The Rho guanine dissociation inhibitor α inhibits skeletal muscle Rac1 activity and insulin action.

The molecular events governing skeletal muscle glucose uptake have pharmacological potential for managing insulin resistance in conditions such as obesity, diabetes, and cancer. With no current pharmacological treatments to target skeletal muscle insulin sensitivity, there is an unmet need to identify the molecular mechanisms that control insulin sensitivity in skeletal muscle. Here, the Rho guanine dissociation inhibitor α (RhoGDIα) is identified as a point of control in the regulation of insulin sensitivity. In skeletal muscle cells, RhoGDIα interacted with, and thereby inhibited, the Rho GTPase Rac1. In response to insulin, RhoGDIα was phosphorylated at S101 and Rac1 dissociated from RhoGDIα to facilitate skeletal muscle GLUT4 translocation. Accordingly, siRNA-mediated RhoGDIα depletion increased Rac1 activity and elevated GLUT4 translocation. Consistent with RhoGDIα's inhibitory effect, rAAV-mediated RhoGDIα overexpression in mouse muscle decreased insulin-stimulated glucose uptake and was detrimental to whole-body glucose tolerance. Aligning with RhoGDIα's negative role in insulin sensitivity, RhoGDIα protein content was elevated in skeletal muscle from insulin-resistant patients with type 2 diabetes. These data identify RhoGDIα as a clinically relevant controller of skeletal muscle insulin sensitivity and whole-body glucose homeostasis, mechanistically by modulating Rac1 activity.

Impact of Ramadan fasting on vision and headache-related quality of life in women with idiopathic intracranial hypertension: A prospective observational study.

BACKGROUND: Ramadan fasting is an obligatory religious practice for Muslims. However, research data on the effect of Ramadan on idiopathic intracranial hypertension (IIH) symptoms are lacking. This study aimed to study the effect of Ramadan fasting on the severity of headache and visual symptoms and related quality-of-life activities. METHODS: This prospective cohort study targeted females diagnosed with IIH (n = 102) who were eligible to fast for Ramadan in 2023. The patients were recruited from the Neurology Clinic in Beni-Suef University Hospital, Egypt. Body mass index (BMI), monthly headache days and intensity of headache attacks, six-item Headache Impact Test (HIT-6), and the 25-item National Eye Institute Visual Function Questionnaire (NEI-VFQ-25) scores during Ramadan were compared to those during the (non-fasting) month of Shaaban, the preceding month to Ramadan. RESULTS: There was a significant increase in the BMI of patients with IIH in Ramadan compared to the (non-fasting) month of Shaaban, at a median (interquartile range [IQR]) of 30.5 (26.6-35.8) kg/m2 and 30.1 (26.6-35.2) kg/m2, respectively (p = 0.002). The median (IQR) value of monthly headache days was significantly increased during Ramadan in comparison to the (non-fasting) month of Shaaban, at 20 (11.5-30) vs. 15 (10-25) (p < 0.001). There was a statistically significant worsening in the visual analog scale (VAS) scores (median [IQR] 7 [5-8] vs. 6.5 [5-8]), HIT-6 scores (median [IQR] 61 [58-67] vs. 59 [53-61.5]), and NEI-VFQ-25 total scores (median [IQR] 1312.5 [1238.8-1435] vs 1290 [1165-1417.5]) during Ramadan in comparison to the (non-fasting) month of Shaaban (p < 0.001 for all comparisons). The change in BMI in Ramadan was positively correlated with the change in monthly headache days (r = 0.24, p = 0.014), VAS (r = 0.20, p = 0.043), HIT-6 (r = 0.25, p = 0.010) and NEI-VFQ-25 scores (r = 0.24, p = 0.016). CONCLUSION: Ramadan fasting had an aggravating effect on headache, visual symptoms, and related quality-of-life activities, which might be attributed to weight gain during this month. Whether proper nutritional management to prevent weight gain during Ramadan may help mitigate this worsening effect is a mission of future studies.

