Cross-tissue single-cell landscape of human monocytes and macrophages in health and disease.

Mononuclear phagocytes (MNPs) encompass dendritic cells, monocytes, and macrophages (MoMac), which exhibit antimicrobial, homeostatic, and immunoregulatory functions. We integrated 178,651 MNPs from 13 tissues across 41 datasets to generate a MNP single-cell RNA compendium (MNP-VERSE), a publicly available tool to map MNPs and define conserved gene signatures of MNP populations. Next, we generated a MoMac-focused compendium that revealed an array of specialized cell subsets widely distributed across multiple tissues. Specific pathological forms were expanded in cancer and inflammation. All neoplastic tissues contained conserved tumor-associated macrophage populations. In particular, we focused on IL4I1+CD274(PD-L1)+IDO1+ macrophages, which accumulated in the tumor periphery in a T cell-dependent manner via interferon-γ (IFN-γ) and CD40/CD40L-induced maturation from IFN-primed monocytes. IL4I1_Macs exhibited immunosuppressive characteristics through tryptophan degradation and promoted the entry of regulatory T cell into tumors. This integrated analysis provides a robust online-available platform for uniform annotation and dissection of specific macrophage functions in healthy and pathological states.

Ocular Gene Therapy in a Patient with Dystrophic Epidermolysis Bullosa.

Dystrophic epidermolysis bullosa is a rare genetic disease caused by damaging variants in COL7A1, which encodes type VII collagen. Blistering and scarring of the ocular surface develop, potentially leading to blindness. Beremagene geperpavec (B-VEC) is a replication-deficient herpes simplex virus type 1-based gene therapy engineered to deliver functional human type VII collagen. Here, we report the case of a patient with cicatrizing conjunctivitis in both eyes caused by dystrophic epidermolysis bullosa who received ophthalmic administration of B-VEC, which was associated with improved visual acuity after surgery.

Error modelled gene expression analysis (EMOGEA) provides a superior overview of time course RNA-seq measurements and low count gene expression.

Temporal RNA-sequencing (RNA-seq) studies of bulk samples provide an opportunity for improved understanding of gene regulation during dynamic phenomena such as development, tumor progression or response to an incremental dose of a pharmacotherapeutic. Moreover, single-cell RNA-seq (scRNA-seq) data implicitly exhibit temporal characteristics because gene expression values recapitulate dynamic processes such as cellular transitions. Unfortunately, temporal RNA-seq data continue to be analyzed by methods that ignore this ordinal structure and yield results that are often difficult to interpret. Here, we present Error Modelled Gene Expression Analysis (EMOGEA), a framework for analyzing RNA-seq data that incorporates measurement uncertainty, while introducing a special formulation for those acquired to monitor dynamic phenomena. This method is specifically suited for RNA-seq studies in which low-count transcripts with small-fold changes lead to significant biological effects. Such transcripts include genes involved in signaling and non-coding RNAs that inherently exhibit low levels of expression. Using simulation studies, we show that this framework down-weights samples that exhibit extreme responses such as batch effects allowing them to be modeled with the rest of the samples and maintain the degrees of freedom originally envisioned for a study. Using temporal experimental data, we demonstrate the framework by extracting a cascade of gene expression waves from a well-designed RNA-seq study of zebrafish embryogenesis and an scRNA-seq study of mouse pre-implantation and provide unique biological insights into the regulation of genes in each wave. For non-ordinal measurements, we show that EMOGEA has a much higher rate of true positive calls and a vanishingly small rate of false negative discoveries compared to common approaches. Finally, we provide two packages in Python and R that are self-contained and easy to use, including test data.

Nuclear Control of Vascular Smooth Muscle Cell Plasticity during Vascular Remodeling.

Control of vascular smooth muscle cell (SMC) gene expression is an essential process for establishing and maintaining lineage identity, contractility, and plasticity. Most mechanisms (epigenetic, transcriptional, and post-transcriptional) implicated in gene regulation occur in the nucleus. Still, intranuclear pathways are directly impacted by modifications in the extracellular environment in conditions of adaptive or maladaptive remodeling. Integration of extracellular, cellular, and genomic information into the nucleus through epigenetic and transcriptional control of genome organization plays a major role in regulating SMC functions and phenotypic transitions during vascular remodeling and diseases. This review aims to provide a comprehensive update on nuclear mechanisms, their interactions, and their integration in controlling SMC homeostasis and dysfunction. It summarizes and discusses the main nuclear mechanisms preponderant in SMCs in the context of vascular disease, such as atherosclerosis, with an emphasis on studies employing in vivo cell-specific loss-of-function and single-cell omics approaches.

