Tissues Of People Research Articles

Differentiation of the structure of dentinal tubules and dentinal canaliculi in human teeth of different ages

The dentinal tubules are designed to protect the odontoblast processes, which leave behind a cytoplasmic process during tooth development. Around the cytoplasmic process, a dentin matrix is deposited, which eventually mineralizes. However, the question of the role and structure of the cytoplasmic process of the odontoblast in each dentinal tubule after dentin has completely finished the formation process remains an unresolved issue. We investigated the dentinal tubules of 20 permanent teeth (premolars and molars) of people of different ages using a scanning electron microscope. The occlusal surfaces and longitudinal fracture planes of both decalcified and non-decalcified native tooth preparations were examined. In longitudinally split teeth at the periphery of the pulp chamber of a young human premolar, odontoblasts can be seen forming a continuous layer adjacent to the parapulpal dentin. Each of the odontoblasts has a separate process that penetrates into the dentinal tubule. More peripheral parts of the dentinal tubules were either empty or contained cylindrical structures that were better visualized after acid etching on longitudinally split samples. Etched split dentinal tubules in the outer dentin more often contained cylindroid tubular structures. In each individual dentinal tubule, the odontoblast processes are arranged in the form of thin-walled tubules, which, with the help of a supporting fibrillar framework, occupy a central position. On the occlusal surface of a mature human molar, the intertubular dentin has the appearance of a smooth-surfaced structure. Practically all dentinal tubules contain more or less preserved dentinal canaliculi, indicating their fairly pronounced resistance to adverse factors. Inside the lumen of the dentinal tubules, three different types of structures are observed: odontoblast processes, cylindrical structures, and collagen fibers. Odontoblast processes are visualized both along the entire length of the dentinal tubules and only in the parapulpal parts of the dentinal tubules. Their peripheral parts were either empty or contained cylindrical structures that likely correspond to the laminae limitantes. Collagen fibers often form a fibrillar network that on one side intertwines into the dentinal canaliculus, and on the other side is connected to the walls of the dentinal tubules due to perpendicular microtubules for anchoring fibrils. Collagen fibers are most numerous in the parapulpal parts of the dentinal tubules. This study only partially explained certain aspects of the dentin microstructure, but further in-depth studies of dentin ultrastructure are necessary to more fully understand the pathology of hard tooth tissues in people of different ages and the possibilities for its treatment and prevention.

Spatial and temporal properties of intra-operatively recorded spikes and high frequency oscillations in focal cortical dysplasia

ObjectiveFocal cortical dysplasias (FCD) are characterized by distinct interictal spike patterns and high frequency oscillations (HFOs; ripples: 80–250 Hz; fast ripples: 250–500 Hz) in the intra-operative electrocorticogram (ioECoG). We studied the temporal relation between intra-operative spikes and HFOs and their relation to resected tissue in people with FCD with a favorable outcome. MethodsWe included patients who underwent ioECoG-tailored epilepsy surgery with pathology confirmed FCD and long-term Engel 1A outcome. Spikes and HFOs were automatically detected and visually checked in 1-minute pre-resection-ioECoG. Channels covering resected and non-resected tissue were compared using a logistic mixed model, assessing event numbers, co-occurrence ratios, and time-based properties. ResultsWe found pre-resection spikes, ripples in respectively 21 and 20 out of 22 patients. Channels covering resected tissue showed high numbers of spikes and HFOs, and high ratios of co-occurring events. Spikes, especially with ripples, have a relatively sharp rising flank with a long descending flank and early ripple onset over resected tissue. ConclusionsA combined analysis of event numbers, ratios, and temporal relationships between spikes and HFOs may aid identifying epileptic tissue in epilepsy surgery. SignificanceThis study shows a promising method for clinically relevant properties of events, closely associated with FCD.

Correlation of osteopontin hormone with TIMI score and cardiac markers in patients with acute coronary syndrome presenting with chest pain.

