Suspected colchicine-induced late myocardial rupture occurring after the late presentation of acute inferior ST-elevation myocardial infarction.

Colchicine is one of the established drugs of choice for post-myocardial infarction (MI) induced pericarditis, given its anti-inflammatory properties. Recently, colchicine received FDA approval for secondary prevention of atherosclerotic cardiovascular disease, which leads to concerns regarding its anti-healing effects on myocardial tissue post-infarction. We present a case of a suspected colchicine-induced myocardial rupture in an elderly male, who presented with a syncopal episode while on colchicine three weeks after the late presentation of infero-posterior ST-elevation myocardial infarction.

Servo torque fault diagnosis implementation for heavy-legged robots using insufficient information.

The reliability of sensors and servos is paramount in diagnosing the Heavy-Legged Robot (HLR). Servo faults stemming from mechanical wear, environmental disturbances, or electrical issues pose significant challenges to traditional diagnostic methods, which rely heavily on delicate sensors. This study introduces a framework that solely relies on joint position and permanent magnet synchronous motor (PMSM) information to mitigate dependency on fragile sensors for servo-fault diagnosis. An essential contribution involves refining a model that directly connects PMSM currents to HLR motion. Moreover, to address scenarios where actual servo outputs and HLR cylinder velocities are unavailable, an improved sliding mode observer (ISMO) is proposed. Additionally, a Fourier expansion model characterizes the relationship between operation time and fault-free disturbance in the HLR. Subsequently, the dual-line particle filter (DPF) algorithm is employed to predict fault-free disturbance. The outputs of DPF serve as a feedforward to the ISMO, enabling the real-time servo torque fault diagnosis. The accuracy and validity of this technical framework are verified through various simulations in MATLAB/SIMSCAPE and real-world experiments.

Fabrication and Investigation of Deformable Rubber-Carbon Nanotube-Glue Gel-Based Impedimetric and Capacitive Tactile Sensors for Pressure and Displacement Measurements.

Carbon nanotube-glue composite gel-based surface-type elastic sensors with a cylindrical shape deformable (flexible) metallic body were fabricated for tactile pressure and compressive displacement sensing. The fabrication of the sensors was performed using the rubbing-in technique. The effect of the pressure and the compressive displacement on the capacitance and the impedance of the sensors were investigated at various frequencies (in the range of 1 kHz to 200 kHz). It was found that under the effect of pressure from 0 to 9 g/cm2, the capacitance increased by 1.86 and 1.78 times, while the impedance decreased by 1.84 and 1.71 times at the frequencies of 1 kHz to 200 kHz, respectively. The effect of displacement on the impedance and the capacitance of the device was also investigated at various frequencies from 1 kHz to 200 kHz. The results showed that under the effect of compressive displacement up to 25 µm, the impedance of the sensors decreased on average by 1.19 times, while the capacitance increased by 1.09 times, accordingly. The frequency response of the displacement sensor showed that it matched with the low-pass filter. The obtained results are explained based on changes in the shape and geometrical parameters of the cylindrical-shaped conductive body. These results have also been explained on the basis of the distance between the conductive plates of the capacitive sensors during compression, which takes place under the effect of applied pressure or displacement. Moreover, the design of the sensors is simple and easy to fabricate, and their use is also earthy. The fabricated sensors have great potential for commercialization.

Real-world treatment patterns and clinical outcomes in patients with stage III non-small cell lung cancer: results of KINDLE-Egypt cohort.

