Potential Mutations Associated With Occult Hepatitis B Virus Status

Context:

Occult hepatitis B virus (HBV) status (OHBS) is simply defined as the presence of HBV DNA in the liver (with or without detectable HBV DNA in the serum), in the absence of serum HBV surface antigen (HBsAg). Importance of OHBS is mostly clinical, related to its possible role in spreading through blood transfusion and liver transplantation; causing classic forms of HBV. Mechanisms underlying this entity are poorly defined. Several possibilities have been suggested, with major classification into two groups: defective host immune response and viral replication activity through mutations of HBV DNA sequence. Mutations are extensively investigated in all four overlapping open reading frames (ORFs) of HBV genome, to define their possible role in the pathogenesis of OHBS. Some of these mutations like S-escape mutants could not be detected by the routine available assays, making them difficult to diagnosis. Therefore, trying to detect this covert condition could be more helpful for defining better preventive and therapeutic strategies.

Evidence Acquisition:

In the present study we provided an in-depth review of the most important new data available on different mutations in HBV genome of patients with OHBS, which may play a role in the pathogenesis of OHBS. The data were collected through reviewing the full-text articles, identified by the PubMed search, using the following keywords and their different combinations: occult hepatitis B, HBV genome, "a" determinant, HBV open reading frames, S mutations, X mutations, P mutations and C mutations.

Results:

Variants within the major hydrophilic region (MHR) of the HBsAg, deletions in the pre-S1region, codon stop in the S open reading frames (ORF), sporadic non common mutations, some mutations affecting the posttranslational production of HBV proteins in the S ORF like deletion mutations, mutations in start codon and nucleotide changes in the X ORF, deletion and point mutations in P ORF and sometimes, nucleotide substitution in the C ORF are among the assumed mutations detected to have a role in OHBS appearance.

Conclusions:

Studies mostly lacked a control group and the whole-length HBV sequencing was scant with conflicting results, suggesting that OHBS is often a result of multiple mechanisms. Additional studies on full-length HBV genomes from occult and non-occult HBV cases may shed more light on the interplay between different mechanisms involved in the pathogenesis of OHBS.     

Knowledge and attitudes of physicians in private practice towards HIV/AIDS in Mashhad, Iran

Being responsible for providing care for HIV/AIDS in a society, physicians should be knowledgeable and have favourable attitudes. We designed a cross-sectional study to assess knowledge and attitudes towards HIV/AIDS of private practicing physicians in Mashhad, Iran. A total of 346 general practitioners and specialists completed anonymous self-administered questionnaires with response rate of 91.1%. For knowledge questions, the mean proportion of correct responses was 53.5% (±13.2). Misconceptions about HIV transmission were the main areas of insufficient knowledge. Surprisingly only 20% knew how to manage a patient who had experienced sexual contact with an HIV-positive partner. While 84% disagreed that 'HIV-infected individuals deserved to catch infection' owing to high-risk behaviours, 38% sympathized less with people who were infected via extramarital sex. It seems that knowledge and attitudes towards HIV/AIDS among the studied physicians is not favourable and is an area that requires attention to enable effective management of the disease in Iran.     

Reversal of Prenatal Morphine Exposure-Induced Memory Deficit in Male But Not Female Rats

Impaired memory performance in offspring is one of the long-lasting neurobehavioral consequences of prenatal opiate exposure. Here, we studied the effects of prenatal morphine exposure on inhibitory avoidance memory performance in male and female offspring and also investigated whether these deficits are reversible during the postnatal development. Pregnant Wistar rats received morphine sulfate through drinking water, from the first day of gestation up to the day 13, M_1–13, or to the time of delivery, M_1–21. Four- and ten-week-old (adolescent and adult, respectively) male and female offspring were subjected to behavioral assays and then analysis of proteins involved in apoptosis or in synaptic plasticity. Results revealed that adolescent and adult female rats failed in passive avoidance retention task in both M_1–13 and M_1–21 groups. Adolescent and adult male offspring were similar to control animals in M_1–13 group. However M_1–21 impaired retention task in prepubertal male offspring, and this memory loss was repaired in postpubertal stage. Consistently, Bax/Bcl-2 ratio and cleaved caspase-3 were significantly increased in both M_1–13 and M_1–21 adolescent and adult female rats, but only in M_1–21 adolescent male rats. Furthermore, prenatal morphine exposure reduced the expression of brain-derived neurotrophic factor precursor protein in adolescent and adult female offspring and also decreased p-ca(2+)/calmodulin-dependent kinase II/ca(2+)/calmodulin-dependent kinase II ratio in adolescent male and female rats. Altogether, the results show that prenatal morphine exposure, depending on the time or duration of exposure, has distinct effects on male and female rats, and postnatal development may reverse these deficits more likely in males.     

