Miniature atom bottle traps enabled by chiral doughnut light.

We highlight what we believe to be a novel optical set-up which enables the confinement of cold atoms in a finite set of sub-wavelength bottle traps. This involves two counter-propagating vortex beams with the same winding number ℓ = ±1 and the same circular polarization ($\sigma =\mp 1)$. Strong focusing generates significant longitudinal field components which become responsible for an on-axis standing wave enabling the axial confinement of far blue-detuned atoms. The off-axis radial confinement is provided by the optical potential due to the transverse components of the light. The trap characteristics are illustrated using experimentally accessible parameters and are tunable by changing the power, focusing and ellipticity of the light. Atoms trapped in such a set-up are useful for applications, including quantum simulation and quantum information processing.

Biometric analysis of furcation area of molar teeth and its relationship with instrumentation.

The anatomy of furcation favours the bacterial retention and makes periodontal debridement as well as oral hygiene procedures difficult. Teeth that have lost attachment to a level of the furcation are said to have a furcal invasion or furcation involved.Involvement of furcation in a multi-rooted tooth poses a very different type of clinical situation in terms of establishment of diagnosis, determination of prognosis and of course planning the treatment modality.The present study was carried out on 200 selected extracted human first and second permanent molar teeth based on a predefined criteria. Teeth with prosthetic crowns, fused or fractured roots, those not fully developed, grossly carious or heavily restored at the cementoenamel junction (CEJ) were excluded from the study. The morphology of the root trunk was recorded by measuring various dimensions of the root trunk,including furcal angle and root trunk volume was calculated by using a custom made special apparatus. The furcation areas were debrided with different types of curettes in the market in order to see how best the instrument could be maneuvered in the furcation area. The data so obtained was statistically analysed using SPSS version 22. The highest root trunk volume and the longest root trunk length were found to be in the maxillary second molar. 48.60% furcations didn't allow instrument engagementof furcation area with standard area specific curettes. The proposal of inclusion of root trunk length (mm) is suggested in addition to classification of FI to have assess prognosis and appropriate treatment for of the involved tooth.

Efficacy of Melatonin as a Sleep Inducer in EEG Procedures in the Pediatric Population: A Cross-Sectional Study.

Introduction Melatonin has been used as an alternative to sleep deprivation for EEG sleep induction in the pediatric population. Our study aims to describe the efficacy of the currently used doses of melatonin for sleep induction among the pediatric age group. Methods A retrospective cross-sectional study included all patients who underwent an EEG after receiving melatonin over the period of one year. A total of 126 patients have been included in the study. Patients aged one year to three years received oral melatonin in doses between 2 mg and 6 mg. Patients in the age of three years and above received 10 mg of melatonin. Patients' success rate in achieving sleep and the exact time required for the patients to fall asleep were obtained using the readings of their EEG. The percentage of patients who have achieved sleep and the time required for those patients to sleep were calculated and correlated with the patient's gender, the presence of any associated neurobehavioral disorders, and their use of antiepileptic drugs (AED). Results Successful sleep was achieved in 84.9% (n:107) of the patients, with a mean time of 24 minutes to fall asleep (SD = 14.36). Patients with neurobehavioral disorders were 20% less likely to fall asleep when compared to other patients without neurobehavioral disorders (p: 0.003). However, there was not a statistically significant difference among different genders and among patients who received AED. Conclusion Melatonin is an effective sleep inducer for patients undergoing EEG procedures. It should be considered in the majority of patients. However, in patients with neurobehavioral disorders, a lower success rate is expected.

Phenotypic Spectrum of STXBP1 Gene Mutations in an Emirati Case Series.

