Summary Background Since December, 2019, Wuhan, China, has experienced an outbreak of coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Epidemiological and clinical characteristics of patients with COVID-19 have been reported but risk factors for mortality and a detailed clinical course of illness, including viral shedding, have not been well described. Methods In this retrospective, multicentre cohort study, we included all adult inpatients (≥18 years old) with laboratory-confirmed COVID-19 from Jinyintan Hospital and Wuhan Pulmonary Hospital (Wuhan, China) who had been discharged or had died by Jan 31, 2020. Demographic, clinical, treatment, and laboratory data, including serial samples for viral RNA detection, were extracted from electronic medical records and compared between survivors and non-survivors. We used univariable and multivariable logistic regression methods to explore the risk factors associated with in-hospital death. Findings 191 patients (135 from Jinyintan Hospital and 56 from Wuhan Pulmonary Hospital) were included in this study, of whom 137 were discharged and 54 died in hospital. 91 (48%) patients had a comorbidity, with hypertension being the most common (58 [30%] patients), followed by diabetes (36 [19%] patients) and coronary heart disease (15 [8%] patients). Multivariable regression showed increasing odds of in-hospital death associated with older age (odds ratio 1·10, 95% CI 1·03–1·17, per year increase; p=0·0043), higher Sequential Organ Failure Assessment (SOFA) score (5·65, 2·61–12·23; p Interpretation The potential risk factors of older age, high SOFA score, and d-dimer greater than 1 μg/mL could help clinicians to identify patients with poor prognosis at an early stage. Prolonged viral shedding provides the rationale for a strategy of isolation of infected patients and optimal antiviral interventions in the future. Funding Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences; National Science Grant for Distinguished Young Scholars; National Key Research and Development Program of China; The Beijing Science and Technology Project; and Major Projects of National Science and Technology on New Drug Creation and Development.

Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study

Due to the comprehensive examination of 50 patients with ovarian polycystosis the authors suggested that ultrasound, laparoscopic, hormonal and endometrial parameters should be employed as diagnostic criteria.

Diagnostic criteria for polycystic ovary syndrome

It has been reported that the triglyceride-glucose (TyG) index may serve as a simple and credible surrogate marker of insulin resistance (IR). However, its association with macrovascular and microvascular damage is unclear. Accordingly, the objective of the present study is to investigate the association of macrovascular and microvascular damage with the TyG index. A total of 2830 elderly participants from the Northern Shanghai Study (NSS) were enrolled. The TyG index was calculated as ln[fasting triglycerides (mg/dL) × fasting glucose (mg/dL)/2]. Parameters of vascular damage, including carotid-femoral pulse wave velocity (cf-PWV), brachial-ankle pulse wave velocity (ba-PWV), ankle–brachial index (ABI), carotid intima–media thickness (CMT), carotid plaque, estimated glomerular filtration rate (eGFR) and the urine albumin-to-creatinine ratio (UACR), were measured and calculated. In univariate logistic regression, an increased TyG index was associated with a higher risk of cf-PWV > 10 m/s, ba-PWV > 1800 cm/s, ABI   10 m/s (OR = 1.86, 95% confidence interval [95% CI] 1.37–2.53, Pfor trend   1800 cm/s (OR = 1.39, [95% CI] 1.05–1.84, Pfor trend= 0.02), MAU (OR = 1.61, [95% CI] 1.22–2.13, Pfor trend < 0.001) and CKD (OR = 1.67, [95% CI] 1.10–1.50, Pfor trend= 0.02) after adjustment for age, sex, BMI, waist circumference, smoking habit, hypertension, family history of premature CVD, diabetes, HDL-C, LDL-C, insulin therapy and statin therapy. However, no significant relationship was observed between the TyG index and lower extremity atherosclerosis, carotid hypertrophy or carotid plaque. An elevated TyG index was significantly associated with a higher risk of arterial stiffness and nephric microvascular damage. This conclusion lends support to the clinical significance of the TyG index for the assessment of vascular damage.

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Association between macro- and microvascular damage and the triglyceride glucose index in community-dwelling elderly individuals: the Northern Shanghai Study.

