The proteolytic airway environment associated with pneumonia acts as a barrier for treatment with anti-infective antibodies.

Like pneumonia, coronavirus disease 2019 (COVID-19) is characterized by a massive infiltration of innate immune cells (such as polymorphonuclear leukocytes) into the airways and alveolar spaces. These cells release proteases that may degrade therapeutic antibodies and thus limit their effectiveness. Here, we investigated the in vitro and ex vivo impact on anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) IgG1s and other IgG subclasses (IgG2 and IgG4) of the neutrophil elastase, proteinase 3 and cathepsin G (the three main neutrophil serine proteases) found in endotracheal aspirates from patients with severe COVID-19. Although the IgGs were sensitive to neutrophil serine proteases, IgG2 was most resistant to proteolytic degradation. The two anti-SARS CoV2 antibodies (casirivimab and imdevimab) were sensitive to the lung's proteolytic environment, although neutrophil serine protease inhibitors only partly limited the degradation. Overall, our results show that the pneumonia-associated imbalance between proteases and their inhibitors in the airways contributes to degradation of antiviral antibodies.

Diagnostic utility of superb microvascular imaging in depiction of corkscrew collaterals in Buerger's disease.

PURPOSE: To evaluate the corkscrew collaterals in Buerger's disease by superb microvascular imaging (SMI) and power Doppler ultrasonography (PDU). METHODS: We evaluated with SMI and PDU 14 patients with Buerger's disease in whom corkscrew collaterals had been identified on digital subtraction angiography (DSA). Corkscrew collaterals were classified on DSA and PDU based on their size and morphology. RESULTS: A total of 17 vascular regions of collateral vessel formation were assessed. Based on DSA classification, there were three cases of type I collaterals (arterial diameter of >2 mm with large helical pattern), seven cases of type III collaterals (arterial diameter of 1-1.5 mm with small helical pattern), and seven cases of type IV collaterals (arterial diameter of <1 mm with tiny helical pattern). On PDU, all type I collaterals on DSA appeared as "large snake" images, all type III collaterals on DSA appeared as "small snake" images, and all type IV collaterals on DSA appeared as dots. SMI imaging, both in color and monochrome mode, provided superior demonstration of the continuity of the vessel of large or small "snake" images. In cases appearing as dot pattern on PDU, color SMI was able to show continuity of the flow signal as a helical pattern. DISCUSSION: SMI is a promising new Doppler imaging technique that is superior to conventional power Doppler imaging in depiction and identification of corkscrew collaterals in Buerger's disease.

Diffuse large B-cell lymphoma presenting with masses in the pineal and adrenal glands.

Magnetic resonance imaging (MRI) may offer several potential advantages in the evaluation of lymphoma with the additive value of H1-MRS for differential diagnosis. Even though lymphoma has unique imaging findings on CT and multiparametric MRI, definite diagnosis must be thoroughly established by histopathological examination.

Adolescent pregnancies: complications, birth outcomes and the possible solutions.

OBJECTIVES: In this study we aim to evaluate antenatal, perinatal and postnatal outcomes and complications of adolescent pregnancies, as well as to discuss the social and psychological consequences of these pregnancies. MATERIAL AND METHODS: We compare a total of 243 pregnant women at age 14-18 years to a vast control group at age 19-36 who all delivered at Bursa Yüksek Ihtisas Training and Research Hospital between years 2005-2014. RESULTS: Antenatal care (folic acid supplementation, pre-conception counseling) was significantly higher in adolescent pregnancy group. Unplanned pregnancy rate was significantly higher in in study group (p < 0.001). Preterm delivery (before 37th week) ratio was statistically higher in pregnancy complications. CONCLUSIONS: Adolescent pregnancy is a social entity which should be regulated and prevented by legal measures. Planned pregnancies should be promoted and the public should be educated and informed about the Hazards of adolescent pregnancies. Press institutions, public broadcasting services support the efforts to decrease adolescent pregnancies.

EEG abnormalities and long term seizure outcome in high functioning autism.

