Introgression of bacterial leaf blight (BLB) resistant gene, Xa7 into MARDI elite variety, MR219 by marker assisted backcrossing (MABC) approach / Introdução do gene resistente à ferragem da folha bacteriana (BLB), xa7 na variedade MARDI elite, MR219 por abordagem de backcrossing assistida por marcador (MABC)

Abstract Bacterial leaf blight (BLB) is one of the major rice diseases in Malaysia. This disease causes substantial yield loss as high as 70%. Development of rice varieties which inherited BLB resistant traits is a crucial approach to promote and sustain rice industry in Malaysia. Hence, this study aims were to enhance BLB disease resistant characters of high yielding commercial variety MR219 through backcross breeding approach with supporting tool of marker-assisted selection (MAS). Broad spectrum BLB resistance gene, Xa7 from donor parent IRBB7 were introgressed into the susceptible MR219 (recurrent parent) using two flanking markers ID7 and ID15. At BC3F4, we managed to generate 19 introgressed lines with homozygous Xa7 gene and showed resistant characteristics as donor parent when it was challenged with Xanthomonas oryzae pv. oryzae through artificial inoculation. Recurrent parent MR219 and control variety, MR263 were found to be severely infected by the disease. The improved lines exhibited similar morphological and yield performance characters as to the elite variety, MR219. Two lines, PB-2-107 and PB-2-34 were chosen to be potential lines because of their outstanding performances compared to parent, MR219. This study demonstrates a success story of MAS application in development of improved disease resistance lines of rice against BLB disease.

Resumo A mancha bacteriana das folhas (BLB) é uma das principais doenças do arroz na Malásia. Essa doença causa perdas substanciais de rendimento de até 70%. O desenvolvimento de variedades de arroz que herdaram características de resistência ao BLB é uma abordagem crucial para promover e sustentar a indústria do arroz na Malásia. Portanto, o objetivo deste estudo foi aumentar os caracteres BLB resistentes a doenças da variedade comercial MR219 de alto rendimento por meio de uma abordagem de cruzamento retrocruzamento com ferramenta de apoio de seleção assistida por marcador (MAS). O gene de resistência a BLB de amplo espectro, Xa7 do pai doador IRBB7, foi introgressado no MR219 suscetível (pai recorrente) usando dois marcadores flanqueadores ID7 e ID15. No BC3F4, conseguimos gerar 19 linhagens introgressadas com o gene Xa7 homozigoto e apresentamos características de resistência como genitor doador quando desafiado com Xanthomonas oryzae pv. oryzae por inoculação artificial. O pai recorrente MR219 e a variedade controle, MR263, estavam gravemente infectados pela doença. As linhas melhoradas exibiram características morfológicas e de desempenho de rendimento semelhantes às da variedade elite, MR219. Duas linhas, PB-2-107 e PB-2-34, foram escolhidas como linhas potenciais por causa de seus desempenhos excelentes em comparação com a mãe, MR219. Este estudo demonstra uma história de sucesso de aplicação de MAS no desenvolvimento de linhas de arroz melhoradas com resistência a doenças contra a doença BLB.

Introgression of bacterial leaf blight (BLB) resistant gene, Xa7 into MARDI elite variety, MR219 by marker assisted backcrossing (MABC) approach

Abstract Bacterial leaf blight (BLB) is one of the major rice diseases in Malaysia. This disease causes substantial yield loss as high as 70%. Development of rice varieties which inherited BLB resistant traits is a crucial approach to promote and sustain rice industry in Malaysia. Hence, this study aims were to enhance BLB disease resistant characters of high yielding commercial variety MR219 through backcross breeding approach with supporting tool of marker-assisted selection (MAS). Broad spectrum BLB resistance gene, Xa7 from donor parent IRBB7 were introgressed into the susceptible MR219 (recurrent parent) using two flanking markers ID7 and ID15. At BC3F4, we managed to generate 19 introgressed lines with homozygous Xa7 gene and showed resistant characteristics as donor parent when it was challenged with Xanthomonas oryzae pv. oryzae through artificial inoculation. Recurrent parent MR219 and control variety, MR263 were found to be severely infected by the disease. The improved lines exhibited similar morphological and yield performance characters as to the elite variety, MR219. Two lines, PB-2-107 and PB-2-34 were chosen to be potential lines because of their outstanding performances compared to parent, MR219. This study demonstrates a success story of MAS application in development of improved disease resistance lines of rice against BLB disease.

