Potential Misinformation in the Official Disability Guidelines About the Diagnosis and Treatment of Rotator Cuff Tendinopathy.

OBJECTIVE: We selected statements in the Official Disability Guidelines (ODG) that had the potential to reinforce misconceptions regarding symptoms from rotator cuff tendinopathy (RCT). These statements were revised and presented with the original statement to specialists. METHODS: Twelve statements regarding RCT were identified as deviating from principles based on ethics, values, and the evidence regarding both pathophysiology and human illness behavior. One hundred fifteen upper extremity surgeons reviewed both original and revised versions of the statements and indicated their preference. RESULTS: We found that upper extremity surgeons preferred 3 revised statements, 4 ODG statements, and 5 were rated as neutral between the 2 statements. CONCLUSION: Statements revised for evidence, ethics, and healthy mindset were not preferred by specialists, which may indicate limited awareness about how negative thoughts and distressing symptoms impact human illness.

Emerging technologies in citizen science and potential for insect monitoring.

Emerging technologies are increasingly employed in environmental citizen science projects. This integration offers benefits and opportunities for scientists and participants alike. Citizen science can support large-scale, long-term monitoring of species occurrences, behaviour and interactions. At the same time, technologies can foster participant engagement, regardless of pre-existing taxonomic expertise or experience, and permit new types of data to be collected. Yet, technologies may also create challenges by potentially increasing financial costs, necessitating technological expertise or demanding training of participants. Technology could also reduce people's direct involvement and engagement with nature. In this perspective, we discuss how current technologies have spurred an increase in citizen science projects and how the implementation of emerging technologies in citizen science may enhance scientific impact and public engagement. We show how technology can act as (i) a facilitator of current citizen science and monitoring efforts, (ii) an enabler of new research opportunities, and (iii) a transformer of science, policy and public participation, but could also become (iv) an inhibitor of participation, equity and scientific rigour. Technology is developing fast and promises to provide many exciting opportunities for citizen science and insect monitoring, but while we seize these opportunities, we must remain vigilant against potential risks. This article is part of the theme issue 'Towards a toolkit for global insect biodiversity monitoring'.

Clinical significance of MUC-4 and associated proteins in Pancreatic and Periampullary Cancers.

OBJECTIVE: This study primarily aimed to assess the expression of MUC-4 in patients with Pancreatic Ductal Adenocarcinoma (PDAC) as compared with controls and assess its clinical relevance. METHODS: Serum MUC-4 levels and MUC-4 gene expression in snap-frozen tissue were analyzed through Surface Plasmon Resonance (SPR) and quantitative PCR respectively. Tumor tissues and control tissues were analyzed for MUC-4 and other mucins through IHC. RESULT: MUC-4 expression in tumor tissue was found to be significantly elevated in PDAC patients as compared to chronic pancreatitis (CP) tissues and normal pancreatic tissues. Periampullary carcinoma and cholangiocarcinoma tissue also showed increased expression of MUC-4 and other mucins. CONCLUSION: Differential expression of MUC-4 in pancreatic tumor tissues can help to differentiate PDAC from benign conditions.

High-Density, Nonvolatile, Flexible Multilevel Organic Memristor Using Multilayered Polymer Semiconductors.

Nonvolatile organic memristors have emerged as promising candidates for next-generation electronics, emphasizing the need for vertical device fabrication to attain a high density. Herein, we present a comprehensive investigation of high-performance organic memristors, fabricated in crossbar architecture with PTB7/Al-AlOx-nanocluster/PTB7 embedded between Al electrodes. PTB7 films were fabricated using the Unidirectional Floating Film Transfer Method, enabling independent uniform film fabrication in the Layer-by-Layer (LbL) configuration without disturbing underlying films. We examined the charge transport mechanism of our memristors using the Hubbard model highlighting the role of Al-AlOx-nanoclusters in switching-on the devices, due to the accumulation of bipolarons in the semiconducting layer. By varying the number of LbL films in the device architecture, the resistance of resistive states was systematically altered, enabling the fabrication of novel multilevel memristors. These multilevel devices exhibited excellent performance metrics, including enhanced memory density, high on-off ratio (>108), remarkable memory retention (>105 s), high endurance (87 on-off cycles), and rapid switching (∼100 ns). Furthermore, flexible memristors were fabricated, demonstrating consistent performance even under bending conditions, with a radius of 2.78 mm for >104 bending cycles. This study not only demonstrates the fundamental understanding of charge transport in organic memristors but also introduces novel device architectures with significant implications for high-density flexible applications.

