Diffuse small bowel thickening in aids patient - a case report

<p>Abstract</p> <p>Background</p> <p>Diarrhea is common in HIV/AIDS patients, caused by both classic enteric pathogens and different opportunistic agents. <it>Infection with these different pathogens may lead to similar radiological findings, thus causing diagnostic confusion</it>.</p> <p>Case presentation</p> <p>A 30-yr-old female with AIDS presented with chronic diarrhea of 4 months duration. She had diffuse small bowel thickening present on CT scan of her abdomen, with stool examination showing no parasites. She was erroneously diagnosed as abdominal tuberculosis and given antituberculosis drugs with which she showed no improvement. Repeat stool examination later at a specialized laboratory revealed <it>Cryptosporidium parvum </it>infection.</p> <p>The patient was given an extended course of nitazoxanide treatment, as her stool examination was positive for <it>Cryptosporidium parvum </it>even after 2 weeks of drug consumption. Parasite clearance was documented after 10 weeks of treatment. Interestingly, the bowel thickening reversed with parasitological clearance.</p> <p>Conclusions</p> <p><it>Cryptosporidium parvum </it>may lead to small bowel thickening in AIDS patients. This small bowel thickening may reverse following parasitological clearance.</p

Reviewing the use of chitosan and polydopamine for electrochemical sensing

Biopolymers possess highly favorable properties for electrochemical biosensing such as their inherent biocompatibility, inexpensive nature, and strong interfacial adhesion. In this mini-review, we will focus on chitosan and polydopamine, two of the most commonly used biopolymers, for electrochemical sensing applications. Chitosan is a polysaccharide that exhibits high chemical resistance, offers straightforward modification and cross-linking, and possesses antibacterial properties and mucoadhesion. Polydopamine has the benefit of universal adhesion, in addition to the ability to form self-assembled structures. We will demonstrate how the unique structural and electrochemical features of these biopolymers can be used in a range of electrochemical biosensing platforms

Rapid electrochemical detection of levodopa using polyaniline-modified screen-printed electrodes for the improved management of Parkinson's disease

A portable test to rapidly determine levels of levodopa, the drug used to treat Parkinson's disease, can improve clinical management of the disease. In this study, screen-printed electrodes (SPEs) were modified with polymers to facilitate the electrochemical detection of levodopa. Cyclic voltammetry was used to deposit a thin layer of polyaniline on the electrode surface. Scanning electron microscopy revealed high surface coverage, which did not impact the electrode's conductivity. Differential pulse voltammetry measurements with the polyaniline-modified electrodes enabled the measurement of levodopa at physiologically relevant concentrations with discrimination between a common interferent (ascorbic acid) and a structurally similar compound (L-tyrosine). However, the use of the polymer layer did not permit differentiation between levodopa and dopamine; the only difference in these molecules is that levodopa has an amino acid moiety whereas dopamine has a free amine group. Density functional theory calculations demonstrated that aniline formed a hydrogen bond between the amino group of the monomer and the meta-hydroxyl group, which is present in both levodopa and dopamine, with similar binding energies (−53.36 vs −50.08 kJ mol−1). Thus, the polymer-functionalised SPEs are a valuable tool to measure compounds important in Parkinson's disease, but further refinement is needed to achieve selective detection

Molecularly imprinted polymer nanoparticles enable rapid, reliable, and robust point-of-care thermal detection of SARS-CoV-2

Rapid antigen tests are currently used for population screening of COVID-19. However, they lack sensitivity and utilize antibodies as receptors, which can only function in narrow temperature and pH ranges. Consequently, molecularly imprinted polymer nanoparticles (nanoMIPs) are synthetized with a fast (2 h) and scalable process using merely a tiny SARS-CoV-2 fragment (∼10 amino acids). The nanoMIPs rival the affinity of SARS-CoV-2 antibodies under standard testing conditions and surpass them at elevated temperatures or in acidic media. Therefore, nanoMIP sensors possess clear advantages over antibody-based assays as they can function in various challenging media. A thermal assay is developed with nanoMIPs electrografted onto screen-printed electrodes to accurately quantify SARS-CoV-2 antigens. Heat transfer-based measurements demonstrate superior detection limits compared to commercial rapid antigen tests and most antigen tests from the literature for both the alpha (∼9.9 fg mL-1) and delta (∼6.1 fg mL-1) variants of the spike protein. A prototype assay is developed, which can rapidly (∼15 min) validate clinical patient samples with excellent sensitivity and specificity. The straightforward epitope imprinting method and high robustness of nanoMIPs produce a SARS-CoV-2 sensor with significant commercial potential for population screening, in addition to the possibility of measurements in diagnostically challenging environments

High mortality during tuberculosis treatment does not indicate long diagnostic delays in Vietnam: a cohort study

