HBeAg testing is better than quantitative HBsAg assay as an alternative to HBV DNA assay among HBV-infected pregnant women.

INTRODUCTION: Using tenofovir disoproxil fumarate (TDF) is recommended in the 3rd trimester for pregnant women with HBV DNA ≥ 200,000 IU/mL to prevent mother-to-child transmission (MTCT) of hepatitis B virus (HBV). However, HBV DNA quantification is unavailable in many resource-limited areas worldwide, hence prophylaxis is often missed. The aim of this study was to determine whether HBeAg or qHBsAg is a better alternative to HBV DNA testing in HBV-infected pregnant women. METHODOLOGY: In this prospective cohort study, pregnant women with HBV infection were recruited in 3 hospitals from October 2019 to November 2020. Socio-demographic and clinical data were collected. Blood samples were taken for qHBsAg and HBV DNA testing. HBeAg results were collected from the medical records of the participants who visited a doctor during the study. RESULTS: 465 pregnant women met the study criteria. 41.9% were HBeAg positive, 33.3% had high qHBsAg levels (> 104 IU/mL), 38.3% had high HBV DNA levels (≥ 200,000 IU/mL). Pregnant women with high qHBsAg levels were 27 times more likely to have high HBV DNA levels (aOR = 27.0, 95% CI: 11.1-65.5, p < 0.001). Participants who were HBeAg positive were 57.5 times more likely to have high HBV DNA levels (aOR = 57.5, 95% CI: 23.0-140.0, p < 0.001). The sensitivity of qHBsAg and HBeAg was 80% and 94%, respectively; and specificity was 95% and 90%, respectively. CONCLUSIONS: HBeAg testing should be considered over qHBsAg assay as an alternative to HBV DNA assay because of its technical simplicity, lower cost, and fewer missed treatments.

Viral load suppression and acquired HIV drug resistance in adults receiving antiretroviral therapy in Viet Nam: results from a nationally representative survey

Objective@#The purpose of this survey was to estimate the prevalence of viral load (VL) suppression and emergence of HIV drug resistance (HIVDR) among individuals receiving antiretroviral therapy (ART) for 36 months or longer in Viet Nam using a nationally representative sampling method.@*Methods@#The survey was conducted between May and August 2014 using a two-stage cluster design. Sixteen ART clinics were selected using probability proportional to proxy size sampling, and patients receiving ART for at least 36 months were consecutively enrolled. Epidemiological information and blood specimens were collected for HIV-1 VL and HIVDR testing; HIVDR was defined by the Stanford University HIVDR algorithm.@*Results@#Overall, 365 eligible individuals were recruited with a mean age of 38.2 years; 68.4% were men. The mean time on ART was 75.5 months (95% confidence interval [CI]: 69.0–81.9 months), and 93.7% of the patients were receiving non-nucleoside reverse transcriptase inhibitor-based regimens. Of the 365 individuals, 345 (94.7%, 95% CI: 64.1–99.4%) had VL below 1000 copies/mL and 19 (4.6%, 95% CI: 2.8-–7.5) had HIVDR mutations.@*Discussion@#Our nationally representative survey found a high level of VL suppression and a low prevalence of HIVDR among individuals who received ART for at least 36 months in Viet Nam. Continued surveillance for HIVDR is important for evaluating and improving HIV programs.

Sexually transmitted infections in female sex workers in five border provinces of Vietnam.

