Renoprotective effect of red grape (Vitis vinifera L.) juice and dark raisins against hypercholesterolaemia-induced tubular renal affection in albino rats

Background: Red grape juice (RGJ) and dark raisins (DR) are rich in polyphenols and antioxidants. This study aimed to assess the efficacy of RGJ and DR in protec- ting the renal tubules against hypercholesteraemic-induced pathological changes.  Materials and methods: Forty albino rats divided into four groups (n = 10) were utilised in this study. They included the control, high cholesterol diet (HCD)-fed, HCD+RGJ-fed, and HCD+DR-fed groups. Body weight gain, food and water in- take, blood and insulin levels, lipid profile and kidney functions were assessed at the start of the experiment and after 12 weeks. The right kidney was dissected out and processed for both light and electron microscopic examination. Desmin and cytokeratin antibodies were utilised as histologic markers to assess the integrity of the proximal (PTs) and distal tubules (DTs) of the kidney.  Results: Administration of HCD resulted in hypercholesterolaemia in rats as evi- denced by the lipid profile. The PTs of hypercholesteraemic rats appeared dilated with hyaline casts and mitochondria in most of the tubular cells were affected. Immunohistochemical assessment revealed affection of both PTs and DTs. Both RGJ and DR, when administered along with the HCD for 12 weeks, improved the lipid profile, kidney functions as well as the histologic and cellular changes-induced by hypercholesterolaemia in the rats. The effect of raisins was superior to RGJ which might be due to its high contents of fibres and proteins.  Conclusions: This study highlighted the importance of supplementation of red grape and raisins in protection against the harmful effects induced by deposition of fat on the renal tubules’ structure and function.

Synthesis and antimicrobial effects of highly dispersed, cellulose-stabilized silver/cellulose nanocomposites

Small, spherical silver nanoclusters were synthesised on the surface of paper as a model cellulosic fibre substrate by a standard chemical reduction method. The concentration of the silver nanoclusters on the substrate surface is roughly proportional to the initial silver salt concentration. However, there is a noticeable degree of nanocluster aggregation to larger agglomerates. The addition of small amounts of α-cellulose, carboxymethyl cellulose or aminocellulose during the synthesis of the silver/cellulose nanocomposites suppresses this aggregation and significantly increases the concentration of the silver nanoclusters on the surface of the fibres of cellulose. These small, surface-stabilised silver nanoclusters, with the desired size and morphology, deposited from aqueous solutions on the surface of cellulosic cotton fibres, show enhanced antibacterial activity against MRSA compared to that of the corresponding silver/cotton nanocomposites prepared in the absence of a cellulosic surface stabiliser

Synthesis and antibacterial effects of cobalt–cellulose magnetic nanocomposites

© The Royal Society of Chemistry. Green synthesis is employed to prepare cobalt/cellulose nanocomposites with cubic (α-cobalt) cobalt as a main component with antibacterial and magnetic properties. An in situ reduction of aqueous solutions of cobalt ions on a model cellulose substrate surface using hydrogen gas affords spherical, cellulose-stabilised cobalt nanoclusters with magnetic properties and an average diameter of 7 nm that are distributed evenly over the surface of the cellulose fibres. These cobalt/cellulose nanocomposites exhibit good antibacterial action against opportunistic pathogens both Gram-positive (S. aureus) and Gram-negative (E. coli, A. baumannii and P. aeruginosa), with zones of inhibition up to 15 mm, thereby encouraging the deployment of these advanced materials for the treatment of wastewater or within medical dressings. This method of preparation is compared with the analogous in situ reduction of cobalt ions on a cellulose surface using sodium borohydride as reducing agent

NGAL is downregulated in oral squamous cell carcinoma and leads to increased survival, proliferation, migration and chemoresistance

