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International Journal of Surgery... Jun 2024Bone and joint infections (BJI) are a significant complication after arthroplasty and fracture fixation, particularly challenging in patients with type 2 diabetes...
BACKGROUND
Bone and joint infections (BJI) are a significant complication after arthroplasty and fracture fixation, particularly challenging in patients with type 2 diabetes mellitus (T2DM) and obesity. Semaglutide, a glucagon-like peptide-1 receptor agonist (GLP-1RA), have shown efficacy in managing T2DM and obesity. However, its impact on BJI risk and neutrophil function remains unclear. To investigate whether preoperative semaglutide treatment (1) reduces the risk of BJI in diabetic and obese mice undergoing intra-articular implants, and (2) outperforms insulin in restoring neutrophil function to mitigate implant-related infection.
METHODS
A C57BL/6 mouse model of T2DM/obesity was induced using a high-fat diet (HFD) for 12 weeks. Mice received preoperative insulin or semaglutide therapy for 1-28 days. BJI risk was assessed using an intraarticular-implant model challenged with S. aureus or E. coli. Neutrophil function was evaluated through bactericidal activity, superoxide production, and migration ability.
RESULTS
Semaglutide treatment led to a significant and sustained reduction in body weight and improved glucose tolerance in HFD mice. Both insulin and semaglutide therapies significantly reduced BJI risk, with semaglutide showing a more pronounced effect over time. Semaglutide therapy also enhanced neutrophil bactericidal activity, superoxide production, and migration ability compared to insulin therapy.
CONCLUSIONS
Preoperative semaglutide treatment effectively reduces BJI risk and improves neutrophil function in diabetic and obese mouse models. These findings suggest that semaglutide may be a promising pharmacological intervention to mitigate infection risk in orthopedic patients with T2DM or obesity.
PubMed: 38935106
DOI: 10.1097/JS9.0000000000001896 -
Endocrinology Jun 2024Thyroid hormone (TH) plays a crucial role in regulating the functions of both bone and adipose tissue. Given that TH exerts its cholesterol-lowering effects in hepatic...
Thyroid hormone (TH) plays a crucial role in regulating the functions of both bone and adipose tissue. Given that TH exerts its cholesterol-lowering effects in hepatic tissue through the TH receptor-β (TRβ), we hypothesized that TRβ agonist therapy using MGL3196 (MGL) would be effective in treating increased adiposity and bone loss in response to a 12-week high-fat diet (HFD) in adult C57BL/6J mice. Transcriptional and serum profiling revealed that HFD-induced Leptin promoted weight gain in both males and females, but MGL only suppressed Leptin induction and weight gain in males. In vitro studies suggest estrogen suppresses MGL activity in adipocytes, indicating estrogen might interfere with MGL-TRβ function. Compared to systemic adiposity, HFD reduced bone mass in male but not female mice. Paradoxically, MGL treatment reversed macroscopic BMD loss in appendicular bones, but micro-CT revealed that MGL exacerbated HFD-induced trabecular bone loss, and bone strength. In studies on the mechanisms for HFD effects on bone, we found that HFD induced Rankl expression in male femurs that was blocked by MGL. By ex vivo assays, we found that RANKL indirectly represses osteoblast lineage allocation of osteoprogenitors by induction of inflammatory cytokines TNFα, Il-1β, and CCL2. Finally, we found that MGL functions in both systemic adiposity and bone by nongenomic TRβ signaling, as HFD-mediated phenotypes were not rescued in TRβ147F knockout mice with normal genomic but defective nongenomic TRβ signaling. Our findings demonstrate that the negative effects of HFD on body fat and bone phenotypes is impacted by MGL in a gender-specific manner.
PubMed: 38935021
DOI: 10.1210/endocr/bqae075 -
Edible bird's nest regulates glucose and lipid metabolic disorders the gut-liver axis in obese mice.Food & Function Jun 2024Edible bird's nest (EBN) is a traditional food known for its nourishing and functional properties and is found to be involved in anti-oxidation, anti-aging, and...
