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The human louse (Pediculus humanus) is an obligatory blood feeding ectoparasite with two ecotypes: the human body louse (Pediculus humanus humanus), a competent vector of several bacterial pathogens, and the human head louse (Pediculus humanus capitis), responsible for pediculosis and affecting millions of people around the globe. GABA (γ-aminobutyric acid) receptors, members of the cys-loop ligand gated ion channel superfamily, are among the main pharmacological targets for insecticides. In insects, there are four subunits of GABA receptors: resistant-to-dieldrin (RDL), glycin-like receptor of drosophila (GRD), ligand-gated chloride channel homologue3 (LCCH3), and 8916 are well described and form distinct phylogenetic clades revealing orthologous relationships. Our previous studies in the human body louse confirmed that subunits Phh-RDL, Phh-GRD, and Phh-LCCH3 are well clustered in their corresponding clades. In the present work, we cloned and characterized a putative new GABA receptor subunit in the human body louse that we named HoCas, for Homologous to Cys-loop α like subunit. Extending our analysis to arthropods, HoCas was found to be conserved and clustered in a new (fifth) phylogenetic clade. Interestingly, the gene encoding this subunit is ancestral and has been lost in some insect orders. Compared to the other studied GABA receptor subunits, HoCas exhibited a relatively higher expression level in all development stages and in different tissues of human body louse. These findings improved our understanding of the complex nature of GABA receptors in Pediculus humanus and more generally in arthropods.

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Human louse Pediculus humanus is a cosmopolitan obligatory blood-feeding ectoparasite causing pediculosis and transmitting many bacterial pathogens. Control of infestation is difficult due to the developed resistance to insecticides that mainly target GABA (γ-aminobutyric acid) receptors. Previous work showed that Pediculus humanus humanus (Phh) GABA receptor subunit resistance to dieldrin (RDL) is the target of lotilaner, a synthetic molecule of the isoxazoline chemical class. To enhance our understanding of how insecticides act on GABA receptors, two other GABA receptor subunits were cloned and characterized: three variants of Phh-grd (glycine-like receptor of Drosophila) and one variant of Phh-lcch3 (ligand-gated chloride channel homolog 3). Relative mRNA expression levels of Phh-rdl, Phh-grd, and Phh-lcch3 revealed that they were expressed throughout the developmental stages (eggs, larvae, adults) and in the different parts of adult lice (head, thorax, and abdomen). When expressed individually in the Xenopus oocyte heterologous expression system, Phh-GRD1, Phh-GRD2, Phh-GRD3, and Phh-LCCH3 were unable to reconstitute functional channels, whereas the subunit combinations Phh-GRD1/Phh-LCCH3, Phh-GRD1/Phh-RDL, and Phh-LCCH3/Phh-RDL responded to GABA in a concentration-dependent manner. The three heteromeric receptors were similarly sensitive to the antagonistic effect of picrotoxin and fipronil, whereas Phh-GRD1/Phh-RDL and Phh-LCCH3/Phh-RDL were respectively about 2.5-fold and 5-fold more sensitive to ivermectin than Phh-GRD1/Phh-LCCH3. Moreover, the heteropentameric receptor constituted by Phh-GRD1/Phh-LCCH3 was found to be permeable and highly sensitive to the extracellular sodium concentration. These findings provided valuable additions to our knowledge of the complex nature of GABA receptors in human louse that could help in understanding the resistance pattern to commonly used pediculicides. SIGNIFICANCE STATEMENT: Human louse is an ectoparasite that causes pediculosis and transmits several bacterial pathogens. Emerging strains developed resistance to the commonly used insecticides, especially those targeting GABA receptors. To understand the molecular mechanisms underlying this resistance, two subunits of GABA receptors were cloned and described: Phh-grd and Phh-lcch3. The heteromeric receptor reconstituted with the two subunits was functional in Xenopus oocytes and sensitive to commercially available insecticides. Moreover, both subunits were transcribed throughout the parasite lifecycle.

