Biaxial Tensile Strain Enhances Electron Mobility of Monolayer Transition Metal Dichalcogenides.

Strain engineering can modulate the properties of two-dimensional (2D) semiconductors for electronic and optoelectronic applications. Recent theory and experiments have found that uniaxial tensile strain can improve the electron mobility of monolayer MoS2, a 2D semiconductor, but the effects of biaxial strain on charge transport are not well characterized in 2D semiconductors. Here, we use biaxial tensile strain on flexible substrates to probe electron transport in monolayer WS2 and MoS2 transistors. This approach experimentally achieves ∼2× higher on-state current and mobility with ∼0.3% applied biaxial strain in WS2, the highest mobility improvement at the lowest strain reported to date. We also examine the mechanisms behind this improvement through density functional theory simulations, concluding that the enhancement is primarily due to reduced intervalley electron-phonon scattering. These results underscore the role of strain engineering in 2D semiconductors for flexible electronics, sensors, integrated circuits, and other optoelectronic applications.

Therapeutic perspectives on PDE4B inhibition in adipose tissue dysfunction and chronic liver injury.

INTRODUCTION: Chronic liver disease (CLD) is a complex disease associated with profound dysfunction. Despite an incredible burden, the first and only pharmacotherapy for metabolic-associated steatohepatitis was only approved in March of this year, indicating a gap in the translation of preclinical studies. There is a body of preclinical work on the application of phosphodiesterase 4 inhibitors in CLD, none of these molecules have been successfully translated into clinical use. AREAS COVERED: To design therapies to combat CLD, it is essential to consider the dysregulation of other tissues that contribute to its development and progression. As such, proper therapies must combat this throughout the body rather than focusing only on the liver. To detail this, literature characterizing the pathogenesis of CLD was pulled from PubMed, with a particular focus placed on the role of PDE4 in inflammation and metabolism. Then, the focus is shifted to detailing the available information on existing PDE4 inhibitors. EXPERT OPINION: This review gives a brief overview of some of the pathologies of organ systems that are distinct from the liver but contribute to disease progression. The demonstrated efficacy of PDE4 inhibitors in other human inflammatory diseases should earn them further examination for the treatment of CLD.

Relaxin-2 is a novel biomarker for differentiated thyroid carcinoma in humans.

Relaxin's role in differentiated thyroid cancer (DTC) has been suggested but its characterization in a large clinical sample remains limited. We performed immunohistochemistry for relaxin-2 (RLN2), CD68 (total macrophages), CD163 (M2 macrophages) on tissue microarrays from 181 subjects with non-distant metastatic DTC, and 185 subjects with benign thyroid tissue. Mean pixels/area for each marker was compared between tumor and adjacent tissue via paired-t test and between DTC and benign subjects via t-test assuming unequal variances. RNA qPCR was performed for expression of RLN2, RLN1, and RXFP1 in cell lines. Amongst 181 cases, the mean age was 46 years, 75 % were females. Tumoral tissue amongst the DTC cases demonstrated higher mean expression of RLN2 (53.04 vs. 9.79; p < 0.0001) compared to tumor-adjacent tissue. DTC tissue also demonstrated higher mean expression of CD68 (14.46 vs. 4.79; p < 0.0001), and CD163 (23.13 vs. -0.73; p < 0.0001) than benign thyroid. These markers did not differ between tumor-adjacent and benign thyroid tissue groups; and amongst cases, did not differ by demographic or clinicopathologic features. RLN1 and RXFP1 expression was detected in a minority of the cell lines, while RLN2 was expressed by 6/7 cell lines. In conclusion, widespread RLN2 expression in DTC tissue and most cell lines demonstrates that RLN2 acts in a paracrine manner, and that RLN1 and RXFP1 are probably not involved in thyroid cancer cell signaling. RLN2 is a biomarker for thyroid carcinogenesis, being associated with but not secreted by immunosuppressive macrophages. These findings will guide further investigations for therapeutic avenues against thyroid cancer.

Modified Graham Patch Repair of Small Bowel Anastomotic Leak.