Edible bird's nest (EBN) is a traditional food known for its nourishing and functional properties and is found to be involved in anti-oxidation, anti-aging, and anti-influenza mechanisms, immune regulation, and improving cardiovascular diseases, among others. However, the potential of EBN to improve glycolipid metabolism disorders in high-fat-diet induced obesity and the underlying mechanisms remain unexplored. We examined the effects of EBN on glycolipid metabolism in obese mice fed a high-fat diet. Male C57BL/6J mice were fed a high-fat diet for 8 weeks to establish an obesity model. The obese mice were selected and divided into six groups: two model control groups (normal and high-fat diets) and four intervention groups [Neu5Ac and low-, medium-, and high-dose EBN], with 12 mice in each group. After 10 weeks of continuous gavage intervention, only mice in the high-dose EBN intervention group had lower body weight and total fat content, especially visceral fat. Meanwhile, intervention with three doses of EBN reduced serum FBG, TC, LDL, Ox-LDL, IL-1β, IL-6, and TNF-α levels and increased serum HDL levels and energy expenditure. Using the high dosage as a paradigm, EBN intervention increased the sialic acid content in LDL, decreased TMAO in the liver, and increased GLP-1 levels in sera. EBN increased the colonic abundances of , , and and reduced those of and . The changes in the microbial community contribute to increasing colonic bile acids, reducing lipopolysaccharide synthesis to protect the intestinal barrier, and lowering inflammation levels. Changes were also observed in colonic transcripts and metabolites and liver gene transcripts and metabolites, which were mainly enriched in pathways of glycolipid metabolism, immune function amelioration, inflammatory signal mitigation, circadian rhythm, bile acid metabolism and insulin resistance. Therefore, EBN may enhance the gut microbiota and intestinal immunity, relieve chronic inflammation levels in serum, improve antioxidant capacity and circadian rhythm in the liver, promote bile acid metabolism, and decrease lipid absorption and lipid synthesis the gut-liver axis. Consequently, this may reduce blood lipid and fat accumulation as well as improve islet function and reduce blood glucose levels.
PubMed: 38934780
DOI: 10.1039/d4fo00563e -
Journal of Food and Drug Analysis Jun 2024Citrus peels contain abundant polyphenols, particularly flavonoids, and have been shown to exert lipid accumulation decreasing ability. In this study, Citrus depressa...
Citrus peels contain abundant polyphenols, particularly flavonoids, and have been shown to exert lipid accumulation decreasing ability. In this study, Citrus depressa peel applied to oven drying and extracted with ethanol extract as CDEE to analyze its flavonoids compositions and investigated its effects on a high-fat diet (HFD)-induced obese mice model. CDEE contained several flavonoids such as hesperidin, sinesentin, nobiletin, tangeretin, 5-demethylnobiletin, and 5-demethyltangeretin. The mice fed an HFD, and administration of 2% CDEE to could decrease weight gain, abdominal fat weight, inguinal fat weight, and the adipocyte size, and CDEE also reduced serum total cholesterol (TCHO), triacylglycerol (TG) compared with mice fed only on HFD. CDEE hindered lipid accumulation through a decreased fatty acid synthase (FAS) protein expression via upregulation of the protein expression of AMP-activated protein kinase α (AMPKα). Moreover, CDEE modulated gut microbiota that altered by HFD through an increased abundance of Lactobacillus reuteri compared with the HFD group. The results demonstrated that CDEE helps decrease lipid accumulation through the AMPK pathway, which also indicates a prebiotic-like effect on gut microbiota.
