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Amputations related to diabetic foot ulcers (DFU) are associated with high morbidity and mortality rates. Glycaemic control and close follow-up protocols are essential to prevent such ulcers. Coronavirus disease (COVID) related restrictions and regulations might have a negative impact on patients who are with DFU or candidates for DFU. We retrospectively analysed 126 cases that had DFU underwent amputation surgery. Comparative analyses were done between cases that were admitted before COVID restrictions (Group A) and cases admitted after COVID restrictions (Group B). Two groups were homogenic demographically. There was no significant difference between groups in terms of mortality (p = 0.239) and amputation rates (p = 0.461). The number of emergent cases in the pandemic period doubled the number in pre-pandemic period even though this finding was not statistically significant (p = 0.112). Fastly adapted consulting practice and follow-up protocols to compensate for the problems created by COVID-related regulations seem to be effective in terms of mortality and amputation rates., (© 2023 The Authors. International Wound Journal published by Medicalhelplines.com Inc and John Wiley & Sons Ltd.)

With the increase in the diabetic foot patients in recent decades, the caregivers of diabetic foot patients increase too. Most of these caregivers are informal caregivers. However, the studies examining the burden of the caregivers and affecting factors are limited. This study was conducted to determine the burden of the caregivers of diabetic foot patients and affecting factors. This cross-sectional study was conducted between the January and October 2020 in a diabetic foot council of a university hospital. Zarit Caregiver Burden Scale and a participant identification form were used for data collection. Most of the caregivers were female (75.2%) and the mean age was 51.27 ± 11.48 years. The burden of the caregivers was at moderate level in the current study. Factors affecting the caregivers' burden were caregivers' age, patients' family structure, caregivers' education level, caregivers' income level, hours per week spending for the care of the patients, and lack of choice., Competing Interests: Declaration of Conflicting InterestsThe authors declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Introduction: Diabetic foot is a consequential and dangerous complication of diabetes, contributing to decreased quality of life, escalated hospitalizations, and increased mortality rates. Using an experimental model of diabetes, this study aims to investigate the effect of Lavandula stoechas on wound healing., Methods: A total of 35 albino Wistar rats, 250-350 grams in weight, were used. The rats were divided into five groups, seven rats in each group. Of these, 21 rats were induced with 50 mg/kg streptozotocin (STZ) to mimic the diabetic condition. Additionally, 14 rats remained non-diabetic and served as the control group. The diabetic rats were further divided into three subgroups. The non-diabetic group was split into two subgroups based on the dressing materials used (allicin, physiological serum, and control). Wound dimensions were assessed on Days 0, 7, 14, and 21. Biopsies were taken from the wound sites at the same time., Results: There were significant differences between groups on Days 7, 14, and 21. The percentage of healing was highest in the Lavandula Stoechas group on Days 7, 14, and 21. Microscopic examination of the biopsies supported accelerated wound healing on Days 7 and 14. Reduced mononuclear cell density and increased hair follicle and adipose tissue development were observed in the DM (diabetes mellitus)-Lavandula Stoechas group on Day 7. On Day 14, the DM-Lavandula Stoechas group increased collagen levels and hair follicles. Similarly, the non-DM-Lavandula Stoechas group showed reduced bullae, dermal edema, and intraepithelial edema on Day 7. This was followed by increased fibroblast levels on Day 14., Conclusions: In conclusion, this study provides compelling evidence for the potential of Lavandula stoechas extract in the enhancement of diabetic wound healing. The multiple interactions revealed here highlight the need for further investigation into the underlying mechanisms. A cost-effective use of Lavandula stoechas opens up promising prospects in managing diabetic foot healing. This warrants additional research and clinical translation., Competing Interests: The authors have declared that no competing interests exist., (Copyright © 2023, Demir et al.)

The purpose of this study is to evaluate the foot care self-efficacy of diabetic foot patients and the effect of an educational intervention for improving it. This study was of a semi-experimental design and was conducted between January and December 2019 in a diabetic foot council of a university hospital. After power analysis to determine sample size, 33 participants meeting the inclusion criteria were included in the study. A Patient Identification Form and Diabetic Foot Care Self-Efficacy Scale (DFCSES) were used to collect data. Of the patients, 51.5% were male and the mean age was 54.91 ± 16.61 years. The mean score of DFCSES was 50.18 ± 20.88 before education and 72.67 ± 20.74 after education. The educational intervention has large effects on self-efficacy ( d = 1.233), perceived knowledge level on diabetic foot ( d = 1.102), perceived health status ( d = 0.859), and perceived quality of life ( d = 0.807). Educational intervention was found to be an effective way to improve foot care self-efficacy, perceived knowledge level on diabetic foot, perceived health status, and perceived quality of life.

This is an open, prospective, comparative parallel-arm medical device clinical study of Dermalix (Dx) in diabetic foot wounds. Dx is a 3-dimensional collagen-laminin porous-structured dermal matrix prepared and additionally impregnated with resveratrol-loaded hyaluronic acid and dipalmitoylphosphatidylcholine-based microparticles. The aim was to evaluate the efficacy and safety of Dx, an investigational medical device, in Wagner 1 and 2 wounds in comparison to a standard wound care (SWC) that consists of irrigation and cleaning with sterile saline solution. Forty-eight patients were randomized to receive either SWC or SWC + Dx. A 4-week treatment period was followed by a 2-month follow-up without treatment. The wound area measurement, total collagen, vascular epidermal growth factor, tumor necrosis factor, interleukin 1, caspase 3, glutathione, reduced/oxidized glutathione, and lipid peroxidation levels were evaluated. At the end of 4 weeks, the percentage closures of wounds were determined as 57.82% for Dx, and 26.63% for SWC groups. Dx had a significant effect on tumor necrosis factor, caspase 3, and reduced/oxidized glutathione levels. Dx provided 2 times faster wound healing and decreased oxidative stress. Application of Dx in the first phase of wound would help the wound area heal faster with a safe profile.

