Surface gene mutations of hepatitis B virus among high-risk patients with occult hepatitis B virus infection

Surface gene mutants of hepatitis B virus (HBV) have been reported in a variety of patient groups. Because of limited data regarding these mutations in patients with occult HBV infections; we aimed to determine these mutations among high-risk patients with occult HBV infection. The presence of HBV-DNA was determined in patients with isolated anti-HBc by real-time polymerase chain reaction (PCR). Then, surface gene region was amplified by nested PCR and mutations were analyzed after sequencing. The mutations that resulted in nonfunctional hepatitis B surface antigen (HBsAg) were insertion of single nucleotide in 2 cases, which causes frameshift and single-nucleotide replacement, and premature stop codons at Leu15 and Gly10 in the other 2 cases. Amino acid substitution at amino acid position 207(S207N) was found in the other isolates. Our study suggested that “a” region mutations did not play a major role in HBsAg detection, and other genetic and nongenetic factors may be responsible for failure to detect HBsAg by routine laboratory tests.     

Green-synthetized selenium nanoparticles using berberine as a promising anticancer agent

Objective: The chemo-preventative and therapeutic properties of selenium nanoparticles(Se NPs) have been documented over recent decades and suggest the potential uses of Se NPs in medicine. Biogenic Se NPs have higher biocompatibility and stability than chemically synthesized nanoparticles, which enhances their medical applications, especially in the field of cancer therapy. This study evaluated the potential of green-synthetized Se NPs by using berberine(Ber) as an antitumor agent and elucidated the mechanism by which these molecules combat Ehrlich solid tumors(ESTs).Methods: Se NPs containing Ber(Se NPs-Ber) were synthesized using Ber and Na2 Se O3 and characterized with Fourier transform infrared spectroscopy. Sixty male Swiss albino mice were then acclimatized for one week, injected with Ehrlich ascites tumor cells, and divided into four groups: EST, EST + cisplatin(5 mg/kg), EST + Ber(20 mg/kg), and EST + Se NPs-Ber(0.5 mg/kg). At the end of a 16-day observation period, 12 mice from each group were euthanized to analyze differences in the body weight, tumor size,gene expression, and oxidative stress markers in the four groups. Three mice from each group were kept alive to compare the survival rates.Results: Treatment with Se NPs-Ber significantly improved the survival rate and decreased the body weight and tumor size, compared to the EST group. Se NPs-Ber reduced oxidative stress in tumor tissue,as indicated by a decrease in the lipid peroxidation and nitric oxide levels and an increase in the glutathione levels. Moreover, Se NPs-Ber activated an apoptotic cascade in the tumor cells by downregulating the B-cell lymphoma 2(Bcl-2) expression rate and upregulating the Bcl-2-associated X protein and caspase-3 expression rates. Se NPs-Ber also considerably improved the histopathological alterations in the developed tumor tissue, compared to the EST group.Conclusion: Our study provides a new insight into the potential role of green-synthesized Se NPs by using Ber as a promising anticancer agent, these molecules could be used alone or as supplementary medication during chemotherapy.     

Lack of occult hepatitis B virus infection among blood donors with isolated hepatitis B core antibody living in an HBV low prevalence region of Iran

BackgroundOccult hepatitis B virus (HBV) infection in blood donors is considered a potential threat for the safety of the blood supply, however conclusive studies on this issue are lacking. The aim of this study was to assess the occult HBV infection in blood donors with isolated hepatitis B core antibody (anti-HBc) living in the city of Arak, in the Central Province of Iran, as a low prevalence region for HBV.MethodsA total of 531 voluntary blood donors in Arak, Iran were included in this study. Hepatitis B surface antigen (HBsAg), hepatitis B surface antibody (anti-HBs), anti-HBc, and hepatitis C antibody (anti-HCV) were tested in all subjects. The presence of HBV-DNA was determined quantitatively in plasma samples of cases with isolated anti-HBc (HBsAg-negative, anti-HBs-negative, and anti-HBc-positive) by real-time PCR using the artus HBV RG PCR kit on the Rotor-Gene 3000 real-time thermal cycler.ResultsOf 531 subjects enrolled in this study, 11 (2.1%, 95% confidence interval 0.8–3.2%) had isolated anti-HBc. HBV-DNA was not detected in any of the cases with isolated anti-HBc.ConclusionsOur study showed that all the blood donors with isolated anti-HBc were negative for HBV-DNA, and occult HBV infection did not occur in the blood donors of this low prevalence region for HBV infection.     

