Synergistic hyperactivation of both mTORC1 and mTORC2 underlies the neural abnormalities of PTEN-deficient human neurons and cortical organoids.

Mutations in the phosphatase and tensin homolog (PTEN) gene are associated with severe neurodevelopmental disorders. Loss of PTEN leads to hyperactivation of the mechanistic target of rapamycin (mTOR), which functions in two distinct protein complexes, mTORC1 and mTORC2. The downstream signaling mechanisms that contribute to PTEN mutant phenotypes are not well delineated. Here, we show that pluripotent stem cell-derived PTEN mutant human neurons, neural precursors, and cortical organoids recapitulate disease-relevant phenotypes, including hypertrophy, electrical hyperactivity, enhanced proliferation, and structural overgrowth. PTEN loss leads to simultaneous hyperactivation of mTORC1 and mTORC2. We dissect the contribution of mTORC1 and mTORC2 by generating double mutants of PTEN and RPTOR or RICTOR, respectively. Our results reveal that the synergistic hyperactivation of both mTORC1 and mTORC2 is essential for the PTEN mutant human neural phenotypes. Together, our findings provide insights into the molecular mechanisms that underlie PTEN-related neural disorders and highlight novel therapeutic targets.

Study of plasmid mediated quinolone resistance genes among Escherichia coli and Klebsiella pneumoniae isolated from pediatric patients with sepsis.

The resistance to antibiotics in Gram-negative bacilli causing sepsis is a warning sign of failure of therapy. Klebsiella pneumoniae (K. pneumoniae) and Escherichia coli (E. coli) represent major Gram-negative bacilli associated with sepsis. Quinolone resistance is an emerging resistance among E. coli and K. pneumoniae. Therefore, the present study aimed to study the presence of plasmid-mediated quinolone resistance (PMQR) genes qnrA, qnrB, and qnrS by polymerase chain reaction (PCR) in E. coli and K. pneumoniae isolated from pediatric patients with sepsis. This was a retrospective cross-sectional study that included pediatric patients with healthcare-associated sepsis. The E. coli and K. pneumoniae isolates were identified by microbiological methods. PMQR genes namely qnrA, qnrB, and qnrS were detected in E. coli and K. pneumoniae isolates by PCR. The results were analyzed by SPPS24, and the qualitative data was analyzed as numbers and percentages and comparison was performed by Chi-square test, P was significant if < 0.05. The most prevalent gene detected by PCR was qnrA (75%), followed by qnrB (28.1%), and qnrS (25%). The most frequently detected qnr gene in E coli and K. pneumoniae was qnrA (28.8%, and 16.3% respectively). The present study highlights the high prevalence of ciprofloxacin resistance among E. coli and K. pneumoniae isolated from pediatric patients with healthcare-associated sepsis. There was a high frequency of PMQR genes in E. coli and K. pneumoniae isolated from pediatric patients. Therefore, it is important to monitor the spread of PMQR genes in clinical isolates to ensure efficient antibiotic use in those children. The finding denotes the importance of an antibiotics surveillance program.

Assessment of shoulder proprioception in patients with chronic mechanical cervical pain: A comparative study.

BACKGROUND: Chronic mechanical cervical pain (CMCP) is a common disabling problem worldwide, interfering with upper extremities function. However studying the impact of CMCP on shoulder proprioception is still lacking. OBJECTIVE: To investigate the impact of CMCP on shoulder proprioception in young adults compared with normal control (NC) individuals. METHODS: A comparative study was conducted between two groups; 40 patients with CMCP (mean age 32.28 ± 6.586) and 40 age and sex matched NC (mean age 33.43 ± 9.021). The Biodex isokinetic dynamometer was used to assess shoulder active sense of position at 30∘ external and internal rotations. The absolute angular error was calculated for the dominant and non-dominant shoulders. RESULTS: The absolute angular error was significantly increased only in the CMCP at both rotation angles for both shoulders, showing a remarkable increase on the dominant shoulder and in the external rotation range compared with NC. CONCLUSIONS: CMCP can significantly impair shoulder proprioception, particularly on the dominant side and in external rotation range. This could emphasize the careful examination of shoulder proprioception for the early detection of shoulders at risk, to eliminate the possibility of shoulder instability and/or injury in young adults with CMCP.