Adverse events in low versus normal body weight patients prescribed apixaban for atrial fibrillation.

Safety and efficacy of direct oral anticoagulants (DOAC) in low weight patients with atrial fibrillation (AF) is unclear due to few low body weight patients enrolled in clinical trials. To assess bleeding and thrombotic event rates for patients with AF that are prescribed apixaban and have a low versus normal body weight. We analyzed patients with AF prescribed apixaban from 2017 to 2020 with at least 12 months of follow-up. Patients were divided into low [< 60 kg (kg)] and normal (60-100 kg) weight cohorts. Bleeding and thrombotic event rates were compared. Poisson regression and Cox proportional hazard models were used to estimate adjusted adverse event rates. A total of 545 patients met inclusion criteria. In the unadjusted analysis, there was an increase in non-major bleeding events requiring an Emergency Department visit more often in the low versus normal weight cohort (10.8 versus 7.4 per 100 patient-years, p = 0.15). Thrombotic event rates also occurred more often in the lower versus normal weight cohort (2.4 versus 0.9 per 100 patient-years, p = 0.09). However, adjusted analysis found no statistically significant difference in bleeding or thrombotic events between low and normal weight cohorts. The adjusted hazard ratio for bleeding was similar between the two weight cohorts. The use of apixaban in low body weight patients was not associated with higher rates of bleeding or thrombotic events, compared to those with normal body weight, after adjusting for potential confounding covariates. Larger studies may offer further insight into the overall safety and efficacy of DOAC therapy in these patients.

Detection of unusual Cryptosporidium parvum subtype in patients with gastrointestinal cancer in Egypt.

While the importance of cryptosporidiosis in immunocompromised persons is well known, the prevalence of Cryptosporidium spp. in cancer patients is not clear. The current study was designed to assess the occurrence and genetic characteristics of Cryptosporidium spp. in patients with gastrointestinal (GI) cancer in Egypt. Stool samples were collected from 100 patients with GI malignancies and 20 healthy individuals without any GI manifestations (control group). They were screened by microscopy and the immunochromatographic RIDA®QUICK Cryptosporidium kit. Subtyping of Cryptosporidium spp. was conducted by sequence analysis of the glycoprotein 60 (gp60) locus. Sociodemographic, environmental data and information on GI symptoms, cancer types, and clinical treatment were obtained via a questionnaire. By microscopy and RIDA®QUICK, only 7% (7/100) of GI cancer patients were positive for Cryptosporidium, compared with 40% (40/100) by gp60 nPCR. No positives were obtained from the control group. Male sex (P = 0.02) and younger age (P = 0.004) were major Cryptosporidium risk factors for infection. The occurrence of Cryptosporidium was also significantly more frequent (P = 0.003) in watery stool samples. Sequence analysis of the gp60 amplicons (~ 400 bp) identified a novel C. parvum subtype with nine TCA repeats and eleven ACATCA repeats. A formal subtype designation could not be made due to the short sequence length. More studies should be conducted to verify the common occurrence of this unusual C. parvum subtype and establish its genetic identity.

Qualitative structure-activity relationships of aryl isoprenoid derivatives as biorational juvenoids - reweighing.

Juvenoids are juvenile hormone (JH) mimetics, with specific structural features and defined molecular size that disrupt the target insect development. Juvenoid activity (= JH-type activity) of various isoprenoid-based derivatives as insecticidal candidates of the insect growth disruptors (IGDs) type were rated against the house fly, Musca domestica L. The epoxidized decenyl and nonenyl phenyl ether derivatives have more active compounds than those of both parent alkoxidized or olefinic structures. The highest juvenoid potency was shown by 3,4-methylenedioxyphenyl ethers of 8,9-epoxy-5,9-dimethy1-3,8-decadiene. Qualitative structure-activity relationships are offered to relate the chemical structure criteria to observed juvenoid-related activity. Differences in activity among the reported isoprenoid-based derivatives were qualitatively rationalized. This study advances understanding of the structural qualifications and activity determinants of isoprenoid juvenoids, which is important for the development of new filth flies eco-friendly insecticides. Supplementary Information: The online version contains supplementary material available at 10.1007/s42690-023-01025-3.

