Obesity is a worldwide epidemic due to the availability of many unhealthy food options and limited physical exercise. Restriction of the daily food intake results in weight loss, which is also ...associated with better health outcomes including triglycerides, total cholesterol, low-density lipoprotein cholesterol, blood pressure, glucose, insulin, and C-reactive protein. Our aim is to briefly discuss the effects of intermittent fasting on weight and other biochemical markers mentioned previously. The study is designed as a systematic review according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) checklist. To assess the effectiveness of intermittent fasting, related studies were reviewed between 2000 and 2018 and 815 studies were identified. Only four articles met the preset inclusion and exclusion criteria. All four studies have shown a significant decrease in fat mass with P-values <0.01. It was also noted that some biochemical markers were significantly reduced such as the reduction in low-density lipoprotein and triglyceride with P-values < 0.05. Other biochemical markers had inconsistent results. Based on the qualitative analysis, intermittent fasting was found to be efficient in reducing weight, irrespective of the body mass index. Further studies are needed to assess the ability to maintain the lost weight without regaining it and the long-term effects of such dietary changes.
Diabetes remains a burgeoning global problem, necessitating ongoing efforts on the part of pharmaceutical and device manufacturers, patients, and society to curb the frightening trends in morbidity ...and mortality attributable to the malady. Since 1835 when phlorizin was discovered, sodium glucose co-transporter 2 (SGLT-2) inhibitors have rested tantalizingly on the horizon, promising a more physiological approach to glucose control. These agents lower glucose by enhancing its excretion by blocking reabsorption in the renal tubules, thus eliminating glucose from the body along with the molecules' attendant effects on caloric balance, plasma osmolality, and lipids. Consequently, SGLT-2 inhibitors improve glucose control to an extent comparable to other hypoglycemic agents while simultaneously reducing body weight, blood pressure, and cholesterol - an admirable portfolio. One agent, canagliflozin, has recently been approved by the US Food and Drug Administration (FDA) and two other agents have progressed through Phase III trials, including dapagliflozin and empagliflozin. Collectively, when used as monotherapy, these agents have demonstrated reductions in hemoglobin A1c (HbA1c), body weight, and blood pressure of -0.34% to -1.03%, -2.0 to -3.4 kg, and -1.7 to -6.4 mmHg/-0.3 to -2.6 mmHg (systolic blood pressure/diastolic blood pressure), respectively. SGLT-2 inhibitors have been well tolerated, with hypoglycemia (0.9% to 4.3%) occurring infrequently in clinical trials. Safety signals related to breast and bladder cancer have arisen with dapagliflozin, though these are unsubstantiated and likely ascribed to the presence of preexisting cancer. As these agents emerge, clinicians should embrace the addition to the formulary for treating type 2 diabetes, but must also weight the risk-benefit of this new class in deciding which patient types are most likely to benefit from their novel mechanism of action.
Hubtic number in graphs Khalaf, Shadi Ibrahim; Mathad, Veena; Mahde, Sultan Senan
Rocznik Akademii Górniczo-Hutniczej im. Stanisława Staszica. Opuscula Mathematica,
2018, Letnik:
38, Številka:
6
Journal Article
Recenzirano
Odprti dostop
The maximum order of partition of the vertex set \(V(G)\) into hub sets is called hubtic number of \(G\) and denoted by \(\xi(G)\). In this paper we determine the hubtic number of some standard ...graphs. Also we obtain bounds for \(\xi(G)\). And we characterize the class of all \((p,q)\) graphs for which \(\xi(G)=p\).
Female hypoactive sexual desire disorder (HSDD) is a multifactorial sexual dysfunction disorder characterized by a decrease in sexual desire and personal distress. HSDD occurs in naturally occurring ...postmenopausal women or secondary to oophorectomy. Multiple studies have assessed the use of transdermal testosterone (TDT) as a management option for patients with HSDD. Our aim is to assess published studies using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) framework for the quality of evidence regarding testosterone use as a short- and long-term therapy for HSDD. We implemented this qualitative systematic review following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) checklist. We set a GRADE score of 4 (high evidence) as a cutoff point for the quality measure of published studies assessing the use of TDT in HSDD. The outcomes of interest were the efficacy of TDT on the total number of satisfying sexual activity, number of orgasms, sexual desire and distress level in patients with HSDD. These outcomes were evaluated through Sexual Activity Log (SAL), Profile of Female Sexual Function (PFSF), and Personal Distress Scale (PDS) evaluation tools. Five randomized controlled trials were identified to meet the inclusion criteria. The selected studies were of high evidence based on the GRADE score as two of the studies scored 4 points, the other two studies scored 5 points and one study scored 6 points. All of the high quality selected studies had similar outcomes suggesting high effectiveness for the use of 300 µg/d TDT with or without estrogen for the management of HSDD with minimal side effects. One study showed a trend for higher risk of breast cancer in long-term use (0.37%). The use of 300 µg/d of TDT in surgical and natural menopause is an effective plan to manage HSDD in the short- and long-term. Although side effects are minimal, further prospective research is needed to assess the more severe side effects such as breast cancer in the long-term use of TDT.
