Modulations in the host cell proteome by the hantavirus nucleocapsid protein.

Hantaviruses have evolved a unique translation strategy to boost the translation of viral mRNA in infected cells. Hantavirus nucleocapsid protein (NP) binds to the viral mRNA 5' UTR and the 40S ribosomal subunit via the ribosomal protein S19. NP associated ribosomes are selectively loaded on viral transcripts to boost their translation. Here we demonstrate that NP expression upregulated the steady-state levels of a subset of host cell factors primarily involved in protein processing in the endoplasmic reticulum. Detailed investigation of Valosin-containing protein (VCP/p97), one of the upregulated host factors, in both transfected and virus infected cells revealed that NP with the assistance of VCP mRNA 5' UTR facilitates the translation of downstream VCP ORF. The VCP mRNA contains a 5' UTR of 987 nucleotides harboring six unusual start codons upstream of the correct start codon for VCP which is located at 988th position from the 5' cap. In vitro translation of a GFP reporter transcript harboring the VCP mRNA 5' UTR generated both GFP and a short polypeptide of ~14 KDa by translation initiation from start codon located in the 5' UTR at 542nd position from the 5' cap. The translation initiation from 542nd AUG in the UTR sequence was confirmed in cells using a dual reporter construct expressing mCherry and GFP. The synthesis of 14KDa polypeptide dramatically inhibited the translation of the ORF from the downstream correct start codon at 988th position from the 5' cap. We report that purified NP binds to the VCP mRNA 5' UTR with high affinity and NP binding site is located close to the 542ndAUG. NP binding shuts down the translation of 14KDa polypeptide which then facilitates the translation initiation at the correct AUG codon. Knockdown of VCP generated lower levels of poorly infectious hantavirus particle in the cellular cytoplasm whose egress was dramatically inhibited in human umbilical vein endothelial cells. We demonstrated that VCP binds to the hantavirus glycoprotein Gn before its incorporation into assembled virions and facilitates viral spread to neighboring cells during infection. Our results suggest that ribosome engagement at the 542nd AUG codon in the 5' UTR likely regulates the endogenous steady state levels of VCP in cells. Hantaviruses interrupt this regulatory mechanism to enhance the steady state levels of VCP in virus infected cells. This augmentation facilitates virus replication, supports the transmission of the virus to adjacent cells, and promotes the release of infectious virus particles from the host cell.

Development and validation of impact of early integration of palliative care and oncology(IEI PCO) questionnaire: a survey for medical oncologists and nurses.

OBJECTIVES: Many associations have recently recommended early integration of oncology and palliative care for more standard cancer care and better quality of life. We aimed to create a questionnaire to assess the opinion of medical oncologists and nurses about the clinical impact of the integrated palliative care and oncology (PCO) program. METHODS: A novel semi-structured questionnaire called Impact of Early Integration of Palliative Care Oncology (IEI PCO) questionnaire was developed and tested for validity and reliability then distributed to the oncologists and nurses working in Kuwait Cancer Control Center. RESULTS: After the pilot stage, testing the final questionnaire for validity and reliability was done with satisfactory results. Finally, the complete questionnaires were 170 out of 256 (response rate 66.41%). More awareness about the available palliative care services and the new available PCO services (p-value < 0.001 for all). Most of the oncologists and nurses agreed with the currently available structure of PCO, appreciated the patients' discharge plan and continuity of care of palliative medicine, admitted less work burden, a better attitude, and higher satisfaction (p-value for all < 0.001) toward palliative care. Significant improvements in symptoms were appreciated by oncologists and nurses after the integration of palliative care (p-value for all < 0.001. Oncologists and nurses valued repeated honest communication, discussion of the goals of care, dealing more effectively with ending active treatment, and higher acceptance of patients and families of PC policy of transfer, and significant progress in the care of end-of-life symptoms (p-value for all < 0.001). CONCLUSIONS: The IEI PCO questionnaire demonstrated the psychometric criteria for content, face, and construct validity and reliability. It provides a valuable tool to assess the impact of PCO integration. The opinion of medical oncologists and nurses was significantly positive toward the early integration of PCO in Kuwait in most aspects of care. This integration led to improved symptom control, end-of-life care, communication, and planned discharge and follow-up plans. Moreover, decreases the work burden, improves attitude, higher satisfaction of the oncology staff, and continuity of care.

