White matter microstructure correlates of narrative production in typically developing children and children with high functioning autism

This study investigated the relationship between white matter microstructure and the development of morphosyntax in a spoken narrative in typically developing children (TD) and in children with high functioning autism (HFA). Autism is characterized by language and communication impairments, yet the relationship between morphosyntactic development in spontaneous discourse contexts and neural development is not well understood in either this population or typical development. Diffusion tensor imaging (DTI) was used to assess multiple parameters of diffusivity as indicators of white matter tract integrity in language-related tracts in children between 6 and 13 years of age. Children were asked to spontaneously tell a story about at time when someone made them sad, mad, or angry. The story was evaluated for morphological accuracy and syntactic complexity. Analysis of the relationship between white matter microstructure and language performance in TD children showed that diffusivity correlated with morphosyntax production in the superior longitudinal fasciculus (SLF), a fiber tract traditionally associated with language. At the anatomical level, the HFA group showed abnormal diffusivity in the right inferior longitudinal fasciculus (ILF) relative to the TD group. Within the HFA group, children with greater white matter integrity in the right ILF displayed greater morphological accuracy during their spoken narrative. Overall, the current study shows an association between white matter structure in a traditional language pathway and narrative performance in TD children. In the autism group, associations were only found in the ILF, suggesting that during real world language use, children with HFA rely less on typical pathways and more on alternative ventral pathways that possibly mediate visual elements of language.     

Depression,Anxiety, and Suicide Risk among Ugandan Youth in Vocational Training

Psychiatric Quarterly - The current study examines the prevalence of depression, anxiety, suicide risk, and PTSD in Ugandan youth (13-25 years) attending vocational training programs. Youth from...     

Identification and dynamics of spontaneous burst initiation zones in unidimensional neuronal cultures

Spontaneous activity is typical of in vitro neural networks, often in the form of large population bursts. The origins of this activity are attributed to intrinsically bursting neurons and to noisy backgrounds as well as to recurrent network connections. Spontaneous activity is often observed to emanate from localized sources or initiation zones, propagating from there to excite large populations of neurons. In this study, we use unidimensional cultures to overcome experimental difficulties in identifying initiation zones in vivo and in dissociated two-dimensional cultures. We found that spontaneous activity in these cultures is initiated exclusively in localized zones that are characterized by high neuronal density but also by recurrent and inhibitory network connections. We demonstrate that initiation zones compete in driving network activity in a winner-takes-most scenario.     

Small area estimation of under-5 mortality in Bangladesh,Cameroon, Chad,Mozambique, Uganda,and Zambia using spatially misaligned data

Background

The under-5 mortality rate (U5MR) is an important metric of child health and survival. Country-level estimates of U5MR are readily available, but efforts to estimate U5MR subnationally have been limited, in part, due to spatial misalignment of available data sources (e.g., use of different administrative levels, or as a result of historical boundary changes).

Methods

We analyzed all available complete and summary birth history data in surveys and censuses in six countries (Bangladesh, Cameroon, Chad, Mozambique, Uganda, and Zambia) at the finest geographic level available in each data source. We then developed small area estimation models capable of incorporating spatially misaligned data. These small area estimation models were applied to the birth history data in order to estimate trends in U5MR from 1980 to 2015 at the second administrative level in Cameroon, Chad, Mozambique, Uganda, and Zambia and at the third administrative level in Bangladesh.

Results

We found substantial variation in U5MR in all six countries: there was more than a two-fold difference in U5MR between the area with the highest rate and the area with the lowest rate in every country. All areas in all countries experienced declines in U5MR between 1980 and 2015, but the degree varied both within and between countries. In Cameroon, Chad, Mozambique, and Zambia we found areas with U5MRs in 2015 that were higher than in other parts of the same country in 1980. Comparing subnational U5MR to country-level targets for the Millennium Development Goals (MDG), we find that 12.8% of areas in Bangladesh did not meet the country-level target, although the country as whole did. A minority of areas in Chad, Mozambique, Uganda, and Zambia met the country-level MDG targets while these countries as a whole did not.

Conclusions

Subnational estimates of U5MR reveal significant within-country variation. These estimates could be used for identifying high-need areas and positive deviants, tracking trends in geographic inequalities, and evaluating progress towards international development targets such as the Sustainable Development Goals.

     

Pharmacokinetic drug evaluation of empagliflozin plus linagliptin for the treatment of type 2 diabetes

Introduction: Type 2 diabetes mellitus has become a growing epidemic and therefore efficient treatment strategies that target its management are needed. The treatment of diabetic patients often requires the combination of antidiabetic drug classes. Sodium-glucose co-transporter 2 inhibitors (SGLT2i) block glucose reabsorption in the proximal renal tubules. Dipeptidyl peptidase-4 inhibitors (DPP-4i) improve glucose metabolism by blocking the enzyme that degrades incretins leading to increased insulin secretion.

Areas covered: The aim of the review is to present the available data on pharmacokinetic properties/pharmacodynamics, metabolic and cardiovascular effects of empagliflozin plus linagliptin combination.

Expert opinion: Both empagliflozin and linagliptin have established safety and efficacy in the treatment of diabetes. Available data demonstrate the absence of pharmacological interactions when the two drugs are given together. The complementary mechanisms of action would be expected to provide additive benefits on carbohydrate metabolism variables, but the results from clinical trials have shown that the empagliflozin/linagliptin combination provides only mild improvements of glycated hemoglobin compared with either monotherapy. However, the single-tablet formulation of empagliflozin/linagliptin is expected to provide better compliance and thus improved glycaemic control coupled with a favourable safety profile. Thus, the fixed-dose combination of empagliflozin/linagliptin has the capacity to both effectively and safely manage diabetic patients.     