Oral cancer is a major public health burden worldwide. The lack of biomarkers for early diagnosis has increased the difficulty in managing this disease. Recent studies have reported that neutrophil gelatinase-associated lipocalin (NGAL), a secreted glycoprotein, is upregulated in various tumors. In our study, we found that NGAL was significantly downregulated in primary malignant and metastatic tissues of oral cancer in comparison to normal tissues. The downregulation of NGAL was strongly correlated with both degree of differentiation and stage (I–IV); it can also serve as a prognostic biomarker for oral cancer. Additionally, tobacco carcinogens were found to be involved in the downregulation of NGAL. Mechanistic studies revealed that knockdown of NGAL increased oral cancer cell proliferation, survival, and migration; it also induced resistance against cisplatin. Silencing of NGAL activated mammalian target of rapamycin (mTOR)signaling and reduced autophagy by the liver kinase B1 (LKB1)-activated protein kinase (AMPK)-p53-Redd1 signaling axis. Moreover, cyclin-D1, Bcl-2, and matrix metalloproteinase-9 (MMP-9) were upregulated, and caspase-9 was downregulated, suggesting that silencing of NGAL increases oral cancer cell proliferation, survival, and migration. Thus, from our study, it is evident that downregulation of NGAL activates the mTOR pathway and helps in the progression of oral cancer

A prospective antibiotic point prevalence survey in two primary referral hospitals during and after pilgrims stay in Madinah, Saudi Arabia

Purpose: To assess current patterns of antibiotic use by carrying out two point-prevalence surveys (PPS) in Madinah after the return of hajj pilgrims from Makkah and when Madinah is free from pilgrims. Methods: In September 2016 and November 2016, a prospective PPS was conducted on two separate dates (during the hajj pilgrims stay in Madinah and after they leave). Data on antibiotics use were generated during these two periods. This involved an audit from all the departments of two referral hospitals (King Fahad Hospital (KFH) - 425 beds, and Al Ansar Hospital - 100 beds) of inpatients records. Data were collected using standard forms adapted from the European Centre for Disease Control (ECDC). Results: A total of 675 inpatients were included in PPS; among them, 332 (49.18 %) patients were receiving antibiotic therapy. In September 2016, 168 patients were treated with antibiotics, with a prevalence rate of 50.60 %, whereas, in November 2016, the prevalence rate was 49.40 %. Overall, 198 patients were identified in surgical wards, of which 132 patients (66.6 %) were receiving antibiotic therapy; 121 patients in ICU of which 70 patients (57.8 %) received antibiotics; 13 patients in other wards of which 6 (46.1 %) received antibiotic treatment; and 343 patients in medical wards of which 126 patients (36.7 %) were treated with antibiotics. There was no significant difference in prevalence of antibiotic prescribing between the two surveys (Pearson Chi-square test, p = 0.56) and with regards to patient age between the two surveys (Mann-Whitney U-test, p = 0.32). Conclusion: The results demonstrate that antibiotic use with adherence to hospital guidelines and PPS helps in identifying targets for quality improvement. Moreover, to escalate the prudent use of antibiotics in hospitals, PPS provides a useful tool. Furthermore, this survey provides a background to evaluate antibiotic use by a standardized methodology. Keywords: Point prevalence survey, Antibiotic use, Prescribing practices, Antibiotic resistance, Quality improvement, Antibiotic stewardship, Hajj, Pilgrim

"Dreaming in colour’: disabled higher education students’ perspectives on improving design practices that would enable them to benefit from their use of technologies"

The focus of this paper is the design of technology products and services for disabled students in higher education. It analyses the perspectives of disabled students studying in the US, the UK, Germany, Israel and Canada, regarding their experiences of using technologies to support their learning. The students shared how the functionality of the technologies supported them to study and enabled them to achieve their academic potential. Despite these positive outcomes, the students also reported difficulties associated with: i) the design of the technologies, ii) a lack of technology know-how and iii) a lack of social capital. When identifying potential solutions to these difficulties the disabled students imagined both preferable and possible futures where faculty, higher education institutions, researchers and technology companies are challenged to push the boundaries of their current design practices

Loss of UGP2 in brain leads to a severe epileptic encephalopathy, emphasizing that bi-allelic isoform-specific start-loss mutations of essential genes can cause genetic diseases.