Trends in the incidence of colorectal cancer in sub-Saharan Africa: A population-based registry study.

In sub-Saharan Africa, colorectal cancer (CRC) has historically been considered a rare disease, although some previous studies have suggested that the incidence is increasing. We examine time trends in the incidence of CRC using data from 12 population-based cancer registries in 11 countries of sub-Saharan Africa that were able to provide time series data for periods of 12 or more years, or with earlier data with which recent rates may be compared. Age-standardized incidence rates were highest in the higher-income countries, and were increasing in all of the populations studied, and these increases were statistically significant in all but three. Current evidence has suggested a link between the increased adoption of western lifestyle habits with colorectal cancer, and along with increasing urbanization of African populations, there is an increase in body weight, as well as evidence of increasing consumption of meat, sugars, and alcohol.

A minimal presynaptic protein machinery mediating synchronous and asynchronous exocytosis and short-term plasticity.

Neurotransmitters are released from synaptic vesicles with remarkable precision in response to presynaptic Ca2+ influx but exhibit significant heterogeneity in exocytosis timing and efficacy based on the recent history of activity. This heterogeneity is critical for information transfer in the brain, yet its molecular basis remains poorly understood. Here, we employ a biochemically-defined fusion assay under physiologically-relevant conditions to delineate the minimal protein machinery sufficient to account for different modes of Ca2+-triggered vesicle fusion and short-term facilitation. We find that Synaptotagmin-1, Synaptotagmin-7, and Complexin, synergistically restrain SNARE complex assembly, thus preserving vesicles in a stably docked state at rest. Upon Ca2+ activation, Synaptotagmin-1 induces rapid vesicle fusion, while Synaptotagmin-7 mediates delayed fusion. Competitive binding of Synaptotagmin-1 and Synaptotagmin-7 to the same SNAREs, coupled with differential rates of Ca2+-triggered fusion clamp reversal, govern the kinetics of vesicular fusion. Under conditions mimicking sustained neuronal activity, the Synaptotagmin-7 fusion clamp is destabilized by the elevated basal Ca2+ concentration, thereby enhancing the synchronous component of fusion. These findings provide a direct demonstration that a small set of proteins is sufficient to account for how nerve terminals adapt and regulate the Ca2+-evoked neurotransmitter exocytosis process to support their specialized functions in the nervous system.

Design and Synthesis of Novel Squaraine-Based Fluorescent Probe for Far-Red Detection of Chymotrypsin Enzyme.

Chymotrypsin, a crucial enzyme in human digestion, catalyzes the breakdown of milk proteins, underscoring its significance in both health diagnostics and dairy quality assurance. Addressing the critical need for rapid, cost-effective detection methods, we introduce a groundbreaking approach utilizing far-red technology and HOMO-Förster resonance energy transfer (FRET). Our novel probe, SQ-122 PC, features a unique molecular design that includes a squaraine dye (SQ), a peptide linker, and SQ moieties synthesized through solid-phase peptide synthesis. Demonstrating a remarkable quenching efficiency of 93.75% in a tailored H2O:DMSO (7:3) solvent system, our probe exhibits absorption and emission properties within the far-red spectrum, with an unprecedented detection limit of 0.130 nM. Importantly, our method offers unparalleled selectivity towards chymotrypsin, ensuring robust and accurate enzyme detection. This pioneering work underscores the immense potential of far-red-based homo-FRET systems in enabling the sensitive and specific detection of chymotrypsin enzyme activity. By bridging the gap between cutting-edge technology and biomedical diagnostics, our findings herald a new era of enzyme sensing, promising transformative advancements in disease diagnosis and dairy quality control.