Topics: Animals; Gastrointestinal Microbiome; Mice; Plant Extracts; Citrus; Male; Obesity; Lipid Metabolism; Prebiotics; Mice, Inbred C57BL; Mice, Obese; Diet, High-Fat; Humans; Triglycerides; Bacteria
PubMed: 38934690
DOI: 10.38212/2224-6614.3504 -
Archivio Italiano Di Urologia,... Jun 2024To present state of the art on the management of urinary stones from a panel of globally recognized urolithiasis experts who met during the Experts in Stone Disease... (Review)
Review
AIM
To present state of the art on the management of urinary stones from a panel of globally recognized urolithiasis experts who met during the Experts in Stone Disease Congress in Valencia in January 2024. Options of treatment: The surgical treatment modalities of renal and ureteral stones are well defined by the guidelines of international societies, although for some index cases more alternative options are possible. For 1.5 cm renal stones, both m-PCNL and RIRS have proven to be valid treatment alternatives with comparable stone-free rates. The m-PCNL has proven to be more cost effective and requires a shorter operative time, while the RIRS has demonstrated lower morbidity in terms of blood loss and shorter recovery times. SWL has proven to be less effective at least for lower calyceal stones but has the highest safety profile. For a 6mm obstructing stone of the pelviureteric junction (PUJ) stone, SWL should be the first choice for a stone less than 1 cm, due to less invasiveness and lower risk of complications although it has a lower stone free-rate. RIRS has advantages in certain conditions such as anticoagulant treatment, obesity, or body deformity. Technical issues of the surgical procedures for stone removal: In patients receiving antithrombotic therapy, SWL, PCN and open surgery are at elevated risk of hemorrhage or perinephric hematoma. URS, is associated with less morbidity in these cases. An individualized combined evaluation of risks of bleeding and thromboembolism should determine the perioperative thromboprophylactic strategy. Pre-interventional urine culture and antibiotic therapy are mandatory although UTI treatment is becoming more challenging due to increasing resistance to routinely applied antibiotics. The use of an intrarenal urine culture and stone culture is recommended to adapt antibiotic therapy in case of postoperative infectious complications. Measurements of temperature and pressure during RIRS are vital for ensuring patient safety and optimizing surgical outcomes although techniques of measurements and methods for data analysis are still to be refined. Ureteral stents were improved by the development of new biomaterials, new coatings, and new stent designs. Topics of current research are the development of drug eluting and bioresorbable stents. Complications of endoscopic treatment: PCNL is considered the most invasive surgical option. Fever and sepsis were observed in 11 and 0.5% and need for transfusion and embolization for bleeding in 7 and 0.4%. Major complications, as colonic, splenic, liver, gall bladder and bowel injuries are quite rare but are associated with significant morbidity. Ureteroscopy causes less complications, although some of them can be severe. They depend on high pressure in the urinary tract (sepsis or renal bleeding) or application of excessive force to the urinary tract (ureteral avulsion or stricture). Diagnostic work up: Genetic testing consents the diagnosis of monogenetic conditions causing stones. It should be carried out in children and in selected adults. In adults, monogenetic diseases can be diagnosed by systematic genetic testing in no more than 4%, when cystinuria, APRT deficiency, and xanthinuria are excluded. A reliable stone analysis by infrared spectroscopy or X-ray diffraction is mandatory and should be associated to examination of the stone under a stereomicroscope. The analysis of digital images of stones by deep convolutional neural networks in dry laboratory or during endoscopic examination could allow the classification of stones based on their color and texture. Scanning electron microscopy (SEM) in association with energy dispersive spectrometry (EDS) is another fundamental research tool for the study of kidney stones. The combination of metagenomic analysis using Next Generation Sequencing (NGS) techniques and the enhanced quantitative urine culture (EQUC) protocol can be used to evaluate the urobiome of renal stone formers. Twenty-four hour urine analysis has a place during patient evaluation together with repeated measurements of urinary pH with a digital pH meter. Urinary supersaturation is the most comprehensive physicochemical risk factor employed in urolithiasis research. Urinary macromolecules can act as both promoters or inhibitors of stone formation depending on the chemical composition of urine in which they are operating. At the moment, there are no clinical applications of macromolecules in stone management or prophylaxis. Patients should be evaluated for the association with systemic pathologies.
