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Background: Cerebellar atrophy is characterized by loss of cerebellar tissue, with evidence on brain imaging of enlarged interfolial spaces compared to the foliae. Genetic ataxias associated with cerebellar atrophy are a heterogeneous group of disorders. We investigated the prevalence in Canada and the diagnostic yield of whole exome sequencing (WES) for this group of conditions. Methods: Between 2011 and 2017, WES was performed in 91 participants with cerebellar atrophy as part of one of two national research programs, Finding of Rare Genetic Disease Genes (FORGE) or Enhanced Care for Rare Genetic Diseases in Canada (Care4Rare). Results: A genetic diagnosis was established in 58% of cases (53/91). Pathogenic variants were found in 24 known genes, providing a diagnosis for 46/53 participants (87%), and in four novel genes, accounting for 7/53 cases (13%). 38/91 cases (42%) remained unsolved. The most common diagnoses were channelopathies in 12/53 patients (23%) and mitochondrial disorders in 9/53 (17%). Inheritance was autosomal recessive in the majority of cases. Additional clinical findings provided useful clues to some of the diagnoses. Conclusions: This is the first report on the prevalence of genetic ataxias associated with cerebellar atrophy in Canada, and the utility of WES for this group of conditions.
Adenoid hypertrophy is a common cause of upper airway obstruction, and adenoidectomy is one of the most frequently performed operations in children. Topical nasal steroids can act directly on nasopharyngeal lymphoid tissue to decrease its reactive inflammatory changes and potentially reduce its size.
To study the light microscopic changes in adenoidal lymphoid tissue after one month of topical steroid use.
Twenty-six children with adenoid hypertrophy grade 3 scheduled for adenoidectomy were randomly divided into two equal groups: one group received mometasone furoate aqueous nasal spray (Nasonex) 100 mcg/day for four weeks, and a control group received nasal normal saline 0.9 per cent for four weeks. The removed adenoids were examined histopathologically.
Adenoidal tissue from the mometasone group had less reactive germinal centres and less spongiosis compared to the control group. The latter showed proliferating, reactive, variable sized and shaped lymphoid follicles, with congested blood vessels in the interfollicular areas.
The use of intranasal mometasone furoate aqueous nasal spray (Nasonex) for one month reduced adenoidal tissue reactive cellular changes and its vascularity. This is, however, a pilot study; a longer treatment period is needed to assess the effect of treatment on adenoidal size.
To investigate a Middle East respiratory syndrome coronavirus (MERS-CoV) outbreak event involving multiple healthcare facilities in Riyadh, Saudi Arabia; to characterize transmission; and to explore infection control implications.
Cases presented in 4 healthcare facilities in Riyadh, Saudi Arabia: a tertiary-care hospital, a specialty pulmonary hospital, an outpatient clinic, and an outpatient dialysis unit.
Contact tracing and testing were performed following reports of cases at 2 hospitals. Laboratory results were confirmed by real-time reverse transcription polymerase chain reaction (rRT-PCR) and/or genome sequencing. We assessed exposures and determined seropositivity among available healthcare personnel (HCP) cases and HCP contacts of cases.
In total, 48 cases were identified, involving patients, HCP, and family members across 2 hospitals, an outpatient clinic, and a dialysis clinic. At each hospital, transmission was linked to a unique index case. Moreover, 4 cases were associated with superspreading events (any interaction where a case patient transmitted to ≥5 subsequent case patients). All 4 of these patients were severely ill, were initially not recognized as MERS-CoV cases, and subsequently died. Genomic sequences clustered separately, suggesting 2 distinct outbreaks. Overall, 4 (24%) of 17 HCP cases and 3 (3%) of 114 HCP contacts of cases were seropositive.
We describe 2 distinct healthcare-associated outbreaks, each initiated by a unique index case and characterized by multiple superspreading events. Delays in recognition and in subsequent implementation of control measures contributed to secondary transmission. Prompt contact tracing, repeated testing, HCP furloughing, and implementation of recommended transmission-based precautions for suspected cases ultimately halted transmission.
Synthesis of ZIF with zinc, cobalt, or copper was carried out by microwaves. The effect of metal center on morphologies and pores of products was studied. Nitrogen adsorption/desorption onto ZIFs was examined by density functional theory. The micro, meso, and macropores of ZIF-8, Zn/Co-ZIF-8, and Cu/ZIF-8 ranged 99.814–99.969%, 0.055–0%, and 0.031–0.130%, respectively. Average pore sizes of ZIF-8, Zn/Co-ZIF-8, and Cu/ZIF-8 are 1.291, 1.194, and 1.164 nm, respectively. Monolayer saturation limits of nitrogen onto ZIF-8, Zn/Co-ZIF-8, and Cu/ZIF-8 were 21.152, 18.943, and 17.784 mmol/g, respectively. Further, the results included densities, total surface areas, total pore volumes, and average particle sizes of ZIF-8, Zn/Co-ZIF-8, and Cu/ZIF-8.