A systematic review of literature on homicide followed by suicide and mental state of perpetrators.

BACKGROUND: Homicide followed by suicide is rare, devastating and perpetrated worldwide. It is commonly assumed that the perpetrator had a mental disorder, raising concomitant questions about prevention. Though events have been reported, there has been no previous systematic review of the mental health of perpetrators. AIMS: Our aims were twofold. First, to identify whether there are recognisable subgroups of homicide-suicides in published literature and, secondly, to investigate the relationship between perpetrator mental state and aspects of the incident. METHODS: We conducted a systematic review of published literature on studies of homicide followed within 24 h by suicide or serious suicide attempt that included measures of perpetrator mental state. RESULTS: Sixty studies were identified, most from North America or Europe. Methodologically, studies were too heterogeneous for meta-analysis. They fell into three main groups: family, mass shooter, and terrorist with an additional small mixed group. There was evidence of mental illness in a minority of perpetrators; its absence in the remainder was only partially evidenced. There was no clear association between any specific mental illness and homicide-suicide type, although depression was most cited. Social role disjunction, motive, substance misuse and relevant risk or threat behaviours were themes identified across all groups. Pre-established ideology was relevant in the mass shooter and terrorism groups. Prior trauma history was notable in the terrorist group. CONCLUSION: Research data were necessarily collected post-incident and in most cases without a standardised approach, so findings must be interpreted cautiously. Nevertheless, they suggest at least some preventive role for mental health professionals. Those presenting to services with depression, suicidal ideation, relationship difficulties and actual, or perceived, changes in social position or role would merit detailed, supportive assessment over time.

Epidemiology and clinical characteristics of adult patients presenting to a low resource, tertiary care emergency department in Pakistan: Challenges & Outcomes.

Objectives: Emergency Departments (EDs) play a major role in managing acute and chronic illnesses, especially in low-to-middle-income countries like Pakistan, which lacks effective primary healthcare. This study reports the epidemiology and clinical characteristics of patients presenting over a two-year period at the Indus Hospital and Health Network (IHHN) adult ED in Karachi, Pakistan. Methods: This is a retrospective observational study conducted through chart review of 264,859 patients, aged 16 years and above, who presented to the IHHN ED, Korangi Campus, from January 2019 to December 2020 after obtaining approval from IHHN IRB. Results: Men were found to be the predominant presenting gender, with a slight rise in the number of women in 2020. The most frequent age group in 2019 was 15-25 (27.7%), whereas it was 25-35 years in 2020 (24.1%), with a decline in total number of elderly visits seen in comparison to previous years. The most frequently seen disposition was 'referral to clinic' in 2019 (48.4%) and 'discharged' in 2020 (39%). Out of all dispositions, maximum Length of stay (LOS) was seen in patients who left against medical advice in both years. Patient acuity showed the highest number of P3 (moderately ill) patients in both years. Infectious diseases accounted for greater than 10% of patients in both years (17.2% and16.5%), followed by gastrointestinal complaints (15.7% and 11.3%), genitourinary complaints (14.9% and 7.9%), and trauma (11.9% and 12.4%). Conclusion: Knowledge of epidemiology and clinical characteristics of patients can help facilitate timely planning of staff deployment and allocation of resources to avoid overcrowding, improve patient outcomes, and increase patient satisfaction through timely management.

"To teach or not to teach- that is the question" The educational and clinical impact of introducing an outcome based, modular curriculum in Social Emergency Medicine (SEM) at a private tertiary care center in Karachi, Pakistan.