Objective: Paget disease of bone (PDB) is a metabolic bone disease that has been rarely reported in the Eastern countries. This study aimed to evaluate the clinical and demographic characteristics of patients with PDB followed up at endocrinology clinics in Turkey., Methods: An invitation was sent to tertiary endocrinology clinics to complete a survey on the demographic, clinical, radiological, and laboratory parameters, as well as treatment modalities of patients with PDB. This study enrolled clinically and radiologically proven 185 patients with PDB from 18 endocrinology centers based in 10 cities of Turkey., Results: This cohort of PDB had female preponderance (women/men: 105/80) with a mean age, during diagnosis, of 57±10 years. Most of the patients (59.6%) were symptomatic at diagnosis. Bone pain and headache were the predominant clinical symptoms. Polyostotic disease was observed in 67.5% (n=125) of patients. Frequently affected bones were skull (41.6%), pelvis (53.5%), spine (41%), and femur (25.4%). Moreover, 17 patients with skull involvement had hearing loss. Mean serum alkaline phosphatase (ALP) level (552±652 IU/L; range: 280-5762 IU/L) was over the normal reference cutoff with normal serum calcium levels. Intravenous bisphosphonates (zoledronic acid, 5 mg; pamidronate, 60-90 mg) were the most used drugs (75%) for the treatment of PDB. Most of the patients (87.1%) treated with intravenous bisphosphonates responded well, with a decrease in serum ALP level (117±114 IU/L) in the 12th month of therapy. Furthermore, 16 patients relapsed after the second year of therapy; 3 patients did not respond to the initial intravenous bisphosphonate treatment., Conclusion: The patients with PDB followed up by endocrinology clinics of Turkey exhibited polyostotic disease with classical clinical, radiological, and biochemical features and women's predominance with good response to intravenous bisphosphonate therapy.

Diabetes mellitus (DM) is a chronic disease that has become a global health problem. As the population of people with diabetes is growing worldwide, the prevalence of complications associated with DM, such as diabetic foot, also increases. Neuropathy and high plantar pressure are the two most frequent causes of foot ulceration. Since diabetic wounds tend to heal slowly, it is crucial to prevent diabetic foot ulcers before they occur. In this study, the efficacy of a sock developed for diabetes in the previous research of the authors was investigated in a clinical study with the participation of patients with diabetes over a 6-month period. At the end of the study, it was observed that none of the participants had experienced any new ulcers, bacterial or fungal infections, or callus formation during this research. Moreover, a slight decrease in pressure was observed for the first, second, and third metatarsal bones when the socks were worn on day 1. On the other hand, pressure reduction was identified for the fourth and fifth metatarsal bones in all following measurements. However, analyses revealed that duration of usage did not have a statistically significant effect on overall plantar pressure. It was also found that pressure on the fourth and fifth metatarsal bones significantly decreased. Assessment of wearing comfort revealed the satisfaction of the patients, as well. Based on the promising outcomes of this clinical evaluation, these socks developed for people with diabetes can be strongly expected to help avoid diabetic foot ulcers.

The purpose of this study was to evaluate the validity and reliability of the Turkish version of the Diabetic Foot Scale-Short Form (DFS-SF). The study was cross-sectional and conducted between January and October 2019 in a diabetic foot council of a university hospital. A total of 194 diabetic foot patients participated in the study. A Patient Identification Form and DFS-SF were used for data collection. Forward and backward translations were used in language validity. Expert opinions were obtained to determine the Content Validity Index. To determine construct validity, exploratory factor analysis and confirmatory factor analysis were used. Cronbach's α internal consistency coefficient, item-scale correlation, and test-retest reliability were used to evaluate reliability. It was found that Content Validity Index was 0.97 (0.86-1.00), the factor loading of scale varied from 0.378 to 0.982, Cronbach's α value varied from 0.81 to 0.94, and item-total correlations were between 0.30 and 0.75. The Turkish version of the DFS-SF was found valid and reliable to measure the quality of life of diabetic foot patients.

Background/aim: High triglyceride (TG) levels are associated with increases in atherosclerotic cardiovascular disease (CVD), hepatic steatosis, and pancreatitis. Acute pancreatitis is a condition with high mortality. Therapeutic plasma exchange (TPE) in the treatment of hypertriglyceridemic pancreatitis (HTGP) is a rapid and effective treatment modality. In this study, the results of TPE were evaluated and the frequency of lipoprotein lipase (LPL) mutation in these patients was determined., Materials and Methods: TPE was performed in 31 patients with HTGP at the Adult Therapeutic Apheresis Center., Results: A TG level under 500 mg/dL was achieved by applying apheresis at a median of 2 times (IQR 2–2, min 1, max 6) in the 31 cases. LPL mutation was detected in 8 (25.8%) of the 31 hypertriglyceridemia cases. When TG levels before and after TPE were evaluated, the mean TG level before TPE was significantly higher (3132 ± 1472 mg/dL) than the mean TG level afterwards (948 ± 465 mg/dL, P < 0.001). This result represented a decrease of 69.7% TG after TPE., Conclusion: TPE is a safe, fast, and effective treatment modality in experienced centers., (This work is licensed under a Creative Commons Attribution 4.0 International License.)