Electroencephalographic abnormalities may occur in autistic spectrum disorders (ASD) even in the absence of clinical seizures. These abnormalities may vary from nonspecific changes to epileptiform abnormalities and are more common compared to the overall population. The level of intelligence is a significant risk factor for epilepsy in ASD. However, the relation between the functionality of the individuals with autism and the electroencephalographic (EEG) abnormalities, and the clinical significance of these abnormalities still remain relatively unclear. In this study we investigated the presence of EEG abnormalities in sixteen children diagnosed with high-functioning ASD. EEG recording was performed for at least 2 h and included at least 90 min of sleep activity. While none of the patients had clinical seizures, 5 patients (31.3%) were detected to have EEG abnormalities. Four of these were epileptiform (25%), and one patient developed seizure during follow-up. Our results support the fact that EEG abnormalities are observed at a higher rate also in ASD with a better functionality. The potential impact of EEG abnormalities on cognition and behavior, and the risk of epilepsy should be considered during long-term follow-up of these patients.

Social competence in children with autism.

Objectives: This paper investigates the associations of social competence with cognitive representation and communication skills in children with Autism Spectrum Disorders (ASD), by measuring these skills in an expansive way through assessing both mental and internal-state understanding, and verbal and non-verbal communication. Methods: The data were collected from 45 Turkish children (M age=8.52 years, SD=3.05, min-max=3-14) with a diagnosis of ASD. Individual assessments were used to measure mental- and internal-state understanding. Teacher-rated scales were used to assess child's verbal and non-verbal communication skills, and social competence. Results: The results showed that social competence, cognitive representation, verbal and non-verbal communication skills were all significantly associated, but over and above cognitive representation skills and verbal communication, non-verbal communication had a salient role in adaptive social relationships of children with ASD. Conclusions: These findings have important applied implications for intervention studies and suggest that improvements of non-verbal communication skills in children with ASD might be important for increasing their positive social relations.

Startle and blink reflex in high functioning autism.

An important clinical feature of autism is the presence of atypical responses to sensory stimuli. In this study, we investigated if high functioning autistic patients had abnormalities in the blink reflex and the startle reaction to auditory or somatosensory stimuli. Fourteen patients aged between 7 and 16 years were included in the study. We found a longer latency of the blink reflex, an increased duration and amplitude of the auditory startle reaction and a lower presence rate of the somatosensorial startle reaction in autistic patients. To better define the sensorial characteristics of the disease could improve the therapeutic management of children with autism spectrum disorder.

First-trimester crown-rump length affects birth size symmetrically.

OBJECTIVE: To investigate the relationship between crown-rump length (CRL) and birth weight, length and head circumference of the newborn. METHODS: From a database of delivery records of 12,000 pregnancies, we identified 999 women with singleton pregnancies who had no medical problems, a normal menstrual history and a first trimester ultrasound scan in which CRL had been measured. All of the pregnancies resulted in live births without evidence of chromosomal and congenital abnormalities. The population in this study was divided into three groups according to CRL measurement; Group A (smaller-than-expected CRL), Group B (normal CRL) and Group C (larger-than-expected CRL). RESULTS: The incidence of low birth weight infant was higher in Group A than in Group C (p = 0.010). The rate of small for gestational age (SGA) infants was similar between groups. The number of macrosomic or large for gestational age (LGA) infants was higher in Group C than Groups A and B. Both birth head circumference and length of infant were greater in Group C than Groups A and B. No significant difference for ponderal index value was observed between the groups (p = 0.927). CONCLUSION: The growth pattern in the first trimester affects neonatal birth weight and length symmetrically without changing the ponderal index.

Theory of mind and neurodevelopmental disorders of childhood.

To a large extent, the human infant is socialized through the acquisition of a specific cognitive mechanism known as theory of mind (ToM), a term which is currently used to explain a related set of intellectual abilities that enable us to understand that others have beliefs, desires, plans, hopes, information, and intentions that may differ from our own. Various neurodevelopmental disorders, such as autism spectrum disorders, attention deficit hyperactivity disorder, developmental language disorders, and schizophrenia, as well as acquired disorders of the right brain (and traumatic brain injury) impair ToM. ToM is a composite function, which involves memory, joint attention, complex perceptual recognition (such as face and gaze processing), language, executive functions (such as tracking of intentions and goals and moral reasoning), emotion processing-recognition, empathy, and imitation. Hence, ToM development is dependent on the maturation of several brain systems and is shaped by parenting, social relations, training, and education; thus, it is an example of the dense interaction that occurs between brain development and (social) environment.