INTRODUCTION: An enhanced knowledge of Emergency Medicine (EM) personnel regarding negative Social Determinants of Health (SDH) can impact EM service provision in a resource limited country like Pakistan. Interventions to build capacity in identifying and addressing these SDH through education in Social Emergency Medicine (SEM) can be one of the ways in which EM key performance indicators (KPIs) can be improved. METHOD: A SEM based curriculum was administered to the EM residents at a tertiary care center in Karachi, Pakistan. Pre, post and delayed post-test was conducted for knowledge of EM residents and analyzed using Repeated Measures ANOVA (RMANOVA). Clinical impact of this intervention was assessed through the ability of the residents to identify the patients' SDH and determining appropriate disposition. Comparison of the bounce-back of patients in the pre-intervention (2020) and post-intervention year (2021) year was appreciated to see the clinical impact of this intervention. RESULT: A significant improvement was seen in post intervention (p < 0.001) and follow up knowledge (p < 0.001) of residents regarding negative SDH. Bounce-back rate was higher in the pre-SEM curriculum (43%) as compared to the post-SEM curriculum year (27.7%). Post-intervention, the residents were able to identify the unique Pakistani SDH, however appropriate patient disposition needs further reinforcement. CONCLUSION: The study highlights the beneficial impact of an educational intervention in SEM upon the knowledge of EM residents and the bounce-back of patients in the emergency department (ED) of a low resource setup. This educational intervention can be scaled up to other EDs across Pakistan for potential improvement in knowledge, EM process flow and KPIs.

Exploring Physical Characterization and Different Bio-Applications of Elaeagnus angustifolia Orchestrated Nickel Oxide Nanoparticles.

Elaeagnus angustifolia (EA) mediated green chemistry route was used for the biofabrication of NiONPs without the provision of additional surfactants and capping agents. The formation of NiONPs was confirmed using advanced different characterization techniques such as Scanning electron microscopy, UV, Fourier transmission-infrared, RAMAN, and energy dispersal spectroscopic and dynamic light scattering techniques. Further, different biological activities of EA-NiONPs were studied. Antibacterial activities were performed using five different bacterial strains using disc-diffusion assays and have shown significant results as compared to standard Oxytetracycline discs. Further, NiONPs exhibited excellent antifungal performance against different pathogenic fungal strains. The biocompatibility test was performed using human RBCs, which further confirmed that NiONPs are more biocompatible at the concentration of 7.51-31.25 µg/mL. The antioxidant activities of NiONPs were investigated using DPPH free radical scavenging assay. The NiONPs were demonstrated to have much better antioxidant potentials in terms of % DPPH scavenging (93.5%) and total antioxidant capacity (81%). Anticancer activity was also performed using HUH7 and HEP-G2 cancer cell lines and has shown significant potential with IC50 values of 18.45 µg/mL and 14.84 µg/mL, respectively. Further, the NiONPs were evaluated against Lesihmania tropica parasites and have shown strong antileishmanial potentials. The EA-NiONPs also showed excellent enzyme inhibition activities; protein kinase (19.4 mm) and alpha-amylase (51%). In conclusion, NiONPs have shown significant results against different biological assays. In the future, we suggest various in vivo activities for EA-NiONPs using different animal models to further unveil the biological and biomedical potentials.

Linum corymbulosum Protects Rats against CCl4-Induced Hepatic Injuries through Modulation of an Unfolded Protein Response Pathway and Pro-Inflammatory Intermediates.

