age was significant for BrAIx and AoAIx (P < 0.001), but there was no evidence that mean AoPWV was different between the study groups (P = 0.729). Women in the control group demonstrated significantly lower BrAIx and AoAIx compared with the combined GDM group at W1-W3, but not at W4. The mean difference in log-transformed BrAIx was -0.37 (95% CI, -0.52 to -0.22), -0.23 (95% CI, -0.35 to -0.12) and -0.29 (95% CI, -0.40 to -0.18) at W1, W2 and W3, respectively. The mean difference in log-transformed AoAIx was -0.49 (95% CI, -0.69 to -0.30), -0.32 (95% CI, -0.47 to -0.18) and -0.38 (95% CI -0.52 to -0.24) at W1, W2 and W3, respectively. Similarly, women in the control group also demonstrated significantly lower BrAIx and AoAIx compared with each of the GDM treatment subgroups (diet, metformin only and metformin + insulin) at W1-W3. The increase in mean BrAIx and AoAIx seen between W2 and W3 in women with GDM treated with dietary management was attenuated in the metformin-only and metformin + insulin groups. However, the mean differences in BrAIx and AoAIx between these treatment groups were not statistically significant at any gestational-age window. CONCLUSIONS: Pregnancies complicated by GDM demonstrate significantly higher AS compared with low-risk pregnancies regardless of treatment modality. Our data provide the basis for further investigation into the association of metformin therapy with changes in AS and risk of placenta-mediated diseases. © 2023 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

Evaluation of efficacy of non-resorbable membranes compared to resorbable membranes in patients undergoing guided bone regeneration.

Background: Replacement of missing teeth in patients with prolonged edentulism poses a challenge for clinicians. An extended period of edentulism results in severe atrophy of alveolar ridges rendering them unsatisfactory for rehabilitation using an implant-supported prosthesis. To overcome this difficulty, Guided Bone Regeneration (GBR) was introduced and constructed upon the principles of Guided Tissue Regeneration (GTR) procedures. Evidence suggests that GBR has proven to be a predictable treatment modality for treating vertical and horizontal ridge deficiencies. Objective: The present systematic review aimed to evaluate the efficacy of non-resorbable (N-RES) membranes compared to resorbable (RES) membranes in patients undergoing GBR. Methods: An electronic search of three databases, including PubMed, Web of Science, and Scopus, was conducted for articles published until March 2022. A supplementary manual search of references from these articles was performed to include any articles that may have been overlooked in the electronic search. Articles that evaluated the efficacy of RES membranes and N-RES membranes in GBR were included. Case reports, case series, commentaries, letters to the editor, narrative or systematic reviews were excluded. Articles in languages other than English were also excluded. The articles were assessed against risk of bias 2 tool for Randomized Control Trials (RCTs) and ROBINS-I tool for Non-Randomized Clinical Trials (N-RCTs). The Grading of Recommendations Assessment, Development and Evaluation (GRADE) assessment was followed based on the Cochrane Handbook for quality assessment. A summary of findings table was used to present the results. Results: One hundred and fifty one articles were identified in an electronic search. Eight articles met the inclusion criteria and were included in the present systematic review. The studies were conducted on partially or completely edentulous patients with alveolar ridge deficiencies undergoing vertical or horizontal bone for subsequent implant placement. The majority of the studies reported similar results for bone gain in both RES and N-RES membrane groups. Conclusion: The available evidence suggests that RES and N-RES membranes are equally effective in GBR. However, the evidence must be interpreted with caution due to its 'low quality' GRADE assessment. Clinical implications: Further research focusing on human clinical trials with well-matched subjects with homogeneity in the type and method of GBR and method of assessment of new bone formation will derive conclusive results on the efficacy of RES and N-RES membranes in achieving new bone formation.

Fecobionics in proctology: review and perspectives.

