Explore the vast range of titles available.

Background Fatty acid oxidation defects are rare autosomal recessive disorders with variable clinical manifestations and outcome. Early detection by systematic neonatal screening may improve their prognosis. Long-term outcome studies of these disorders in the Middle East and North Africa region are limited. The purpose of this study is to report the diagnostic challenges and outcome of fatty acid oxidation defects in a major tertiary care center in Lebanon, a resource-constrained country in the Middle East. Methods A retrospective review of charts of all fatty acid oxidation defects sequential patients diagnosed and followed at our center was conducted. Collected data included: parental consanguinity, age at diagnosis, clinical presentation, biochemical profile, confirmatory diagnosis, treatment and outcome. A genotype–phenotype correlation was also performed, when available. Results Seven types of fatty acid oxidation defects were identified in a total of 34 patients from 21 families. Most families (79%) were consanguineous (first-degree cousins). The majority were diagnosed when clinically symptomatic (78%), at various ages between 10 days and 19 years (average: 2 years). Follow-up duration spanned between 2 months and 15 years (average: 5 years). The remainder of the patients were detected while still asymptomatic by systematic neonatal screening (9%) or due to positive family history (9%). The most common defect was carnitine transporter deficiency (50%) with an exclusive cardiac presentation related to a founder variant c.981C > T, (p.Arg254*) in the SLC22A5 gene. Medium chain acyl-CoA dehydrogenase deficiency was found in 13% only, which could be explained by the absence of systematic neonatal screening. Rare gene variants were detected in very long chain and multiple acyl-CoA dehydrogenase deficiency. The worse prognosis was observed in very long chain acyl-CoA dehydrogenase deficiency. The overall survival at last follow-up reached 75% with a complete reversal of symptoms with treatment in most patients (63%), despite their late diagnosis. Conclusions Our experience highlights the diagnostic challenges and outcome of fatty acid oxidation defects in a resource-constrained country with high consanguinity rates. Physicians’ awareness and systematic neonatal screening are key for diagnosis. Larger genotype–phenotype studies are still needed to understand the natural history of these rare diseases and possibly improve their outcome.

Hyperornithinemia-hyperammonemia-homocitrullinuria syndrome is an extremely rare disorder of urea cycle, with few patients reported worldwide. Despite hyperammonemia control, the long-term outcome remains poor with progressive neurological deterioration. We report the clinical, biochemical, and molecular features of two Lebanese siblings diagnosed with this disorder and followed for 8 and 15 years, respectively. Variable clinical manifestations and neurological outcome were observed. The patient with earlier onset of symptoms had a severe neurological deterioration while the other developed a milder form of the disease at an older age. Diagnosis was challenging in the absence of the complete biochemical triad and the non-specific clinical presentations. Whole exome sequencing revealed a homozygous variant, p.Phe188del, in the SLC25A15 gene, a French- Canadian founder mutation previously unreported in Arab patients. Hyperammonemia was controlled in both patients but hyperonithinemia persisted. Frequent hyperalaninemia spikes and lactic acidosis occured concomitantly with the onset of seizures in one of the siblings. Variable neurological deterioration and outcome were observed within the same family. This is the first report from the Arab population of the long-term outcome of this devastating neurometabolic disorder.

Background: Advances in genomic technologies combined with tandem mass newborn screening have enabled early detection and management of several common inborn errors of metabolism. Fructose-1,6-bisphosphatase deficiency, an autosomal recessive treatable disorder reported in around 150 patients worldwide, remains underdiagnosed despite an excellent prognosis with early detection. Although common in highly consanguineous populations, diagnosis is often delayed due to the non-specific clinical and biochemical profile. Methods: This report explores the diagnostic pathway using first-tier next-generation sequencing of three novel cases of fructose-1,6-bisphosphatase deficiency in a tertiary care center in Lebanon. Results: Two patients were diagnosed with first-tier exome sequencing within one month of presentation and had an excellent outcome at 6 years of follow-up. The third patient, undiagnosed for 10 years, suffered from neurological sequalae. The molecular profile was remarkable in two patients for exon 2 deletion in the FBP1 gene, a founder mutation reported in Turkish and Armenian patients, and a rare frameshift mutation in the third case. Conclusions: The use of next-generation sequencing as as a first-tier test for FBP deficiency is a non-invasive and rapid method for early diagnosis and management of this rare yet treatable disorder. It can detect both disease-causing variants and large deletions, founder mutations as well, delineating the molecular profile in populations where this disorder is highly prevalent.

