A qualitative investigation of dental internships in Saudi Arabia: Exploring the experiences of dental interns.

BACKGROUND: For dental graduates, internships are a vital transitional phase that gives them the invaluable opportunity to close the gap between their academic studies and the reality of professional dentistry. Research on dental internships remains limited and most of the existing studies focus on the clinical aspects of dental internships with little attention given to dental interns' experiences overall. This study aims to bridge this gap in the literature by gaining an in-depth understanding of Saudi dental graduates' range of experiences as dental interns. METHODS: To achieve the research objective, this study adopted a qualitative approach. Using purposive and snowball sampling, the study recruited 23 dental interns from Riyadh Province, Saudi Arabia, who had completed at least nine months of their internship. Data was gathered across three months via diaries and virtual semi-structured interviews based on participants' preferences. The data was then analysed thematically using an inductive analytical strategy. RESULTS: The data analysis revealed three major themes and four sub-themes regarding the experiences of dental interns. The core three themes were "activities", "autonomy" and "transitioning to a balanced life" whereby interns have the time and freedom to explore their interests, rekindle their social lives and focus on self-care, resulting in a better work-life balance. CONCLUSION: This study suggests that dental interns will benefit from the retention and strengthening of key internship activities such as research, community work and clinical rotations. Additionally, the experiences of dental interns can be improved by encouraging interns to progress in their clinical training with a high level of autonomy. Also, due to the limited research in this area, further studies are required to improve our understanding of the lived experiences of dental interns and dental internships in general.

Investigating the impact of wet rendering (solventless method) on PUFA-rich oil from catfish (Clarias magur) viscera.

Catfish (Clarias magur) is a popular freshwater fish food worldwide. The processing of this fish generates a significant amount of waste, mainly in the form of viscera, which constitutes around 10-12% of the fish's total weight. This study was focused on extracting polyunsaturated fatty acid (PUFA)-rich oil from catfish viscera, aiming to enhance the extraction process and make the production of oil and handling of fish byproducts more cost-effective. The wet reduction method, a solvent-free approach, was used for extraction, with yield optimization done via the Box-Behnken design. The resulting oil was evaluated for its oxidative quality and chemical characteristics. The optimal conditions for the wet rendering process were as follows: viscera to water ratio, 1:0.5 (w/v); temperature, 90℃; and time, 20 min, yielding 12.40 g/100 g of oil. The oil extracted under optimal wet rendering conditions had quality and oxidative stability comparable to solvent extraction and fewer secondary oxidation compounds. This oil had a higher PUFA content, specifically a 4:1 ratio of omega 6 to omega 3. Such oil, derived from catfish viscera, is suitable for the food industry due to its solvent-free extraction method.

Insights into recent innovations in barrier resistance of edible films for food packaging applications.

The utilization of biopolymer-based food packaging holds significant promise in aligning with sustainability goals and enhancing food safety by offering a renewable, biodegradable, and safer alternative to traditional synthetic polymers. However, these biopolymer-derived films often exhibit poor barrier and mechanical properties, potentially limiting their commercial viability. Desirable barrier properties, such as moisture and oxygen resistance, are critical for preserving and maintaining the quality of packaged food products. This review comprehensively explores different traditional and advance methodologies employed to access the barrier properties of edible films. Additionally, this review thoroughly examines various approaches aimed at enhancing the barrier properties of edible films, such as the fabrication of multilayer films, the selection of biopolymers for composite films, as well as the integration of plasticizers, crosslinkers, hydrophobic agents, and nanocomposites. Moreover, the influence of process conditions, such as preparation techniques, homogenization, drying conditions, and rheological behavior, on the barrier properties of edible films has been discussed. The review provides valuable insights and knowledge for researchers and industry professionals to advance the use of biopolymer-based packaging materials and contribute to a more sustainable and food-safe future.

Antidiabetic Property Optimization from Green Leafy Vegetables Using Ultrasound-Assisted Extraction to Improve Cracker Production.

