Combined Multivariate Statistical Techniques and Water Quality Index (WQI) to Evaluate Spatial Variation in Water Quality.

In present study, Water Quality Index (WQI) has been assessed of the Rawal Lake which is a major source of drinking water for people in the Federal Capital, Islamabad, and its adjacent city Rawalpindi in Pakistan. For this, the principal component analysis (PCA) and WQI were applied as an integrated approach to quantitatively explore difference based on spatial variation in 11 water quality parameters of the five major feeding tributaries of the Rawal Lake, Pakistan. The results of temperature in water, total dissolved solids, pH, electrical conductivity, chlorides and sulfates were well within the allowable World Health Organisation's (WHO) limits. However, the heavy metals like cadmium and lead were above permissible limits by the WHO in tributaries of Bari Imam and Rumli. Moreover, this has been proven by the Pearson correlation which suggested strong positive correlation (0.910*) between lead and cadmium. The results of present study were subjected to statistical analysis, i.e., PCA which gave three major factors contributing 96.5% of the total variance. For factor 1, pH, TDS, alkalinity, chlorides, sulfates and zinc have highest factor loading values (>0.60) and presented that these parameters were among the most significant parameters of first factor. As per the WQI results, the water was categorised in two major classes indicating that water of Bari Imam and Rumli is highly contaminated with heavy metals and totally unsuitable for drinking purposes. Based on the results of the present study, it is suggested to make heavy metals consideration as an integrated component in future planning for maintaining water quality of the Rawal Lake and its tributaries.

Early recognition and management of maternal sepsis in Pakistan: a feasibility study of the implementation of FAST-M intervention.

OBJECTIVE: Maternal sepsis is the third leading cause of maternal mortality globally. WHO and collaborators developed a care bundle called FAST-M (Fluids, Antibiotics, Source identification and treatment, Transfer and Monitoring) for early identification and management of maternal sepsis in low-resource settings. This study aimed to determine feasibility of FAST-M intervention in a low-resource setting in Pakistan. The FAST-M intervention consists of maternal sepsis screening tools, treatment bundle and implementation programme. DESIGN AND SETTING: A feasibility study with before and after design was conducted in women with suspected maternal sepsis admitted at the Liaquat University of Medical and Health Sciences hospital Hyderabad. The study outcomes were compared between baseline and intervention phases. In the baseline phase (2 months), the existing sepsis care practices were recorded, followed by a training programme for healthcare providers on the application of FAST-M tools. These tools were implemented in the intervention phase (4 months) to assess any change in clinical practices compared with the baseline phase. RESULTS: During the FAST-M implementation, 439 women were included in the study. 242/439 were suspected maternal infection cases, and 138/242 were women with suspected maternal sepsis. The FAST-M bundle was implemented in women with suspected maternal sepsis. Following the FAST-M intervention, significant changes were observed. Improvements were seen in the monitoring of oxygen saturation measurements (25.5% vs 100%; difference: 74%; 95% CI: 68.4% to 80.5%; p<0.01), fetal heart rate assessment (58% vs 100%; difference: 42.0%; 95% CI: 33.7% to 50.3%; p≤0.01) and measurement of urine output (76.5% vs 100%; difference: 23.5%; 95% CI: 17.6% to 29.4%; p<0.01). Women with suspected maternal sepsis received all components of the treatment bundle within 1 hour of sepsis recognition (0% vs 70.5%; difference: 70.5%; 95% CI: 60.4% to 80.6%; p<0.01). CONCLUSION: Implementation of the FAST-M intervention was considered feasible and enhanced early identification and management of maternal sepsis at the study site. TRIAL REGISTRATION NUMBER: ISRCTN17105658.

Efficacy and safety of combination of empagliflozin and metformin with combination of sitagliptin and metformin during Ramadan: an observational study.