The triglyceride glucose (TyG) index is an inexpensive clinical surrogate marker for insulin resistance. However, the relationship between TyG index and atherosclerotic cardiovascular disease (CVD) remains unclear. We evaluated the relationship between TyG index and CVD using a large-scale population dataset from the National Health Information Database (NHID). We performed a retrospective observational cohort study of 5,593,134 persons older than 40 years from 2009 to 2017 using the NHID. We divided the participants into TyG index quartiles. Outcome variables were stroke, myocardial infarction, and both. The incidence of outcomes was estimated for each TyG quartile over the total follow-up period. All outcomes were analyzed by Cox proportional hazards regression analysis while controlling for baseline covariates. During 8.2 years of mean follow-up, stroke was diagnosed in 89,120 (1.59%), MI in 62,577 (1.12%), and both stroke and MI in 146,744 (2.62%) participants. Multivariate-adjusted hazard ratios (HRs) for patients in the highest TyG index quartile demonstrated that these patients were at higher risk for stroke (HR = 1.259; 95% confidence interval [CI] 1.233–1.286), for MI (HR = 1.313; 95% CI 1.28–1.346), and for both (HR = 1.282; 95% CI 1.261–1.303) compared with participants in the lowest TyG index quartile. These effects were independent of age, sex, smoking, alcohol consumption, physical activity, body mass index, systolic blood pressure, and total cholesterol. In our large population study, TyG index, a simple measure reflecting insulin resistance, was potentially useful in the early identification of individuals at high risk of experiencing a cardiovascular event.

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The triglyceride glucose index is a simple and low-cost marker associated with atherosclerotic cardiovascular disease: a population-based study

Continuous contamination of the environment with xenobiotics and related recalcitrant compounds has emerged as a serious pollution threat. Bioremediation is the key to eliminating persistent contaminants from the environment. Traditional bioremediation processes show limitations, therefore it is necessary to discover new bioremediation technologies for better results. In this review we provide an outlook of alternative strategies for bioremediation via synthetic biology, including exploring the prerequisites for analysis of research data for developing synthetic biological models of microbial bioremediation. Moreover, cell coordination in synthetic microbial community, cell signaling, and quorum sensing as engineered for enhanced bioremediation strategies are described, along with promising gene editing tools for obtaining the host with target gene sequences responsible for the degradation of recalcitrant compounds. The synthetic genetic circuit and two-component regulatory system (TCRS)-based microbial biosensors for detection and bioremediation are also briefly explained. These developments are expected to increase the efficiency of bioremediation strategies for best results.

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Alternative Strategies for Microbial Remediation of Pollutants via Synthetic Biology.

The traditional healthcare system is at the doorstep for entering into the arena of molecular medicine. The enormous knowledge and ongoing research have now been able to demonstrate methodologies that can alter DNA coding. The techniques used to edit or change the genome evolved from the earlier attempts like nuclease technologies, homing endonucleases, and certain chemical methods. Molecular techniques like meganuclease, transcription activator-like effector nucleases (TALENs), and zinc-finger nucleases (ZFNs) initially emerged as genome-editing technologies. These initial technologies suffer from lower specificity due to their off-targets side effects. Moreover, from biotechnology's perspective, the main obstacle was to develop simple but effective delivery methods for host cell entry. Later, small RNAs, including microRNA (miRNA) and small interfering RNA (siRNA), have been widely adopted in the research laboratories to replace lab animals and cell lines. The latest discovery of CRISPR/Cas9 technology seems more encouraging by providing better efficiency, feasibility, and multi-role clinical application. This later biotechnology seem to take genome-engineering techniques to the next level of molecular engineering. This review generally discusses the various gene-editing technologies in terms of the mechanisms of action, advantages, and side effects.

Genome-Editing Technologies: Concept, Pros, and Cons of Various Genome-Editing Techniques and Bioethical Concerns for Clinical Application.