Genetic mutations are increasingly recognized as etiologic factors for epilepsy and neurodevelopmental disorders. Loss of function mutations in STXBP1, one of such genes, has, in recent years, been demonstrated to cause a broad spectrum of epilepsy syndromes and chronic neurodisabilities. Syntaxin-binding protein 1 (STXBP1) is a well-recognized membrane trafficking protein responsible for synaptic transmission and is expressed ubiquitously across the brain. Our case series presents the neurodevelopmental phenotype of children with STXBP1 mutations and is the first to be reported in an Emirati patient cohort. We gathered data on five children with genetically confirmed STXBP1 mutations, each displaying varying symptomatology, EEG features, response to antiepileptic medications, and eventual disease progression. This report reveals that a majority of STXBP1 mutations were de-novo in origin; heterozygous; pathogenic to likely pathogenic variants; clinical disease onset was predominantly during infancy in the form of developmental delays with or without seizures; most of the children had co-existing ADHD or autism spectrum disorders; typical seizure semiology at onset was in the form of infantile spasms, progressing to a melange of mixed seizure types; seizure control on antiepileptic drug therapy was variable, with all cases requiring more than two medications; global developmental delay was noted in all studied children; and MRI brain findings were unremarkable in all cases. This case series demonstrates a degree of uniformity of STXBP1 mutation disease phenotypes with international literature and provides a unique insight into the genetic profile of affected children within the Emirati population.

The genomic landscape of rare disorders in the Middle East.

BACKGROUND: Rare diseases collectively impose a significant burden on healthcare systems, especially in underserved regions, like the Middle East, which lack access to genomic diagnostic services and the associated personalized management plans. METHODS: We established a clinical genomics and genetic counseling facility, within a multidisciplinary tertiary pediatric center, in the United Arab Emirates to locally diagnose and manage patients with rare diseases. Clinical genomic investigations included exome-based sequencing, chromosomal microarrays, and/or targeted testing. We assessed the diagnostic yield and implications for clinical management among this population. Variables were compared using the Fisher exact test. Tests were 2-tailed, and P < .05 was considered statistically significant. RESULTS: We present data on 1000 patients with rare diseases (46.2% females; average age, 4.6 years) representing 47 countries primarily from the Arabian Peninsula, the Levant, Africa, and Asia. The cumulative diagnostic yield was 32.5% (95% CI, 29.7-35.5%) and was higher for genomic sequencing-based testing than chromosomal microarrays (37.9% versus 17.2%, P = 0.0001) across all indications, consistent with the higher burden of single gene disorders. Of the 221 Mendelian disorders identified in this cohort, the majority (N = 184) were encountered only once, and those with recessive inheritance accounted for ~ 62% of sequencing diagnoses. Of patients with positive genetic findings (N = 325), 67.7% were less than 5 years of age, and 60% were offered modified management and/or intervention plans. Interestingly, 24% of patients with positive genetic findings received delayed diagnoses (average age, 12.4 years; range 7-37 years), most likely due to a lack of access to genomic investigations in this region. One such genetic finding ended a 15-year-long diagnostic odyssey, leading to a life-threatening diagnosis in one patient, who was then successfully treated using an experimental allogenic bone marrow transplant. Finally, we present cases with candidate genes within regions of homozygosity, likely underlying novel recessive disorders. CONCLUSIONS: Early access to genomic diagnostics for patients with suspected rare disorders in the Middle East is likely to improve clinical outcomes while driving gene discovery in this genetically underrepresented population.

Non-surgical management of dens invaginatus type IIIB in maxillary lateral incisor with three root canals and 6-year follow-up: A case report and review of literature.