Haplotype analysis and linkage disequilibrium of ApoB gene polymorphisms and its relationship with hyperlipidemia in patients with acne vulgaris.

BACKGROUND: Acne vulgaris (AV) is a chronic, multifactorial inflammatory disease of the pilosebaceous unit brought on by hormonal imbalance, excessive sebum production, follicular hyperkeratinization, inflammation and Cutibacterium acne. Acne patients are characterized by alteration of the lipid profile. Apolipoprotein B gene (ApoB) plays an essential role in lipoprotein biosynthesis and multiple single-nucleotide polymorphisms (SNPs) in ApoB are associated with dyslipidemia. AIM: The aim of this study was to estimate the alteration of lipid profiles in AV, determine the genetic association with lipid profile alteration by studying the ApoB gene polymorphisms, and to identify the exact haplotypes associated with acne and lipid profile alteration. SUBJECTS AND METHODS: In a case-control study consisting of 63 non-obese acne patients and 43 healthy controls, all participants underwent biochemical, anthropological assessments, and genetic analysis for ApoB polymorphisms. RESULT: Our results indicate that serum ApoB and the lipid profile were higher in acne patients compared with healthy subject. The most common haplotypes in acne patients were rs562338 A/rs17240441 I/c.12669 A/rs1042034 G, whereas the most common haplotypes in healthy subjects were rs562338 G/rs17240441 D/c.12669 A/rs1042034 G. Patients with mild acne had higher serum ApoB levels p = 0.005. Also, the low-density lipoprotein cholesterol (LDL-C) level was higher in mild acne compared with other acne groups, with a highly significant variation of p ≤ 0.001. CONCLUSION: We found a significant variation between the acne group and healthy controls in serum ApoB, triglycerides, total cholesterol and LDL-C. The most common haplotypes in acne patients are rs562338 A/, rs17240441 I/, c.12669 A/ and rs1042034 G, and there is a linkage disequilibrium between the four selected SNPs.

Ejection fraction and ventricular volumes on rubidium positron emission tomography: Validation against cardiovascular magnetic resonance.

BACKGROUND: Cardiovascular magnetic resonance (CMR) is the non-invasive gold standard for non-invasively determining left ventricular volumes (LVVs) and ejection fraction (EF). We aimed to assess the accuracy of LVV and left ventricular ejection fraction measured by positron emission tomography (PET) as compared to CMR. METHODS: Patients who underwent both PET and CMR within 1 year were identified from prospective institutional registries. Analysis was performed to evaluate the agreement between the raw and body-surface-area-normalized left ventricular volume (LVV) and EF derived from PET vs. those derived from CMR. RESULTS: The study population consisted of 669 patients (mean age 62 ± 13 years, 65% male). The median (interquartile range [IQR]) duration between CMR and PET imaging was 36 (7-118) days. The median (IQR) EF values were 52% (38-63%) on CMR and 53% (37-65%) on PET (mean difference: 0.53% ± 9.1, P = 0.129) with a strong correlation (Spearman rho = 0.84, P < 0.001; Intraclass Correlation Coefficient 0.84, 95% confidence interval [CI]: 0.82-0.86, P < 0.001; Lin's concordance correlation coefficient was 0.844, 95% CI: 0.822 to 0.865). Results were similar with LVV, normalized LVV/EF, and in subgroups of patients with reduced EF, coronary artery disease scar, and LV hypertrophy as well as in patients with defibrillators. However, PET tended to underestimate LVV compared to CMR. CONCLUSION: Our analysis showed a strong correlation of EF and LVV by PET against a reference standard of CMR, whereas PET significantly underestimated LVV, but not EF, compared to CMR.

Hard and soft tissue alterations using dual-zone concept versus connective tissue graft at maxillary immediate implant placement: A 1-year randomized clinical and volumetric trial.