Background/aim: Clinicians often neglect fungal infections and do not routinely investigate deep tissue from the wound for fungal culture and sensitivity due to insufficient information in the literature. In this study, we aimed to evaluate fungal etiology of invasive fungal diabetic foot which is rarely reported in the literature., Materials and Methods: The patients who were unresponsive to antibiotic therapy and those with positive fungal in bone or deep tissue culture were enrolled in the study. Detailed hospital records were retrieved for demographics and clinical features., Results: A total of 13 patients who were diagnosed with invasive fungal diabetic foot (ten females, three males, mean age 59.8 ± 9 years) were included. All of the patients had type-2 diabetes mellitus. Eleven (84.6%) patients had mixed infection. The most common cause of fungal infections of diabetic foot ulcers was the Candida species. Ten (76.9%) patients underwent amputation, two (15.4%) patients refused amputation, and one patient died before surgery., Conclusion: Invasive fungal infections may also be a causative pathogen in deep tissue infections. Therefore, fungal pathogens should be considered in patients unresponsive to long-term antibiotic therapy. Early detection of fungal infections in high-risk individuals is critical for the prevention of severe consequences such as foot amputation.

Maturity onset diabetes is a genetic form of diabetes mellitus characterized by an early age at onset and several etiologic genes for this form of diabetes have been identified in many patients. Maturity onset diabetes type 2 [MODY2 (#125851)] caused by mutations in the glucokinase gene (GCK). Although its prevalence is not clear, it is estimated that 1%-2% of patients with diabetes have the monogenic form. The aim of this study was to evaluate the molecular spectrum of GCK gene mutations in 177 Turkish MODY type 2 patients. Mutations in the GCK gene were identified in 79 out of 177. All mutant alleles were identified, including 45 different GCK mutations, 20 of which were novel., (Copyright © 2017. Published by Elsevier B.V.)

There is a variety of diagnostic and therapeutic algorithms for diabetic foot infections (DFIs). Some of them are too difficult to be applied in routine clinical approach. In the routine clinical approach, it is necessary to find new risk factors and end up with a quick and easy assessment of DFIs. In this study, we aimed to evaluate the independent risk factors for osteomyelitis, amputation and major amputation in patients with DFI using standard scoring procedures. We prospectively studied 379 patients with DFI. The variables were analysed using logistic analysis. A total of 126 cases (33·2%) underwent amputation. The odds ratios in the amputation model were 3·09 for osteomyelitis (P < 0·001), 4·90 for arterial stenosis (AS) (P < 0·001), 3·67 for the history of DFI (P = 0·001), 2·47 for ulcer duration >60 days (P = 0·001), 3·10 for ulcer depth > 15 mm (P < 0·001) and 10·28 for fungal DFI (P = 0·015). In this study, the unusual result of well-known literature was fungal DFI as an independent risk factor for amputation in patients with DFI., (© 2017 Medicalhelplines.com Inc and John Wiley & Sons Ltd.)

Background/aim: Intralesional recombinant epidermal growth factor (EGF) is a new treatment approach for diabetic foot ulcer, approved in 2006. EGF therapy is given as an adjunct to the standard treatment regimen of antibiotics, surgery, and hyperbaric oxygen. EGF accelerates the healing of diabetic foot ulcers and reduces healing time. This single-center study was conducted to evaluate the outcomes of intralesional EGF therapy in patients with diabetic foot ulcers.Materials and methods: We present the data of the follow-up patients treated in our clinics. Fifteen patients with diabetic foot ulcers or infections, who had been followed up and treated in our clinics, were included in this retrospective study. All patients were administered intralesional injections of 75 μg of EGF after treatment for infection on their diabetic foot ulcers, three times a week on alternate days. The patients were monitored with respect to treatment response and side effects of EGF.Results: Thirteen patients (86.7%) developed new granulation tissue, 10 patients (66.7%) had complete wound closure, and three patients (20%) showed partial wound closure. No serious side effects requiring discontinuation of EGF therapy were observed. A total of twenty-one bacterial agents were isolated in thirteen patients, and no bacterial growth was observed in the tissue cultures of two patients. Pseudomonas aeruginosa was the most common isolated infectious agent in the tissue cultures (n: 6, 28%). Conclusion: Intralesional injection of EGF on top of the standard treatment regimen appears to be a useful adjuvant therapy option in selected patients.

Objective: The aim of the present study was to determine gingival crevicular fluid (GCF) levels of monocyte chemotactic protein-1 (MCP-1), regulated on activation, normal T-cell expressed and secreted protein (RANTES) and macrophage migration inhibitory factor (MIF) in metabolic syndrome patients with gingivitis., Design: Twenty metabolic syndrome patients with gingivitis (MSG), 20 MetS patients with clinically healthy periodontium (MSH), 20 systemically healthy subjects with gingivitis and 20 subjects who were both systemically and periodontally healthy were included. Periodontal and systemical parameters were recorded. GCF MCP-1, RANTES and MIF levels were assayed by enzyme-linked immunosorbent assay method., Results: MSG and MSH groups had elevated blood pressure, triglyceride, waist circumference and fasting glucose values in comparison to gingivitis and healthy groups (P<0.0001). Clinical periodontal parameters were higher in MSG and gingivitis groups when compared to those of the MSH and healthy groups (P<0.0001). MCP-1 and RANTES levels (ng/mg total protein) of MSG group were higher than those of the MSH groups (P=0.005, P=0.0001, respectively). Also gingivitis group had higher MCP-1, RANTES and MIF levels compared to the healthy group (P=0.011, P=0.0001, P=0.011 respectively). The RANTES level of MSG group was significantly higher than those of the gingivitis group (P=0.01), but MCP-1 and MIF levels were similar in the MSG and gingivitis groups (P>0.05)., Conclusion: Elevated levels of GCF RANTES in MetS patients with gingivitis might associate with the presence of increased gingival inflammation by MetS. Low-grade systemic inflammation associated with MetS and adipose tissue-derived RANTES might lead to altered GCF RANTES levels in the presence of gingival inflammation., (Copyright © 2016. Published by Elsevier Ltd.)

