Analysis of blood stream infections: Antimicrobial susceptibility and associated types of extended spectrum β-lactamases

Purpose: To investigate the antimicrobial susceptibility and extended spectrum β-lactamase (ESBL) production by clinical isolates of Escherichia coli (ESBL-EC) and Klebsiella species (ESBL-KP) associated with blood stream infections (BSIs).Methods: Bacteria isolation and identification were carried out using basic bacteriological and biochemical techniques. Antimicrobial susceptibility test was performed according to the guidelines of the Clinical Laboratory Standard Institute (CLSI). Vitek 2 Compact automated system was used toconfirm the identifications (ID) and antimicrobial susceptibility test (AST). The ESBL produced by E. coli and K. pneumoniae isolates were  phenotypically characterised using Modified Double Disc Synergy Test (MDDST), as recommended by CLSI.Results: All (100 %) isolates were sensitive to imipenem and meropenem, while susceptibility to other antibiotics varied. ESBL genotypes, viz, blaTEM, blaSHV and blaCTX were encountered in the BSIs. For ESBL-EC, TEM, SHV and CTX producers accounted for 33, 16.67 and 58.3 %,  respectively, while 75, 91.7 and 100 % of ESBL-KP were TEM, SHV and CTX producers, respectively. In ESBL-KP, 67 % coexisted with all three genotypes (blaTEM, blaSHV, and blaCTX, while 8.3 % of ESBL-EC coexisted with the three encoding genes (CTX, SHV and TEM).Conclusion: ESBL E. coli and K. pneumoniae associated with BSI have been identified as TEM, SHV and CXT producers, with more ESBL-KP coexisting with all three than ESBL-EC. Keywords: β-Lactamases, Genes, Klebsiella pneumoniae, Escherichia col

Blood protozoa findings in pet dogs screened in Ipoh, Malaysia

A total of 103 blood samples from pet dogs around Ipoh were screened for common blood protozoa. A total of 14 samples were found positive for Erhlichia canis and one sample was found positive for microfilaria of Dirofilaria immitis. Both these diseases are transmitted by vectors; ticks (Rhipicephalus sangiuneus) and mosquitoes respectively. In the hot and wet tropical environment where vectors are abundant, pet care, hygiene and regular screening will help veterinarians detect these infections early to facilitate treatment

Distinct Signature of Altered Homeostasis in Aging Rod Photoreceptors: Implications for Retinal Diseases

Advanced age contributes to clinical manifestations of many retinopathies and represents a major risk factor for age-related macular degeneration, a leading cause of visual impairment and blindness in the elderly. Rod photoreceptors are especially vulnerable to genetic defects and changes in microenvironment, and are among the first neurons to die in normal aging and in many retinal degenerative diseases. The molecular mechanisms underlying rod photoreceptor vulnerability and potential biomarkers of the aging process in this highly specialized cell type are unknown.To discover aging-associated adaptations that may influence rod function, we have generated gene expression profiles of purified rod photoreceptors from mouse retina at young adult to early stages of aging (1.5, 5, and 12 month old mice). We identified 375 genes that showed differential expression in rods from 5 and 12 month old mouse retina compared to that of 1.5 month old retina. Quantitative RT-PCR experiments validated expression change for a majority of the 25 genes that were examined. Macroanalysis of differentially expressed genes using gene class testing and protein interaction networks revealed overrepresentation of cellular pathways that are potentially photoreceptor-specific (angiogenesis and lipid/retinoid metabolism), in addition to age-related pathways previously described in several tissue types (oxidative phosphorylation, stress and immune response).Our study suggests a progressive shift in cellular homeostasis that may underlie aging-associated functional decline in rod photoreceptors and contribute to a more permissive state for pathological processes involved in retinal diseases

Effect of a multicomponent intervention on antihypertensive medication intensification in rural South Asia: post-hoc analysis of a cluster RCT