Rapid evaluation of patients with acute coronary syndrome (ACS) attending the emergency service under emergency room conditions and using appropriate risk scoring would improve treatment success. Calcium levels accumulate in the tissue in people with coronary artery disease and this has been found to correlate with osteopontin levels in some studies. It is predicted that osteopontin level could be used as a biomarker to detect coronary artery calcification. In this study, we aimed to evaluate the use of osteopontin levels in the differential diagnosis of ACS in conjunction with cardiac troponin I (cTnI) levels, and HEART (history, ECG, age, risk factors, troponin) and thrombolysis in myocardial infarction (TIMI) scores in patients with chest pain who attended the emergency service. This study was conducted as a prospective observational clinical study in the Department of Emergency Medicine, Faculty of Medicine, Ataturk University. There was a total of 90 participants, including 60 patients and 30 healthy individuals in the control group. All participants' demographic information, electrocardiography (ECG) findings, cTnI level, TIMI and HEART score, and osteopontin level were evaluated. The patients' mean age was 51.61 ± 17.56 years and 63.3% (n = 57) were male. The body mass index (BMI) of the patients was 25.63 ± 4.67 kg/m2. Patients with chest pain [CP(+)] and high cardiac troponin I levels [cTnl(+)] were found to be older and to have higher HEART and TIMI scores than individuals with CP(+) and normal cardiac troponin I levels [cTnl(-)] and the healthy control group (p < 0.001). While the HEART score was zero in 22 (24.4%) of the patients, the TIMI score was zero in 42 (46.7%). In terms of gender distribution, vital signs and serum osteopontin levels, there was no significant difference between the patient groups (p > 0.05). It was found that patients with CP(+) and cTnl(+) had a higher rate of ECG abnormalities than the CP(+) and cTnl (-) group and the healthy control group (p = 0.13 and p < 0.001, respectively). In 65 (72.2%) of the patients, the ECG results were normal. ST-segment elevation was detected in 13 (14.4%) patients. In our study, cTnl levels were found to be positively correlated with age (r = 0.624), BMI (r = 0.291), HEART score (r = 0.794) and TIMI score (r = 0.805) (p = 0.001, p = 0.005, p = 0.001 and p = 0.001, respectively). In our study, we discovered that osteopontin levels could not reach the differential diagnostic level for ST-elevation myocardial infarction or non-ST-elevation myocardial infarction. No statistically significant difference was found in osteopontin levels between the groups (p > 0.05). While very positive results were obtained in this approach to the ACS diagnosis using HEART and TIMI scores in patients with chest pain who attended the emergency service and were diagnosed with ACS, no significant results could be obtained regarding the use of osteopontin levels as a biomarker. More comprehensive, multicentre studies involving a large number of appropriately selected patients are considered to be necessary.

Assessment of the condition of organs and tissues of the oral cavity in people with dentition defects against the background of metabolic syndrome

The aim of the study is comparative analysis of the condition of oral organs and tissues in people with metabolic syndrome (MS) of varying severity before orthopedic dental rehabilitation based on dental implants. 255 patients (151 women and 104 men) aged from 35 to 65 years were examined. 3 groups were formed: 2 study groups and a comparison group. Groups 1 and 2 included individuals with excess body weight and MS. The control group consisted of 88 people without MS. An index assessment of the condition of the periodontium and tissue structures of the alveolar bone (according to cone-beam computed tomography), microcirculation in the gingival mucosa was carried out using laser Doppler flowmetry. The analysis of the periodontal condition indicators showed that in all groups of patients with MS, periodontal pathology occurred, the value of which was significantly higher than in patients of the control group (p <0.05). The analysis of bone tissue according to CBCT data showed that the most favorable conditions (type 1 and type 2 of bone according to Misch) for dental implantation are found in people without MS, respectively 3.5% and 35.1% of cases. The intensity of blood flow (σ) was 21.2% lower in group 1 and 48% in group 2, compared with the control group. Vasomotor activity (Kv) was 13.2% lower in the first group and 35% lower in the second group. A decrease in amplitudes in the area of all rhythms in the LDF gram was found: low-frequency - by 15.6%, high-frequency - by 16.9%, pulse - by 3.6%. Changes occurring in the organs and tissues of the mouth against the background of MS of varying severity lead to a decrease in tissue perfusion with blood and blood flow activity, a local decrease in bone density, and as a result, pathological changes in periodontal tissues. Before performing dental rehabilitation, it is necessary to take into account all the risks of possible complications caused by the general condition of organs and systems of people with MS.

The Impact of Interventional Weight Loss on Bone Marrow Adipose Tissue in People Living with Obesity and Its Connection to Bone Metabolism.

This review focuses on providing physicians with insights into the complex relationship between bone marrow adipose tissue (BMAT) and bone health, in the context of weight loss through caloric restriction or metabolic and bariatric surgery (MBS), in people living with obesity (PwO). We summarize the complex relationship between BMAT and bone health, provide an overview of noninvasive imaging techniques to quantify human BMAT, and discuss clinical studies measuring BMAT in PwO before and after weight loss. The relationship between BMAT and bone is subject to variations based on factors such as age, sex, menopausal status, skeletal sites, nutritional status, and metabolic conditions. The Bone Marrow Adiposity Society (BMAS) recommends standardizing imaging protocols to increase comparability across studies and sites, they have identified both water-fat imaging (WFI) and spectroscopy (1H-MRS) as accepted standards for in vivo quantification of BMAT. Clinical studies measuring BMAT in PwO are limited and have shown contradictory results. However, BMAT tends to be higher in patients with the highest visceral adiposity, and inverse associations between BMAT and bone mineral density (BMD) have been consistently found in PwO. Furthermore, BMAT levels tend to decrease after caloric restriction-induced weight loss. Although weight loss was associated with overall fat loss, a reduction in BMAT did not always follow the changes in fat volume in other tissues. The effects of MBS on BMAT are not consistent among the studies, which is at least partly related to the differences in the study population, skeletal site, and duration of the follow-up. Overall, gastric bypass appears to decrease BMAT, particularly in patients with diabetes and postmenopausal women, whereas sleeve gastrectomy appears to increase BMAT. More research is necessary to evaluate changes in BMAT and its connection to bone metabolism, either in PwO or in cases of weight loss through caloric restriction or MBS, to better understand the role of BMAT in this context and determine the local or systemic factors involved.