Here we test a method of incorporating of plant extracts into popular snack foods to help control diabetes. Since some fresh vegetables contain antidiabetic compounds, ultrasound-assisted extraction was used to optimize their extraction of from spring onions, bunching onions, and celery for later incorporation into crackers. We compared various concentrations of ethanol used during extraction, after which they were exposed to an ultrasound processor whose amplitude and sonication time were also varied. The optimal extraction conditions were found to be an ethanol concentration of 44.08%, an amplitude of 80%, and a sonication time of 30 min. This resulted in the highest level of α-glucosidase inhibitory activity (i.e., 1,449.73 mmol ACE/g) and the highest extraction yield (i.e., 24.16%). The extract produced from these optimum conditions was then used as a constituent component of crackers at 0.625%, 1.25%, or 2.5% w/w. These biscuits were then produced at baking temperatures of 140°C, 150°C, or 160°C. We then measured the physical characteristics and bioactivities of sample biscuits from each treatment. We found that biscuits containing 2.5% vegetable combination extract and baked at 140°C had the highest total phenolic content, the strongest antioxidant performance, and showed the most substantial antidiabetic and antiobesity effects. Here we establish conditions for the effective extraction of antidiabetic functional ingredients via ultrasound from green leafy vegetables. We also provide a method of using these ingredients to prepare crackers with the aim of developing a functional antidiabetic snack food.

Carcinoma arising from thyroglossal duct remnants.

Thyroglossal duct cysts (TGDCs) are unusual remnants of the thyroid gland that are rarely observed in association with carcinoma. The present study aimed to showcase the clinical characteristics, diagnosis and management of patients with TGDC carcinoma. It was a single-center study conducted from February 2016 to February 2020. The study involved the retrospective analysis of a series of cases with TGDC carcinoma. A total of 10 patients were included in the study, of whom eight (80%) were females. Their age ranged from 25 to 48 years with a mean age of 39.1 years. A total of five cases (50%) underwent only Sistrunk's procedure, four patients (40%) underwent total thyroidectomy along with Sistrunk's procedure and one patient (10%) was treated by Sistrunk operation and lobectomy. In all of the cases (100%), histopathological examination confirmed papillary thyroid carcinoma in TGDCs. In addition, in the thyroid tissue, 2 cases (20%) also had papillary thyroid carcinoma and 3 cases (30%) had papillary thyroid microcarcinoma. Radioiodine was administered in one patient (10%) with suppressive thyroxine. A three-year follow-up with ultrasound revealed no suspicious lesions in any of the cases. Although rare, carcinoma may develop in the thyroglossal cysts. In this situation, both the thyroid gland and different lymph node compartments should be evaluated for malignancy. Surgical intervention is the cornerstone of management.

Influence of solvent-free extraction of fish oil from catfish (Clarias magur) heads using a Taguchi orthogonal array design: A qualitative and quantitative approach.

This study aimed to efficiently utilize catfish heads, enhancing the oil extraction process while improving the cost-effectiveness of fish byproduct management. The study employed the wet rendering method, a solvent-free approach, utilizing a two-factor Taguchi orthogonal array design to identify critical parameters for optimizing oil yield and ensuring high-quality oil attributes. The extraction temperature (80-120°C) and time (5-25 min) were chosen as variables in the wet rendering process. Range analysis identified the extraction time as a more significant (p < 0.05) factor for most parameters, including oil yield, oil recovery, acid value, free fatty acids, peroxide value, and thiobarbituric acid reactive substances. The extraction temperature was more significant (p < 0.05) for oil color. Consequently, the wet rendering method was optimized, resulting in an extraction temperature of 80°C and an extraction time of 25 min, yielding the highest oil yield. This optimized wet rendering process recovered 6.37 g/100 g of oil with an impressive 54.16% oil recovery rate, demonstrating comparable performance to traditional solvent extraction methods. Moreover, Fourier transfer infrared spectra analysis revealed distinct peaks associated with triacylglycerols and polyunsaturated fatty acids (PUFA). The oil recovered under optimized conditions contained higher levels of PUFA, including oleic acid (189.92 µg/g of oil), linoleic acid (169.92 µg/g of oil), eicosapentaenoic acid (17.41 µg/g of oil), and docosahexaenoic acid (20.82 µg/g of oil). Volatile compound analysis revealed lower levels of secondary oxidation compounds under optimized conditions. This optimized wet rendering method offers practical advantages in terms of cost-efficiency, sustainability, reduced environmental impact, and enhanced oil quality, making it an attractive option for the fish processing industries. Future research possibilities may include the purification of the catfish head oil and its application in the food and pharmaceutical industries.

