Canagliflozin for weight loss in non-diabetic individuals

Canagliflozin, a sodium-glucose co-transporter 2 (SGLT2) inhibitor, is primarily used as an anti-diabetic medication, but recent evidence suggests its potential role in promoting weight loss in individuals without diabetes. A comprehensive literature review was conducted, analysing relevant studies published between 2013-2021, focusing on the efficacy and safety of canagliflozin for weight loss in non-diabetic populations. Four relevant studies were identified, which consistently demonstrated that canagliflozin treatment in non-diabetic individuals resulted in significant weight loss compared to placebo or other comparators. The weight loss effect of canagliflozin appears to be mediated by increased urinary glucose excretion, caloric loss, and reduction in body fat mass. Canagliflozin also showed improvements in cardiometabolic risk factors, such as blood pressure and lipid profiles. This review, therefore, provides substantial evidence supporting the potential use of canagliflozin as an effective treatment for weight loss in non-diabetic individuals, suggesting it could be a valuable therapeutic option for addressing the rising prevalence of obesity and associated comorbidities. However, further well-designed clinical trials are needed to elucidate the optimal dosing, long-term safety, and potential side effects of canagliflozin in this specific population

Expanding the role of 3-O sulfated heparan sulfate in herpes simplex virus type-1 entry

AbstractHeparan sulfate (HS) proteoglycans are commonly exploited by multiple viruses for initial attachment to host cells. Herpes simplex virus-1 (HSV-1) is unique because it can use HS for both attachment and penetration, provided specific binding sites for HSV-1 envelope glycoprotein gD are present. The interaction with gD is mediated by specific HS moieties or 3-O sulfated HS (3-OS HS), which are generated by all but one of the seven isoforms of 3-O sulfotransferases (3-OSTs). Here we demonstrate that several common experimental cell lines express unique sets of 3-OST isoforms. While the isoforms 3-OST-3, -5 and -6 were most commonly expressed, isoforms 3-OST-2 and -4 were undetectable in the cell lines examined. Since most cell lines expressed multiple 3-OST isoforms, we addressed the significance of 3-OS HS in HSV-1 entry by down-regulating 2-O-sulfation, a prerequisite for 3-OS HS formation, by knocking down 2-OST expression by RNA interference (RNAi). 2-OST knockdown was verified by reverse-transcriptase PCR and Western blot analysis, while 3-OS HS knockdown was verified by immunofluorescence. Cells showed a significant decrease in viral entry, suggesting an important role for 3-OS HS. Implicating 3-OS HS further, cells knocked down for 2-OST expression also demonstrated decreased cell–cell fusion when cocultivated with effector cells transfected with HSV-1 glycoproteins. Our findings suggest that 3-OS HS may play an important role in HSV-1 entry into many different cell lines

Comparison of intra-articular lidocaine versus intravenous sedative and analgesic for reduction of anterior shoulder dislocation in terms of mean pain reduction using vas score

INTRODUCTION: The most common dislocation presenting to emergency department is anterior shoulder dislocation. Posterior dislocations and inferior dislocations are rare. Dislocations of the anterior shoulder mostly occur with the position of the arm is abducted and externally rotated. This results in injury of the humeral head, labrum, capsuloligamentous structures and glenoid. Such patients experience severe pain, therefore prompt reduction is necessary to ameliorate the pain. Intravenous analgesia combined with sedation or intra-articular lidocaine injection can be used for closed reduction of anterior shoulder dislocation. Due to its side effects, Intra-articular lidocaine (IAL) is recommended for use as a probable alternative to intravenous sedation-analgesia especially for patients with contraindication to intravenous sedation-analgesia. OBJECTIVE: To compare intra-articular lidocaine versus intravenous sedative and analgesic for management of anterior shoulder dislocation in terms of mean pain using VAS during reduction of shoulder joint. STUDT DESIGN:   Randomized controlled trial (RCT). SETTING: Removed for blind review DURATION: 6 months (November 22nd, 2017 to May 21st, 2018) SAMPLE SIZE: 60 patients (30 in each group) RESULTS: We included sixty patients in my study. 19 (31.7%) were females and 41 (68.3%) were male patients. Out of all the patients 38 (63.3%) had right sided shoulder dislocation, while the rest 22 (36.7%) patients had left sided shoulder dislocation. Patients mean age was 33.27±10.535 years and mean pain score of all the patients was 4.966±1.930. The mean pain score in Group A was 4.200±1.648, while the mean pain score in Group B was 5.733±1.910 (p value = 0.002. Stratification was done according to gender and age group of the patients, and post-stratification t-test was applied. CONCLUSION:   Intra-articular lidocaine is better option in pain control during reduction of anterior shoulder dislocation. KEY WORDS: Intra venous analgesia, Intra-articular lidocaine, shoulder dislocation

Increasing Awareness and Use of Iodised Salt in a Marginalised Community Setting in North-West Pakistan

Iodine deficiency is still prevalent in parts of Pakistan, despite the introduction of a national Iodine Deficiency Disorder Control Programme in 1994. The purpose of this study was to gain an understanding of the knowledge, attitudes and practice regarding the use of iodised salt in a brick kiln community, and to use this information to design an intervention to increase its consumption. A cross-sectional survey was used to assess the use of iodised salt and focus group discussions explored the attitudes and barriers to its use. Thematically analysed transcripts informed the design of a 4-month intervention. Iodised salt sales and urine iodine concentration (UIC) were monitored to assess the effectiveness of the intervention. At baseline, 2.6% of households reported use of iodised salt and barriers included its higher cost and belief about a negative impact on reproduction. During the intervention, sales of salt labelled as iodised increased by 45%, however this was not reflected in an increase in UIC. This study highlighted the positive impact of education and awareness raising on iodised salt consumption in a hard to reach, marginalised community. However, issues regarding adequate iodisation by local producers and appropriate storage also need to be urgently addressed at a provincial level