Oxidative stress is a major cause of defective embryo development during in vitro culture. Retinoids are recognized as non-enzymatic antioxidants and may have an important role in the regulation of cell differentiation and vertebrate development. However, there are not enough reports discussing the antioxidant and developmental capacity of retinoids, including retinol (RT), on the in vitro development of embryos recovered from livestock animals, particularly in rabbit species. Therefore, morula embryos obtained from nulliparous Red Baladi rabbit does were cultured for 48 h in TCM199 medium in the absence of RT (control group) or in the presence of RT at concentrations of 10, 100 and 1000 nM. The developmental capacity to the hatched blastocyst stage, the antioxidant biomarker assay and the expression of several selected genes were analyzed in each RT group. The data show that RT significantly (P<0.001) promoted the embryo hatchability rate at the concentration of 1000 nM to 69.44% versus 29.71% for the control. The activity of malondialdehyde (MDA) level was significantly (P<0.05) lower in the RT groups than in the control group, while the total antioxidant capacity (TAC), superoxide dismutase (SOD) and glutathione peroxidase (GPx) activities were significantly (P<0.05) higher following treatment with RT. Furthermore, RT treatment considerably upregulated the relative expression of gap junction protein alpha 1 (GJA1), POU class 5 homeobox 1 (POU5F1) and superoxide dismutase 1 (SOD1) genes compared with the control group. The current study highlights the potential effects of RT as antioxidant in the culture medium on the in vitro development of rabbit embryos.
To assess whether pre-operative assessment with a bone conduction hearing device on a softband is an accurate predictor of performance with one of two transcutaneous hearing implants.
Cohort study comparing pre-and post-operative speech audiometry using correlation analysis.
Pre-operative pure tone audiometry and aided half optimum speech recognition thresholds were compared with post-operative aided results for each ear that had undergone implantation. Data were collected prospectively.
Full data were available in 24 ears. In 19 out of 24 ears (79 per cent), the difference between pre- and post-operative speech scores was less than 10 dB, demonstrating a good clinical correlation. The Pearson correlation coefficient was calculated at 0.66 (95 per cent confidence interval = 0.357–0.842), indicating a strong statistical correlation.
Pre-operative softband testing shows good clinical correlation and strong statistical correlation with hearing implant performance. The findings suggest there is value in using the test to predict performance and guide patients’ expectations.
This work aims to develop simple and cost-effective methods in reduction of Cr(VI) from water to less toxic and easy separated Cr(III) using Titanium dioxide (TiO2).
TiO2 nanoparticles are prepared by a sol-gel method using titanium tetra-chloride and characterized using X-Ray Diffraction (XRD), Scanning electron microscope (SEM), Energy dispersive X-ray Fluorescence spectrometer (EDX) and UV-visible spectroscopy. XRD shows Anatase structure of TiO2 after annealing at 600°C for four hours. The particles size is estimated to be 70 nm using SEM.UV-Visible spectroscopy indicated that TiO2 nanoparticles played important role in decreasing the concentration of Cr (VI) in water samples for different pH range of 1 to 4. The decrease in Cr(VI) concentration after the treatment is ascribed to the reduction caused by the photocatalyst effect that resulted from the presence of TiO2 nanoparticle in water samples under direct exposure to direct sunlight.
Improving understanding of the pathogen-specific seasonality of enteric infections is critical to informing policy on the timing of preventive measures and to forecast trends in the burden of diarrhoeal disease. Data obtained from active surveillance of cohorts can capture the underlying infection status as transmission occurs in the community. The purpose of this study was to characterise rotavirus seasonality in eight different locations while adjusting for age, calendar time and within-subject clustering of episodes by applying an adapted Serfling model approach to data from a multi-site cohort study. In the Bangladesh and Peru sites, within-subject clustering was high, with more than half of infants who experienced one rotavirus infection going on to experience a second and more than 20% experiencing a third. In the five sites that are in countries that had not introduced the rotavirus vaccine, the model predicted a primary peak in prevalence during the dry season and, in three of these, a secondary peak during the rainy season. The patterns predicted by this approach are broadly congruent with several emerging hypotheses about rotavirus transmission and are consistent for both symptomatic and asymptomatic rotavirus episodes. These findings have practical implications for programme design, but caution should be exercised in deriving inferences about the underlying pathways driving these trends, particularly when extending the approach to other pathogens.