Background: Stage III non-small cell lung cancer (NSCLC) being highly heterogeneous requires multimodal therapeutic strategies for optimal management. We present findings on treatment patterns and their associated survival outcomes in patients with stage III NSCLC from the Egypt subset of the KINDLE global real-world study conducted across countries from Asia, Middle East, Africa, and Latin America. Method: Retrospective data from the Egypt subset (21 centers) of adult patients diagnosed with stage III NSCLC between January 2013 and December 2017 were analyzed. Descriptive and inferential statistics summarized treatment modalities, progression-free survival (PFS), and overall survival (OS). Results: Of 421 patients enrolled (median age: 59.0 years), 77.9% were males, 53.5% had stage IIIA disease, 60.8% had adenocarcinoma, 78.4% had an unresectable disease, and 81.5% had Eastern Cooperative Oncology Group performance status ⩽1. Overall, chemotherapy alone (40.4%) was predominantly used in the initial line, whereas definite radiotherapy was used in only 5.0% of patients. In resectable patients, chemotherapy plus surgery (33.8%), surgery alone (20.6%), or other surgery (20.6%) were the top three modalities used in initial line of treatment. Chemotherapy alone was most preferred (48.8%) in unresectable patients, followed by sequential chemoradiotherapy (CRT) (17.6%) and concurrent CRT (9.3%). The overall median PFS was 10.3 months [95% confidence interval (CI), 9.43-12.02], whereas the median OS was 18.5 months (95% CI, 16.46-21.88). Overall, female gender, adenocarcinoma histology, and radical therapy as surgery or CRT predicted significantly longer OS (all p < 0.05). Conclusion: KINDLE-Egypt cohort revealed wide heterogeneities in the treatment patterns of stage III NSCLC. Although deemed resectable, few patients did not undergo surgery, probably due to high smoking rates leading to poor lung function. Lower survival outcomes than other published real-world studies highlight the need for timely approval and availability of novel targeted and immunotherapies to enhance patient outcomes. Trial registration: NCT03725475.

Effect of ondansetron compared to lidocaine and placebo for reducing propofol injection pain: A systematic review and meta-analysis of randomized controlled trials.

OBJECTIVE: Propofol is the most commonly used intravenous anesthetic medication and is most commonly associated with post-operative pain. Several drugs are investigated to reduce post-operative pain caused by propofol injection. Ondansetron is a potent anti-emetic drug showing promising results as an analgesic. This meta-analysis aims to compare the efficacy of ondansetron to placebo and lidocaine in reducing post-operative pain caused by propofol injection. METHODS: PubMed, Embase, Cochrane Library, Web of Science, and Scopus were searched for relevant randomized controlled trials (RCTs) till May 2022. We conducted a meta-analysis using RevMan software version 5.4, and we assessed the quality of included RCTs using the Cochrane risk of bias tool. RESULTS: In our study, we included 23 RCTs with 2957 participants. Compared to placebo, ondansetron significantly increased the rate of no pain [risk ratio (RR) = 2.36, 95% confidence interval (CI) (1.39-4.01)], and reduced moderate [RR = 0.39, 95% CI (0.30-0.52)] and severe pain [RR = 0.34, 95% CI (0.24-0.50)]. Furthermore, ondansetron significantly reduced PONV [RR = 0.73, 95% CI (0.58, 0.91)]. On the other hand, ondansetron showed an inferior efficacy to lidocaine regarding the incidence of no, moderate, and severe pain. CONCLUSION: Ondansetron is effective in reducing post-operative propofol-induced pain. However, lidocaine is more effective than it.

Hypercalcemia as a rare presentation of hyaline fibromatosis syndrome from different Sudanese families: two case reports.

BACKGROUND: Hyaline fibromatosis syndrome is a rare progressive autosomal recessive connective tissue disorder caused by a mutation in the ANTXR2/CMG2 gene. According to its severity, patients may present with skin nodules or visceral infiltration, which carries a poor prognosis. Hypercalcemia has not been reported as a presenting feature of this syndrome. Stimulation of osteoclasts by inflammatory factors and immobilization--induced hypercalcemia have played role in the pathophysiology. To our knowledge, this is the first report of hypercalcemia-associated hyaline fibromatosis syndrome. CASE PRESENTATION: Here, we describe cases of two Sudanese patients, a boy aged 9 months and a girl aged 3.5 years with hypercalcemia as an associated presenting feature of hyaline fibromatosis syndrome. Other features include gingival hypertrophy, painful joint swellings, and restriction of movement, which was misdiagnosed as juvenile rheumatoid arthritis. Workup showed normal phosphate, normal to mildly elevated parathyroid hormone, low vitamin D 25. Genetic testing confirmed the mutation of the ANTXR2/CMG2 gene. Both patients responded well to medical therapy for hypercalcemia, but one of them with the severe form of juvenile hyaline fibromatosis died due to sepsis, while the other one has maintained normocalcemic status. CONCLUSIONS: These cases highlight the rare presentation of this syndrome and reflect the importance of biopsy and genetic testing in reaching the diagnosis, especially when the clinical presentation can mimic other inflammatory bone disorders. Calcium levels should be checked in such cases.