Spermatocytic tumor of the testis: A case report and mini­review of the literature.

Spermatocytic tumors are a rare type of testicular cancer, comprising <1% of all testicular malignancies. This type of cancer typically affects males in their 60s and 70s and rarely metastasizes; however, it poses a threat to the health of affected individuals if left untreated. The present study describes the case of a 68-year-old male patient with this type of tumor, including a presentation of his initial symptoms, treatment and subsequent monitoring. A male patient, aged 68 years, visited the authors' clinic with an asymptomatic mass in the right testicle. The mass had been progressively increasing in size for a duration of 5 years following a history of blunt injury. During the examination, a noticeable, painless enlargement was detected in the right testis, whereas the left testis appeared to be in a normal state. Tumor markers were within normal limits. Imaging revealed a complex mass (11x8x7 cm) almost replacing the right testis, with no detectable lymph nodes. A right radical orchidectomy was performed under spinal anesthesia. A histopathological examination revealed a spermatocytic tumor. The post-operative period was uneventful, with no metastasis detected in the CT scans. The patient was discharged with instructions for regular follow-up appointments. The case presented herein highlights a rare spermatocytic tumor in a 68-year-old male. The early detection and treatment of testicular tumors, regardless of age, are crucial for a good prognosis.

COVID-19 vaccine hesitancy among people living with HIV in a low-resource setting: A multi-center study of prevalence, correlates and reasons.

BACKGROUND: Hesitancy to COVID-19 vaccine may worsen the burden of COVID-19 among people living with HIV (PLHIV), who are at a higher risk of COVID-19-related hospitalization and death, compared to HIV non-infected individuals. Therefore, we evaluate the predictors and reasons for COVID-19 vaccine hesitancy among unvaccinated PLHIV in six antiretroviral therapy (ART) clinics across northern Nigeria. METHODOLOGY: In this cross-sectional study, conducted between October 2021 and February 2022 in six hospitals across two geopolitical regions of Nigeria, we utilized interviewer-administered questionnaires to assess COVID-19 vaccine hesitancy among a convenience sample of 790 eligible adult PLHIV. Hesitancy was defined as answering 'no' or 'maybe' to a question asking participants their willingness to accept the COVID-19 vaccine. A multivariate logistic regression model was used to estimate the adjusted odds ratio (aOR) and 95% confidence interval (CI) of the factors associated with COVID-19 vaccine hesitancy among PLHIV. RESULTS: Of the total 660 unvaccinated participants included in the analysis (61.82% female, mean age [SD] of 39.76 [10.75]), 381 (57.72%) were hesitant to COVID-19 vaccine. Being 50 years and older (aOR: 0.43; 95% CI: 0.21-0.89), being unemployed (aOR: 0.57; 95% CI: 0.34-0.95), experiencing the adverse effects of ART (aOR: 0.36; 95% CI: 0.15-0.86), and perception of being at high risk of contracting COVID-19 (aOR: 0.22; 95% CI: 0.13-0.37) were associated with significantly lower odds of hesitancy. Conversely, being female (aOR: 1.64; 95% CI: 1.02-2.61) and attending ART clinics at state administrative capital cities (IIDH Kano [aOR: 2.40; 95% CI: 1.10-5.25], MMSH Kano [aOR: 5.59; 95% CI: 1.97-10.66], YSSH Damaturu [aOR: 9.88; 95% CI: 4.02-24.29] vs. GH Gashua) were associated with significantly higher odds of hesitancy. The most common reasons for hesitancy include fear of potential adverse effects, skepticism about vaccine efficacy, the rapid development of the COVID-19 vaccine, and the perceived lack of effort to develop a cure or vaccine for HIV/AIDS. CONCLUSION: Interventions aimed at combating misperceptions and misinformation regarding the COVID-19 vaccination program may reduce the prevalence of COVID-19 vaccine hesitancy among unvaccinated PLHIV.

