Politics of un/re/claiming: critical feminist interventions in Global policy, rights and development

Informed by intersectional feminist sensibilities, this compilation of four critical interventions weaves together existing and emergent threads of women’s studies to interrogate one-dimensional framings of global policy, rights and development in hegemonic discourse. Attending to contemporary geopolitical issues as diverse as they are rich, what interconnects these seemingly disparate sites of complexity and contestation is a politics of un/re/claiming. ‘Instrumental Women or Women-as-Instruments? Assessing Gender Mainstreaming and Claims to Microcredit’ problematises the myriad ways in which economic (dis)empowerment, vis-à-vis the staking of microcredit claims, is constitutive of and constituted by neoliberal globalisation. ‘Medicinal and Aromatic Plants: Territorial Resource Claims and the Feminisation of Global Agricultural Production’ navigates topographies of agricultural supply-chain management to tease out the textured intersections between global(ised) trade, natural resource claims and gendered labour divisions. Straddling the neoliberal epoch’s hyper-precarious borders and boundaries, patient lifeworlds are multiply inflected by their in/capacity to articulate healthcare-based claims - ‘Patienthood and its Dis/claimers: Embodied Citizenship Politics in Neoliberal Welfare Restructuring’ invokes an anthropologically-attuned analytic frame to unearth such ambivalences. Finally, ‘On Wendy Brown’s “Suffering Rights as Paradoxes”: Theorising the Im/possibility of Rights-Based Claims’ offers an incisive, nuanced commentary on Wendy Brown’s seminal scholarship in search of new political and epistemological possibilities for redressing rights-based claims

The effectiveness of public health interventions to reduce the health impact of climate change:a systematic review of systematic reviews

Climate change is likely to be one of the most important threats to public health in the coming years. Yet despite the large number of papers considering the health impact of climate change, few have considered what public health interventions may be of most value in reducing the disease burden. We aimed to evaluate the effectiveness of public health interventions to reduce the disease burden of high priority climate sensitive diseases

The functional, social and economic impact of acute encephalitis syndrome in Nepal--a longitudinal follow-up study.

notes: PMCID: PMC3772013Open Access JournalOver 133,000 children present to hospitals with Acute Encephalitis Syndrome (AES) annually in Asia. Japanese encephalitis (JE) accounts for approximately one-quarter of cases; in most cases no pathogen is identified and management is supportive. Although JE is known to result in neurological impairment, few studies have examined the wider impact of JE and AES on patients and their families.Wellcome TrustUniversity of Liverpool Clinical Fellowshi

Effects of Simulated Equestrian Therapy in improving Motor Proficiency among Down Syndrome Children- A Randomized Controlled Trial

International Journal of Exercise Science 17(1): 1193-1207, 2024. The objective of this study was to investigate the effectiveness of Simulated Equestrian Therapy and Neuro-Motor Therapy in improving Motor Proficiency among Down syndrome children using a double-blinded Randomized Controlled Trial. This study was conducted at Dar-ul-Sukun Institute and Dr. Ziauddin Hospital from April to September 2023 by enrolling a total of 56 participants with Down syndrome (DS) after obtaining informed, voluntary assent from the guardians of the participants. Each participant was allocated randomly to the treatment group (n = 28) that received Simulated Equestrian Therapy (SET) and the control group (n = 28) that received Neuro-motor Therapy (NMT) using the envelop method of simple random sampling. The participants and their guardians were blind to the allocations. Participants’ blood pressure and heart rate were recorded before and after each session to ensure safety. Each participant was assessed at baseline and after 6th and 12th week of intervention using Bruinink’s test of motor proficiency (BOT-2). The data was analyzed using Medcalc software. The results reveal significant findings for improving motor proficiency after 12th week of intervention of SET and NMT. No protocol was found to be superior to another in improvement of the tested parameters. Hence, our study concludes that SET and NMT effectively improve motor proficiency among DS children. However, studies with a follow-up period should be conducted to further evaluate these therapies’ long-term benefits