Liver fibrosis is a major pathological feature of chronic liver disease and effective therapies are limited at present. The present study focuses on the hepatoprotective potential of L. corymbulosum against carbon tetrachloride (CCl4)-induced liver damage in rats. Analysis of Linum corymbulosum methanol extract (LCM) using high-performance liquid chromatography (HPLC) revealed the presence of rutin, apigenin, catechin, caffeic acid and myricetin. CCl4 administration lowered (p < 0.01) the activities of antioxidant enzymes and reduced glutathione (GSH) content as well as soluble proteins, whereas the concentration of H2O2, nitrite and thiobarbituric acid reactive substances was higher in hepatic samples. In serum, the level of hepatic markers and total bilirubin was elevated followed by CCl4 administration. The expression of glucose-regulated protein (GRP78), x-box binding protein-1 total (XBP-1 t), x-box binding protein-1 spliced (XBP-1 s), x-box binding protein-1 unspliced (XBP-1 u) and glutamate-cysteine ligase catalytic subunit (GCLC) was enhanced in CCl4-administered rats. Similarly, the expression of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and monocyte chemo attractant protein-1 (MCP-1) was strongly increased with CCl4 administration to rats. Co-administration of LCM along with CCl4 to rats lowered (p < 0.05) the expression of the above genes. Histopathology of the liver showed hepatocyte injury, leukocyte infiltration and damaged central lobules in CCl4-treated rats. However, LCM administration to CCl4-intoxicated rats restored the altered parameters towards the levels of control rats. These outcomes indicate the existence of antioxidant and anti-inflammatory constituents in the methanol extract of L. corymbulosum.

Evaluation of Phytochemistry and Pharmacological Properties of Alnus nitida.

In the current study, the anti-inflammatory and analgesic potential of Alnus nitida (leaves and fruits) was evaluated in the Sprague-Dawley rat. Traditionally, A. nitida was used for the treatment of inflammatory ailments. However, A. nitida leaves and fruits have not been yet reported regarding any potential medicinal effects. Leaves/fruits of A. nitida were extracted with methanol and fractionated to attain n-hexane, chloroform, ethyl acetate and aqueous fractions. These extracts were then evaluated for in vivo analgesic and anti-inflammatory potential. For in vivo anti-inflammatory activity, carrageenan-induced paw edema assay, Freunds' complete adjuvant-induced edema, xylene-induced ear edema and histamine-induced paw edema models were used in rats, which showed significant (p < 0.01) reduction (70−80%) in edema in comparison of inflammatory controls. On other hand, for the analgesic assessment, hot plate assay and acetic acid-induced writhing tests were used, which showed a significant (p < 0.01) rise in latency time (40−60%) as compared with pain-induced controls. These results were comparable with standard drugs in a concentration-dependent manner and no mortality or toxicity was observed during all experiments. Then, for the identification of chemical constituents gas chromatography−mass spectrometry (GC-MS) analysis was performed, which indicated the presence of neophytadiene, 3,7,11,15-Tetramethyl-2-hexadecen-1-ol, phytol and vitamin E, justifying the use of A. nitida to treat inflammatory disorders.

Combining Non-invasive Ventilation with timed position change in the Emergency Department to improve oxygenation and outcomes in patients with COVID-19: A prospective analysis from a low resource setup.

Background: Moving away from invasive ventilation towards timed position change and non-invasive ventilation is especially of benefit in low and middle income countries, where judicious use of the available healthcare resources is the need of the day. Our study was conducted prospectively to develop strategies for non-invasive ventilation in combination with timed position change of patients to see its impact on their outcome. Objectives: Non-invasive ventilation has proven to be of benefit in COVID-19 related acute lung injury. The objective of this prospective, cross sectional study was to develop a protocol for the use of non-invasive ventilation with timed position change to improve COVID-19 patients' outcomes in the Emergency Department (ED). Methods: All patients presenting with confirmed or suspected COVID-19 were enrolled in the study from March 2020 to October 2020. Data was collected to see the effect of timed position change and non-invasive ventilation on these patients and its effect on delaying or avoiding invasive ventilation. Results: Of the 207 COVID-19 patients presenting to the IHHN ED, 109(52.7%) had oxygen saturation in the nineties in supine position followed by right lateral in 37(17.9%), sitting up in 30(14.5%), left lateral in 29(14%) and prone position in 2(1%). Maximal oxygenation was achieved with non rebreather mask (NRM) and nasal prongs in 87(42%) of the patients, followed by the use of continuous positive airway pressure (CPAP) in 29(14%). Conclusion: Most of the patients preferred to stay in the supine position and described it as the position of comfort. When used in combination supine position, patients on NRM with nasal prongs and on CPAP, had oxygen saturation in the nineties. Central obesity was found to be the prime reason for the inability to prone our patients. This needs to be followed up in the current fourth wave of COVID-19 to see the effectiveness of the said modalities.