Resumo A mancha bacteriana das folhas (BLB) é uma das principais doenças do arroz na Malásia. Essa doença causa perdas substanciais de rendimento de até 70%. O desenvolvimento de variedades de arroz que herdaram características de resistência ao BLB é uma abordagem crucial para promover e sustentar a indústria do arroz na Malásia. Portanto, o objetivo deste estudo foi aumentar os caracteres BLB resistentes a doenças da variedade comercial MR219 de alto rendimento por meio de uma abordagem de cruzamento retrocruzamento com ferramenta de apoio de seleção assistida por marcador (MAS). O gene de resistência a BLB de amplo espectro, Xa7 do pai doador IRBB7, foi introgressado no MR219 suscetível (pai recorrente) usando dois marcadores flanqueadores ID7 e ID15. No BC3F4, conseguimos gerar 19 linhagens introgressadas com o gene Xa7 homozigoto e apresentamos características de resistência como genitor doador quando desafiado com Xanthomonas oryzae pv. oryzae por inoculação artificial. O pai recorrente MR219 e a variedade controle, MR263, estavam gravemente infectados pela doença. As linhas melhoradas exibiram características morfológicas e de desempenho de rendimento semelhantes às da variedade elite, MR219. Duas linhas, PB-2-107 e PB-2-34, foram escolhidas como linhas potenciais por causa de seus desempenhos excelentes em comparação com a mãe, MR219. Este estudo demonstra uma história de sucesso de aplicação de MAS no desenvolvimento de linhas de arroz melhoradas com resistência a doenças contra a doença BLB.

Effectiveness of Valsartan's Single-Pill Combination Therapies on Blood Pressure Control in Hypertensive Patients: Malaysian Single-Centre Real-World Experience.

Background: Uncontrolled hypertension can cause cardiovascular disease and is an important public health issue. Single-pill combination (SPC) therapies possess combined blood pressure (BP)-lowering effect and may improve compliance to treatment. This study assessed the effectiveness of valsartan (Val)-based SPC therapies in achieving BP control in hypertensive patients. Methods: This was a retrospective study. Data were extracted from the hybrid medical records of patients from the Institut Jantung Negara (IJN), Malaysia. Adults with established diagnosis of hypertension and on prescription of Val-based SPC therapies as part of routine medical care from 1 January 2013 to 31 December 2018, with ≥ 1 year of follow-up were included. Primary endpoint was proportion of patients achieving therapeutic BP control (BP < 140/90 mmHg). Secondary outcomes included change from baseline (CFB) in systolic BP (SBP) and diastolic BP (DBP), and subgroup analysis was based on baseline SBP categories and presence of diabetes. Results: Study included 409 hypertensive patients. The mean (standard deviation [SD]) age of the population was 65.1 (10.6) years old, with male predominance (61.6%). Proportion of patients achieving target BP between baseline and follow-up were 57.0% (P < 0.001). Mean CFB in SBP and DBP were recorded as 19.52 mmHg and 7.47 mmHg, respectively. Over half of the patients achieved the target BP in all subgroups categorised by SBP at baseline, except the subgroup of SBP 160 mmHg-179 mmHg. SPC therapies were continued in 97.3% of patients at 1-year follow-up. Conclusion: Patients using Val-based SPC therapies had significant reduction in BP with good tolerability, with 57% of patients achieving target BP over a prolonged 1-year follow-up period. Uptake of SPC therapy is warranted to improve patient care and outcomes in hypertension.

[Genetic diffuse cystic lung disease in adults]. / Maladies kystiques pulmonaires de l'adulte d'origine génétique.

