Two siblings presenting with novel ADA2 variants, lymphoproliferation, persistence of large granular lymphocytes, and T-cell perturbations.

The presence of large granular lymphocytes has been reported in patients with ADA2 deficiency and T-LGL leukemia. Here we describe two siblings with novel ADA2 variants, expanding the mutational spectrum of ADA2 deficiency. We show that lymphoproliferation, persistence of large granular lymphocytes, T-cell perturbations, and activation of PI3K pathway, measured by means of phosphorylation levels of S6, are detectable in DADA2 patients without T-LGL leukemia.

Comparison of Oral Health-Related Quality of Life scores in children treated for early childhood caries under general and local anesthesia: a quasi-experimental study.

PURPOSE: The purpose of this study was to compare the changes in oral health-related quality of life (OHRQoL) scores in children treated for Early Childhood Caries (ECC) under general (GA) and local anesthesia (LA). METHODS: A quasi-experimental study was carried out on 73 children, with 37 in the GA group and 36 in the LA group. The early childhood oral health impact scale (ECOHIS) was used to measure OHRQoL, with the type of anesthesia (LA or GA) serving as the explanatory variable. A Friedman test was used to assess the difference between the LA and GA groups at baseline, one-week, and one-month follow-up points. RESULTS: The results showed a significant difference in the overall mean ECOHIS scores between the LA and GA groups at 1-week (LAmean ± SD = 6.12 ± 1.11, GAmean ± SD = 5.50 ± 0.88; P = 0.01) and 1-month (LAmean ± SD = 5.87 ± 1.12, GAmean ± SD = 4.96 ± 0.99; P < 0.001) follow-up points. Irrespective of the administered anesthesia, a significant (P < 0.001) reduction in the mean score for dental pain was observed at both 1-week (mean ± SD = 1.30 ± 1.16) and 1-month (mean ± SD = 0.81 ± 0.89) timepoints after the treatment, as compared to the baseline assessment (mean ± SD = 2.02 ± 1.02). CONCLUSION: Early treatment for ECC reduces pain, restore normal activities, and improves the quality of life of affected children. Specifically, GA was found to be more beneficial for both children and parents. However, further studies using more robust study designs and carefully considering related factors are necessary to confirm these findings.

Wound healing activity of topical herbal aerosol sprays on diabetic and Varicose Ulcers: A randomized, controlled, open labelled, multi-centric clinical trial.

BACKGROUND: Panchavalkala Kwatha and Jatyadi Taila are recommended for cleaning and healing of non-healing ulcers such as Diabetic Foot Ulcer (DFU) and Varicose Ulcers (VU). OBJECTIVES: Innovative topical aerosol sprays viz. Panchavalkala Kwatha Aerosol Spray (PKS) and Jatyadi Taila (Healz) Aerosol Spray (JTS) were evaluated for healing in DFU & VU against conventional treatment. MATERIALS & METHODS: After obtaining approval from Ethics Commitees & informed consent, 53 patients were randomized in two study groups. In one group, ulcer cleaning was done with PKS and then JTS was used for dressing while in other group, cleaning was done with Hydrogen peroxide and/or Hypochlorite followed by dressing with 10% Povidone iodine. Ulcer examination was done from baseline to every 7th day by Bates Jensen ulcer assessment tool, digital photographs and photographic ulcer assessment tool. Comparison of categorical variables was done using t-test. RESULTS: The dual action of PKS and JTS exhibited potentially comparable effect to the conventional treatment. CONCLUSION: PKS and JTS were found to be effective, comfortable, hygenic and acceptable in management of chronic ulcers.

Neuropathological and genetic characteristics of a post-mortem series of cases with dementia with Lewy bodies clinically suspected of Creutzfeldt-Jakob's disease.