BACKGROUND: Inadequate treatment of hypertension is a widespread problem, especially in South Asian countries where cardiovascular disease mortality rates are high. We aimed to explore the effect of a multicomponent intervention (MCI) on antihypertensive medication intensification among rural South Asians with hypertension. METHODS: A post-hoc analysis of a two-year cluster-randomized controlled trial including 2645 hypertensives aged≥ 40 years from 30 rural communities, 10 each, in Bangladesh, Pakistan, and Sri Lanka. Independent assessors collected information on participants' self-reports and physical inspection of medications. The main outcomes were the changes from baseline to 24 months in the following: 1) the therapeutic intensity score (TIS) for all (and class specific) antihypertensive medications; 2) the number of antihypertensive medications in all trial participants. RESULTS: At 24 months, the mean increase in the TIS score of all antihypertensive medications was 0.11 in the MCI group and 0.03 in the control group, with a between-group difference in the increase of 0.08 (95% CI (0.03, 0.12); P=0.002). In MCI compared to controls, a greater increase in the TIS of renin angiotensin-aldosterone system blockers (0.05; 95% CI (0.02, 0.07); P<0.001) and calcium channel blockers (0.03; 95% CI (0.00, 0.05);p=0.031) , and in the number of antihypertensive medications (0.11, 95% CI (0.02, 0.19);P=0.016) was observed. CONCLUSIONS: In rural communities in Bangladesh, Pakistan, and Sri Lanka, MCI led to a greater increase in antihypertensive medication intensification compared to the usual care among adults with hypertension. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT02657746

Evaluating the antidiabetic and antioxidant properties of 5- benzyl-1,3,4-oxadiazole-2-thiol

Purpose: To evaluate 5-Benzyl-1,3,4-oxadiazole-2-thiol (OXPA) for antidiabetic and antioxidant properties. Methods: Antidiabetic activity was evaluated using three in vitro models, glucose uptake by yeast cells, alpha amylase inhibition assay and hemoglobin glycosylation inhibition assays. Antioxidant potential was determined by DPPH radical scavenging, reducing power and lipid peroxidation assays. Results: OXPA showed antidiabetic activity in all the three models. The activity of the compound was comparable with that of metronidazole in glucose uptake by yeast cells, but the alpha amylase inhibition activity of the compound was slightly lower than that of acarbose, whereas the hemoglobin glycosylation inhibition activity of the compound was higher than that of vitamin E. DPPH free radical and hydrogen peroxide scavenging activity of the compound was comparable with that of vitamin C. In reducing power assay, the activity of the compound was lower than that of vitamin C (p &gt; 0.05). Conclusion: The results of antidiabetic and antioxidant activity indicate that OXPA may be a drugcandidate for treating both diabetes and its associated oxidative stress

The Deubiquitinating Enzyme Ataxin-3 Regulates Ciliogenesis and Phagocytosis in the Retina

Expansion of a CAG repeat in ATXN3 causes the dominant polyglutamine disease spinocerebellar ataxia type 3 (SCA3), yet the physiological role of ATXN3 remains unclear. Here, we focus on unveiling the function of Ataxin-3 (ATXN3) in the retina, a neurological organ amenable to morphological and physiological studies. Depletion of Atxn3 in zebrafish and mice causes morphological and functional retinal alterations and, more precisely, photoreceptor cilium and outer segment elongation, cone opsin mislocalization, and cone hyperexcitation. ATXN3 localizes at the basal body and axoneme of the cilium, supporting its role in regulating ciliary length. Abrogation of Atxn3 expression causes decreased levels of the regulatory protein KEAP1 in the retina and delayed phagosome maturation in the retinal pigment epithelium. We propose that ATXN3 regulates two relevant biological processes in the retina, namely, ciliogenesis and phagocytosis, by modulating microtubule polymerization and microtubule-dependent retrograde transport, thus positing ATXN3 as a causative or modifier gene in retinal/macular dystrophies

A systematic review and meta-analysis of the prevalence of common mental disorders in people with non-communicable diseases in Bangladesh, India, and Pakistan

Background: The prevalence of mental and physical comorbidities is unknown in South Asia, as estimates of mental ill health in patients with non-communicable diseases (NCDs) have predominantly come from studies based in the United States, Europe and Australasia. This systematic review and meta-analysis summarises evidence and provides pooled estimates of the prevalence of common mental disorders in adults with non-communicable diseases in South Asia. Methods: We included prevalence studies of depression and anxiety in adults with diabetes, cancer, cardiovascular disease, and chronic respiratory conditions in Bangladesh, India, and Pakistan, published from 1990 onwards in international and country-specific databases. Results: Out of 96 included studies, 83 provided data for random effects meta-analyses. The pooled prevalence of depression was 44% (95% confidence interval (CI) = 26 to 62) for patients with COPD, 40% (95% CI = 34 to 45) for diabetes, 39% (95% CI = 23 to 56) for stroke, 38% (95% CI = 32 to 45) for hypertension, and 37% (95% CI = 30 to 45) for cancer. The pooled prevalence of anxiety based on 28 studies was 29% (95% CI = 22 to 36). Many quality issues were identified in a critical appraisal of included studies, mostly relating to the sampling frame and selection process, the description of the methods and basic data, and the description of non-responders. Conclusions: Depression and anxiety are prevalent and underdiagnosed in people with physical comorbidities in Bangladesh, India, and Pakistan