Evaluation of QuantiFERON SARS-CoV-2 interferon-γ release assay following SARS-CoV-2 infection and vaccination.

T cells are important in preventing severe disease from SARS-CoV-2, but scalable and field-adaptable alternatives to expert T-cell assays are needed. The interferon-gamma release assay QuantiFERON platform was developed to detect T-cell responses to SARS-CoV-2 from whole blood with relatively basic equipment and flexibility of processing timelines. Forty-eight participants with different infection and vaccination backgrounds were recruited. Whole blood samples were analysed using the QuantiFERON SARS-CoV-2 assay in parallel with the well-established 'Protective Immunity from T Cells in Healthcare workers' (PITCH) ELISpot, which can evaluate spike-specific T-cell responses. The primary aims of this cross-sectional observational cohort study were to establish if the QuantiFERON SARS-Co-V-2 assay could discern differences between specified groups and to assess the sensitivity of the assay compared with the PITCH ELISpot. The QuantiFERON SARS-CoV-2 distinguished acutely infected individuals (12-21 days post positive PCR) from naïve individuals (P < 0.0001) with 100% sensitivity and specificity for SARS-CoV-2 T cells, whilst the PITCH ELISpot had reduced sensitivity (62.5%) for the acute infection group. Sensitivity with QuantiFERON for previous infection was 12.5% (172-444 days post positive test) and was inferior to the PITCH ELISpot (75%). Although the QuantiFERON assay could discern differences between unvaccinated and vaccinated individuals (55-166 days since second vaccination), the latter also had reduced sensitivity (44.4%) compared to the PITCH ELISpot (66.6%). The QuantiFERON SARS-CoV-2 assay showed potential as a T- cell evaluation tool soon after SARS-CoV-2 infection but has lower sensitivity for use in reliable evaluation of vaccination or more distant infection.

Effects of Subnormothermic Regulated Hepatic Reperfusion on Mitochondrial and Transcriptomic Profiles in a Porcine Model.

OBJECTIVE: We sought to investigate the biological effects of pre-reperfusion treatments of the liver after warm and cold ischemic injuries in a porcine donation after circulatory death model. SUMMARY OF BACKGROUND DATA: Donation after circulatory death represents a severe form of liver ischemia and reperfusion injury that has a profound impact on graft function after liver transplantation. METHODS: Twenty donor pig livers underwent 60 minutes of in situ warm ischemia after circulatory arrest and 120 minutes of cold static preservation prior to simulated transplantation using an ex vivo perfusion machine. Four reperfusion treatments were compared: Control-Normothermic (N), Control- Subnormothermic (S), regulated hepatic reperfusion (RHR)-N, and RHR-S (n = 5 each). The biochemical, metabolic, and transcriptomic profiles, as well as mitochondrial function were analyzed. RESULTS: Compared to the other groups, RHR-S treated group showed significantly lower post-reperfusion aspartate aminotransferase levels in the reperfusion effluent and histologic findings of hepatocyte viability and lesser degree of congestion and necrosis. RHR-S resulted in a significantly higher mitochondrial respiratory control index and calcium retention capacity. Transcriptomic profile analysis showed that treatment with RHR-S activated cell survival and viability, cellular homeostasis as well as other biological functions involved in tissue repair such as cytoskeleton or cytoplasm organization, cell migration, transcription, and microtubule dynamics. Furthermore, RHR-S inhibited organismal death, morbidity and mortality, necrosis, and apoptosis. CONCLUSION: Subnormothermic RHR mitigates IRI and preserves hepatic mitochondrial function after warm and cold hepatic ischemia. This organ resuscitative therapy may also trigger the activation of protective genes against IRI. Sub- normothermic RHR has potential applicability to clinical liver transplantation.

Assessment of Textbook Oncologic Outcomes Following Proctectomy for Rectal Cancer.