The modified Graham patch repair is a well-established technique for management of perforating foregut injuries, often learned by surgeons during general surgery training. There is, however, little to no data regarding the utilization of this technique for perforation of the distal midgut or in the re-operative field. We present two cases of midgut anastomotic complications successfully managed with modified graham patch repair at our institution. The first case is a 79-year-old female who underwent an emergent right hemicolectomy at an outside institution for management of an iatrogenic perforation during endoscopic polypectomy. Over the course of two years she underwent numerous abdominal operations, due to various complications, ultimately resulting in multiple resections and end ileostomy creation. She then had her ileostomy reversed by laparoscopic single incision (SILS) technique at our institution. This was also complicated by anastomotic leak. Intraoperatively, adequate mobilization of the anastomosis for resection was deemed not safe due to dense fibrosis and adhesions in the re-operative field; therefore, she underwent a SILS modified Graham patch repair of an ileocolic anastomotic defect with diverting loop ileostomy. Post-operatively, she had no radiographic evidence of leak from the repaired anastomosis, which facilitated successful loop ileostomy reversal five months later. Our second case is a 64-year-old male referred to our institution for management of his stage IV colon cancer. He underwent an open right hemicolectomy and hepatic metastectomy, which was complicated by anastomotic leak. The small defect was repaired via a SILS modified Graham patch technique. Five months postoperatively, he had neither radiographic nor endoscopic evidence of a leak; therefore, he successfully underwent ileostomy reversal without complication. We encourage further investigation and reporting of the role of the modified graham patch repair in management of midgut anastomotic complications, particularly when resection and re-anastomosis is unsafe due to a hostile re-operative field.

Examining surgeon stress in robotic and laparoscopic surgery.

Robotic surgery may decrease surgeon stress compared to laparoscopic. To evaluate intraoperative surgeon stress, we measured salivary alpha-amylase and cortisol. We hypothesized robotic elicited lower increases in surgeon salivary amylase and cortisol than laparoscopic. Surgical faculty (n = 7) performing laparoscopic and robotic operations participated. Demographics: age, years in practice, time using laparoscopic vs robotic, comfort level and enthusiasm for each. Operative data included operative time, WRVU (surgical "effort"), resident year. Saliva was collected using passive drool collection system at beginning, middle and end of each case; amylase and cortisol measured using ELISA. Standard values were created using 7-minute exercise (HIIT), collecting saliva pre- and post-workout. Linear regression and Student's t test used for statistical analysis; p values < 0.05 were significant. Ninety-four cases (56 robotic, 38 laparoscopic) were collected (April-October 2022). Standardized change in amylase was 8.4 ± 4.5 (p < 0.001). Among operations, raw maximum amylase change in laparoscopic and robotic was 23.4 ± 11.5 and 22.2 ± 13.4; raw maximum cortisol change was 44.21 ± 46.57 and 53.21 ± 50.36, respectively. Values normalized to individual surgeon HIIT response, WRVU, and operative time, showing 40% decrease in amylase in robotic: 0.095 ± 0.12, vs laparoscopic: 0.164 ± 0.16 (p < 0.02). Normalized change in cortisol was: laparoscopic 0.30 ± 0.44, robotic 0.22 ± 0.4 (p = NS). On linear regression (p < 0.001), surgeons comfortable with complex laparoscopic cases had lower change in normalized amylase (p < 0.01); comfort with complex robotic was not significant. Robotic may be less physiologically stressful, eliciting less increase in salivary amylase than laparoscopic. Comfort with complex laparoscopic decreased stress in robotic, suggesting laparoscopic experience is valuable prior to robotic.

Synthesis of core@shell catalysts guided by Tammann temperature.

Designing high-performance thermal catalysts with stable catalytic sites is an important challenge. Conventional wisdom holds that strong metal-support interactions can benefit the catalyst performance, but there is a knowledge gap in generalizing this effect across different metals. Here, we have successfully developed a generalizable strong metal-support interaction strategy guided by Tammann temperatures of materials, enabling functional oxide encapsulation of transition metal nanocatalysts. As an illustrative example, Co@BaAl2O4 core@shell is synthesized and tracked in real-time through in-situ microscopy and spectroscopy, revealing an unconventional strong metal-support interaction encapsulation mechanism. Notably, Co@BaAl2O4 exhibits exceptional activity relative to previously reported core@shell catalysts, displaying excellent long-term stability during high-temperature chemical reactions and overcoming the durability and reusability limitations of conventional supported catalysts. This pioneering design and widely applicable approach has been validated to guide the encapsulation of various transition metal nanoparticles for environmental tolerance functionalities, offering great potential to advance energy, catalysis, and environmental fields.