Multiple cystic lung diseases comprise a wide range of various diseases, some of them of genetic origin. Lymphangioleiomyomatosis (LAM) is a disease occurring almost exclusively in women, sporadically or in association with tuberous sclerosis complex (TSC). Patients with LAM present with lymphatic complications, renal angiomyolipomas and cystic lung disease responsible for spontaneous pneumothoraces and progressive respiratory insufficiency. TSC and LAM have been ascribed to mutations in TSC1 or TSC2 genes. Patients with TSC are variably affected by cutaneous, cognitive and neuropsychiatric manifestations, epilepsy, cerebral and renal tumors, usually of benign nature. Birt-Hogg-Dubé syndrome is caused by mutations in FLCN encoding folliculin. This syndrome includes lung cysts of basal predominance, cutaneous fibrofolliculomas and various renal tumors. The main complications are spontaneous pneumothoraces and renal tumors requiring systematic screening. The mammalian target of rapamycin (mTOR) pathway is involved in the pathophysiology of TSC, sporadic LAM and Birt-Hogg-Dubé syndrome. MTOR inhibitors are used in LAM and in TSC while Birt-Hogg-Dubé syndrome does not progress towards chronic respiratory failure. Future challenges in these often under-recognized diseases include the need to reduce the delay to diagnosis, and to develop potentially curative treatments. In France, physicians can seek help from the network of reference centers for the diagnosis and management of rare pulmonary diseases.

Biosynthesis of natural and halogenated plant monoterpene indole alkaloids in yeast.

Monoterpenoid indole alkaloids (MIAs) represent a large class of plant natural products with marketed pharmaceutical activities against a wide range of indications, including cancer, malaria and hypertension. Halogenated MIAs have shown improved pharmaceutical properties; however, synthesis of new-to-nature halogenated MIAs remains a challenge. Here we demonstrate a platform for de novo biosynthesis of two MIAs, serpentine and alstonine, in baker's yeast Saccharomyces cerevisiae and deploy it to systematically explore the biocatalytic potential of refactored MIA pathways for the production of halogenated MIAs. From this, we demonstrate conversion of individual haloindole derivatives to a total of 19 different new-to-nature haloserpentine and haloalstonine analogs. Furthermore, by process optimization and heterologous expression of a modified halogenase in the microbial MIA platform, we document de novo halogenation and biosynthesis of chloroalstonine. Together, this study highlights a microbial platform for enzymatic exploration and production of complex natural and new-to-nature MIAs with therapeutic potential.

Addressing the impact of high glucose microenvironment on the immunosuppressive characteristics of human mesenchymal stem cells.

Mesenchymal stem cells (MSCs) are a therapeutically efficient type of stem cells validated by their ability to treat many inflammatory and chronic conditions. The biological and therapeutic characteristics of MSCs can be modified depending on the type of microenvironment at the site of transplantation. Diabetes mellitus (DM) is a commonly diagnosed metabolic disease characterized by hyperglycemia, which alters over time the cellular and molecular functions of many cells and causes their damage. Hyperglycemia can also impact the success rate of MSCs transplantation; therefore, it is extremely significant to investigate the effect of high glucose on the biological and therapeutic attributes of MSCs, particularly their immunomodulatory abilities. Thus, in this study, we explored the effect of high glucose on the immunosuppressive characteristics of human adipose tissue-derived mesenchymal stem cells (hAD-MSCs). We found that hAD-MSCs cultured in high glucose lost their immunomodulatory abilities and became detectable by immune cells. The decline in the immunosuppressive capabilities of hAD-MSCs was mediated by significant decrease in the levels of IDO, IL-10, and complement factor H and substantial increase in the activity of immunoproteasome. The protein levels of AMP-activated protein kinase (AMPK) and phosphofructokinase-1 (PFK-1), which are integral regulators of glycolysis, revealed a marked decline in high glucose exposed MSCs. The findings of our study indicated the possibility of immunomodulatory shift in MSCs after being cultured in high glucose, which can be translationally employed to explain their poor survival and short-lived therapeutic outcomes in diabetic patients.

Development and validation of a predictive models for predicting the cardiac events within one year for patients underwent percutaneous coronary intervention procedure at IJN.

PURPOSE: Percutaneous coronary intervention (PCI) is a common treatment modality for coronary artery disease. Accurate prediction of patients at risk for complications and hospital readmission after PCI could improve the overall clinical management. We aimed to develop and validate predictive models to predict any cardiac event within a year post PCI procedure. METHODS: This is a retrospective cohort study utilizing data from the National Cardiovascular Disease (NCVD)-PCI registry. The data collected (N = 28,007) were split into training set (n = 24,409) and testing set (n = 3598). Four predictive models (logistic regression [LR], random forest method, support vector machine [SVM], and artificial neural network) were developed and validated. The outcome on risk prediction were compared. RESULTS: The demographic and clinical features of patients in the training and testing cohorts were similar. Patients had mean age ± standard deviation of 58.15 ± 10.13 years at admission with a male majority (82.66%). In over half of the procedures (50.61%), patients had chronic stable angina. Within 1 year of follow up mortality, target vessel revascularization (TVR), and composite event of mortality and TVR were 3.92%, 9.48%, and 12.98% respectively. LR was the best model in predicting mortality event within 1-year post-PCI (AUC: 0.820). SVM had the highest discrimination power for both TVR event (AUC: 0.720) and composite event of mortality and TVR (AUC: 0.720). CONCLUSIONS: This study successfully identified optimal prediction models with the good discriminatory ability for mortality outcome and good discrimination ability for TVR and composite event of mortality and TVR with a simple machine learning framework.