BACKGROUND: Although high prevalences of sexually transmitted infections (STIs) have been reported among female sex workers (FSWs) in some countries of Asia, there is little data about this issue in Vietnam. GOAL: The goal of this study was to determine 1) the prevalence of selected STIs and correlates of chlamydia or gonococcal infection, and 2) contraceptive practices, STI-related symptoms, and healthcare-seeking behavior in FSWs in border provinces of Vietnam. METHODS: Nine hundred eleven FSWs in five border provinces of Vietnam (Lai Chau, Quang Tri, Dong Thap, An Giang, and Kien Giang) were enrolled in a cross-sectional study between December 2002 and January 2003. Study subjects were interviewed about selected sociodemographic and behavioral characteristics, history of STIs, and information about cohabiting partners by a standard interview schedule. Serologic samples were collected for syphilis and urine specimens for gonorrhea and chlamydia. Univariate and multivariate logistic regression analysis was used to determine behavioral and other selected risk factors for gonorrhea/chlamydia among FSWs. RESULTS: Overall, the prevalences of syphilis, gonorrhea, chlamydia, and gonorrhea/chlamydia among FSWs in the five border provinces were 10.7%, 10.7%, 11.9%, and 19.9%, respectively. The prevalence of gonorrhea/chlamydia was higher in the northern and central regions (27-33%) than in the southern region (11-24%). The prevalence of syphilis was low in Lai Chau (1%), but higher than 10% in the other four border provinces. Among FSWs with cohabiting partners, income < or =33 US$ per month (odds ratio [OR] = 5.8, P = 0.009), ever having worked outside Vietnam (OR = 78.2, P = 0.007), partner's age <30 years (OR = 11.7, P = 0.001), and partner's complaint of burning or pain during sex (OR = 15.6, P = 0.02) were significantly associated with gonorrhea/chlamydia. Among single FSWs, sex work <6 months (OR = 2.6, P <0.001) and ever douching in the last month (OR = 1.7, P = 0.026) were associated with gonorrhea/chlamydia. For all FSWs, a complaint of lower abdominal pain (OR = 1.6, P = 0.028) and sex work <6 months (OR = 2.3, P = 0.001) were significantly associated with gonorrhea/chlamydia. CONCLUSIONS: There is a high prevalence of gonorrhea/chlamydia among FSWs in these border provinces of Vietnam. Correlates of gonorrhea/chlamydia identified in this study could be incorporated into treatment algorithms for cervicitis in FSWs in Vietnam.

Synergistic control of keratinocyte adhesion through muscarinic and nicotinic acetylcholine receptor subtypes.

The biological mechanisms involved in initiating, coordinating, and ultimately terminating cell-cell adhesion in the stratified epithelium are not well understood at present. This study was designed to elucidate the roles of the muscarinic M3, the nicotinic alpha3, and the mixed muscarinic-nicotinic alpha9 acetylcholine receptors in physiologic control of keratinocyte adhesion. Both muscarinic and nicotinic antagonists caused keratinocyte detachment and reversibly increased the permeability of keratinocyte monolayers, indicative of the involvement of both muscarinic and nicotinic pathways in the cholinergic control of keratinocyte adhesion. Since phosphorylation of adhesion proteins plays an important role in rapid assembly and disassembly of intercellular junctions, we measured muscarinic and nicotinic effects on phosphorylation of keratinocyte adhesion molecules. The phosphorylation levels of E-cadherin, beta-catenin, and gamma-catenin increased following pharmacological blockage of muscarinic receptors. Long-term blocking of alpha3, alpha9, and M3 receptor signaling pathways with antisense oligonucleotides resulted in cell-cell detachment and changes in the expression levels of E-cadherin, beta-catenin, and gamma-catenin in cultured human keratinocytes. Simultaneous inhibition of several receptor subtypes with a mixture of antisense oligonucleotides produced intensified abnormalities with cell adhesion. Moreover, altered cell-cell adhesion was found in the stratified epithelium of alpha3, alpha9, and M3 receptor knockout mice. Keratinocytes from these mice exhibited abnormal expression of adhesion molecules at both the protein and the mRNA levels. Thus, our data indicate that the alpha3, alpha9, and M3 acetylcholine receptors play key roles in regulating in a synergistic mode keratinocyte adhesion, most probably by modulating cadherin and catenin levels and activities. These findings may aid in the development of novel methods useful for the treatment of skin adhesion diseases and tumor metastasis.

Pemphigus vulgaris acantholysis ameliorated by cholinergic agonists.

BACKGROUND: Pemphigus vulgaris (PV) is an autoimmune, IgG autoantibody-mediated disease of skin and mucosa leading to progressive blistering and nonhealing erosions. Patients develop autoantibodies to adhesion molecules mediating intercellular adhesion and to keratinocyte cholinergic receptors regulating cell adhesion. OBSERVATIONS: To determine whether a cholinergic agonist can abolish PV IgG-induced acantholysis, litter mates of neonatal athymic nude mice were injected with PV IgG together with carbachol (0.04 micro g/g body weight). None of these mice developed skin lesions. Through in vitro experiments, we measured the expression of adhesion molecules in monolayers of normal human keratinocytes incubated overnight in the presence of 0.25mM carbachol using semiquantitative Western blot and immunofluorescence. Carbachol caused an elevation of the relative amount of E-cadherin in keratinocytes (P<.05) without changing that of plakoglobin (P>.05). The phosphorylation level of E-cadherin and plakoglobin was increased by PV IgG, whereas this effect of PV IgG was attenuated in the presence of 0.5mM carbachol. Pyridostigmine bromide, an acetylcholinesterase inhibitor, produced effects similar to those of carbachol, which helps explain its clinical efficacy in a patient with active PV that was resistant to treatment with systemic glucocorticosteroids. Treatment with pyridostigmine bromide (360 mg/d) in a patient with PV allowed to keep his disease under control at a lower dose of prednisone than that used before starting pyridostigmine bromide treatment. Conclusion Elucidation of the cholinergic control of keratinocyte adhesion merits further consideration because of a potential for the development of novel antiacantholytic therapies using cholinergic drugs.