Fecobionics is a novel integrated technology for assessment of anorectal function. It is a defecatory test with simultaneous measurements of pressures, orientation, and device angle (a proxy of the anorectal angle). Furthermore, the latest Fecobionics prototypes measure diameters (shape) using impedance planimetry during evacuation of the device. The simultaneous measurement of multiple variables in the integrated test allows new metrics to be developed including more advanced novel defecation indices, enabling mechanistic insight in the defecation process at an unprecedented level in patients with anorectal disorders including patients suffering from obstructed defecation, fecal incontinence, and low anterior resection syndrome. The device has the consistency and shape of a normal stool (type 3-4 on the Bristol Stool Form Scale). Fecobionics has been validated on the bench and in animal studies and used in clinical trials to study defecation phenotypes in normal human subjects and patients with obstructed defecation, fecal incontinence, and low anterior resection syndrome after rectal cancer surgery. Subtypes have been defined, especially of patients with obstructed defecation. Furthermore, Fecobionics has been used to monitor biofeedback therapy in patients with fecal incontinence to predict the outcome of the therapy (responder versus non-responder). Most Fecobionics studies showed a closer correlation to symptoms as compared to current technologies for anorectal assessment. The present article outlines previous and ongoing work, and perspectives for future studies in proctology, including in physiological assessment of function, diagnostics, monitoring of therapy, and as a tool for biofeedback therapy.

Questionnaire-Based Study on the Prevalence, Awareness, and Preventive Measures of Occupational Hazards Among Dental Professionals.

BACKGROUND In this questionnaire-based study, we evaluated the prevalence and awareness level of occupational hazards among dental professionals (students, interns, dentists, and specialists) at different dentistry colleges. MATERIAL AND METHODS A self-administered questionnaire was designed from previously conducted studies and distributed to 310 participants from different dental colleges of dentistry in Sana'a City, Yemen. The questionnaire was divided into 4 parts. The first part comprised questions involving sex, age, and clinical professions; the second part, questions on awareness about different occupational hazards; the third part, questions about prevalence of occupational hazards; and the fourth part, questions related to bringing down the prevalence of occupational hazards associated with a dental practice. Data were analyzed using one­way analysis of variance and chi-square tests. RESULTS Significant differences were detected between sex, age groups, and clinical professions. Musculoskeletal disorders were the most common physical hazard, whereas infections were the greatest biological hazard, accounting for 68% and 74%, respectively. Of the participants, 63.5% answered that "patient, practice, and finance'' together were the most common causes of stress among practicing dentists and dental students. The use of gloves and/or masks was the most efficient preventive measure among participants. A significant difference was found among most of the parameters, with P≤0.001. Almost 50% of respondents answered "yes'' in relation to vaccination for hepatitis-B, with P=0.062. CONCLUSIONS The prevalence of occupational hazards was low among dentists and dental students among the tested participants, with significant differences for most of the parameters.

Assessing the Effect of Curcumin on the Oral Mucosal Cytomorphometry and Candidal Species Specificity in Tobacco Users: A Pilot Study.

OBJECTIVES: Tobacco consumption is of major concern for public health. Compromised oral hygiene accentuated by tobacco leads to alteration in the oral mucosa and microbiome, including Candida, and its species can be identified rapidly using CHROMagar. Curcumin, a naturally available compound possesses antioxidant, anti-inflammatory, anti-microbial, anti-carcinogenic, anti-fungal, and immunomodulatory properties. Hence, a comprehensive study was planned. AIM: To evaluate and compare cytomorphometric analysis and Candida colonization and speciation in tobacco users before and after the use of curcumin gel. MATERIALS AND METHODS: The study comprised a total of 120 participants (the study (tobacco habit) group, n = 60 and control (healthy) group, n = 60). The intervention was the application of curcumin gel over the lesion area three times daily for 2 months. All participants' oral health status was assessed, followed by cytomorphometric analysis and Candida colonization and speciation using CHROMagar. RESULTS: Cytomorphometric analysis showed statistically significant differences in the control and study group for cell diameter (CD), nuclear diameter (ND), CD:ND ratio, and micronuclei (p = 0.0001). Candida colonization had a significantly higher number of colonies in the habit group when compared to the control group. Candida tropicalis was predominant in the study group, whereas Candida albicans was predominant in the control group. In the study group, after intervention with curcumin, a statistically significant difference was seen in nuclear diameter, CD:ND ratio, and micronuclei. There was a reduction in the number of Candida colonies, and Candida albicans was the predominant species observed in the study group after the intervention of curcumin and discontinuation of habit. CONCLUSION: Curcumin was found to reduce the number of micronuclei and also decreased Candida colonization, along with the discontinuation of habit in tobacco users.