INTRODUCTION: The disease course of dementia with Lewy bodies (DLB) can be rapidly progressive, clinically resembling Creutzfeldt-Jakob's disease (CJD). To better understand factors contributing to this rapidly progressive disease course, we describe load and distribution of neuropathology, and the presence of possible disease-associated genetic defects in a post-mortem series of DLB cases clinically suspected of CJD. METHODS: We included pathologically confirmed DLB cases with a disease duration of 3.5 years or less from the Dutch Surveillance Center for Prion Diseases, collected between 1998 and 2014. Lewy body disease (LBD) and Alzheimer's disease (AD)-related pathology were staged and semi-quantitatively scored in selected brain regions. Whole exome sequencing analysis of known disease-associated genes, copy number analysis, APOE ε genotyping and C9orf72 repeat expansion analysis were performed to identify defects in genes with a well-established involvement in Parkinson's disease or AD. RESULTS: Diffuse LBD was present in nine cases, transitional LBD in six cases and brainstem-predominant LBD in one case. Neocortical alpha-synuclein load was significantly higher in cases with intermediate-to-high than in cases with low-to-none AD-related pathology (p = 0.007). We found two GBA variants (p.D140H and p.E326K) in one patient and two heterozygous rare variants of unknown significance in SORL1 in two patients. CONCLUSION: A high load of neocortical alpha-synuclein pathology was present in most, but not all DLB cases. Additional burden from presence of concomitant pathologies, synergistic effects and specific genetic defects in the known disease-associated genes may have contributed to the rapid disease progression.

Oral Hygiene Practices among Saudi Arabian Children and Its Relation to Their Dental Caries Status.

Dental caries is one of the most common preventable diseases occurring among children. The aim here is to survey the oral hygiene practices that are commonly followed by Arab children and to see its relationship with their dental caries status. A cross-sectional study with multistage random sampling technique was conducted. Sociodemographic data and information on oral hygiene practices like use of toothbrush, dental floss, siwak, frequency of brushing along with number of snack between meals per day, and consumption of sugar per day was obtained. Presence of plaque on tooth surfaces was reported using plaque index, which was followed by DMFT index to determine the dental caries status. Among the sample of 500 school children, the mean plaque score in male (mean = 0.69; SD = 0.50) was slightly higher than the female (mean = 0.66; SD = 0.46). Increased frequency of snacks (P=0.05; ß=0.08; CI = -0.00, 0.09) and sugar consumption (P=0.01; ß=0.16; CI = 0.04, 0.27) per day significantly showed higher values of DMFT. Also, the odds of dental caries among the school children who were irregular in brushing their teeth was higher in contrast to the children brushing once (P=0.03; OR = 0.89; CI = 0.70, 1.12) or twice (P=0.03; OR = 0.80; CI = 0.64, 0.93) per day. It is recommended that the dental public health practitioners here should consider the effect of oral hygiene practices on oral health status in order to design the future health promotion interventions.

Novel GCH1 variant in Dopa-responsive dystonia and Parkinson's disease.

BACKGROUND: GTP cyclohydrolase I (GCH1) mutations are the commonest cause of Dopa-responsive dystonia (DRD). Clinical phenotypes can be broad, even within a single family. METHODS: We present clinical, genetic and functional imaging data on a British kindred in which affected subjects display phenotypes ranging from DRD to Parkinson's disease (PD). Twelve family members were studied. Clinical examination, dopamine transporter (DAT) imaging, and molecular genetic analysis of GCH1 and the commonest known familial PD-related genes were performed. RESULTS: We have identified a novel missense variant, c.5A > G, p.(Glu2Gly), within the GCH1 gene in affected family members displaying a range of phenotypes. Two affected subjects carrying this variant had abnormal DAT imaging. These two with abnormal DAT imaging had a PD phenotype, while the remaining three subjects with the novel GCH1 variant had normal DAT imaging and a DRD phenotype. CONCLUSIONS: We propose that this GCH1 variant is pathogenic in this family and these findings suggest that similar mechanisms involving abnormal GTP cyclohydolase I may underlie both PD and DRD. GCH1 genetic testing should be considered in patients with PD and a family history of DRD.

Synthesis and anticonvulsant and sedative-hypnotic activity of 4-(alkylimino)-2,3-dihydro-4H-1-benzopyrans and -benzothiopyrans.

A series of 4-(alkylimino)-5-hydroxy-7-alkyl-2,3-dihydro-4H-1-benzopyrans and -thiopyrans were synthesized and evaluated for anticonvulsant activity. Preliminary screening of these compounds revealed that 2,2-dimethyl-4-[(2-hydroxyalkyl)imino]-5-hydroxy-7-pentyl-2,3- dihydro-4H-1-benzopyrans 19 and 29, the 7-butyl analogue 34, and the corresponding 7-pentyl-4H-1-benzothiopyrans 38 and 39 had the most promising anticonvulsant activity. Synthesis of both enantiomers of 29 and 39 indicated that the R isomers 30 and 40 were the most active and showed very good protection against MES, pentylenetetrazole, and mercaptopropionic acid induced seizures after oral administration in mice. In the Irwin test these compounds showed a generalized depressant activity but at dosages higher than those showing anticonvulsant activity, whereas acute toxicity after oral administration was low (LD50 higher than 400 mg/kg).