Understanding neural development and diseases using CRISPR screens in human pluripotent stem cell-derived cultures.

The brain is arguably the most complex part of the human body in form and function. Much remains unclear about the molecular mechanisms that regulate its normal and pathological physiology. This lack of knowledge largely stems from the inaccessible nature of the human brain, and the limitation of animal models. As a result, brain disorders are difficult to understand and even more difficult to treat. Recent advances in generating human pluripotent stem cells (hPSCs)-derived 2-dimensional (2D) and 3-dimensional (3D) neural cultures have provided an accessible system to model the human brain. Breakthroughs in gene editing technologies such as CRISPR/Cas9 further elevate the hPSCs into a genetically tractable experimental system. Powerful genetic screens, previously reserved for model organisms and transformed cell lines, can now be performed in human neural cells. Combined with the rapidly expanding single-cell genomics toolkit, these technological advances culminate to create an unprecedented opportunity to study the human brain using functional genomics. This review will summarize the current progress of applying CRISPR-based genetic screens in hPSCs-derived 2D neural cultures and 3D brain organoids. We will also evaluate the key technologies involved and discuss their related experimental considerations and future applications.

Neutrophil-to-lymphocyte ratio as a predictive and prognostic marker in children with dilated cardiomyopathy.

OBJECTIVES: We aimed to evaluate neutrophil-to-lymphocyte ratio in children with acute heart failure due to dilated cardiomyopathy, to assess the predictive and prognostic values of neutrophil-to-lymphocyte ratio, and to correlate its levels with brain natriuretic peptide and other various data in these patients. METHOD: We included 50 children with acute heart failure due to dilated cardiomyopathy as the patient group. Fifty healthy children of matched age and sex served as the control group. Patients were evaluated clinically and by echocardiography. A complete blood count with differentiation to evaluate neutrophil-to-lymphocyte ratio was done, and the serum level of brain natriuretic peptide was also measured. All patients were followed up for death or readmission for a period of one year. RESULTS: Neutrophil-to-lymphocyte ratio was significantly higher in patient group as compared to the control group. Neutrophil-to-lymphocyte ratio was significantly increased in patients with higher severity of heart failure. There was a significant increase in neutrophil-to-lymphocyte ratio in patients with bad prognoses compared to those with good prognoses. There was a significant positive correlation between neutrophil-to-lymphocyte ratio and both brain natriuretic peptide and clinical stage of heart failure while there was a significant negative correlation between neutrophil-to-lymphocyte ratio and left ventricular systolic function. The best cut-off of neutrophil-to-lymphocyte ratio to predict adverse outcomes in children with dilated cardiomyopathy was >3.6 with 87% sensitivity and 79% specificity. The cut-off of neutrophil-to-lymphocyte ratio to predict patients who will not respond to conventional treatment was ≥3.85 with 85% sensitivity and 100% specificity. CONCLUSION: Neutrophil-to-lymphocyte ratio is a cheap good predictive and prognostic biomarker in children with dilated cardiomyopathy.

Nutritional rehabilitation of malnourished children: are nutritional supplements a must?

OBJECTIVE: Malnutrition threatens children worldwide. The objective of the current study was to highlight the role of nutritional screening, evaluate the effectiveness of nutritional intervention program, and whether nutritional supplements have surplus benefit. PATIENTS AND METHODS: Screening Tool for the Assessment of Malnutrition in Pediatrics (STAMP) was used to screen 3640 clinically stable 2-5 years old children recruited from the outpatient clinics, Children's Hospital, Ain Shams University. A total of 100 patients at high risk of malnutrition were enrolled. Full nutritional assessment was done and according to the distribution of the calories in the daily meal plan, the patients were randomly divided into two groups each comprised 50 patients. Group A received tailored nutritional dietary rehabilitation plan including dietary supplements, while Group B received only dietary advice. Anthropometric measurements, laboratory tests, as well as STAMP scoring were reassessed after the nutritional rehabilitation programs. RESULTS: Nutritional screening revealed that 5.14% were at high risk of malnutrition. Both studied groups showed significant improvement in caloric intake and all anthropometric measurements upon nutritional rehabilitation, except for the height z scores. Patients who received nutritional supplements showed significantly better changes regarding weight, BMI, caloric intake, and hemoglobin. Regarding STAMP categories during follow up, Group A had only 6% of the patients still in the high-risk category and 76% were at low risk compared to 14% high risk and only 54% were at low risk in Group B. CONCLUSIONS: Nutritional screening in pediatric outpatient facilities can lead to implementing prompt nutritional rehabilitation, which can reflect on the patients' overall health. Tailored nutritional plan can accomplish good response in terms of improvement of caloric intake, anthropometric measurements and laboratory parameters. Adding a nutritional supplement to the dietary plan during nutritional rehabilitation isn't a must but it ensures superior goal achievement.