Novel VLDLR microdeletion identified in two Turkish siblings with pachygyria and pontocerebellar atrophy.

Congenital ataxia with cerebellar hypoplasia is a heterogeneous group of disorders that presents with motor disability, hypotonia, incoordination, and impaired motor development. Among these, disequilibrium syndrome describes a constellation of findings including non-progressive cerebellar ataxia, mental retardation, and cerebellar hypoplasia following an autosomal recessive pattern of inheritance and can be caused by mutations in the Very Low Density Lipoprotein Receptor (VLDLR). Interestingly, while the majority of patients with VLDL-associated cerebellar hypoplasia in the literature use bipedal gait, the previously reported patients of Turkish decent have demonstrated similar neurological sequelae, but rely on quadrupedal gait. We present a consanguinous Turkish family with two siblings with cerebellar atrophy, predominantly frontal pachygyria and ataxic bipedal gait, who were found to have a novel homozygous deletion in the VLDLR gene identified by using high-density single nucleotide polymorphism microarrays for homozygosity mapping and identification of CNVs within these regions. Discovery of disease causing homozygous deletions in the present Turkish family capable of maintaining bipedal movement exemplifies the phenotypic heterogeneity of VLDLR-associated cerebellar hypoplasia and ataxia.

Four novel SCN1A mutations in Turkish patients with severe myoclonic epilepsy of infancy (SMEI).

Severe myoclonic epilepsy of infancy (SMEI) (OMIM #607208), also known as Dravet syndrome, is a rare genetic disorder characterized by frequent generalized, unilateral clonic or tonic-clonic seizures that begin during the first year of life. Heterozygous de novo mutations in the SCN1A gene, which encodes the neuronal voltage-gated sodium channel α subunit type 1 (Nav1.1), are responsible for Dravet syndrome, with a broad spectrum of mutations and rearrangements having been reported. In this study, the authors present 4 novel mutations and confirm 2 previously identified mutations in the SCN1A gene found in a cohort of Turkish patients with Dravet syndrome. Mutational analysis of other responsible genes, GABRG2 and PCDH19, were unrevealing. The authors' findings add to the known spectrum of mutations responsible for this disease phenotype and once again reinforce our understanding of the allelic heterogeneity of this disease.

Functional deficiencies of sulfite oxidase: Differential diagnoses in neonates presenting with intractable seizures and cystic encephalomalacia.

Sulfite oxidase is a mitochondrial enzyme encoded by the SUOX gene and essential for the detoxification of sulfite which results mainly from the catabolism of sulfur-containing amino acids. Decreased activity of this enzyme can either be due to mutations in the SUOX gene or secondary to defects in the synthesis of its cofactor, the molybdenum cofactor. Defects in the synthesis of the molybdenum cofactor are caused by mutations in one of the genes MOCS1, MOCS2, MOCS3 and GEPH and result in combined deficiencies of the enzymes sulfite oxidase, xanthine dehydrogenase and aldehyde oxidase. Although present in many ethnic groups, isolated sulfite oxidase deficiency and molybdenum cofactor deficiency are rare inborn errors of metabolism, which makes awareness of key clinical and laboratory features of affected individuals crucial for early diagnosis. We report clinical, radiologic, biochemical and genetic data on a Brazilian and on a Turkish child with sulfite oxidase deficiency due to the isolated defect and impaired synthesis of the molybdenum cofactor, respectively. Both patients presented with early onset seizures and neurological deterioration. They showed no sulfite oxidase activity in fibroblasts and were homozygous for the mutations c.1136A>G in the SUOX gene and c.667insCGA in the MOCS1 gene, respectively. Widely available routine laboratory tests such as assessment of total homocysteine and uric acid are indicated in children with a clinical presentation resembling that of hypoxic ischemic encephalopathy and may help in obtaining a tentative diagnosis locally, which requires confirmation by specialized laboratories.

Mucolipidosis type IV in a Turkish boy associated with a novel MCOLN1 mutation.