Association of both intrinsic and extrinsic risk factors leading to accelerated skin ageing is reflected in excessive ROS production and ir/reversible mitochondrial injury and burnout, as abundantly demonstrated by accumulating research data. Due to the critical role of mitochondrial stress in the pathophysiology of skin ageing and disorders, maintained (primary care) and restored (secondary care) mitochondrial health, rejuvenation and homoeostasis are considered the most effective holistic approach to advance dermatological treatments based on systemic health–supportive and stimulating measures. Per evidence, an effective skin anti-ageing protection, wound healing and scarring quality – all strongly depend on the sustainable mitochondrial functionality and well-balanced homoeostasis. The latter can be objectively measured and, if necessary, restored in a systemic manner by pre- and rehabilitation algorithms tailored to individualised patient profiles. The entire spectrum of corresponding innovations in the area includes natural and systemic skin rejuvenation, aesthetic and reconstructive medicine, sustainable skin protection and targeted treatments of skin disorders. Contextually, mitochondria-centric dermatology is instrumental for advanced 3PM-guided approach which makes a good use of predictive multi-level diagnostics and targeted protection of skin against both — the health-to-disease transition and progression of relevant disorders. Cost-effective targeted protection and new treatment avenues focused on sustainable mitochondrial health and physiologic homoeostasis are proposed in the article including in-depth analysis of patient cases and exemplified 3PM-guided care with detailed mechanisms and corresponding expert recommendations presented. [ABSTRACT FROM AUTHOR]

Background and aims: Osseointegration (OI) surgery of the appendicular skeleton for repair in amputees is a treatment in which a metal implant is directly fixed to the residual bone and subsequently connected to a prosthetic limb via a transcutaneous connector through a small incision in the skin. Current treatment does not consider nutritional advice for patients undergoing the OI procedure. However, since the group of patients is very heterogeneous, the results may not be always satisfactory for patients and clinicians. Furthermore, in some individuals, incorrect nutrition and diet habits may lead to complications and rejection of the implant. Methods: We created an extensive narrative evaluation by conducting a methodical search. A comprehensive search was conducted across three major databases: PubMed, Embase, and Scopus. The search was carried out in October 2024 with no time limit specified. The approach involved using specific, pre-defined search terms, which were first applied in PubMed, followed by Embase and Scopus to ensure a broad and diverse range of articles was captured. The search process was refined by considering studies published in high-impact journals, as identified based on impact factors and subject relevance. To ensure consistency and rigor, the selection criteria were applied uniformly across all databases, and irrelevant or incomplete articles were excluded. Results: Based on the specific nature of the OI procedure, it is crucial to adapt patients' diets and nutrition after the process. To translate the findings from the reviewed literature into practical clinical guidance for osseointegration (OI) procedures, we developed dietary recommendations for both patients and clinicians, presented as proposed dietary plans and summarized in tables. These recommendations were informed by evidence from various studies, highlighting findings that were supported by randomized controlled trials (RCTs) as well as areas where the evidence remains inconclusive or unsupported by RCTs. Major vitamins and micro- and macroelements were distinguished and presented as guidelines for clinicians. Conclusions: OI is currently the most promising therapeutic options for amputees. To promote efficient tissue healing and provide energy for rehabilitation, it is recommended to follow a healthy, well-balanced diet that contains all the essential micronutrients, macronutrients, vitamins, and minerals. We also provide suggestions for future studies. [ABSTRACT FROM AUTHOR]

Purpose: This study examined the differences in pathogen survival between single and revision amputations in diabetic foot infections. Current research lacks data on the postoperative pathogen profiles, particularly in cases involving repeated surgeries, making this study essential for targeted infection management. Materials and Methods: The medical records of 168 diabetic foot ulcer patients treated at a single center, divided into single (n=113) and revision amputation groups (n=55) were analyzed retrospectively. Preoperative deep tissue samples and postoperative wound swab samples were collected to analyze the pathogens. The C-reactive protein (CRP) levels were measured as an inflammation marker. The pathogen diversity, frequency, and survival rate were compared. The 'survival rate' was defined as the frequency of postoperative persistence of pathogens relative to the preoperative detection frequency. Results: Revision amputation cases showed a higher diversity (p=0.0029) and persistence of pathogens, with methicillin-resistant Staphylococcus aureus and Pseudomonas aeruginosa, and most other detected pathogens displaying higher survival rates. The CRP levels generally decreased postoperatively, but the variability was more pronounced in the revision group, suggesting that CRP may not consistently correlate with infection control in complex cases. Conclusion: These findings revealed significant differences in the pathogen profiles between single and revision amputations, with revision cases facing more significant infection challenges because of the higher resistant pathogen persistence. [ABSTRACT FROM AUTHOR]

A biomarker is defined as a characteristic that is measured as an indicator of a normal biological or pathological process, a response to an exposure or intervention. Biomarkers with a diagnostic approach must identify not only the presence but also the absence of the disease with high precision, so having the biological source of the said marker is of vital importance to ensure precision and accuracy; the aim was to carry out a review of its diagnostic potential. The search strategy was carried out in three databases: PubMed, ScienceDirect, and Scopus. The keywords that were used were as follows: "gingival crevicular fluid", "Biomarker", and "Diagnosis", using the Boolean operator "AND". The filter was used at 10 years. Within the type of molecules most studied, the cytokine family was the most abundant with 25.42% of the studies, followed by metalloproteinases and proteins with 16.9% each one. Studies that included RNA‐type genetic material were less frequently found. As has been demonstrated, the use of GCF as a source of biomolecules for diagnostic use has been increasing, both for oral diseases, which reflects the local conditions of the disease; it also has the ability to reflect the development of distant diseases; and this is because GCF is a blood ultrafiltrate. [ABSTRACT FROM AUTHOR]