Abstract Objective Hyperglycemia-induced endothelial cell dysfunction in vascular disease can occur due to increased oxidative stress and a concomitant increase in endoplasmic reticulum (ER) stress. ...To investigate whether these cellular stresses are independent or causally linked, we determined whether or not specific glycolytic intermediates that induce oxidative stress also induce ER stress. Methods Human umbilical vein endothelial cells were treated with dextrose, partially metabolizable (e.g., fructose and galactose) and non-metabolizable sugars (e.g., 3-O-methyglucose), and various intermediates of the glycolytic and tricarboxylic acid pathways. Activation of the unfolded protein response and subsequent generation of ER stress was measured by the ER stress-responsive alkaline phosphatase method, and superoxide (SO) generation was measured using the hydro-ethidene–fluorescence method. The mitochondrial origin of the SO and the generation of ER stress by dextrose and the intermediate metabolites were confirmed with experiments using allopurinol and diphenyleneiodonium chloride to block SO generation by xanthine oxidase and nicotinamide adenosine dinucleotide phosphate oxidase, respectively. Results Although ER stress could be induced by glycolytic intermediates up to and including pyruvate, the SO generation occurred in the presence of glycolytic and mitochondrial metabolites. Conclusion Although the mitochondria are the site of signals generated by dextrose to initiate oxidative stress, the dextrose-induced ER stress, unlike SO generation, does not require pyruvate oxidation in the mitochondria.
The hub-integrity of a graph G = (V (G);E(G)) is denoted as HI(G) and dened by HI(G) = minfjSj + m(G S); S is a hub set of Gg, where m(G S) is the order of a maximum component of G S. In this paper, ...we discuss hub-integrity of splitting graph and duplication of an edge by vertex and duplication of vertex by an edge of some graphs.
The Minimum Hub Distance Energy of a Graph Mathad, Veena; Mahde, Sultan Senan
International journal of computer applications,
01/2015, Letnik:
125, Številka:
13
Journal Article
Odprti dostop
In this paper, the concept of minimum hub distance energy EHd(G) of a connected graph G is introduced and minimum hub distance energies of some standard graphs and a number of wellknown families of ...graphs are computed. Upper and lower bounds for EHd(G) are also established.
Abstract Aim Hyperglycemia-induced endothelial cell dysfunction can be the result of increased oxidative stress and concomitant increase in endoplasmic reticulum (ER) stress. To test the extent of ...coupling between these two stresses, the effect of antioxidant vitamins on glucose-induced oxidative stress and ER stress in endothelial cells were studied. Methods Human umbilical vein endothelial cells (HUVEC) were treated with physiological (5.5 mM) or supra-physiological (27.5 mM) dextrose concentrations, and ER stress and oxidative stress were measured. Additional experiments were carried out in HUVEC over-expressing exogenous glucose transporter-1 (Glut-1) and treated with 5.5 mM dextrose. Results Supra-physiological dextrose concentrations increased both ER stress and oxidative stress. However, while oxidative stress could be effectively inhibited with alpha-tocopherol and ascorbic acid, these antioxidants had no effect on ER stress. Increasing intracellular glucose levels by exogenous expression of Glut-1 in endothelial cells also increased oxidative stress and ER stress. Whereas the oxidative stress in these cells was reduced with alpha-tocopherol and ascorbic acid and dimethylsulfoxide, the ER stress could not be ameliorated with alpha-tocopherol and ascorbic acid. Conclusions These results indicate that ER stress can be uncoupled from oxidative stress and antioxidants can ameliorate the latter without altering the ER stress induced by hyperglycemia.
Abstract
Introduction
Posterior reversible encephalopathy syndrome (PRES) is a clinico-radiological entity that can present with headaches, focal neurological deficits, altered mental status, and ...seizures. Common etiologies are uncontrolled hypertension, preeclampsia/eclampsia, and chemotherapeutic agents. Hereby, we present a patient with status epilepticus secondary to PRES induced by hypercalcemia due to primary hyperparathyroidism.