ITF2357 regulates NF-κB signaling pathway to protect barrier integrity in retinal pigment epithelial cells.

The robust integrity of the retinal pigment epithelium (RPE), which contributes to the outer brain retina barrier (oBRB), is compromised in several retinal degenerative and vascular disorders, including diabetic macular edema (DME). This study evaluates the role of a new generation of histone deacetylase inhibitor (HDACi), ITF2357, in regulating outer blood-retinal barrier function and investigates the underlying mechanism of action in inhibiting TNFα-induced damage to RPE integrity. Using the immortalized RPE cell line (ARPE-19), ITF2357 was found to be non-toxic between 50 nM and 5 µM concentrations. When applied as a pre-treatment in conjunction with an inflammatory cytokine, TNFα, the HDACi was safe and effective in preventing epithelial permeability by fortifying tight junction (ZO-1, -2, -3, occludin, claudin-1, -2, -3, -5, -19) and adherens junction (E-cadherin, Nectin-1) protein expression post-TNFα stress. Mechanistically, ITF2357 depicted a late action at 24 h via attenuating IKK, IκBα, and p65 phosphorylation and ameliorated the expression of IL-1ß, IL-6, and MCP-1. Also, ITF2357 delayed IκBα synthesis and turnover. The use of Bay 11-7082 and MG132 further uncovered a possible role for ITF2357 in non-canonical NF-κB activation. Overall, this study revealed the protection effects of ITF2357 by regulating the turnover of tight and adherens junction proteins and modulating NF-κB signaling pathway in the presence of an inflammatory stressor, making it a potential therapeutic application for retinal vascular diseases such as DME with compromised outer blood-retinal barrier.

Impact of mediterranean diet promotion on environmental sustainability: a longitudinal analysis.

OBJECTIVE: This article aims to estimate the differences in environmental impact (greenhouse gas [GHG] emissions, land use, energy used, acidification and potential eutrophication) after one year of promoting a Mediterranean diet (MD). METHODS: Baseline and 1-year follow-up data from 5800 participants in the PREDIMED-Plus study were used. Each participant's food intake was estimated using validated semi-quantitative food frequency questionnaires, and the adherence to MD using the Dietary Score. The influence of diet on environmental impact was assessed through the EAT-Lancet Commission tables. The influence of diet on environmental impact was assessed through the EAT-Lancet Commission tables. The association between MD adherence and its environmental impact was calculated using adjusted multivariate linear regression models. RESULTS: After one year of intervention, the kcal/day consumed was significantly reduced (-125,1 kcal/day), adherence to a MD pattern was improved (+0,9) and the environmental impact due to the diet was significantly reduced (GHG: -361 g/CO2-eq; Acidification:-11,5 g SO2-eq; Eutrophication:-4,7 g PO4-eq; Energy use:-842,7 kJ; and Land use:-2,2 m2). Higher adherence to MD (high vs. low) was significantly associated with lower environmental impact both at baseline and one year follow-up. Meat products had the greatest environmental impact in all the factors analysed, both at baseline and at one-year follow-up, in spite of the reduction observed in their consumption. CONCLUSIONS: A program promoting a MD, after one year of intervention, significantly reduced the environmental impact in all the factors analysed. Meat products had the greatest environmental impact in all the dimensions analysed.

Ion Channels and Metal Ions in Parkinson's Disease: Historical Perspective to the Current Scenario.