Ensemble Deep-Learning-Based Prognostic and Prediction for Recurrence of Sporadic Odontogenic Keratocysts on Hematoxylin and Eosin Stained Pathological Images of Incisional Biopsies.

(1) Background: Odontogenic keratocysts (OKCs) are enigmatic developmental cysts that deserve special attention due to their heterogeneous appearance in histopathological characteristics and high recurrence rate. Despite several nomenclatures for classification, clinicians still confront challenges in its diagnosis and predicting its recurrence. This paper proposes an ensemble deep-learning-based prognostic and prediction algorithm, for the recurrence of sporadic odontogenic keratocysts, on hematoxylin and eosin stained pathological images of incisional biopsies before treatment. (2) Materials and Methods: In this study, we applied a deep-learning algorithm to an ensemble approach integrated with DenseNet-121, Inception-V3, and Inception-Resnet-V3 classifiers. Around 1660 hematoxylin and eosin stained pathologically annotated digital images of OKC-diagnosed (60) patients were supplied to train and predict recurrent OKCs. (3) Results: The presence of SEH (p = 0.004), an incomplete epithelial lining, (p = 0.023), and a corrugated surface (p = 0.049) were the most significant histological parameters distinguishing recurrent and non-recurrent OKCs. Amongst the classifiers, DenseNet-121 showed 93% accuracy in predicting recurrent OKCs. Furthermore, integrating and training the traditional ensemble model showed an accuracy of 95% and an AUC of 0.9872, with an execution time of 192.9 s. In comparison, our proposed model showed 97% accuracy with an execution time of 154.6 s. (4) Conclusions: Considering the outcome of our novel ensemble model, based on accuracy and execution time, the presented design could be embedded into a computer-aided design system for automation of risk stratification of odontogenic keratocysts.

Evaluation of Candidiasis in Upper-Aerodigestive Squamous Cell Carcinoma Patients-A Clinico-Mycological Aspect.

Candida is a commensal yeast. It can be infective when the host's defense mechanism is weakened, as in the case of squamous cell carcinoma patients. We aimed to evaluate the prevalence and clinical mycological manifestation of candidiasis in 150 cancer cases comprised of preoperative and post-operative (with or without radiotherapy) upper aerodigestive squamous cell carcinoma. A total of 150 patients suffering from squamous cell carcinoma of the Upper Aero-Digestive Tract (UADT) were divided into preoperative (n = 48), post-operative without radiotherapy (n = 29) and post-operative with radiotherapy (n = 73). Samples were collected using cotton swabs and cultured. Candida species were identified according to color pigmentation on Candida Differential Agar (CDA) plate. The clinico-mycological association of patients was evaluated by the chi-square test, and 98 out of 150 patients showed the presence of various Candida species. The major species isolated was Candida albicans (53%), followed by Candida tropicalis (16%). There was a significant statistical difference between patients who showed mycological associations and patients who did not have any such association (p = 0.0008). The prevalence of oral candidiasis was found to be 65.33% among total cases of upper aero-digestive squamous cell carcinoma. Chronic erythematous cases of candidiasis were mainly seen in preoperative squamous cell carcinoma cases, whereas the acute erythematous type of candidiasis was mainly seen in post-operative cases who received radiotherapy. The clinicomycological assessment can help to correlate the signs and symptoms with the presence of candidiasis in upper aerodigestive squamous cell carcinoma patients. Meticulous testing and examination can help in the early detection of candidiasis. Future studies are needed to develop advance scientific preventive strategies for high-risk cases.

