Tissue Resistance Research Articles

Fatty Liver Disease and its Impaction on Insulin Resistance

Abstract Background Non-alcoholic fatty liver disease (NAFLD) involves excess liver fat accumulation without specific causes like alcohol or viral infections, categorized into simple steatosis and nonalcoholic steatohepatitis (NASH). While simple steatosis is generally stable, NASH is linked to progressive liver disease. Diagnosis excludes secondary causes, and NAFLD, marked by hepatocyte changes, inflammation, and fibrosis, may lead to severe complications. Strongly associated with insulin resistance in liver and adipose tissues, NAFLD disrupts glucose-insulin interplay, compromising insulin's regulatory functions and contributing to metabolic disorders and disease progression. Aim of the Work The aim of the study is to investigate fatty liver disease and evaluate its impact of on insulin resistance. Patients and Methods This cross-sectional study, conducted at Ain Shams University, focuses on adults with NAFLD to assess insulin resistance. Inclusion criteria involve fatty liver disease, impaired glucose tolerance, and informed consent, while exclusions include alcohol intake and hepatitis. Data collection comprises demographics, anthropometrics, metabolic syndrome assessment, ultrasound grading of steatosis, and laboratory tests for liver function, FIB-4 index, and insulin resistance using HOMA-IR. The study aims to understand the relationship between NAFLD and insulin resistance in a clinical setting. Results In this study of 98 patients with Non-alcoholic Fatty Liver Disease (NAFLD), characterized by liver fat accumulation, insulin resistance (IR) was prevalent in 63.3%. The cases, predominantly females (52%), had mean age of 43 years, 50% were hypertensive, and 48% were diabetic. IR was directly related to age, and its prevalence was significantly higher in patients with diabetes and hypertension. IR correlated positively with body weight, BMI, ALT, AST, FIB-4, TG, and cholesterol. Fatty liver grading showed a significant association with IR, particularly in grade 2 cases. The optimal HOMA-IR cutoff for distinguishing between grade I and II fatty liver was >2.56, with high sensitivity (100%) and specificity (88.73%). These findings emphasize the intricate relationship between NAFLD, IR, and associated metabolic factors. Conclusion The study established a robust link between insulin resistance (IR) and Non- alcoholic Fatty Liver Disease (NAFLD), noting a 63.3% prevalence of IR in the subjects. Employing HOMA-IR, a cutoff point >2.56 effectively differentiated between NAFLD grades I and II, demonstrating 100% sensitivity, 88.73% specificity, and a remarkable AUC of 98. This underscores HOMA-IR's valuable role in identifying and stratifying NAFLD, especially in individuals with diabetes.

Oscillatory airflow through the hypopharyngeal and supraglottic airway

Exercise-induced laryngeal obstruction (EILO) is a known cause of exertional dyspnoea, characterised by paradoxical inward collapse of laryngeal tissues. The pathophysiological mechanisms of EILO remain to be fully established, but insufficient mechanical resistance of laryngeal tissues to air-induced loads is hypothesised. It is understood that airflow and anatomic configurations of the airway play a key role in the wall pressure distribution of the larynx. While breathing is a cyclic process with directional changes of airflow, the literature is confined to steady, unidirectional airflow. It is necessary to assess the role of oscillatory airflow on the loads on the laryngeal airway. This study investigates the effect of oscillatory airflow on the laryngeal flow fields and air-induced loads. A computational fluid dynamics model of the upper respiratory tract (URT) is developed using the Reynolds-averaged Navier-Stokes equations. Five oscillatory airflow cases through a single geometry are considered, utilising sinusoidal breathing cycles with different breathing frequencies (24, 32 and 40 breaths per minute) and peak inspiratory flow rates (96, 168 and 240 L/min). Results include the airflow velocity distribution in the URT, and the air-induced pressure and forces. It is demonstrated that inspiratory velocity distribution varies with breathing frequency and intensity. The force acting on the URT walls are in-phase with the airflow rate and therefore exhibit quasi-steady behaviour. These findings are also reflected in the force vectors acting on the aryepiglottic folds and indicate that air-induced closure of the supraglottis in EILO is influenced by the breathing intensity rather than the breathing frequency.