OBJECTIVES: To evaluate the esthetic outcome, as well as clinical, radiographic, and volumetric tissue alterations 1 year after immediate implant placement (IIP) with connective tissue grafting (CTG) versus dual-zone concept (DZ) at sites with thin labial bone in the esthetic zone. MATERIALS AND METHODS: This randomized clinical trial included 30 patients treated with IIP simultaneous with either CTG or DZ (n = 15 each). Pink esthetic score (PES) was assessed 6 months after crown placement as the primary outcome. Amount of bone labial to the implant, labio-palatal ridge reduction, and crestal bone changes were measured via CBCT after 1 year. Volumetric analysis of linear labial soft tissue contour, interdental, and mid-facial soft tissue level changes, and total volume loss (mm3) were measured after 1 year. RESULTS: Similar PES was observed in the CTG (12.53 ± 1.13) and DZ (12.13 ± 1.55) groups, with no significant difference (p = 0.42). Likewise, there were no statistically significant differences found between the two groups in labio-palatal bone reduction (mm&%), interdental papillae, and mid-facial gingival levels (p > 0.05). However, the mean vertical crestal bone changes in the CTG and DZ groups were -1.1 ± 0.6 mm and 0.2 ± 1.0 mm, respectively, with a statistically significant difference (p = 0.0002). Moreover, CTG revealed less linear and total volume (mm3) loss in the labial soft tissue which was statistically significant compared to DZ (p = 0.007). CONCLUSION: Both groups demonstrated the same PES, nevertheless, volumetric analysis revealed twice total labial volume loss in DZ compared to CTG. It might be concluded that the use of CTG with IIP caused less horizontal reduction in the supra-implant complex compared to the DZ.

Predictive value of optical coherence tomography angiography in management of diabetic macular edema.

BACKGROUND: Optical coherence tomography angiography (OCTA) is a relatively new extension of Optical coherence tomography (OCT) that generates non-invasive, depth-resolved images of the retinal microvasculature which allows for the detection of various features of diabetic retinopathy. OBJECTIVES: This study aimed to detect biomarkers that may predict an early anatomical response to the treatment of diabetic macular edema (DME) with intravitreal ranibizumab (IVR) by means of OCTA. PATIENTS AND METHODS: This prospective interventional study was undertaken on 111 eyes of 102 naïve participants who had diabetic macular edema; enrolled patients were evaluated by taking a complete ophthalmologic history, examination and investigations by use of a pre-designed checklist involving Optical Coherence Tomography Angiography. RESULTS: Regarding the best corrected visual acuity (BCVA) the Mean ± SD was 0.704 ± 0.158 preoperatively and 0.305 ± 0.131 postoperatively in good responder patients; and was 0.661 ± 0.164 preoperatively and 0.54 ± 0.178 postoperatively in poor responders. The central macular thickness (CMT) was 436.22 ± 54.66 µm preoperatively and 308.12 ± 33.09 µm postoperatively in good responder patients; and was 387.74 ± 44.05 µm preoperatively and 372.09 ± 52.86 µm postoperatively in poor responders. By comparing the pre injection size of the foveal avascular zone area (FAZ-A) in both groups, it found that the mean ± SD of FAZ-A was 0.297 ± 0.038 mm in good responder patients compared to 0.407 ± 0.05 mm in non-responder patients. The preoperative superficial capillary plexus (SCP) foveal vascular density (VD) was 24.02 ± 3.01% in good responder patients versus 17.89 ± 3.19% um in poor responders. The preoperative SCP parafoveal VD was 43.06 ± 2.67% in good responder patients versus 37.96 ± 1.82% um in poor responders. The preoperative deep capillary plexus (DCP) foveal VD was 30.58 ± 2.89% in good responder patients versus 25.45 ± 3.14% in poor responders. The preoperative DCP parafoveal VD was 45.66 ± 2.21% in good responder patients versus 43.26 ± 2.35% um in poor responders, this was statistically significant. CONCLUSION: OCTA offers an accurate measurement for VD in the macula as well as the FAZ-A which could be used to predict an early anatomical response of anti-VEGF treatment in DME.

MiR-200c-3p as a novel genetic marker and therapeutic tool for alopecia areata.