Monitoring the effects of fungi isolated from archival document on model albumen silver prints.

Fungi are a common problem in the photographic collection, so the aim of this study focused on isolating and molecular identification of fungi from old albumen prints dating to an archive of Dr. Francis and belonging to the Al-Hagar Family and dating back to 1880-1890. The isolated fungi were identified according to their morphological traits and PCR sequencing. The ability of these isolates to cause deterioration was evaluated on model samples (2 × 2 cm) of albumen silver prints. The effect of these fungi on the morphology and structure of the tested samples were examined by SEM, ATR-FTIR, and chromatic alternations. Four fungal species Aspergillus sydowii, A. flavus, Talaromyces atroroseus, and Penicillium chrysogenum were identified. All isolates were able to grow on the surface of the model Albumen silver print and were capable of causing damage to the binder and able to extend their growth to the paper fibers. A. sydowii, A. flavus, and P. chrysogenum caused hydrolysis and oxidation to the albumen prints, while no significant chemical damage to the albumen was detected for the photographic sample infected with T. atroroseus. All the inoculated samples were significantly affected in terms of color change and the high-light areas have become darker. ATR-FTIR spectra showed the degradation of the protein content in Albumen silver prints inoculated with A. sydowii, A. flavus, and P. chrysogenum.

The potential impact of insulin resistance and metabolic syndrome on migraine headache characteristics.

BACKGROUND & OBJECTIVES: Studying comorbidities with migraine aids in a better understanding of its pathophysiology and potential therapeutic targets. This case-control study aimed to study the impact of insulin resistance and metabolic syndrome on the characteristics of migraine headache attacks. METHODS: A case-control study was conducted on 30 migraine patients and 30 healthy controls. The following data were assessed in migraine patients: type of migraine, duration of attacks, Migraine Severity Scale (MIGSEV), and Headache Impact Test-6 (HIT-6). Both groups were assessed for waist circumference and underwent the following tests: fasting blood glucose, fasting insulin, high-density lipoprotein cholesterol level, and triglycerides, and homeostasis model assessment-insulin resistance (HOMA-IR) was applied. RESULTS: This study included age and sex-matched patients and controls. Migraine patients had significantly higher waist circumference, higher mean values of serum insulin, HOMA-IR and higher frequency of insulin resistance and metabolic syndrome than the control group (P-value = 0.005, 0.049, 0.01, 0.012, 0.024, respectively). Migraine patients with insulin resistance had significantly higher intensity and tolerability scores, MIGSEV total score, and HIT-6 total score compared to those without (P-value = 0.005, 0.005, 0.002, 0.018, respectively). There was a significantly positive correlation between the MIGSEV and HIT-6 scores and fasting insulin levels, and HOMA-IR value (P-value = 0.006, ≤ 0.001, 0.017, ≤ 0.001, respectively). CONCLUSION: Insulin resistance and metabolic syndrome are more common in migraine patients than in healthy controls. The severity and impact of migraine attacks are higher in patients with insulin resistance than in those without.

Anti-Cryptosporidium efficacy of Citrus sinensis peel extract: Histopathological and ultrastructural experimental study.