Genotoxic and cytotoxic potential of whole plant extracts of Kalanchoe laciniata by Ames and MTT assay

Lack of data on safety of herbal medicines have endangered human health and life. The present study evaluated the genotoxic and mutagenic effect of Kalanchoe laciniata to access the safety and usefulness of the medicinal plant. Aqua-methanolic and n-hexane extracts of K. laciniata were evaluated for the genotoxic potential using Ames assay and cytotoxicity was evaluated using MTT assay. Ames assay was conducted using two strains of Salmonella typhimurium TA-100 and TA-102 whereas MTT assay was performed on baby hamster kidney cell line BHK-21. Aqua-methanolic extract of K. laciniata exhibited significant mutagenicity when exposed to TA- 102 strain with a mutagenic index of 50.66 and 54.74 at maximum dose 150 mg/plate. The extract was also muta- genic to TA-100 strain but to a lesser extent. M.I of n-hexane extract was 12.15 and 15.51 for TA-100 and TA- 102 respectively. n-hexane extract was mutagenic but little difference was observed between results of two strains. Both extracts were found to be cytotoxic with an IC50 of 321.9 and 638.5 µg/mL for aqua-methanolic and n-hexane extracts respectively. On the basis of results it was concluded that aqua-methanolic and n-hexane extracts of K. mutagenic and cytotoxic potential. It is suggested to explore the plant further to evaluate its safety in rodents and other species

Integrating ethics, health policy and health systems in low and middle income countries : case studies from Malaysia and Pakistan.

Scientific progress is a significant basis for change in public-health policy and practice, but the field also invests in value-laden concepts and responds daily to sociopolitical, cultural and evaluative concerns. The concepts that drive much of public-health practice are shaped by the collective and individual mores that define social systems. This paper seeks to describe the ethics processes in play when public-health mechanisms are established in low- and middle-income countries, by focusing on two cases where ethics played a crucial role in producing positive institutional change in public-health policy. First, we introduce an overview of the relationship between ethics and public health; second, we provide a conceptual framework for the ethical analysis of health system events, noting how this approach might enhance the power of existing frameworks; and third, we demonstrate the interplay of these frameworks through the analysis of a programme to enhance road safety in Malaysia and an initiative to establish a national ethics committee in Pakistan. We conclude that, while ethics are gradually being integrated into public-health policy decisions in many developing health systems, ethical analysis is often implicit and undervalued. This paper highlights the need to analyse public-health decision-making from an ethical perspective

Effective contracting for high operational performance in projects

PurposeThe purpose of this paper is to examine combinations of contract clauses in order to ascertain which combinations correlate to high operational performance (OP).Design/methodology/approachTwo hypotheses were formulated from contracting theory and tested on data collected from 45 projects. Fuzzy set qualitative comparative analysis was used and validated with multiple regression and simulation.FindingsThe hypotheses were tested to determine whether combinations of classical, relational, and/or associational contract clauses correlate to high OP. The results show that whereas high OP correlates to combinations of relational and associational contract clauses, classical and relational clauses should not be combined.Research limitations/implicationsDirections are proposed to guide future research in order to produce a more nuanced testing of contractual complementarity.Practical implicationsThe managerial implications of the findings include a more thorough understanding of the use of contract clauses and of which clauses managers should combine to achieve high OP.Originality/valueThis study contributes to the theory of contractual incompleteness and complementarity, specifically in the context of project contracting. The analysis produced two theoretical implications: first, that better performing contracts are created when combining relational and associational contract clauses; and second, that in projects, relational and classical contract clauses are not complementary with regards to realizing high OP

The Text of the Memorandum ‘Sikhs and the New Constitution for India’ (1930). Political Importance and Linguistic Sentiment Analysis.

Communication research has often been performed through text analysis and content analysis. They are research techniques that vary in nature and allow the researcher to make inferences from data present in a text and extract relevant information from them. Content analysis has been used in a variety of contexts with diverse research objectives, goals and methods including computerized and automated methods. In our textual analysis we have selected the Sikh Memorandum from the Indian Round Table Conference (1930) in order to extract linguistic information about its contents that can be related to its historical context through automated methods and in this manner find out word patterns to denote sentiment importance. The purpose is to find out the agreement of some of the automated online sentiment analysis tools that are available on the net as well as whether the Memorandum had positive, neutral or negative polarity. The results will be analyzed

How Slight Solidification Rate Variations within Cast Plate Affect Mechanical Response: A Study on As-Cast A356 Alloy with Cu Additions

The present work investigates a narrow range of secondary dendrite arm spacing (SDAS), in an as-cast A356 alloy with and without copper (Cu) additions. Cu was added to the base A356 alloy melt to reach the target concentration of 0.5 and 1 wt.%. Samples were selected from 3 different positions within the cast plate, offering 30, 35, and 40 μm SDAS variants. Tensile curves revealed a strong influence between the specimen cutting position and strength, with a pronounced effect in the Cu-containing alloys. Hardness measurements did not confirm the tensile response; hence, to understand the phenomenon, microstructural features have been investigated in detail. Eutectic silicon (Si) particle equivalent diameter (ED) size decreased from the top (T) to the bottom (B) position of the cast. Eutectic Si particle surface area (A%) was found to be denser at the B as compared to the T and simultaneously in the Cu-containing alloy as compared to the Cu-free reference alloy. Backscattered electron (BSE) images were employed to investigate the nature of the Cu-rich intermetallic phases. In conclusion, electrical conductivity measurements were performed to confirm the trends observed