BACKGROUND: Management of diabetes during fasting is a clinical challenge. Sodium glucose co-transporter -2 inhibitors (SGLT2i) are considered safe with a low risk of hypoglycemia. However, studies on SGLT2i are scarce. This study was designed to compare the efficacy, safety, and tolerability of empagliflozin with metformin during Ramadan in comparison with sitagliptin and metformin. METHODS: It was a prospective, observational study, conducted at 11 different sites all across Pakistan on an outpatient basis during Ramadan (May 2021-June 2021). including 132 patients, 88 who received metformin and sitagliptin, and 44 patients who received metformin and empagliflozin. RESULTS: Patients of the SGLT-2i group experienced similar symptomatic hypoglycemic episodes (15.9%) as the sitagliptin group. There was an improvement in blood sugar levels after the use of SGLT-2i (RBS 181 ± 64 before Ramadan vs 162 ± 53 after Ramadan). HbA1c also improved after the use of SGLT-2i before and after Ramadan (7.2 ± 0.8 vs 6.9 ± 0.9 for Metformin + Empagliflozin and 7.8 ± 1.5 vs 7.6 ± 1.6 for Metformin and sitagliptin). Weight and BMI improved after the use of SGLT-2i (BMI 36.5 ± 4.8 before Ramadan and 33.7 ± 2.4 after Ramadan). There were no reported cases of urinary tract infection in the empagliflozin group. CONCLUSION: SGLT-2 inhibitors combined with metformin for patients with diabetes during Ramadan fasting is as effective, safe and well tolerated as DPP4 combined with metformin.

A Survey of Current Practices and Adherence to Coronavirus Disease Airway Management Guidelines Among Frontline Healthcare Professionals in a Resource-Limited Country.

OBJECTIVE: The coronavirus disease 2019 (COVID-19) has brought anaesthesiologists, intensive care and emergency physicians to the forefront due to their airway management skills. The aim of survey was to determine current practice trends in COVID-19 airway management among frontline healthcare professionals of Pakistan and their adherence to standard principles proposed by most consensus guidelines. METHODS: An online questionnaire was designed based on consensus guidelines from international societies. We contacted consultants and trainees nationwide working in anaesthesia, intensive care, and emergency departments through emails, phone calls, and social media platforms. RESULTS: A total of 285 individuals participated in this cross-sectional descriptive study. Intubations were largely performed by anaesthetists followed by emergency physicians. Deteriorating respiratory failure (89%) was the most frequent indication. Availability of trained staff, use of intubation checklist, limited staff presence during intubation, and use of appropriate personal protective equipment were positive findings. One-third reported that their workplace did not have negative pressure rooms for aerosol-generating procedures, and 63.3% responders do not perform airway assessment before intubation. The device of choice for the first attempt at laryngoscopy was Macintosh laryngoscope (51.6%) followed by videolaryngoscopes with disposable blades (24.2%). Availability of rescue devices in case of unanticipated difficult airway is variable; laryngeal mask airway (70.1%), bougie (82.2%), and stylet (68.7%) were present at majority places. Frequency of airway-related adverse events including hypoxemia (69.8%) and failed first attempt intubation (35.2%) was significant. CONCLUSION: This survey found satisfactory knowledge, comparable practices, and offers some important insights about airway management in COVID-19 patients by healthcare professionals of Pakistan.

Adapting the FAST-M maternal sepsis intervention for implementation in Pakistan: a qualitative exploratory study.

OBJECTIVE: A maternal sepsis management bundle for resource-limited settings was developed through a synthesis of evidence and international consensus. This bundle, called 'FAST-M' consists of: Fluids, Antibiotics, Source control, assessment of the need to Transport/Transfer to a higher level of care and ongoing Monitoring (of the mother and neonate). The study aimed to adapt the FAST-M intervention including the bundle care tools for early identification and management of maternal sepsis in a low-resource setting of Pakistan and identify potential facilitators and barriers to its implementation. SETTING: The study was conducted at the Liaquat University of Medical and Health Sciences, which is a tertiary referral public sector hospital in Hyderabad. DESIGN AND PARTICIPANTS: A qualitative exploratory study comprising key informant interviews and a focus group discussion was conducted with healthcare providers (HCPs) working in the study setting between November 2020 and January 2021, to ascertain the potential facilitators and barriers to the implementation of the FAST-M intervention. Interview guides were developed using the five domains of the Consolidated Framework for Implementation Research: intervention characteristics, outer setting, inner setting, characteristics of the individuals and process of implementation. RESULTS: Four overarching themes were identified, the hindering factors for implementation of the FAST-M intervention were: (1) Challenges in existing system such as a shortage of resources and lack of quality assurance; and (2) Clinical practice variation that includes lack of sepsis guidelines and documentation; the facilitating factors identified were: (3) HCPs' perceptions about the FAST-M intervention and their positive views about its execution and (4) Development of HCPs readiness for FAST-M implementation that aided in identifying solutions to potential hindering factors at their clinical setting. CONCLUSION: The study has identified potential gaps and probable solutions to the implementation of the FAST-M intervention, with modifications for adaptation in the local context TRIAL REGISTRATION NUMBER: ISRCTN17105658.