Effect of Clozapine and Olanzapine on the Expression of Selected Genes and Epigenetic Regulators of Insulin Resistance Pathway in Human Preadipocytes – a Preliminary Study

Clozapine and olanzapine, popular second-generation antipsychotics used for various psychiatric disorders, cause significant side effects such as metabolic syndrome, but the exact mechanism remains unclear. The present study aimed to assess clozapine and olanzapine effects on the expression of mRNA insulin pathway genes (IRS-1, PTEN, PIK3CG and PIK3R1), microRNAs (miR-152-3p, miR-214-3p, miR-15b-5p, miR-16-5p, miR-126-3p) and long non-coding RNAs (lncRNAs: XIST, H19, SNHG16, PVT1), in human visceral preadipocytes (HPAd). Expression was examined by real - time PCR. Cell viability was determined by MTT assay. The findings revealed that in HAPd, both clozapine and olanzapine (at doses of 5 µM and 25 µM) decreased IRS-1 gene expression after 24 hours. After 48 hours, IRS-1 expression was reduced by clozapine at both concentrations and olanzapine at 5 µM. In addition, olanzapine (at 25 µM) decreased the expression of PIK3CG, miR-152-3p, miR-214-3p, miR-15b-5p and miR-16-5p after 24 hours, while increasing the expression of miR-126-3p at 5 µM. Clozapine at 25 µM decreased miR-16-5p expression and increased SNHG16 lncRNA expression at 5 µM after 24 hours. After 48 hours, olanzapine (at 25 µM) increased PIK3R1 expression and decreased PIK3CG expression at 5 µM. Both drugs at 5 µM increased the expression of miR-152-3p, miR-214-3p, miR-15b-5p and miR-16-5p after 48 hours, with clozapine further increasing the expression of miR-126-3p at this concentration. The results suggest that clozapine and olanzapine may affect the expression of key genes and epigenetic molecules in the insulin pathway, which is one potential cause leading to insulin resistance in adipose tissue.

Antibiogram development for Australian residential aged care facilities.

Knowledge of local antibiotic resistance data, provided by antibiograms (a cumulative summary of in vitro-antimicrobial-susceptibility-test results), can aid prescribing of appropriate empirical antibiotics. This study aimed to explore the feasibility of antibiogram development for residential aged care facilities (RACFs). Retrospective observational study of culture and sensitivity data. Nine RACFs in Queensland, Australia. Available antimicrobial susceptibility results were collected retrospectively for all residents of recruited RACFs from January 1, 2020, to December 31, 2022. Data were managed and analyzed with WHONET software®, and antibiograms were developed in accordance with the CLSI-M39 guidelines. Antibiogram data beyond the standard 12-months and pooling of data from geographically similar RACFs were explored as options to improve feasibility and validity of the antibiograms. The most prevalent bacteria in the RACFs were Escherichia coli and Staphylococcus aureus. Due to the low number of positive cultures (less than 30) for individual RACFs, an annual antibiogram was not feasible. Extending the time-period to three years improved feasibility of antibiograms for E.coli in seven RACFs and S.aureus in five RACFs. Combining the data from closely located RACFs allowed for sufficient urinary and skin swab isolates to produce annual pooled antibiograms for all three years. Use of extended time period antibiograms can provide RACF specific urinary and skin/soft tissue resistance data without the necessity of private pathology provider input. However, pooled syndromic antibiograms can be made available on an annual basis, which may be the preferred option.

Advancing Boiling Histotripsy Dose in Ex Vivo And In Vivo Renal Tissues Via Quantitative Histological Analysis and Shear Wave Elastography

ObjectiveIn the context of developing boiling histotripsy (BH) as a potential clinical approach for non-invasive mechanical ablation of kidney tumors, the concept of BH dose (BHD) was quantitatively investigated in porcine and canine kidney models in vivo and ex vivo. MethodsVolumetric lesions were produced in renal tissue using a 1.5-MHz 256-element HIFU-array with various pulsing protocols: pulse duration tp = 1–10 ms, number of pulses per point ppp = 1–15. Two BHD metrics were evaluated: BHD1 = ppp, BHD2 = tp × ppp. Quantitative assessment of lesion completeness was performed by their histological analysis and assignment of damage score to different renal compartments (i.e., cortex, medulla, and sinus). Shear wave elastography (SWE) was used to measure the Young's modulus of renal compartments in vivo vs ex vivo, and before vs after BH treatments. ResultsIn vivo tissue required lower BH doses to achieve identical degree of fractionation as compared to ex vivo. Renal cortex (homogeneous, low in collagen) was equal or higher in stiffness than medulla (anisotropic, collagenous), 5.8–12.2 kPa vs 4.7–9.6 kPa, but required lower BH doses to be fully fractionated. Renal sinus (fatty, irregular, with abundant collagenous structures) was significantly softer ex vivo vs in vivo, 4.9–5.1 kPa vs 9.7–15.2 kPa, but was barely damaged in either case with any tested BH protocols. BHD1 was shown to be relevant for planning the treatment of renal cortex (sufficient BHD1 = 5 pulses in vivo and 10 pulses ex vivo), while none of the tested doses resulted in complete fractionation of medulla or sinus. Post-treatment SWE imaging revealed reduction of tissue stiffness ex vivo by 27–58%, increasing with the applied dose, and complete absence of shear waves within in vivo lesions, both indicative of tissue liquefaction. ConclusionThe results imply that tissue resistance to mechanical fractionation, and hence required BH dose, are not solely determined by tissue stiffness but also depend on its composition and structural arrangement, as well as presence of perfusion. The SWE-derived reduction of tissue stiffness with increasing BH doses correlated with tissue damage score, indicating potential of SWE for post-treatment confirmation of BH lesion completeness.