A Systematic Review of Cross-Sectional Studies Conducted in the Kingdom of Saudi Arabia on Levels of Dental Anxiety Between Genders and Demographic Groups.

BACKGROUND Dental anxiety can impact oral health and dental treatment in patients of all age groups, which seems to be an obstacle to quality dental care. This systematic review of the literature aimed to evaluate the findings from cross-sectional studies conducted in the Kingdom of Saudi Arabia (KSA) on levels of dental anxiety (DA) between genders and among various demographic groups. MATERIAL AND METHODS An electronic search of PubMed, Embase, and Web of Science databases was carried out in January 2022. Studies that measured dental anxiety in Saudis in all regions of the KSA by direct evaluation and interviews were included. Studies that were not in the English language or used proxy measures were excluded. Quality assessment was carried out using Joanna Briggs Institute's critical appraisal tool for cross-sectional studies. RESULTS A total of 19 cross-sectional studies from the KSA were identified that used validated anxiety scales, including the Corah Dental Anxiety Scale (DAS), the Corah Dental Anxiety Scale, Revised (DAS-R), and the Modified Dental Anxiety Scale (MDAS). All studies were rated as having a high risk of bias. A mild level of DA was the most common among participants in the KSA. CONCLUSIONS The findings from this systematic review showed that in the KSA, although a mild level of dental anxiety was most common in the study participants, women, young adults, and university students showed a higher prevalence of dental anxiety. However, the lack of sufficient literature to support the current findings make an overall conclusion about DA extremely difficult.

Comparison of the C-Reactive Protein Level and Visual Analog Scale Scores between Piezosurgery and Rotatory Osteotomy in Mandibular Impacted Third Molar Extraction.

This study aimed to compare the C-reactive protein level and visual analog scale scores of piezo- and rotatory-based surgical extraction of the third molar. As a split-mouth study, the comparative groups consisted of 25 patients, each of whom underwent surgical removal of the third molar by piezo on one side and rotatory bur on the other side. C-reactive protein levels were quantitatively assessed (enzyme-linked immunosorbent assay) before and immediately post-extraction. The immediate postoperative blood sample (baseline) C-reactive protein levels were compared with 24 h and 72 h post-op samples, both within and between the groups. Pain was assessed using the visual analog scale at 24 h and 72 h post-operatively. The C-reactive protein levels were lower in the piezo group than in the rotatory group, although the difference was not significant (p > 0.05). The visual analog scale score was significantly (p < 0.01) lower in the piezo group than in the rotatory group. The C-reactive protein levels increased in both the rotary and piezo groups from the pre-op to the immediate post-op value, but in the piezo group, the levels dropped back after 24 h. On the contrary, in the rotatory group, the C-reactive level kept increasing until 24 h; the visual analog scale score dropped significantly from 24 to 72 h for both the rotatory and piezo groups. Surgical techniques that could spare the surrounding soft tissues, such as the piezo, could aid in reducing overall postoperative morbidity.

Cross-tissue immune cell analysis reveals tissue-specific features in humans.

Despite their crucial role in health and disease, our knowledge of immune cells within human tissues remains limited. We surveyed the immune compartment of 16 tissues from 12 adult donors by single-cell RNA sequencing and VDJ sequencing generating a dataset of ~360,000 cells. To systematically resolve immune cell heterogeneity across tissues, we developed CellTypist, a machine learning tool for rapid and precise cell type annotation. Using this approach, combined with detailed curation, we determined the tissue distribution of finely phenotyped immune cell types, revealing hitherto unappreciated tissue-specific features and clonal architecture of T and B cells. Our multitissue approach lays the foundation for identifying highly resolved immune cell types by leveraging a common reference dataset, tissue-integrated expression analysis, and antigen receptor sequencing.

Identification of epilepsy concomitant candidate genes recognized in Saudi epileptic patients.