Evaluation of Green Silver Nanoparticles Fabricated by Spirulina platensis Phycocyanin as Anticancer and Antimicrobial Agents.

Green nanotechnology has attracted attention worldwide, especially in treating cancer and drug-resistant section 6 microbes. This work aims to investigate the anticancer activity of green silver nanoparticles synthesized by Spirulina platensis phycocyanin (SPAgNPs) on two cancer cell lines: Lung cancer cell line (A-549) and breast cancer cell line (MCF-7), compared to the normal human lung cell line (A138). We also aimed to investigate the bactericidal activity against Staphylococcus aureus ATCC29737, Bacillus cereus ATCC11778, Escherichia coli ATCC8379, and Klebsiella pneumonia, as well as the fungicidal activity against Candida albicans (ATCC6019) and Aspergillus niger. The obtained SPAgNPs were spherical and crystalline with a size of 30 nm and a net charge of -26.32 mV. Furthermore, they were surrounded by active groups responsible for stability. The SPAgNPs scavenged 85% of the DPPH radical with a relative increase of approximately 30% over the extract. The proliferation of cancer cells using the MTT assay clarified that both cancer cells (A-549 and MCF-7) are regularly inhibited as they grow on different concentrations of SPAgNPs. The maximum inhibitory effect of SPAgNPs (50 ppm) reached 90.99 and 89.51% against A-549 and MCF7, respectively. Regarding antimicrobial activity, no inhibition zones occurred in bacterial or fungal strains at low concentrations of SPAgNPs and the aqueous Spirulina platensis extract. However, at high concentrations, inhibition zones, especially SPAgNPs, were more potent for all tested microorganisms than their positive controls, with particular reference to Staphylococcus aureus, since the inhibition zones were 3.2, 3.8, and 4.3 mm, and Bacillus cereus was 2.37 mm when compared to tetracycline (2.33 mm). SPAgNPs have more potent antifungal activity, especially against Aspergillus niger, compared to their positive controls. We concluded that SPAgNPs are powerful agents against oxidative stress and microbial infection.

Integrating experimental model, LC-MS/MS chemical analysis, and systems biology approach to investigate the possible antidiabetic effect and mechanisms of Matricaria aurea (Golden Chamomile) in type 2 diabetes mellitus.