Characterizing the morbid genome of ciliopathies

Background Ciliopathies are clinically diverse disorders of the primary cilium. Remarkable progress has been made in understanding the molecular basis of these genetically heterogeneous conditions; however, our knowledge of their morbid genome, pleiotropy, and variable expressivity remains incomplete. Results We applied genomic approaches on a large patient cohort of 371 affected individuals from 265 families, with phenotypes that span the entire ciliopathy spectrum. Likely causal mutations in previously described ciliopathy genes were identified in 85% (225/265) of the families, adding 32 novel alleles. Consistent with a fully penetrant model for these genes, we found no significant difference in their “mutation load” beyond the causal variants between our ciliopathy cohort and a control non-ciliopathy cohort. Genomic analysis of our cohort further identified mutations in a novel morbid gene TXNDC15, encoding a thiol isomerase, based on independent loss of function mutations in individuals with a consistent ciliopathy phenotype (Meckel-Gruber syndrome) and a functional effect of its deficiency on ciliary signaling. Our study also highlighted seven novel candidate genes (TRAPPC3, EXOC3L2, FAM98C, C17orf61, LRRCC1, NEK4, and CELSR2) some of which have established links to ciliogenesis. Finally, we show that the morbid genome of ciliopathies encompasses many founder mutations, the combined carrier frequency of which accounts for a high disease burden in the study population. Conclusions Our study increases our understanding of the morbid genome of ciliopathies. We also provide the strongest evidence, to date, in support of the classical Mendelian inheritance of Bardet-Biedl syndrome and other ciliopathies

Traditional knowledge of wild edible plants used in Palestine (Northern West Bank): A comparative study

<p>Abstract</p> <p>Background</p> <p>A comparative food ethnobotanical study was carried out in fifteen local communities distributed in five districts in the Palestinian Authority, PA (northern West Bank), six of which were located in Nablus, two in Jenin, two in Salfit, three in Qalqilia, and two in Tulkarm. These are among the areas in the PA whose rural inhabitants primarily subsisted on agriculture and therefore still preserve the traditional knowledge on wild edible plants.</p> <p>Methods</p> <p>Data on the use of wild edible plants were collected for one-year period, through informed consent semi-structured interviews with 190 local informants. A semi-quantitative approach was used to document use diversity, and relative importance of each species.</p> <p>Results and discussion</p> <p>The study recorded 100 wild edible plant species, seventy six of which were mentioned by three informants and above and were distributed across 70 genera and 26 families. The most significant species include <it>Majorana syriaca, Foeniculum vulgare, Malvasylvestris</it>, <it>Salvia fruticosa, Cyclamen persicum, Micromeria fruticosa, Arum palaestinum, Trigonella foenum-graecum</it>, <it>Gundelia tournefortii</it>, and <it>Matricaria aurea</it>. All the ten species with the highest mean cultural importance values (mCI), were cited in all five areas. Moreover, most were important in every region. A common cultural background may explain these similarities. One taxon (<it>Majoranasyriaca</it>) in particular was found to be among the most quoted species in almost all areas surveyed. CI values, as a measure of traditional botanical knowledge, for edible species in relatively remote and isolated areas (Qalqilia, and Salfit) were generally higher than for the same species in other areas. This can be attributed to the fact that local knowledge of wild edible plants and plant gathering are more spread in remote or isolated areas.</p> <p>Conclusion</p> <p>Gathering, processing and consuming wild edible plants are still practiced in all the studied Palestinian areas. About 26 % (26/100) of the recorded wild botanicals including the most quoted and with highest mCI values, are currently gathered and utilized in all the areas, demonstrating that there are ethnobotanical contact points among the various Palestinian regions. The habit of using wild edible plants is still alive in the PA, but is disappearing. Therefore, the recording, preserving, and infusing of this knowledge to future generations is pressing and fundamental.</p

Development of validated stability-indicating chromatographic method for the determination of fexofenadine hydrochloride and its related impurities in pharmaceutical tablets