Isongifolene Improves Crohn's Disease-Like Colitis in Mice by Reducing Apoptosis of Intestinal Epithelial Cells

To investigate the effect and molecular mechanism of isolongifolene (ISO) on the apoptosis of intestinal epithelial cells and 2,4,6-trinitrobenzenesulfonic acid (TNBS)-induced Crohn's disease (CD)-like colitis in mice. In the animal experiments, mice were randomly assigned to the wild type (WT) group, TNBS group and TNBS+ISO group, with 8 mice in each group. Colitis models of mice were established in the TNBS group and the TNBS+ISO group by rectal injection of TNBS. After modeling, the mice in the TNBS+ISO group were given ISO intervention via intragastric gavage (10 mg/kg), and the other two groups were given the same amount of normal saline via intragastric gavage. The mice were sacrificed on the 7th day. The changes in body mass, disease activity scores (DAI), and the colon length of mice were measured, and transepithelial electrical resistance (TEER) of the colon tissues was determined. The score of colon inflammation was calculated according to HE staining. The levels of intestinal mucosal inflammatory factors, including tumor necrosis factor alpha (TNF-α), interferon (IFN)-γ, interleukin (IL)-1β, and IL-6, were measured by RT-PCR and ELISA. The apoptosis of colon tissue cells was determined by TUNEL assay. The expressions of apoptotic proteins (cleaved caspase-3/caspase-3 and Bax), an anti-apoptotic protein (Bcl-2), and tight junction proteins (ZO-1 and claudin-1) were detected by Western blot and immunofluorescence. In the cell experiment, TNF-α was used to induce intestinal epithelial cell Caco-2 apoptosis model, which was treated with ISO. Then, intervention with the AMPK inhibitor Compound C was given. TUNEL assay, Western blot assay, and immunofluorescence assay were performed to measure apoptosis and the expression of apoptosis proteins in the Caco-2 cells. Gene Ontology (GO) enrichment analysis was performed to predict the biological function of ISO. Then, the mechanism involved was verified by examination of the mice and Caco-2 cells. Western blot was performed to determine the expression levels of p-AMPK/AMPK and p-PGC1α in the colon tissues from the mice of different groups and Caco-2 cells. The apoptosis of the cells was determined by TUNEL assay. According to the results of the animal experiment, ISO could alleviate experimental colitis and intestinal barrier dysfunction, leading to improvements in body mass loss, colon length shortening, DAI score, inflammatory rating, and TEER values (all P<0.05) in mice. Furthermore, ISO decreased the expression of pro-inflammatory factors TNF-α, IFN-γ, IL-1β, and IL-6 and increased the expression of the tight junction proteins ZO-1 and claudin-1 (all P<0.05). In the cell experiment, in a TNF-α-induced intestinal epithelial cell model, ISO was also found to protect intestinal barrier against damage. ISO reduced the proportion of apoptotic intestinal epithelial cells, reduced the expression of cleaved-caspase-3/caspase-3 and Bax, and upregulated the level of Bcl-2 (all P<0.05). GO enrichment predictive analysis showed that the role of ISO in improving CD-like enteritis might be associated with the negative regulation of apoptosis. Verification of the mechanism showed that the expression of p-AMPK and p-PGC1α in the mice colon tissue was significantly upregulated after ISO intervention (P<0.05). In contrast, the AMPK inhibitor Compound C increased the apoptosis rate of ISO-treated Caco-2 cells and decreased the relative expression levels of ZO-1 and claudin-1 (P<0.05). ISO reduces intestinal epithelial cell apoptosis at least in part by activating AMPK/PGC1α signaling pathway, thereby alleviating TNBS-induced intestinal barrier dysfunction and CD-like colitis in mice.