Selenium influences thyroid hormones, myricetin has anti-cancer effects on human papillary thyroid cancer cells, and thyroid hormones have been associated with psychological disorders: Thyroid evaluation and therapy during pregnancy

Introduction: A micronutrient called selenium; a non-metallic element is necessary to manufacture selenoproteins, including selenocysteine. The thyroid has the highest concentration of selenium per gram of tissue in people. The majority of known selenoproteins, including glutathione peroxidase, are expressed in the thyroid and are crucial for the metabolism of thyroid hormones, control of redox states, and preservation of cellular homeostasis. It has been demonstrated that selenium therapy for Graves orbitopathy patients can slow the disease's course and enhance the quality of life. Different selenium supplements have demonstrated varying anticancer efficacy in thyroid cancer. It also looked at how different treatment plans affected patients' thyroid function, mood, and inflammatory markers. TSH (thyroid-stimulating hormone) is slightly elevated in subclinical hypothyroidism, while T4 or T3 levels are normal. Objective: The purpose of this study was to evaluate the therapeutic effects of levothyroxine sodium given alone or in combination with selenium on patients with chronic lymphocytic thyroiditis and hypothyroidism to serve as a guide for clinical treatment. The purpose of the current study is to ascertain the impact of selenium supplementation on thyroid hormone and anti-thyroid peroxidase antibody (anti-TPO AB) levels. The pathophysiology of this illness may be affected by the imbalance in the activity of T cells such as Th1, Th2, Th17, and Treg. This study was to evaluate any changes in the release of cytokines by these cells after selenium administration in patients with HT. The diagnosis and management of thyroid problems during pregnancy are covered in detail in this article. It also includes a summary of the main recommendations made by several medical associations for the diagnosis, treatment, and interpretation of thyroid function during pregnancy. Results: The combined group's overall effective rate was much greater than the control group's. After therapy, both groups' TT3, TT4, TSH, TgAb, and TPOAb levels, SAS and SDS scores, and levels of inflammatory mediators such as IL-2, IL-10, and TNF- all showed a significant improvement. In the combination group, IL-10 levels increased more, and TGAb, TPOAb, IL-2, TNF-, SAS, and SDS scores reduced more when compared to the control group, whereas the differences in the other indices were not statistically significant. According to research, LT4 has some efficacy in treating CLT with hypothyroidism, and selenium therapy in combination with LT4 can increase its therapeutic effect and help patients' immunological and inflammatory responses as well as their mood. Conclusions: Myo-inositol, vitamin D, and selenium supplementation together had an impact on the decline in cytokine markers, Ab-TPO, and Ab-TG levels, which helped to compensate for the underlying condition. Since myricetin is a strong inducer of HATC cell death, it may be helpful in the creation of HATC therapeutic medicines. Myricetin significantly reduced the growth of HATC cells, by almost 70%. A significant number of dead cells showed sub-G1 phase arrest. In SNU-80 HATC cells, myricetin similarly displayed cytotoxicity and caused DNA condensation in a dose-dependent manner. Additionally, myricetin induced the mitochondria to release apoptosis-inducing factor (AIF) into the cytoplasm and changed the potential of the mitochondrial membrane.

Super Glue Production by Dermatophytes: Review

Dermatophytosis can be caused on by the invasion and infection of keratinized tissues in people and animals via a group of filamentous fungus known as dermatophytes. About a quarter of the world’s population is affected by it which is one of the most prevalent superficial fungal diseases. Some of these fungi have the capacity to develop complex 3-D biofilm structures, or “biofilm,” which are distinguished by the creation of extracellular polymeric molecules and a heightened drug resistance. The assessment of biofilm now relies on a variety of different methods, which frequently results in various evaluations of the microbial strains’ capacity to create biofilms. It has only recently been discovered the architecture and growth features of dermatophytic biofilms (Trichophyton spp., Microsporum spp.). Additionally, the structural complexity and lack of research on filamentous fungal biofilms make therapy challenging. Therefore, there is a demand for newer antifungals or methods for treating resistant dermatophytosis to offer an efficient, original, and safe substitute to current treatments. Therefore, this review highlighted on the significance, characterization and evaluation of biofilm that produced from dermatophytes.

The Genetics of Neurodevelopment in Congenital Heart Disease.