Type 2 diabetes mellitus (T2DM) is a heterogeneous disease with numerous abnormal targets and pathways involved in insulin resistance, low-grade inflammation, oxidative stress, beta cell dysfunction, and epigenetic factors. Botanical drugs provide a large chemical space that can modify various targets simultaneously. Matricaria aurea (MA, golden chamomile) is a widely used herb in Middle Eastern communities for many ailments, including diabetes mellitus, without any scientific basis to support this tradition. For the first time, this study aimed to investigate the possible antidiabetic activity of MA in a type 2 diabetic rat model, identify chemical constituents by LC-MS/MS, and then elucidate the molecular mechanism(s) using enzyme activity assays, q-RTPCR gene expression analysis, network pharmacology analysis, and molecular docking simulation. Our results demonstrated that only the polar hydroethanolic extract of MA had remarkable antidiabetic activity. Furthermore, it improved dyslipidemia, insulin resistance status, ALT, and AST levels. LC-MS/MS analysis of MA hydroethanolic extract identified 62 compounds, including the popular chamomile flavonoids apigenin and luteolin, other flavonoids and their glycosides, coumarin derivatives, and phenolic acids. Based on pharmacokinetic screening and literature, 46 compounds were chosen for subsequent network analysis, which linked to 364 candidate T2DM targets from various databases and literature. The network analysis identified 123 hub proteins, including insulin signaling and metabolic proteins: IRS1, IRS2, PIK3R1, AKT1, AKT2, MAPK1, MAPK3, and PCK1, inflammatory proteins: TNF and IL1B, antioxidant enzymes: CAT and SOD, and others. Subsequent filtering identified 40 crucial core targets (major hubs) of MA in T2DM treatment. Functional enrichment analyses of the candidate targets revealed that MA targets were mainly involved in the inflammatory module, energy-sensing/endocrine/metabolic module, and oxidative stress module. q-RTPCR gene expression analysis showed that MA hydroethanolic extract was able to significantly upregulate PIK3R1 and downregulate IL1B, PCK1, and MIR29A. Moreover, the activity of the antioxidant hub enzymes was substantially increased. Molecular docking scores were also consistent with the networks' predictions. Based on experimental and computational analysis, this study revealed for the first time that MA exerted antidiabetic action via simultaneous modulation of multiple targets and pathways, including inflammatory pathways, energy-sensing/endocrine/metabolic pathways, and oxidative stress pathways.

A systematic investigation of four ports MIMO antenna depending on flexible material for UWB networks.

A flexible quad-port MIMO antenna with good isolation features with both flat and bending configurations is presented and investigated in this work. The single unit of the MIMO is composed of a crescent-shaped monopole antenna connected with a curved coplanar waveguide (CPW) fed to enhance the operating bandwidth. A thin and flexible Roger 3003 material with thickness = 0.13 mm, εr = 3, and tan δ = 0.001 is used. To improve the isolation between ports which in turn improves the performance of the MIMO system, the single unit antenna is repeated four times and placed orthogonal to each other. A 54 mm × 54 mm × 0.13 mm (0.63λo × 0.63λo × 0.0015λo @ 3.5 GHz) is the total size of the quad ports MIMO antenna. The flexible MIMO antennas in both flat and bending layouts are simulated, tested and the outcomes achieved S11 < - 10 dB from 3.5 GHz up to 11 GHz with mutual coupling ≤ - 17 dB between ports. The radiation patterns of the MIMO antenna are tested with 5 dB peak gain and with semi-omnidirectional and bidirectional patterns in both two planes. The Diversity Gain (DG) values ≥ 9.9 dB through the designed working band, Envelop Correlation Coefficient (ECC) lower than 0.03 from 3.5 GHz to 4 GHz and lower than 0.01 from 4 to 11 GHz, and Channel Capacity Loss (CCL) value ≤ 0.5 bit/s/Hz over the worked band are calculated and extracted in flat and bending configurations and achieved suitable values which support the suggested antenna in the UWB flexible networks.

Dandy-Walker malformation and intermittent explosive disorder: A case report.

Dandy-Walker malformation is a group of brain malformations that sometimes present with psychotic features, violent and impulsive behavior, or mood symptoms. Here, we present a case report of a patient with Dandy-Walker malformation who presented with intermittent explosive disorder. A young man, aged 18 years, was brought to the author's hospital [Hamad Medical Corporation] with anger outbursts, irritable mood, and violent behavior. His magnetic resonance imaging scans showed typical alterations of Dandy-Walker malformation. He also had mild intellectual disabilities and epilepsy. After a few weeks of treatment with sodium valproate 1000 mg/day and risperidone 2 mg/day, his condition improved, and his violent behavior was significantly reduced in 3 months, 6 months, and 1 year of follow-up. There is broad consensus that Dandy-Walker malformation is associated with psychosis and other behavioral abnormalities because of a possible disruption in the prefrontal, thalamic, and cerebellar circuits. The link between Dandy-Walker malformation and intermittent explosive disorder may help us understand this type of brain malformation as a potential psychiatric comorbidity.

Strip1 regulates retinal ganglion cell survival by suppressing Jun-mediated apoptosis to promote retinal neural circuit formation.