Pemphigus vulgaris IgG and methylprednisolone exhibit reciprocal effects on keratinocytes.

Pemphigus vulgaris (PV) is a life-threatening autoimmune disease of skin adhesion associated with IgG autoantibodies against keratinocytes (KC). Treatment of PV with systemic corticosteroids is life-saving, but the mechanism of the therapeutic action has not been fully understood. We have developed an animal model that demonstrates that methylprednisolone (MP) can block PV IgG-induced acantholysis, decreasing the extent of keratinocyte detachment in the epidermis of 3-5-day-old nude mice from 77.5 +/- 0.6 to 24.1 +/- 1.5% (p < 0.05). We hypothesized that in addition to immunosuppression, MP may exhibit direct anti-acantholytic effects in epidermis, and we compared the effects of PV IgG and MP on KC. The use of DNA microarray showed that PV IgG down-regulated and MP up-regulated expression of the genes encoding keratinocyte adhesion molecules, antigen-processing proteins, regulators of cell cycle and apoptosis, differentiation markers, Na+,K+-ATPase, protein kinases and phosphatases, and serine proteases and their inhibitors. Overall, PV IgG decreased transcription of 198 genes and increased transcription of 31 genes. MP decreased transcription of 14 genes and increased transcription of 818 genes. Specific effects of PV IgG and MP on keratinocyte adhesion molecules were further investigated by Western blot and immunofluorescence assays. By immunoblotting, MP increased the protein levels of E-cadherin and desmogleins 1 and 3 by 300, 180, and 40%, respectively. Specific staining of KC for E-cadherin and desmogleins 1 and 3 increased by 235, 228, and 148%, respectively. In addition, PV IgG increased the level of phosphorylation of E-cadherin by 42%, beta-catenin by 37%, gamma-catenin by 136%, and desmoglein 3 by 300%, whereas pretreatment with 0.25 mm MP abolished phosphorylation of these adhesion molecules. These results suggested that therapeutic effects of MP in PV include both the up-regulated synthesis and post-translational modification of the keratinocyte adhesion molecules.

The role of peer collaborators on HIV/STis education in Mekong delta

Within 3 year implementing of the project there was the contribution of 24 peer collaborators. In overall the peer collaborators had got rather low education, difficult economical condition, but they were active with rather high efficacy in the access of health education for female sex worker in community. Knowledge about HIV increased year by year with 62%, 89%, 95%. Fundamental knowledge about STIs also increased with 50%, 83%, 92%. The skills of communication was evaluated concurrently with the knowledge. The level of satisfaction through 3 years was 67%, 86% and 94% consecutively. The supply of condom was adequate consistantly.

Desmoglein 4 in hair follicle differentiation and epidermal adhesion: evidence from inherited hypotrichosis and acquired pemphigus vulgaris.

Cell adhesion and communication are interdependent aspects of cell behavior that are critical for morphogenesis and tissue architecture. In the skin, epidermal adhesion is mediated in part by specialized cell-cell junctions known as desmosomes, which are characterized by the presence of desmosomal cadherins, known as desmogleins and desmocollins. We identified a cadherin family member, desmoglein 4, which is expressed in the suprabasal epidermis and hair follicle. The essential role of desmoglein 4 in skin was established by identifying mutations in families with inherited hypotrichosis, as well as in the lanceolate hair mouse. We also show that DSG4 is an autoantigen in pemphigus vulgaris. Characterization of the phenotype of naturally occurring mutant mice revealed disruption of desmosomal adhesion and perturbations in keratinocyte behavior. We provide evidence that desmoglein 4 is a key mediator of keratinocyte cell adhesion in the hair follicle, where it coordinates the transition from proliferation to differentiation.