Wound healing involves a carefully regulated sequence of events, encompassing pro-inflammatory and anti-inflammatory stages, tissue regeneration, and remodeling. However, in individuals with diabetes, this process gets disrupted due to dysregulation caused by elevated glucose levels and pro-inflammatory cytokines in the bloodstream. Consequently, the pro-inflammatory stage is prolonged, while the anti-inflammatory phase is delayed, leading to impaired tissue regeneration and remodeling with extended healing time. Furthermore, the increased glucose levels in open wounds create an environment conducive to microbial growth and tissue sepsis, which can escalate to the point of limb amputation. Managing diabetic wounds requires meticulous care and monitoring due to the lack of widely available preventative and therapeutic measures. Existing clinical interventions have limitations, such as slow recovery rates, high costs, and inefficient drug delivery methods. Therefore, exploring alternative avenues to develop effective wound-healing treatments is essential. Nature offers a vast array of resources in the form of secondary metabolites, notably polyphenols, known for their antimicrobial, anti-inflammatory, antioxidant, glucose-regulating, and cell growth-promoting properties. Additionally, nanoparticles synthesized through environmentally friendly methods hold promise for wound healing applications in diabetic and non-diabetic conditions. This review provides a comprehensive discussion and summary of the potential wound-healing abilities of specific natural polyphenols and their nanoparticles. It explores the mechanisms of action underlying their efficacy and presents effective formulations for promoting wound-healing activity. [ABSTRACT FROM AUTHOR]

Aim: To provide further data from a population with different genetic background for the contrary views on the ensuing question of "whether iodine status influence the onset and course of thyroid cancer" by examining trends in thyroid cancer incidence and prevalence of main sub types of thyroid cancer in a population from formerly iodine deficient geographic area in Türkiye. Materials and Methods: Data were retrieved for 2,705 patients (2,161 female, 544 male) who were diagnosed with histopathologically confirmed thyroid cancer at Karadeniz Technical University Farabi Hospital, a university hospital serving a geographic region which remains an endemic goiter area and was formerly iodine-deficient, shortly after mandatory national salt iodization, between 2000 and 2018. Age, gender, subtype, tumor size, stage, and the changes and trends over the years were retrospectively evaluated. Results: Thyroid cancer rates had a trend of increase from 2000 to 2012 and then began to decline. In our region, papillary thyroid cancer (PTC) is more prevalent (93.5%). Among all thyroid cancers, the ratio of micro papillary thyroid cancer (mPTC) is 46.5%, follicular thyroid cancer (FTC) is only 3.5%. mPTC (tumor size =10 mm) (49.8%) and macroPTC (tumor size >10 mm) (50.2%) are approximately equal in proportion, and these ratios remained similar over the years covered in this analysis. Stage I PTC is 95.3%. M0 PTC is 98.9%. Conclusion: Data from this retrospective epidemiologic study indicates that the rate of PTC is notably high and thyroid cancer may have a more benign course in our endemic goiter region probably due to iodine supplementation that may affect late-stage thyroid carcinogenesis. [ABSTRACT FROM AUTHOR]

The prevalence of testicular dysfunction is increasing as it is a common diabetes mellites (DM) complication. The objective of this study is to explore the potential protective effect of sulbutiamine against testicular hypofunction associated with streptozotocin (STZ)‐induced DM in rats. Sulbutiamine was administered orally (60 mg/kg) to male Wistar rats for 8 weeks starting 72 h after a single injection of STZ (45 mg/kg, i.p.). Blood glucose level (BGL), serum testosterone level, sperm number, and motility were determined. Testicular tissue was examined histopathologically, and the Johnson score was evaluated. Levels of malondialdehyde (MDA), protein kinase C (PKC), nuclear factor erythroid‐derived 2‐like 2 (Nrf2), and proliferating cell nuclear antigen (PCNA) were measured. Apoptosis was evaluated by immunohistochemical determination of B‐cell lymphoma protein 2 (Bcl‐2), Bcl‐2 associated X‐protein (Bax), and caspase‐3. Sulbutiamine administration managed to reduce BGL and boost testicular function as manifested by increased testicular weight, testosterone level, sperm number, and motility compared to the STZ group. Additionally, histopathological examination revealed an improved histological picture and Johnson score of testicular tissue after sulbutiamine treatment. Sulbutiamine administration reduced testicular PKC, MDA, and PCNA levels and increased Nrf2 compared to the untreated group. Moreover, sulbutiamine treatment suppressed apoptosis triggered by STZ as evidenced by elevated Bcl‐2, decreased Bax and reduced caspase‐3. The present work revealed for the first time a promising protective role of sulbutiamine against STZ‐induced testicular dysfunction which may add to the clinical utility of sulbutiamine. The underlying mechanisms involve reducing BGL and PKC, activating Nrf2 and inhibiting apoptosis. [ABSTRACT FROM AUTHOR]

Maturity-onset diabetes of the young (MODY) is part of the heterogeneous group of monogenic diabetes (MD) characterized by the non-immune dysfunction of pancreatic β-cells. The diagnosis of MODY still remains a challenge for clinicians, with many cases being misdiagnosed as type 1 or type 2 diabetes mellitus (T1DM/T2DM), and over 80% of cases remaining undiagnosed. With the introduction of modern technologies, important progress has been made in deciphering the molecular mechanisms and heterogeneous etiology of MD, including MODY. The aim of our study was to identify genetic variants associated with MODY in a group of patients with early-onset diabetes/prediabetes in whom a form of MD was clinically suspected. Genetic testing, based on next-generation sequencing (NGS) technology, was carried out either in a targeted manner, using gene panels for monogenic diabetes, or by analyzing the entire exome (whole-exome sequencing). GKC-MODY 2 was the most frequently detected variant, but rare forms of KCNJ11-MODY 13, specifically, HNF4A-MODY 1, were also identified. We have emphasized the importance of genetic testing for early diagnosis, MODY subtype differentiation, and genetic counseling. We presented the genotype–phenotype correlations, especially related to the clinical evolution and personalized therapy, also emphasizing the particularities of each patient in the family context. [ABSTRACT FROM AUTHOR]