In the vertebrate retina, an interplay between retinal ganglion cells (RGCs), amacrine (AC), and bipolar (BP) cells establishes a synaptic layer called the inner plexiform layer (IPL). This circuit conveys signals from photoreceptors to visual centers in the brain. However, the molecular mechanisms involved in its development remain poorly understood. Striatin-interacting protein 1 (Strip1) is a core component of the striatin-interacting phosphatases and kinases (STRIPAK) complex, and it has shown emerging roles in embryonic morphogenesis. Here, we uncover the importance of Strip1 in inner retina development. Using zebrafish, we show that loss of Strip1 causes defects in IPL formation. In strip1 mutants, RGCs undergo dramatic cell death shortly after birth. AC and BP cells subsequently invade the degenerating RGC layer, leading to a disorganized IPL. Mechanistically, zebrafish Strip1 interacts with its STRIPAK partner, Striatin 3 (Strn3), and both show overlapping functions in RGC survival. Furthermore, loss of Strip1 or Strn3 leads to activation of the proapoptotic marker, Jun, within RGCs, and Jun knockdown rescues RGC survival in strip1 mutants. In addition to its function in RGC maintenance, Strip1 is required for RGC dendritic patterning, which likely contributes to proper IPL formation. Taken together, we propose that a series of Strip1-mediated regulatory events coordinates inner retinal circuit formation by maintaining RGCs during development, which ensures proper positioning and neurite patterning of inner retinal neurons.

The back of the eye is lined with an intricate tissue known as the retina, which consists of carefully stacked neurons connecting to each other in well-defined 'synaptic' layers. Near the surface, photoreceptors cells detect changes in light levels, before passing this information through the inner plexiform layer to retinal ganglion cells (or RGCs) below. These neurons will then relay the visual signals to the brain. Despite the importance of this inner retinal circuit, little is known about how it is created as an organism develops. As a response, Ahmed et al. sought to identify which genes are essential to establish the inner retinal circuit, and how their absence affects retinal structure. To do this, they introduced random errors in the genetic code of zebrafish and visualised the resulting retinal circuits in these fast-growing, translucent fish. Initial screening studies found fish with mutations in a gene encoding a protein called Strip1 had irregular layering of the inner retina. Further imaging experiments to pinpoint the individual neurons affected showed that in zebrafish without Strip1, RGCs died in the first few days of development. Consequently, other neurons moved into the RGC layer to replace the lost cells, leading to layering defects. Ahmed et al. concluded that Strip1 promotes RGC survival and thereby coordinates proper positioning of neurons in the inner retina. In summary, these findings help to understand how the inner retina is wired; they could also shed light on the way other layered structures are established in the nervous system. Moreover, this study paves the way for future research investigating Strip1 as a potential therapeutic target to slow down the death of RGCs in conditions such as glaucoma.

Anti-inflammatory and cytotoxic specialised metabolites from the leaves of Glandularia × hybrida.

In our ongoing effort to investigate active specialised metabolites from genus Glandularia, phytochemical studies on the ethanolic extract of Glandularia × hybrida (Groenl. & Rümpler) G.L. Nesom & Pruski leaves resulted in the isolation of three undescribed compounds, a dibenzylbutyrolactolic lignan and two echinocystic acid based triterpenoid saponins, in addition to two known compounds. Interestingly, this study reports isolation of chemo-systematically valuable specialised metabolites for the first time from the genus under investigation. Additionally, the isolated metabolites were evaluated for their iNOS inhibition and cytotoxic activities using a combination of in silico and in vitro studies. The pharmacokinetics properties (ADMET) of some of the isolated compounds were determined using pkCSM-pharmacokinetics server. Molecular docking analysis showed that saponin compound possesses higher negative score (-9.59 kcal/mol) than the lignan compound (-6.56 kcal/mol). The isolated compounds also showed iNOS inhibition activity with IC50 values ranging between 6.6 and 49.7 µM and significant cytotoxic activity against a series of cell lines including SK-MEL, KB, BT-549, SK-OV-3, LLC-PK1 and VERO cells. Hence, this study reveals that specialised metabolites from G. hybrida plant are of significant anti-inflammatory and cytotoxicity potentials.

CT-P13 subcutaneous infliximab in gastroenterology and rheumatology.