BACKGROUND: The presence of dens invaginatus (DI) complicates treatment of any tooth, from diagnosis to access cavity and biomechanical preparation and obturation. Reports of successful non-surgical management of DI type IIIB in maxillary lateral incisor are rare. Here, we report such a case, with three root canals and a long follow-up. CASE SUMMARY: A 13-year-old female patient presented with mild pain in the maxillary right lateral incisor (#7) for 10-15 d. On examination, the tooth was slightly rotated, with slight tenderness on percussion and grade I mobility but with no caries, pockets or restorations and non-vital pulp (via vitality tests). Radiographic examination revealed unusual configuration of the tooth's root canals, with an enamel-lined invagination extending to the apex, suggesting the possibility of DI Oehler's type IIIB and a periapical radiolucency. Widening the access cavity lingually revealed one distinct buccal orifice and two distinct palatal orifices; under higher magnification of a dental operating microscope (DOM), the mesio-palatal and disto-palatal orifices were observed as connected by a C-shaped groove. The root canals were prepared with hand K-files following a step-back technique, and obturated using a combination technique of lateral condensation and vertical compaction. At the 6-year follow-up, the patient was asymptomatic, and the periapical radiography displayed significant healing around the apical end of the root. CONCLUSION: Proper knowledge of unusual root canal anatomy is required in treating DI. Conventional methods of root canal treatment can successfully resolve such complex cases, facilitated by DOM and cone-beam computed tomography.

Case report: First case report of an Emirati child with a novel gene variant causing aromatic L-amino acid decarboxylase deficiency.

Aromatic L-amino acid decarboxylase (AADC) deficiency is a rare, neurometabolic disorder resulting from biallelic mutations in the dopa decarboxylase (DDC) gene. This is the first reported case of AADC deficiency in the United Arab Emirates (UAE) and describes an Emirati male patient who presented in the first few months of life with a severe phenotype of global hypotonia, developmental delay and oculogyric crisis. Following whole exome sequencing, a novel homozygous mutation in the DDC gene (c.1144G>T, p.Val382Phe) was reported and the patient underwent further testing, after which a diagnosis of AADC deficiency was confirmed. This mutation has not been previously described, but the clinical phenotype and corresponding biochemical profile confirmed that it is a pathogenic variant. The patient is currently managed at a tertiary referral center in the UAE and is treated in accordance with published guidance on AADC deficiency, including the recommended medical therapy combined with multidisciplinary care from a team of specialists. Some symptomatic improvements have been reported but at 5 years of age the patient continues to exhibit profound developmental delay, oculogyric crisis and is prone to recurrent respiratory infections. In order to improve outcomes for patients with AADC deficiency in the Middle Eastern region, there is an urgent need to raise the index of clinical suspicion, particularly among primary care physicians, pediatricians, and pediatric neurologists, and to improve access to diagnostic testing. This is particularly relevant at the current time, given the ongoing development of potentially disease-modifying gene therapy for AADC deficiency.

Evidence-based clinical practice guidelines for the management of perioperative hypothermia: Systematic review, critical appraisal, and quality assessment with the AGREE II instrument.

Inadvertent perioperative hypothermia is considered an emergency life-threatening situation. Clinical practice guidelines (CPGs) on how to manage hypothermia, based on evidence and expert opinions, could save lives. This systematic review assessed and compared the most recently approved international CPGs with the AGREE II instrument. We searched international bibliographic databases to identify relevant guidelines for managing perioperative hypothermia. Four independent reviewers (consultant anesthesiologists) critically appraised the selected guidelines with the AGREE II instrument. We analyzed inter-rater agreement and calculated an intra-class correlation coefficient (Kappa). We identified five CPGs for perioperative hypothermia that were eligible for critical appraisal. These CPGs were issued by the National Institute for Health and Care Excellence (NICE-2016); the American Society of Peri-Anesthesia Nurses/Agency for Health Care Research and Quality (ASPAN/AHRQ-2006); the University of Southern Mississippi (USM/CPG-2017); The University Assistance Complex of Salamanca (UACS/CPG-2018); and the Justus-Liebig University of Giessen (UKGM/CPG-2015). The overall assessments of NICE-2016 and ASPAN/AHRQ-2006 scored >80%. These results were consistent with high scores achieved in the six domains of AGREE II: (1) scope and purpose, (2) stakeholder involvement, (3) rigor of development, (4) clarity of presentation, (5) applicability, and (6) editorial independence domains. The NICE-2016, ASPAN/AHRQ-2006, and USM/CPG-2017) scored, respectively, 94%, 81%, and 70% for domain 3, 91%, 87%, and 66% for domain 5, and 90%, 82%, and 77% for domain 6. Generally, the NICE CPGs received significantly better clinical recommendations. However, all five evidence-based CPGs were of high methodological quality and were recommended for use in practice. Saudi Arabia should formulate its own national CPGs for diagnosis and management of perioperative hypothermia and to be published on NICE.