Diagnostic challenges and prognostic implications of extranodal extension in head and neck cancer: a state of the art review and gap analysis.

Extranodal extension (ENE) is a pattern of cancer growth from within the lymph node (LN) outward into perinodal tissues, critically defined by disruption and penetration of the tumor through the entire thickness of the LN capsule. The presence of ENE is often associated with an aggressive cancer phenotype in various malignancies including head and neck squamous cell carcinoma (HNSCC). In HNSCC, ENE is associated with increased risk of distant metastasis and lower rates of locoregional control. ENE detected on histopathology (pathologic ENE; pENE) is now incorporated as a risk-stratification factor in human papillomavirus (HPV)-negative HNSCC in the eighth edition of the American Joint Committee on Cancer (AJCC) and the Union for International Cancer Control (UICC) TNM classification. Although ENE was first described almost a century ago, several issues remain unresolved, including lack of consensus on definitions, terminology, and widely accepted assessment criteria and grading systems for both pENE and ENE detected on radiological imaging (imaging-detected ENE; iENE). Moreover, there is conflicting data on the prognostic significance of iENE and pENE, particularly in the context of HPV-associated HNSCC. Herein, we review the existing literature on ENE in HNSCC, highlighting areas of controversy and identifying critical gaps requiring concerted research efforts.

Determination of Appropriate Umbilicus Position during Abdominoplasty in Male Patients.

Background: Abdominoplasty techniques are well documented. The ideal position of the umbilicus has, however, received limited attention. Unfortunately, umbilicus position is not universally agreed upon in male cosmetic abdominoplasty. This study was conducted to determine the ideal umbilicus anthropometric measurements in young men, and the relationships between umbilical position and anterior trunk and torso reference points that may be applicable to intraoperative positioning. It is aimed also at investigating whether umbilicus position would be more accurately determined by considering nipple position instead of the abdominal crease, as recently proposed. Methods: Several anthropometric measurements of various anterior abdominal and thoracic landmarks were conducted on 60 young and middle-aged male volunteers and 30 cadavers at São Paulo city. All statistical analysis was completed using Stata software. Results: Of all the measured reference points, a much stronger correlation (0.513) was demonstrated between umbilicus-anterior axillary fold (U-AX) and inter-nipple (N-N) distances with a constant golden number ratio relationship (N-N = U-AX × 0.618) compared with the weak correlation of 0.034 between umbilicus-xiphisternum and umbilicus-abdominal crease. In 75% of volunteers, the calculated U-AX was within ±3 cm of actual measurement, and in 33.33% within ±1 cm. Conclusions: U-AX = 1.618 × N-N equation is more predictive of adequate umbilicus repositioning during abdominoplasty in male patients. Chest and abdomen of men are a single aesthetic unit. Proper positioning of the nipples and umbilicus, as well as harmonious abdominal and torso proportions are critical for an optimal final aesthetic outcome.

Clinical Characteristics of Hospitalized Patients With COVID-19: A Retrospective Cohort Study in Pakistan.