BACKGROUND: MicroRNAs (miRNAs) are small RNA molecules that regulate gene expression in diverse biological processes. They hold promise as therapeutic candidates for targeting human disease pathways, although our understanding of their gene regulatory mechanism remains incomplete. Alopecia areata (AA) is a prevalent inflammatory ailment distinguished by the infiltration of T cells targeting the anagen-stage hair follicles. The scarcity of effective remedies for AA may stem from limited understanding regarding its precise cellular mechanism. AIM: To investigate and examine the importance and role of the miR-200c-3p as a genetic indicator for AA, and its possible impact on disease progression. SUBJECTS AND METHODS: Case-control study included 65 patients with AA and 65 matched healthy controls. A real-time PCR technique was used to measure the expression of miR-200c-3p for both groups. Bioinformatic tools were used for prediction with genes and gene-gene interaction, and protein-protein interaction. RESULTS: The expression levels of miR-200c-3p were significantly higher in AA patients than in healthy controls. We predicted that miR-200c-3p plays a markable role in the development of AA by its effect on the EGFR tyrosine kinase inhibitor resistance pathway. CONCLUSION: We were able to identify the influence of miR-200c-3p on both PLCG1 and RPS6KP1 genes which in turn regulate the EGFR tyrosine kinases resistance pathway that displayed the most substantial increase in activity. Our outcomes shed light on the era of the potential theranostic role of this innovative miRNA in AA.

The role of hsa-miR-193a-5p as an important factor for control of inositol in alopecia areata.

BACKGROUND: MicroRNAs (miRNAs) are small RNA molecules that play a regulatory role in various biological processes by acting as intracellular mediators. They hold great potential as therapeutic agents for targeting human disease pathways; however, there is still much to be uncovered about their mechanism of gene regulation. Alopecia areata (AA) is a commonly occurring inflammatory condition characterized by the infiltration of T cells that specifically target the anagen-stage hair follicle. The limited understanding of its precise cellular mechanism may be the reason behind the scarcity of effective treatments for AA. AIM: The significance and function of hsa-miR-193a-5p as a genetic marker for AA and its potential influence on the advancement of the disease. SUBJECTS AND METHODS: A case-control study comprised 77 individuals diagnosed with AA who were matched with 75 healthy controls. In order to measure the expression of miR-200c-3p in both groups, the real-time PCR technique was utilized. The prediction of suitable genes for hsa-miR-193a-5p, as well as the identification of pathways and gene-gene interactions, were carried out using bioinformatic tools. RESULTS: The levels of hsa-miR-193a-5p expression were notably elevated in AA patients in comparison to healthy controls. Our prediction suggests that the involvement of hsa-miR-193a-5p in the development of AA is significant due to its influence on the inositol phosphorylation pathway and the Phosphatidylinositol signaling system, achieved through its direct impact on the IPPK gene. CONCLUSION: For the first time, our study demonstrates the significant over-expression of a new miRNA, hsa-miR-193a-5p, in the blood of AA patients compared to controls, and highlights its impact on the IPPK gene and the inositol phosphorylation and Phosphatidylinositol signaling pathways, suggesting a potential therapeutic role for hsa-miR-193a-5p in AA.

C-reactive protein as a novel biomarker for vitamin D deficiency in alopecia areata.

BACKGROUND: Alopecia areata (AA) is an autoimmune condition characterized by sudden and unpredictable hair loss, with a lifetime incidence of 2%. AA can be divided into three categories: patchy alopecia, alopecia totalis, and alopecia universalis. It can affect a person's psychological health and overall quality of life. Elevated C-reactive protein (CRP) levels in the liver may indicate an inflammatory response in autoimmune diseases. Vitamin D, essential for immune system control and skin health, may be related to AA. Hair follicles contain vitamin D receptors, which control immunological responses in the skin. However, no study has found a relationship between CRP and vitamin D in AA patients in our region. SUBJECTS AND METHODS: An analytical cross-sectional study with a case-control design research investigation of 82 AA patients and 81 healthy controls was carried out. Both groups' medical histories were taken. Biochemical analysis was done for both groups as well as the serum vitamin D levels, and CRP. Genetic analysis for CDX2 rs11568820 variant detected by PCR (T-ARMS-PCR) method and vitamin D receptor (VDR) gene expression measured by real-time PCR analysis for both patients and healthy subjects. RESULTS: CRP levels are higher in AA patients, AA patients with G/G genotypes exhibited higher concentrations of CRP when compared to those with A/A and A/G genotypes while patients with A/A genotypes have higher levels of Serum vitamin D as compared to the A/G and G/G genotypes. G allele was more abundant in AA patients. VDR gene expression was lower in AA compared to control and lower in ophiasis compared to localized and multiple patchy AA. An important inverse linear correlation was observed between vitamin D and CRP levels in ophiasis AA. CONCLUSION: CRP concentrations were found to be elevated in AA patients. The considerable accuracy of CRP in the diagnosis of AA is substantiated by a statistically significant al. A noteworthy inverse linear association was observed between serum vitamin D and CRP concentrations in ophiasis AA.