Evidence-based clinical practice guidelines for the management of psoriasis: systematic review, critical appraisal, and quality assessment with the AGREE II instrument.

BACKGROUND: Psoriasis is considered one of the stubborn lifelong dermatologic diseases, making the patients seized in their social cage. Evidence-based clinical practice guidelines (CPGs) and expert opinions ensure that patients with psoriasis render the most recent and developed care. This systematic review assessed and compared the most recently approved international CPGs with the AGREE II instrument. METHODS: After we identified our research question, we searched the bibliographic international databases to identify and screen for relevant and eligible guidelines that address the topic of interest. Four independent reviewers (Senior Expert Dermatologist in Psoriasis) have critically appraised the selected guidelines via the AGREE II instrument. We conducted inter-rater analysis and percent agreement among raters and calculation of intra-class correlation coefficient (ICC) 'Kappa'. RESULTS: Out of 33 articles for CPGs, only Four eligible CPGs fulfill the inclusion criteria. Selected CPGs were critically appraised; first from the American College of Rheumatology that is also National Psoriasis Foundation (ACR/NPF-2018), second from the UK's National Institute for Health and Care Excellence (NICE-2017) for Psoriasis: Assessment and Management, third from the Saudi practical guidelines on the biologic treatment for Psoriasis (Saudi CPGs, 2015), and lastly from the American Academy of Dermatology (AAD/NPF-2019) Management and Treatment of Psoriasis with Awareness and Attention to Comorbidities. The complete assessments (OA) of two CPGs (AAD/NPF and NICE) scored greater than 80%; 'six domains' of AGREE II had greater score that is congruent with results; (1) scope and motive, (2) shareholder involvement, (3) rigor of growth, (4) clarity of speech, (5) validity, and (6) journalistic independence domains. Domain (3) scored (84, 71, and 90%), domain (5) (51%, 47, and 90%), domain (6) (70, 52, and 90%) for (Saudi CPGs, AAD/NPF, and NICE), respectively. Generally, the clinical recommendations were significantly better for NICE CPGs. CONCLUSIONS: Four evidence-based 'CPGs' introduced a high-quality methodological analysis. NICE indicated the greatest quality followed by Saudi CPGs and AAD/NPF and all four CPGs were suggested for practice.

In Vitro Assessment of Sealing Ability of Various Materials Used for Repair of Furcal Perforation: A SEM Study.

AIM: The aim of the current in vitro research was to evaluate the sealing capacity of three different agents employed for the repair of perforations at the furcation area. MATERIALS AND METHODS: Recently 60 extracted human mandibular permanent molars having well apart plus fully formed roots, and intact furcation were chosen. The 60 samples were allocated at random to three groups of 20 samples: Group I: Furcation perforation repair by means of mineral trioxide aggregate (MTA)-Angelus, Group II: Furcal perforation repair using Biodentine, Group III: Furcal perforation repair by EndoSequence. The specimens were subjected to sectioning with a hard tissue microtome and the sectioned parts of the samples were then examined. The specimens were subjected to gold sputtering and visualizing beneath scanning electron microscope (SEM) at 2000× magnification for assessing the sealing capacity of the agents. RESULTS: The highest sealing capacity was noted with the use of Biodentine at 0.96 ± 0.10, in pursuit by EndoSequence use at 1.18 ± 0.14 and MTA-Angelus use at 1.74 ± 0.08. The disparity amid the three groups was statistically significant with p < 0.001. CONCLUSION: In conclusion, it may be inferred that Biodentine exhibited the finest sealing capacity than EndoSequence and MTA- Angelus. It may thus be given consideration as a substance of preference for the repair of furcal perforation. CLINICAL SIGNIFICANCE: Using biologically compatible substances may be suggested to amend perforations thereby decreasing the occurrence of inflammatory response in the neighboring tissues. The sealing capacity is a significant feature in supporting the result of a root canal treatment of a tooth.