Guinea worm disease, dracunculiasis or dracontiasis, is an ancient disease with records going back over 4500 years, but until the beginning of the 20th century, little was known about its life cycle, particularly how humans became infected. In 1905, Robert Thomas Leiper was sent by the British colonial authorities to West Africa to investigate the spread of Guinea worm disease and to recommend measures to prevent it. While carrying out his investigations, he made important contributions to the aetiology, epidemiology and public health aspects of Guinea worm disease and provided definitive answers to many outstanding questions. First, he tested the validity of previous theories; second, he confirmed the role of water fleas, which he identified as Cyclops, as the intermediate hosts in the life cycle; third, he investigated the development of the parasite in its intermediate host; and fourth, he recommended measures to prevent the disease.
[The crustacean Order Cyclopoida in the Family Cyclopidae contains 25 genera, including Cyclops which itself contains over 400 species and may not even be a valid taxon. It is not known how many of these species (or indeed species belonging to related genera) can act as intermediate hosts of Dracunculus medinensis nor do we know which species Fedchenko, Leiper and other workers used in their experiments. It is, therefore, best to use the terms copepod, or copopoid crustacean rather than Cyclops in scientific texts. In this paper, these crustaceans are referred to as copepods except when referring to an original text.]
Leiper described the remarkable changes that took place when an infected copepod was placed in a dilute solution of hydrochloric acid; the copepod was immediately killed, but the Dracunculus larvae survived and were released into the surrounding water. From this, he concluded that if a person swallowed an infected copepod, their gastric juice would produce similar results. He next infected monkeys by feeding them copepods infected with Guinea worm larvae, and thus conclusively demonstrated that humans became infected by accidentally ingesting infected crustaceans. Based on these conclusions, he advocated a number of control policies, including avoidance of contaminated drinking water or filtering it, and these preventive measures paved the way for further research. The challenge to eradicate Guinea worm disease was not taken up until about seven decades later since when, with the support of a number of governmental and non-governmental organizations, the number of cases has been reduced from an estimated 3·5 million in 1986 to 25 in 2016 with the expectation that this will eventually lead to the eradication of the disease.
Background: AHEM is a rare form of acute disseminated encephalomyelitis (ADEM) characterized by fulminant encephalopathy with hemorrhagic necrosis and most often fatal outcome. Methods: A case report and review of literature. Results: A 6-year-old girl known SCD presented an acute demyelinating syndrome (ADS) with diplopia due to unilateral fourth nerve palsy. She received (20mg/kg/day for 5 days) of IVMP (intravenous methylprednisolone). Two weeks after steroid weaning, she presented right hemiplegia. Brain MRI showed a left frontal necrotico-hemorrhagic lesion and new areas of demyelination. She showed signs of herniation and underwent craniotomy. Investigations ruled out vascular and infectious process in both events. The deterioration stopped concomitantly to the initiation of IVMP. She was discharged with a longer oral wean. Later, she was diagnosed with Crohn’s disease and primary sclerosing cholangitis. We considered AHEM as the most plausible diagnosis based on the clinical and radiological presentation, the preceding ADS, the exclusion of other etiologies, and the response to IVMP including resolution of non-necrotic lesions. Similar - but fatal - AHEM has been reported in 2 SCD patients. Conclusions: In any ADS occurring in the context of SCD and/or auto-immune condition, we recommend to slowly wean steroids, and to closely monitor the patient after weaning to quickly treat any recurrence with IVMP.
In the present study a comparison of the otolith morphology of two species of parrotfish, family Scaridae, collected from the Red Sea coast of Egypt, is conducted to identify the most appropriate taxonomic characters that separate these species. Ontogenetic changes in the otoliths of the two scarid fishes become evident. In the otoliths of Chlorurus sordidus, the following characters are comparable in small-sized adult fishes: otolith width, otolith depth, mesial surface shape, lateral surface shape, shape of sulcus acusticus, column, rostrum and size of rostrum. The otoliths of young adults (GI) C. sordidus differ from the adult ones in 14 out of the 22 characteristics studied. In the otoliths of Hipposcarus harid, the following characters are comparable in small and large fish: otolith width, otolith depth, mesial and lateral surface shapes, shape of sulcus acusticus, rostrum and size of rostrum.