<p>Abstract</p> <p>Background</p> <p>Delay in tuberculosis diagnosis and treatment initiation may increase disease severity and mortality. In evaluations of tuberculosis control programmes high fatality rates during tuberculosis treatment, are used as an indicator of long delays in low HIV-prevalence settings. However, data for this presumed association between delay and fatality are lacking. We assessed the association between diagnostic delay and mortality of new smear-positive pulmonary tuberculosis patients in Vietnam.</p> <p>Methods</p> <p>Follow-up of a patient cohort included in a survey of diagnostic delay in 70 randomly selected districts. Data on diagnosis and treatment were extracted from routine registers. Patients who had died during the course of treatment were compared to those with reported cure, completed treatment or failure (survivors).</p> <p>Results</p> <p>Complete data were available for 1881/2093 (89.9%) patients, of whom 82 (4.4%) had died. Fatality was 4.5% for patients with ≤ 4 weeks delay, 5.0% for 5- ≤ 8 weeks delay (aOR 1.11, 95%CI 0.67–1.84) and 3.2% for > 9 weeks delay (aOR 0.69, 95%CI 0.37–1.30). Fatality tended to decline with increasing delay but this was not significant. Fatality was not associated with median diagnostic delay at district level (Spearman's rho = -0.08, P = 0.5).</p> <p>Conclusion</p> <p>Diagnostic delay is not associated with treatment mortality in Vietnam at individual nor district level, suggesting that high case fatality should not be used as an indicator of long diagnostic delay in national tuberculosis programmes.</p

Polycomb-Like 3 Promotes Polycomb Repressive Complex 2 Binding to CpG Islands and Embryonic Stem Cell Self-Renewal

Polycomb repressive complex 2 (PRC2) trimethylates lysine 27 of histone H3 (H3K27me3) to regulate gene expression during diverse biological transitions in development, embryonic stem cell (ESC) differentiation, and cancer. Here, we show that Polycomb-like 3 (Pcl3) is a component of PRC2 that promotes ESC self-renewal. Using mass spectrometry, we identified Pcl3 as a Suz12 binding partner and confirmed Pcl3 interactions with core PRC2 components by co-immunoprecipitation. Knockdown of Pcl3 in ESCs increases spontaneous differentiation, yet does not affect early differentiation decisions as assessed in teratomas and embryoid bodies, indicating that Pcl3 has a specific role in regulating ESC self-renewal. Consistent with Pcl3 promoting PRC2 function, decreasing Pcl3 levels reduces H3K27me3 levels while overexpressing Pcl3 increases H3K27me3 levels. Furthermore, chromatin immunoprecipitation and sequencing (ChIP-seq) reveal that Pcl3 co-localizes with PRC2 core component, Suz12, and depletion of Pcl3 decreases Suz12 binding at over 60% of PRC2 targets. Mutation of conserved residues within the Pcl3 Tudor domain, a domain implicated in recognizing methylated histones, compromises H3K27me3 formation, suggesting that the Tudor domain of Pcl3 is essential for function. We also show that Pcl3 and its paralog, Pcl2, exist in different PRC2 complexes but bind many of the same PRC2 targets, particularly CpG islands regulated by Pcl3. Thus, Pcl3 is a component of PRC2 critical for ESC self-renewal, histone methylation, and recruitment of PRC2 to a subset of its genomic sites

Identifying a Window of Vulnerability during Fetal Development in a Maternal Iron Restriction Model

It is well acknowledged from observations in humans that iron deficiency during pregnancy can be associated with a number of developmental problems in the newborn and developing child. Due to the obvious limitations of human studies, the stage during gestation at which maternal iron deficiency causes an apparent impairment in the offspring remains elusive. In order to begin to understand the time window(s) during pregnancy that is/are especially susceptible to suboptimal iron levels, which may result in negative effects on the development of the fetus, we developed a rat model in which we were able to manipulate and monitor the dietary iron intake during specific stages of pregnancy and analyzed the developing fetuses. We established four different dietary-feeding protocols that were designed to render the fetuses iron deficient at different gestational stages. Based on a functional analysis that employed Auditory Brainstem Response measurements, we found that maternal iron restriction initiated prior to conception and during the first trimester were associated with profound changes in the developing fetus compared to iron restriction initiated later in pregnancy. We also showed that the presence of iron deficiency anemia, low body weight, and changes in core body temperature were not defining factors in the establishment of neural impairment in the rodent offspring

Subcellular Location of PKA Controls Striatal Plasticity: Stochastic Simulations in Spiny Dendrites

Dopamine release in the striatum has been implicated in various forms of reward dependent learning. Dopamine leads to production of cAMP and activation of protein kinase A (PKA), which are involved in striatal synaptic plasticity and learning. PKA and its protein targets are not diffusely located throughout the neuron, but are confined to various subcellular compartments by anchoring molecules such as A-Kinase Anchoring Proteins (AKAPs). Experiments have shown that blocking the interaction of PKA with AKAPs disrupts its subcellular location and prevents LTP in the hippocampus and striatum; however, these experiments have not revealed whether the critical function of anchoring is to locate PKA near the cAMP that activates it or near its targets, such as AMPA receptors located in the post-synaptic density. We have developed a large scale stochastic reaction-diffusion model of signaling pathways in a medium spiny projection neuron dendrite with spines, based on published biochemical measurements, to investigate this question and to evaluate whether dopamine signaling exhibits spatial specificity post-synaptically. The model was stimulated with dopamine pulses mimicking those recorded in response to reward. Simulations show that PKA colocalization with adenylate cyclase, either in the spine head or in the dendrite, leads to greater phosphorylation of DARPP-32 Thr34 and AMPA receptor GluA1 Ser845 than when PKA is anchored away from adenylate cyclase. Simulations further demonstrate that though cAMP exhibits a strong spatial gradient, diffusible DARPP-32 facilitates the spread of PKA activity, suggesting that additional inactivation mechanisms are required to produce spatial specificity of PKA activity