Parkinson's disease (PD) is a neurodegenerative condition linked to the deterioration of motor and cognitive performance. It produces degeneration of the dopaminergic neurons along the nigrostriatal pathway in the central nervous system (CNS), which leads to symptoms such as bradykinesias, tremors, rigidity, and postural instability. There are several medications currently approved for the therapy of PD, but a permanent cure for it remains elusive. With the aging population set to increase, a number of PD cases are expected to shoot up in the coming times. Hence, there is a need to look for new molecular targets that could be investigated both preclinically and clinically for PD treatment. Among these, several ion channels and metal ions are being studied for their effects on PD pathology and the functioning of dopaminergic neurons. Ion channels such as N-methyl-D-aspartate (NMDA), γ-aminobutyric acid A (GABAA), voltage-gated calcium channels, potassium channels, HCN channels, Hv1 proton channels, and voltage-gated sodium channels and metal ions such as mercury, zinc, copper, iron, manganese, calcium, and lead showed prominent involvement in PD. Pharmacological agents have been used to target these ion channels and metal ions to prevent or treat PD. Hence, in the present review, we summarize the pathophysiological events linked to PD with an emphasis on the role of ions and ion channels in PD pathology, and pharmacological agents targeting these ion channels have also been listed.

The Influence of a Microstructural Conformation of Oriented Floating Films of Semiconducting Polymers on Organic Device Performance.

Extended π-conjugation with backbone-planarity-driven π-π stacking dominates charge transport in semiconducting polymers (SCPs). The roles of SCP film morphology and macromolecular conformation concerning the substrate in influencing charge transport and its impact on device performance have been a subject of extensive debate. Face-on SCPs promote out-of-plane charge transport primarily through π-π stacking, with conjugated polymeric chains assisting transport in connecting crystalline domains, whereas edge-on SCPs promote in-plane charge transport primarily through conjugation and π-π stacking. In this work, we fabricated three different types of devices, namely, organic field effect transistors, organic Schottky diodes, and organic bistable memristors, as representatives of planar and vertical devices. We demonstrate that a planar device, i.e., an organic field effect transistor, performs well in an edge-on conformation exhibiting a field-effect mobility of 0.12 cm2V-1s-1 and on/off ratio >104, whereas vertical devices, i.e., organic Schottky diodes and organic memristors, perform well in a face-on conformation, exhibiting exceptionally high on/off ratios of ~107 and 106, respectively.

PRAME Expression in Melanocytic Proliferations in Special Sites.

The subset of nevi occurring at special sites (eg, acral skin, anogeni-tal region, breast, ear, flexural surfaces) have normal histologic variations that preclude the use of routinely used diagnostic criteria for malignancy. Suggested criteria for differentiating malignant special-site lesions from benign lesions have been described, but there is an unmet need for a validated test aiding in the delineation of benign and malignant lesions at special sites. Preferentially expressed antigen of melanoma (PRAME) expression has been characterized as a relatively specific marker of melanoma, but not within the specific population of special-site lesions. This study aimed to determine if PRAME may serve as a specific marker of melanoma within the population of special-sites lesions.

Scrub Typhus: An Acute Precipitant for Acute on Chronic Liver Failure.

Acute-on-chronic liver failure (ACLF) is a clinical syndrome with high mortality. Many acute precipitating factors have been implicated in triggering the acute event of ACLF, with bacterial infections being a common precipitant. However, many other precipitants can cause ACLF; therefore, identification of these factors early in the golden window and their treatment can result in improved prognosis. Scrub typhus usually presents as uncomplicated acute febrile illness but rarely as complicated. Few case reports of scrub-typhus-induced acute liver failure have been reported but none with scrub-typhus-precipitating ACLF so far. Therefore, we are reporting a case of scrub-typhus-precipitating ACLF, where timely intervention with antibiotics results in improved outcome.

Ovarian cancer survival in sub-Saharan Africa by human development index and histological subtypes: A population-based registry study.