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@#Male infertility is a relatively common condition affecting approximately 1 in 20 of the male population. DNA fragmentation is an important factor in the etiology of male infertility. Men with high DNA fragmentation levels have significantly lower odds of conceiving, naturally or through procedures such as intrauterine insemination and IVF. The most common contributing factor of male infertility is smoking. Studies have shown that smoking intensity is positively associated with job demands and stress. Therefore, we believe that work stress increases the nicotine-dependent thus causing lower male fertility rate. As proper protamine to histone ratio is essential to produce viable sperm, smoking is strongly suspected to reduce sperm viability through histone-to-protamine transition abnormalities. These abnormalities, results in sperm with high DNA damage when exposed to excessive free radical. This present study was undertaken to evaluate the relationship of work stress, smoking and sperm quality. A total of 210 infertile patients attending Medical Assisted Contraceptive Clinic (MAC), UKMMC were selected for the study. Smoking status and stress level of patients were collected after obtaining relevant consent. Histone-to-protamine ratio was acquired using Aniline Blue staining and Chromomycin A3 staining respectively. Sperm DNA fragmentation was estimated using Comet Assay. Result revealed that smokers tend to be more stressful (r = .446, p <. 001). The result showed a significantly increased level of histone (r = .385, p <. 001) and incomplete protamination (r = .492, p <. 001) in smokers. The imbalance of histone-to-protamine ratio lead to increase of DNA damage. All the data were analyzed using SPSS version 20.0. Result revealed that patients who smoke are more stressful at work. Higher proportion of abnormal sperm histone to protamine ratio were found among smokers suggesting that cigarette smoking may inversely affect male fertility.

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Male infertility is a relatively common condition affecting approximately 1 in 20 of the male population. DNA fragmentation is an important factor in the etiology of male infertility. Men with high DNA fragmentation levels have significantly lower odds of conceiving, naturally or through procedures such as intrauterine insemination and IVF. The most common contributing factor of male infertility is smoking. Studies have shown that smoking intensity is positively associated with job demands and stress. Therefore, we believe that work stress increases the nicotine-dependent thus causing lower male fertility rate. As proper protamine to histone ratio is essential to produce viable sperm, smoking is strongly suspected to reduce sperm viability through histone-to-protamine transition abnormalities. These abnormalities, results in sperm with high DNA damage when exposed to excessive free radical. This present study was undertaken to evaluate the relationship of work stress, smoking and sperm quality. A total of 210 infertile patients attending Medical Assisted Contraceptive Clinic (MAC), UKMMC were selected for the study. Smoking status and stress level of patients were collected after obtaining relevant consent. Histone-to-protamine ratio was acquired using Aniline Blue staining and Chromomycin A3 staining respectively. Sperm DNA fragmentation was estimated using Comet Assay. Result revealed that smokers tend to be more stressful (r = .446, p <. 001). The result showed a significantly increased level of histone (r = .385, p <. 001) and incomplete protamination (r = .492, p <. 001) in smokers. The imbalance of histone-to-protamine ratio lead to increase of DNA damage. All the data were analyzed using SPSS version 20.0. Result revealed that patients who smoke are more stressful at work. Higher proportion of abnormal sperm histone to protamine ratio were found among smokers suggesting that cigarette smoking may inversely affect male fertility.

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Growing teratoma syndrome is rare and usually it occurs in the younger aged group. The use of chemotherapy following initial surgical resection will yield the diagnosis following tumour enlargement. Complete resection is usually curative and renders better prognosis.

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A 33 year-old woman had an emergency caesarean section for retained second twin which was complicated by utero-cutaneous fistula due to red degeneration of intramural fibroid. The utero-cutaneous communication was demonstrated by an examination under anaesthesia using dye test. She then underwent excision of the fistula tract and myomectomy. She recovered well following the surgery. This is the first case of utero-cutaneous fistula where the communication is between the endometrial cavity and skin lesion via a necrotic intramural fibroid following caesarean section. Fistulogram might fail to demonstrate the communication. In highly suspected case, other modalities of investigations could be utilised.

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