Congenital heart disease (CHD) is the most common birth anomaly, affecting almost 1% of infants. Neurodevelopmental delay is the most common extracardiac feature in people with CHD. Many factors may contribute to neurodevelopmental risk, including genetic factors, CHD physiology, and the prenatal/postnatal environment. Damaging variants are most highly enriched among individuals with extracardiac anomalies or neurodevelopmental delay in addition to CHD, indicating that genetic factors have an impact beyond cardiac tissues in people with CHD. Potential sources of genetic risk include large deletions or duplications that affect multiple genes, such as 22q11 deletion syndrome, single genes that alter both heart and brain development, such as CHD7, and common variants that affect neurodevelopmental resiliency, such as APOE. Increased use of genome-sequencing technologies in studies of neurodevelopmental outcomes in people with CHD will improve our ability to detect relevant genes and variants. Ultimately, such knowledge can lead to improved and more timely intervention of learning support for affected children.

Abnormal immune activation and fibrosis of epicardial adipose tissue in people living with HIV: results from the PIECVIH study

Abstract Background Increased Epicardial Adipose Tissue (EAT) volume has been associated with increased risk of CAD in people living with HIV (PLWH). However, the underlying mechanisms remain unknown. Purpose We conducted the PIECVIH study to compare EAT properties in relation with CAD between PLWH and HIV-negative patients, all undergoing coronary artery bypass graft (CABG). Methods The PIECVIH study is a cross sectional prospective study performed in a single center enrolling 11 ART-controlled PLWH and 11 matched (age ± 3 years and sex) HIV-negative patients requiring CABG. During surgery, EAT and thoracic subcutaneous fat samples were taken. Gene expression was analyzed in samples with sufficient mRNA quality (7 PLWH and 7 HIV− for subcutaneous fat, 9 PLWH and 8 HIV− samples for EAT). The expression of 30 genes, mainly related to inflammation, immune activation, fibrosis and adipokines, was evaluated and related to the expression of the reference gene 18S. Results The mean age of the cohort was 59.8 years (100% male). The cardiovascular risk profile was quite similar between both groups including 66% smokers, 64% hypercholesterolemia, 36% hypertriglyceridemia and 56% hypertension. However, HIV− subjects had a higher prevalence of diabetes (73% vs 18%, p=0.002) and a higher body mass index than HIV− (23,2 vs 27.5 kg/m2, p=0.017). The level of gene expression of all tested genes was not different between PLWH and HIV− subjects in subcutaneous fat. Conversely, in EAT, the relative expression of IL-6 and CCL2 was 3–5-fold higher in samples issued from PLWH than from HIV−: respectively 0.46 vs 0.13 (p=0.03) and 1.13 vs 0.24 (p=0.03). Moreover, only in EAT, and only in PLWH, the expression of the chemokines CCL2 and CCL5 and of the macrophage immune activation markers (CD68, CD163, CD206), was globally related to the expression of genes involved into fibrosis: collagen genes (COL1A1, COL3A1, COL3A1, COL6A2, COL6A3), TGFB, LOX (lysyl-oxidase) and ASAH1 (acid ceraminidase). Only in EAT and only in PLWH, the expression of IGF1 and CES (carboxylesterase 1), two genes associated with increased cardiovascular risk, was related to the expression of genes associated with immune activation, fibrosis and vascularization (VEGFA). Only in PLWH, the Gensini score, evaluating the severity of CAD, was associated with EAT expression of collagen 6 and of the CV risk factors IGF1 and CES. Conclusion In very high CV risk subjects undergoing CABG, inflammation/immune activation of EAT was higher in PLWH as compared to controls. In EAT of PLWH, immune activation was strongly associated with fibrosis stressing for a dysfunctional EAT. Moreover, the severity of CAD, as addressed by the Gensini score, was associated with collagen 6 expression, a deleterious collagen in the context of EAT fibrosis. We propose that in PLWH, altered EAT immune profile and fibrosis could be responsible for reported accelerated CAD. Funding Acknowledgement Type of funding sources: Public grant(s) – National budget only. Main funding source(s): French Agency for Research on AIDS and Viral Hepatitis

Diyet Polifenollerinin Kahverengileşme ve Kahverengi Yağ Dokusu Aktivitesi Üzerine Etkileri

Dünya Sağlık Örgütü (DSÖ) dünya yetişkin nüfusunun yaklaşık %13'ünün obez olduğunu belirtmektedir. Bu durum obeziteyi ve komplikasyonlarını, en önemli küresel halk sağlığı endişelerinden ve önlenebilir hastalıklardan biri haline getirmektedir. Beslenme, obezitenin önlenmesinde ve yönetiminde kilit role sahiptir. Birçok çalışma, besin kaynaklı ögelerin (özellikle polifenollerin) obezitenin önlenmesinde ve yönetiminde rol oynayabileceğini göstermektedir. Yetişkin insanlarda aktif kahverengi yağ dokusu varlığının tespiti ve kahverengi yağ dokusunun (KYD) aktivasyonu yoluyla enerji harcaması, obezite yönetiminde umut verici bir yöntem olarak gösterilmektedir. Polifenollerle ilişkilendirilen bazı anti-diyabetik ve obeziteyi önlemeye yönelik aktivitelerin, enerji harcaması üzerinde olumlu etkileri olabileceği düşünülmektedir. Bu derleme enerji harcamasının kahverengileşme yoluyla düzenlenmesinde bazı polifenollerin olası etkilerini değerlendirmektedir.