T cell antigenicity and immunogenicity of allogeneic exosomes.

Extracellular vesicles, including exosomes, are regularly released by allogeneic cells after transplantation. Recipient antigen-presenting cells (APCs) capture these vesicles and subsequently display donor MHC molecules on their surface. Recent evidence suggests that activation of alloreactive T cells by the so-called cross-dressed APCs plays an important role in initiating the alloresponse associated with allograft rejection. On the other hand, whether allogeneic exosomes can bind to T cells on their own and activate them remains unclear. In this study, we showed that allogeneic exosomes can bind to T cells but do not stimulate them in vitro unless they are cultured with APCs. On the other hand, allogeneic exosomes activate T cells in vivo and sensitize mice to alloantigens but only when delivered in an inflammatory environment.

Analgesia and sedation modalities used with botulinum toxin injections in children with cerebral palsy: a literature review.

Cerebral palsy (CP) is a non-progressive motor dysfunction leading to multiple morbidities, including spasticity, which can be managed with botulinum toxin injection (BTI). This literature review aims to examine published studies on the efficacy and safety of different interventions used to reduce pain and anxiety associated with BTI in children with CP. A literature review of all published evidence in English language, or with an English translation between 1999 and 2019, using PubMed, EBSCO host, and Medline databases was carried out. All identified papers were screened for inclusion criteria. Data from included papers were entered and analyzed on an Excel database. Twenty-one studies conducted in multiple clinical settings identified 10 different analgesia and sedation modalities including intravenous ketamine, midazolam, inhaled nitrous oxide, general anesthesia, and Eutectic Mixture of Local Anesthetics (EMLA®) cream. Most of the studies were descriptive with the exception of two clinical trials and one qualitative study. All interventions had some adverse effects, but they were generally mild and no long-term sequelae were reported. The combination of inhaled nitrous oxide with EMLA® cream showed promising primary results. However, ketamine and midazolam combination could be a safe alternative. Currently, there is no sufficient data to draw on the superiority of any modality. Further high-quality studies are warranted.

A Rare Cause of Recurrent Febrile Encephalopathy in a Child: The Expanding Spectrum of ATP1A3 Mutations.

ATP1A3 mutations have been recognized in infants and children presenting with a diverse group of neurological phenotypes, including rapid-onset dystonia parkinsonism (RDP), alternating hemiplegia of childhood (AHC), and cerebellar ataxia, areflexia, pes cavus, optic atrophy, and sensorineural hearing loss (CAPOS) syndrome. A new phenotype of fever-induced paroxysmal muscle weakness and encephalopathy (FIPWE) in patients with ATP1A3 mutations at c.2267G>A p residue 756H has been described most recently in few cases. Here, we report an additional case with an ATP1A3 mutation at c.2267G>A p residue 756H presenting with fever-induced paroxysmal muscle weakness and encephalopathy. To the best of our knowledge, this is the first reported case from the Middle East. This 18-month-old boy presented with recurrent, reversible fever-induced episodes of seizures, central hypotonia, areflexia, and developmental regression. The mainstay management for patients with ATP1A3 related diseases is symptomatic treatment as there is no specific proposed treatment. Aggressive management of febrile illness may be helpful in alleviating the symptoms.

Can short-term heart rate variability predict coronary artery disease in patients undergoing elective coronary angiography due to typical chest pain?