In severe acne vulgaris, TNF-α gene variants are connected to increased TNF-α gene expression and insulin resistance.

BACKGROUND: Acne vulgaris (AV) is a chronic inflammatory skin condition affecting the pilosebaceous unit, commonly presenting as comedones, papules, pustules, or nodules on the face, upper limbs, torso, and back, with comedones formation being the primary pathology leading to disfiguring inflammation, hyperpigmentation, scarring, and psychological impact. AIM: The purpose of this study was to investigate the significance of two genetic variants in the promoter region of the tumor necrosis factor-alpha (TNF-α) gene and their association with insulin resistance (IR) in acne patients. To understand how these variants contribute to AV and its associated IR. SUBJECTS AND METHODS: An analytical cross-sectional study with a case-control design and research evaluation was carried out on 87 AV patients and 73 healthy volunteers. The medical histories of both groups were obtained, as well as the severity and duration of inflammation among acne sufferers, as well as demographic data. Biochemical analysis was performed on both sets of participants, including fasting blood glucose levels, insulin levels while fasting, IR, and serum TNF-α. PCR-RFLP analysis identified -863 G > A (rs1800630) and -308 G > A (rs1800629) variations, and real-time PCR analysis evaluated TNF-α gene expression in both patients and healthy people. RESULTS: Acne patients exhibited significantly higher levels of IR, fasting glucose, fasting insulin, serum TNF-α, and TNF-α folding change, when compared to healthy controls. The co-dominant model for -863 G > A and -308 G > A variants exhibited significant variations between the two groups. Severe acne patients who had the A/A genotype for -308 variants exhibited higher levels of IR, serum TNF-α, and TNF-α folding change. Highly significant positive linear correlation between IR, serum TNF-α, and TNF-α folding change in severe AV. CONCLUSION: There is a correlation between AV, especially severe acne, and the -863 G > A and -308 G > A polymorphism, which influences TNF-α gene expression and serum TNF-α levels.

Assessment of myeloid response and iron status among Sudanese pediatric ESKD on hemodialysis through reticulocyte parameters and ß-globin mRNA expression.

BACKGROUND: Sudanese children with End-Stage Kidney Disease (ESKD) often show limited improvement in hemoglobin levels despite treatment with recombinant human erythropoietin (rHuEPO). This study aims to assess the response to rHuEPO therapy by analyzing ß-globin mRNA expression and reticulocyte parameters. Additionally, it classifies anemia among Sudanese pediatric patients based on iron status, considering age and gender as biological markers for evaluating treatment response. METHODS: A prospective observational cohort study was conducted from January 2019 to February 2020 in Khartoum, Sudan, involving 45 anemic children aged 2 to 15 years diagnosed with ESKD. The treatment protocol included rHuEPO injections and maintenance hemodialysis. Laboratory assessments consisted of complete blood count (CBC), absolute reticulocyte count, ferritin, and transferrin measurements. ß-globin mRNA expression was quantified using reverse transcription polymerase chain reaction (RT-PCR), and reticulocyte parameters, including Reticulocyte Hemoglobin Content (CHr), percentage of hypochromic reticulocytes (HYPO%), and Immature Reticulocyte Fraction (IRF), were measured via flow cytometry. RESULTS: Significant variations in hemoglobin levels were observed across different age groups (p = 0.011). Gender analysis revealed a significant association with IRF, showing a lower IRF in male patients (p = 0.017). However, there were no significant differences in hemoglobin levels between genders (p = 0.999). ß-globin mRNA expression showed considerable variability, with a strong positive correlation with hemoglobin levels (r = 0.875, p < 0.0001). CONCLUSION: Age and gender significantly influence treatment responses in children with ESKD, highlighting the need to consider growth physiology in anemia management. This study underscores the variability in ß-globin mRNA expression and its association with Flow Cytometry parameters, demonstrating their effectiveness in evaluating iron status and guiding rHuEPO dosage.