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Objective: Periodontitis is an inflammatory disease that involves an imbalance in the oral microbiota, activation of inflammatory and immune responses, and alveolar bone destruction. Macrophage migration inhibitory factor (MIF) is a versatile cytokine involved in several pathological reactions, including inflammatory processes and bone destruction, both of which are characteristics of periodontitis. While the roles of MIF in cancer and other immune diseases have been extensively characterized, its role in periodontitis remains inconclusive. Results: In this review, we describe a comprehensive analysis of the potential roles of MIF in periodontitis from the perspective of immune response and bone regulation at the cellular and molecular levels. Moreover, we discuss its potential reliability as a novel diagnostic and therapeutic target for periodontitis. Conclusion: This review can aid dental researchers and clinicians in understanding the current state of MIF‐related pathogenesis, diagnosis, and treatment of periodontitis. [ABSTRACT FROM AUTHOR]

Objective: The present study was designed to investigate the role of macrophage migration inhibitory factor (MIF) in the exacerbation of pregestational periodontal disease (PGPD). Background: Periodontitis (PT) is a severe stage of periodontal disease characterized by inflammation of the supporting tissues of the teeth, which usually worsens during pregnancy. MIF is a proinflammatory cytokine that is significantly elevated in periodontitis, both at the beginning and at the end of pregnancy. Although periodontitis usually presents with greater severity during pregnancy, the participation of MIF in the evolution of periodontitis has not been established. Methods: To analyze the relevance of MIF in the exacerbation of PGPD, we employed a model of PGPD in WT and Mif‐/‐ mice, both with a BALB/c genetic background. PT was induced with nylon suture ligatures placed supramarginally around the second upper right molar. For PGPD, PT was induced 2 weeks before mating. We evaluated histological changes and performed histometric analysis of the clinical attachment loss, relative expression of MMP‐2 and MMP‐13 by immunofluorescence, and relative expression of the cytokines mif, tnf‐α, ifn‐γ, and il‐17 by quantitative real‐time polymerase chain reaction (qRT‐PCR). Results: Our data revealed that periodontal tissue from PGPD WT mice produced a twofold increase in MIF compared with PT WT mice. Moreover, the evolution of periodontitis in Mif‐/‐ mice was less severe than in PGDP WT mice. Periodontal tissue from Mif‐/‐ mice with PGPD produced 80% less TNF‐α and no IFN‐γ, as well as 50% lower expression of matrix metalloproteinase (MMP)‐2 and 25% less MMP‐13 compared to WT PGDP mice. Conclusions: Our study suggests that MIF plays an important role in the exacerbation of periodontitis during pregnancy and that MIF is partially responsible for the inflammation associated with the severity of periodontitis during pregnancy. [ABSTRACT FROM AUTHOR]

The Serra da Estrela Natural Park (NPSE) in Portugal stands out as a well-preserved region abundant in medicinal plants, particularly known for their pharmaceutical applications in diabetes prevention and treatment. This comprehensive review explores these plants' botanical diversity, traditional uses, pharmacological applications, and chemical composition. The NPSE boast a rich diversity with 138 medicinal plants across 55 families identified as traditionally and pharmacologically used against diabetes globally. Notably, the Asteraceae and Lamiaceae families are prevalent in antidiabetic applications. In vitro studies have revealed their significant inhibition of carbohydrate-metabolizing enzymes, and certain plant co-products regulate genes involved in carbohydrate metabolism and insulin secretion. In vivo trials have demonstrated antidiabetic effects, including glycaemia regulation, insulin secretion, antioxidant activity, and lipid profile modulation. Medicinal plants in NPSE exhibit various activities beyond antidiabetic, such as antioxidant, anti-inflammatory, antibacterial, anti-cancer, and more. Chemical analyses have identified over fifty compounds like phenolic acids, flavonoids, terpenoids, and polysaccharides responsible for their efficacy against diabetes. These findings underscore the potential of NPSE medicinal plants as antidiabetic candidates, urging further research to develop effective plant-based antidiabetic drugs, beverages, and supplements. [ABSTRACT FROM AUTHOR]

The pathophysiology of sarcoidosis includes defective T cells and macrophages, which lead to the formation of granulomas. On the other hand, increased turnover of osteoclasts has been observed in Paget's disease, where osteoclasts are a member of the macrophage family. There may be a common intrinsic factor associated with the vitamin D receptor gene receptor that triggers the defective activation of macrophages in both disorders. More than half of patients with Paget's disease are asymptomatic; thus, the coexistence of the two disorders may go unnoticed. To the best of our knowledge, the coexistence of Paget's disease and pulmonary sarcoidosis in the same patient has not been previously reported. Whether bisphosphonate can be used for the treatment of osseos sarcoidosis is a subject for future research. Herein, we report a case of Paget's disease in an older patient with pulmonary sarcoidosis. [ABSTRACT FROM AUTHOR]

Lipodystrophies involve the loss of subcutaneous adipose tissue, resulting in severe metabolic issues such as insulin resistance and challenging diabetes management. This case series aims to assess bromocriptine treatment response in lipodystrophy patients, offering insights into its antidiabetic effects. This retrospective analysis focused on four female lipodystrophy patients with poor glycemic control who were undergoing bromocriptine treatment. Statistical analysis used nonparametric tests. Metabolic parameters were assessed before and 3 months post-bromocriptine treatment, revealing a modest reduction in median daily insulin dose and decreased hemoglobin A1c and fasting glucose levels. Body weight remained constant, while triglyceride levels increased. Dopamine receptor expression in pancreatic ß-cells and adipocytes suggests a direct impact on glucose homeostasis. While this case series hints at bromocriptine's positive influence on glycemic control and insulin requirements in lipodystrophy patients, larger studies are essential for establishing efficacy and safety. [ABSTRACT FROM AUTHOR]