BACKGROUND: Presence of typical chest pain and normal coronary angiography suggests the possibility of microvascular ischemia of the myocardium as well as other non-cardiac causes that are also likely to decrease heart rate variability (HRV). This raises a question of whether poor HRV can predict abnormal elective coronary angiography (ECA). AIM: The aim of this study was to compare HRV in patients with typical chest pain when they are classified according to ECA outcomes. METHODS: The study enrolled 150 patients planned for ECA in the cardiac center of AlShaab Teaching Hospital, Khartoum, Sudan, due to typical chest pain. Following assessment of medical history and clinical examination, the Bluetooth electrocardiography (ECG) transmitter and receiver were used for ECG recording and evaluation of time and frequency domains HRV. ECA confirmed the diagnosis of coronary artery disease (CAD) in 108 patients, who were considered as the test group. The other 42 subjects were considered as a control group after the exclusion of CAD. RESULTS: The Mean±SD of Ln(pNN10), Ln(pNN20), LnLF, and LnHF was significantly higher in subjects with normal angiography compared with CAD patients. However, these statistically significant differences disappeared when the comparison was adjusted for age, gender, BMI, and HR of the studied groups. CONCLUSION: HRV is comparable in patients with typical chest pain regardless of ECA outcomes. RELEVANCE FOR PATIENTS: The HRV differences between patients with normal and abnormal ECA are likely to be biased by CAD risk factors such as old age, male gender, and tachycardia that are known to disturb HRV. The possibility of microvascular ischemia in patients with normal ECA may have attenuated HRV in this group and make it comparable to those suffering from macrovascular ischemia due to CAD.

Multi-focal Clostridioides (Clostridium) difficile osteomyelitis in a patient with sickle cell anemia: case presentation and literature review.

Clostridioides (Clostridium) difficile infection manifests as intestinal infections, namely pseudomembranous colitis. The occurrence of extra-intestinal disease is thought to be rare with a rate of 1.08% of 2034 isolates of C. difficile and an incidence of 4/100,000 admissions. C. difficile had been rarely associated with osteomyelitis. Here, we report the occurrence of C. difficile osteomyelitiin a patient with sickle cell disease. The patient had multiple surgeries and a prolonged antimicrobial therapy to achieve a cure. The patient had C. difficile infection of native bone and of a prosthetic joint. The patient received prolonged therapy with amoxicillin-clavulanic acid and metronidazole and she remained free of C. difficile infection for 3 years off antibiotics.

Chest Pain Characteristics in Cardiac Syndrome X Compared to Coronary Artery Disease.

AIM: This study aimed to assess if clinical remarks gained by analysis of the present and past medical history of patients undergoing elective coronary angiography (ECA) due to typical chest pain can help to predict the outcome of ECA. MATERIAL AND METHODS: One hundred and fifty-four ECA candidates with a history of typical chest were seen on the same day intended for ECA in the cardiac centre of AlShaab Teaching Hospital, Khartoum, Sudan. The details of the present complaints, characteristics of chest pain, past medical and socioeconomic history were recorded from each subject guided by a questionnaire. ECA confirmed CAD in 112 of the studied patients and were considered as the test group. The remaining patients (N = 42) were diagnosed as CSX after exclusion of significant narrowing of the coronary vessels and were considered as the control group. RESULTS: Univariate analysis of pain characteristics among patients undergoing coronary angiography revealed that pain is less likely to radiate to the neck (OR = 0.44, 95% CI = 0.21 - 0.91, P = 0.027) and the back (OR = 0.48, 95% CI = 0.23 - 1.00, P = 0.049) in patients with CAD. Presence of shortness of breathing and/or dizziness significantly decrease the odds of having abnormal coronary angiography (OR = 0.30 and 0.48, 95% CI = 0.12 - 0.77 and 0.22 - 0.92, P = 0.013 and 0.030 respectively). Past history of diabetes mellitus significantly increases the odds of having abnormal coronary angiography (OR = 3.96, 95% CI = 1.68 - 9.30, P = 0.002). In contrast, past medical history of migraine decreases the odds of having positive finding in ECA (OR = 0.31, 95% CI = 0.13 - 0.72, P = 0.006). CONCLUSION: Characteristics of chest pain are comparable in CAD and CSX. However, pain is less likely to radiate to the neck and/or the back in the first group. Presence of dyspnea and dizziness during angina attacks as well as the history of migraine significantly decreases the odds of having abnormal coronary angiography.