CNPAS2 induced β cell dysfunction by regulating KANK1 expression in type 2 diabetes.

Diabetes mellitus type 2 (T2DM) is formed by defective insulin secretion with the addition of peripheral tissue resistance of insulin action. It has been affecting over 400 million people all over the world. To explore the pathogenesis of T2DM and to develop and implement new prevention and treatment strategies for T2DM. Receiver operating characteristic (ROC) curve analysis was used to conduct diagnostic markers. The expression level of genes was determined by reverse transcription-PCR as well as Western blot. Cell proliferation assays were performed by cell counting kit-8 (CCK-8) tests. At last, T2DM mice underwent Roux-en-Y gastric bypass surgery. We found that NPAS2 was significantly up-regulated in islet β cell apoptosis of T2DM. The ROC curve revealed that NPAS2 was capable of accurately diagnosing T2DM. NPAS2 overexpression did increase the level of KANK1. In addition, the CCK-8 test revealed knocking down NPAS2 and KANK1 increased the proliferation of MIN6 cells. At last, we found that gastric bypass may treat type 2 diabetes by down-regulating NPAS2 and KANK1. This study demonstrated that NPAS2 induced β cell dysfunction by regulating KANK1 expression in type 2 diabetes, and it may be an underlying therapy target of T2DM.

Remotely Powered Two-Wire Cooperative Sensors for Bioimpedance Imaging Wearables.

Bioimpedance imaging aims to generate a 3D map of the resistivity and permittivity of biological tissue from multiple impedance channels measured with electrodes applied to the skin. When the electrodes are distributed around the body (for example, by delineating a cross section of the chest or a limb), bioimpedance imaging is called electrical impedance tomography (EIT) and results in functional 2D images. Conventional EIT systems rely on individually cabling each electrode to master electronics in a star configuration. This approach works well for rack-mounted equipment; however, the bulkiness of the cabling is unsuitable for a wearable system. Previously presented cooperative sensors solve this cabling problem using active (dry) electrodes connected via a two-wire parallel bus. The bus can be implemented with two unshielded wires or even two conductive textile layers, thus replacing the cumbersome wiring of the conventional star arrangement. Prior research demonstrated cooperative sensors for measuring bioimpedances, successfully realizing a measurement reference signal, sensor synchronization, and data transfer though still relying on individual batteries to power the sensors. Subsequent research using cooperative sensors for biopotential measurements proposed a method to remove batteries from the sensors and have the central unit supply power over the two-wire bus. Building from our previous research, this paper presents the application of this method to the measurement of bioimpedances. Two different approaches are discussed, one using discrete, commercially available components, and the other with an application-specific integrated circuit (ASIC). The initial experimental results reveal that both approaches are feasible, but the ASIC approach offers advantages for medical safety, as well as lower power consumption and a smaller size.

Tailored lateral internal sphincterotomy (T-LIS) for chronic anal fissure by LigaSure Small Jaws©: a comparison with other non-conservative treatments for anal fissures

An anal fissure is a small tear in the thin tissue (mucosa) that lines the anus. Anal fissures typically cause pain and bleeding with bowel movements. The cause is not fully understood, but low intake of dietary fiber may be a risk factor. Chronic anal fissure was defined as a split or ulceration in the posterior or anterior anoderm for at least 6 weeks: have distinct anatomic features such as muscle fibers visible in the wound. Anal fissures can be attributed to constipation or repeated straining: a hard fecal bolus cut the mucosa of anal canal that is relatively thigh at sphincter level management and optimal treatment of the disease is controversial. Many studies recommend conservative and medical treatment modalities as the initial treatment options since they are non-invasive and do not have risks such as anal sphincter injury. Lateral internal sphincterotomy (LIS) is considered the gold standard for treatment of chronic anal fissure. Nonetheless, anal incontinence is one of the worrisome complications of LIS. Fissurectomy is another option among those techniques which address the issues with LIS. LigaSure© (Valleylab) is a bipolar electrosurgical device designed to deliver high current and very low voltage to tissue. It monitors tissue impedance between the jaws of the instrument and continuously adjusts the delivery of energy. The use of LigaSure Small Jaw was never reported for anal fissures in literature. We have applied the use of this device to a group of patients complaining for chronic anal fissure in order to verify if there is any advantage to perform it compared to traditional technique (blade, scissors, electrocautery).