Patient perception regarding privacy and confidentiality: A study from the emergency department of a tertiary care hospital in Karachi, Pakistan.

Background and Objective: Maintaining privacy and ensuring confidentiality with patients is paramount to developing an effective patient-provider relationship. This is often challenging in over-crowded Emergency Departments (EDs). This survey was designed to explore patients' perceptions on maintenance of privacy and confidentiality and their subsequent interactions with providers in a busy tertiary care hospital in Karachi. Methods: Trained nursing staff conducted structured interviews with 571 patients who presented to The Indus Hospital (TIH) ED from January to December 2020. All patients were 14 years of age or older, could speak and understand Urdu, and provide informed consent. Patients were asked about their perceptions of privacy and confidentiality in the ED and whether this affected their interactions with providers. Results: Respondents were primarily men (64%) under the age of 45 (62%) presenting for the first time (49%). The majority of patients felt that privacy and confidentiality were maintained, however 10% of patients reported that they had rejected examination due to privacy concerns and 15% of patients reported that they had changed or omitted information provided to a provider due to confidentiality concerns. There was correlation between privacy and confidentiality concerns and patient-provider interactions (p<0.0001). Conclusions: Despite the often over-crowded and busy environment of the ED, patients generally felt that privacy and confidentiality were maintained. Given the correlation between perception and behavior and the importance of an effective patient-provider relationship, particularly in the acute setting when morbidity and mortality is high, initiatives that focus on maintaining privacy and confidentiality should be pursued.

Synthesis and evaluation of novel 1, 2, 4-substituted triazoles for urease and anti-proliferative activity.

1,2,4-triazoles are a major group of heterocyclic compounds. In the current work, a concise library of such triazoles synthesized through a multistep protocol. The synthesis involved hydrazinolysis of ethyl-2-(p-Cl-phenoxy) acetate followed by reflux with phenyl isothiocyanate to yield the intermediate 2-[2-(p-Cl-phenoxy)acetyl)-N-phenyl-hydrazinecarbothioamide. This intermediate was then cyclized to form 5-[p-(Cl-phenoxy)-methyl]-4-phenyl-4H-1,2,4-triazole-3-thiol (the parent moiety) at alkaline pH. In parallel, 3-bromopropionyl bromide was reacted with a series of phenylamines to yield N-(substituted-phenyl)bromopropanamides. In the final step, N-substitution of 5-[p-(Cl-phenoxy)-methyl]-4- phenyl-4H-1,2,4-triazole-3-thiol was carried out with N-(substituted-phenyl)bromopropanamides to give desired library of 3-[5-[(p-Cl-phenoxy)-methyl]-4- phenyl-4H-1,2,4-triazole-3-ylthio]-N-(substituted-phenyl) propan-amides (8a-l). The prepared moieties were identified via IR, NMR, & EIMS and evaluated for urease and anti-proliferative activities. 3-[5-[(p-Cl-phenoxy)-methyl]-4- phenyl-4H-1,2,4-triazole-3-ylthio]-N-(3-methyl-phenyl)propanamide 8k, was found to be most prominent hit as urease inhibitor (IC50= 42.57± 0.13 µM) using thiourea as standard (IC50= 21.25±0.15µM). The interaction of 8k with urease were studied using docking studies. Anti-proliferative activity results showed 8k as promising candidates and rest of the synthesized derivatives were found to be moderately anti-proliferative. Molecular docking results also displayed 8k, 8h, and 8c as potential hits for further study.

Biomarkers for liver disease in urea cycle disorders.