BACKGROUND: Cryptosporidiosis is a crucial zoonotic global health concern which can be treated by alternative medicinal plants extracts. AIM OF THE STUDY: The study was carried out to assess the therapeutic efficacy of Citrus sinensis peel ethanolic extract on Cryptosporidium-infected mice. METHODS: Two doses of Citrus sinensis extract; high dose (30 mg/kg) and low dose (15 mg/kg) were investigated compared to the common commercial drug nitazoxanide (NTZ). Assessment of the extract was carried out by calculating oocysts count in fecal samples, in addition to histopathological and electron microscopic examination of intestinal mucosa.. RESULTS: There was a statistically significant reduction in the percentage of oocyst shedding more in high dose than low dose Citrus-treated mice group till negligible numbers of oocysts were found at day 22nd post infection. Histopathologically, the intestinal tissues from high dose Citrus-treated group showed improvement of the pathological changes, the villi retained their normal appearance with minimal inflammatory cells in comparison to infected control mice groups. Also, ultra-structurally, the high dose Citrus-treated mice showed few Cryptosporidium trophozoites, while moderate number of parasitic stages and mucous in the low dose Citrus-treated mice, and large numbers of parasitic stages with sever mucous in the control infected non-treated mice epithelium. CONCLUSION: Our study established for the first time that Citrus sinensis is a promising natural candidate that could be efficiently used for developing of new anti-cryptospordial drugs.

Serotonin-release assay-positive but platelet factor 4-dependent enzyme-immunoassay negative: HIT or not HIT?

IgG-specific and polyspecific PF4-dependent enzyme-immunoassays (EIAs) have exceptionally high sensitivity (≥99%) for diagnosis of heparin-induced thrombocytopenia (HIT), a drug reaction caused by platelet-activating antibodies detectable by serotonin-release assay (SRA). The IgG-specific EIAs are recommended for screening, as their high sensitivity is accompanied by relatively high specificity vis-à-vis polyspecific EIAs. We investigated the frequency of SRA-positive/EIA-negative (SRA+/EIA-) HIT, prompted by referral to our reference HIT laboratory of serial blood samples from a patient ("index case") with false-negative IgG-specific EIAs. Despite initial clinical suspicion for HIT, repeat negative IgG-specific EIAs prompted heparin resumption, which triggered recurrent thrombocytopenia and near-fatal cardiac arrest, indicating likely post-heparin HIT-associated anaphylactoid reaction. Further investigations revealed a strong-positive SRA, whether performed with heparin alone, PF4 alone, or PF4/heparin, with inhibition by Fc receptor-blocking monoclonal antibody (indicating IgG-mediated platelet activation); however, five different IgG-specific immunoassays yielded primarily negative (or weak-positive) results. To investigate the frequency of SRA+/EIA- HIT, we reviewed the laboratory and clinical features of patients with this serological profile during a 6-year period in which our reference laboratory investigated for HIT using both SRA and IgG-specific EIA. Although ~0.2% of 8546 patients had an SRA+/EIA- profile, further review of 15 such cases indicated clerical/laboratory misclassification or false-positive SRA in all, with no SRA+/EIA- HIT case identified. We conclude that while SRA+/EIA- HIT is possible-as shown by our index case-this clinical picture is exceptionally uncommon. Moreover, the requirement for a positive EIA is a useful quality control maneuver that reduces risk of reporting a false-positive SRA result.

Efficacy and Safety of Topical Silymarin Versus Low Fluence 1064-nm Q Switched Nd:YAG Laser in the Treatment of Melasma: A Comparative Randomized Trial.

BACKGROUND AND OBJECTIVES: The management of melasma is challenging and requires multiple uses of available therapeutic options. To compare the short-term efficacy and safety of topical silymarin and low fluence 1064-nm Q-switched ND:YAG laser for treatment of melasma with dermoscopic follow-up. STUDY DESIGN/MATERIALS AND METHODS: Fifty female patients with melasma were included in this study. They were randomly divided into two groups. Group A: 25 patients were treated with six sessions of low fluence Q switched ND:YAG 1064-nm laser, and group B: 25 patients were treated with topical silymarin cream 1.4% with a 3-month treatment duration. Patients were evaluated clinically by the modified melasma area and severity index (mMASI) score. Dermoscopic examinations were performed before and after the treatment sessions. RESULTS: The severity of melasma, as evaluated dermoscopically and clinically by mMASI score, was significantly reduced after treatment in all patients with no recorded side effects. There was no statistically significant difference between both studied groups regarding the change in mMASI score and dermoscopic assessment of the patients after the treatment sessions. CONCLUSION: Both low fluence Q switched ND:YAG 1064-nm laser and topical silymarin cream appear to be safe and effective modalities in the treatment of melasma. © 2021 Wiley Periodicals LLC.