Metabolic syndrome over the years have structured definitions to classify an individual with the disease. Literature review suggests insulin resistance is hallmark of these metabolic clustering. While measuring insulin resistance directly or indirectly remains technically difficult in general practice, along with multiple stability issues for insulin, various indirect measures have been suggested by authorities. Fasting triglycerides-glucose (TyG) index is one such marker, which is recently been suggested as a useful diagnostic marker to predict metabolic syndrome. However, limited data is available on the subject with almost no literature from our region on the subject. 1. To correlate TyG index with insulin resistance, anthropometric indices, small dense LDLc, HbA1c and nephropathy. 2. To evaluate TyG index as a marker to diagnose metabolic syndrome in comparison to other available markers. Place and duration of study-From Jun-2016 to July-2017 at PSS HAFEEZ hospital Islamabad. From a finally selected sample size of 227 male and female subjects we evaluated their anthropometric data, HbA1c, lipid profile including calculated sdLDLc, urine albumin creatinine raito(UACR) and insulin resistance (HOMAIR). TyG index was calculated using formula of Simental-Mendia LE et al. Aforementioned parameters were correlated with TyG index, differences between subjects with and without metabolic syndrome were calculated using Independent sample t-test. Finally ROC curve analysis was carried out to measure AUC for candidate parameters including TyG Index for comparison. TyG index in comparison to other markers like fasting triglycerides, HOMAIR, HDLc and non-HDLc demonstrated higher positive linear correlation with BMI, atherogenic dyslipidemia (sdLDLc), nephropathy (UACR), HbA1c and insulin resistance. TyG index showed significant differences between various markers among subjects with and without metabolic syndrome as per IDF criteria. AUC (Area Under Curve) demonstrated highest AUC for TyG as [(0.764, 95% CI 0.700–0.828, p-value ≤ 0.001)] followed by fasting triglycerides [(0.724, 95% CI 0.656–0.791, p-value ≤ 0.001)], sdLDLc [(0.695, 95% CI 0.626–0.763, p-value ≤ 0.001)], fasting plasma glucose [(0.686, 95% CI 0.616–0.756, p-value ≤ 0.001)], Non-HDLc [(0.640, 95% CI 0.626–0.763, p-value ≤ 0.001)] and HOMAIR [(0.619, 95% CI 0.545–0.694, p-value ≤ 0.001)]. TyG index, having the highest AUC in comparison to fasting glucose, triglycerides, sdLDLc, non-HDLc and HOMAIR can act as better marker for diagnosing metabolic syndrome.

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Metabolic clustering of risk factors: evaluation of Triglyceride-glucose index (TyG index) for evaluation of insulin resistance.

Objective: To compare insulin resistance between hypertensive and non-hypertensive subjects. Methodology: It is a comparative cross-sectional study which was carried out between April 2004 to March 2006 at department of chemical pathology and endocrinology, Armed Forces Institute of Pathology, Rawalpindi. A total of sixty-three subjects with metabolic syndrome were selected as per the criteria of National Cholesterol Education Program, Adult Treatment Panel III (NCEP, ATP III) from a target population diagnosed to have impaired glucose regulation at AFIP, along with forty-seven age and sex-matched controls. Insulin resistance was calculated by the method of HOMA-IR, using the formula of Mathew’s et al. Blood pressure was measured as per recommendations of JNC7 report on prevention, detection, evaluation and treatment of high blood pressure. Results: The difference for hypertension for diastolic blood pressure between subjects with and without metabolic syndrome were found to be significant [Metabolic syndrome: 86.79 mm of Hg (95 % CI: 83.75-89.84), Age and sex matched controls: 80.21(95 % CI: 76.80-83.62) (p<0.05). However the difference for systolic blood pressure were not found to be significant between the two groups (p=0.860).Hypertensive individuals had higher HOMA-IR [(n=33): 2.87 (95 % CI: 2.373.05)] than non-hypertensive [(n=30): 1.76(95 % CI: 1.53-2.05)] (p<0.05).The effect of obesity as determined by waist circumference between patients with and without hypertension remained significant (p=< 0.05) Conclusion: Hypertensive individuals have higher insulin resistance than subjects without hypertension. Thus it is recommended that vigorous search be made to diagnose insulin resistance in subjects diagnosed to have hypertension, and to demonstrate other components of metabolic syndrome.