Background Genetic literacy among primary healthcare providers is crucial for appropriate patient care with the advances in genetic and genomic medicine. Studies from high-income countries highlight the lack of knowledge in genetics and the need to develop curricula for continuing professional development of non-geneticists. Scarce data is available from resource-constrained countries in Middle East and North Africa. Lebanon is a small country in this region characterized by high rates of consanguinity and genetic disorders like several surrounding countries, such as Jordan, Syria, and Turkey. Methods The primary aim of this study assessed the genetic literacy, self-perceived and actual knowledge as well as practices among primary care providers in Lebanon. The secondary aim identified their educational needs and proposed evidence-based continuing education programs. A cross-sectional survey-based study, using a self-administered questionnaire, was conducted targeting physicians from Family Medicine, Obstetrics and Gynecology, and Pediatrics. The questionnaire was divided into five sections: demographics, familiarity with genetic tests, self-reported and actual knowledge, genetic practices, and educational needs. Statistics were performed using SPSS v24. The Chi-square test was used for independent variables. Differences between mean scores were measured using paired sample t-tests for groups of two levels and one-way ANOVA for more than two. Multiple linear regression was used to study the variables associated with the knowledge score while controlling for other variables. Results The survey included 123 physicians. They were mostly familiar with karyotype as first-tier genetic test. Although 38% perceived their knowledge as good, only 6% scored as such in knowledge assessment. A better knowledge score was observed in academic institutions as well as in urban settings ( p <0.05). One third never ordered any genetic testing, mostly due to poor knowledge. Almost all (98%) were ready to attend continuing professional development sessions in genetics. Conclusion Our findings show the need to improve genetic literacy among healthcare frontliners, focusing on remote regions and nonacademic centers in Lebanon, a model for other resource-constrained country in the Middle East and North Africa region. This study advances recommendations for evidence-based genetic continuing education programs and highlighted the role of that the few genetic specialists can play in their successful implementation.

Background: Riboflavin transporter deficiency type 2 is an ultra-rare, yet treatable, inborn error of metabolism. This autosomal recessive disorder is caused by pathogenic mutations in the SLC52A2 gene leading to progressive ataxia, polyneuropathy, and hearing and visual impairment. The early initiation of riboflavin therapy can prevent or mitigate the complications. To date, only 200 cases have been reported, mostly in consanguineous populations. The p.Gly306Arg founder mutation, identified in patients of Lebanese descent, is the most frequently reported worldwide. It was described in a homozygous state in a total of 21 patients. Therefore, studies characterizing the phenotypic spectrum of this mutation remain scarce. Methods: A retrospective review of charts of patients diagnosed with riboflavin transporter deficiency type 2 at a tertiary-care reference center in Lebanon was performed. Clinical, biochemical, and molecular profiles were analyzed and compared to reported cases in the literature. Results: A total of six patients from three unrelated families were diagnosed between 2018 and 2023. All patients exhibited the homozygous founder mutation, p.Gly306Arg, with variable phenotypes, even among family members. The median age of onset was 3 years. Diagnosis was achieved by exome sequencing at a median age of 5 years, as clinical and biochemical profiles were inconsistently suggestive. The response to riboflavin was variable. One patient treated with high-dose riboflavin recovered his motor function, while the others were stabilized. Conclusions: This study expands the current knowledge of the phenotypic spectrum associated with the p.Gly306Arg mutation in the SLC52A2 gene. Increased awareness among physicians of the common manifestations of this rare disorder is crucial for early diagnosis and treatment. In the absence of a consistent clinical or biochemical phenotype, the use of next-generation sequencing as a first-tier diagnostic test may be considered.

BackgroundWorldwide, music is commonly played in the operation room. The effect of music on surgical performance reportedly has varying results, while its effect on mental workload and key surgical stressor domains has only sparingly been investigated. Therefore, the aim is to assess the effect of recorded preferred music versus operating room noise on laparoscopic task performance and mental workload in a simulated setting.MethodsA four-sequence, four-period, two-treatment, randomized controlled crossover study design was used. Medical students, novices to laparoscopy, were eligible for inclusion. Participants were randomly allocated to one of four sequences, which decided the exposure order to music and operation room noise during the four periods. Laparoscopic task performance was assessed through motion analysis with a laparoscopic box simulator. Each period consisted of ten alternating peg transfer tasks. To account for the learning curve, a preparation phase was employed. Mental workload was assessed using the Surgery Task Load Index. This study was registered with the Netherlands Trial Register (NL7961).ResultsFrom October 29, 2019 until March 12, 2020, 107 participants completed the study, with 97 included for analyzation. Laparoscopic task performance increased significantly during the preparation phase. No significant beneficial effect of music versus operating room noise was observed on time to task completion, path length, speed, or motion smoothness. Music significantly decreased mental workload, reflected by a lower score of the total weighted Surgery Task Load Index in all but one of the six workload dimensions.ConclusionMusic significantly reduced mental workload overall and of several previously identified key surgical stressor domains, and its use in the operating room is reportedly viewed favorably. Music did not significantly improve laparoscopic task performance of novice laparoscopists in a simulated setting. Although varying results have been reported previously, it seems that surgical experience and task demand are more determinative.