Effects of ozone phytotoxicity in reducing the yield and nutritional quality of chilli (Capsicum annuum L.).

This study was designed to assess the effects of tropospheric ozone (O3) on the yield and nutritional quality of chilli (Capsicum annuum L. cv. Pusa Jwala) using ethylene diurea (EDU) under field conditions in Peshawar, Pakistan. Average O3 concentration ranged between 38 and 68 ppb which is high enough to cause phytotoxic effects. Accumulated ozone exposure over a threshold of 40 ppm h (AOT40) value calculated for 3-month period was found to be substantially higher, i.e., 7.3 ppm h. Various growth and yield parameters analyzed on weekly basis showed that the plant height (6.3%), number of flowers (15%), fruits (36%), and total dry biomass (30%) and its nutritional quality parameters such as mean crude protein, fat, and fiber showed 24%, 100%, and 12% better results in EDU-treated plants as compared with control, respectively. However, mineral contents showed no significant difference (p < 0.05) for both the groups. The results of this study concluded that ambient O3 is a threat to the selected plant species thus affecting its quality and yield and EDU remains successful in protecting the chilli (Capsicum annuum L.) against the negative effects of tropospheric ozone.

Printing in a Pandemic: 3D printing solutions for healthcare during COVID-19. A Protocol for a PRISMA systematic review.

Introduction: The COVID-19 pandemic had an unprecedented global socioeconomic impact. Responses to pandemics include strategies to accumulate vast stockpiles of vital medical equipment. In such times of desperation, 3D-printing could be a life-saving alternative. Methods: We undertook a PRISMA systematic review of 3D printing solutions in response to COVID-19 utilising the PICO methodology. The objectives were to identify the uses of 3D printing during the COVID-19 pandemic, determine the extent of preclinical testing, comparison to commercial alternatives, presence of regulatory approvals and replicability regarding the description of the printing parameters and the availability of the print file. Results: Literature searches of MEDLINE (OVID interface)/ PubMed identified 601 studies. Of these, 10 studies fulfilled the inclusion and exclusion criteria. Reported uses of 3D printing included personal protective equipment (PPE), nasopharyngeal swabs and adjunctive anaesthetic equipment. Few studies undertook formal safety and efficacy testing before clinical use with only one study comparing to the commercial equivalent. Six articles made their model print files available for wider use. Conclusion: We describe a protocol for a systematic review of 3D-printed healthcare solutions in response to COVID-19. This remains a viable method of producing vital healthcare equipment when supply chains are exhausted. We hope that this will serve as a summary of innovative 3D-printed solutions during the peak of the pandemic and also highlight concerns and omissions regarding safety and efficacy testing that should be addressed urgently in preparation for a subsequent resurgences and future pandemics.

Seed Priming Improved Antioxidant Defense System and Alleviated Ni-Induced Adversities in Rice Seedlings Under N, P, or K Deprivation.