Discovery of tetrahydro γ-carboline based novel glucose uptake agent for the treatment of diabetes and Alzheimer’s diseases

The emergence of diabetes mellitus (DM), one of the prevalent metabolic disorders, has increased at alarming rates around the globe in the past few decades. The early discovery of insulin paved the way for the broadened non-invasive anti-hyperglycemic drug therapies to manage and treat diabetes. Recently, insulin resistance in brain tissues has been considered a new hallmark of disease progression, leading to neurodegeneration. Tetrahydro γ-carbolines are privileged scaffolds with various activities against obesity, cancer, and central nervous system (CNS) diseases. The failure of Latrepirdine in clinical phase trials as anti-AD, prompted us to explore further the γ-Carboline derivatives with anti-diabetic activity. To address this, we have leveraged our expertise in drug design to develop tetrahydro γ-carboline derivatives and studied their effect on glucose uptake. All the compounds exhibited low cytotoxicity towards the mammalian cell line 3T3-L1. Next, we screened the 10 derivatives to identify the novel anti-diabetic activities using a fluorescent glucose analog 2-NBDG (2-(N-(7-nitrobenz-2-oxa-1, 3-diazol-4-yl)-2-deoxy-D-glucose) based on a glucose-uptake assay in differentiated 3T3-L1 adipocytes. Compound 11a has significantly increased glucose uptake at 100 µM compared to rH-Insulin. The dose optimization (1 nM-100 nM) of lead compounds for 2-NBDG-glucose uptake clearly indicated that 11a is superior compared to Insulin. The 11a is the close analog of Latrepirdine, an anti-histamine drug, reported for Alzheimer disease (AD). Further, to understand its anti-AD potential we carried out in silico docking studies with its probable targets, Acetylcholinesterase (AChE), 5-hydroxytryptamine (5HT6) receptor, Butyrylcholinesterase (BChE), and N-methyl-D-aspartate (NMDA) receptor. The docking studies revealed that 11a had stronger binding to these targets than Latrepirdine, correlating with the glucose uptake assay. Thus, 11a is a potential lead disease-modifying agent and could be considered for the management and treatment of type 2 DM and AD.

353. INNOVATIVE SURGICAL TECHNIQUES TO REDUCE RECURRENCE IN LAPAROSCOPIC RADICAL TREATMENT OF GIANT HIATAL HERNIA

Abstract Background In Japan, there is an increasing trend in the number of esophageal hiatal hernia (EHH) surgeries performed in elderly patients. EHH in the elderly patients are associated with surgical invasiveness and complications, but safe surgery can contribute to improving quality of life (QOL). We report on the safe surgical technique and treatment results for giant hiatal hernia. Methods The most important point to be careful of when suturing the esophageal hiatus is damage to the diaphragm leg. If the esophageal hiatus is large, reducing the pneumoperitoneum pressure as much as possible will reduce the tissue resistance during suturing, allowing suture closure without placing excessive tension on the diaphragm legs. If the esophageal hiatus is large, the pneumoperitoneum pressure should be kept as low as possible to reduce tissue resistance during suturing and prevent damage to the diaphragm legs. Surgery is usually performed with a high pneumo-abdominal pressure of 10 mmHg, but if suture closure of the esophageal hiatus is difficult, suturing is performed with a low pneumo-abdominal pressure of 6 mmHg. We underwent 103 cases of EHH surgery between 2012 and 2022. There were 73 cases (70.8%) of over 75 years old patients, and 71 cases (68.9%) of giant mixed type EHH. We compared the surgical outcomes in the early group up to 2018, in which surgery was performed with high pneumo-abdominal pressure during hiatal closure, and the latter group, from 2019 onwards, in which surgery was performed with low pneumo-abdominal pressure during hiatal closure. Results 67 cases in the early group: 23 cases with sliding type/44 cases with mixed type (65.6%), 36 cases in the latter group: 8 cases with sliding type/27 cases with mixed type (75.0%), the proportion of mixed type was higher in the late group. Mesh was used in 1 case in the early group and 0 cases in the latter group. The recurrence rate was 7 cases (10.4%) in the early group and 1 case (2.8%) in the late group, and although the proportion of mixed type cases was higher in the latter group, the recurrence rate was lower. Reoperation for recurrence was performed in 1 patient in the early group. In one case of recurrent surgery in the early group, the type of recurrence was that the muscle bundle of the diaphragm leg on one side was torn, the hiatus was dilated, and the transverse colon was invaginated into the mediastinum. From this experience, I reaffirmed the importance of reliably suturing the esophageal hiatus without damaging tissue in order to reduce recurrence of giant hiatal hernia surgery. Although there are differences in observation periods, in recent years, appropriate management of intraoperative pneumoperitoneum pressure has been able to reduce recurrence and complications, and it has also been possible to safely improve QOL in elderly patients. Conclusions In giant hiatal hernia surgery, appropriate control of intraoperative pneumoperitoneum pressure can reduce recurrence.