Fertility sparing double discoid excision of rectosigmoid deep endometriosis under robotic-integrated ultrasound guidance.

OBJECTIVE: To present the use of robotic-integrated ultrasound for performing a double discoid excision of multifocal rectosigmoid endometriosis. DESIGN: Video article. STATEMENT OF CONSENT: The patient included in this video gave consent for publication of the video and posting of the video online, including social media, journal website, scientific literature websites (such as PubMed, ScienceDirect, Scopus), and other applicable sites. PATIENT: A 26-year-old G0 woman with chronic pelvic pain, dyschezia, and dysmenorrhea refractory to medical management desired future fertility. Imaging was suggestive of deep infiltrating endometriosis involving the rectosigmoid colon. INTERVENTION: Not applicable. MAIN OUTCOME MEASURES: Double discoid excision of multifocal rectosigmoid endometriosis using robotic-integrated ultrasound. RESULTS: Not applicable. CONCLUSIONS: Performing a complete preoperative evaluation in patients with suspected endometriosis is important for determining the extent of disease and necessity of a multidisciplinary approach. Robotic-integrated ultrasound can provide additional information, including the size and depth of bowel endometriosis lesions, which can play a role in surgical decision making. Performing a double discoid excision of multifocal rectosigmoid endometriosis using robotic-integrated ultrasound is a technique that can avoid the need for a segmental bowel resection.

Optimizing mood prior to influenza vaccination in older adults: A three-arm randomized controlled trial.

OBJECTIVE: This trial explored the psychological and immunological effects of two brief interventions, targeting improving positive mood, administered to older adults immediately prior to influenza vaccination. The primary aim was to examine whether the interventions resulted in greater positive mood compared to usual care, and if so, which was superior. Secondary outcomes included antibody responses to vaccination and feasibility of collecting clinical outcome data (e.g., respiratory infections). METHOD: Six hundred and fifty-four older adults (65-85 years) participated in a three-arm, parallel, randomized controlled trial between September 2019 and May 2020. Immediately prior to receiving an adjuvanted trivalent influenza vaccine (Fluad, Seqirus UK Ltd), participants viewed one of two brief (15-min) video-based positive mood interventions (one fixed content, one allowing participant choice) or received usual care. State affect was measured immediately prior to, and following, intervention exposure or usual care. Antibody responses were measured prevaccination and 4 weeks postvaccination. Clinical outcomes were extracted from primary care records for 6 months following vaccination. RESULTS: Both interventions were equally effective at improving mood prior to vaccination compared to usual care. Antibody responses were highly robust with postvaccination seroprotection rates of > 88% observed for all vaccine strains. Antibody responses did not significantly differ between groups. Clinical outcome data were feasible to collect. CONCLUSIONS: Brief psychological interventions can improve mood prior to vaccination. However, altering antibody responses to highly immunogenic adjuvanted vaccines may require more targeted or prolonged interventions. The provision of choice did not notably enhance the interventions impact on mood or antibody outcomes. (PsycInfo Database Record (c) 2024 APA, all rights reserved).

Reduction in Obesity-Related Hepatic Fibrosis by SR1664.

Peroxisome-proliferator-activated receptor gamma (PPARγ) is a transcription factor with adipogenic, insulin-sensitizing, and antifibrotic properties. Strong PPARγ activators, such as the thiazolidinediones, can induce unwanted effects such as edema, weight gain, and bone loss, and therefore selective modulators of PPARγ are in development. We previously reported that one selective PPARγ modulator, SR1664, reduced toxin-induced hepatic fibrosis and the activation of hepatic stellate cells (HSCs), the main collagen-producing liver cell in fibrosis. In this study, we used a high fat and high carbohydrate (HFHC) model of hepatic steatosis and fibrosis to determine the effect of SR1664. Mice were placed on a standard chow or HFHC diet for 16 weeks, with SR1664 or control treatment for the final 4 weeks. SR1664 did not alter weight gain or fasting insulin or glucose levels. The size of lipid droplets in the HFHC group was reduced by SR1664, but there was no effect on total liver triglyceride levels. The degree of fibrosis was significantly reduced by SR1664 in mice on the HFHC diet, and this was accompanied by a decrease in activated HSC. In summary, SR1664 improved insulin sensitivity and reduced fibrosis in the HFHC diet, suggesting selective PPARγ modulation is effective in obesity-related liver fibrosis.