Methylated DNA markers discriminate ovarian cancer from benign tissue in BRCA carriers.

e17610 Background: Methylated DNA markers (MDMs) associated with sporadic ovarian cancer (OC) are detected in plasma from patients with treatment naïve tumors, but not cancer-free controls. To assess potential benefits to patients at risk for hereditary OC, the aim of this study was to measure the performance of validated sporadic OC MDMs in OC and benign ovarian tissue (BOT), surgically obtained from germline BRCA1 or BRCA2 ( BRCA1/2) mutation carriers. Methods: BRCA1/2 carriers with OC and BRCA1/2 carriers who had undergone risk-reducing salpingo-oophorectomy (SO) were identified at a comprehensive cancer center. BRCA1/2 carriers in both OC and BOT groups were balanced on age and year of surgery with non- BRCA carriers with sporadic OC or benign indications for SO. OC and BOT formalin fixed paraffin embedded (FFPE) tissues were macrodissected following pathologist selection of representative sites; DNA was extracted, and bisulfite converted. 15 OC MDMs ( GDF6, IFFO1, MAX.chr1.147790358, MAX.chr6.10382190, MAX.chr11.14926602, C2CD4D, PDRM14, NCOR2, SKI, DSCR6, SIM2, PALLD, CDO1, GPRIN1, BCAT1) previously identified in sporadic OC were assayed by quantitative methylation specific PCR, normalized by β-actin, by blinded personnel. Areas under the receiver operating characteristic curve (AUC) were generated for each MDM to assess discrimination of OC from benign tissue and compared between BRCA1/2 and sporadic (non- BRCA) patients, using a z-test. Results: Among BRCA1/2 carriers, there were 48 OC ( BRCA-OC) and 48 BOT ( BRCA-BOT); among non- BRCA, we matched 48 OC (Sporadic-OC) and 48 BOT (non- BRCA-BOT). The median AUC for OC MDM discriminated between OC and BOT with AUCs in BRCA1/2 carriers was 0.87, (IQR, 0.83-0.93). Sporadic-OC vs non- BRCA-BOT median AUC was 0.88 (IQR, 0.83-0.92). AUCs were not significantly different for each MDM when stratified by BRCA or sporadic status. MDMs with an AUC of ≥0.9 in either group are shown (Table). Conclusions: OC MDMs identified and validated in sporadic OC are highly discriminant for OC from BOT in DNA extracted from tissues of people who carry a BRCA1/2 mutation. Testing the performance of these OC MDMs in plasma from BRCA1/2 carriers with and without OC may be of clinical value for high-risk patients and inform multi-cancer early detection testing strategies.[Table: see text]

Effect of tirzepatide versus insulin degludec on liver fat content and abdominal adipose tissue in people with type 2 diabetes (SURPASS-3 MRI): a substudy of the randomised, open-label, parallel-group, phase 3 SURPASS-3 trial

Tirzepatide is a novel dual glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 receptor agonist under development for the treatment of type 2 diabetes. The aim of this substudy was to characterise the changes in liver fat content (LFC), volume of visceral adipose tissue (VAT), and abdominal subcutaneous adipose tissue (ASAT) in response to tirzepatide or insulin degludec in a subpopulation of the SURPASS-3 study. This substudy of the randomised, open-label, parallel-group, phase 3 SURPASS-3 trial was done at 45 medical research centres and hospitals across eight countries (Argentina, Austria, Greece, Hungary, Italy, Romania, Spain, and the USA). Eligible participants were adults with type 2 diabetes, a baseline HbA1c 7·0-10·5% (53-91 mmol/mol), a BMI of at least 25 kg/m2, stable weight, were insulin-naive, and on treatment with metformin alone or in combination with a SGLT2 inhibitor for at least 3 months before screening. In addition to the main study inclusion criteria, substudy participants had a fatty liver index of at least 60. Participants had an MRI scan and were randomised (1:1:1:1) in the main study to subcutaneous injection once per week of tirzepatide 5 mg, 10 mg, or 15 mg, or subcutaneous injection once per day of titrated insulin degludec, using an interactive web-response system, and were stratified by country, HbA1c, and concomitant oral anti-hyperglycaemic medication. The primary efficacy endpoint was the change from baseline in LFC (as measured by MRI-proton density fat fraction [MRI-PDFF]) at week 52 using pooled data from the tirzepatide 10 mg and 15 mg groups versus insulin degludec. Analyses were assessed in the enrolled MRI population, which consisted of participants in the modified intention-to-treat population of the main study who also had a valid MRI at either baseline or after baseline. This is a substudy of the trial registered with ClinicalTrials.gov, number NCT03882970, and is complete. From April 1, 2019, to Nov 15, 2019, 502 participants were assessed for eligibility to participate in this substudy, 296 (59%) of whom were included in the enrolled MRI population and randomly assigned to treatment (tirzepatide 5 mg, n=71; tirzepatide 10 mg, n=79; tirzepatide 15 mg, n=72; and insulin degludec, n=74). Baseline demographics and clinical characteristics were similar across all treatment groups. From an overall mean baseline LFC of 15·71% (SD 8·93), the absolute reduction in LFC at week 52 was significantly greater for the pooled tirzepatide 10 mg and 15 mg groups (-8·09%, SE 0·57) versus the insulin degludec group (-3·38%, 0·83). The estimated treatment difference versus insulin degludec was -4·71% (95% CI -6·72 to -2·70; p<0·0001). The reduction in LFC was significantly correlated (p≤0·0006) with baseline LFC (ρ=-0·71), reductions in VAT (ρ=0·29), reductions in ASAT (ρ=0·33), and reductions in body weight (ρ=0·34) in the tirzepatide groups. Tirzepatide showed a significant reduction in LFC and VAT and ASAT volumes compared with insulin degludec in this subpopulation of patients with type 2 diabetes in the SURPASS-3 study. These data provide additional evidence on the metabolic effects of this novel dual GIP and GLP-1 receptor agonist. Eli Lilly and Company.