Effect of sequential delivery of 1- and 2-MHz bipolar microneedling radiofrequency energy on thermal tissue reactions in a minipig model.

Bipolar microneedling radiofrequency (RF) treatment generates different patterns of thermal reactions, depending on the skin impedance and RF treatment parameters, including the frequency, power, conduction time, settings of sub-pulse packs, and penetrating depth and type of microneedles used. We compared the effect of sequential delivery of 1- and 2-MHz bipolar RF energy to in vivo minipig skin on thermal tissue reaction. RF treatments at frequencies of 1 and 2MHz were sequentially delivered to minipigs' skin in vivo. A histological study was performed to analyze RF-induced skin reactions at 1-h and at 3-, 7-, and 14-days post-treatment. The skin specimens demonstrated that the two different frequencies of RF treatment generated mixed patterns of the peri-electrode coagulative necrosis (PECN) according to the experimental settings and tissue impedance. In the PECN zone, the tissue coagulation induced by the first RF treatment was surrounded by the effect of the later RF treatment at the other RF frequency. In the inter-electrode non-necrotic thermal reaction zone, the effect of the latter RF treatment was widespread and deep through the dermis, which had received RF treatment at the other frequency first. The delivery of pulsed-type RF energy at sub-pulse packs of 6 or 10 provided effective RF delivery over long conduction time without excessive thermal damage of the epidermis. Nonetheless, by sequential delivery of two different RF frequencies, RF-induced tissue reactions were found to be markedly enhanced. The sequential delivery of 1- and 2-MHz RF energy induces novel histological patterns of tissue reactions, which can synergistically enhance the thermostimulatory effects of each RF setting. Moreover, variations in patterns of tissue reactions can be generated by regulating the order of frequencies and the number of sub-pulse packs of RF used.

A controlled release antibiotic wound protectant gel formulated for use in austere environments.

Battlefield wounds are at high risk of infection due to gross contamination and delays in evacuation from forward-deployed locations. The aim of this study was to formulate an antibiotic wound gel for application by a field medic in austere environments to protect traumatic wounds from infection during transport. Formulation development was conducted over multiple phases to meet temperature, handling, in vitro elution, and in vivo tissue response requirements. Thermal properties were evaluated by vial inversion, DSC, and syringe expression force in a temperature range of 4-49°C. Handling was evaluated by spreading onto blood-contaminated tissue and irrigation resistance. Controlled antibiotic release was evaluated by a modified USP immersion cell dissolution method. Local tissue effects were evaluated in vivo by subcutaneous implantation in rats for 7 and 28 days. An oleogel composition of cholesterol, hydrogenated castor oil, soybean oil, and glyceryl monocaprylocaprate met the target performance criteria. Peak expression force from a 5 mL syringe at 4°C was 48.3 N, the dropping point temperature was 68°C, and the oleogel formulation could be spread onto blood-contaminated tissue and resisted aqueous irrigation. The formulation demonstrated sustained release of tobramycin in PBS at 32°C for 5 days. Implantation in a rat dorsal pocket demonstrated a slight tissue reaction after 7 days with minimal to no reaction after 28 days, comparable to a commercial hemostat control. Material resorption was evident after 28 days. The formulation met target characteristics and is appropriate for further evaluation in a large animal contaminated blast wound model.

Drying the mystery: a novel electronic sensor to quantify soft-tissue desiccation and natural mummification for forensic taphonomy

This study investigates the desiccation process of soft-tissue in South Africa, analyzing its interaction with environmental parameters and its implications for estimating the post-mortem interval. Through the examination of four decomposing porcine bodies across two summer seasons and one winter season, the research quantifies desiccation patterns using custom-designed and constructed printed circuit boards to measure the moisture content of body tissue over time. Generalized additive models were used to determine the environmental forces driving desiccation. Tissue resistivity was tested against the environmental predictor variables to determine the amount of variation they account for, and predicted values of the region-specific tissue resistivity variables were measured for each decomposing body. Results reveal distinct desiccation trajectories between summer and winter, with summer conditions conducive to precocious natural mummification. Environmental factors, particularly temperature and solar radiation, emerge as significant drivers of desiccation. This study represents the first quantitative analysis of deep tissue desiccation internationally, but also the first quantitative assessment of desiccation and natural precocious mummification in the Western Cape, South Africa. The exploration of desiccation as a potential indicator for estimating PMI opens new avenues for research and the integration of innovative methodologies and technologies promises to revolutionize forensic taphonomy practices.