Excess nickel (Ni) concentration in the growing medium severely hampers the plant growth by disturbing oxidative metabolism and nutrient status. The present study was carried out to investigate the individual and interactive effects of Ni toxicity (0.25 mM NiSO4.6H2O) and nutrient deprivation (no-N, no-P, or no-K) on growth, oxidative metabolism, and nutrient uptake in primed and non-primed rice seedlings. Rice seed was primed with distilled water (hydropriming), selenium (5 mg L-1), or salicylic acid (100 mg L-1). The Ni toxicity and deprivation of N, P, or K posed negative effects on the establishment of rice seedlings. The shoot length and fresh biomass were severely reduced by Ni toxicity and nutrient stresses; the minimum shoot growth was recorded for rice seedlings grown under Ni toxicity and no-N stress. The Ni toxicity reduced the root fresh biomass but did not significantly affect the root length of N-deprived seedlings. The rice seedlings with no-P or no-K recorded similar root fresh biomass compared with those grown with sufficient nutrient supply. The Ni toxicity alone or in combination with nutrient stresses triggered the production of reactive oxygen species (ROS) and caused lipid peroxidation in rice seedlings. Among antioxidants, only glutathione reductase and vitamin E were significantly increased by Ni toxicity under different nutrient stress treatments. The Ni toxicity also reduced the concentrations of N particularly in shoot of rice seedlings. The N-deprived (no-N) seedlings recorded maximum Ni concentration in shoot, while K-deprived (no-K) seedlings showed higher Ni concentrations in root. Seed priming with selenium or salicylic acid was effective to alleviate the detrimental effects of Ni toxicity and/or nutrient stresses on rice seedlings. The better growth and greater stress tolerance of primed seedlings was coordinately attributed to lower ROS production, higher membrane stability, strong antioxidative defense system, and maintenance of mineral nutrient status.

Effect of Intravenous Vitamin C, Thiamine, and Hydrocortisone (The Metabolic Resuscitation Protocol) on Early Weaning from Vasopressors in Patients with Septic Shock. A Descriptive Case Series Study.

OBJECTIVES:  The aim of this study was to assess the efficacy of intravenous vitamin C, hydrocortisone, and thiamine in early weaning (within 48 hours) from vasopressor support in patients with septic shock. We also aimed to assess mortality and intensive care unit (ICU) stay. STUDY DESIGN:  We conducted a descriptive case series study of 50 patients with septic shock who were admitted in the ICU of the Combined Military Hospital Rawalpindi in Pakistan from August 2017 until April 2018. MATERIALS AND METHODS:  The study included men and women (16 to 80 years of age) who were admitted to the ICU with septic shock. Data were analysed using the IBM Statistical Package for Social Sciences (SPSS), version 18.0 (IBM Corp., Armonk, NY, USA). Inferential analysis was done with the help of simple and multivariate binary logistic regression that generated unadjusted and adjusted odds ratios (OR), respectively. RESULTS:  Of the 50 patients, 56% (N = 28) were male with a mean age of the respondents being 46.7 ± 18.4. Eighty-four percent were successfully weaned off vasopressors within 48 hours. Median days in the ICU were reported as 8.3 (interquartile range (IQR) = 5). Primary bacteremia (34%) was the most reported cause of ICU admission. The most common vasopressor was norepinephrine and its mean dose was 21.6 ± 10.7 microgram/min. The ICU mortality was observed at 52% (N = 26). Unadjusted OR showed a dose of norepinephrine, Sequential Organ Failure Assessment (SOFA) score, plasma procalcitonin, and plasma lactate to be significant predictors (p-value < 0.05), while the adjusted odds ratio (AOR) showed only a dose of norepinephrine to be a statistically significant predictor (AOR = 0.804, 95% CI = 0.674 - 0.960; p-value = 0.016). CONCLUSION:  The administration of intravenous vitamin C, hydrocortisone, and thiamine to patients with septic shock was successful in early weaning from vasopressors. There was also a reduction in procalcitonin and lactate levels, as well as the SOFA score. Further trials are needed to determine whether the metabolic resuscitation protocol can become part of the treatment for septic shock.

Synthesis, Molecular Modeling and Biological Evaluation of 5-arylidene-N,N-diethylthiobarbiturates as Potential α-glucosidase Inhibitors.