Mucolipidosis type IV is a rare neurodegenerative lysosomal storage disorder that usually presents during the first year of life with severe mental retardation, delayed motor milestones and corneal opacities. Mucolipidosis IV is caused by mutations in MCOLN1, a gene encoding mucolipin-1 which is responsible for maintaining lysosomal function. The majority of known patients with this disorders are Ashkenazi Jews, and most have a splice IVS3-2 A>G, or a 6.4kb deletion mutation in MCOLN1. Here, we present a Turkish patient who, in addition to the typical neurological and visceral characteristics of mucolipidosis type IV, also demonstrates defects in the posterior limb of internal capsule by MRI, micrognathia and clinodactyly of the fifth fingers. Direct sequencing of his DNA revealed a homozygous c.1364C>T (S456L) mutation in MCOLN1, which was heterozygous in both consanguineous parents. This mutation, like several previously described, changes the protein sequence in the channel pore domain of the protein. Serine 456 is conserved in mucolipin proteins throughout evolution, therefore the mutation is considered as causative for the severe phenotype of this patient.

Novel NTRK1 mutations cause hereditary sensory and autonomic neuropathy type IV: demonstration of a founder mutation in the Turkish population.

Hereditary sensory and autonomic neuropathy type IV (HSAN IV), or congenital insensitivity to pain with anhidrosis, is an autosomal recessive disorder characterized by insensitivity to noxious stimuli, anhidrosis from deinnervated sweat glands, and delayed mental and motor development. Mutations in the neurotrophic tyrosine kinase receptor type 1 (NTRK1), a receptor in the neurotrophin signaling pathway phosphorylated in response to nerve growth factor, are associated with this disorder. We identified six families from Northern Central Turkey with HSAN IV. We screened the NTRK1 gene for mutations in these families. Microsatellite and single nucleotide polymorphism (SNP) markers on the Affymetrix 250K chip platform were used to determine the haplotypes for three families harboring the same mutation. Screening for mutations in the NTRK1 gene demonstrated one novel frameshift mutation, two novel nonsense mutations, and three unrelated kindreds with the same splice-site mutation. Genotyping of the three families with the identical splice-site mutation revealed that they share the same haplotype. This report broadens the spectrum of mutations in NTRK1 that cause HSAN IV and demonstrates a founder mutation in the Turkish population.

Migration abnormality in the left cingulate gyrus presenting with autistic disorder.

Autism, characterized by an impairment in communication, including language, narrowly focused interests, and poor sociability, is a neurodevelopmental disorder of still largely unknown pathogenesis. In children with autistic symptomatology, the most consistent functional or anatomic abnormalities are found in the cingulate gyrus, particularly in the anterior regions. Neuronal migration malformations caused by incomplete neuronal migration and characterized by loss of the normal gyral patterns in the cerebral hemispheres and prominent disorganization of the cerebral cortical cytoarchitecture are generally associated with profound neurologic deficits, epilepsy, and autism. In this report, we present a case with an isolated migration abnormality located in the anterior part of the left cingulate gyrus who was admitted with the complaints of epileptic seizures and autism. In addition, the role of the localization of the migration abnormality in the appearance of autistic symptomatology is discussed.

The consequences of idiopathic partial epilepsies in relation to neuropsychological functioning: a closer look at the associated mathematical disability.

Although the seizure prognosis is mostly favorable in idiopathic partial epilepsies, there is some empirical evidence showing that subtle neuropsychological impairments, with a consequent risk of academic underachievement, are not rare. We investigated neuropsychological functioning including attention, memory, visuomotor ability, and executive functioning with a closer look at the associated mathematical ability in patients with idiopathic partial epilepsies. A battery of age-appropriate, neuropsychological and mathematics achievement tests was administered to 30 participants with idiopathic partial epilepsy [13 children with benign epilepsy with centrotemporal spikes (BECTS), 17 children with idiopathic childhood occipital epilepsies (ICOE)], and to 30 healthy participants matched for age, sex, handedness, and socioeconomic status. Results did not support any impairment in overall neuropsychological functioning in participants with idiopathic partial epilepsies, whereas, isolated deficits did exist. The mean performance of the IPE group was significantly lower than the control group in six out of 12, neuropsychological measures: drawing (p < 0.01), digit span (p < 0.05), verbal learning (p < 0.01), object assembly (p < 0.01), similarities (p < 0.05), and vocabulary (p < 0.001). Results suggested that one should be cautious regarding neuropsychological and academic prognosis in the so-called benign idiopathic partial epilepsies of childhood.