Developmental and/or epileptic encephalopathies (DEEs) are a group of devastating genetic disorders, resulting in early-onset, therapy-resistant seizures and developmental delay. Here we report on 22 individuals from 15 families presenting with a severe form of intractable epilepsy, severe developmental delay, progressive microcephaly, visual disturbance and similar minor dysmorphisms. Whole exome sequencing identified a recurrent, homozygous variant (chr2:64083454A > G) in the essential UDP-glucose pyrophosphorylase (UGP2) gene in all probands. This rare variant results in a tolerable Met12Val missense change of the longer UGP2 protein isoform but causes a disruption of the start codon of the shorter isoform, which is predominant in brain. We show that the absence of the shorter isoform leads to a reduction of functional UGP2 enzyme in neural stem cells, leading to altered glycogen metabolism, upregulated unfolded protein response and premature neuronal differentiation, as modeled during pluripotent stem cell differentiation in vitro. In contrast, the complete lack of all UGP2 isoforms leads to differentiation defects in multiple lineages in human cells. Reduced expression of Ugp2a/Ugp2b in vivo in zebrafish mimics visual disturbance and mutant animals show a behavioral phenotype. Our study identifies a recurrent start codon mutation in UGP2 as a cause of a novel autosomal recessive DEE syndrome. Importantly, it also shows that isoform-specific start-loss mutations causing expression loss of a tissue-relevant isoform of an essential protein can cause a genetic disease, even when an organism-wide protein absence is incompatible with life. We provide additional examples where a similar disease mechanism applies

ICAR: endoscopic skull‐base surgery

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Bi-allelic variants in HOPS complex subunit VPS41 cause cerebellar ataxia and abnormal membrane trafficking.

Membrane trafficking is a complex, essential process in eukaryotic cells responsible for protein transport and processing. Deficiencies in vacuolar protein sorting (VPS) proteins, key regulators of trafficking, cause abnormal intracellular segregation of macromolecules and organelles and are linked to human disease. VPS proteins function as part of complexes such as the homotypic fusion and vacuole protein sorting (HOPS) tethering complex, composed of VPS11, VPS16, VPS18, VPS33A, VPS39 and VPS41. The HOPS-specific subunit VPS41 has been reported to promote viability of dopaminergic neurons in Parkinson's disease but to date has not been linked to human disease. Here, we describe five unrelated families with nine affected individuals, all carrying homozygous variants in VPS41 that we show impact protein function. All affected individuals presented with a progressive neurodevelopmental disorder consisting of cognitive impairment, cerebellar atrophy/hypoplasia, motor dysfunction with ataxia and dystonia, and nystagmus. Zebrafish disease modelling supports the involvement of VPS41 dysfunction in the disorder, indicating lysosomal dysregulation throughout the brain and providing support for cerebellar and microglial abnormalities when vps41 was mutated. This provides the first example of human disease linked to the HOPS-specific subunit VPS41 and suggests the importance of HOPS complex activity for cerebellar function

A Novel Poly-N-Epoxy Propyl Carbazole Based Memory Device

Generally, polymer-based memory devices store information in a manner distinct from that of silicon-based memory devices. Conventional silicon memory devices store charges as either zero or one for digital information, whereas most polymers store charges by the switching of electrical resistance. For the first time, this study reports that the novel conducting polymer Poly-N-Epoxy-Propyl Carbazole (PEPC) can offer effective memory storage behavior. In the current research, the electrical characterization of a single layer memory device (metal/polymer/metal) using PEPC, with or without doping of charge transfer complexes 7,7,8,8-tetra-cyanoquino-dimethane (TCNQ), was investigated. From the current–voltage characteristics, it was found that PEPC shows memory switching effects in both cases (with or without the TCNQ complex). However, in the presence of TCNQ, the PEPC performs faster memory switching at relatively lower voltage and, therefore, a higher ON and OFF ratio (ION/IOFF ~ 100) was observed. The outcome of this study may help to further understand the memory switching effects of conducting polymer