MiRNAs are a large group of non-coding RNAs which participate in different cellular pathways like inflammation and oxidation through transcriptional, post-transcriptional, and epigenetic regulation. In the post-transcriptional regulation, miRNA interacts with the 3′-UTR of mRNAs and prevents their translation. This prevention or dysregulation can be a cause of pathological conditions like diabetic complications. A huge number of studies have revealed the association between miRNAs and diabetic complications, including diabetic nephropathy, cardiomyopathy, neuropathy, retinopathy, and delayed wound healing. To address this issue, recent studies have focused on the use of polyphenols as selective and safe drugs in the treatment of diabetes complications. In this article, we will review the involvement of miRNAs in diabetic complications' occurrence or development. Finally, we will review the latest findings on targeting miRNAs by polyphenols like curcumin, resveratrol, and quercetin for diabetic complications therapy. [ABSTRACT FROM AUTHOR]

Diabetes, particularly type 2 diabetes (T2D), is the main component of metabolic syndrome. It is highly prevalent and has drastically increased with sedentary lifestyles, notably behaviors linked to ease of access and minimal physical activity. Central to this condition is insulin, which plays a pivotal role in regulating glucose levels in the body by aiding glucose uptake and storage in cells, and what happens to diabetes? In diabetes, there is a disruption and malfunction in insulin regulation. Despite numerous efforts, effectively addressing diabetes remains a challenge. This article explores the potential of photoactivatable drugs in diabetes treatment, with a focus on light-activated insulin. We discuss its advantages and significant implications. This article is expected to enrich the existing literature substantially, offering a comprehensive analysis of potential strategies for improving diabetes management. With its minimal physical intrusion, light-activated insulin promises to improve patient comfort and treatment adherence. It offers precise regulation and localized impact, potentially mitigating the risks associated with conventional diabetes treatments. Additionally, light-activated insulin is capable of explicitly targeting RNA and epigenetic factors. This innovative approach may pave the way for more personalized and effective diabetes treatments, addressing not only the symptoms but also the underlying biological causes of the disease. The advancement of light-activated insulin could revolutionize diabetes management. This study represents a pioneering introduction to this novel modality for diabetes management. [ABSTRACT FROM AUTHOR]

Background: Diabetes mellitus (DM) is a category of metabolic conditions affecting about 5% of people worldwide. High mortality associated with DM is mostly due to its severe clinical complications, including diabetic nephropathy, retinopathy, neuropathy, and cardiomyopathy. Resveratrol (RSV) is a natural, biologically active polyphenol known to have various health-promoting effects in animal models and humans. Objective: In this review, we have reviewed the preventive and therapeutic role of RSV on diabetes complications with emphasis on its molecular mechanisms of action. Methods: To prepare this review, all the basic and clinical available literatures regarding this topic were gathered through electronic databases, including PubMed, Web of Science, Scopus, and Google Scholar. Therefore, we summarized previous studies that have evaluated the effects of RSV on diabetic complications and their mechanisms. Only English language studies published up to January 2023 were included in this review. Results: RSV improves glucose homeostasis, decreases insulin resistance, induces autophagy, regulates lipid metabolism, protects pancreatic β-cells, ameliorates metabolic disorders, and increases the GLUT4 expression. These effects induced by RSV are strongly associated with ability of this polyphenol agent to elevation expression/ activity of AMP-activated protein kinase and Sirtuin 1 in various organs of diabetic subjects, which leads to prevention and therapy of diabetic complications. In addition, antioxidant and anti-inflammatory properties of RSV were reported to be involved in its action in diabetic complications, such as retinopathy and nephropathy. Conclusion: RSV is a promising compound for improving diabetic complications. However, the exact antidiabetic mechanisms of RSV need to be further investigated. [ABSTRACT FROM AUTHOR]

Background: The aim of this study is to evaluate the immune regulation and tissue remodeling responses during experimental gingivitis (EG) and naturally occurring gingivitis (NG) to provide a comprehensive analysis of host responses. Gingival crevicular fluid (GCF) was obtained from 2 human studies conducted in university settings., Methods: The EG study enrolling 26 volunteers provided controls for the baseline (Day 0) from healthy disease-free participants, while Day 21 (the end of EG induction of the same group) was used to represent EG. Twenty-six NG participants age-matched with those of the EG group were recruited. GCF samples were analyzed for 39 mediators of inflammatory/immune responses and tissue remodeling using commercially available bead-based multiplex immunoassays. The differences in GI and mediator expression among groups were determined at a 95% confidence level (p ≤ 0.05) by a 2-way analysis of variance (ANOVA) with a post-hoc Tukey's test., Results: Our findings showed that EG had a greater gingival index than NG and was healthy (p < 0.01 of all comparisons). Furthermore, EG showed significantly higher levels of MPO (p < 0.001), CCL3 (p < 0.05), and IL-1B (p < 0.001) than NG. In contrast, NG had increased levels of MIF (p < 0.05), Fractalkine (p < 0.001), angiogenin (p < 0.05), C3a (p < 0.001), BMP-2 (p < 0.001), OPN (p < 0.05), RANKL (p < 0.001), and MMP-13 (p < 0.001) than EG., Conclusions: Consistent with the findings from chronic (NG) versus acute (EG) inflammatory lesions, these data reveal that NG displays greater immune regulation, angiogenesis, and bone remodeling compared to EG., (© 2024 American Academy of Periodontology.)