Creatinine monitoring patterns in the setting of direct oral anticoagulant therapy for non-valvular atrial fibrillation.

Guidelines and experts note that patients with atrial fibrillation require regular renal function monitoring to ensure safe use of direct oral anticoagulants (DOACs). Insufficient monitoring could lead to inappropriate dosing and adverse events. Our objective was to describe the frequency of insufficient creatinine monitoring among patients on DOACs, and to describe clinical factors associated with insufficient monitoring. We hypothesized that renal impairment would be associated with insufficient monitoring. A retrospective cohort study was performed with data from the Michigan Anticoagulant Quality Improvement Initiative. Patients were included if they initiated DOAC therapy for stroke prevention related to atrial fibrillation, remained on therapy for ≥ 1 year, and had baseline creatinine and weight measurements. Creatinine clearance (CrCl) was calculated via Cockcroft-Gault equation. Our outcome was the presence of insufficient creatinine monitoring, defined as: < 1 creatinine level/year for patients with CrCl > 50, or < 2 creatinine levels/year for patients with CrCl ≤ 50. Multivariable analysis was done via logistic regression. Study population included 511 patients. In overall, 14.0% of patients received insufficient monitoring. Among patients with CrCl > 50, 11.5% had < 1 creatinine level/year. Among patients with CrCl ≤ 50, 27.1% received < 2 creatinine levels/year. Baseline renal dysfunction was associated with a higher likelihood of insufficient creatinine monitoring (adjusted odds ratio 3.64, 95% confidence interval 1.81-7.29). This shows a significant gap in the monitoring of patients on DOACs-patients with renal impairment are already at higher risk for adverse events. Future studies are needed to describe the barriers in monitoring these patients and to identify how to optimally address them.

Rac1 muscle knockout exacerbates the detrimental effect of high-fat diet on insulin-stimulated muscle glucose uptake independently of Akt.

KEY POINTS: The actin cytoskeleton regulating GTPase, Rac1, is a novel player in insulin-stimulated glucose uptake in muscle in vivo. High-fat diet (HFD) exacerbates muscle insulin resistance in Rac1 muscle knockout (mKO) mice. Muscle Rac1 KO protects against HFD-induced insulin resistance in fat tissue indicating tissue cross-talk. A fatty diet markedly reduces insulin clearance in mice. ABSTRACT: Insulin resistance and perturbations in glucose metabolism underpin common lifestyle diseases such as type 2 diabetes and obesity. Insulin resistance in muscle is characterized by compromised activity of the GTPase, Ras-related C3 Botulinum toxin substrate 1 (Rac1), yet the role of Rac1 in insulin-stimulated glucose uptake in vivo and diet-induced insulin resistance is unknown. Inducible muscle-specific Rac1 knockout (Rac1 mKO) and wild type (WT) littermate mice were either fed a chow or a 60% high-fat diet (HFD). Insulin-stimulated 2-deoxy-glucose uptake, intracellular signalling, protein expression, substrate utilization, and glucose and insulin tolerance were assessed. In chow-fed mice, in vivo insulin-stimulated glucose uptake was reduced in triceps, soleus and gastrocnemius muscles from Rac1 mKO mice. HFD-induced whole body insulin resistance was exacerbated by the lack of muscle Rac1 and glucose uptake was reduced in all muscles, except for soleus. Muscle Akt (also known as protein kinase B) signalling was unaffected by diet or genotype. In adipose tissue, Rac1 mKO mice were protected from HFD-induced insulin resistance (with respect to both glucose uptake and phosphorylated-Akt), rendering their whole body glucose tolerance comparable to WT mice on HFD. Our findings show that lack of Rac1 exacerbates HFD-induced insulin resistance in skeletal muscle. Whole body glucose tolerance, however, was largely unaffected in Rac1 mKO mice, likely due to improved insulin-stimulated glucose uptake in adipose tissue. We conclude that lack of Rac1 in the context of obesity is detrimental to insulin-stimulated muscle glucose uptake in muscle independently of Akt signalling.