Effects of canagliflozin and metformin on insulin resistance and visceral adipose tissue in people with newly-diagnosed type 2 diabetes

BackgroundThe current study was to evaluate the effects of canagliflozin and metformin on insulin resistance and visceral adipose tissue in people with newly-diagnosed type 2 diabetes.MethodsThis is an open-label, parallel and controlled study. Participants were divided into canagliflozin (100 mg/qd) or metformin (1000 mg/bid) groups. At baseline and after 12 weeks’ therapy, insulin resistance [Homeostatic Model Assessment of Insulin Resistance (HOMA-IR)], subcutaneous and visceral adipose tissue, fasting blood glucose (FBG), glycated hemoglobin A1c (HbA1c), C-reactive protein (CRP) and nitric oxide (NO) were evaluated and compared.ResultsThere was no significant between-group difference in baseline characteristics. After 12 weeks’ therapy, in canagliflozin group (n = 67), compared to baseline, FBG, HbA1c and HOMA-IR were decreased, accompanying with reduction of visceral adipose tissue. Compared to metformin group (n = 73), FBG, HbA1c and HOMA-IR were lower in canagliflozin group, accompanying with less visceral adipose tissue and lower serum CRP level and higher NO level. After multivariable regression analysis, age, visceral adipose tissue and CRP remained associated with increased insulin resistance, while canagliflozin treatment and higher NO level were associated with reduced insulin resistance. Body mass index, waist/hip ratio, CRP and HOMA-IR remained associated with increased visceral adipose tissue, while canagliflozin treatment and higher NO level were associated with reduced visceral adipose tissue. There was no difference in adverse event between these two groups.ConclusionCanagliflozin reduces visceral adipose tissue and improves blood glucose, insulin resistance and systemic inflammation in people with newly-diagnosed type 2 diabetes.

Mercury is present in neurons and oligodendrocytes in regions of the brain affected by Parkinson's disease and co-localises with Lewy bodies.

ObjectiveEnvironmental toxicants are suspected to play a part in the pathogenesis of idiopathic Parkinson’s disease (PD) and may underlie its increasing incidence. Mercury exposure in humans is common and is increasing due to accelerating levels of atmospheric mercury, and mercury damages cells via oxidative stress, cell membrane damage, and autoimmunity, mechanisms suspected in the pathogenesis of PD. We therefore compared the cellular distribution of mercury in the tissues of people with and without PD who had evidence of previous mercury exposure by mercury being present in their locus ceruleus neurons.Materials and methodsParaffin sections from the brain and general organs of two people with PD, two people without PD with a history of mercury exposure, and ten people without PD or known mercury exposure, were stained for inorganic mercury using autometallography, combined with immunostaining for a-synuclein and glial cells. All had mercury-containing neurons in locus ceruleus neurons. Laser ablation-inductively coupled plasma-mass spectrometry (LA-ICP-MS) was used to confirm the presence of mercury and to look for other potentially toxic elements. Autometallography-stained locus ceruleus paraffin sections were examined to compare the frequency of previous mercury exposure between 20 PD and 40 non-PD individuals.ResultsIn PD brains, autometallography-detected mercury was seen in neurons affected by the disease, such as those in the substantia nigra, motor cortex, striatum, thalamus, and cerebellum. Mercury was seen in oligodendrocytes in white and grey matter. Mercury often co-localised with Lewy bodies and neurites. A more restricted distribution of brain mercury was seen in people without PD (both with or without known mercury exposure), with no mercury present in the substantia nigra, striatum, or thalamus. The presence of autometallography-detected mercury in PD was confirmed with LA-ICP-MS, which demonstrated other potentially toxic metals in the locus ceruleus and high iron levels in white matter. Autometallography-detected mercury was found in locus ceruleus neurons in a similar proportion of PD (65%) and non-PD (63%) individuals.ConclusionsIn people with PD, mercury was found in neurons and oligodendrocytes in regions of the brain that are affected by the disease, and often co-localised with aggregated a-synuclein. Mercury in the motor cortex, thalamus and striatum could result in bradykinesia and rigidity, and mercury in the cerebellum could cause tremor. People without PD had a restricted uptake of mercury into the brain. The similar frequency of mercury in the locus ceruleus of people with and without PD suggests these two groups have had comparable previous mercury exposures but that PD brains have a greater predisposition to take up circulating mercury. While this post mortem study does not provide a direct link between mercury and idiopathic PD, it adds to the body of evidence that metal toxicants such as mercury play a role in the disease. A precautionary approach would be to reduce rising mercury levels in the atmosphere by limiting the burning of fossil fuels, which may be contributing to the increasing incidence of PD.