BACKGROUND: Outcomes of rectal adenocarcinoma vary considerably. Composite "textbook oncologic outcome" (TOO) is a single metric that estimates optimal clinical performance for cancer surgery. METHODS: Patients with stage II/III rectal adenocarcinoma who underwent single-agent neoadjuvant chemoradiation and proctectomy within 5-12 weeks were identified in the National Cancer Database (NCDB). TOO was defined as achievement of negative distal and circumferential resection margin (CRM), retrieval of ≥ 12 nodes, no 90-day mortality, and length of stay (LOS) < 75th percentile of corresponding year's range. Multivariable logistic regression was used to identify predictors of TOO. RESULTS: Among 318,225 patients, 8869 met selection criteria. Median age was 62 years (IQR 54-71), and 5550 (62.6%) were males. Low anterior resection was the most common procedure (LAR, 6,037 (68.1%) and 3084 (34.8%) were treated at a high-volume center (≥ 20 rectal resections/year). TOO was achieved in 3967 patients (44.7%). Several components of TOO were achieved commonly, including negative CRM (87.4%), no 90-day mortality (98.0%), no readmission (93.0%), and no prolonged hospitalization (78.8%). Logistic regression identified increasing age, non-private insurance, low-volume centers, open approach, Black race, Charlson score ≥ 3, and abdominoperineal resection (APR) as predictors of failure to achieve TOO. Over time, TOOs were attained more commonly which correlated with increased minimally invasive surgery (MIS) adoption. TOO achievement was associated with improved survival. CONCLUSIONS: Rectal adenocarcinoma patients achieve TOO uncommonly. Treatment at high-volume centers and MIS approach were among modifiable factors associated with TOO in this study.

Combined Percutaneous Tracheostomy and Endoscopic Gastrostomy Tubes in COVID-19: A Prospective Series of Patient Outcomes.

Background: A significant number of patients with severe respiratory failure related to COVID-19 require prolonged mechanical ventilation. Minimal data exists regarding the timing, safety, and efficacy of combined bedside percutaneous tracheostomy and endoscopy gastrostomy tube placement in these patients. The safety for healthcare providers is also in question. This study's objective was to evaluate the effectiveness and safety of combined bedside tracheostomy and gastrostomy tube placement in COVID-19 patients. Design and Methods: This is a single arm, prospective cohort study in patients with COVID-19 and acute respiratory failure requiring prolonged mechanical ventilation who underwent bedside tracheostomy and percutaneous endoscopic gastrostomy placement. Detailed clinical and procedural data were collected. Descriptive statistics were employed and time to event curves were estimated and plotted using the Kaplan Meier method for clinically relevant prespecified endpoints. Results: Among 58 patients, the median total intensive care unit (ICU) length of stay was 29 days (24.7-33.3) with a median of 10 days (6.3-13.7) postprocedure. Nearly 88% of patients were weaned from mechanical ventilation postprocedure at a median of 9 days (6-12); 94% of these were decannulated. Sixty-day mortality was 10.3%. Almost 90% of patients were discharged alive from the hospital. All procedures were done at bedside with no patient transfer required out of the ICU. A median of 3.0 healthcare personnel total were present in the room per procedure. Conclusion: This study shows that survival of critically ill COVID-19 patients after tracheostomy and gastrostomy was nearly 90%. The time-to-event curves are encouraging regarding time to weaning, downsizing, decannulation, and discharge. A combined procedure minimizes the risk of virus transmission to healthcare providers in addition to decreasing the number of anesthetic episodes, transfusions, and transfers patients must undergo. This approach should be considered in critically ill COVID-19 patients requiring prolonged mechanical ventilation.

Bioconservation of iron and enhancement of antioxidant and antibacterial properties of chicken gizzard protein hydrolysate fermented by Pediococcus acidilactici ATTC 8042.