BACKGROUND: Urea cycle disorders (UCDs) are among the most common inborn errors of liver metabolism. As therapies for hyperammonemia associated with urea cycle dysfunction have improved, chronic complications, such as liver disease, have become increasingly apparent in individuals with UCDs. Liver disease in UCDs may be associated with hepatic inflammation, hepatic fibrosis, portal hypertension, liver cancer and even liver failure. However, except for monitoring serum aminotransferases, there are no clear guidelines for screening and/or monitoring individuals with UCDs for liver disease. Thus, we systematically evaluated the potential utility of several non-invasive biomarkers for liver fibrosis in UCDs. METHODS: We evaluated grey-scale ultrasonography, liver stiffness obtained from shear wave elastography (SWE), and various serum biomarkers for hepatic fibrosis and necroinflammation, in a cohort of 28 children and adults with various UCDs. RESULTS: Overall, we demonstrate a high burden of liver disease in our participants with 46% of participants having abnormal grey-scale ultrasound pattern of the liver parenchyma, and 52% of individuals having increased liver stiffness. The analysis of serum biomarkers revealed that 32% of participants had elevated FibroTest™ score, a marker for hepatic fibrosis, and 25% of participants had increased ActiTest™ score, a marker for necroinflammation. Interestingly, liver stiffness did not correlate with ultrasound appearance or FibroTest™. CONCLUSION: Overall, our results demonstrate the high overall burden of liver disease in UCDs and highlights the need for further studies exploring new tools for identifying and monitoring individuals with UCDs who are at risk for this complication. TRIAL REGISTRATION: This study has been registered in ClinicalTrials.gov (NCT03721367).

A Generic Sequential Stimulation Adapter for Reducing Muscle Fatigue during Functional Electrical Stimulation.

BACKGROUND: Clinical applications of conventional functional electrical stimulation (FES) administered via a single electrode are limited by rapid onset neuromuscular fatigue. "Sequential" (SEQ) stimulation, involving the rotation of pulses between multiple active electrodes, has been shown to reduce fatigue compared to conventional FES. However, there has been limited adoption of SEQ in research and clinical settings. METHODS: The SEQ adapter is a small, battery-powered device that transforms the output of any commercially available electrical stimulator into SEQ stimulation. We examined the output of the adaptor across a range of clinically relevant stimulation pulse parameters to verify the signal integrity preservation ability of the SEQ adapter. Pulse frequency, amplitude, and duration were varied across discrete states between 4 and 200 Hz, 10 and100 mA, and 50 and 2000 µs, respectively. RESULTS: A total of 420 trials were conducted, with 80 stimulation pulses per trial. The SEQ adapter demonstrated excellent preservation of signal integrity, matching the pulse characteristics of the originating stimulator within 1% error. The SEQ adapter operates as expected at pulse frequencies up to 160 Hz, failing at a frequency of 200 Hz. CONCLUSION: The SEQ adapter represents an effective and low-cost solution to increase the utilization of SEQ in existing rehabilitation paradigms.

Standing at the edge of mortality; Five-year audit of an emergency department of a tertiary care hospital in a low resource setup.

BACKGROUND & OBJECTIVE: Understanding the demographics of mortality and its burden in the emergency department of a tertiary care setup can lead to better planning and allocation of resources to streamline process flow. This can be achieved systematically through mortality audit that can identify the loopholes and areas of improvement. Our objective was to characterize the epidemiology of ED mortality in a tertiary care hospital of Karachi, Pakistan. METHODS: A five-year retrospective chart review of 322 adult mortalities presenting between January l, 2014 - December 31, 2018 was conducted in the emergency department (ED) of The Indus Hospital (TIH), Karachi. All expiries in ED were included while those brought dead and with do not resuscitate order (DNAR) were excluded. RESULTS: Mortality incidence of 0.076% (7.6/10,000 ED visits in five years) was reported. Amongst 507,759 adult ED visits, 322 mortalities were documented. Mean time lapse before presentation was 44±147 hours and mean length of stay before death was 3.4±2.8 hours. Acute coronary syndrome (ACS) was the predominant cause of death with 109 (33.8%) expiries. Significant association was reported between no history of prior care and high priority (P1) cases (p=0.013). CONCLUSIONS: This study identified the contributing factors to adverse outcome such as delayed presentation with systemic gaps in management and unknown disposition. The need to improve these factors at local and national level can lead to improvement in Pakistani healthcare sector.