BACKGROUND: The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) caused a global pandemic of severe upper respiratory tract infections known as COVID-19. This single-center study aimed to investigate the demographics, comorbidities, symptoms, and disease severity of COVID-19 patients in Pakistan. METHODS: A retrospective descriptive study was conducted at the Pakistan Kidney and Liver Institute and Research Center from April 2020 to August 2020. A total of 430 PCR-positive COVID-19 patients were categorized into symptomatic and asymptomatic groups. The symptomatic group was further classified into severe and non-severe subgroups. Patients' demographics, comorbid conditions, presenting symptoms, laboratory parameters, and clinical outcomes were assessed in these two subgroups. Statistical tests were applied to determine significant differences. RESULTS: A total of 430 patients with COVID-19 presented in our center, of whom 334 (78%) were symptomatic and included in the study. Severe disease was observed in 83 (24.8%) symptomatic patients, with a male predominance (75.9%) and higher mean age (61.7 ± 13.2). Travel to high-risk destinations (p < 0.002) and close contact with COVID-19 patients (p < 0.001) were significant risk factors. Major comorbid conditions included diabetes mellitus (30.5%) and hypertension (39.8%). Frequent symptoms included fever (71.8%), cough (68.8%), dyspnea (53.8%), and myalgias (35.9%). Higher C-reactive protein (median = 12.76 vs. 1.45, p = 0.001), ferritin (median = 996.70 vs. 628, p = 0.004), and D-dimers (median = 1121 vs. 439.50, p = 0.009) were noted in severe vs non-severe disease. Lymphopenia was more prevalent in severe vs. non-severe disease (83.1% vs. 14.3% p-value = 0.033). More deaths (28.9%) and ICU admissions (53%) with a prolonged hospital stay (median = 25 days, IQR = 16.0-31.0) were noted in the severe group. CONCLUSION: This retrospective study provides insights into the clinical characteristics and outcomes of COVID-19 patients. Age, male gender, comorbidities, and specific symptoms were associated with disease severity. Inflammatory markers, including D-dimers, ferritin, and CRP, were elevated in severe cases. These findings contribute to a better understanding of COVID-19 and may aid in clinical management and decision-making for patients affected by the disease.

The Effect of Chronic Laxative Use on Lipid Profile and HbA1c: A Hospital-Based Retrospective Study.

BACKGROUND: Laxatives are over-the-counter medications used as a treatment for constipation. The lipid-lowering effect of the long-term use of laxatives has been proposed. AIM: To investigate the possible impact of the chronic use of laxatives on serum lipid profile, body mass index (BMI), and hemoglobin A1c (HbA1c). METHODS: An observational retrospective cohort study was conducted to analyze data related to patients who received laxatives for six or 12 months or more in the KAUH database system. BMI, weight, cholesterol, triglycerides, low-density lipoprotein (LDL), high-density lipoprotein (HDL), aspartate aminotransferase (AST), alanine aminotransferase (ALT), and HbA1c data were collected retrospectively from hospital records for three time points: baseline, six months, and 12 months of laxative treatment from the starting date for each patient. RESULTS: A total of 106 patients' records fulfilled the inclusion criteria, 46 (43%) males with a mean age of 66 and 60 (57%) females with a mean age of 63. A significant decrease in plasma cholesterol and low-density lipoprotein-cholesterol (LDL-C) levels was observed in those who used laxatives for 12 months. Furthermore, an overall BMI and ALT reduction was seen in the combined. On the other hand, HbA1c levels appeared to improve in the combined group but not statistically significant. The change in the cholesterol level could be observed in patients receiving statin treatment and those without, with no statistical significance between the two groups. CONCLUSION: Chronic laxative use for 12 months or more is associated with a decreased total and LDL-C level with no significant effect on high-density lipoprotein-cholesterol (HDL-C) levels. Additionally, there was a significant reduction in BMI and ALT. This effect is more prominent with combined therapy. Further multicentric studies on larger sample sizes are recommended to confirm our findings.

Prevalence of Risk Factors of Chronic Rhinosinusitis With Nasal Polyps Among the Saudi Population.

Background The burden of chronic rhinosinusitis symptoms experienced by Saudi citizens is considered an important factor in getting an overall insight of the problem in the region, therefore our study aimed to determine the prevalence of risk factors of chronic rhinosinusitis with nasal polyps and correlate the risk factors with various sociodemographic parameters among Saudi population. Methods This study analyzed five-year cross-sectional data from 2017-2021. A total of 386 participants were enrolled and subsequently divided into four groups: aged 18-25 years, 26-35 years, 36-45 years, and > 45 years. A study was conducted utilizing non-probability sampling targeting a population of Saudi nationality living in selected regions of Saudi Arabia. Data was collected through an online questionnaire which had been distributed through social media and had been analyzed accordingly using a statistical package for social sciences. Results In this study, 272 (70.5%) participants were female and 114 (29.5%) were male. A total of 374 (96.9%) participants were Saudis while 12 (3.1%) were non-Saudis. Risk factors were compared by age and gender of study participants. Having polyps in the nose (p-value 0.016) and a family history of polyps (p-value 0.049) showed a significant association with the gender of study participants. The frequency of having nasal polyps was significantly higher among male participants, however, having a family history of nasal polyps was significantly higher among female participants. The educational status of study participants showed a significant association with the use of cortisone (p-value 0.032) and having a broken nose (p-value 0.032). Having a family history of nasal polyps showed a significant (p-value 0.017) association with the socioeconomic status of study participants. Conclusion Nasal polyps are more common in males than females, however, having a family history of nasal polyps was significantly higher among female participants.