Functional role of alpha7 nicotinic receptor in physiological control of cutaneous homeostasis.

Non-neuronal nicotinic acetylcholine receptors (nAChRs) are abundantly expressed in skin and their function remains to be elucidated. Herein, we report that cutaneous alpha7 nAChR plays a role in the physiological control of cutaneous homeostasis. We studied in vitro effects of functional inactivation of alpha7 receptor on the expression of apoptosis regulators in keratinocytes (KC) lacking alpha7 nAChR, and extracellular matrix regulators in the skin of alpha7 knockout (KO) mice. Elimination of the alpha7 component of nicotinergic signaling in KC decreased relative amounts of the pro-apoptotic Bad and Bax at both the mRNA and the protein levels, suggesting that alpha7 nAChR is coupled to stimulation of keratinocyte apoptosis. The skin of alpha7 KO mice featured decreased amounts of the extracellular matrix proteins collagen 1alpha1 and elastin as well as the metalloproteinase-1. Taken together, these results suggest an important role for alpha7 nAChR in mediating plethoric effects of non-neuronal acetylcholine on cutaneous homeostasis.

The M4 muscarinic receptor-selective effects on keratinocyte crawling locomotion.

We have investigated how the cholinergic system of epidermal keratinocytes (KC) controls migratory function of these cells. Several molecular subtypes of muscarinic acetylcholine receptors (mAChRs) have been detected in KC. Early results suggested that M(4) is the predominant mAChR regulating cell motility. To determine muscarinic effects on lateral migration of KC, we used an agarose gel keratinocyte outgrowth system (AGKOS) which provides for measurements of the response of large cell populations (> 10(4) cells). Muscarine produced a dose-dependent stimulatory effect on cell migration (p < 0.05). This activity was abolished by atropine, which decreased migration distance when given alone. To identify the mAChR subtype(s) mediating these muscarinic effects, we substituted atropine with subtype-selective antagonists. Tropicamide (M(4)-selective) was more effective at decreasing the migration distance than pirenzepine and 4-DAMP at nanomolar concentrations. We then compared lateral migration of KC obtained from M(4) mAChR knockout mice with that of wild-type murine KC, using AGKOS. In the absence of M(4) mAChR, the migration distance of KC was significantly (p < 0.05) decreased. These results indicate that the M(4) mAChR plays a central role in mediating cholinergic control of keratinocyte migration by endogenous acetylcholine produced by these cells.

Keratinocyte acetylcholine receptors regulate cell adhesion.

We investigated the mechanism mediating cholinergic control of cell-to-cell adhesion of human epidermal keratinocytes (KC) by non-neuronal acetylcholine produced by KC themselves. We first measured cholinergic effects on the expression of desmoglein (Dsg) 1 and 3 in KC using the semi-quantitative immunofluorescence and Western blot assays. Monolayers of KC were treated overnight with 0.25 mM of the cholinergic agonist carbachol (CCh) or the acetylcholinesterase inhibitor pyridostigmine bromide (PBr). Both CCh and PBr increased the relative amounts of Dsg 1 and Dsg 3. To determine the role for cholinergic receptor-mediated phosphorylation of Dsg molecules in assembly/disassembly of keratinocyte desmosomes, we tested the effects of a cholinergic antagonist on keratinocyte adhesion and Dsg phosphorylation status in DJM-1 cell line. Atropine (Atr), 0.02 mM, induced rapid detachment of cells from each other (acantholysis), and also increased phosphorylation of Dsg 3 by 33%. The Atr-dependent phosphorylation of Dsg 3 was inhibited in the presence of 0.5 mM CCh. Thus, keratinocyte cholinergic receptors regulate desmosomal adhesion of KC by altering the level of expression of both Dsg 1 and Dsg 3 and the phosphorylation status of Dsg 3.

Central role of fibroblast alpha3 nicotinic acetylcholine receptor in mediating cutaneous effects of nicotine.