BACKGROUND: Barbituric acid derivatives are a versatile group of compounds which are identified as potential pharmacophores for the treatment of anxiety, epilepsy and other psychiatric disorders. They are also used as anesthetics and have sound effects on the motor and sensory functions. Barbiturates are malonylurea derivatives with a variety of substituents at C-5 position showing resemblance with nitrogen and sulfur containing compounds like thiouracil which exhibited potent anticancer and antiviral activities. Recently, barbituric acid derivatives have also received great interest for applications in nanoscience. OBJECTIVE: Synthesis of 5-arylidene-N,N-diethylthiobarbiturates, biological evaluation as potential α-glucosidase inhibitors and molecular modeling. METHODS: In the present study, N,N-Diethylthiobarbituric acid derivatives were synthesized by refluxing of N,N-diethylthiobarbituric acid and different aromatic aldehydes in distilled water. In a typical reaction; a mixture of N,N-diethylthiobarbituric acid 0.20 g (1 mmol) and 5-bromo-2- hydroxybenzaldehyde 0.199 g (1 mmol) mixed in 10 mL distilled water and reflux for 30 minutes. After completion of the reaction, the corresponding product 1 was filtered and dried and yield calculated. It was crystallized from ethanol. The structures of synthesized compounds 1-25 were carried out by using 1H, 13C NMR, EI spectroscopy and CHN analysis used for the determination of their structures. The α-glucosidase inhibition assay was performed as given by Chapdelaine et al., with slight modifications and optimization. RESULTS: Our newly synthesized compounds showed a varying degree of α-glucosidase inhibition and at least four of them were found as potent inhibitors. Compounds 6, 5, 17, 11 exhibited IC50 values (Mean±SEM) of 0.0006 ± 0.0002, 18.91 ± 0.005, 19.18 ± 0.002, 36.91 ± 0.003 µM, respectively, as compared to standard acarbose (IC50, 38.25 ± 0.12 µM). CONCLUSION: Our present study has shown that compounds 6, 5, 17, 11 exhibited IC50 values of 0.0006 ± 0.0002, 18.91 ± 0.005, 19.18 ± 0.002, 36.91 ± 0.003 µM, respectively. The studies were supported by in silico data analysis.

Monitoring the Use of Telemonitor: A Resident-run Quality Improvement Initiative Decreases Inappropriate Use of Telemonitor in a Community Hospital.

Background Cardiac telemetry is an important tool to detect life-threatening conditions in hospitalized patients but is used widely and inappropriately. We sought to assess current usage and improve the appropriate use of telemetry in a community hospital. Methods We conducted a quality improvement project on patients who were admitted on telemetry floors between January and March 2017 (pre-intervention). The indication(s) and duration of telemonitor use, event(s) recorded on telemonitor and outcome of the event(s) were documented. A six-month educational intervention was undertaken and the effect of intervention was assessed among patients admitted between December 2017 and February 2018 (post-intervention). Results In the pre-intervention group, 329 patients qualified for the study, with a median age of 78 years. The post-intervention group had 383 qualified patients with a median age of 77 years. Mean duration of telemonitor use was four days in both groups. In the pre-intervention group, 54% had class I, 32% had class II, and 14% had class III indications. In post-intervention group, 46% had class I, 42% had class II, and 12% had class III indications. The educational intervention resulted in a trend towards less inappropriate use of telemetry, particularly in teaching service. Telemonitor events were recorded in 22 (7%) of the pre-intervention patients and 13 (4%) of the post-intervention group. Two patients died in the pre-intervention group and one in the post-intervention group from non-cardiac causes. Conclusion Our results highlight that change in practice requires sustained education interventions.

Coordinated effects of lead toxicity and nutrient deprivation on growth, oxidative status, and elemental composition of primed and non-primed rice seedlings.

Rice crop is highly susceptible to the toxic levels of lead (Pb) during early growth stages. Moreover, a sufficient availability of mineral nutrients is critical for survival of plants particularly under stressful conditions. An experiment was carried out to unravel the coordinated effects of Pb stress (1-mM PbCl2) and different nutrient treatments (sufficient nutrient supply, nitrogen (N) deprivation, phosphorus (P) deprivation, and potassium (K) deprivation) on morphological growth, reactive oxygen species (ROS), antioxidants, and nutrient status in primed and non-primed rice seedlings. Seeding were primed with distilled water, 60-µM selenium, or 100-mg L-1 salicylic acid. Results indicated that Pb toxicity did not affect the root growth, but severely reduced the shoot growth (length and biomass) of rice in N- or P-deprived seedlings. Rice seedlings grown with sufficient supply of nutrients or K-deprivation showed no growth reduction under Pb toxicity. Exposure of Pb stress triggered the production of ROS (H2O2, O2˙-, OH-) and lipid peroxidation rate particularly under N- or P-deprivation. Moreover, the shoot accumulations of macronutrients (P in particular) were also restricted under Pb toxicity. Seed priming treatments effectively alleviated the undesirable effects of Pb stress on rice growth. The primed rice seedlings showed minimal oxidative damage caused by excessive generation of ROS under Pb stress and/or nutrient deprivation. Seed priming strengthened the antioxidative defense system of rice seedlings by regulating the activities/levels of superoxide dismutase, catalase, peroxidase, and glutathione in rice leaves. Moreover, better accumulation of essential nutrients in primed rice seedlings prevented the excess uptake and translocation of Pb, as evident by the lowered shoot accumulation of Pb.