Proteomic Analyses on an Ancient Egyptian Cheese and Biomolecular Evidence of Brucellosis.

The material analyzed in this study is probably the most ancient archeological solid residue of cheese ever found to date. The sample was collected during the Saqqara Cairo University excavations in the tomb of Ptahmes dated to XIX dynasty ( El-Aguizy, O. Bulletin de l'Institut Française d'Archéologie Orientale (BIFAO) 2010 , 110 , 13 - 34 (ref (1) ); Staring, N. Bulletin de Institut Français d'Archéologie Orientale (BIFAO) 2015 , 114 , 455 - 518 (ref (2) )). Our biomolecular proteomic characterization of this archeological sample shows that the constituting material was a dairy product obtained by mixing sheep/goat and cow milk. The interactions for thousands of years with the strong alkaline environment of the incorporating soil rich in sodium carbonate and the desertic conditions did not prevent the identification of specific peptide markers which showed high stability under these stressing conditions. Moreover, the presence of Brucella melitensis has been attested by specific peptide providing a reasonable direct biomolecular evidence of the presence of this infection in the Ramesside period for which only indirect paleopathological evidence has been so far provided ( Pappas, G.; Papadimitriou P. Int. J. Antimicrob. Agents 2007 , 30 , 29 - 31 (ref (3) ); Bourke, J. B. Medical History 1971 , 15 ( 4 ), 363 - 375 (ref (4) )). Finally, it is worth noting that, although proteomic approaches are successfully and regularly used to characterize modern biological samples ( D'Ambrosio, C.; Arena, S.; Salzano, A. M.; Renzone, G.; Ledda, L.; and Scaloni, A. Proteomics 2008 8 , 3657 - 3666 (ref (5) ), their application in ancient materials is still at an early stage of progress, only few results being reported about ancient food samples ( Yang, Y.; Shevchenko, A.; Knaust, A.; Abuduresule, I.; Li, W.; Hu, X.; Wang, C.; Shevchenko, A. J. Archaeol. Sci. 2014 , 45 , 178 - 186 (ref (6) ). In the absence of previous relevant evidence of cheese production and/or use, this study, undoubtedly has a clear added value in different fields of knowledge ranging from archaeometry, anthropology, archeology, medicine history to the forensic sciences.

Using Skin Gene Markers for Estimating Early Postmortem Interval at Different Temperatures.

Many researches document long-term RNA persistence in a variety of tissues and its applicability in estimating the postmortem interval (PMI). Skin-specific mRNA marker, late cornified envelope 1C (LCE1C), was used to identified skin samples. Before using the LCE1C in criminal casework, its persistence and applicability for estimating PMI in different temperatures were tested. Twelve skin samples were collected from 6 patients, and 6 samples were kept at 24°C and others were kept at 40°C for 5 days. The expression levels of LCE1C mRNA are serially detected and quantified using real-time polymerase chain reaction. The expression levels of LCE1C were decreased with increasing the time interval in time-dependent manner, whereas changing the surrounding temperatures did not show any statistical significance. These results could suggest using LCE1C in estimation of PMI. Moreover, these encourage investigators and crime laboratories to know environmental conditions before interpreting the results.

Natural history and response to treatment of HCV infection among Egyptian survivors of childhood malignancy.