Smoking is associated with aberrant cutaneous tissue remodeling, such as precocious skin aging and impaired wound healing. The mechanism is not fully understood. Dermal fibroblasts (DF) are the primary cellular component of the dermis and may provide a target for pathobiologic effects of tobacco products. The purpose of this study was to characterize a mechanism of nicotine (Nic) effects on the growth and tissue remodeling function of DF. We hypothesized that the effects of Nic on DF result from its binding to specific nicotinic acetylcholine receptors (nAChRs) expressed by these cells and that downstream signaling from the receptors alters normal cell functioning, leading to changes in skin homeostasis. Using RT-PCR and Western blotting, we found that a 24-hour exposure of human DF to 10 micro M Nic causes a 1.9- to 28-fold increase of the mRNA and protein levels of the cell cycle regulators p21, cyclin D1, Ki-67, and PCNA and a 1.7- to 2-fold increase of the apoptosis regulators Bcl-2 and caspase 3. Nic exposure also up-regulated expression of the dermal matrix proteins collagen type Ialpha1 and elastin as well as matrix metalloproteinase-1. Mecamylamine (Mec), the specific antagonist of nAChRs, abolished Nic-induced alterations, indicating that they resulted from a pharmacologic stimulation of nAChRs expressed by DF. To establish the relevance of these findings to a specific nicotinergic pathway, we studied human DF transfected with anti-alpha3 antisense oligonucleotides and murine DF from alpha3 nAChR knockout mice. In both cases, lack of alpha3 was associated with alterations in fibroblast growth and function that were opposite to those observed in DF treated with Nic, suggesting that the nicotinic effects on DF were mostly mediated by alpha3 nAChR. In addition to alpha3, the nAChR subunits detected in human DF were alpha5, alpha7, beta2, and beta4. The exposure of DF to Nic altered the relative amounts of each of these subunits, leading to reciprocal changes in [(3)H]epibatidine-binding kinetics. Thus, some of the pathobiologic effects of tobacco products on extracellular matrix turnover in the skin may stem from Nic-induced alterations in the physiologic control of the unfolding of the genetically determined program of growth and the tissue remodeling function of DF as well as alterations in the structure and function of fibroblast nAChRs.

History and clinical significance of mechanical symptoms in blistering dermatoses: a reappraisal.

In the era before the advent of routine microscopy and immunopathology, mechanical symptoms were described in an attempt to facilitate clinical diagnosis of blistering dermatoses. A plethora of eponyms and signs were described, but no proper original quotations exist. All the eponyms haunt the student and specialist. In the case of an ominous and, therefore, very important clinical phenomenon termed the Nikolskiy sign, this creates confusion about the specific meaning of the term, obscuring diagnosis and delaying initiation of an adequate treatment of pemphigus. We try to set this record straight and go to the sources. Russian, German, French, and English, at the least, are required to properly interpret the relevant descriptions. We provide an accurate interpretation of the major mechanical symptoms pathognomonic for acantholysis, dermoepidermal separation, and peeling of the entire epidermis. Correct performance of the tests and proper interpretation of the results can serve as an invaluable diagnostic tool to assist in the preliminary bedside diagnosis of serious and potentially lethal bullous dermatoses.

Central role of alpha7 nicotinic receptor in differentiation of the stratified squamous epithelium.

Several ganglionic nicotinic acetylcholine receptor (nAChR) types are abundantly expressed in nonneuronal locations, but their functions remain unknown. We found that keratinocyte alpha7 nAChR controls homeostasis and terminal differentiation of epidermal keratinocytes required for formation of the skin barrier. The effects of functional inactivation of alpha7 nAChR on keratinocyte cell cycle progression, differentiation, and apoptosis were studied in cell monolayers treated with alpha-bungarotoxin or antisense oligonucleotides and in the skin of Acra7 homozygous mice lacking alpha7 nAChR channels. Elimination of the alpha7 signaling pathway blocked nicotine-induced influx of 45Ca2+ and also inhibited terminal differentiation of these cells at the transcriptional and/or translational level. On the other hand, inhibition of the alpha7 nAChR pathway favored cell cycle progression. In the epidermis of alpha7-/- mice, the abnormalities in keratinocyte gene expression were associated with phenotypic changes characteristic of delayed epidermal turnover. The lack of alpha7 was associated with up-regulated expression of the alpha3 containing nAChR channels that lack alpha5 subunit, and both homomeric alpha9- and heteromeric alpha9alpha10-made nAChRs. Thus, this study demonstrates that ACh signaling through alpha7 nAChR channels controls late stages of keratinocyte development in the epidermis by regulating expression of the cell cycle progression, apoptosis, and terminal differentiation genes and that these effects are mediated, at least in part, by alterations in transmembrane Ca2+ influx.