Clinical Case
A 59-year-old Caucasian female with history of T2DM, GERD, gout, and bowel resection for an incarcerated abdominal hernia three weeks ago presented to the emergency department due to seizure-like movements. She had no history of seizures. Initial vitals showed HR of 96 bpm, BP of 148/67 mmHg, RR of 20 rpm, Temperature of 97.7F, and a BMI of 31.5 kg/m2. Physical exam revealed the presence of abdominal wound-vac and tonic-clonic movements that failed to improve with lorazepam, midazolam, and levetiracetam; hence she was intubated for airway protection and started on propofol. Lumbar puncture performed in the ED was unremarkable. Laboratory studies were pertinent for acute kidney injury (AKI) with a serum creatinine of 1.78 mg/dL, lactic acid of 6.1 mmol/L, and serum calcium of 14.5 mg/dL (8.7-10.4) with albumin of 4.2 g/dL. AKI and lactic acidosis rapidly improved with IV fluids. CT-head without contrast was negative for any acute pathologies. MRI-brain showed abnormal subcortical FLAIR signals within the bilateral parietal and occipital lobes with corresponding diffusion restriction in bilateral occipital lobes consistent with PRES. Continuous EEG (cEEG) showed ongoing epileptiform activity with an intermittent suppression pattern. Hypercalcemia workup revealed inappropriately normal intact-PTH of 45.9 pg/mL (10. 0-66. 0), PTHrP <2pmol/L, and 25-(OH)-Vitamin-D3 level of 34 ng/mL (30. 0-100. 0). Paraproteinemia work-up was negative. Thyroid ultrasound demonstrated an incidental nodule in the external aspect of the inferior right lobe measuring 6×3×3mm suggestive of parathyroid gland enlargement. Hypercalcemia was successfully treated with aggressive IV fluids and zoledronic acid. Repeat cEEG showed resolution of epileptiform discharges. She was successfully extubated without recurrence of seizures. She was determined to have hypercalcemia induced PRES secondary to primary hyperparathyroidism. Given the significant elevation of calcium and associated neurological symptoms, she met the surgical criteria and was discharged with outpatient parathyroidectomy plan.
Conclusion
PRES secondary to severe hypercalcemia has been described in the literature, albeit rarely. The exact pathophysiology is unclear but thought to be due to vasospasm based on cerebral angiogram studies. Early recognition of hypercalcemia as a culprit for PRES along with prompt treatment is crucial to treat life-threatening complications of PRES.
Presentation: Saturday, June 11, 2022 1:00 p.m. - 3:00 p.m.
Weight reduction is essential for improving health outcomes in people with obesity and type 2 diabetes. We assessed the efficacy and safety of tirzepatide, a glucose-dependent insulinotropic ...polypeptide and glucagon-like peptide-1 receptor agonist, versus placebo, for weight management in people living with obesity and type 2 diabetes.
This phase 3, double-blind, randomised, placebo-controlled trial was conducted in seven countries. Adults (aged ≥18 years) with a body-mass index (BMI) of 27 kg/m2 or higher and glycated haemoglobin (HbA1c) of 7–10% (53–86 mmol/mol) were randomly assigned (1:1:1), using a computer-generated random sequence via a validated interactive web-response system, to receive either once-weekly, subcutaneous tirzepatide (10 mg or 15 mg) or placebo for 72 weeks. All participants, investigators, and the sponsor were masked to treatment assignment. Coprimary endpoints were the percent change in bodyweight from baseline and bodyweight reduction of 5% or higher. The treatment-regimen estimand assessed effects regardless of treatment discontinuation or initiation of antihyperglycaemic rescue therapy. Efficacy and safety endpoints were analysed with data from all randomly assigned participants (intention-to-treat population). This trial is registered with ClinicalTrials.gov, NCT04657003.
Between March 29, 2021, and April 10, 2023, of 1514 adults assessed for eligibility, 938 (mean age 54·2 years SD 10·6, 476 51% were female, 710 76% were White, and 561 60% were Hispanic or Latino) were randomly assigned and received at least one dose of tirzepatide 10 mg (n=312), tirzepatide 15 mg (n=311), or placebo (n=315). Baseline mean bodyweight was 100·7 kg (SD 21·1), BMI 36·1 kg/m2 (SD 6·6), and HbA1c 8·02% (SD 0·89; 64·1 mmol/mol SD 9·7). Least-squares mean change in bodyweight at week 72 with tirzepatide 10 mg and 15 mg was –12·8% (SE 0·6) and –14·7% (0·5), respectively, and –3·2% (0·5) with placebo, resulting in estimated treatment differences versus placebo of –9·6% percentage points (95% CI –11·1 to –8·1) with tirzepatide 10 mg and –11·6% percentage points (–13·0 to –10·1) with tirzepatide 15 mg (all p<0·0001). More participants treated with tirzepatide versus placebo met bodyweight reduction thresholds of 5% or higher (79–83% vs 32%). The most frequent adverse events with tirzepatide were gastrointestinal-related, including nausea, diarrhoea, and vomiting and were mostly mild to moderate in severity, with few events leading to treatment discontinuation (<5%). Serious adverse events were reported by 68 (7%) participants overall and two deaths occurred in the tirzepatide 10 mg group, but deaths were not considered to be related to the study treatment by the investigator.
In this 72-week trial in adults living with obesity and type 2 diabetes, once-weekly tirzepatide 10 mg and 15 mg provided substantial and clinically meaningful reduction in bodyweight, with a safety profile that was similar to other incretin-based therapies for weight management.
Eli Lilly and Company.
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