A simple reversed phase high performance liquid chromatographic method with diode array detector (HPLC-DAD) has been developed and subsequently validated for the determination of fexofenadine hydrochloride (FEX) and its related compounds; keto fexofenadine (Impurity A), meta isomer of fexofenadine (Impurity B), methyl ester of fexofenadine (Impurity C) in addition to the methyl ester of ketofexofenadine (Impurity D). The separation was based on the use of a Hypersil BDS C-18 analytical column (250 × 4.6 mm, i.d., 5 μm). The mobile phase consisted of a mixture of phosphate buffer containing 0.1 gm% of 1-octane sulphonic acid sodium salt monohydrate and 1% (v/v) of triethylamine, pH 2.7 and methanol (60:40, v/v). The separation was carried out at ambient temperature with a flow rate of 1.5 ml/min. Quantitation was achieved with UV detection at 215 nm using lisinopril as internal standard, with linear calibration curves at concentration ranges 0.1-50 μg/ml for FEX and its related compounds. The optimized conditions were used to develop a stability-indicating HPLC-DAD method for the quantitative determination of FEX and its related compounds in tablet dosage forms. The drugs were subjected to oxidation, hydrolysis, photolysis and heat to apply stress conditions. Complete separation was achieved for the parent compounds and all degradation products. The method was validated according to ICH guidelines in terms of accuracy, precision, robustness, limits of detection and quantitation and other aspects of analytical validation

SLC4A10 mutation causes a neurological disorder associated with impaired GABAergic transmission

SLC4A10 is a plasma-membrane bound transporter which utilizes the Na+ gradient to drive cellular HCO3- uptake, thus mediating acid extrusion. In the mammalian brain, SLC4A10 is expressed in principal neurons and interneurons, as well as in epithelial cells of the choroid plexus, the organ regulating the production of cerebrospinal fluid. Using next generation sequencing on samples from five unrelated families encompassing ten affected individuals, we show that biallelic SLC4A10 loss-of-function variants cause a clinically recognizable neurodevelopmental disorder in humans. The cardinal clinical features of the condition include hypotonia in infancy, delayed psychomotor development across all domains and typically severe intellectual impairment. Affected individuals commonly display traits associated with autistic spectrum disorders including anxiety, hyperactivity and stereotyped movements. In two cases isolated episodes of seizures were reported in the first few years of life, and a further affected child displayed bitemporal epileptogenic discharges on EEG without overt clinical seizures. While occipitofrontal circumference was reported to be normal at birth, progressive postnatal microcephaly evolved in 7 out of 10 affected individuals. Neuroradiological features included a relative preservation of brain volume compared to occipitofrontal circumference, characteristic narrow sometimes 'slit-like' lateral ventricles and corpus callosum abnormalities. Slc4a10 -/- mice, deficient for SLC4A10, also display small lateral brain ventricles and mild behavioral abnormalities including delayed habituation and alterations in the 2-object novel object recognition task. Collapsed brain ventricles in both Slc4a10-/- mice and affected individuals suggests an important role of SLC4A10 in the production of the cerebrospinal fluid. However, it is notable that despite diverse roles of the cerebrospinal fluid in the developing and adult brain, the cortex of Slc4a10-/- mice appears grossly intact. Co-staining with synaptic markers revealed that in neurons, SLC4A10 localizes to inhibitory, but not excitatory, presynapses. These findings are supported by our functional studies which show the release of the inhibitory neurotransmitter GABA is compromised in Slc4a10-/- mice, while the release of the excitatory neurotransmitter glutamate is preserved. Manipulation of intracellular pH partially rescues GABA release. Together our studies define a novel characteristic neurodevelopmental disorder associated with biallelic pathogenic variants in SLC4A10 and highlight the importance of further analyses of the consequences of SLC4A10 loss-of-function for brain development, synaptic transmission and network properties

Interpreting Expression Data with Metabolic Flux Models: Predicting Mycobacterium tuberculosis Mycolic Acid Production