New IRAM KID array 2 (NIKA2) is a camera dedicated to millimeter-wave astronomy based upon kilopixel arrays of kinetic inductance detectors [ 1 ] (KID). The pathfinder instrument, NIKA [ 2 ], has already shown state-of-the-art detector performance. NIKA2 builds upon this experience but goes one step further, increasing the total pixel count by a factor ∼ 10 while maintaining the same per pixel performance. For the next decade, this camera will be the resident photometric instrument of the Institut de Radio Astronomie Millimetrique (IRAM) 30 m telescopes in Sierra Nevada (Spain). In this paper, we give an overview of the main components of NIKA2 and describe the achieved detector performance. The camera has been permanently installed at the IRAM 30 m telescope in October 2015. It will be made accessible to the scientific community at the end of 2016, after a 1-year commissioning period. When this happens, NIKA2 will become a fundamental tool for astronomers worldwide.

Congenital bile acid synthesis disorder type 1 is an extremely rare disease with around 100 cases identified worldwide. Diagnosis remains challenging for pediatricians in view of the non-specific, variable clinical presentations of cholestasis, fat malabsorption, and liver cirrhosis. Early diagnosis and therapy with cholic acid are crucial to reverse the hepatopathy and prevent fatal outcomes. This paper sheds light on the diagnostic challenges of congenital bile acid synthesis disorder type 1 in a patient with an unusual presentation and a previously unreported mutation in the HSD3B7 gene. Moreover, this report aims to increase awareness of this treatable disorder among pediatricians. A 4-year-old child presented to our Medical Center with splenomegaly, fever, multiple lymphadenopathies, and mild cholestasis without hepatomegaly. History was remarkable for recurrent infections since the age of 3 years. Differential diagnosis included viral infections, malignancies, and inherited metabolic disorders. After an extensive negative work-up, genetic testing by next-generation sequencing identified a previously unreported homozygous disease-causing variant in the HSD3B7 gene, confirming the diagnosis of congenital bile acid synthesis disorder type 1. Suggestive abnormal urinary bile acids metabolites were also identified. Bile acid replacement therapy was initiated with reversal of cholestasis. This case highlights an unusual phenotypic presentation and the diagnostic challenges of an extremely rare disorder of bile acid synthesis. An increased awareness among pediatricians and the use of next-generation sequencing as a first-tier test in the setting of non-specific clinical presentations may shortcut the list of extensive investigations, allowing an early diagnosis of such treatable disorders, thus improving the patients’ outcomes.

We retrospectively studied patients diagnosed with P. aeruginosa bloodstream infections (BSIs) in two Italian university hospitals. Risk factors for the isolation of multidrug-resistant (MDR) or non-MDR P. aeruginosa in blood cultures were identified by a case-case-control study, and a cohort study evaluated the clinical outcomes of such infections. We identified 106 patients with P. aeruginosa BSI over the 2-year study period; 40 cases with MDR P. aeruginosa and 66 cases with non-MDR P. aeruginosa were compared to 212 controls. Independent risk factors for the isolation of MDR P. aeruginosa were: presence of central venous catheter (CVC), previous antibiotic therapy, and corticosteroid therapy. Independent risk factors for non-MDR P. aeruginosa were: previous BSI, neutrophil count <500/mm3, urinary catheterization, and presence of CVC. The 21-day mortality rate of all patients was 33·9%. The variables independently associated with 21-day mortality were presentation with septic shock, infection due to MDR P. aeruginosa, and inadequate initial antimicrobial therapy.

The blackbody radiation left over from the Big Bang has been transformed by the expansion of the Universe into the nearly isotropic 2.73 K cosmic microwave background. Tiny inhomogeneities in the early Universe left their imprint on the microwave background in the form of small anisotropies in its temperature. These anisotropies contain information about basic cosmological parameters, particularly the total energy density and curvature of the Universe. Here we report the first images of resolved structure in the microwave background anisotropies over a significant part of the sky. Maps at four frequencies clearly distinguish the microwave background from foreground emission. We compute the angular power spectrum of the microwave background, and find a peak at Legendre multipole l peak = (197 ± 6), with an amplitude Δ T 200 = (69 ± 8) µK. This is consistent with that expected for cold dark matter models in a flat (euclidean) Universe, as favoured by standard inflationary models.