Urinary tract infection (UTI) is common in children aged <5 years with diarrhoea, but little is known about risk factors, aetiology and outcome of such children. We aimed to evaluate these knowledge gaps of UTI in children aged <5 years with diarrhoea. We enrolled all children aged <5 years with diarrhoea admitted to Dhaka Hospital of the International Centre for Diarrhoeal Disease Research, Bangladesh, between May 2011 and April 2013, who had history of fever (⩾38 °C) and obtained a urine sample for culture. Diarrhoea with UTI (confirmed by culture) constituted cases (n = 26) and those without UTI constituted controls (n = 78). Threefold controls were randomly selected. The case-fatality rate was comparable in cases and controls (4% vs. 1%, P = 0·439). Escherichia coli (69%) and Klebsiella (15%) were the most commonly isolated pathogens. Persistent diarrhoea, pneumonia and prior antibiotics use were identified as risk factors for UTI in logistic regression analysis (P < 0·05 for all). Thus, children with diarrhoea presenting with persistent diarrhoea, pneumonia, and prior antibiotic use should be investigated for UTI for their prompt management that may reduce morbidity.
Dengue fever is an arthropod-borne viral infection that has become endemic in several parts of India including Delhi. We studied occurrence of co-infection with dengue viruses during an outbreak in New Delhi, India in 2014. For the present study, blood samples collected from symptomatic patients were analysed by RT–PCR. Eighty percent of the samples were positive for dengue virus. The result showed that DENV-1 (77%) was the predominant serotype followed by DENV-2 (60%). Concurrent infection with more than one serotype was identified in 43% of the positive samples. Phylogenetic analysis clustered DENV-1 strains with the American African and DENV-2 strains in Cosmopolitan genotypes. Four common amino-acid mutations were identified in the envelope gene of DENV-1 sequences (F337I, A369T, V380I and L402F) and one common mutation (N390S) in the DENV-2 sequences. Further analysis revealed purifying selection in both the serotypes. A significant number of patients were co-infected with DENV-1 and DENV-2 serotypes. Although we do not have direct evidence to demonstrate co-evolution of these two stereotypes, nonetheless their simultaneous occurrence does indicate that they are favoured by evolutionary forces. An ongoing surveillance and careful analysis of future outbreaks will strengthen the concept of co-evolution or otherwise. Whether the concurrent dengue viral infection is correlated with disease severity in a given population is another aspect to be pursued. This study is envisaged to be useful for future reference in the context of overall epidemiology.
A gravitational search algorithm (GSA) is a meta-heuristic development that is modelled on the Newtonian law of gravity and mass interaction. Here we propose a new hybrid algorithm called the Direct Gravitational Search Algorithm (DGSA), which combines a GSA that can perform a wide exploration and deep exploitation with the Nelder-Mead method, as a promising direct method capable of an intensification search. The main drawback of a meta-heuristic algorithm is slow convergence, but in our DGSA the standard GSA is run for a number of iterations before the best solution obtained is passed to the Nelder-Mead method to refine it and avoid running iterations that provide negligible further improvement. We test the DGSA on 7 benchmark integer functions and 10 benchmark minimax functions to compare the performance against 9 other algorithms, and the numerical results show the optimal or near optimal solution is obtained faster.
Objective: Idiopathic normal pressure hydrocephalus (INPH) is a neurological disorder presenting with gait, cognitive, and bladder symptoms in the context of ventricular enlargement. Although gait is the primary indicator for treatment candidacy and outcome, additional monitoring tools are needed. Line Tracing Test (LTT) and Serial Dotting Test (SDT), two psychomotor tasks, have been introduced as potential outcome measures but have not been widely studied. This preliminary study examined whether LTT and SDT are sensitive to motor dysfunction in INPH and determined if accuracy and time are important aspects of performance. Methods: Eighty-four INPH subjects and 36 healthy older adults were administered LTT and SDT. Novel error scoring procedures were developed to make scoring practical and efficient; interclass correlation showed good reliability of scoring procedures for both tasks (0.997; p<.001). Results: The INPH group demonstrated slower performance on SDT (p<.001) and made a greater number of errors on both tasks (p<.001). Combined Time/Error scores revealed poorer performance in the INPH group for original-LTT (p<.001), modified-LTT (p≤.001) and SDT (p<.001). Conclusions: These findings indicate LTT and SDT may prove useful for monitoring psychomotor skills in INPH. While completion time reflects impaired processing speed, reduced accuracy may suggest planning and self-monitoring difficulties, aspects of executive functioning known to be compromised in INPH. This is the first study to underscore the importance of performance accuracy in INPH and introduce practical/reliable error scoring for these tasks. Future work will establish reliability and validity of these measures and determine their utility as outcome tools. (JINS, 2016, 22, 341–349)