BACKGROUND: The poultry industry is one of the fastest growing sectors, and it generates considerable quantities of chicken gizzards (CG) every day. However, due to their hard texture and high microbial load, and due to cultural beliefs, they are not preferred by consumers. Chicken gizzards are a substantial source of proteins, iron, and other nutrients, which can be used effectively to produce nutraceuticals, rich in peptides (antioxidants and antibacterial), bio-iron, essential free amino acids, and fatty acids vital for human health. RESULTS: Lactic acid fermentation of CG by Pediococcus acidilactici ATTC 8042 increased the antioxidant activity of 2,2-diphenyl-1-picrylhydrazyl (DPPH), azino-bis (3-ethylbenzothiaziline-6-sulphonic acid) (ABTS), and ferric reducing antioxidant power (FRAP) by up to 26 times compared with unfermented CG (P < 0.05). The amount of hydrolysis and solvents (ethanol and water) used for extracting protein hydrolysates significantly affected the antioxidant properties. Moreover, fermented CG showed a negligible reduction in bio-iron (2-3%) compared with heat-processed CG (85 °C for 15 min), in which bio-iron was reduced by up to 20.3% (P < 0.05). The presence of unsaturated fatty acids such as C20:4 and C22:4 n-6 indicated a low level of lipid oxidation. CONCLUSION: Fermented CG, with its reasonably high antioxidant and antibacterial activity, together with a substantial amount of bio-iron and other nutritional components can serve as a functional food or feed additive to reduce oxidative stress and to treat iron deficiency. © 2020 Society of Chemical Industry.

Antimicrobial resistance: more than 70 years of war between humans and bacteria.

Development of antibiotic resistance in bacteria is one of the major issues in the present world and one of the greatest threats faced by mankind. Resistance is spread through both vertical gene transfer (parent to offspring) as well as by horizontal gene transfer like transformation, transduction and conjugation. The main mechanisms of resistance are limiting uptake of a drug, modification of a drug target, inactivation of a drug, and active efflux of a drug. The highest quantities of antibiotic concentrations are usually found in areas with strong anthropogenic pressures, for example medical source (e.g., hospitals) effluents, pharmaceutical industries, wastewater influents, soils treated with manure, animal husbandry and aquaculture (where antibiotics are generally used as in-feed preparations). Hence, the strong selective pressure applied by antimicrobial use has forced microorganisms to evolve for survival. The guts of animals and humans, wastewater treatment plants, hospital and community effluents, animal husbandry and aquaculture runoffs have been designated as "hotspots for AMR genes" because the high density of bacteria, phages, and plasmids in these settings allows significant genetic exchange and recombination. Evidence from the literature suggests that the knowledge of antibiotic resistance in the population is still scarce. Tackling antimicrobial resistance requires a wide range of strategies, for example, more research in antibiotic production, the need of educating patients and the general public, as well as developing alternatives to antibiotics (briefly discussed in the conclusions of this article).

Purification, physicochemical properties, and statistical optimization of fibrinolytic enzymes especially from fermented foods: A comprehensive review.

Fibrinolytic enzymes are proteases responsible for cleavage of fibrin mesh in thrombus clots, which are the primary causative agents in cardiovascular diseases. Developing safe, effective and cheap thrombolytic agents are important for prevention and cure of thrombosis. Although a wide variety of sources have been discovered for fibrinolytic enzymes, only few of them have been employed in clinical and therapeutic applications due to the drawbacks such as high cost of production, low stability of enzyme or therapeutic side effects. However, the discovery of new fibrinolytic enzymes requires complex purification stages and characterization, which gives an insight into their diverse modes of action. Post-discovery, approaches such as a) statistical optimization for fermentative bioprocessing and b) genetic engineering are advantageous in providing economic viability by finding simple and cost-effective medium, strain development with sufficient nutrient supplements for stable and high-level production of recombinant enzyme. This review provides a comprehensive understanding of different sources, purification techniques, production through genetic engineering approaches and statistical optimization of fermentation parameters as proteases have a wide variety of industrial and biotechnological applications making 60% of total enzyme market worldwide. New strategies targeting increased enzyme yields, non-denaturing environments, improved stability, enzyme activity and strain improvement have been discussed.

Improved Beta Cell Glucose Sensitivity Plays Predominant Role in the Decrease in HbA1c with Cana and Lira in T2DM.