Surgical Outcomes of Single-Level Bilateral Selective Dorsal Rhizotomy for Spastic Diplegia in 150 Consecutive Patients.

OBJECTIVES: Selective dorsal rhizotomy (SDR) is used to improve spasticity, gait, and pain in children with spastic diplegia. There is growing evidence supporting its long-term benefits in terms of functional outcomes, independence, and quality of life. There is, however, little contemporary work describing the surgical morbidity of this irreversible procedure. The purpose of this study is to evaluate the surgical outcomes and complications of SDR at a single United Kingdom center. METHODS: Demographics, surgical, postoperative, and follow-up data for all patients undergoing SDR between 2011 and 2016 were collected from medical records. RESULTS: Preoperative Gross Motor Function Classification System levels in 150 consecutive patients were II (35%), III (65%), and IV (1%). Median age was 6 years and 58% were male patients. There were no deaths, cerebrospinal fluid leaks, returns to theater, or readmissions within 30 days. There were no new motor or sphincter deficits. Postoperative neuropathic pain was reported by 5.3% and sensory symptoms by 8.7%. Other complications included: postoperative nausea and vomiting (19.3%), superficial wound infection (3.3%), urinary retention (1.3%), headache (6.7%), and urine or chest infection (4.7%). Follow-up data were available for all patients (93% to 12 months, 72% to 24 months). Persistent neuropathic symptoms were reported in 6.5% at 24 months. CONCLUSIONS: SDR using a single-level approach is a safe procedure with low surgical morbidity. This study complements the growing evidence base in support of SDR for spastic diplegia and should help inform decisions when considering treatment options.

Loss of tubulin deglutamylase CCP1 causes infantile-onset neurodegeneration.

A set of glutamylases and deglutamylases controls levels of tubulin polyglutamylation, a prominent post-translational modification of neuronal microtubules. Defective tubulin polyglutamylation was first linked to neurodegeneration in the Purkinje cell degeneration (pcd) mouse, which lacks deglutamylase CCP1, displays massive cerebellar atrophy, and accumulates abnormally glutamylated tubulin in degenerating neurons. We found biallelic rare and damaging variants in the gene encoding CCP1 in 13 individuals with infantile-onset neurodegeneration and confirmed the absence of functional CCP1 along with dysregulated tubulin polyglutamylation. The human disease mainly affected the cerebellum, spinal motor neurons, and peripheral nerves. We also demonstrate previously unrecognized peripheral nerve and spinal motor neuron degeneration in pcd mice, which thus recapitulated key features of the human disease. Our findings link human neurodegeneration to tubulin polyglutamylation, entailing this post-translational modification as a potential target for drug development for neurodegenerative disorders.

Congenital brain malformations in Sudanese children: an outpatient-based study.

Congenital brain malformations (CBMs) are a heterogeneous group characterised by abnormal structure of the developing brain. Their aetiology includes in-utero infections, teratogenicity and in a considerable group, genetic causes. Due to the high rate of consanguineous marriages and the possible high prevalence of prenatal infections in Sudan, CBMs are likely to be common. The main aim of this study was to review the clinical profile of children with CBMs attending two main tertiary paediatrics neurology outpatient clinics in Khartoum State, Sudan. Children under the age of 18 years who presented with developmental delay, seizures or abnormal head size were evaluated clinically and with neuroimaging for possible CBMs. Out of 2,114 patients seen within 6 months (September 2016-March 2017) at the Outpatient Departments, 105 patients (5%) were diagnosed with CBMs. Sixty patients (57.1%) had a single brain anomaly, 36 patients (34.1%) had two brain anomalies while nine patients (8.6%) had multiple brain anomalies. Collectively, cortical malformations either isolated or in combination with other anomalies were observed in 37 patients (35.1%), thus by representing the commonest CBMs. Community-based epidemiological studies are needed to ascertain CBMs prevalence, common causes and long-term outcomes.