Comparison of the effects of high dose testosterone and 19-nortestosterone to a replacement dose of testosterone on strength and body composition in normal men

We examined the extent to which supraphysiological doses of androgen can modify body composition and strength in normally virilized men. In doubly blind tests, 30 healthy young men received testosterone enanthate (TE) or 19-nortestosterone decanoate (ND), at 100 mg/wk or 300 mg/wk for 6 weeks. The TE-100 mg/wk group served as replacement dose comparison, maintaining pretreatment serum testosterone levels, while keeping all subjects blinded to treatment, particularly through reduction in testicular volumes. Isokinetic strength measurements were made for the biceps brachii and quadriceps femoris muscle groups before treatment and 2–3 days after the 6th injection. Small improvements were noted in all groups but the changes were highly variable; a trend to greater and more consistent strength gain occured in the TE-300 mg/wk group. There was no change in weight for TE-100 mg/wk but an average gain of 3 kg in each of the other groups. No changes in 4 skinfold thickness or in estimated percent body fat were observed. Of 15 circumferences, significant increases were observed only for men receiving TE-300 mg/wk (shoulders) and ND-300 mg/wk (shoulders and chest). The data suggest that high dose androgens increase body mass and may increase strength in normal men but, except for a consistent weight gain with greater than replacement doses, the detectable changes were highly variable and relatively small, especially in comparison to the significant alterations which were observed for other markers of androgen action.     

Marked prolongation of porcine renal xenograft survival in baboons through the use of alpha1,3-galactosyltransferase gene-knockout donors and the cotransplantation of vascularized thymic tissue

The use of animal organs could potentially alleviate the critical worldwide shortage of donor organs for clinical transplantation. Because of the strong immune response to xenografts, success will probably depend upon new strategies of immune suppression and induction of tolerance. Here we report our initial results using alpha-1,3-galactosyltransferase knockout (GalT-KO) donors and a tolerance induction approach. We have achieved life-supporting pig-to-baboon renal xenograft survivals of up to 83 d with normal creatinine levels.     

Heart transplantation in baboons using alpha1,3-galactosyltransferase gene-knockout pigs as donors: initial experience

Hearts from alpha1,3-galactosyltransferase knockout pigs (GalT-KO, n = 8) were transplanted heterotopically into baboons using an anti-CD154 monoclonal antibody-based regimen. The elimination of the galactose-alpha1,3-galactose epitope prevented hyperacute rejection and extended survival of pig hearts in baboons for 2-6 months (median, 78 d); the predominant lesion associated with graft failure was a thrombotic microangiopathy, with resulting ischemic injury. There were no infectious complications directly related to the immunosuppressive regimen. The transplantation of hearts from GalT-KO pigs increased graft survival over previous studies.     

Intradermal Immunization with Wall Teichoic Acid (WTA) Elicits and Augments an Anti-WTA IgG Response that Protects Mice from Methicillin-Resistant Staphylococcus aureus Infection Independent of Mannose-Binding Lectin Status

The objectives of this study were to investigate the immune response to intradermal immunization with wall teichoic acid (WTA) and the effect of MBL deficiency in a murine model of infection with methicillin-resistant Staphylococcus aureus (MRSA). WTA is a bacterial cell wall component that is implicated in invasive infection. We tested susceptibility to MRSA infection in wild type (WT) and MBL deficient mice using two strains of MRSA: MW2, a community-associated MRSA (CA-MRSA); and COL, a healthcare-associated MRSA (HA-MRSA). We also performed in vitro assays to investigate the effects of anti-WTA IgG containing murine serum on complement activation and bacterial growth in whole blood. We found that MBL knockout (KO) mice are relatively resistant to a specific MRSA strain, MW2 CA-MRSA, compared to WT mice, while both strains of mice had similar susceptibility to a different strain, COL HA-MRSA. Intradermal immunization with WTA elicited and augmented an anti-WTA IgG response in both WT and MBL KO mice. WTA immunization significantly reduced susceptibility to both MW2 CA-MRSA and COL HA-MRSA, independent of the presence of MBL. The protective mechanisms of anti-WTA IgG are mediated at least in part by complement activation and clearance of bacteria from blood. The significance of these findings is that 1) Intradermal immunization with WTA induces production of anti-WTA IgG; and 2) This anti-WTA IgG response protects from infection with both MW2 CA-MRSA and COL HA-MRSA even in the absence of MBL, the deficiency of which is common in humans.     

Exogenous Zeaxanthin Alleviates Low Temperature Combined with Low Light Induced Photosynthesis Inhibition and Oxidative Stress in Pepper (Capsicum annuum L.) Plants