Characterization of Hashimoto´s thyroiditis in Sudanese children: a cross-sectional study at Gaafar Ibnauf Hospital, Khartoum.

Introduction: literature on Hashimoto´s thyroiditis, the common thyroid illness in the young populations, in Sudan and Africa is scarce. We aimed to study its clinical profile and outcome among Sudanese children and adolescents. Methods: records of 73 patients were reviewed. Data related to demographics, presenting features, family history and coexistence of autoimmune diseases, physical examination findings, and biochemical progression over time were obtained. Results: patients´ mean age at the diagnosis was 10.6 ± 2.9 years, 80.8% (n = 59) of them were female and 83.6% (n = 61) were residing in iodine-sufficient areas. The commonest presenting features were thyromegaly and fatigability (79.5%, n = 58 and 43.8%, n = 32, respectively) after an illness duration of 0.5-48 months. Autoimmune comorbidities were documented in 8.2% (n = 6) of our series and more than half (53.4%, n = 39) of them were pre-pubertal at the diagnosis. Sixty point three percent (60.3%) (n = 44), 20.5% (n = 15), 13.7% (n = 10) and 5.5% (n = 4) of patients presented with overt hypothyroidism, sub-clinical hypothyroidism, euthyroidism and hyperthyroidism respectively, and there were no significant differences in the clinical profile between them. In patients' continued follow-up, 94.1% (n = 32/34) of those presented with overt hypothyroidism required levothyroxine therapy to maintain euthyroidism for 0.5-13 years, while 85.7% (n = 6/7) of those with euthyroidism remained so for 0.5-6 years. Remission was reported in all hyperthyroid patients and in only 5.9% (n = 2/34) of those with overt hypothyroidism at diagnosis. The majority of our patients with subclinical hypothyroidism were treated with levothyroxine and continued to be euthyroid for 10 months to 13 years. Conclusion: goiter was the commonest presenting feature of Hashimoto´s thyroiditis. The majority of patients had overt or subclinical hypothyroidism and almost all of them required long-term levothyroxine therapy.

Clinical phenotyping and genetic diagnosis of a large cohort of Sudanese families with hereditary spinocerebellar degenerations.

Hereditary spinocerebellar degenerations (SCDs) is an umbrella term that covers a group of monogenic conditions that share common pathogenic mechanisms and include hereditary spastic paraplegia (HSP), cerebellar ataxia, and spinocerebellar ataxia. They are often complicated with axonal neuropathy and/or intellectual impairment and overlap with many neurological conditions, including neurodevelopmental disorders. More than 200 genes and loci inherited through all modes of Mendelian inheritance are known. Autosomal recessive inheritance predominates in consanguineous communities; however, autosomal dominant and X-linked inheritance can also occur. Sudan is inhabited by genetically diverse populations, yet it has high consanguinity rates. We used next-generation sequencing, genotyping, bioinformatics analysis, and candidate gene approaches to study 90 affected patients from 38 unrelated Sudanese families segregating multiple forms of SCDs. The age-at-onset in our cohort ranged from birth to 35 years; however, most patients manifested childhood-onset diseases (the mean and median ages at onset were 7.5 and 3 years, respectively). We reached the genetic diagnosis in 63% and possibly up to 73% of the studied families when considering variants of unknown significance. Combining the present data with our previous analysis of 25 Sudanese HSP families, the success rate reached 52-59% (31-35/59 families). In this article we report candidate variants in genes previously known to be associated with SCDs or other phenotypically related monogenic disorders. We also highlight the genetic and clinical heterogeneity of SCDs in Sudan, as we did not identify a major causative gene in our cohort, and the potential for discovering novel SCD genes in this population.

Oncoplastic versus conventional breast-conserving surgery in breast cancer: a pooled analysis of 6941 female patients.