CRISPR/Cas9: the Jedi against the dark empire of diseases.

Advances in Clustered Regularly Interspaced Short Palindromic Repeats/CRISPR associated system (CRISPR/Cas9) has dramatically reshaped our ability to edit genomes. The scientific community is using CRISPR/Cas9 for various biotechnological and medical purposes. One of its most important uses is developing potential therapeutic strategies against diseases. CRISPR/Cas9 based approaches have been increasingly applied to the treatment of human diseases like cancer, genetic, immunological and neurological disorders and viral diseases. These strategies using CRISPR/Cas9 are not only therapy oriented but can also be used for disease modeling as well, which in turn can lead to the improved understanding of mechanisms of various infectious and genetic diseases. In addition, CRISPR/Cas9 system can also be used as programmable antibiotics to kill the bacteria sequence specifically and therefore can bypass multidrug resistance. Furthermore, CRISPR/Cas9 based gene drive may also hold the potential to limit the spread of vector borne diseases. This bacterial and archaeal adaptive immune system might be a therapeutic answer to previous incurable diseases, of course rigorous testing is required to corroborate these claims. In this review, we provide an insight about the recent developments using CRISPR/Cas9 against various diseases with respect to disease modeling and treatment, and what future perspectives should be noted while using this technology.

Domain analyses of Usher syndrome causing Clarin-1 and GPR98 protein models.

Usher syndrome is an autosomal recessive disorder that causes hearing loss, Retinitis Pigmentosa (RP) and vestibular dysfunction. It is clinically and genetically heterogeneous disorder which is clinically divided into three types i.e. type I, type II and type III. To date, there are about twelve loci and ten identified genes which are associated with Usher syndrome. A mutation in any of these genes e.g. CDH23, CLRN1, GPR98, MYO7A, PCDH15, USH1C, USH1G, USH2A and DFNB31 can result in Usher syndrome or non-syndromic deafness. These genes provide instructions for making proteins that play important roles in normal hearing, balance and vision. Studies have shown that protein structures of only seven genes have been determined experimentally and there are still three genes whose structures are unavailable. These genes are Clarin-1, GPR98 and Usherin. In the absence of an experimentally determined structure, homology modeling and threading often provide a useful 3D model of a protein. Therefore in the current study Clarin-1 and GPR98 proteins have been analyzed for signal peptide, domains and motifs. Clarin-1 protein was found to be without any signal peptide and consists of prokar lipoprotein domain. Clarin-1 is classified within claudin 2 super family and consists of twelve motifs. Whereas, GPR98 has a 29 amino acids long signal peptide and classified within GPCR family 2 having Concanavalin A-like lectin/glucanase superfamily. It was found to be consists of GPS and G protein receptor F2 domains and twenty nine motifs. Their 3D structures have been predicted using I-TASSER server. The model of Clarin-1 showed only α-helix but no beta sheets while model of GPR98 showed both α-helix and ß sheets. The predicted structures were then evaluated and validated by MolProbity and Ramachandran plot. The evaluation of the predicted structures showed 78.9% residues of Clarin-1 and 78.9% residues of GPR98 within favored regions. The findings of present study has resulted in the three dimensional structure prediction and conserved domain analysis which will be quite beneficial in better understanding of molecular components, protein-protein interaction, clinical heterogeneity and pathophysiology of Usher syndrome.