Prospects for the sustainability of delivering the basic package of Health Services in Afghanistan: a stakeholder analysis

This study explored the readiness of stakeholders in Afghanistan for sustaining delivery of the Basic Package of Health Services (BPHS) without external technical and financial assistance. A stakeholder analysis was applied using qualitative methods. Fifteen stakeholders were purposively drawn from the Afghanistan ministries of public health and finance, political representatives, development partners, nonprofit organizations and public health experts. Data were collected through in-depth interviews with the stakeholders and desk review of pertinent documents. We found that sustainability of the BPHS in Afghanistan is questionable as stakeholders are sub optimally organized to come up with effective alternatives. Uneven ownership and divisive positioning are bottlenecks to the evolution of a realistic continuation plan. Those with the most significant influence are lukewarm, while those who are most supportive have the least influence. Sustainability needs to be tackled at the start in designing the BPHS rather than in the wake of eventual donor withdrawal

Contact dermatitis: one for the books

Allergic contact dermatitis (ACD) is a frequent problem, often caused from repeated exposure to an object or substance related to the patient's routine activities. We present a case of a well-demarcated, erythematous, scaly plaque on a finger caused from reading with an e-book device. Although metal from mobile devices can cause ACD, mobile device cases may cause irritation or contain additives that can also cause contact dermatitis. Similar presentations of contact dermatitis may become more common as technology use increases

the CUTHIVAC-001 randomized trial

Targeting of different tissues via transcutaneous (TC), intradermal (ID) and intramuscular (IM) injection has the potential to tailor the immune response to DNA vaccination. In this Phase I randomised controlled clinical trial in HIV-1 negative volunteers we investigate whether the site and mode of DNA vaccination influences the quality of the cellular immune responses. We adopted a strategy of concurrent immunization combining IM injection with either ID or TC administration. As a third arm we assessed the response to IM injection administered with electroporation (EP). The DNA plasmid encoded a MultiHIV B clade fusion protein designed to induce cellular immunity. The vaccine and regimens were well tolerated. We observed differential shaping of vaccine induced virus-specific CD4 + and CD8 + cell-mediated immune responses. DNA given by IM + EP promoted strong IFN-γ responses and potent viral inhibition. ID + IM without EP resulted in a similar pattern of response but of lower magnitude. By contrast TC + IM (without EP) shifted responses towards a more Th-17 dominated phenotype, associated with mucosal and epidermal protection. Whilst preliminary, these results offer new perspectives for differential shaping of desired cellular immunity required to fight the wide range of complex and diverse infectious diseases and cancers

Spectrophotometric Determination of Sulfanilamide in Pure and in Synthetic Sample based on Condensation Reaction Method

A new, Simple, sensitive and accurate spectrophotometric methods have been developed for the determination of sulfanilamide (SNA) drug in pure and in synthetic sample. This method based on the reaction of sulfanilamide (SNA) with 1,2-napthoquinone-4-sulphonic acid (NQS) to form N-alkylamono naphthoquinone by replacement of the sulphonate  group of the naphthoquinone sulphonic acid by an amino group. The colored chromogen shows absorption maximum at 455 nm. The optimum conditions of condensation reaction forms were investigated by: (1) univariable method, by optimizing the effect of experimental variables; (different bases, reagent concentration, borax concentration and reaction time),     (2) central  composite design (CCD) including the effect of three experimental factors (reagent concentration, borax concentration, and reaction time). The linearity ranges of sulfanilamide are (5-30 µg.mL-1) at 455 nm with molar absorptivity (6.9568×104 - 7.0774×104 L.mol-1.cm-1), Sandell's sensitivity index (2.4753 - 2.4330 μg.cm-2) and detection limit of (0.546 – 0.536 µg.mL-1) for each procedure respectively. The results showed there are no interferences of excipients on the determination of the drug. The proposed method has been successfully applied for the determination of sulfanilamide in pure and in synthetic sample. Keywords: Spectrophotometric determination, Sulfanilamide, Central  composite design, 1, 2-napthoquinone-4-sulphonic acid (NQS)

An organelle-specific protein landscape identifies novel diseases and molecular mechanisms

Cellular organelles provide opportunities to relate biological mechanisms to disease. Here we use affinity proteomics, genetics and cell biology to interrogate cilia: poorly understood organelles, where defects cause genetic diseases. Two hundred and seventeen tagged human ciliary proteins create a final landscape of 1,319 proteins, 4,905 interactions and 52 complexes. Reverse tagging, repetition of purifications and statistical analyses, produce a high-resolution network that reveals organelle-specific interactions and complexes not apparent in larger studies, and links vesicle transport, the cytoskeleton, signalling and ubiquitination to ciliary signalling and proteostasis. We observe sub-complexes in exocyst and intraflagellar transport complexes, which we validate biochemically, and by probing structurally predicted, disruptive, genetic variants from ciliary disease patients. The landscape suggests other genetic diseases could be ciliary including 3M syndrome. We show that 3M genes are involved in ciliogenesis, and that patient fibroblasts lack cilia. Overall, this organelle-specific targeting strategy shows considerable promise for Systems Medicine

Charge Transport in UV-Oxidized Graphene and Its Dependence on the Extent of Oxidation