BACKGROUND: Breast cancer is the most prevalent cancer in women. In the past few years, surgical interventions for breast cancer have experienced massive changes from radical excision to conserving approaches. In this study, we aim to compare the two breast surgery interventions, including conventional breast-conserving surgery (CBCS) versus oncoplastic breast-conserving surgery (OPBCS). METHODS: We searched on PubMed, Web of Science (WOS), Scopus, Embase, and Cochrane till 2 October 2021. All relevant randomized controlled trials (RCTs) and observational studies were included. The data were extracted and pooled using Review Manager software (RevMan 5.4). RESULTS: The pooled meta-analysis of the included studies showed that OPBCS was significantly superior to CBCS in most of the outcomes. Re-excision significantly favoured CBCS (RR = 0.49, 95% CI [0.37, 0.63], P < 0.00001). However, local recurrence (RR = 0.55, 95% CI [0.27, 1.09], P = 0.09), close surgical margins (RR = 0.37, 95% CI [0.14, 1.00], P = 0.05) and end up to the risk of mastectomy (RR = 0.73, 95% CI [0.54, 97], P = 0.06) showed no significant difference between both techniques. Notably, while performing a sensitivity analysis, other outcomes as local recurrence, significantly showed favourable results towards OPBCS. In terms of safety outcomes, there was no significant difference between OPBCS and CBCS. CONCLUSION: We recommend the oncoplastic approach rather than the conventional one in females with breast cancer. Re-excision rates showed better results following OPBCS.

Central precocious puberty in Sudan: 10 years' experience of paediatric endocrinology centres.

Central precocious puberty (CPP) is frequently seen among cases presenting to our endocrine clinics. The purpose of this study was to have base line data on this condition with an attempt to point out any possible unique features of Sudan and to explore challenges faced in management and how that cultural and traditional practices may hamper care. Here, we are reporting the first data on this aspect from Sudanese subjects. Patients labelled as having CPP in Gafaar Ibnauf Children's Hospital and Soba University Hospital Endocrinology Clinics from January 2006 to 2016 are included in a descriptive hospital-based study which was conducted over 10 years in these two main paediatric endocrinology centres. Records of all patients with CPP were reviewed and challenges in diagnosis and management were identified. Most of the children with CPP presented late. Organic causes were more frequent among girls than what has been reported in the literature; in most boys, it was idiopathic. Almost half of the patients with underlying pathology were older than 6 years of age. Most cases including girls have an organic cause, thus magnetic resonance image should be done in all patients. Management of precocious puberty in a resource-limited country is faced with various challenges (e.g., expensive investigations and medications). We suggest establishing a unified protocol for managing these cases and creating collaboration between governmental, nongovernmental organisations and health services.

Pitfalls in the Diagnosis of Primary Hyperparathyroidism in a Sudanese Adolescent Boy; a case disguised as rickets.

BACKGROUND: Juvenile primary hyperparathyroidism (PHPT) is a rare endocrine disease. Its diagnosis might be masked by clinical, biochemical, and radiological features of rickets. CASE PRESENTATION: A 12-year-old Sudanese boy presented with progressive lower limbs deformity and difficulty in walking for six months. It was associated with fatigability, poor appetite, and generalized bone pain. On examination, he was thin, disproportionately short and pubertal, and had bilateral genu valgum deformity. X-rays showed osteopenia and signs of rickets. Biochemical workup revealed mildly elevated serum calcium, low phosphate, high alkaline phosphatase, and high parathyroid hormone with low 25-hydroxy vitamin D3. Celiac screening, liver function test and renal profile were normal. Serum calcium rose dramatically after vitamin D therapy. Genetic testing was negative for CYP2R1 and MEN1 genes. Ultrasound neck showed left inferior parathyroid adenoma which was surgically excised. Histopathology confirmed the diagnosis of parathyroid adenoma. Postoperatively, he had hypocalcemia which was treated with calcium and alfacalcidol. Corrective surgery is planned for the genu valgum deformity which markedly improved after parathyroidectomy. CONCLUSION: Although PHPT is extremely rare in the young population, it should be considered in patients with rickets and elevated serum calcium at baseline or after initiating vitamin D therapy.