Hypertension and metabolic syndrome: impact of clustering of hypertension in subjects with metabolic syndrome

Objective- 
1-To correlate age with fasting plasma glucose, triglycerides and total cholesterol 
2-To compare fasting blood glucose levels among different quartiles of age
3-To compare the effect of gender on lipids and fasting blood glucose 
Methods- 
This cross-sectional study was carried out between May-2010 to April-2011 at the department of pathology & medicine, PNS RAHAT. Target population were adult subjects who visited the lab in exact medical fasting status for measurement of blood glucose to rule out diabetes mellitus. Based upon non-probability convenience sampling a total of 516 subjects were finally included in the study and sampled for fasting blood glucose, total cholesterol, and triglycerides. The results were grouped as: Fasting blood glucose: [(Normal Glucose Tolerance=NGT 6.9 mmol/L)], Serum triglycerides:[ (Group-1 4.0 mmol/L)], [Total cholesterol:(Group-1 6.2 mmol/L)] and different age groups were made to compare the occurrence of different categories of glycemia and lipidemias. 
Results- 
The mean differences for fasting blood glucose across age groups were observed to rise from 21-30 years age group [5.01 (95% CI: 4.77-5.25) mmol/L] to higher levels [6.25 (95% CI: 5.63-6.87) mmol/L] in people having ages between 50-60 years; however, later in life the mean fasting blood glucose were observed to be lower. [P < 0.001].The lipids including total cholesterol and triglycerides rose till the 5th decade of life, and then settled/fall from ensuing 6th decade. Percentage wise most cases of diabetes mellitus were observed between ages 41-50 years. Gender differences were not significant between groups based upon glycemia and lipidemia. 
Conclusion- 
Fasting glycemia and lipidemia were observed to show significant differences among different age groups.

Effect of age and gender on blood lipids and glucose

Objective To compare insulin resistance and glycemic indicators among subjects with euthyroidism and subclinical hypothyroidism. Study design Comparative cross-sectional study. Place and duration of study Department of Pathology and Medicine, PNS Hafeez, Islamabad, in collaboration with the Department of Chemical Pathology and Endocrinology at the Armed Forces Institute of Pathology (AFIP), Rawalpindi, from December 2015 to September 2016. Methodology Subjects referred for executive screening of apparently healthy population (without any known history of diabetes, hypertension, heart disease or other chronic ailments), were included. Subjects were grouped as euthyroidism and subclinical hypothyroidism. Results Median (IQR) insulin resistance indices including fasting insulin and Homeostasis Model Assessment for Insulin Resistance in subjects with group-1 (n=176, 87%, Thyroid Stimulating Hormone: 0.5 - 3.5 mIU/L) and group-2 (n=26, 13%, Thyroid Stimulating Hormone: 3.51 - 15 mIU/L) were 7.6 (6.70) vs. 11.4 (13.72, p=0.040) and 1.77 (1.79) vs. 2.8 (3.07, p=0.071). The median differences for fasting plasma glucose were 5.0 (1.0) in group-1 vs. 5.0 (1.47) for Group-2 [p=0.618], and glycated hemoglobin was 5.60 (1.1) vs. 5.60 (1.7, p=0.824). Homeostasis Model Assessment for beta sensitivity index in paradox showed slightly higher values for group-2 [median (IQR) 86.67 (92.94)] than group-1 [111.6 (189.64, p= 0.040)]. Conclusion Measures of insulin resistance including Homeostasis Model Assessment for Insulin Resistance and fasting insulin levels were significantly different between subjects with euthyroidism and having subclinical hypothyroidism.

Sikandar Hayat Khan

Papers

Genome-Editing Technologies: Concept, Pros, and Cons of Various Genome-Editing Techniques and Bioethical Concerns for Clinical Application.

Metabolic clustering of risk factors: evaluation of Triglyceride-glucose index (TyG index) for evaluation of insulin resistance.

Hypertension and metabolic syndrome: impact of clustering of hypertension in subjects with metabolic syndrome

Effect of age and gender on blood lipids and glucose

Insulin Resistance and Glucose Levels in Subjects with Subclinical Hypothyroidism.