Executive functions of children with developmental dyspraxia: Assessment combining neuropsychological and ecological tests

ObjectiveTo assess executive function in children with developmental dyspraxia.Patients and methodInclusion criteria: children aged 8 years to 12 years 5 months at the time of the study, diagnosed with developmental dyspraxia between January, 2008 and August, 2009 by a multidisciplinary team in one single center.Assessment tools(1) Paper-and-pencil neuropsychological and ecological tests to assess flexibility, planning, inhibition and prospective memory; (2) two questionnaires answered by parents; (3) the ‘Children's Cooking Task’ (CCT), an ecological task performed in a real environment (Chevignard et al., 2009 [15]). In this last test, children were compared to matched controls. Non-parametric statistical tests were used.ResultsThirteen patients participated in the study (11 boys–2 girls; mean age 10.3 years [SD = 1.3]). Neuropsychological tests highlighted planning and inhibition disorders, but no impaired flexibility. For more than half of the children, the questionnaires indicated impaired executive functions in daily life tasks. Finally, patients showed a significantly increased rate of errors during the CCT, compared with the control group (P < 0.001).ConclusionOverall results suggest that some children diagnosed with developmental dyspraxia also exhibit executive function disorders. Ecological tests seem more sensitive for identifying executive function disorders than conventional tests.     

Meta‐Analysis on Induction Chemotherapy in Locally Advanced Nasopharyngeal Carcinoma

PurposeConcurrent chemo radiotherapy (CCRT) has been the standard of care in locally advanced nasopharyngeal carcinoma (LA‐NPC) for many years. The role of induction chemotherapy (ICT) has always been controversial. This systematic review and meta‐analysis investigates the value of adding ICT to CCRT in LA‐NPC.Materials and MethodsTwo reviewers independently assessed the eligibility of randomized controlled trials (RCTs) comparing ICT followed by CCRT versus CCRT alone, including treatment‐naive adult patients with histologically proven nonmetastatic LA‐NPC.ResultsEight RCTs with in total 2,384 randomized patients, of whom 69% had N2–N3 disease, were selected. ICT was the allocated treatment in 1,200 patients, of whom 1,161 actually received this. Treatment compliance varied, with a median rate of 92% (range, 86%–100%) of patients receiving all cycles of ICT. The percentage of patients completing radiotherapy was 96% and 95% [(Combined Risk difference(CRD)= 0.004; 95% Confidence Interval (CI) –0.001–0.01; p = 0.14)] in the ICT group and CCRT group, respectively, whereas chemotherapy during radiotherapy could be completed in only 28% of the ICT group versus 61% in the CCRT group (CRD, −0.243; 95% CI, −0.403 to −0.083; p = .003). Grade 3–4 acute toxicity was mostly hematologic during the ICT phase (496 events vs. 191 nonhematologic) and was predominant in the ICT group (1,596 events vs. 1,073 in the CCRT alone group) during the CCRT. Adding ICT to CCRT provided a significant benefit in overall survival (hazard ratio [HR], 0.680; 95% CI, 0.511–0.905; p = .001) and progression‐free survival (HR, 0.657; 95% CI, 0.568–0.760; p < .001).ConclusionAlthough ICT followed by CCRT is associated with more acute toxicity and a lower compliance of the chemotherapy during the CCRT phase, this association resulted in a clinically meaningful survival benefit. ICT should be considered as a standard option in patients with LA‐NPC, but further study on optimal patient selection for this treatment is warranted.Implications for PracticeLocally advanced nasopharyngeal carcinoma (LA‐NPC) is a relatively common disease in some parts of the world, with a rather poor prognosis due to its high metastatic potential. The role of induction chemotherapy (ICT) has always been controversial. This meta‐analysis found that ICT followed by concurrent chemoradiotherapy (CCRT) in LA‐NPC is associated with a significant clinical improvement in both overall survival and progression‐free survival compared with CCRT alone. ICT should be considered as a standard option in patients with LA‐NPC.     

Lactate transporters in the rat barrel cortex sustain whisker-dependent BOLD fMRI signal and behavioral performance

Lactate is an efficient neuronal energy source, even in presence of glucose. However, the importance of lactate shuttling between astrocytes and neurons for brain activation and function remains to be established. For this purpose, metabolic and hemodynamic responses to sensory stimulation have been measured by functional magnetic resonance spectroscopy and blood oxygen level-dependent (BOLD) fMRI after down-regulation of either neuronal MCT2 or astroglial MCT4 in the rat barrel cortex. Results show that the lactate rise in the barrel cortex upon whisker stimulation is abolished when either transporter is down-regulated. Under the same paradigm, the BOLD response is prevented in all MCT2 down-regulated rats, while about half of the MCT4 down-regulated rats exhibited a loss of the BOLD response. Interestingly, MCT4 down-regulated animals showing no BOLD response were rescued by peripheral lactate infusion, while this treatment had no effect on MCT2 down-regulated rats. When animals were tested in a novel object recognition task, MCT2 down-regulated animals were impaired in the textured but not in the visual version of the task. For MCT4 down-regulated animals, while all animal succeeded in the visual task, half of them exhibited a deficit in the textured task, a similar segregation into two groups as observed for BOLD experiments. Our data demonstrate that lactate shuttling between astrocytes and neurons is essential to give rise to both neurometabolic and neurovascular couplings, which form the basis for the detection of brain activation by functional brain imaging techniques. Moreover, our results establish that this metabolic cooperation is required to sustain behavioral performance based on cortical activation.