BACKGROUND: Children with cancer are at a high risk for hepatitis C virus infection due to immunosuppression secondry to chemotherapy and multiple transfusions of blood products. We aim to evaluate the presence of HCV infection in children with malignant diseases, risk factors, clinical course, laboratory, histopathological findings, and response to HCV treatment. METHOD: We described 31 patients referred to the pediatric hepatology clinic at Cairo University pediatric hospital and presenting with postmalignant virus C infection. Data collected included that of medical history, physical examination, and periodic evaluation clinically, laboratory, and histopathologically during their follow up. RESULTS: The mean age at diagnosis of HCV infection was 8 ± 3.3 years, the period of follow up of the patients in the hepatology clinic ranged from 0.3 to 15 years with a mean of 2.6 ± 2.3 years. Risk factors for HCV acquisition were chemotherapy in 93.5%, blood transfusions in 83.9%, and operations in 64.5%. Out of the 31 cases, 51.6% had leukemia. At first presentation, serum ALT level was elevated in 83.9% and AST level was elevated in 80.6%. Liver biopsy was performed in 26 cases; 96.1% had mild to moderate activity, 32% had no fibrosis, and 68% had mild to moderate fibrosis. Eighteen cases received HCV treatment. The response to HCV treatment was 27.7%. Although hepatitis C infection acquired by childhood cancer survivors was presented initially with high rate of elevated liver enzymes and PCR positivity, it seems to have a relatively benign clinical course with mild to moderate chronic hepatitis.

External nasal parameters in Egyptians: an in-depth nasal photogrammatic analysis.

PURPOSE: As ethnic influences can result in different appearances of the nose, the purpose of this study was to provide a set of standard values of the external form of the nose with special emphasis on the influence of age and sex on these values to establish norms for the Egyptians. METHODS: Several soft-tissue landmarks on the external nose were obtained by a non-invasive, photogrammetric analysis in 1,000 healthy Egyptians aged 20-70 years. From these landmarks, ten linear distances and six nasal angles were measured and six nasal indices were calculated. RESULTS: A significant sexual dimorphism was found for nasal external volume and area and most linear distances where males presented with higher values than those in females of the corresponding age except for alar length where females showed higher values. Moreover, age significantly influenced nasal volume, area and distances as they showed statistically significant increase till old age. Concerning angles, nasofrontal, nasofacial, nasomental and nasolabial angles were wider in females while mentocervical angle was wider in males. Moreover, nasofrontal, mentocervical and alar slope angles showed significant increase with advancing age while nasofacial, nasomental and nasolabial showed significant decrease. Regarding nasal indices, sexual dimorphism was recognized for anatomic nasal index, nasal tip protrusion, nasal height ratio and nasal tip protrusion-nasal width indices. Moreover, results also showed that the Egyptians have a Mesorrhine type of nose. CONCLUSION: Data collected in the present investigation could serve as a database for the quantitative description of the Egyptian nasal morphology.

Association of Anxiety and Depressive Symptoms and Treatment Adherence Among Patients With Type 2 Diabetes Mellitus in Jazan, Saudi Arabia: A Cross-Sectional Study.

BACKGROUND: Diabetes mellitus is a serious public health concern. It is associated with many psychological problems, such as depression, anxiety, and eating disorders. These co-morbidities are associated with improper adherence to treatment, self-care, poor glycemic control, more complications, and worse outcomes. METHODS: This study aimed to measure the level of medication adherence among type 2 diabetics in Jazan, Saudi Arabia, and to find its association with their psychological status (specifically, depression and anxiety). A cross-sectional descriptive design was used among adults with type 2 diabetes at the Diabetes and Endocrinology Center in Jazan, Saudi Arabia. The estimated sample size was 480 patients. The General Medication Adherence Scale and Patient Health Questionnaire-4 (PHQ-4) were used as tools to achieve the study objectives. RESULTS: A total of 449 diabetic patients completed the survey (93.5% response rate). Patients with poor, low, and partial adherence account for 337 (75%) of patients and only 112 (25%) have good and high medication adherence. Employment and duration of illness were highly significant with a positive relationship to treatment adherence (p = 0.010 and 0.000, respectively). On the other hand, age and disease duration had a significant relationship with psychological disorders (p = 0.029 and 0.002, respectively). Of the patients, 64 (14.3%) had high scores on the PHQ-4, with depressive symptoms in 46 (10.24%) and anxiety symptoms in 75 (16.7%). Correlation analysis reveals that there is a highly significant negative correlation between psychological disorders and adherence to medications (r = -0.288, p = 0.000). CONCLUSION: A negative correlation between psychological disorders and adherence to medications was found. The findings indicate the importance of psychological support for diabetic patients for better treatment adherence.