Mechanism of sleep-induced periodic breathing in convalescing stroke patients and healthy elderly subjects.

Cerebral vascular ischemic strokes are known to precipitate Cheyne-Stokes periodic breathing. Interestingly, Cheyne-Stokes-like breathing during sleep may be associated with obstructive sleep apnea (OSA) in some individuals. Therefore, it was reasoned that stroke patients with periodic breathing in sleep would be susceptible to OSA. Because oscillations in upper airway resistance can occur as a component of sleep-induced periodic breathing, we hypothesized that stroke patients with sleep-induced periodic breathing would have oscillations in upper airway resistance. These oscillations in resistance would be expected to contribute to OSA. We studied stroke patients with sleep-induced periodic breathing and control subjects to evaluate the relationship between upper airway resistance and ventilation in periodic breathing in sleep. Ventilation and upper airway resistance were measured in presleep wakefulness and in stage 2 NREM sleep. Mean tidal volume, minute ventilation, respiratory cycle timing variables, and upper airway resistance were not different between stroke and control subjects, either awake or asleep. Upper airway resistance increased and ventilation volume decreased from wakefulness to sleep in both groups. In an equivalent number of subjects from each group, reciprocal patterned oscillations in tidal volume and upper airway resistance were present at a 5 to 12.5 breath frequency during sleep. As upper airway resistance increased, tidal volume decreased. Stroke patients had wider fluctuations in upper airway resistance than control subjects, likely contributing to the higher number of sleep-disordered breathing events observed in the stroke patients.

Electrophoretic separation of the soluble proteins of different fractions of the sarcocyst of Sarcocystis fusiformis of buffalo (Bubalus bubalis).

The electrophoretic fractionation of the various compounds of the soluble proteins in the cyst wall (CW), cyst fluid (CF) and zoites (ZT) of the sarcocyst of Sarcocystis fusiformis from buffalo (Bubalus bubalis) was studied by polyacrylamide disc gel electrophoresis. The CW fraction was found to contain at least six components, and ZT and CF contained at least four components with varied Rf values. Each gel was subjected to the gel scanner, and the corresponding areas of the peaks along with the percentage of the proteins in the bands were calculated.

Synthesis and anticonvulsant activity of some benzopyranone imino derivatives of GABA and related compounds.

The synthesis of some 5-hydroxy-4-imino-2,3-dihydrobenzopyran derivatives of GABA and alkylamines is described. The products were tested for their GABA-receptor binding and anticonvulsant activity in mice. Some compounds showed anticonvulsant activity. No binding to GABA receptors was observed.

EFFECT OF NIKETHAMIDE AND DIAZEPAM ON THE LEVELS OF BIOGENIC AMINES IN THE DIFFERENT PARTS OF THE POULTRY BRAIN AT THREE AGE GROUPS.

Fifty four female poultry birds of 3, 4 and 5 months age were given nikethamide and diazepam intramuscularly as stimulant and depresent, respectively. The effects of above two drugs on the levels of biogenic amines were measured Fluorometrically in the rostral, middle and caudal portions of poultry brain. Diazepam increased the levels of 5-HT and dopamine in the caudal and middle portion of the brain respectively. The levels of dopamine and non-epinephrine increased with the nikethamide administration and also with increasing age of the birds, but the effect of diazepam was inconsistant. Unlike the levels of dopamine and nor-epinephrine which were maximum in middle protion, the epinephrine concentration was highest in the caudal portion of brain. It was concluded that 5-HT acted as inhibitory particularly in the caudal portion, whereas, catecholamines as excitatory neurotransmitter of the poultry brain. The increased levels of catecholamines in the poultry brain with increasing age speaks of their positive role in sexual maturity and subsequently in reproduction of the birds.

Hairy cell leukemia-variant.