Recent Updates on Source, Biosynthesis, and Therapeutic Potential of Natural Flavonoid Luteolin: A Review.

Nature gives immense resources that are beneficial to humankind. The natural compounds present in plants provide primary nutritional values to our diet. Apart from food, plants also provide chemical compounds with therapeutic values. The importance of these plant secondary metabolites is increasing due to more studies revealing their beneficial properties in treating and managing various diseases and their symptoms. Among them, flavonoids are crucial secondary metabolite compounds present in most plants. Of the reported 8000 flavonoid compounds, luteolin is an essential dietary compound. This review discusses the source of the essential flavonoid luteolin in various plants and its biosynthesis. Furthermore, the potential health benefits of luteolins such as anti-cancer, anti-microbial, anti-inflammatory, antioxidant, and anti-diabetic effects and their mechanisms are discussed in detail. The activity of luteolin and its derivatives are diverse, as they help to prevent and control many diseases and their life-threatening effects. This review will enhance the knowledge and recent findings regarding luteolin and its therapeutic effects, which are certainly useful in potentially utilizing this natural metabolite.

Estimating the total incidence of type 1 diabetes in children and adolescents aged 0-19 years from 1990 to 2050: a global simulation-based analysis.

BACKGROUND: Previous studies of type 1 diabetes in childhood and adolescence have found large variations in reported incidence around the world. However, it is unclear whether these reported incidence levels are impacted by differences in country health systems and possible underdiagnosis and if so, to what degree. The aim of this study was to estimate both the total and diagnosed incidence of type 1 diabetes globally and to project childhood type 1 diabetes incidence indicators from 1990 to 2050 for each country. METHODS: We developed the type 1 diabetes global microsimulation model to simulate the natural history and diagnosis of type 1 diabetes for children and adolescents (aged 0-19 years) in 200 countries and territories, accounting for variability in underlying incidence and health system performance. The model follows an open population of children and adolescents in monthly intervals and simulates type 1 diabetes incidence and progression, as well as health system factors which influence diagnosis. We calibrated the model to published data on type 1 diabetes incidence, autoantibody profiles, and proportion of cases diagnosed with diabetic ketoacidosis from 1990 to 2020 and assessed the predictive accuracy using a randomly sampled test set of data withheld from calibration. FINDINGS: We estimate that in 2021 there were 355 900 (95% UI 334 200-377 300) total new cases of type 1 diabetes globally among children and adolescents, of which 56% (200 400 cases, 95% UI 180 600-219 500) were diagnosed. Estimated underdiagnosis varies substantially by region, with over 95% of new cases diagnosed in Australia and New Zealand, western and northern Europe, and North America, but less than 35% of new cases diagnosed in west Africa, south and southeastern Asia, and Melanesia. The total number of incident childhood cases of type 1 diabetes is projected to increase to 476 700 (95% UI 449 500-504 300) in 2050. INTERPRETATION: Our research indicates that the total global incidence of childhood and adolescent type 1 diabetes is larger than previously estimated, with nearly one-in-two children currently undiagnosed. Policymakers should plan for adequate diagnostic and medical capacity to improve timely type 1 diabetes detection and treatment, particularly as incidence is projected to increase worldwide, with highest numbers of new cases in Africa. FUNDING: Novo Nordisk.

Dupilumab efficacy and safety in patients with moderate to severe asthma: A systematic review and meta-analysis.

Background: Dupilumab is a human monoclonal antibody directed against the alpha subunit of the interleukin-4 receptor and inhibits the signaling of IL-4 and IL-13. It is approved for treating asthma and other type-2 inflammatory diseases. There is a conflict in the literature regarding the safety and efficacy of dupilumab. Thus, we aimed to assess the safety and efficacy of dupilumab in patients with moderate to severe asthma. Methods: Six databases (PubMed, Embase, Scopus, Web of Science, Cochrane library, and clinicaltrials.gov registry) were searched until January 2022. We included randomized controlled trials that compared dupilumab with the placebo in moderate to severe asthma patients. We extracted the data at 12 and 24 weeks and analyzed them using review manager 5.4. Findings: Thirteen trials were included. Dupilumab significantly improved the forced expiratory volume in 1 s, asthma control questionnaire score, the fraction of exhaled nitric oxide level, and immunoglobulin E level at 12 and 24 weeks (p < 0.05). However, it was associated with increased blood eosinophils at 12 and 24 weeks. Dupilumab was generally a safe agent for asthmatic patients. It showed no significant difference compared with the placebo regarding most adverse events. Conclusion: Dupilumab improves pulmonary function and reduces local and systemic inflammatory markers with minimal adverse events in patients with moderate to severe asthma.