Ovarian cancer (OC) is the fourth most common cancer of women in sub-Saharan Africa (SSA), although few data have been published on population-level survival. We estimate ovarian cancer survival in SSA by human development index and histological subtype, using data from seven population-based cancer registries in six countries: Kenya (Nairobi and Eldoret), Mauritius, Uganda (Kampala), Cote d'Ivoire (Abidjan), Ethiopia (Addis Ababa) and South Africa (Eastern Cape). A total of 644 cases diagnosed during 2008-2014 were included, with 77% being of epithelial subtypes (range 47% [Abidjan]-80% [Mauritius]). The overall observed survival in the study cohort was 73.4% (95% CI: 69.8, 77.0) at 1 year, 54.4% (95% CI: 50.4, 58.7) at 3 years and 45.0% (95% CI: 41.0, 49.4) at 5 years. Relative survival at Year 1 ranged from 44.4% in Kampala to 86.3% in Mauritius, with a mean for the seven series of 67.4%. Relative survival was highest in Mauritius at 72.2% and lowest in Kampala, Uganda at 19.5%, with a mean of 47.8%. There was no difference in survival by age at diagnosis. Patients from high and medium HDI countries had significantly better survival than those from low HDI countries. Women with cancers of epithelial cell origin had much lower survival compared to women with other histological subtypes (p = .02). Adjusted for the young age of the African patients with ovarian cancer (44% aged <50) survival is much lower than in USA or Europe, and underlines the need for improvements in the access to diagnosis and treatment of OC in SSA.

MicroRNA Signatures for Pancreatic Cancer and Chronic Pancreatitis: Expression Profiling by NGS.

BACKGROUND: Pancreatic ductal adenocarcinoma (PDAC) is a deadly disease due to the lack of early detection. Because chronic pancreatitis (CP) patients are a high-risk group for pancreatic cancer, this study aimed to assess the differential miRNA profile in pancreatic tissue of patients with CP and pancreatic cancer. METHODS: MiRNAs were isolated from formalin-fixed paraffin-embedded pancreatic tissue of 22 PDAC patients, 18 CP patients, and 10 normal pancreatic tissues from autopsy (C) cases and processed for next-generation sequencing. Known and novel miRNAs were identified and analyzed for differential miRNA expression, target prediction, and pathway enrichment between groups. RESULTS: Among the miRNAs identified, 166 known and 17 novel miRNAs were found exclusively in PDAC tissues, while 106 known and 10 novel miRNAs were found specifically in CP tissues. The pathways targeted by PDAC-specific miRNAs and differentially expressed miRNAs between PDAC versus CP tissues and PDAC versus control tissues were the proteoglycans pathway, Hippo signaling pathway, adherens junction, and transforming growth factor-ß signaling pathway. CONCLUSIONS: This study resulted in a set of exclusive and differentially expressed miRNAs in PDAC and CP can be assessed for their diagnostic value. In addition, studying the role of miRNA-target gene interactions in carcinogenesis may open new therapeutic avenues.

Long non-coding RNAs in cancer: multifaceted roles and potential targets for immunotherapy.

Cancer remains a major global health concern with high mortality rates mainly due to late diagnosis and poor prognosis. Long non-coding RNAs (lncRNAs) are emerging as key regulators of gene expression in human cancer, functioning through various mechanisms including as competing endogenous RNAs (ceRNAs) and indirectly regulating miRNA expression. LncRNAs have been found to have both oncogenic and tumor-suppressive roles in cancer, with the former promoting cancer cell proliferation, migration, invasion, and poor prognosis. Recent research has shown that lncRNAs are expressed in various immune cells and are involved in cancer cell immune escape and the modulation of the tumor microenvironment, thus highlighting their potential as targets for cancer immunotherapy. Targeting lncRNAs in cancer or immune cells could enhance the anti-tumor immune response and improve cancer immunotherapy outcomes. However, further research is required to fully understand the functional roles of lncRNAs in cancer and the immune system and their potential as targets for cancer immunotherapy. This review offers a comprehensive examination of the multifaceted roles of lncRNAs in human cancers, with a focus on their potential as targets for cancer immunotherapy. By exploring the intricate mechanisms underlying lncRNA-mediated regulation of cancer cell proliferation, invasion, and immune evasion, we provide insights into the diverse therapeutic applications of these molecules.