Deep Endometriosis of the Terminal Ileum Presenting With Cyclic Recurrent Small Bowel Obstruction.

Here, we discuss a case of a 42-year-old premenopausal female who presented with chronic pelvic pain and recurrent small bowel obstruction during menstruation. The patient reported a nine-year history of pelvic pain and a four-year history of episodic small bowel obstruction requiring multiple prior inpatient admissions. During these admissions, the obstruction was managed conservatively with bowel rest and nasogastric tube placement; however, symptoms would recur with subsequent menstrual cycles. Computed tomography showed diffusely dilated loops of small bowel with a transition point in the central anterior pelvis, and magnetic resonance enterography revealed a mass-like area involving small bowel loops in the mid pelvis. The patient underwent laparoscopic surgical intervention including bowel resection with re-anastomosis, hysterectomy, bilateral salpingectomy, and left oophorectomy. Intraoperative findings included severe distention of the proximal bowel with a discrete deep endometriosis lesion of the terminal ileum which was confirmed on final pathologic examination. This case emphasizes the importance of considering endometriosis as the etiology of recurrent catamenial small bowel obstruction, particularly in premenopausal women.

Laparoscopic vs. robotic colectomy for left-sided diverticulitis.

Diverticulitis is a prevalent gastrointestinal disease that often warrants surgical intervention. However, the optimal approach between traditional laparoscopy (LC) and robotic-assisted laparoscopy (RAC) for diverticulitis remains unclear. Our research compares these techniques in patients diagnosed with left-sided diverticulitis treated at a single, tertiary referral center from 2019 to 2022. Among the 134 patients, 86 underwent laparoscopic and 48 robotic-assisted surgeries. The surgeries included in this analysis are left colectomy, sigmoid colectomy, low anterior resection, and Hartmann's procedure. Primary outcomes were major morbidity and 30-day mortality. Secondary outcomes were operative time, conversion to open, length of stay, unplanned return to the operating room, 30-day readmission rate, and overall morbidity. While demographics and comorbidities were similar for both groups, the robotic-assisted group displayed a statistically significant longer operative time (198.0 ± 84.4 LC vs. 264.8 ± 78.5 min RAC, p < 0.001). When investigated further, there was a significant difference in operative time for uncomplicated diverticulitis cases favoring the LC approach (169.17 ± 58.1 LC vs. 244.82 ± 58.79 min RAC, p < 0.001). This significant difference, however, was not present in complicated diverticulitis cases. Other factors, such as overall and major morbidity, rate of conversion to open approach, ostomy creation, estimated blood loss, time to return of bowel function, length of stay, and 30-day readmission rate, did not significantly differ between the groups. There was no 30-day mortality in either group. Favorable patient outcomes, lack of significant difference in operative time compared with traditional laparoscopy, and absence of differences in morbidities or efficacy, raises an interesting question in the world of minimally invasive surgery: is the robotic-assisted approach emerging as the advantageous approach for complicated diverticulitis cases? We encourage additional, multi-center analysis of specifically complicated diverticulitis managed with both surgical approaches to investigate if these findings are replicated outside of our institution.

Laparoscopic shaving of rectosigmoid deep infiltrating endometriosis under laparoscopic ultrasound guidance.

OBJECTIVE: To present laparoscopic shaving of rectosigmoid endometriosis using the novel approach of laparoscopic ultrasound guidance to enhance complete excision. DESIGN: Video article. SETTING: Academic Tertiary Hospital. PATIENT(S): A 41-year-old G3P2012 female with longstanding history of pelvic pain refractory to medical management. Imaging was suggestive of deep infiltrating endometriosis involving the rectosigmoid colon. INTERVENTION(S): Laparoscopy for rectosigmoid endometriosis with the use of intraoperative ultrasound. MAIN OUTCOME MEASURE(S): Laparoscopic excision of rectosigmoid endometriosis under ultrasound guidance. RESULT(S): N/A. CONCLUSION(S): It is important to perform a complete pre-operative evaluation to determine the extent of disease and the necessity of a multidisciplinary approach. Intraoperative laparoscopic ultrasound can provide additional information including size and depth of lesions, which could play a role in surgical decision making. Laparoscopic ultrasound may enhance complete excision of deep endometriosis lesions and decrease the incidence of recurrence.