Transmembrane 163 (TMEM163) protein effluxes zinc.

Recent investigations of rodent Tmem163 suggest that it binds to and transports zinc as a dimer, and that alanine mutagenesis of its two species-conserved aspartate (D123A/D127A) residues proposed to bind zinc, perturbs protein function. Direct corroboration, however, is lacking whether it is an influx or efflux transporter in cells. We hypothesized that human TMEM163 is a zinc effluxer based on its predicted protein characteristics. We used cultured human cell lines that either stably or transiently expressed TMEM163, and pre-loaded the cells with zinc to determine transport activity. We found that TMEM163-expressing cells exhibited significant reduction of intracellular zinc levels as evidenced by two zinc-specific fluorescent dyes and radionuclide zinc-65. The specificity of the fluorescence signal was confirmed upon treatment with TPEN, a high-affinity zinc chelator. Multiple sequence alignment and phylogenetic analyses showed that TMEM163 is related to distinct members of the cation diffusion facilitator (CDF) protein family. To further characterize the efflux function of TMEM163, we substituted alanine in two homologous aspartate residues (D124A/D128A) and performed site-directed mutagenesis of several conserved amino acid residues identified as non-synonymous single nucleotide polymorphism (S61R, S95C, S193P, and E286K). We found a significant reduction of zinc efflux upon cellular expression of D124A/D128A or E286K protein variant when compared with wild-type, suggesting that these particular amino acids are important for normal protein function. Taken together, our findings demonstrate that TMEM163 effluxes zinc, and it should now be designated ZNT11 as a new member of the mammalian CDF family of zinc efflux transporters.

Phytochemical investigation and antimicrobial appraisal of Parrotiopsis jacquemontiana (Decne) Rehder.

BACKGROUND: Parrotiopsis jacquemontiana (Decne) Rehder. is locally used for skin infections and in wound healing. In this study we have evaluated methanol extract of its leaves and derived fractions against the clinical multi-drug resistant bacterial strains. METHODS: P. jacquemontiana leaves powder extracted with 95% methanol (PJM) and fractionated in escalating polarity of solvents; n-hexane (PJH), chloroform (PJC), ethyl acetate (PJE), n-butanol (PJB) and the remaining as aqueous fraction (PJA). Clinical as well as environmental 19 bacterial strains and 8 fungal strains were screened for minimum inhibitory concentration (MIC) and minimum bactericidal/fungicidal concentration (MBC/MFC). Preliminary phytochemical investigation for various phytochemical classes was also carried out. RESULTS: PJM contained the coumarins, phenols, flavonoids, tannins, alkaloids, glycosides, saponins, sterols, phlobatannins, steroids, phytosterols, triterpenoids, acids, quinones, proteins, vitamin C, betacyanins, oils and resins while anthraquinones, phytosteroids, carbohydrates and anthocyanins were not detected. Disc diffusion assay (1 mg/disc) indicated the sensitivity of all the MDR strains of bacteria with PJM, PJE and PJB, while no inhibition was recorded with PJA. PJH and PJC inhibited the growth of all the strains of Staphylococcus aureus, Pseudomonas aeruginosa and Coagulase negative staphylococci used in this study. Maximum zone of inhibition (35.5 ± 1.32 mm) was obtained with PJM against Staphylococcus lugdenesis MDR (6197). Comparatively lower MIC (8-64 µg/ml) and MBC (32-256 µg/ml) values were recorded for PJM and PJE. In case of fungal strains only PJM, PJE and PJB markedly inhibited the growth and lower MIC (8-128 µg/ml) and MFC (32-512 µg/ml) values were determined for PJM and PJE. CONCLUSION: The remarkable inhibition of various bacterial and fungal strains at low doses of the extract/fractions suggested the strong antibacterial, antifungal and anti-candidal potential of P. jacquemontiana leaves.

Role of Spiritual Sentiments in Improving the Compliance of Water Intake in Patients with Urolithiasis.