Graphene oxides with different degrees of oxidation are prepared by controlling UV irradiation on graphene, and the charge transport and the evolution of the transport gap are investigated according to the extent of oxidation. With increasing oxygenous defect density [Formula: see text] , a transition from ballistic to diffusive conduction occurs at [Formula: see text] cm [Formula: see text] and the transport gap grows in proportion to [Formula: see text]. Considering the potential fluctuation related to the [Formula: see text] puddle, the bandgap of graphene oxide is deduced to be [Formula: see text] meV. The temperature dependence of conductivity showed metal–insulator transitions at [Formula: see text] cm [Formula: see text] , consistent with Ioffe–Regel criterion. For graphene oxides at [Formula: see text] cm [Formula: see text] , analysis indicated charge transport occurred via 2D variable range hopping conduction between localized [Formula: see text] domain. Our work elucidates the transport mechanism at different extents of oxidation and supports the possibility of adjusting the bandgap with oxygen content

Comprehensive overview of the toxicities of small-molecule cryoprotectants for carnivorous spermatozoa: foundation for computational cryobiotechnology

BackgroundThe specific and non-specific toxicities of cryoprotective agents (CPAs) for semen or spermatozoa cryopreservation/vitrification (SC/SV) remain challenges to the success of assisted reproductive technologies.ObjectiveWe searched for and integrated the physicochemical and toxicological characteristics of small-molecule CPAs as well as curated the information of all extenders reported for carnivores to provide a foundation for new research avenues and computational cryobiology.MethodsThe PubMed database was systematically searched for CPAs reported in SC/SV of carnivores from 1964 to 2024. The physicochemical features, ADMET parameters, toxicity classes, optimized structures, biological activities, thermodynamic equilibrium constants, and kinetic parameters were curated and assessed computationally.ResultsSixty-two relevant papers pertaining to CPAs used in SC/SV were found, and 11 CPAs were selected. Among the properties of CPAs, the molecular weight range (59–758 g/mol), melting point (−60°C to 236°C), XlogP3 (−4.5 to 12.9), topological polar surface area (TPSA; 20–160 Å2), Caco2 permeability (−0.62 to 1.55 log(Papp) in 10–6 cm/s), volume of distribution (−1.04 to 0.19 log L/kg), unbound fraction of a CPA in plasma (0.198–0.895), and Tetrahymena pyriformis toxicity (log µg/L; −2.230 to 0.285) are reported here. Glutathione, dimethyl formamide, methyl formamide, and dimethyl sulfoxide were used as the P-glycoprotein substrates. Ethylene glycol, dimethyl sulfoxide, dimethyl formamide, methyl formamide, glycerol, and soybean lecithin showed Caco2 permeabilities in this order, whereas fructose, glutathione, glutamine, glucose, and citric acid were not Caco2-permeable. The CPAs were distributed in various compartments and could alter the physiological properties of both seminal plasma and spermatozoa. Low volume distributions of all CPAs except glucose indicate high water solubility or high protein binding because higher amounts of the CPAs remain in the seminal plasma.ConclusionADMET information of the CPAs and extenders in the bipartite compartments of seminal plasma and intracellular spaces of spermatozoa are very important for systematic definition and integration because the nature of the extenders and seminal plasma could alter the physiology of cryopreserved spermatozoa

Slow graft function after pediatric renal transplantation from volunteer live donors

Slow graft function (SGF) may occur during the early post-transplant period. In this paper, we present our findings regarding SGF after pediatric renal transplantation and its predictive variables. From 1985 to 2004, a total of 300 pediatric renal transplants were performed at our institution. A total of 10 cases with SGF and 50 controls that were operated by the same surgeons were enrolled in this study. The mean age of the recipients and donors was 11.4 (3-15 yr) and 28.05 yr (20-50 yr), respectively. All kidneys were retrieved from living donors. We compared patients with SGF with controls regarding four independent variables: age difference between donors and recipients, serum hemoglobin difference between donors and recipients, mean blood pressure (systolic blood pressure + 2 diastolic blood pressure/3) difference between donors and recipients, and weight difference between donors and recipients. The mean age of recipients was 10.5 ± 4.1 in SGF group and 11.6 ± 2.5 in control group (p = 0.4). The differences between donors and recipients regarding weight and mean blood pressure in subjects with SGF were not higher than other patients (42 kg vs. 37.4 kg, p = 0.4; -3 mmHg vs. -4.1 mmHg, p = 0.8). The mean hemoglobin difference between donors and recipients was 6.3 ± 2.1 g/dL in SGF group and 6.7 ± 2.3 g/dL in control group (p = 0.6). The differences between donors and recipients regarding age, weight, mean blood pressure and serum hemoglobin level are not predictive variables for SGF. © 2007 Blackwell Munksgaard

Inhibition of MLC Phosphorylation Restricts Replication of Influenza Virus—A Mechanism of Action for Anti-Influenza Agents

Influenza A viruses are a severe threat worldwide, causing large epidemics that kill thousands every year. Prevention of influenza infection is complicated by continuous viral antigenic changes. Newer anti-influenza agents include MEK/ERK and protein kinase C inhibitors; however, the downstream effectors of these pathways have not been determined. In this study, we identified a common mechanism for the inhibitory effects of a significant group of anti-influenza agents. Our studies showed that influenza infection activates a series of signaling pathways that converge to induce myosin light chain (MLC) phosphorylation and remodeling of the actin cytoskeleton. Inhibiting MLC phosphorylation by blocking RhoA/Rho kinase, phospholipase C/protein kinase C, and HRas/Raf/MEK/ERK pathways with the use of genetic or chemical manipulation leads to the inhibition of influenza proliferation. In contrast, the induction of MLC phosphorylation enhances influenza proliferation, as does activation of the HRas/Raf/MEK/ERK signaling pathway. This effect is attenuated by inhibiting MLC phosphorylation. Additionally, in intracellular trafficking studies, we found that the nuclear export of influenza ribonucleoprotein depends on MLC phosphorylation. Our studies provide evidence that modulation of MLC phosphorylation is an underlying mechanism for the inhibitory effects of many anti-influenza compounds