Metabolism is central to cell physiology, and metabolic disturbances play a role in numerous disease states. Despite its importance, the ability to study metabolism at a global scale using genomic technologies is limited. In principle, complete genome sequences describe the range of metabolic reactions that are possible for an organism, but cannot quantitatively describe the behaviour of these reactions. We present a novel method for modeling metabolic states using whole cell measurements of gene expression. Our method, which we call E-Flux (as a combination of flux and expression), extends the technique of Flux Balance Analysis by modeling maximum flux constraints as a function of measured gene expression. In contrast to previous methods for metabolically interpreting gene expression data, E-Flux utilizes a model of the underlying metabolic network to directly predict changes in metabolic flux capacity. We applied E-Flux to Mycobacterium tuberculosis, the bacterium that causes tuberculosis (TB). Key components of mycobacterial cell walls are mycolic acids which are targets for several first-line TB drugs. We used E-Flux to predict the impact of 75 different drugs, drug combinations, and nutrient conditions on mycolic acid biosynthesis capacity in M. tuberculosis, using a public compendium of over 400 expression arrays. We tested our method using a model of mycolic acid biosynthesis as well as on a genome-scale model of M. tuberculosis metabolism. Our method correctly predicts seven of the eight known fatty acid inhibitors in this compendium and makes accurate predictions regarding the specificity of these compounds for fatty acid biosynthesis. Our method also predicts a number of additional potential modulators of TB mycolic acid biosynthesis. E-Flux thus provides a promising new approach for algorithmically predicting metabolic state from gene expression data. Author Summary The ability of cells to survive and grow depends on their ability to metabolize nutrients and create products vital for cell function. This is done through a complex network of reactions controlled by many genes. Changes in cellular metabolism play a role in a wide variety of diseases. However, despite the availability of genome sequences and of genome-scale expression data, which give information about which genes are present and how active they are, our ability to use these data to understand changes in cellular metabolism has been limited. We present a new approach to this problem, linking gene expression data with models of cellular metabolism. We apply the method to predict the effects of drugs and agents on Mycobacterium tuberculosis (M. tb). Virulence, growth in human hosts, and drug resistance are all related to changes in M. tb's metabolism. We predict the effects of a variety of conditions on the production of mycolic acids, essential cell wall components. Our method successfully identifies seven of the eight known mycolic acid inhibitors in a compendium of 235 conditions, and identifies the top anti-TB drugs in this dataset. We anticipate that the method will have a range of applications in metabolic engineering, the characterization of disease states, and drug discovery.: National Institute of Allergy and Infectious Disease; National Institutes of Health (HHSN 26620040000IC); Department of Health and Human Services (HHSN266200400001C) National Institue of Allergy and Infectious Diseases (1U19AI076217, R01 071155, 014334-001); the Bill & Melinda Gates Foundation Dedicated Tuberculosis Gene Expression Database; the Ellison Medical Foundation (ID-SS-0693-04); Burroughs Wellcome Fun

Phase II trial of fenretinide in advanced renal carcinoma

Purpose : Fenretinide, a synthetic form of retinoid, induced apoptosis even in chemotherapy resistant cell lines. A phase II study was hence conducted to evaluate toxicity and efficacy of fenretinide in metastatic renal cancer. Methods : Eligibility included unresectable or metastatic renal cell carcinoma (RCC), adequate organ function and Zubrod performance status ≦2. Prior immunotherapy and a maximum of one prior chemotherapy regimen were allowed. Fenretinide was administered at a dose of 900 mg/m 2 twice daily orally for 7 days in a 21-day cycle. Toxicity was assessed at the start of each cycle, and response every 2 cycles. Results : Nineteen eligible patients enrolled of which fifteen had visceral/bone metastases. Seventeen patients had prior nephrectomy and 11 had prior immunotherapy. 76 cycles of therapy were delivered. Therapy was very well tolerated with few severe toxicities consisting of thrombosis in 1 individual and grade 3 fatigue, nausea and diarrhea in 1 patient. 5 patients had grade 2 nyctalopia and 3 patients had transient grade 2 visual toxicity. No objective responses were noted. Stable disease was seen in seven of nineteen cases (37%, 90% C.I. 0.21–0.59). Median time to progression was 1.5 months and median duration of stable disease was 5.8 months (90% C.I. 3.0–8.4). Median survival was 10 months. Tumor fenretinide levels were obtained in three patients and were in the lower end of the therapeutic range. Conclusion : Fenretinide was well tolerated but demonstrated minimal activity that was consistent with results of intratumoral drug measurements. Strategies are needed that will increase systemic and tumor levels of fenretinide.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/45264/1/10637_2005_Article_5864.pd