Low temperature combined with low light (LL) affects crop production, especially the yield and quality of peppers, in northwest China during the winter and spring seasons. Zeaxanthin (Z) is a known lipid protectant and active oxygen scavenger. However, whether exogenous Z can mitigate LL-induced inhibition of photosynthesis and oxidative stress in peppers remains unclear. In this study, we investigated the effects of exogenous Z on photosynthesis and the antioxidant machinery of pepper seedlings subject to LL stress. The results showed that the growth and photosynthesis of pepper seedlings were significantly inhibited by LL stress. In addition, the antioxidant machinery was disturbed by the uneven production and elimination of reactive oxygen species (ROS), which resulted in damage to the pepper. For example, membrane lipid peroxidation increased ROS content, and so on. However, exogenous application of Z before LL stress significantly increased the plant height, stem diameter, net photosynthetic rate (Pn), and stomata, which were obviously closed at LL. The activities of antioxidant enzymes superoxide dismutase (SOD), catalase (CAT), mono de-hydroascorbate reductase (MDHAR), de-hydroascorbate reductase (DHAR), ascorbate peroxidase (APX), and ascorbate oxidase (AAO) improved significantly due to the increased expression of CaSOD, CaCAT, CaAPX, CaMDHAR, and CaDHAR. The ascorbic (AsA) and glutathione (GSH) contents and ascorbic/dehydroascorbate (AsA/DHA) and glutathione/oxidized glutathione (GSH/GSSG) ratios also increased significantly, resulting in the effective removal of hydrogen peroxide (H₂O₂) and superoxide anions (O₂^•−) caused by LL stress. Thus, pre-treatment with Z significantly reduced ROS accumulation in pepper seedlings under LL stress by enhancing the activity of antioxidant enzymes and accumulation of components of the ascorbate–glutathione (AsA–GSH) cycle and upregulated key genes in the AsA–GSH cycle.     

Trends and spatial distribution of animal bites and vaccination status among victims and the animal population,Uganda: A veterinary surveillance system analysis, 2013–2017

Rabies is a vaccine-preventable fatal zoonotic disease. Uganda, through the veterinary surveillance system at National Animal Disease Diagnostics and Epidemiology Centre (NADDEC), captures animal bites (a proxy for rabies) on a monthly basis from districts. We established trends of incidence of animal bites and corresponding post-exposure prophylactic anti-rabies vaccination in humans (PEP), associated mortality rates in humans, spatial distribution of animal bites, and pets vaccinated during 2013–2017. We reviewed rabies surveillance data at NADDEC from 2013–2017. The surveillance system captures persons reporting bites by a suspected rabid dog/cat/wild animal, human deaths due to suspected rabies, humans vaccinated against rabies, and pets vaccinated. Number of total pets was obtained from the Uganda Bureau of Statistics. We computed incidence of animal bites and corresponding PEP in humans, and analyzed overall trends, 2013–2017. We also examined human mortality rates and spatial distribution of animal bites/rabies and pets vaccinated against rabies. We identified 8,240 persons reporting animal bites in Uganda during 2013–2017; overall incidence of 25 bites/ 100,000population. The incidence significantly decreased from 9.2/100,000 in 2013 to 1.3/100,000 in 2017 (OR = 0.62, p = 0.0046). Of the 8,240 persons with animal bites, 6,799 (82.5%) received PEP, decreasing from 94% in 2013 to 71% in 2017 (OR = 0.65, p<0.001). Among 1441 victims, who reportedly never received PEP, 156 (11%) died. Western region had a higher incidence of animal bites (37/100,000) compared to other regions. Only 5.6% (124,555/2,240,000) of all pets in Uganda were vaccinated. There was a decline in the reporting rate (percentage of annual district veterinary surveillance reports submitted monthly to Commissioner Animal Health by districts) of animal bites. While reported animal bites by districts decreased in Uganda, so did PEP among humans. Very few pets received anti-rabies vaccine. Evaluation of barriers to complete reporting may facilitate interventions to enhance surveillance quality. We recommended improved vaccination of pets against rabies, and immediate administration of exposed humans with PEP.     

Exploring optical spectroscopic techniques and nanomaterials for virus detection

Viral infections pose significant health challenges globally by affecting millions of people worldwide and consequently resulting in a negative impact on both socioeconomic development and health. Corona virus disease 2019 (COVID-19) is a clear example of how a virus can have a global impact in the society and has demonstrated the limitations of detection and diagnostic capabilities globally. Another virus which has posed serious threats to world health is the human immunodeficiency virus (HIV) which is a lentivirus of the retroviridae family responsible for causing acquired immunodeficiency syndrome (AIDS). Even though there has been a significant progress in the HIV biosensing over the past years, there is still a great need for the development of point of care (POC) biosensors that are affordable, robust, portable, easy to use and sensitive enough to provide accurate results to enable clinical decision making. The aim of this study was to present a proof of concept for detecting HIV-1 pseudoviruses by using anti-HIV1 gp41 antibodies as capturing antibodies. In our study, glass substrates were treated with a uniform layer of silane in order to immobilize HIV gp41 antibodies on their surfaces. Thereafter, the HIV pseudovirus was added to the treated substrates followed by addition of anti-HIV gp41 antibodies conjugated to selenium nanoparticle (SeNPs) and gold nanoclusters (AuNCs). The conjugation of SeNPs and AuNCs to anti-HIV gp41 antibodies was characterized using UV–vis spectroscopy, transmission electron microscopy (TEM) and zeta potential while the surface morphology was characterized by fluorescence microscopy, atomic force microscopy (AFM) and Raman spectroscopy. The UV–vis and zeta potential results showed that there was successful conjugation of SeNPs and AuNCs to anti-HIV gp41 antibodies and fluorescence microscopy showed that antibodies immobilized on glass substrates were able to capture intact HIV pseudoviruses. Furthermore, AFM also confirmed the capturing HIV pseudoviruses and we were able to differentiate between substrates with and without the HIV pseudoviruses. Raman spectroscopy confirmed the presence of biomolecules related to HIV and therefore this system has potential in HIV biosensing applications.