Timed Up and Go and Five Times Sit to Stand Test among community ambulant, overweight, obese Saudi elderly population.

OBJECTIVE: To investigate the effect of Timed Up and Go category on the Five Times Sit to Stand Test, and to determine the role of recreational status on Timed Up and Go rating. METHODS: The descriptive, cross-sectional study was conducted between October 2018 and April 2019 at the College of Medical Rehabilitation Sciences, Taibah University, Madina, Saudi Arabia, and comprised community-ambulant retired overweight or obese subjects of either gender aged 60-69 years. Timed Up and Go, Five Times Sit to Stand Test and Single-Leg Stance Test were used to measure basic mobility, transitional skills and static balance respectively. Data was analysed using SPSS 23. RESULTS: Of the 150 subjects, 108(72%) were males and 42(28%) were females. The overall mean age was 63.1}2.5 years and the mean body mass index was 29.6}3.8 kg/m2. There were 46(31.5%) subjects who were freely mobile, 60(41.1%) who were mostly independent and 40(27.4%) who had variable mobility. Also, 36(24%) subjects were recreationally active, while 114(76%) were recreationally inactive. The freely mobile subjects managed to finish the Five Times Sit to Stand Test in less time than the other groups (p<0.05). The recreationally active subjects took significantly less time to finish the Timed Up and Go test compared to the inactive. Besides, the males had longer Single-Leg Stance Test timing than females (p<0.05). CONCLUSIONS: The elderly belonging to different Timed Up and Go mobility categories demonstrated variable Five Times Sit to Stand abilities, with the recreational mobility status significantly affecting the category.

Endothelial nitric oxide synthase gene polymorphism (786T/C) in childhood acute lymphoblastic leukemia survivors.

OBJECTIVES: To detect eNOS gene polymorphism and its relation to cardiovascular complications in pediatric acute lymphoblastic leukemia (ALL) survivors. METHODS: CBC, renal and liver function tests, lipid profile, Carotid artery Intima Media Thickness (CIMT), and Brachial artery Intima Media Thickness (BIMT). eNOS gene polymorphism was done in 40 childhood ALL survivors and 40 controls. RESULTS: There was no significant difference between survivors and control groups regarding 786 T/C polymorphism. There was a significant increase in serum cholesterol, TGs, LDL, VLDL, and HbA1c in the TC and CC group more than in the TT group, while there was a significant decrease in serum HDL in the TC and CC group more than in the TT group. There was no significant difference as regards echocardiography findings between different polymorphisms of 786 T/C, but there was a significant difference between 786 T/C groups with regard to the carotid and brachial arteries intima media thickness (IMT) measurements being significantly higher in the TC and CC group more than in the TT group. CONCLUSION: Carotid and brachial arteries intima media thickness measurements were higher in the survivors when compared to healthy controls. eNOS gene polymorphism may play a role in modifying or developing CVD in pediatric ALL survivors.

Clinical presentation and molecular genetic analysis of a Sudanese family with a novel mutation in the CYP2R1 gene.