Changes in sub-calcaneal fat pad composition and their association with dynamic plantar foot pressure in people with diabetic neuropathy

BackgroundDiabetic foot disease is associated with physiological and biomechanical abnormalities in the foot that increase risk for ulceration. The objective was to assess MRI changes in the composition of sub-calcaneal fat pad tissue and its association with plantar pressure during walking. MethodsFourteen people with diabetes and peripheral neuropathy and five age-matched healthy controls underwent T1-weighted sagittal plane spin-echo Dixon MRI of the rearfoot. Dixon Chemical Shift Imaging was used to create fat-only and water-only images from which the fat signal fraction in a defined ROI of the sub-calcaneal fat pad was calculated. Barefoot plantar pressure distribution during walking was assessed and associated with fat pad outcomes. FindingsMean ± SD fat signal fraction was significantly lower in the neuropathic subjects than in the healthy controls (0.55 ± 0.11 vs. 0.72 ± 0.03, p < 0.005), and was explained by a lowering in fat signal (R2 0.87), more than an increase in water signal (R2 0.32). Mean ± SD peak pressure at the heel was 391 ± 119 kPa for the neuropathic subjects and 325 ± 53 kPa for the healthy controls (non-significantly different). Fat signal fraction and peak pressure were significantly inversely correlated (r = −0.59, p < 0.01). InterpretationDixon chemical shift MRI showed a reduced fat signal fraction in sub-calcaneal fat pad tissue in people with diabetic neuropathy. Both neuropathic and non-neuropathic factors may be attributed to this outcome. Fat pad function also seems to be compromised, as indicated by an associated increase in peak plantar pressures. This may increase risk for foot ulceration.

Growth Hormone Releasing Hormone Reduces Circulating Markers of Immune Activation in Parallel with Effects on Hepatic Immune Pathways in Individuals with HIV-infection and Nonalcoholic Fatty Liver Disease.

The growth hormone (GH)/insulin-like growth factor-1 (IGF-1) axis modulates critical metabolic pathways; however, little is known regarding effects of augmenting pulsatile GH secretion on immune function in humans. This study used proteomics and gene set enrichment analysis to assess effects of a GH releasing hormone (GHRH) analog, tesamorelin, on circulating immune markers and liver tissue in people with human immunodeficiency virus (HIV) (PWH) and nonalcoholic fatty liver disease (NAFLD). 92 biomarkers associated with immunity, chemotaxis, and metabolism were measured in plasma samples from 61 PWH with NAFLD who participated in a double-blind, randomized trial of tesamorelin versus placebo for 12 months. Gene set enrichment analysis was performed on serial liver biopsies targeted to immune pathways. Tesamorelin, compared to placebo, decreased interconnected proteins related to cytotoxic T-cell and monocyte activation. Circulating concentrations of 13 proteins were significantly decreased, and no proteins increased, by tesamorelin. These included 4 chemokines (CCL3, CCL4, CCL13 [MCP4], IL8 [CXCL8]), 2 cytokines (IL-10 and CSF-1), and 4 T-cell associated molecules (CD8A, CRTAM, GZMA, ADGRG1), as well as ARG1, Gal-9, and HGF. Network analysis indicated close interaction among the gene pathways responsible for these proteins, with imputational analyses suggesting down-regulation of a closely related cluster of immune pathways. Targeted transcriptomics using liver tissue confirmed a significant end-organ signal of down-regulated immune activation pathways. Long-term treatment with a GHRH analog reduced markers of T-cell and monocyte/macrophage activity, suggesting that augmentation of the GH axis may ameliorate immune activation in an HIV population with metabolic dysregulation, systemic and end organ inflammation. Clinical Trials Registration. NCT02196831.

CLASSES & Diagnosis of Parasitic Diseases

A parasite is a daily routine structure that experiences on or inside a host life form and gets its food from the cost of its host. There are three rule classes of parasites that can cause infections in people: Protozoa, Helminths, and Ectoparasites. Protozoa are minuscule, single-celled living beings that can be free-living or parasitic in nature. They can duplicate in people, which adds to their endurance and moreover allows genuine illnesses to create from a solitary life form. Transmission of protozoa that live in a human's stomach related framework to another human that normally happens through a fecal-oral course (for instance, tainted food or water or individual to-singular contact). Protozoa that live in the blood or tissue of people are communicated to different people by an arthropod vector (for instance, through the nibble of a mosquito or sand fly).