AIM: To examine the effect of combination therapy with canagliflozin plus liraglutide versus each agent alone on beta cell function in type 2 diabetes mellitus (T2DM) patients. RESEARCH DESIGN AND METHODS: A total of 45 poorly controlled (HbA1c = 7%-11%) T2DM patients received an oral glucose tolerance test (OGTT) before and after 16 weeks of treatment with: (i) liraglutide (LIRA); (ii) canagliflozin (CANA); (iii) liraglutide plus canagliflozin (CANA/LIRA). RESULTS: Both liraglutide and canagliflozin significantly lowered HbA1c with no significant additive effect of the combination on HbA1c (0.89%, 1.43%, and 1.67% respectively). Insulin secretion during the OGTT, measured with (∆C-Pep/∆G)0-120, increased in the 3 groups (from 0.30 ± 0.06 to 0.48 ± 0.10; 0.29 ± 0.05 to 0.98 ± 0.23; and 0.24 ± 0.06 to 1.09 ± 0.12 in subjects receiving CANA, LIRA and CANA/LIRA respectively; P = 0.02 for CANA vs LIRA, P < 0.0001, CANA/LIRA vs CANA), and the increase in insulin secretion was associated with an increase in beta cell glucose sensitivity (29 ± 5 to 55 ± 11; 33 ± 6 to 101 ± 16; and 28 ± 6 to 112 ± 12, respectively; P = 0.01 for CANA vs LIRA, P < 0.0001, CANA/LIRA vs CANA). No significant difference in the increase in insulin secretion or beta cell glucose sensitivity was observed between subjects in LIRA or CANA/LIRA groups. The decrease in HbA1c strongly and inversely correlated with the increase in beta cell glucose sensitivity (r = 0.71, P < 0.001). In multivariate regression model, improved beta cell glucose sensitivity was the strongest predictor of HbA1c decrease with each therapy. CONCLUSION: Improved beta cell glucose sensitivity with canagliflozin monotherapy and liraglutide monotherapy or in combination is major factor responsible for the HbA1c decrease. Canagliflozin failed to produce an additive effect to improve beta cell glucose sensitivity above that observed with liraglutide.

Combination Therapy With Canagliflozin Plus Liraglutide Exerts Additive Effect on Weight Loss, but Not on HbA1c, in Patients With Type 2 Diabetes.

OBJECTIVE: To examine the effect of combination therapy with canagliflozin plus liraglutide on HbA1c, endogenous glucose production (EGP), and body weight versus each therapy alone. RESEARCH DESIGN AND METHODS: Forty-five patients with poorly controlled (HbA1c 7-11%) type 2 diabetes mellitus (T2DM) on metformin with or without sulfonylurea received a 9-h measurement of EGP with [3-3H]glucose infusion, after which they were randomized to receive 1) liraglutide 1.2 mg/day (LIRA), 2) canagliflozin 100 mg/day (CANA), or 3) liraglutide 1.2 mg plus canagliflozin 100 mg (CANA/LIRA) for 16 weeks. At 16 weeks, the EGP measurement was repeated. RESULTS: The mean decrease from baseline to 16 weeks in HbA1c was -1.67 ± 0.29% (P = 0.0001), -0.89 ± 0.24% (P = 0.002), and -1.44 ± 0.39% (P = 0.004) in patients receiving CANA/LIRA, CANA, and LIRA, respectively. The decrease in body weight was -6.0 ± 0.8 kg (P < 0.0001), -3.5 ± 0.5 kg (P < 0.0001), and -1.9 ± 0.8 kg (P = 0.03), respectively. CANA monotherapy caused a 9% increase in basal rate of EGP (P < 0.05), which was accompanied by a 50% increase (P < 0.05) in plasma glucagon-to-insulin ratio. LIRA monotherapy reduced plasma glucagon concentration and inhibited EGP. In CANA/LIRA-treated patients, EGP increased by 15% (P < 0.05), even though the plasma insulin response was maintained at baseline and the CANA-induced rise in plasma glucagon concentration was blocked. CONCLUSIONS: These results demonstrate that liraglutide failed to block the increase in EGP caused by canagliflozin despite blocking the rise in plasma glucagon and preventing the decrease in plasma insulin concentration caused by canagliflozin. The failure of liraglutide to prevent the increase in EGP caused by canagliflozin explains the lack of additive effect of these two agents on HbA1c.

Evidence Against an Important Role of Plasma Insulin and Glucagon Concentrations in the Increase in EGP Caused by SGLT2 Inhibitors.