Role of impedance drop and lesion size index (LSI) to guide catheter ablation for atrial fibrillation.

When using lesion size index (LSI) to guide catheter ablation, it is unclear what combination of power, contact force and time would be preferable to use and what LSI target value to aim for. This study aimed at identifying desirable ablation settings and LSI targets by using tissue impedance drop as indicator of lesion formation. Consecutive patients, undergoing their first left atrial (LA) catheter ablation for atrial fibrillation, with radiofrequency energy (RF) powers of 20, 30 and 40W were enrolled. Tissue impedance, contact force (CF), Force Time Integral (FTI) and LSI values were continuously recorded during ablation and sampled at 100Hz. Mean CF and Contact Force Variability (CFV) were calculated for every lesion. The effect of RF power, ablation time, CF and CFV on impedance drop and LSI were assessed. A total of 3258 lesions were included in the analysis. For any target LSI value, use of higher RF powers translated into progressively higher impedance drops. The impact of lower CF and higher CFV on impedance drop was more relevant when using lower powers. Target LSI values corresponding to maximum impedance drop were identified depending on RF power, mean CF and CFV used. Even in the context of an LSI-guided ablation strategy, use of lower or higher powers might lead to different lesion sizes. Different LSI targets might be needed depending on the combination of RF power, CF and CFV used for ablation. Incorporating indicators of catheter stability, like CFV, in the LSI formula could improve the predictive value of LSI for lesion size. Studies with clinical outcomes are required to confirm the clinical relevance of these findings.

Intraoperative pelvic neuromonitoring based on bioimpedance signals: a new method analyzed on 30 patients

PurposeIncreasing importance has been attributed in recent years to the preservation of the pelvic autonomic nerves during rectal resection to achieve better functional results. In addition to improved surgical techniques, intraoperative neuromonitoring may be useful.MethodsThis single-arm prospective study included 30 patients who underwent rectal resection performed with intraoperative neuromonitoring by recording the change in the tissue impedance of the urinary bladder and rectum after stimulation of the pelvic autonomic nerves. The International Prostate Symptom Score, the post-void residual urine volume and the Low Anterior Resection Syndrome Score (LARS score) were assessed during the 12-month follow-up period.ResultsA stimulation-induced change in tissue impedance was observed in 28/30 patients (93.3%). In the presence of risk factors such as low anastomosis, neoadjuvant radiotherapy and a deviation stoma, an average increase of the LARS score by 9 points was observed 12 months after surgery (p = 0,04). The function of the urinary bladder remained unaffected in the first week (p = 0,7) as well as 12 months after the procedure (p = 0,93).ConclusionThe clinical feasibility of the new method for pelvic intraoperative neuromonitoring could be verified. The benefits of intraoperative pelvic neuromonitoring were particularly evident in difficult intraoperative situations with challenging visualization of the pelvic nerves.

Circ_0002722-induced regulation of YAP promotes platinum resistance in oral squamous cell carcinoma: Implications for verteporfin therapy

Oral squamous cell carcinoma (OSCC) poses a significant public health burden due to its high prevalence and poor prognosis. Platinum resistance is one of the major challenges in OSCC treatment. Yes-associated protein (YAP) has been identified as a pivotal player in OSCC tumorigenesis and progression. Circular RNA (circRNA) has been implicated in chemoresistance in various cancers by regulation the function of microRNA. Nevertheless, the specific mechanisms linking circRNA to YAP expression in OSCC remain poorly understood. In this study, we detected the YAP and circRNA hsa_circ_0002722 (circ_0002722) expression by western blot (WB) and quantitative polymerase chain reaction (qPCR). We found that YAP and circ_0002722 were up-regulated in platinum resistance in OSCC tissues. Furthermore, transfection of circ_0002722 siRNA into platinum-resistant cells revealed that circ_0002722 acted as a regulator of miR-1305, which influenced YAP expression and thereby affected platinum sensitivity. In vivo experiments corroborated the synergistic effects of cisplatin and verteporfin (a YAP inhibitor) in combating platinum resistance. Targeting YAP emerges as a promising therapeutic strategy for addressing platinum resistance in OSCC, with circ_0002722 serving as a potential therapy target and valuable diagnostic marker. These findings shed light on the underlying mechanisms of platinum resistance, paving the way for the development of effective treatment approaches.