The drug infliximab has been a key milestone in the treatment of inflammatory conditions such as Crohn's disease, ulcerative colitis, rheumatoid arthritis and the seronegative spondyloarthritides. Biosimilar drugs followed the originator, further improving access and diversity of therapy choice. Subcutaneous infliximab (CT-P13) holds potential for greater patient flexibility by self administration, reducing travel and hospital attendance for infusion, particularly relevant at a time of pandemic. We highlight the pharmacodynamic and pharmacokinetic basis of the subcutaneous device, clinical trials in rheumatology and gastroenterology and consider the safety and cost implications. Real-world switching data is required to confirm the efficacy data from clinical trials given the reduction in dosing flexibility compared with intravenous therapy.

Interplay of Biochemical, Genetic, and Immunohistochemical Factors in the Etio-Pathogenesis of Gastric Ulcer in Rats: A Comparative Study of the Effect of Pomegranate Loaded Nanoparticles Versus Pomegranate Peel Extract.

BACKGROUND: Few data are available about the role of herbal extract loaded nanoparticles as an alternative safe medicine for the management of a gastric ulcer. AIM: This work is targeted at exploring the physiological effects of pomegranate loaded nanoparticles (PLN) against an indomethacin IND-induced gastric ulcer and comparing the results with traditional pomegranate peel extract (PPE). METHODS: Twenty-four rats were equally distributed into four groups: control, IND-treated, PLN-treated, and PPE-treated groups. Gross examination of gastric mucosa, and the calculation of ulcer and inhibition indices were done. Serum malondialdehyde (MDA), total antioxidant capacity (TAC), interleukin 2 (IL-2), IL-6, IL-10, gastric homogenate prostaglandin E2 (PGE2), and nitric oxide (NO) were estimated. Mucosal endothelial nitric oxide synthase (eNOS mRNA) expression was identified by qPCR. Histological and immuno-histochemical staining of Tumor necrosis factor-α (TNF-α) and eNOS of stomach mucosa were performed. RESULTS: In comparison with the control group, IND-treated rats showed visible multiple ulcers with ulcer index, serum MDA, IL-2 and IL-6 were elevated while IL-10, PGE2, NO, and eNOS mRNA expression were significantly reduced. Damaged surface epithelium with disrupted glandular architecture and heavy leucocyte infiltration of lamina propria was noticed. Immunohistochemical staining of stomach mucosa revealed marked increased TNF-α and reduced eNOS. Oral administration of PLN and PPE succeeded in improving the gross mucosal picture, and all biochemical, histological, and immunohistochemical alterations. CONCLUSION: Both PLN and PPE potently alleviated IND-induced gastric ulceration via increasing TAC, PGE2, NO, eNOS mRNA, and protein expression. However, the healing effect of PLN was obviously greater than PPE-treated rats.

Clinico-pathological relationship between androgen receptor and tumour infiltrating lymphocytes in triple negative breast cancer.

BACKGROUND: Triple negative breast cancer (TNBC) is an aggressive subtype of breast cancer (BC) with ill-defined therapeutic targets. Androgen receptor (AR) and tumour-infiltrating lymphocytes (TILs) had a prognostic and predictive value in TNBC. The relationship between AR, TILs and clinical behaviour is still not fully understood. METHODS: Thirty-six TNBC patients were evaluated for AR (positive if ≥1% expression), CD3, CD4, CD8 and CD20 by immunohistochemistry. Stromal TILs were quantified following TILs Working Group recommendations. Lymphocyte-predominant breast cancer (LPBC) was defined as stromal TILs ≥ 50%, whereas lymphocyte-deficient breast cancer (LDBC) was defined as <50%. RESULTS: The mean age was 52.5 years and 27.8% were ≥60 years. Seven patients (21.2%) were AR+. All AR+ cases were postmenopausal (≥50 years old). LPBC was 32.2% of the whole cohort. Median TILs were 37.5% and 10% (p = 0.1) and median CD20 was 20% and 7.5% (p = 0.008) in AR- and AR+, respectively. Mean CD3 was 80.7% and 93.3% (p = 0.007) and CD8 was 75% and 80.8% (p= 0.41) in AR- and AR+, respectively. All patients who were ≥60 years old expressed CD20. LDBC was found to be significantly higher in N+ versus N- patients (p = 0.03) with median TILs of 20% versus 50% in N+ versus N-, respectively (p = 0.03). LDBC was associated with higher risk of lymph node (LN) involvement (odds ratio = 6; 95% CI = 1.05-34.21; p = 0.04). CONCLUSIONS: AR expression was evident in older age (≥50 years). Median CD20 was higher in AR- TNBC, while mean CD3 was higher in AR+ tumours. LDBC was associated with higher risk of LN involvement. Larger studies are needed to focus on the clinical impact of the relation between AR and TILs in TNBC.