PROPHYLAXIS
Personalized medicine and public health interventions are complementary to prevent stone recurrence. Personalized medicine addresses a small part of stone patients with a high risk of recurrence and systemic complications requiring specific dietary and pharmacological treatment to prevent stone recurrence and complications of associated systemic diseases. The more numerous subjects who form one or a few stones during their entire lifespan should be treated by modifications of diet and lifestyle. Primary prevention by public health interventions is advisable to reduce prevalence of stones in the general population. Renal stone formers at "high-risk" for recurrence need early diagnosis to start specific treatment. Stone analysis allows the identification of most "high-risk" patients forming non-calcium stones: infection stones (struvite), uric acid and urates, cystine and other rare stones (dihydroxyadenine, xanthine). Patients at "high-risk" forming calcium stones require a more difficult diagnosis by clinical and laboratory evaluation. Particularly, patients with cystinuria and primary hyperoxaluria should be actively searched.
FUTURE RESEARCH
Application of Artificial Intelligence are promising for automated identification of ureteral stones on CT imaging, prediction of stone composition and 24-hour urinary risk factors by demographics and clinical parameters, assessment of stone composition by evaluation of endoscopic images and prediction of outcomes of stone treatments. The synergy between urologists, nephrologists, and scientists in basic kidney stone research will enhance the depth and breadth of investigations, leading to a more comprehensive understanding of kidney stone formation.
Topics: Humans; Urinary Calculi; Forecasting
PubMed: 38934520
DOI: 10.4081/aiua.2024.12703 -
Journal of the International Society of... Dec 2024The International Society of Sports Nutrition (ISSN) provides an objective and critical review of the use of a ketogenic diet in healthy exercising adults, with a focus... (Review)
Review
POSITION STATEMENT
The International Society of Sports Nutrition (ISSN) provides an objective and critical review of the use of a ketogenic diet in healthy exercising adults, with a focus on exercise performance and body composition. However, this review does not address the use of exogenous ketone supplements. The following points summarize the position of the ISSN.
UNLABELLED
1. A ketogenic diet induces a state of nutritional ketosis, which is generally defined as serum ketone levels above 0.5 mM. While many factors can impact what amount of daily carbohydrate intake will result in these levels, a broad guideline is a daily dietary carbohydrate intake of less than 50 grams per day.
UNLABELLED
2. Nutritional ketosis achieved through carbohydrate restriction and a high dietary fat intake is not intrinsically harmful and should not be confused with ketoacidosis, a life-threatening condition most commonly seen in clinical populations and metabolic dysregulation.
UNLABELLED
3. A ketogenic diet has largely neutral or detrimental effects on athletic performance compared to a diet higher in carbohydrates and lower in fat, despite achieving significantly elevated levels of fat oxidation during exercise (~1.5 g/min).
UNLABELLED
4. The endurance effects of a ketogenic diet may be influenced by both training status and duration of the dietary intervention, but further research is necessary to elucidate these possibilities. All studies involving elite athletes showed a performance decrement from a ketogenic diet, all lasting six weeks or less. Of the two studies lasting more than six weeks, only one reported a statistically significant benefit of a ketogenic diet.
UNLABELLED
5. A ketogenic diet tends to have similar effects on maximal strength or strength gains from a resistance training program compared to a diet higher in carbohydrates. However, a minority of studies show superior effects of non-ketogenic comparators.
UNLABELLED
6. When compared to a diet higher in carbohydrates and lower in fat, a ketogenic diet may cause greater losses in body weight, fat mass, and fat-free mass, but may also heighten losses of lean tissue. However, this is likely due to differences in calorie and protein intake, as well as shifts in fluid balance.
UNLABELLED
7. There is insufficient evidence to determine if a ketogenic diet affects males and females differently. However, there is a strong mechanistic basis for sex differences to exist in response to a ketogenic diet.
Topics: Diet, Ketogenic; Humans; Athletic Performance; Sports Nutritional Physiological Phenomena; Body Composition; Ketosis; Sports Nutritional Sciences; Dietary Carbohydrates; Exercise; Physical Endurance
PubMed: 38934469
DOI: 10.1080/15502783.2024.2368167 -
Journal of Pediatric Gastroenterology... Jun 2024Diacylglycerol acyltransferase (DGAT) catalyzes the final step in triglyceride synthesis. DGAT1 is expressed in human enterocytes and is essential for fat absorption....