Wound healing is a multifaceted, complex process that factors like aging, metabolic diseases, and infections may influence. The potentiality of polyphenols, natural compounds, has shown anti-inflammatory and antimicrobial properties in promoting wound healing and their potential applications in wound management. The studies reviewed indicate that polyphenols have multiple mechanisms that promote wound healing. This involves enhancing antioxidant defenses, reducing oxidative stress, modulating inflammatory responses, improving healing times, reducing infection rates, and enhancing tissue regeneration in clinical trials and in vivo and in vitro studies. Polyphenols have been proven to be effective in managing hard-to-heal wounds, especially in diabetic and elderly populations. Polyphenols have shown significant benefits in promoting angiogenesis and stimulating collagen synthesis. Polyphenol treatment has been demonstrated to have therapeutic effects in wound healing and chronic wound management. Their ability to regulate key healing processes makes them suitable for new wound care products and treatments. Future research should enhance formulations and delivery methods to optimize polyphenols' bioavailability and therapeutic efficacy in wound management approaches., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Diabetes mellitus (DM) is a significant global health issue, associated with various microvascular and macrovascular complications that significantly impair patients' quality of life as well as healthspan and lifespan. Despite the availability of several anti-diabetic medications with different mechanisms of action, there remains no definite curative treatment. Hence, discovering new efficient complementary therapies is essential. Natural products have received significant attention due to their advantages in various pathological conditions. Resveratrol is a natural polyphenol that possesses antioxidant and anti-inflammatory properties, and its efficacy has been previously investigated in several diseases, including DM. Herein, we aimed to provide a holistic view of the signaling pathways and mechanisms of action through which resveratrol exerts its effects against DM and its complications., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Resveratrol (RSV) that possesses anti-oxidative, anti-inflammatory, and pro-angiogenic effects is an effective drug for diabetic wound (DW), while its pharmacological mechanism remains to be elucidated. In this study, we apply network pharmacology and experimental validation approach to reveal the potential mechanism of RSV against DW. We obtained potential targets for RSV and DW from the publicly available database. Using interaction networks and conducting GO and KEGG pathway enrichment analyses, we constructed target-pathway networks to explore the relationship between RSV and DW. To validate the pharmacological mechanism of RSV, we induced the DW model. Ninety overlapped targets between RSV and DW were obtained, and the hub genes of the PPI network included TNF, IL-6, CASP3, MAPK3, VEGFA, IL-1β, AKT1, and JUN. Based on target-pathway networks, the AGE-RAGE signalling pathway was involved in the RSV treatment of DW. Furthermore, in vivo experiments revealed that RSV significantly promoted wound healing in diabetic mice and attenuated the expression of pro-inflammatory cytokines in wound tissue. Meanwhile, RSV could inhibit the AGE-RAGE signalling pathway and thus reduce the activation of NF-κB. This study initially revealed the biological mechanism of RSV for treating DW through multi-target and multi-pathway. AGE-RAGE, FoxO, MAPK, PI3K-AKT and other signalling pathways may be the main pathways of RSV in treating DW. RSV reduces the inflammatory response by inhibiting the AGE-RAGE signalling pathway, which in turn promotes DW healing. [ABSTRACT FROM AUTHOR]

Persistent host inflammatory and immune responses to biofilm play a critical role in the mechanisms that govern soft and hard tissue destruction in periodontal disease. Among the less explored facets of these mechanisms are chemokines, including CCL5 (C-C motif chemokine ligand 5), also known as RANTES (regulated on activation, normal T cell expressed and secreted), a proinflammatory CC subfamily chemokine synthesized by T lymphocytes. Despite its importance, there is currently no comprehensive review of the role of CCL5 in periodontitis in the literature. Therefore, this paper aims to fill this gap by summarizing the existing knowledge on the involvement of CCL5 in the onset and progression of periodontitis. In addition, we aim to stimulate interest in this relatively overlooked factor among periodontitis researchers, potentially accelerating the development of drugs targeting CCL5 or its receptors. The review examines the association of CCL5 with periodontitis risk factors, including aging, cigarette smoking, diabetes, and obesity. It discusses the involvement of CCL5 in pathological processes during periodontitis, such as connective tissue and bone destruction. The data show that CCL5 expression is observed in affected gums and gingival crevicular fluid of periodontitis patients, with bacterial activity contributing significantly to this increase, but the reviewed studies of the association between CCL5 expression and periodontal disease have yielded inconclusive results. Although CCL5 has been implicated in the pathomechanism of periodontitis, a comprehensive understanding of its molecular mechanisms and significance remains elusive, hindering the development of drugs targeting this chemokine or its receptors. [ABSTRACT FROM AUTHOR]

Background: Inflammatory bowel disease (IBD) represents a group of chronic gastrointestinal disorders characterised by complex and multifaceted pathologies. The pursuit of non-invasive, accurate and rapid diagnostic methods and therapeutic monitoring tools has led to the emergence of Raman spectroscopy (RS) as a promising analytical technique in the field of IBD. RS offers molecular specificity with the potential to uncover valuable insights of the pathophysiology of IBD, posing it as a rapidly growing field of interest in both research and clinical settings. Main: This comprehensive review aims to provide an overview of the current state of research in the field of IBD-RS, with an emphasis on its potential diagnostic, prognostic, and therapeutic monitoring capabilities. We explore the molecular characterisation of bodily fluids including blood, urine and saliva and the ability of RS to rapidly determine the underpinning biochemical changes in their composition. The review also highlights recent studies and advances, that have employed RS to differentiate between healthy and diseased states, classify the IBD subtypes, identify candidate biomarkers and to monitor the therapeutic response to treatment in the form of mucosal healing. Additionally, we comment on the challenges and limitations associated with current research as well as with the clinical translation of RS for IBD diagnosis. Conclusions: As the field of vibrational spectroscopies continues to evolve particularly in the broader IBD context, to aid the diagnosis, prognosis and treatment, this review serves as a valuable resource for clinicians and researchers alike, examining the potential of Raman-based spectroscopy and the emerging technologies to advance the understanding and triaging of IBD. Ultimately, the integration of RS into everyday clinical practice holds promise for more effective management of IBDs, addressing the major unmet need in the fields of gastroenterology and of clinical medicine as a whole. [ABSTRACT FROM AUTHOR]