Saudi Genome program is a revolutionary nationwide transformation initiative of Saudi Vision 2030. The program goals are to recognize and reduce the incidence of genetic diseases in the Kingdom of Saudi Arabia (KSA). Accordingly, the program will establish the foundation for personalized and genomic medicine in the KSA. Epilepsy has a high prevalence in KSA reaching around 6.54 of 1000 individuals with a subsequent massive financial burden. One of the main risk factors for this high prevalence and associated with increased risk of epilepsy development is consanguinity marriage, which is traditional in KSA. In this review, we executed a comprehensive state-of-art literature review regarding epilepsy genetics to offer a perception into the genes associated with epilepsy recognized in Saudi epileptic patients. Several genes' mutations were incorporated in this review including AFG3L2, ASPM, ATN1, ATP1A2, BMP5, CCDC88A, C12orf57, DNAJA1, EML1, ERLIN2, FRRS1L, GABRG3, NRXN3, MDH1, KCNJ10, KCNMA1, KCNT1, KIAA0226, OPHN1, PCCA, PCCB, PEX, PGAP2, PI4K2A, PODXL, PRICKLE1, PNKP, RELN, SCN2A, SCN1B, SLC2A1, SLC19A3, SLC25, SIAH1, SYNJ1, SZT2, TBCK, TMX2, TSC1, TSC2, TSEN, WDR45B, WWOX, UBR, UGDH, and YIF1B. For each of these genes, we tried to explain a little about the gene associated proteins and their roles in epilepsy development.

Maternal hemodynamics and neonatal birth weight in pregnancies complicated by gestational diabetes: new insights from novel causal inference analysis modeling.

OBJECTIVE: Normal pregnancy is characterized by significant changes in maternal hemodynamics that are associated with fetal growth. Pregnancies complicated by gestational diabetes mellitus (GDM) are associated with large-for-gestational age and macrosomia, but the relationship between maternal hemodynamic parameters and birth weight (BW) among women with GDM has not been established. Our objective was to investigate the influence of maternal hemodynamics on neonatal BW in healthy pregnancies and in those complicated by GDM. METHODS: This was a prospective, cross-sectional case-control study of women aged ≥ 16 years with a singleton viable pregnancy, recruited between January 2016 and February 2021 at Leicester Royal Infirmary, Leicester, UK. GDM was defined as a fasting glucose level ≥ 5.3 mmol/L and/or serum glucose level ≥ 7.8 mmol/L, 2 h following a 75-g oral glucose load. We collected data on maternal characteristics and pregnancy outcome, including body mass index (BMI) at booking and BW centile adjusted for gestational age at delivery. Maternal hemodynamic parameters were assessed at 34-42 weeks' gestation using the Arteriograph® and bioreactance techniques. Graphical causal inference methodology was used to identify causal effects of the measured variables on neonatal BW centile. RESULTS: Included in the analysis were 141 women with GDM and 136 normotensive non-diabetic pregnant controls. 62% of the women with GDM were managed pharmacologically, with metformin and/or insulin. Variables included in the final model were cardiac output (CO), mean arterial pressure (MAP), total peripheral resistance (TPR), aortic augmentation index (AIx), aortic pulse wave velocity (PWV) and BMI at booking. Among the controls, maternal BMI, CO and aortic PWV were significantly associated with neonatal BW. Each SD increase in booking BMI produced an increase of 8.4 BW centiles (P = 0.002), in CO produced an increase of 9.4 BW centiles (P = 0.008) and in aortic PWV produced an increase of 7.1 BW centiles (P = 0.017). We found no significant relationship between MAP, TPR or aortic AIx and neonatal BW. Maternal hemodynamics influenced neonatal BW among the women with GDM in a similar manner to that in the control group, but only the relationship between maternal BMI and neonatal BW reached statistical significance, with a 1-SD increase in BMI producing an increase of 6.1 BW centiles (P = 0.019). CONCLUSIONS: Maternal BMI, CO and PWV were determinants of BW in our control group. The relationship between maternal hemodynamics and neonatal BW was similar between women with GDM and healthy controls. Our findings therefore suggest that fetal growth restriction in pregnancies complicated by GDM may indicate maternal cardiovascular dysfunction. © 2022 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.