Following the removal of antibiotic growth promoters in animal feed, various products have been suggested as alternatives to the poultry feed industry. Among these products some types of clay or derivatives were used as a natural supply in order to optimise performance. Clay is indeed abundant naturally, cheap, widely used by hens raised outdoors voluntarily or by ingesting earthworms and soil fauna insects. As an indication it was estimated that a laying hen kept outdoors consumes 10g of soil, 7g of plant and 20g of insects and worms per day. In further studies it was reported that soil ingestion can reach 30% of dry matter intake. Considering their specific absorption capacities of ions, clays are considered real molecular sieves. Various studies have concluded that clays promote a hygienic digestive tract, increase food retention time and contribute to improving water retention and reducing the moisture content of droppings. The use of clays was accompanied by positive responses in nutrient digestibility, weight gain and feed conversion ratio. Also the addition of clay enhances meat sensorial value and organoleptic characteristics, the cutting yield and meat processing abilities. The antimicrobial and antitoxic properties of clay were shown to improve the appetite and weight gain of chickens eating food containing aflatoxins. In laying hens literature states that the use of clay improves egg size, egg internal qualities, shell strength and wet droppings. Clay use is also reported to reduce mite infestation in hens and improve ambient conditions in animal husbandry with substantially lower levels of NH3 and CH4.
Here we present an alternative approach to coarse graining, based on the multiresolution diffusion-wavelet approach to operator compression, which does not require explicit atomistic-to-coarse-grained mappings. Our diffusion-wavelet method takes as input the topology and sparsity of the molecular bonding structure of a system, and returns as output a hierarchical set of degrees of freedom (DoFs) of system-specific coarse-grained variables. Importantly, the hierarchical compression provides a clear framework for modeling at many model scales (levels), beyond the common two-level CG representation. Our results show that the resulting hierarchy separates localized modes, such as a single C-C vibrational mode, from larger-scale motions, e.g., long-range concerted backbone vibrational modes. Our approach correctly captures small-scale chemical features, such as cellulose ring structures, and alkane side chains or CH2 units, as well as large-scale features of the backbone. In particular, the new method’s finest-scale modes describe DoFs similar to united atom models and other chemically-defined CG models. Modes at coarser levels describe increasingly large connected portions of the target polymers. For polyethylene and polystyrene, spatial coordinates and their associated forces were compressed by up to two orders of magnitude. The compression in forces is of particular interest as this allows larger timesteps as well as reducing the number of DoFs.
There is limited information on percent expenditure of household income due to childhood diarrhoea especially in rural Bangladesh. A total of 4205 children aged <5 years with acute diarrhoea were studied. Percent expenditure was calculated as total expenditure for the diarrhoeal episode divided by monthly family income, multiplied by 100. Overall median percent expenditure was 3·04 (range 0·01–94·35). For Vibrio cholerae it was 6·42 (range 0·52–82·85), for enterotoxigenic Escherichia coli 3·10 (range 0·22–91·87), for Shigella 3·17 (range 0·06–77·80), and for rotavirus 3·08 (range 0·06–48·00). In a multinomial logistic regression model, for the upper tertile of percent expenditure, significant higher odds were found for male sex, travelling a longer distance to reach hospital (⩾median of 4 miles), seeking care elsewhere before attending hospital, vomiting, higher frequency of purging (⩾10 times/day), some or severe dehydration and stunting. V. cholerae was the highest and rotavirus was the least responsible pathogen for percent expenditure of household income due to childhood diarrhoea.
The aim of this study was to assess the feasibility of radiographer led verification of cone-beam computed tomography (CBCT) images for patients with solitary lung tumours treated with stereotactic body radiotherapy treatment (SBRT).
Material and methods
CBCT setup images of 20 patients from the first fraction of each patient were retrospectively registered by therapeutic radiographers. The displacements recorded were compared with the clinical oncologist’s original online match. The time taken by radiographers to verify the CBCT images was also recorded.
Overall agreement for all radiographers when compared with the clinical oncologist match was 91%. Interobserver variations between radiographers were X plane 0·87 (0·76–0·94); Y plane 0·74 (0·51–0·88); and Z plane 0·88 (0·78–0·95) intraclass correlation coefficient and 95% confidence interval. The average time taken for verification was 128 seconds.
Therapeutic radiographers are able to verify CBCT images for thorax SBRT with results comparable to the ‘gold standard’ clinical oncologists’ match, however additional training will be provided for online verification. The time taken was within acceptable limits.