OBJECTIVES
Diacylglycerol acyltransferase (DGAT) catalyzes the final step in triglyceride synthesis. DGAT1 is expressed in human enterocytes and is essential for fat absorption. Homozygous DGAT1 deficiency often presents with severe diarrhea and protein-losing enteropathy (PLE) in the 1st weeks of life. Because severe restriction of fat intake controls diarrhea and decreases PLE, total parenteral nutrition (TPN) was the initial standard therapy in infants and children. We present tertiary center experience managing infants and children with DGAT1 deficiency resulting in the development of a nutritional approach that minimizes the use of TPN.
METHODS
From 2014 to 2020, 12 infants with DGAT1 deficiency were treated. Stool output, growth, and development, as well as essential fatty acid status, were monitored. This retrospective experience formed the basis for treatment recommendations, which include an ultralow fat formula with intermittent peripheral intravenous lipid infusions during the 1st year of life.
RESULTS
All patients with prolonged intestinal fat exposure had PLE, which resolved when treated with the nutrition protocol. Essential fatty acid status as measured by triene:tetraene ratios normalized in all treated patients. Over time, early genetic diagnosis and prompt initiation of an ultralow fat diet with peripheral intravenous lipid infusions replaced the need for TPN.
CONCLUSIONS
Children with DGAT1 deficiency respond to dietary restriction of lipids. Management with a novel nutritional approach provides effective treatment for infants with DGAT1 deficiency, treats diarrhea and PLE, promotes growth and development, avoids TPN dependency, and decreases the potential for essential fatty acid deficiency.
PubMed: 38934410
DOI: 10.1002/jpn3.12241 -
Obesity (Silver Spring, Md.) Jul 2024Higher intake of ultraprocessed foods (UPFs) is associated with obesity. We examined whether replacing UPFs (NOVA 4) with minimally processed foods and culinary... (Randomized Controlled Trial)
Randomized Controlled Trial
OBJECTIVE
Higher intake of ultraprocessed foods (UPFs) is associated with obesity. We examined whether replacing UPFs (NOVA 4) with minimally processed foods and culinary ingredients (NOVA 1 + 2) was associated with differential weight change in this secondary prospective analysis of the Preventing Overweight Using Novel Dietary Strategies (POUNDS) Lost trial.
METHODS
We estimated percent energy intake (%kcal) from the four NOVA groups using 24-h dietary recalls in a subset of 356 participants. Multivariable-adjusted substitution models examined whether replacing %kcal from UPFs with NOVA 1 + 2 was associated with greater weight, body fat percentage, trunk fat, and waist circumference reduction at 6 months; changes in parameters were compared among NOVA 1 + 2 tertiles (T).
RESULTS
Participants were on average 52.3 years of age, 85% White, 55% female, and 58.2% nonsmoking, with a mean BMI of 32.7 kg/m. Replacing 10%kcal of UPFs with NOVA 1 + 2 was associated with greater 6-month weight (ß = 0.51, 95% CI: -0.93 to -0.09, p = 0.02), body fat percentage (ß = 2.7, 95% CI: -5.10 to -0.43, p = 0.02), and trunk fat reduction (ß = 3.9, 95% CI: -7.01 to -0.70, p = 0.02), but not waist circumference reduction. Participants in T3 (-8.33 kg) versus T1 (-5.32 kg) of NOVA 1 + 2 had greater weight loss (p < 0.001).
CONCLUSIONS
Isocaloric substitution of UPFs with NOVA 1 + 2 was associated with marginally greater weight loss under energy restriction. These modest findings support more research exploring the mechanisms linking UPFs with body weight regulation beyond energy intake.
Topics: Humans; Female; Male; Middle Aged; Weight Loss; Energy Intake; Obesity; Body Mass Index; Prospective Studies; Waist Circumference; Adult; Food Handling; Diet, Reducing; Fast Foods; Overweight
PubMed: 38932724
DOI: 10.1002/oby.24044 -
The American Journal of Case Reports Jun 2024BACKGROUND When people in their 60s experiences abdominal pain, vomiting, and unexplained weight loss without a history of abdominal surgery, the usual diagnosis is...