Assessment of Intraday Variations in Skin Indentation Resistance.

Information about the mechanical properties of skin and their changes with age and other conditions is important to help characterize skin physiology and pathological changes. One method to obtain this information is to measure the force required to indent the skin to a specified indentation depth (FORCE). This process measures the tissue's resistance to indentation or its compressibility and is related to the tissue's elastic modulus. Since such measurements are made in clinical and other settings at various times of day (TOD), it is useful to estimate the extent of intraday variations in FORCE that may be expected. This report focuses on this issue. FORCE was self-measured on the volar forearm, 5 cm distal to the antecubital fossa, every two hours from 08:00 to 24:00 hours on two consecutive days by 12 medical students (six females and six males) who were trained in the measurement process using an indentation device (SkinFibroMeter). Variability in FORCE versus TOD was analyzed using the nonparametric Friedman test and differences between genders by the nonparametric Wilcoxon test. Differences between the first day (day 1) and the second day (day 2) were tested at each TOD. The whole-body fat percentage (FAT%) and water percentage (H2O%) were determined for each participant via bioimpedance measurements at 50 KHz. The age and BMI of the combined group (mean ± SD) were 24.5 ± 1.5 years and 23.2 ± 3.3 kg/m2.The overall average FORCE (mean ± SD) for the day over the 16 hours was 84.1 ± 22.7 mN and for day 2, it was 83.4 ± 28.5 mN with no significant difference between day 1 and day 2. For females, the overall two-day average FORCE (mean ± SD) over the 16 hours was 81.8 ± 20.3 mN and for males, it was 85.7 ± 30.1 mN with no significant difference between them (p = 0.271). Overall, there was no statistically significant difference in FORCE among TOD (p = 0.568). FORCE was not correlated with either FAT%, HTO%, or BMI. The findings indicate no statistically significant variation in indentation force in females, males, or combined concerning the TODof the measurement or differences between consecutive days at corresponding times. This suggests that whether such measurements are done in a research setting or within a clinic, they can be done at various TODwith minimal expected variation for a given subject. However, an extension of these findings to persons with skin conditions or ages not herein evaluated must await further study.

Reverberating Action Potentials and the Emergence of Short Circuit Propagation in Gliosis

This study explores the intriguing phenomenon of action potentials reverberating and propagating in high-resistance tissues, such as gliosis, leading to the emergence of short circuits within the brain. Gliosis, characterized by increased tissue resistance, presents a unique environment for electrical signals. My research investigates the possible mechanisms behind these reverberations and their role in the creation of self-empowering short circuits that can potentially affect the entire brain's functionality. Understanding these processes may have significant implications for the treatment and management of neurological disorders associated with gliosis and abnormal electrical activity in the brain.

Review of clinical practice guidelines for hypoparathyroidism

Hypoparathyroidism is an endocrine disease characterized by reduced production of parathyroid hormone by the parathyroid glands or tissue resistance to its action. This is accompanied by disturbances in phosphorus-calcium metabolism.The main cause of hypoparathyroidism is damage or removal of the parathyroid glands during surgery on the neck organs. Autoimmune hypoparathyroidism is the second most common form of the disease, which occurs, as a rule, within the autoimmune polyglandular syndrome type 1.The development of chronic hypoparathyroidism of any etiology requires lifelong appointment of multicomponent therapy, as well as careful monitoring and an individual approach. In the absence of adequate dynamic monitoring, multiple complications develop from vital organs, in particular calcification of the urinary system, soft tissues and the brain; cardiovascular pathology; visual disturbances; muscle and bone diseases leading to decreased quality of life of patients.Thus, timely diagnosis, rationally selected drug therapy and competent patient management will reduce the risks of complications, improve the prognosis, and reduce the frequency of hospitalizations and disability of patients with chronic hypoparathyroidism.The article presents the main recommendations of the new project of clinical guidelines for patients with hypoparathyroidism, approved by the Ministry of Health of the Russian Federation in 2021. They include the algorithms of diagnosis, treatment and dynamic monitoring of hypoparathyroidism, as well as management of postsurgical hypocalcemia and medical care of and the disease during pregnancy.