In the past 25 y, a major revolution in the field of brain energy metabolism has occurred. While it was believed classically that glucose is the sole valuable energy substrate for neurons, it is now admitted that under certain circumstances, alternative substrates can serve as fuels and replace glucose, at least partially, even in the adult brain. This is the case for lactate. Indeed, it was shown that lactate provided from the periphery through the blood circulation is efficiently used by the brain in animals (1) and humans (2–4). In addition to peripheral supply, the brain itself has the capacity to internally produce lactate from blood-borne glucose. This process of activity-dependent lactate transfer is named the astrocyte–neuron lactate shuttle (ANLS) (5) and has received a large support in the literature based on in vitro (6, 7), ex vivo (1), and in vivo experiments (8–11). It was also shown that lactate supply by glial cells to neurons is a fundamental process that has been conserved during evolution, as it was found to be present in invertebrates as well (e.g., flies) (12, 13). Nevertheless, some recent studies have provided evidence that direct glucose utilization by neurons also takes place during activation (14, 15). It might be essential for some aspects of neurotransmission (16) or when metabolized via the pentose phosphate pathway to regenerate glutathione and ensure antioxidant protection (17). These observations call for further in vivo investigations to assess the contribution of these energy-supply modes to sustain brain activities, ranging from metabolic and hemodynamic responses associated with brain activation to behavioral performances.It has been well documented that activation of a brain region (e.g., hippocampus or cortex) leads to a transient increase in lactate concentration within the activated area in rodents (18–20) and in humans (21, 22). Such an observation might reflect a transient mismatch between lactate production attributed to astrocytes and utilization/disposal by other brain cells, although the importance of each remains to be confirmed in vivo. The capacity to release or utilize lactate is determined by the expression of specific transporters, named monocarboxylate transporters (MCTs). Three members of this family have been identified in the central nervous system (23): MCT2 is the predominant neuronal lactate transporter (24); MCT4 expression is prominent on astrocytes (25); while MCT1 expression is more ubiquitous with strong expression on endothelial cells of blood vessels as well as on glial cells (26). Previously, it was shown that reducing MCT2 expression (which allows neuronal lactate uptake) interfered with blood oxygen level-dependent (BOLD) fMRI signal, which depends on local, activity-dependent change in blood flow and is used as a surrogate marker for neuronal activity to perform functional brain imaging (20). Recently, new viral vector tools have been developed that allow the down-regulation of either MCT2 or MCT4 expression in a cell-specific manner in vivo (27). In the present study, we took advantage of this approach to determine the importance of both transporters—and by extension, of lactate shuttling between astrocytes and neurons—in both metabolic and hemodynamic responses, as well as in behavioral performances associated with activation of the whisker-to-barrel system in rats.     

A 1D Model for Predicting Heat and Moisture Transfer through a Hemp-Concrete Wall Using the Finite-Element Method

Plant-based concrete is a construction material which, in addition to having a very low environmental impact, exhibits excellent hygrothermal comfort properties. It is a material which is, as yet, relatively unknown to engineers in the field. Therefore, an important step is to implement reliable mass-transfer simulation methods. This will make the material easy to model, and facilitate project design to deliver suitable climatic conditions. In recent decades, numerous studies have been carried out to develop models of the coupled transfers of heat, air and moisture in porous building envelopes. Most previous models are based on Luikov’s theory, considering mass accumulation, air and total pressure gradient. This theory considers the porous medium to be homogeneous, and therefore allows for hygrothermal transfer equations on the basis of the fundamental principles of thermodynamics. This study presents a methodology for solving the classical 1D (one-dimensional) HAM (heat, air, and moisture) hygrothermal transfer model with an implementation in MATLAB. The resolution uses a discretization of the problem according to the finite-element method. The detailed solution has been tested on a plant-based concrete. The energy and mass balances are expressed using measurable transfer quantities (temperature, water content, vapor pressure, etc.) and coefficients expressly related to the macroscopic properties of the plant-based concrete (thermal conductivity, specific heat, water vapor permeability, etc.), determined experimentally. To ensure this approach is effective, the methodology is validated on a test case. The results show that the methodology is robust in handling a rationalization of the model whose parameters are not ranked and not studied by their degree of importance.