Knowledge, risk perception and uptake of COVID-19 vaccination among internally displaced persons in complex humanitarian emergency setting, Northeast Nigeria.

BACKGROUND: Owing to crowded and unsanitary conditions, internally displaced persons (IDPs) have an increased risk of COVID-19 infection. Adoption of COVID-19 preventive measures among this population is premised on accurate information, adequate knowledge, and risk perception. We assessed COVID-19 knowledge and risk perception and investigated the association between risk perception and COVID-19 preventive measures, including vaccination among IDPs in Northeast Nigeria. METHODS: We conducted a cross-sectional study during July-December 2022 and sampled 2,175 IDPs using stratified sampling. We utilized a 12-point assessment tool to evaluate COVID-19 knowledge. Participants who scored ≥ 6 points were considered to have adequate knowledge. We used a 30-item Risk Behavior Diagnosis Scale to assess COVID-19 risk perception and evaluated each item on a 5-point Likert scale. Participants were divided into risk perception categories by the median of Likert scale scores. We performed weighted logistic regression analysis to identify factors associated with risk perception. Pearson's chi-squared with Rao-Scott adjustment was used to determine the relationship between risk perception and COVID-19 preventive measures. RESULTS: Of 2,175 participants, 55.7% were 18-39 years old, 70.9% were females, and 81.7% had no formal education. Among the IDPs, 32.0% (95% CI: 28.8 - 35.0) were considered to have adequate COVID-19 knowledge, and 51.3% (95% CI: 47.8 - 54.8) perceived COVID-19 risk as high. Moreover, 46.3% (95% CI: 42.8 - 50.0) had received one dose of COVID-19 vaccine, and 33.1% (95% CI: 29.8 - 36.0) received two doses. Adequate knowledge (Adjusted Odds Ratio (AOR) = 2.10, [95% CI: 1.46 - 3.03]) and post-primary education (AOR = 3.20, [95% CI: 1.59 - 6.46]) were associated with risk perception. Furthermore, high risk perception was significantly associated with wearing face masks (χ2 = 106.32, p-value < .001), practicing hand hygiene (χ2 = 162.24, p-value < .001), physical distancing (χ2 = 60.84, p-value < .001) and vaccination uptake (χ2 = 46.85, p-value < .001). CONCLUSIONS: This study revealed gaps in COVID-19 knowledge, risk perception, and vaccination uptake but demonstrated a significant relationship between risk perception and COVID-19 preventive practices. Health education and risk communication should be intensified to improve knowledge, elicit stronger risk perception, and enhance COVID-19 preventive practices.

The Use of a Unilateral Curved Spreader Graft in the Management of Crooked Nose Deformity.

AIM OF WORK: The aim of this study is to present a new technique of using spreader grafts in the correction of crooked nose deformity with C-shaped deviation of the middle third of the nose. PATIENTS AND METHODS: This is a prospective case series study conducted on 18 patients with crooked nose deformity with C-shaped deviation of the middle third of the nose. All of the patients were managed by open septorhinoplasty. During surgery, a curved spreader graft was harvested from the nasal septum and placed on the convex side of the C-shaped deviation of the dorsal part of the nasal septum. Objective measurements of the angles of external nasal deviation (END) and the internal nasal valve (INV) angles were performed before and 6 months after the surgery. Subjective assessment of aesthetic satisfaction by the visual analog scale and nasal function by the nasal obstruction symptom evaluation scale was also performed before and 6 months after surgery. RESULTS: Eighteen patients were enrolled in the study and completed the minimum follow-up period of 6 months. The mean follow-up period was 17.3 months. Objectively, there was highly significant ( P < 0.00001) improvement of the END angle and INV angle. Subjectively, there was also highly significant ( P < 0.00001) improvement of both the nasal obstruction symptom evaluation score and the visual analog scale score for aesthetic satisfaction. CONCLUSIONS: The insertion of a curved unilateral spreader graft over the convexity of the deviated nasal dorsum can correct the END, improve the collapsed INV on both sides, and consequently achieve satisfactory aesthetic and functional outcomes.