The aim of this study was to identify the genetic basis of two female siblings - born to consanguineous Sudanese parents - diagnosed clinically as having the rare condition of 25-hydroxylase deficiency (vitamin D-dependent rickets type 1B). The initial diagnosis was established based on clinical data, laboratory and radiological findings retrospectively. Primers for all exons (5) of human CYP2R1 (NM_024514) were generated followed by Sanger sequencing on exons 1-5 for both girls and their parents. Homozygosity for a point mutation (c.85C > T) was detected, leading to a nonsynonymous variant at position 29 in exon 1, resulting in a premature stop codon (p.Q29X). This is a previously unknown variant that leads to a severely truncated protein and predicted to be among the 0.1 % most deleterious genomic variants(CADD score 36). To our knowledge, this family represents the first case series from Sudan with a confirmed CYP2R1 gene mutation and the 6th world-wide. With the lack of genetic facilities, diagnosis should be suspected by the persistently low 25 hydroxyvitamin D level in spite of proper treatment and after ruling out liver disease and malabsorption. Patients in this case series showed healing of rickets when treated with high doses of 1,25-dihydroxyvitamin D3 (1,25(OH)D3; calcitriol) and oral calcium.

Comparative efficacy and mechanism of action of cardiac progenitor cells after cardiac injury.

Successful cell therapy requires cells to resist the hostile ischemic myocardium, be retained to continue secreting cardioprotective growth factors/exosomes, and resist immunological host responses. Clinically relevant stem/progenitor cells in a rodent model of acute myocardial infarction (MI) demonstrated that neonatal cardiac mesenchymal stromal cells (nMSCs) provide the most robust cardiac functional recovery. Transplanted nMSCs significantly increased the number of tissue reparative macrophages and regulatory T-cells and decreased monocyte-derived inflammatory macrophages and neutrophils in the host myocardium. mRNA microarray and single-cell analyses combined with targeted depletion studies established CD47 in nMSCs as a key molecule responsible for cell retention in the myocardium through an antiphagocytic mechanism regulated by miR34a-5p. Gain and loss-of-function studies demonstrated that miR34a-5p also regulated the production of exosomes and cardioprotective paracrine factors in the nMSC secretome. In conclusion, miR34a-5p and CD47 play an important role in determining the composition of nMSCs' secretome and immune evasion, respectively.

Clinical profile and aetiologies of delayed puberty: a 15 years' experience from a tertiary centre in Sudan.

OBJECTIVES: Delayed puberty is a common presentation to endocrine clinics, with adult height, sexual capability and fertility being the main concerns for the child and his/her family. Presentation is variable including short stature and/or absence of secondary sexual characteristics. The aetiology can either be constitutional, functional or permanent hypogonadotropic hypogonadism, permanent hypergonadotropic hypogonadism or unclassified. Despite the importance of this subject, there are no publications from Sudan. METHODS: A retrospective hospital-based study. Records of all patients who were seen in the endocrinology unit at Gaffar Ibn Auf Children's Hospital and were diagnosed as having delayed puberty were reviewed and demographic, clinical, and investigations data were obtained. RESULTS: A total of 136 patients were included in this study. Presentation includes short stature in 52.2%, both short stature and delayed puberty in 27.2%, and delayed puberty in 20.6%. The most common aetiologies were permanent hypogonadotropic hypogonadism and functional hypogonadotropic hypogonadism presented in 37.5% and 36% respectively, while constitutional delay of growth and puberty was found in only 14.7%. Type 1 diabetes mellitus (T1DM) was the most frequent chronic illness followed by coeliac disease. Hypergonadotropic hypogonadism was diagnosed in 11.7%, the majority of which were females. CONCLUSIONS: The aetiological pattern reported in this series highlights the role of nutrition and general well-being in pubertal development, as well as the major impact of genetics and consanguinity on disease patterns. Data from African countries are limited and this is the first reported cohort on delayed puberty from Sudan.

TAVR - From inoperable to younger, lower-risk patients: A slippery slope?

Despite current valve guidelines recommending both transcatheter and surgical aortic valve replacement (TAVR and SAVR, respectively) in patients with symptomatic severe aortic stenosis (AS), TAVR has recently become the preferred treatment over SAVR, driven by its minimal invasiveness, faster recovery and earlier improvement in quality of life. However, several limitations and unresolved issues remain with TAVR, including stroke, conduction system disorder, durability, bicuspid anatomy, coronary reaccess and lifetime management with aortic valve reintervention. Our review aims to highlight the above issues and discuss them in depth, to demonstrate the complementary role of TAVR and SAVR in the treatment of AS.