An exploration of individual knowledge and behavior for utilizing OTC drugs and dietary supplements for health enhancement: An empirical analysis from Dubai.

Background: Self-medication and acquisition of over-the-counter (OTC) drugs are emerging community health issues. Besides being a cheap alternative for treating common illnesses, the behavior entails serious ramifications, such as medication wastage, increasing pathogen resistance, and adverse drug reactions. So, the purpose of the present study was to explore and understand the consumption of commonly used OTC drugs and dietary supplements in Dubai and also assess individuals' self-care behaviors related to OTC and dietary supplements. Methodology: A cross-sectional study design was adopted in the present study and 200 participants were included in this study. Data was entered and analyzed through SPSS version 22. While the chi-square test was conducted to find out significance among variables. Findings: Results from the current study showed that more than a quarter of the participants (31%) were male and 69% of them were females. The prevalence of OTC drugs and dietary supplements was higher (98%) among the individuals living in Dubai. The majority of participants (80%) used analgesics as OTC drugs. Results also revealed that 35.5% of participants used vitamins on a daily basis, 11% used them on weekly basis, and 5.5% used them on monthly basis. While 79.5% of participants obtained their OTC drugs and dietary supplements from community pharmacies. Conclusion: This study provides significant findings regarding an individual's knowledge and behavior for utilizing OTC drugs and dietary supplements. The result has drawn from the present study can help the policymakers, and stakeholders to promulgate and effectiveness of policies and program implementation within the country. Lastly future studies with larger samples are required for the generalizability of the study results.

Validity of mini-fluid challenge for predicting fluid responsiveness following liver transplantation.

BACKGROUND: Mini-fluid challenge is a well tested and effective tool to predict fluid responsiveness under various clinical conditions. However, mini-fluid challenge has never been tested in patients with end-stage liver disease. This study investigated whether infusion of 150 ml albumin 5% can predict fluid responsiveness in cirrhotic patients following liver transplant. METHODS: Fifty patients receiving living donor liver transplant were included in the analysis. Mini-fluid challenge composed of 150 ml of albumin 5% administered over 1 min in three consecutive 50-ml fluid boluses. An additional 350 ml was then infused at a constant rate over 15 min (for a total of 500 ml). Stroke volume (SV) was measured as the product of the subaortic velocity time integral (VTI) and left ventricular outflow tract (LVOT) area. Fluid responsiveness was defined as an increase in SV by ≥15% after the infusion. RESULTS: Fifty patients were enrolled in the study. Fourteen patients were classified with Child A, 15 patients with Child B, and 21 patients with Child C cirrhosis. Thirty four patients were fluid responders and 16 patients were fluid non-responders. After 150 ml of albumin 5%, the SV increased significantly in our cohort. The area under receiver operating curve (AUROC) was 0.7 (95% confidence interval [CI] 0.5-0.8, P = 0.005). In subgroup analysis, the SV increased significantly after mini fluid challenge in the Child A group (P = 0.017) but not Child B or C groups (P = 0.3 and 0.29, respectively). The AUROC for mini-fluid challenge in the Child A group was 0.86 (95% confidence interval [CI] 0.6-0.9, P = 0.0004), while mini-fluid challenge failed to discriminate between responders and non-responders in Child B and C groups. CONCLUSION: A mini-fluid challenge of 150 ml albumin 5% can predict fluid responsiveness in liver transplant patients with fair sensitivity and specifiicty. Subgroup analyis revealed that minifluid challenge can predict fluid responsiveness in patients with Child A cirrhosis but not patients with Child B or C cirrhosis. TRIAL REGISTRATION: NCT03396159 . (Prospective registered). Initial registration date was 10/01/2018.