The aim of this study was to compare the compliance for water intake and rate of recurrence between spiritually motivated and non-motivated patients of renal tract stone disease. It is a multi centric prospective cohort study, conducted in Department of Urology, Institute of Kidney Diseases and Peshawar Medical College, from January 10, 2009 to December 2012. A total of 180 patients with comparable demographic, IQ, EQ and BMI after achieving complete stone clearance were divided into two equal groups. Both groups were instructed to increase the water intake timetable according to AUA guidelines. Group 'A' comprising of 90 patients who were identified as spiritually motivated patients based on questioner of FICA 12 is also instructed that increasing the water intake is mentioned in contemporary Islamic medicine. No spiritual instruction was given to Group B. The instructed guidelines and practice for amount and timing of water intake were recalled from participants at the end of 6 and 12 months. The data were recorded on structured proforma and was analyzed using SPSS version 17. The mean age of the patient in Group A was 37.5 years (18-70 years), while in Group B it was 34 years (18-65 years). Urolithiasis affected predominantly male gender in both groups. Sixty-five patients (72.2 %) in Group A have significant compliance (p < 0.001) for water intake over Group B (46 %). The spiritually motivated Group A has significantly reduced rate of recurrence of stones in 23 patients versus 37 in Group B. The spiritually motivated patients had significantly better compliance for water intake and reduced rate of recurrence versus non-motivated individuals in urolithiasis.

Fatigue reduction during aggregated and distributed sequential stimulation.

INTRODUCTION: Transcutaneous neuromuscular electrical stimulation (NMES) can generate muscle contractions for rehabilitation and exercise. However, NMES-evoked contractions are limited by fatigue when they are delivered "conventionally" (CONV) using a single active electrode. Researchers have developed "sequential" (SEQ) stimulation, involving rotation of pulses between multiple "aggregated" (AGGR-SEQ) or "distributed" (DISTR-SEQ) active electrodes, to reduce fatigue (torque-decline) by reducing motor unit discharge rates. The primary objective was to compare fatigue-related outcomes, "potentiation," "variability," and "efficiency" between CONV, AGGR-SEQ, and DISTR-SEQ stimulation of knee extensors in healthy participants. METHODS: Torque and current were recorded during testing with fatiguing trains using each NMES type under isometric and isokinetic (180°/s) conditions. RESULTS: Compared with CONV stimulation, SEQ techniques reduced fatigue-related outcomes, increased potentiation, did not affect variability, and reduced efficiency. CONCLUSIONS: SEQ techniques hold promise for reducing fatigue during NMES-based rehabilitation and exercise; however, optimization is required to improve efficiency. Muscle Nerve 56: 271-281, 2017.

Thermal conductivity of amorphous Al2O3/TiO2 nanolaminates deposited by atomic layer deposition.

The thermophysical properties of Al2O3/TiO2 nanolaminates deposited by atomic layer deposition (ALD) are studied as a function of bilayer thickness and relative TiO2 content (0%-100%) while the total nominal thickness of the nanolaminates was kept at 100 nm. Cross-plane thermal conductivity of the nanolaminates is measured at room temperature using the nanosecond transient thermoreflectance method. Based on the measurements, the nanolaminates have reduced thermal conductivity as compared to the pure amorphous thin films, suggesting that interfaces have a non-negligible effect on thermal transport in amorphous nanolaminates. For a fixed number of interfaces, we find that approximately equal material content of Al2O3 and TiO2 produces the lowest value of thermal conductivity. The thermal conductivity reduces with increasing interface density up to 0.4 nm(-1), above which the thermal conductivity is found to be constant. The value of thermal interface resistance approximated by the use of diffuse mismatch model was found to be 0.45 m(2) K GW(-1), and a comparative study employing this value supports the interpretation of non-negligible interface resistance affecting the overall thermal conductivity also in the amorphous limit. Finally, no clear trend in thermal conductivity values was found for nanolaminates grown at different deposition temperatures, suggesting that the temperature in the ALD process has a non-trivial while modest effect on the overall thermal conductivity in amorphous nanolaminates.