Endoscopic Endonasal Approach to the Craniovertebral Junction Lesions: A Case Series of 18 Patients.

Introduction Odontoid pathologies constitute a special category because they may lead to instability. Instability is defined by abnormal spinal alignment under physiologic conditions (loads) such as standing, walking, bending, or lifting. Since instability poses a risk of cord damage, surgical interventions may be required for durable long-term stabilization. This study demonstrates operative technique and results of endoscopic endonasal approach to the odontoid pathologies. Methods We conducted a retrospective study involving 18 patients who underwent endoscopic endonasal odontoidectomy (EEO) due to craniovertebral pathologies. Demographic data, clinical features of the patients, risk factors, and intraoperative and postoperative complications were reported in this series. Results Satisfactory outcomes achieved in 16 patients based on comparing the modified Rankin scale before and after the surgery ( p = 0.0001). The mean duration for EEO was 232.6 ± 18.8 minutes. The mean blood loss during surgery was 386.67 ± 153.04 mL. The mean duration of hospital stay was 7 days. All patients were extubated within a few hours after surgery. Despite of successful anterior decompression in the aforementioned cases, intraoperative cerebrospinal fluid (CSF) leakage, postoperative meningitis, and pulmonary thromboembolism occurred as complications. However, two intraoperative CSF leakages were managed by direct dural repair and fat graft; two patients died due to postoperative meningitis and pulmonary thromboembolism at 7 and 4 days after the second surgery. Conclusion In conclusion, EEO can be effectively used for anterior decompression of the odontoid pathologies, despite the risk of complications.

Comparison of acetaminophen, ketamine, or ketorolac versus morphine in the treatment of acute renal colic: A network meta-analysis.

BACKGROUND: Renal colic is a disease in which a calculus obstructs the urinary tract, resulting in severe pain do ureteric peristaltic movements. Other symptoms, such as hematuria, nausea, and vomiting, may accompany the pain. This network meta-analysis aimed to compare the efficacy and safety of different analgesic agents for the treatment of acute renal colic. METHODS: Medline, Embase, and CENTRAL databases were searched. Randomized controlled trials (RCTs) that compared different analgesic agents, either alone or in combination were included. For the management of acute renal colic, analgesic agents were selected based on the current standard medical practice. The medications included intravenous acetaminophen, ketamine, ketorolac, and morphine. This study sought to evaluate the pain score on the visual analog scale (VAS) at 15, 30, and 60 min; adverse events; and the utilization of rescue therapy. The efficacy of different analgesic agents was explored through a frequentist network meta-analysis using the Netmeta statistical package in R software. All treatments were ranked using the Netrank function, yielding P-scores. RESULTS: Twelve RCTs were deemed eligible. As per the P-scores, acetaminophen was the most effective in reducing pain score at 15 min (P-score = 0.74). Ketorolac was the most effective in reducing the pain score at 30 and 60 min (P-score = 0.84) (P-score = 0.99), whereas morphine was the least effective (P-score = 0.07). Moreover, morphine was correlated with the highest odds of adverse events after treatment (P-score = 0.89). Morphine was the most frequently required rescue therapy in cases of suboptimal pain relief (P-score = 0.96). CONCLUSION: This network meta-analysis demonstrated that ketorolac and acetaminophen were the most effective analgesic agents according to the pain score. Morphine showed the highest adverse event profile and the highest rate at which rescue therapy was required for the management of acute renal colic.

Single and two-cells shape analysis from energy functionals for three-dimensional vertex models.