Enrichment, Propagation, and Characterization of Mouse Testis-Derived Mesenchymal Stromal Cells.

The therapeutic potential of multipotent stromal cells (MSCs) largely depends on the isolation and expansion methods used. In this study, we propose a laminin-based technique to select and enrich for MSCs isolated from the mouse testis. Primary cell cultures were prepared from juvenile mouse testes and the capacity to generate colony forming units together with population doubling time (PDT) during expansion were determined. The identity of MSCs was assayed using reverse transcription-polymerase chain reaction (RT-PCR) and flow cytometry for the active expression of cell surface markers, such as CD44, CD73, and CD29; absence of the CD45 hematopoietic cell marker; and in vitro differentiation of the cells into osteoblasts and adipocytes. Testis-derived MSCs (tMSCs) displayed self-renewal properties and in the early passages, exhibited high proliferation patterns with an average PDT of 44.1 hours. The lack of Vasa expression implied that the tMSCs were not of germ cell origin. The RT-PCR data, which were confirmed by immunophenotyping, revealed high expression of CD44 and the absence of CD45 expression in tMSCs. The strong Alizarin Red stain in tMSCs that were stimulated into making bone cells was indicative of the presence of calcium-producing cells (osteoblasts). Likewise, the adipogenic potential of tMSCs was demonstrated based on Oil Red O staining of lipid vacuoles in differentiated cells. Loss of fibroblast-like morphology in late passage cells along with the increase in PDT and the decrease in the mRNA levels of CD73 and CD29 suggested that the tMSCs developmental program is reformed at this stage.

Visualizing the Spatial Relationship of the Genome with the Nuclear Envelope Using Fluorescence In Situ Hybridization.

The genome has a special relationship with the nuclear envelope in cells. Much of the genome is anchored at the nuclear periphery, tethered by chromatin binding proteins such nuclear lamins and other integral membrane proteins. Even though there are global assays such as DAM-ID or ChIP to assess what parts of the genome are associated with the nuclear envelope, it is also essential to be able to visualize regions of the genome in order to reveal their individual relationships with nuclear structures in single cells. This is executed by fluorescence in situ hybridization (FISH) in 2-dimensional flattened nuclei (2D-FISH) or 3-dimensionally preserved cells (3D-FISH) in combination with indirect immunofluorescence to reveal structural proteins. This chapter explains the protocols for 2D- and 3D-FISH in combination with indirect immunofluorescence and discusses options for image capture and analysis. Due to the nuclear envelope proteins being part of the non-extractable nucleoskeleton, we also describe how to prepare DNA halos through salt extraction and how they can be used to study genome behavior and association when combined with 2D-FISH.

Evaluation of Perfusion Index as a Predictor of Vasopressor Requirement in Patients with Severe Sepsis.

We evaluated the ability of perfusion index (PI) to predict vasopressor requirement during early resuscitation in patients with severe sepsis. All consecutive patients with clinically suspected severe sepsis as defined by the criteria of the American College of Chest Physicians/Society of Critical Care Medicine Consensus Conference were included. Perfusion variables included PI, arterial lactate level, central venous oxygen saturation, and the difference between central venous carbon dioxide and arterial carbon dioxide pressures, and were recorded before resuscitation and 6 h thereafter. We enrolled 36 patients with severe sepsis. Twenty-one patients required vasopressors, whereas 15 did not. The cut-off of the PI value for predicting vasopressor requirement was ≤0.3. This cut-off value had a sensitivity of 100% and a specificity of 93%; the area under the curve was 0.96 (95% confidence interval 0.8-0.99, P < 0.0001). The cut-off of the arterial lactate level for predicting vasopressor requirement was ≥1.8 mg dL. This cut-off value had a sensitivity of 82% and a specificity of 80%; the area under the curve was 0.84 (95% confidence interval 0.68-0.94, P < 0.0001). Other perfusion variables failed to predict vasopressor requirement in patients with severe sepsis. We concluded that PI and arterial lactate level are good predictors of vasopressor requirement during early resuscitation in patients with severe sepsis. Further studies are warranted to investigate whether monitoring PI during resuscitation improves the outcome of patients with septic shock.