Trunk exercise training improves muscle size,strength, and function in older adults: A randomized controlled trial

The aim of this study was to assess the effectiveness of a multimodal exercise program to increase trunk muscle morphology and strength in older individuals, and their associated changes in functional ability. Using a single‐blinded parallel‐group randomized controlled trial design, 64 older adults (≥60 years) were randomly allocated to a 12‐week exercise program comprising walking and balance exercises with or without trunk strengthening/motor control exercises; followed by a 6‐week walking‐only program (detraining; 32 per group). Trunk muscle morphology (ultrasound imaging), strength (isokinetic dynamometer), and functional ability and balance (6‐Minute Walk Test; 30 second Chair Stand Test; Sitting and Rising Test; Berg Balance Scale, Multi‐Directional Reach Test; Timed Up and Go; Four Step Square Test) were the primary outcome measures. Sixty‐four older adults (mean [SD]; age: 69.8 [7.5] years; 59.4% female) were randomized into two exercise groups. Trunk training relative to walking‐balance training increased (mean difference [95% CI]) the size of the rectus abdominis (2.08 [1.29, 2.89] cm²), lumbar multifidus (L4/L5:0.39 [0.16, 0.61] cm; L5/S1:0.31 [0.07, 0.55] cm), and the lateral abdominal musculature (0.63 [0.40, 0.85] cm); and increased trunk flexion (29.8 [4.40, 55.31] N), extension (37.71 [15.17, 60.25] N), and lateral flexion (52.30 [36.57, 68.02] N) strength. Trunk training relative to walking‐balance training improved 30‐second Chair Stand Test (5.90 [3.39, 8.42] repetitions), Sitting and Rising Test (1.23 [0.24, 2.23] points), Forward Reach Test (4.20 [1.89, 6.51] cm), Backward Reach Test (2.42 [0.33, 4.52] cm), and Timed Up and Go Test (?0.76 [?1.40, ?0.13] seconds). Detraining led to some declines but all outcomes remained significantly improved when compared to pre‐training. These findings support the inclusion of trunk strengthening/motor control exercises as part of a multimodal exercise program for older adults.     

Synthesis and anticholinesterase activity of new substituted benzo[d]oxazole‐based derivatives

A series of novel benzo[d]oxazole derivatives ( 6a–n ) have been synthesized and biologically evaluated as potential inhibitors of acetylcholinesterases (AChE) and butyrylcholinesterase (BChE). The chemical structures of all final compounds were confirmed by spectroscopic methods. In vitro studies showed that most of the synthesized compounds are potent acetylcholinesterase and butyrylcholinesterase inhibitors. Among them, compounds 6a and 6j strongly inhibited AChE and BChE activities with IC₅₀ values of 1.03–1.35 and 6.6–8.1 μm , respectively. Docking studies also provided the binding modes of action and identified hydrophobic pi forces as the main interaction.     

Effect of melatonin supplementation on sleep quality: a systematic review and meta-analysis of randomized controlled trials

Journal of Neurology - The Present study was conducted to systematically review the effect of the melatonin on sleep quality. We summarized evidence from randomized clinical trials (RCTs) that...     

Comparison of novel risk factors for cardiovascular disease between hemodialysis patients with and without protein-energy wasting

Purpose

The present study was designed to compare novel risk factors for cardiovascular diseases (CVD) between hemodialysis (HD) patients with or without protein-energy wasting (PEW) for determining novel risk factors for CVD in HD patients with PEW.

Methods

In this cross-sectional study, 291 HD patients were randomly selected from among 2,302 adult HD patients in Tehran hemodialysis centers. The presence of PEW in HD patients was determined by subjective global assessment. In addition, 4 mL blood was obtained before dialysis and analyzed for serum concentrations of novel risk factors for CVD, including C-reactive protein (CRP), soluble intercellular adhesion molecule type 1 (sICAM-1), soluble vascular cell adhesion molecule type 1 (sVCAM-1), sE-selectin, malondialdehyde (MDA), nitric oxide (NO), endothelin-1 and lipoprotein (a) [Lp (a)].

Results

Serum CRP and sICAM-1 were significantly higher in HD patients with PEW as compared to those without PEW (P < 0.01), whereas there were no significant differences in serum sVCAM-1, sE-selectin, MDA, NO, endothelin-1 and Lp (a) between the two groups. Serum CRP and sICAM-1 were significantly higher in HD patients with PEW type IIa and IIb than in those with PEW type I (P < 0.01).

Conclusion

The present study indicates that serum CRP and sICAM-1, as two CVD risk factors, increase in HD patients with PEW as compared to those without PEW and these increases occur in HD patients with PEW type IIa and IIb who have inflammation.