BACKGROUND When people in their 60s experiences abdominal pain, vomiting, and unexplained weight loss without a history of abdominal surgery, the usual diagnosis is obstruction caused by a neoplastic mass. Nevertheless, in exceptionally rare cases, these symptoms arise from complications linked to a visceral artery aneurysm. CASE REPORT We present a case of a 60-year-old man with immunodeficiency and Sneddon-Wilkinson disease (a rare subcorneal pustular dermatosis), who developed a pancreaticoduodenal aneurysm of uncertain origin, associated with pancreatic mass, retroperitoneal hematoma, and duodenal obstruction. The treatment approach included transcatheter arterial coil embolization with supportive measures such as parenteral nutrition, a nasogastric tube, octreotide administration, and antiemetics. Despite these interventions, persistence gastrointestinal symptoms prompted an endoscopic ultrasound fine-needle aspiration to rule out malignancy. The biopsy confirmed localized fibro-inflammation. Although he was initially considered for a gastro-jejunal bypass, conservative management effectively improved the pancreatic lesion and duodenal obstruction, leading to discontinuation of parenteral nutrition. The patient was able to resume a regular diet 4 weeks after embolization. CONCLUSIONS Pancreaticoduodenal artery aneurysm is a rare visceral aneurysm with multiple etiologies and potentially fatal consequences. We report an unusual case of a pancreaticoduodenal artery aneurysm associated with pancreatic mass and duodenal obstruction. This diagnosis warrants consideration when an immunodeficient patient presents symptoms of abdominal pain and vomiting. Early endovascular embolization, combined with conservative approaches, effectively alleviated the symptoms in our patient.
Topics: Humans; Male; Middle Aged; Aneurysm, False; Pancreas; Duodenal Obstruction; Duodenum; Embolization, Therapeutic
PubMed: 38932438
DOI: 10.12659/AJCR.943879 -
Pharmaceuticals (Basel, Switzerland) Jun 2024Obesity and its associated hepatic steatosis have become a global concern, posing numerous health hazards. Photodynamic therapy (PDT) is a unique approach that promotes...
Obesity and its associated hepatic steatosis have become a global concern, posing numerous health hazards. Photodynamic therapy (PDT) is a unique approach that promotes anti-obesity by releasing intracellular fat. Chlorin e6 (Ce6)-PDT was tested for its anti-obesity properties in male ovariectomized (OVX) beagle dogs, as well as male C57BL/6 and Balb/c mice. The 12 OVX beagles were randomly assigned to one of four groups: high-fat diet (HFD) only, Ce6 only, Ce6 + 10 min of light-emitting diode light (LED) treatment, and Ce6 + 15 min of light treatment. We assessed several parameters, such as body weight, adipose tissue morphology, serum biochemistry, and body fat content analysis by computed tomography (CT) scan in HFD-fed beagle dogs. At the end of the study period, dogs that were treated for 35 days with Ce6 and exposed to LED irradiation (660 nm) either for 10 min (Ce6 + 10 min of light) or for 15 min (Ce6 + 15 min of light) had decreased body weight, including visceral and subcutaneous fats, lower aspartate transaminase (AST)/alanine transaminase (ALT) ratios, and a reduction in the area of individual adipocytes with a concomitant increase in the number of adipocytes. Furthermore, C57BL/6 male mice following an HFD diet were effectively treated by Ce6-PDT treatment through a reduction in weight gain and fat accumulation. Meanwhile, Ce6-PDT attenuated hepatocyte steatosis by decreasing the epididymal adipose tissue and balloon degeneration in hepatocytes in HFD-fed Balb/c mice. Taken together, our results support the idea that Ce6-PDT is a promising therapeutic strategy for the recovery of obesity and obesity-related hepatic steatosis.
PubMed: 38931396
DOI: 10.3390/ph17060729