Sodium-glucose cotransport 2 inhibitors (SGLT2i) lower plasma glucose but stimulate endogenous glucose production (EGP). The current study examined the effect of dapagliflozin on EGP while clamping plasma glucose, insulin, and glucagon concentrations at their fasting level. Thirty-eight patients with type 2 diabetes received an 8-h measurement of EGP ([3-3H]-glucose) on three occasions. After a 3-h tracer equilibration, subjects received 1) dapagliflozin 10 mg (n = 26) or placebo (n = 12); 2) repeat EGP measurement with the plasma glucose concentration clamped at the fasting level; and 3) repeat EGP measurement with inhibition of insulin and glucagon secretion with somatostatin infusion and replacement of basal plasma insulin and glucagon concentrations. In study 1, the change in EGP (baseline to last hour of EGP measurement) in subjects receiving dapagliflozin was 22% greater (+0.66 ± 0.11 mg/kg/min, P < 0.05) than in subjects receiving placebo, and it was associated with a significant increase in plasma glucagon and a decrease in the plasma insulin concentration compared with placebo. Under glucose clamp conditions (study 2), the change in plasma insulin and glucagon concentrations was comparable in subjects receiving dapagliflozin and placebo, yet the difference in EGP between dapagliflozin and placebo persisted (+0.71 ± 0.13 mg/kg/min, P < 0.01). Under pancreatic clamp conditions (study 3), dapagliflozin produced an initial large decrease in EGP (8% below placebo), followed by a progressive increase in EGP that was 10.6% greater than placebo during the last hour. Collectively, these results indicate that 1) the changes in plasma insulin and glucagon concentration after SGLT2i administration are secondary to the decrease in plasma glucose concentration, and 2) the dapagliflozin-induced increase in EGP cannot be explained by the increase in plasma glucagon or decrease in plasma insulin or glucose concentrations.

The impact of bariatric surgery on the resolution of obstructive sleep apnoea.

OBJECTIVE: Obesity is associated with a high incidence of obstructive sleep apnoea (OSA). Bariatric surgery is postulated to lead to OSA resolution, but there is inconclusive evidence on its efficacy. We used objective measurements to determine the rate of resolution or improvement of OSA in patients who had bariatric procedures in our unit. RESULTS: Data was analysed on all patients with OSA who underwent bariatric procedures [laparoscopic Roux-en-Y gastric bypass (LRYGB) and sleeve gastrectomy (LSG)] between June 2012 and September 2016 in our unit. 47 patients (26.7%) were diagnosed with OSA. Mean age was 48.5 years. 63.8% were female. 43 required nocturnal continuous positive airway pressure (CPAP) support. Procedures were LRYGB (n = 26) and LSG (n = 21). Mean excess weight loss was 56.1%. Mean start apnoea-hypopnoea index (AHI) on CPAP was 6.4 events/hr and end AHI was 1.4 events/h. 14 patients (32.6%) had complete OSA resolution and 12 (27.9%) showed improvement in pressure support requirements. We demonstrated that 55.3% of patients had resolution or improvement in OSA following bariatric surgery. However, there was a high rate of non-attendance of follow-up appointments. Future efforts will involve analysis of the reasons for this to ensure more robust monitoring.

Medication adherence and its associated factors among diabetic patients at Zewditu Memorial Hospital, Addis Ababa, Ethiopia.

OBJECTIVE: Diabetes is a global problem with devastating human, social and economic impact. Anti-diabetic medications play a major role in the glycemic control of patients with diabetes. However, inadequate adherence compromises safety and treatment effectiveness, leading to increased mortality and morbidity. The aim of this study was to assess adherence to anti-diabetic medications and associated factors among patient with diabetes mellitus receiving care at Zewditu Memorial Hospital. RESULTS: Among the total of 146 diabetic patients (mean age 46.5 ± 14.7), the level of adherence to anti diabetic medication was 54.8% (80) whilst 45.2% (66) of the participants were non adherent. Multiple logistic regression showed that knowledge of medication (AOR = 4.905, 95% CI 1.64-14.62, medication availability (AOR = 0.175, 95% CI 0.031-0.987) and education level (AOR = 13.65, 95% CI 1.45-128.456) were reasons for non-adherence.