Вплив фізичних навантажень на ультраструктурні зміни тканин волосяних фолікулів людини

Мета. Вивчити вплив фізичного навантаження на ультраструктурні морфологічнізміни тканин волосяних фолікулів голови людини. Методи. Ультрамікроскопічні дослідженняультразрізів тканин за допомогою електронного мікроскопа УЕМВ-100К в умовахприскорюючої напруги 75 кВ і збільшеннях на екрані мікроскопа 2000Х – 124000Х з наступ-ним фотографуванням та цифровою обробкою мікрофотографій. Результати. В роботіпроаналізовано результати електронно-мікроскопічного дослідження ультрамікроскопічноїкартини морфологічних змін волосяних фолікулів осіб, які в процесі життєдіяльності регуляр-но відвідували фізичні заняття (основна група) та таких, які не практикували фізичні заняттята не мали в побуті достатньої рухової активності (контрольна група). Як виявилось під часаналізу результатів, зокрема обробці мікрофотографій, кількість мітохондрій була більшоюу клітинах тканин осіб, які регулярно займались фізичними навантаженнями, ніж у осібконтрольної групи. Кількість піноцитозних пухирців, ліпідних і білково-патологічних включеньта гранул трихогліаліну, навпаки, реєстрували меншою мірою в осіб основної групи порівняноз контрольною, що свідчить про відсутність застійних явищ у клітинах та міжклітинній речовинітканин осіб, які в процесі життєдіяльності регулярно відвідували фізичні заняття і, відповідно,проявляли достатню рекреаційну рухову активність. Висновки. Покращення ультраструктуритканин у осіб основної групи свідчить про саногенну, енерговідновлюючу та регулюючу іншіфізіологічні процеси роль фізичного навантаження в осіб, які регулярно займаються фізичнимизаняттями та проявляють достатню рекреаційну рухову активність у процесі їх життєдіяльності.

Hubungan Klasifikasi Perokok dengan Kesehatan Jaringan Periodontal Masyarakat yang Merokok di Pulau Harapan diukur dengan Skor CIPTN

The Ministry of Health in Alamsyah, (2017) states that smoking behavior is an activity of burning one of the tobacco products, then smoking or inhaling the smoke, including clove cigarettes, white cigarettes, cigars or other forms produced from the nicotina tabacum, nicotina rustica and other species. The classification of smokers consists of: light smokers (1-4 cigarettes/day), moderate smokers (5-14 cigarettes/day), heavy smokers (&gt; 15 cigarettes/day). This study was conducted to obtain an overview of the health of the periodontal tissue in people who smoke on the island of Harapan. Data were collected by classifying smokers and intra-oral examination of CPITN on every community who smoked on the island of Harapan whose results were recorded on the examination sheet. This examination was carried out in January 2020. The data were analyzed by Univariate and Bivariate. Based on the results of research on male smokers in Harapan Island, Seribu Islands region, it can be concluded that there are no smokers who have a score of 0 or have healthy periodontal tissue. In the category of moderate smokers, the highest number of CIPTN 2 scores or had tartar on the sub gingiva was 9 people (52.9%), while in the heavy smoker group the highest score also had CIPTN 2 scores or had tartar on the sub gingiva as many as 18 people (48,6%). The statistical test results obtained P = 0.029 where the P value &lt;0.05, it can be concluded that there is a difference in the proportion of the classification of smokers to the state of the periodontal tissue calculated based on the CIPTN status or there is a significant relationship between the classification of smokers and the state of the periodontal tissue calculated by the CIPTN score).

Effects of Simvastatin on the Metabolism of Fatty Acids in Combined Secondary Prevention of Coronary Heart Disease: Dosage and Gender Differences between the Effects

Statins are currently used for secondary prevention of Coronary Heart Disease (CHD), as the lipid-lowering therapy with them is proven safe and effective. The purpose of this research is to investigate the dose-dependent effect of statins used for secondary prevention of coronary heart disease, as well as mechanisms of quantitative and qualitative changes in lipoproteins, fatty acids and cholesterol in the blood and tissues of people of both sexes. In a clinical trial (n=125, of which 89 patients belong to group 1 and 36 to group 2) and an experiment on laboratory animals (n = 100), simvastatin reduced the total level of fatty acids in blood plasma, when given in the amount that was within the therapeutic dose range. This effect was achieved through a drug-induced improvement in the capacity of hepatic cells to absorb Low-density (LDL) and Very-low-density (VLDL) lipoproteins. Considering the formation of saturated fatty acids, statin performed better in males. With Omega-3 polyunsaturated fatty acids involved, changes in lipoproteins, cholesterol and fatty acids (liver and myocardium) were similar to those caused by small doses of a statin drug. Effects of the combination of bisoprolol and acetylsalicylic acid were completely different from those caused by the use of statin.