A method to isolate and cryopreserve cerebrospinal fluid mononuclear cells from external ventricular drains to investigate immunological processes in acute brain injuries.

The inflammatory response to acute brain injuries is a key contributor to subsequent outcome. The study of local central nervous system inflammatory responses is hindered by raised intracranial pressure precluding cerebrospinal fluid sampling by lumbar puncture. External ventricular drains are sited in some acute brain injury patients to divert cerebrospinal fluid and thus reduce intracranial pressure, and represent a potential route to safely gather large volumes of cerebrospinal fluid for immunological studies. In this manuscript we show that mononuclear cells can be isolated from cerebrospinal fluid collected from external ventricular drains, and that the large volumes of cerebrospinal fluid available yield sufficient mononuclear cells to allow cryopreservation. Prolonged storage of cerebrospinal fluid in the external ventricular drain collection bag can alter the phenotype of cells recovered, but the predicted effect of this can be estimated for a given flow cytometry panel by assessing the changes in peripheral blood mononuclear cells exposed to the same conditions. The described method will allow clinical studies of acute brain injuries to investigate the immunological processes occurring within the central nervous system compartment, rather than relying on changes in the peripheral circulation.

Peripheral nerve regeneration: A comparative study of the effects of autologous bone marrow-derived mesenchymal stem cells, platelet-rich plasma, and lateral saphenous vein graft as a conduit in a dog model.

BACKGROUND: The quality of healing of peripheral nerve injuries remains a common challenge causing pain and poor quality of life for millions of people and animals annually. AIMS: The objectives of this study were to evaluate the healing quality of facial nerve injury in a dog model following local treatment using an autologous injection of platelet-rich plasma (PRP) or bone marrow-derived mesenchymal stem cells (BM-MSCs) at the injury site in combination with the application of an autologous saphenous vein graft as a conduit. METHODS: 20 apparently healthy adult Mongrel dogs were randomly divided into 4 equal groups. Dogs in groups 1, 2, and 3 were subjected to facial nerve neurectomy and saphenous vein conduit graft implantation at the site of facial nerve injury. Dogs in groups 2 and 3 received 1 ml of autologous PRP and BM-MSCs, respectively. Injections were administered directly in the vein conduit immediately after nerve injury. Dogs in group 1 (grafted but not treated; control) received only an autologous vein graft, and those in group 4 (normal control) received no graft and no PRP or BM-MSCs treatment. The dogs were monitored daily for 8 weeks after surgery. Clinical evaluation of the facial nerve, including lower eyelid, ear drooping, upper lip, and tongue functions, was carried out once per week using a numerical scoring system of 0-3. At the end of the study period (week 8), the facial nerve injury site was evaluated grossly for the presence of adhesions using a numerical scoring system of 0-3. The facial nerve injury site was histopathologically assessed for the existence of perivascular mononuclear cell infiltration, fibrous tissue deposition, and axonal injury using H&E-stained tissue sections. RESULTS: Clinically, BM-MSCs treated dogs experienced significant (p < 0.05) improvement in the lower eyelid, ear, lip, and tongue functions 4 weeks postoperatively compared to other groups. Grossly, the facial nerve graft site in the BM-MSCs treated group showed significantly (p < 0.05) lesser adhesion scores than the other groups. Histopathologically, there was significantly (p < 0.05) less perivascular mononuclear cell infiltration, less collagen deposition, and more normal axons at the facial nerve injury site in the BM-MSCs treated group compared to the other groups. CONCLUSION: This study showed clinically significant enhancement of nerve regeneration by applying autologous BM-MSCs and autologous vein grafting at the site of facial nerve injury. However, further clinical trials are warranted before this application can be recommended to treat traumatic nerve injuries in the field.