Dynamics of MRI lesion development in an animal model of viral-induced acute progressive CNS demyelination

Theiler's murine encephalitis virus (TMEV) infection in mice is an established model of CNS demyelinating diseases. The aim of the study was to determine the chronological pattern of lesion development in this model of monophasic fulminant demyelinating disease. We followed six highly susceptible interferon-gamma receptor knockout mice with serial in vivo brain magnetic resonance imaging (MRI) studies to determine changes in overall T2 lesion load and gadolinium enhancement. Altogether, 163 individual lesions were followed over 52 days. The number of lesions increased linearly with time. Four chronological patterns of lesion development were seen: (a) expanding lesions (48.5% of all lesions, 54.05% volume contribution); (b) expanding-retracting lesions (20.85% of all lesions, 15.03% volume contribution); (c) fluctuating lesions (16.6% of all lesions, 28.8% volume contribution); (d) stable lesions (14.05% of all lesions, 2.12% volume contribution). Gadolinium enhancement was not seen in the evolution of every lesion. Enhancement was both time- and lesion type-dependent. Early in the disease course (<43 days after infection), enhancement was almost always seen, later on (>43 days after infection) it was only seen in 8% of new lesions. All of fluctuating, 85.3% of expanding, 83.5% of expanding-retracting, and 56.5% of stable lesions were associated with gadolinium enhancement. We conclude that the MRI features of TMEV-induced demyelination in this model showed four unique chronological patterns, and inconsistent gadolinium enhancement. These novel findings may provide new insights into the pathogenesis of acute fulminant multiple sclerosis (MS).     

Perceptions and acceptability of piloted Taenia solium control and elimination interventions in two endemic communities in eastern Zambia

Infections with Taenia solium cause significant public health and economic losses worldwide. Despite effective control tools, long‐term sustained control/elimination of the parasite has not been demonstrated to date. Success of intervention programs is dependent on their acceptability to local communities. Focus group discussions (FGDs) and questionnaires (QS) were conducted in two study communities in eastern Zambia to assess local perceptions and acceptance of two piloted intervention strategies: one targeting pigs only (‘control’ study arm), and one integrated human‐ and pig‐based (‘elimination’) strategy. QS (n = 227) captured data regarding participation in project activities, knowledge and perceptions of T. solium and of the interventional drugs used in the study. FGDs (n = 18) discussed perceived advantages and disadvantages of the interventions and of the project's delivery and value. QS data revealed 67% of respondents participated in at least one educational activity, and 80% correctly identified at least one disease targeted by the education. All elimination study arm respondents (n = 113) had taken the human treatment, and 98% intended to do so next time. Most (70%) indicated willingness to pay for future treatments (median 0.20 USD per dose). Of pig‐owning respondents, 11/12 (92%) had allowed their pigs to be treated/vaccinated and all intended to do so again next time. Four pig owners indicated willingness to pay 0.10–0.50 USD per dose of treatment or vaccine. FGD feedback revealed positive perceptions of interventions; people reported improved health in themselves and their pigs, and fewer cysticerci in pork. Latrine use, hand washing, meat inspection and proper cooking of pork had reportedly increased since the program's inception. Preliminary assessment indicates that the piloted intervention methods are generally acceptable to the communities. The reported willingness of many respondents to pay for the medications would contribute to the feasibility of long‐term, government‐led T. solium intervention programs in future.     

Anicteric hepatoxicity: a potential health risk of occupational exposures in Nigerian petroleum oil refining and distribution industry

Background

Literature abounds linking one’s job to certain unpalatable health outcomes. Since exposures to hazardous conditions in industrial environments often results in sundry health effects among workers, we embarked on this study to investigate the hepatic health effects of occupational activities in the petroleum refining and distribution industry.

Method

Biochemical markers of liver functions were assayed in plasma, using Reflotron dry chemistry spectrophotometric system. The study was conducted on randomly selected workers of Port Harcourt Refining Company (PHRC) and Pipelines and Petroleum Product Marketing Company (PPMC) both in Alesa-Eleme near Port Harcourt, Nigeria, as well as non-oil work civil servants serving as control subjects.

Result and conclusion

Results showed that, bilirubin ranged 0.3-1.6 mg/dl with a mean of 0.66±0.20mg/dl among the oil workers as against 0.5-1.00mg/dl with a mean of 0.58±0.13mg/dl in non-oil workers, Alkaline phosphatase ranged 50.00-296.00u/l (mean: 126.21±39.49u/l) in oil workers as against 40.20-111u/l (mean: 66.83±18.54u/l) for non-oil workers, Aspartic transaminases (AST) ranged 5.80-140.20u/l (mean: 21.81±11.49u/l) in oil workers against 18.00-44.00u/l (mean: 26.89±6.99u/l) for non-oil workers, while Alanine transaminases (ALT) ranged 4.90-86.00u/l (mean: 22.14±11.28u/l) in oil workers as against 10.00-86.60u/l (mean: 22.30±10.22u/l) for the non-oil workers. A close study of the results revealed that although the mean values for all the studied parameters were still within the parametric reference ranges, however, relative to the referents, there were significant increases (P<0.05) in plasma bilirubin (though anicteric) and alkaline phosphatase that was not matched with a corresponding increase in the plasma transaminases, suggesting a possibility that toxic anicteric hepatoxicity is part of the potential health effects of sundry exposures in the Nigeria petroleum oil refining and distribution industry. Gender differentiation data showed that though the mean values for the parameters were higher in males than females, the increases were not significant in most cases (P>0.05), whereas data for age and exposure period classifications revealed that irrespective of the age of the worker, the effects are likely to start after the first five years, manifesting fully after the first decade of occupational exposures. Thus, an update of industrial/occupational health measures is necessary for a safer and healthier work environment.