Prevalence of Guideline-Discordant Aspirin Use and Associated Adverse Events in Patients on Warfarin for Mechanical Valve Replacement.

BACKGROUND: For patients on warfarin for mechanical heart valve replacement, the 2020 American College of Cardiology and American Heart Association Guidelines recommend only adding aspirin in patients with a specific indication for antiplatelet therapy. This contrasts with prior guidelines, which recommended concomitant aspirin therapy. We sought to assess the prevalence of guideline-discordant aspirin use among patients on warfarin for mechanical heart valve replacement and to compare adverse event rates among patients with and without concomitant aspirin. METHODS: Patients on warfarin for mechanical heart valve replacement were identified from the Michigan Anticoagulation Quality Improvement Initiative registry. Patients with myocardial infarction, percutaneous coronary intervention, or coronary artery bypass within the past 12 months were excluded. Patients were divided into 2 groups based on aspirin use. Patient characteristics and bleeding and thromboembolic outcomes were compared. RESULTS: Four hundred forty-four patients met the inclusion criteria, with 341 (76.8%) on concomitant aspirin. The aspirin group was older (50.6 vs 46.3 years, P = .028) and had more hypertension (57.8% vs 46.6%, P = .046) but other patient characteristics were similar. The aspirin group had a higher rate of bleeding events (28.3 vs 13.3 per 100 patient-years, P < .001) and bleed-related emergency department visits (11.8 vs 2.9 per 100 patient-years, P = .001) compared with the non-aspirin group. There was no observed difference in rates of ischemic stroke (0.56 vs 0.48 per 100 patient-years, P = .89). CONCLUSIONS: A significant proportion of patients on warfarin for mechanical heart valve replacement are on guideline-discordant aspirin. Aspirin deprescribing in select patients may safely reduce bleeding events.

Timing of Off-Label Dosing of Direct Oral Anticoagulants in Three Large Health Systems.

BACKGROUND: While direct oral anticoagulants (DOACs) may be viewed as simpler to manage then warfarin, they present their own unique management challenges resulting in frequent off-label dosing. It is unknown to what extent off-label dosing occurs when a patient is started on a DOAC versus later in their treatment. OBJECTIVES: We aimed to characterize when off-label DOAC dosing is occurring and to evaluate the effectiveness of prescribing oversight using a registry-based intervention. METHODS: We evaluated data from the Michigan Anticoagulation Quality Improvement Initiative (MAQI2) registry, a retrospective quality improvement process using data abstractors, from 2018 - 2022 on the number of "alerts" that are generated in response to dosing deviating from evidence-based guidelines. RESULTS: Among a sample of 1,261 to 1,563 annual DOAC-treated patients in the MAQI2 registry, off-label dosing was relatively common. Over the 5-year period from 2018 through 2022, there were 735 total dosing alerts. Alerts occurred more frequently during a follow-up than at the time of initial prescribing, 69.0% (507) versus 31.0% (228) respectively. After initial review by quality improvement abstractors, 18.2% of alerts (134) resulted in contact to the prescriber. When the prescriber was contacted, it led to an intervention 74.6% of the time. The most common intervention was a change in DOAC dosing. CONCLUSIONS: This study demonstrates the benefit of DOAC prescribing oversight using a registry-based intervention to monitor for off-label dosing for the entirety of the time period a patient is prescribed DOAC as deviations in evidence-based prescribing occur frequently during the follow-up period.