Alcohol-induced tubulin post-translational modifications directly alter hepatic protein trafficking.

BACKGROUND: Chronic ethanol exposure leads to enhanced protein acetylation and acetaldehyde adduction. Of the multitude of proteins that are modified on ethanol administration, tubulin is among the best studied. However, an open question is whether these modifications are observed in patient samples. Both modifications have also been implicated in promoting alcohol-induced defects in protein trafficking, but whether they do so directly is also unanswered. METHODS AND RESULTS: We first confirmed that tubulin was hyperacetylated and acetaldehyde-adducted in the livers from ethanol-exposed individuals to a similar extent as observed in the livers from ethanol-fed animals and hepatic cells. Livers from individuals with nonalcohol-associated fatty liver showed modest increases in tubulin acetylation, whereas nonalcohol-associated fibrotic human and mouse livers showed virtually no tubulin modifications. We also asked whether tubulin acetylation or acetaldehyde adduction can directly explain the known alcohol-induced defects in protein trafficking. Acetylation was induced by overexpressing the α-tubulin-specific acetyltransferase, αTAT1, whereas adduction was induced by directly adding acetaldehyde to cells. Both αTAT1 overexpression and acetaldehyde treatment significantly impaired plus-end (secretion) and minus-end (transcytosis)-directed microtubule-dependent trafficking and clathrin-mediated endocytosis. Each modification led to similar levels of impairment as observed in ethanol-treated cells. The levels of impairment by either modification showed no dose dependence or no additive effects suggesting that substoichiometric tubulin modifications lead to altered protein trafficking and that lysines are not selectively modified. CONCLUSIONS: These results not only confirm that enhanced tubulin acetylation is observed in human livers but that it is most relevant to alcohol-induced injury. Because these tubulin modifications are associated with altered protein trafficking that alters proper hepatic function, we propose that changing the cellular acetylation levels or scavenging free aldehydes are feasible strategies for treating alcohol-associated liver disease.

Detection of microplastics in human saphenous vein tissue using µFTIR: A pilot study.

Microplastics (MPs) are ubiquitous in the environment, in the human food chain, and have been recently detected in blood and lung tissues. To undertake a pilot analysis of MP contamination in human vein tissue samples with respect to their presence (if any), levels, and characteristics of any particles identified. This study analysed digested human saphenous vein tissue samples (n = 5) using µFTIR spectroscopy (size limitation of 5 µm) to detect and characterise any MPs present. In total, 20 MP particles consisting of five MP polymer types were identified within 4 of the 5 vein tissue samples with an unadjusted average of 29.28 ± 34.88 MP/g of tissue (expressed as 14.99 ± 17.18 MP/g after background subtraction adjustments). Of the MPs detected in vein samples, five polymer types were identified, of irregular shape (90%), with alkyd resin (45%), poly (vinyl propionate/acetate, PVAc (20%) and nylon-ethylene-vinyl acetate, nylon-EVA, tie layer (20%) the most abundant. While the MP levels within tissue samples were not significantly different than those identified within procedural blanks (which represent airborne contamination at time of sampling), they were comprised of different plastic polymer types. The blanks comprised n = 13 MP particles of four MP polymer types with the most abundant being polytetrafluoroethylene (PTFE), then polypropylene (PP), polyethylene terephthalate (PET) and polyfumaronitrile:styrene (FNS), with a mean ± SD of 10.4 ± 9.21, p = 0.293. This study reports the highest level of contamination control and reports unadjusted values alongside different contamination adjustment techniques. This is the first evidence of MP contamination of human vascular tissues. These results support the phenomenon of transport of MPs within human tissues, specifically blood vessels, and this characterisation of types and levels can now inform realistic conditions for laboratory exposure experiments, with the aim of determining vascular health impacts.

Robotic Transanal Minimally Invasive Surgery (rTAMIS): Large Tubulovillous Adenoma.