Vertex models have been extensively used for simulating the evolution of multicellular systems, and have given rise to important global properties concerning their macroscopic rheology or jamming transitions. These models are based on the definition of an energy functional, which fully determines the cellular response and conclusions. While two-dimensional vertex models have been widely employed, three-dimensional models are far more scarce, mainly due to the large amount of configurations that they may adopt and the complex geometrical transitions they undergo. We here investigate the shape of single and two-cells configurations as a function of the energy terms, and we study the dependence of the final shape on the model parameters: namely the exponent of the term penalising cell-cell adhesion and surface contractility. In single cell analysis, we deduce analytically the radius and limit values of the contractility for linear and quadratic surface energy terms, in 2D and 3D. In two-cells systems, symmetrical and asymmetrical, we deduce the evolution of the aspect ratio and the relative radius. While in functionals with linear surface terms yield the same aspect ratio in 2D and 3D, the configurations when using quadratic surface terms are distinct. We relate our results with well-known solutions from capillarity theory, and verify our analytical findings with a three-dimensional vertex model.

Utilization of Telemedicine during COVID-19 in Saudi Arabia: A Multicenter Study.

BACKGROUND: The outbreak of the novel Coronavirus disease 2019 (COVID-19) has influenced all aspects of life and significantly impacted healthcare services. It has collectively necessitated the use of telemedicine in providing healthcare. Through this study, we aim to report the statistics on telemedicine utilization and satisfaction across the Kingdom of Saudi Arabia during COVID-19. METHODS: This is a cross-sectional study to report the utilization and patient satisfaction with telemedicine services across Saudi Arabia. The data was collected retrospectively from March 2020 to July 2020 on 22,620 patients who used telemedicine services for consultations, medicine refills, and home healthcare visits during COVID-19. RESULTS: The patients received a quick response to their calls within a mean (± SD) waiting time of 2.54 (± 6.8) minutes corresponding to a median (IQR) of 0 (0-1) minutes. Home healthcare services were presented within a median (IQR) time of 20.16 (4.64 - 42.28) hours, and patients received medication at home with a median (IQR) time of 18.8 (12.15 - 36.1) hours. Conversations over the phone varied for a median (IQR) time of 5 (3-7) minutes. The highest number of telemedicine calls were for family medicine consultations, i.e., 6729 (29.7%), and the lowest was for infectious diseases 04 (0.1%), followed by cardiology consultations, i.e., 635 (2.8%). A total of 13,154 (58.15) rated their overall satisfaction, of which 11,684 (88.82%) found telemedicine services satisfactory. CONCLUSION: The utilization of telemedicine across Saudi Arabia results have shown telemedicine to be a satisfactory service for convenient and safe communication between patients and their healthcare providers. It can thus be established as a smart and indissoluble service across the kingdom. However, there is a need to raise awareness of insurance coverage for such services to make them more feasible and accessible to the public.

Pediatric glaucoma in aniridia in a population of Egyptian children.

PURPOSE: To report on the incidence, characteristics, and treatment of glaucoma in association with aniridia in a population of Egyptian children. METHODS: A retrospective chart review was conducted of children (<18 years of age) presenting with aniridia between 2007 and 2022. Diagnosis of glaucoma was based on cup:disk ratio (>0.3) and IOP (>16 mm Hg). Success of glaucoma surgery was defined as IOP ≤16 mm Hg and stable or regressing cup:disk ratio. RESULTS: A total of 93 eyes of 47 children were included. The mean patient age at presentation was 41.2 ± 44.7 months. The mean intraocular pressure (IOP), corneal diameter, cup:disk ratio, and axial length on presentation were 16.4 ± 10.3 mm Hg, 11.4 ± 1.3 mm, 0.4 ± 0.3, and 22.43 ± 2.6 mm Hg. Of eyes with IOP and cup:disk ratio data at presentation, 23 (30%) were diagnosed with glaucoma. Fourteen eyes underwent surgery after presentation; follow-up data were available for half the remaining eyes. At the final follow-up, glaucoma was present in 20 eyes (49%). Glaucoma surgery was performed in 17 eyes, with a complete or qualified success rate of 82.4% at final follow-up, with 15 eyes having at least 12 months' follow-up. CONCLUSIONS: In this study cohort, children with aniridia presented at around 3 years of age, with glaucoma at presentation in almost one-third of the cases.

Design, Synthesis, and Biological Evaluation of Novel Spiro Imidazobenzodiazepines to Identify Improved Inhaled Bronchodilators.