Effect of soft tissue volume on midfacial gingival margin alterations following immediate implant placement in the esthetic zone: a 1-year randomized clinical and volumetric trial.

BACKGROUND: The current trial evaluated the midfacial gingival margin changes, volumetric, radiographic and clinical alterations 1-year following immediate implant placement with customized healing abutment (IIP + CHA) either solely, or in combination with xenograft (IIP + Bonegraft) or with connective tissue grafting (IIP + CTG) at sites with thin labial bone in the esthetic zone. METHODS: Thirty-nine non-restorable maxillary teeth indicated for extraction in the esthetic zone were included. Participants were randomly assigned into three equal group; IIP + Bonegraft (Control), IIP + CTG and IIP + CHA. Midfacial gingival margin changes(mm) as primary outcome, labial soft tissue contour change(mm), interdental tissue height changes and total volume(mm3) were assessed. Amount of bone labial to the implant and crestal bone level changes were also recorded. All outcomes were measured 1-year post-operative. RESULTS: The midfacial gingival margin changes demonstrated a significant difference (P ≤ 0.05) between the groups showing -0.98, -0.74 and -1.54 mm in sites treated with IIP + Bone graft, IIP + CTG and IIP + CHA respectively after1-year. While labial soft tissue contour change (mm), total volume (mm3) and distal interdental tissue height changes (mm) revealed a significant difference after one-year between the studied groups, yet mesial interdental tissue height changes showed no difference (P > 0.05). Both IIP + Bone graft and IIP + CHA groups revealed a significant positive correlation between the total volume loss (mm3) after 1 year and mid-facial gingival margin changes (P ≤ 0.05). However, no significant correlation was observed in the IIP + CTG group (P = 0.63). CBCT measurements showed a significant difference in crestal bone changes between the three groups (P ≤ 0.05), yet, there was no significant difference regarding mean amount of bone labial to the implant(P > 0.05). CONCLUSIONS: This investigation suggests that the mere presence of CTG simultaneous with IIP in the anterior maxilla reduced the midfacial gingival margin alterations (mm), besides, CTG decreased the overall volume loss (mm3) by 5-folds compared to the other studied groups after one year. Meanwhile, using CHA alone with IIP failed to maintain the peri-implant soft tissues contour. TRIAL REGISTRATION: The current trial was retrospectively registered at Clinical trials.gov (ID: NCT05975515, Date: 27-July-2023).

Gout: A Rapid Review of Presentation, Diagnosis and Management.

Gout is inflammatory arthritis caused by monosodium urate crystal deposition in articular and non-articular structures. Acute gout flares are often monoarticular/polyarticular involving lower extremity joints characteristically involving 1st metatarsophalangeal joint. However, gout flares can also be polyarticular, involving upper extremity joints, especially in patients with multiple comorbidities and contraindications to urate-lowering therapies (ULT). Risk factors exacerbating gout flares include obesity, high alcohol and purine-rich food consumption, and the use of diuretics. Diagnosis requires synovial fluid analysis with direct visualization of monosodium urate crystals. Acute flares are managed with steroids, non-steroidal anti-inflammatory drugs, or colchicine. Long-term management includes lifestyle modifications including a heavy emphasis on weight loss, avoidance of alcohol, purine-rich foods, and diuretics. ULT is indicated in patients with 2 or more gout flares/year, tophi, or radiographic evidence of gouty arthropathy. Although allopurinol is the first-line ULT agent, it does carry a risk of inducing severe cutaneous adverse reactions, especially in patients with chronic kidney disease and patients harboring the HLA-B*5801 allele. Other ULT agents include febuxostat and probenecid. ULT is usually titrated to achieve goal serum uric acid (SUA) levels below 6 mg/dL. However, in patients with tophi, a lower SUA target of less than 5 mg/dL should be implemented for prompt urate crystal dissolution.