Many transanal platforms have recently evolved to manage rectal pathologies. Transanal endoscopic microsurgery (TEM) and transanal laparoscopic minimally invasive surgery (TAMIS) have been developed to address the limitations of conventional transanal surgery. More recently, the addition of the robotic platform to the surgeon's armamentarium has made it possible to combine the dexterity of the robotic surgical system with the standard TAMIS single-port platform to treat complex rectal lesions. In this article, we present the case of a patient who underwent rTAMIS for the management of a large endoscopically unresectable rectal mass.

Rare Presentation of Umbilical Condyloma.

Syphilis is associated with 3 stages of infection-primary, secondary, and tertiary-each with their own associated clinical findings. Secondary syphilis manifests with condyloma lata and other cutaneous findings, and typically occurs several months after the initial infection. Condyloma lata are primarily found in the genital area, but may also be found in other locations such as the umbilicus, axilla, and neck. This brief report describes an umbilical condyloma lata discovered in a patient with secondary syphilis and HIV co-infection and discusses surgical excision and fulguration as an option for definitive management.

How Do Quantum Effects Influence the Capacitance and Carrier Density of Monolayer MoS2 Transistors?

When transistor gate insulators have nanometer-scale equivalent oxide thickness (EOT), the gate capacitance (CG) becomes smaller than the oxide capacitance (Cox) due to the quantum capacitance and charge centroid capacitance of the channel. Here, we study the capacitance of monolayer MoS2 as a prototypical two-dimensional (2D) channel while considering spatial variations in the potential, charge density, and density of states. At 0.5 nm EOT, the monolayer MoS2 capacitance is smaller than its quantum capacitance, limiting the single-gated CG of an n-type channel to between 63% and 78% of Cox, for gate overdrive voltages between 0.5 and 1 V. Despite these limitations, for dual-gated devices, the on-state CG of monolayer MoS2 is 50% greater than that of silicon at 0.5 nm EOT and more than three times that of InGaAs at 1 nm EOT, indicating that such 2D semiconductors are promising for improved gate control of nanoscale transistors at future technology nodes.

Out-of-hours task allocation: implications for foundation training and practice.

Introduction: The role of foundation year-1 (FY1) doctors during the out-of-hours (OOHs) period was explored, identifying areas to improve their training. Methods: Data were retrospectively collected for 1 year of foundation training (2018-2019) from an electronic task system between 17:00 to 08:00, Monday to Sunday, in a 798-bed teaching hospital in Exeter, UK. Results: Thirty-two thousand, two hundred and sixty OOHs jobs were requested with 21,816 (67.6%) assigned to FY1 doctors and the clinical site practitioner. Jobs were distributed with 12,044 (55.2%) for FY1 medicine, 5,739 (26.3%) for FY1 surgery and 4,033 (18.5%) for the clinical site practitioner. The three most common jobs requested were prescribing (31.1%), patient reviews (17.9%), and interpreting or taking bloods (11.6%). Procedural jobs accounted for 22.2% of all jobs. Prescribing and patient review jobs were further categorised into commonly encountered themes. Conclusion: This study describes the nature of jobs performed by FY1 doctors working OOHs and identifies three areas to focus foundation doctor training. First, improving the preparedness of new graduates as guided by commonly identified jobs. Second, monitoring the appropriateness of performed jobs. Third, ensuring the evolving roles of allied health professionals and foundation doctors are clearly understood in relation to one another.

Polymeric Chloroquine as an Effective Antimigration Agent in the Treatment of Pancreatic Cancer.

Hydroxychloroquine (HCQ) has been the subject of multiple recent preclinical and clinical studies for its beneficial use in the combination treatments of different types of cancers. Polymeric HCQ (PCQ), a macromolecular multivalent version of HCQ, has been shown to be effective in various cancer models both in vitro and in vivo as an inhibitor of cancer cell migration and experimental lung metastasis. Here, we present detailed in vitro studies that show that low concentrations of PCQ can efficiently inhibit cancer cell migration and colony formation orders of magnitude more effectively compared to HCQ. After intraperitoneal administration of PCQ in vivo, high levels of tumor accumulation and penetration are observed, combined with strong antimetastatic activity in an orthotopic pancreatic cancer model. These studies support the idea that PCQ may be effectively used at low doses as an adjuvant in the therapy of pancreatic cancer. In conjunction with previously published literature, these studies further undergird the potential of PCQ as an anticancer agent.