Novel gamma-aminobutyric acid receptor (GABAAR) ligands structurally related to imidazobenzodiazepine MIDD0301 were synthesized using spiro-amino acid N-carboxyanhydrides (NCAs). These compounds demonstrated increased resistance to phase 2 metabolism and avoided the formation of a 6H isomer. Compound design was guided by molecular docking using the available crystal structure of the α1ß3γ2 GABAAR and correlated with in vitro binding data. The carboxylic acid containing GABAAR ligands have high aqueous solubility, low permeability, and low cell toxicity. The inability of GABAAR ligands to cross the blood-brain barrier was confirmed in vivo by the absence of sensorimotor inhibition. Pharmacological activities at lung GABAARs were demonstrated by ex vivo relaxation of guinea pig airway smooth muscle and reduction of methacholine-induced airway hyperresponsiveness (AHR) in conscious mice. We identified bronchodilator 5c with an affinity of 9 nM for GABAARs that was metabolically stable in the presence of human and mouse microsomes.

Nursing internship students' knowledge regarding the care and management of people with diabetes: A multicenter cross-sectional study.

BACKGROUND: Nursing students in their final year of study will soon become responsible for the care and management of people with diabetes, and they need to be knowledgeable to provide adequate information. OBJECTIVES: The aim of this study was to assess nursing students' knowledge regarding diabetes care and management. DESIGN: A descriptive cross-sectional multicenter study. SETTINGS AND PARTICIPANTS: A convenience sample of all nursing students' internship enrolled at three government universities in Saudi Arabia. METHODS: 306 Saudi nursing students were surveyed with a self-administered questionnaire of the sociodemographic characteristics of the participants. The second part contained 23 multiple-choice questions of the Michigan Diabetes Knowledge Test. Data were collected from July to September 2022. RESULTS: The overall percentage of correct responses was 49.28 %. There was a significant difference between sex, the university attended, attendance in courses related to diabetes, and diabetes management guidelines in any course and their knowledge about diabetes care and management (p = 0.024, 0.001, 0.036, and 0.038, respectively). There was a significant difference between nursing students' general knowledge and insulin use knowledge (p = 0.001). A multiple regression analysis revealed that the university attended was the only statistically significant factor (p = 0.001). CONCLUSION: Nursing internship students are likely to be responsible for providing people with diabetes care and management once they qualify. Inappropriate knowledge negatively affects the care and management of people with diabetes. Information related to diabetic insulin therapy should be provided in more detail in the nursing curriculum.

Accurate prediction of dynamic viscosity of polyalpha-olefin boron nitride nanofluids using machine learning.

This study focuses on predicting the dynamic viscosity of nanofluids, specifically Polyalpha-Olefin-hexagonal boron nitride (PAO-hBN) using machine learning models. The primary goal of this research is to assess and contrast the effectiveness of three distinct machine learning models: Support Vector Regression (SVR), Artificial Neural Networks (ANN), and Adaptive Neuro-Fuzzy Inference System (ANFIS). The main objective is the identification of a model that demonstrates the highest level of accuracy in predicting a nanofluid's viscosity namely, PAO-hBN nanofluids. The models were trained and validated using 540 experimental data points, where the mean square error (MSE) and the coefficient of determination R2 were utilized for performance evaluation. The results demonstrated that all three models could predict the viscosity of PAO-hBN nanofluids accurately, but the ANFIS and ANN models outperformed the SVR model. The ANFIS and ANN models had similar performance, but the ANN model was preferred due to its faster training and computation time. The optimized ANN model had an R2 of 0.99994, which indicates a high level of accuracy in predicting the viscosity of PAO-hBN nanofluids. The elimination of the shear rate parameter from the input layer improved the accuracy of the ANN model to an absolute relative error of less than 1.89% over the full temperature range (-19.7 °C-70 °C) compared to 11% in the traditional correlation-based model. These results suggest that the use of machine learning models can significantly improve the accuracy of predicting the viscosity of PAO-hBN nanofluids. Overall, this study demonstrated that the use of machine learning models, specifically ANN, can be effective in predicting PAO-hBN nanofluids' dynamic viscosity. The findings provide a new perspective on how to predict the thermodynamic properties of nanofluids with high accuracy, which could have important applications in various industries.