An Unusual Case of Takotsubo Cardiomyopathy with Cardiac Arrest: The Importance of Clinical Context in Implanted Cardioverter Defibrillator Candidacy.

Takotsubo syndrome (TTS), also known as stress-induced cardiomyopathy, is characterized by acute heart failure, reversible left ventricular dysfunction, and other complications such as life-threatening arrhythmias. The management of TTS is challenging due to its unpredictable clinical course and the lack of evidence-based treatment recommendations. In this case report, we present a 71-year-old female who developed TTS with ventricular tachycardia (VT) cardiac arrest following septic shock and an exploratory laparotomy for appendicitis. Despite the presence of VT cardiac arrest and a left ventricular ejection fraction of 30-35%, an implanted cardioverter-defibrillator (ICD) was not indicated due to the rapid and satisfactory recovery of the patient's ventricular function. This case highlights the importance of considering the clinical context and the transient nature of TTS in the decision-making process for ICD candidacy.

A critical review of workplace drug testing methods for old and new psychoactive substances: Gaps, advances, and perspectives.

Workplace drug testing (WDT) is essential to prevent drug abuse disorders among the workforce because it can impair work performance and safety. However, WDT is limited by many challenges, such as urine adulteration, specimen selection, and new psychoactive substances (NPS). This review examined the issues related to WDT. Various scientific databases were searched for articles on WDT for drug detection published between 1986 (when WDT started) and January 2024. The review discussed the history, importance, and challenges of WDT, such as time of specimen collection/testing, specimen adulteration, interference in drug testing, and detection of NPS. It evaluated the best methods to detect NPS in forensic laboratories. Moreover, it compared different techniques that can enhance WDT, such as immunoassays, targeted mass spectrometry, and nontargeted mass spectrometry. These techniques can be used to screen for known and unknown drugs and metabolites in biological samples. This review assessed the strengths and weaknesses of such techniques, such as their validation, identification, library search, and reference standards. Furthermore, this review contrasted the benefits and drawbacks of different specimens for WDT and discussed studies that have applied these techniques for WDT. WDT remains the best approach for preventing drug abuse in the workplace, despite the challenges posed by NPS and limitations of the screening methods. Nontargeted techniques using high-resolution liquid chromatography-mass spectrometry (MS)/gas chromatography-tandem MS can improve the detection and identification of drugs during WDT and provide useful information regarding the prevalence, trends, and toxicity of both traditional and NPS drugs. Finally, this review suggested that WDT can be improved by using a combination of techniques, multiple specimens, and online library searches in case of new NPS as well as by updating the methods and databases to include new NPS and metabolites as they emerge. To the best of the author's knowledge, this is the first review to address NPS as an issue in WDT and its application and propose the best methods to detect these substances in the workplace environment.

Current situation and barriers to women's leadership in health care education in Saudi Arabia: A cross-sectional study.

Background: The aims of the current study were to explore the true representation of female academic staff who have advanced to leadership positions in Saudi health academic institutions and to determine the possible barriers to women's advancement to leadership positions in academia. Methodology: This was a cross-sectional study conducted between August 2022 and August 2023 using an adapted self-reported online questionnaire via Google form. Data was analyzed descriptively and comparatively by presenting frequencies with percentages besides means with standard deviations across various background categories and comparing them using student t test. Results: A total of 115 educators in health care professions participated in the study, three fifths of them were Saudi and female, with the majority being married and employed by government organizations. The most impactful structural challenges for female leadership included the centralization of decision-making within the institution, unclear organizational bylaws for leadership qualifications and appointment processes, and the existence of a wide range of administrative units. The prevailing belief that men possess superior capacity and management skills compared to women in leadership roles and the reluctance to accept women's authority by their subordinates were identified as the most influential culture challenges for female leadership. Most influential personality-related challenges included difficulty of balancing professional responsibilities with family obligations, stress and tension arising from reconciling the needs of subordinates with organizational goals and the complexity of traveling for work. Conclusions: The study identified the most influential structural, culture, and personality-related barriers and other potential perceived challenges faced by female leadership. A collective effort involving academic institutions, leadership, and relevant stakeholders is critical to address these barriers. Academic institutions must eliminate these challenges to utilize female leaders' talent fully, as they contribute unique perspectives and skills to their institutions.