Hairy cell leukaemia variant is a very rare chronic lymphoproliferative disorder and is closely related to hairy cell leukemia. We hereby describe a case of hairy cell leukaemia variant for the first time in Saudi Arabia. An elderly Saudi man presented with pallor, massive splenomegaly, and moderate hepatomegaly. Hemoglobin was 7.7 g/dl, Platelets were 134 x109/l and white blood count was 140x10 9/l with 97% being abnormal lymphoid cells with cytoplasmic projections. The morphology, cytochemistry, and immunophenotype of the lymphoid cells were classical of hairy cell leukaemia variant. The bone marrow was easily aspirated and findings were consistent with hairy cell leukaemia variant.

Immunophenotypic pattern of childhood acute lymphoblastic leukemia.

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Spectrum of hereditary coagulation factor deficiencies in eastern province, Saudi Arabia.

In a 7-year retrospective analysis (1991-97) of the records of the Department of Haematology, Regional Laboratory and Blood Bank (Dammam), 54 patients from all parts of Saudi Arabia's Eastern Province were diagnosed with hereditary coagulation factor deficiencies. The largest group of patients, 42 haemophiliacs, included 4 non-Saudi patients. There were 39 haemophilia A or factor VIII deficiency patients, 2 haemophilia B or factor IX deficiency patients and 1 combined factor VIII and V deficiency patient. There were 5 Saudi patients with probable factor XIII deficiency, and 7 patients, all but one who were Saudi, had von Willebrand disease. The distribution of haemophilia patients in Eastern Province showed some differences compared with those reported from Riyadh and from Western countries. Among Saudis in Eastern Province, the number with suspected factor XIII deficiency, although low, was higher than that reported for other regions. The number of patients with haemophilia B and von Willebrand disease was lower than expected, when compared with the number of haemophilia A cases.

The effect of alpha-thalassemia on cord blood red cell indices and interaction with sickle cell gene.

BACKGROUND: AA+/--thalassemia is known to be prevalent in the Eastern region of Saudi Arabia. There are no large scale reports regarding the effect of alpha-thalassemia on red cell indices of cord blood from Saudi Arabia. Similarly, there are no reports regarding the interaction of AA+/--thalassemia and the sickle cell gene in relation to red cell indices in cord blood. To address these issues, we undertook a study on neonatal cord blood samples. MATERIALS AND METHODS: In a prospective study, cord blood samples from 504 neonates from the Qatif area of the Eastern Province of Saudi Arabia were analyzed for complete blood counts (CBC) and cellulose acetate Hb electrophoresis. Hb S was confirmed by citrate agar Hb electrophoresis. RESULTS: There were 243 case samples with normal Hb electrophoresis (Hb A 27.2+/-7% and Hb F 72.6+/-7.7%). Their mean Hb (g/dL), RBC (x10(12) /L), Hct (%), MCV (fl), MCH (pg), MCHC (g/dL), RDW-SD (fl) and RDWCV (%) were 15.05+/-1.6, 4.5+/-0.5, 47.4+/-5.3, 106+/-8, 33.6+/-2.3, 31.8+/-1.7, 69.2+/-9.5 and 17.9+/-1.7, respectively. There were 136 cases with alpha-thalassemia trait (alphaTT), 57 cases with sickle cell trait (SCT) and 50 cases of sickle cell trait with alpha-thalassemia trait (SCT/alphaTT). There were 10 cases of Hb H disease (6 definite), including one with sickle cell disease (SCD) and two with SCT, Hb Bart's 23.9%-43.6%; four probable with Hb Bart's 10.9%-16.1%, and one with SCT. The effect on red cell parameters in Hb H disease were most pronounced. In addition, there were seven cases of SCD, four of whom had coexistent AA+/--thalassemia trait (SCD/alphaTT). CONCLUSION: The prevalence of alpha-thalassemia in this cohort of Saudi population was 39.99%. Hb H disease appeared as common as SCD. Sickle cell gene was seen in 23.4% of neonatal samples. alpha-Thalassemia gene significantly reduces MCH, MCV, RDW-SD, Hct, Hb, and increases RBC count in both normal or sickle cell trait neonates. Generally, the variation of red cell parameters is directly proportional to the amount of Hb Bart's in the cord blood. Sickle cell gene in itself produces low MCV, RDW-SD and MCH in cord blood. Further, normal reference values for red cell parameters of cord blood are established.