Altered retinal structure and function in Spinocerebellar ataxia type 3

Spinocerebellar ataxia type 3 (SCA3) is an autosomal dominant neurodegenerative disorder caused by expansion of a polyglutamine (polyQ)-encoding CAG repeat in the ATXN3 gene. Because the ATXN3 protein regulates photoreceptor ciliogenesis and phagocytosis, we aimed to explore whether expanded polyQ ATXN3 impacts retinal function and integrity in SCA3 patients and transgenic mice. We evaluated the retinal structure and function in five patients with SCA3 and in a transgenic mouse model of this disease (YACMJD84.2, Q84) using optical coherence tomography (OCT) and electroretinogram (ERG). In the transgenic mice, we further: a) determined the retinal expression pattern of ATXN3 and the distribution of cones and rods using immunofluorescence (IF); and b) assessed the retinal ultrastructure using transmission electron microscopy (TEM). Some patients with SCA3 in our cohort revealed: i) reduced central macular thickness indirectly correlated with disease duration; ii) decreased thickness of the macula and the ganglion cell layer, and reduced macula volume inversely correlated with disease severity (SARA score); and iii) electrophysiological dysfunction of cones, rods, and inner retinal cells. Transgenic mice replicated the human OCT and ERG findings with aged homozygous Q84/Q84 mice showing a stronger phenotype accompanied by further thinning of the outer nuclear layer and photoreceptor layer and highly reduced cone and rod activities, thus supporting severe retinal dysfunction in these mice. In addition, Q84 mice showed progressive accumulation of ATXN3-positive aggregates throughout several retinal layers and depletion of cones alongside the disease course. TEM analysis of aged Q84/Q84 mouse retinas supported the ATXN3 aggregation findings by revealing the presence of high number of negative electron dense puncta in ganglion cells, inner plexiform and inner nuclear layers, and showed further thinning of the outer plexiform layer, thickening of the retinal pigment epithelium and elongation of apical microvilli. Our results indicate that retinal alterations detected by non-invasive eye examination using OCT and ERG could represent a biological marker of disease progression and severity in patients with SCA3

“You can’t die here”: an exploration of the barriers to dying-in-place for structurally vulnerable populations in an urban centre in British Columbia, Canada

Abstract Background One measure of quality in palliative care involves ensuring people approaching the end of life are able to receive care, and ultimately die, in the places they choose. Canadian palliative care policy directives stem from this tenet of autonomy, acknowledging that most people prefer to die at home, where they feel safe and comfortable. Limited research, however, considers the lack of ‘choice’ people positioned as structurally vulnerable (e.g., experiencing extreme poverty, homelessness, substance-use/criminalization, etc.) have in regard to places of care and death, with the option of dying-in-place most often denied. Methods Drawing from ethnographic and participatory action research data collected during two studies that took place from 2014 to 2019 in an urban centre in British Columbia, Canada, this analysis explores barriers preventing people who experience social and structural inequity the option to die-in-place. Participants include: (1) people positioned as structurally vulnerable on a palliative trajectory; (2) their informal support persons/family caregivers (e.g., street family); (3) community service providers (e.g., housing workers, medical professionals); and (4) key informants (e.g., managers, medical directors, executive directors). Data includes observational fieldnotes, focus group and interviews transcripts. Interpretive thematic analytic techniques were employed. Results Participants on a palliative trajectory lacked access to stable, affordable, or permanent housing, yet expressed their desire to stay ‘in-place’ at the end of life. Analysis reveals three main barriers impeding their ‘choice’ to remain in-place at the end of life: (1) Misaligned perceptions of risk and safety; (2) Challenges managing pain in the context of substance use, stigma, and discrimination; and (3) Gaps between protocols, policies, and procedures for health teams. Conclusions Findings demonstrate how the rhetoric of ‘choice’ in regard to preferred place of death is ethically problematic because experienced inequities are produced and constrained by socio-structural forces that reach beyond individuals’ control. Ultimately, our findings contribute suggestions for policy, programs and practice to enhance inclusiveness in palliative care. Re-defining ‘home’ within palliative care, enhancing supports, education, and training for community care workers, integrating palliative approaches to care into the everyday work of non-health care providers, and acknowledging, valuing, and building upon existing relations of care can help to overcome existing barriers to delivering palliative care in various settings and increase the opportunity for all to spend their end of life in the places that they prefer