Supplementation of probiotic Bifidobacterium breve Bif11 reverses neurobehavioural deficits, inflammatory changes and oxidative stress in Parkinson's disease model.

Human gut microbiota are thought to affect different physiological processes in the body, including brain functions. Gut dysbiosis has been linked to the progression of Parkinson's disease (PD) and thus, restoring the healthy gut microbiota with supplementation of putative probiotic strains can confer some benefits in PD. In the current study, we explored the neuroprotective potential of Bifidobacterium breve Bif11 supplementation in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine hydrochloride (MPTP) treated female Sprague Dawley rats. This study investigated the behavioural, molecular and biochemical parameters in the MPTP rat model. A pharmacological intervention of Bif11 at doses of 1 × 1010 CFU and 2 × 1010 CFU for 21 days was found to attenuate the cognitive and motor changes in the MPTP rat model. Furthermore, it also increased the tyrosine hydroxylase levels, reduced pro-inflammatory markers and decreased oxidative and nitrosative stress in the mid brain of MPTP-lesioned rats. Bif11 supplementation even restored the levels of short-chain fatty acids and decreased intestinal epithelial permeability in MPTP-induced PD model rats. In summary, these findings demonstrate that B. breve Bif11 has the potential to ameliorate symptoms of PD. However, this therapy needs to be further investigated with in-depth mechanistic insights in the future for the treatment of PD.

Guidelines on antibody use in physiology research.

Antibodies are one of the most used reagents in scientific laboratories and are critical components for a multitude of experiments in physiology research. Over the past decade, concerns about many biological methods, including those that use antibodies, have arisen as several laboratories were unable to reproduce the scientific data obtained in other laboratories. The lack of reproducibility could be largely attributed to inadequate reporting of detailed methods, no or limited verification by authors, and the production and use of unvalidated antibodies. The goal of this guideline article is to review best practices concerning commonly used techniques involving antibodies, including immunoblotting, immunohistochemistry, and flow cytometry. Awareness and integration of best practices will increase the rigor and reproducibility of these techniques and elevate the quality of physiology research.

Tissue-targeted and localized AAV5-DCN and AAV5-PEDF combination gene therapy abrogates corneal fibrosis and concurrent neovascularization in rabbit eyes in vivo.

PURPOSE: Corneal fibrosis and neovascularization (CNV) after ocular trauma impairs vision. This study tested therapeutic potential of tissue-targeted adeno-associated virus5 (AAV5) mediated decorin (DCN) and pigment epithelium-derived factor (PEDF) combination genes in vivo. METHODS: Corneal fibrosis and CNV were induced in New Zealand White rabbits via chemical trauma. Gene therapy in stroma was delivered 30-min after chemical-trauma via topical AAV5-DCN and AAV5-PEDF application using a cloning cylinder. Clinical eye examinations and multimodal imaging in live rabbits were performed periodically and corneal tissues were collected 9-day and 15-day post euthanasia. Histological, cellular, and molecular and apoptosis assays were used for efficacy, tolerability, and mechanistic studies. RESULTS: The AAV5-DCN and AAV5-PEDF combination gene therapy significantly reduced corneal fibrosis (p < 0.01 or p < 0.001) and CNV (p < 0.001) in therapy-given (chemical-trauma and AAV5-DCN + AAV5-PEDF) rabbit eyes compared to the no-therapy given eyes (chemical-trauma and AAV5-naked vector). Histopathological analyses demonstrated significantly reduced fibrotic α-smooth muscle actin and endothelial lectin expression in therapy-given corneas compared to no-therapy corneas on day-9 (p < 0.001) and day-15 (p < 0.001). Further, therapy-given corneas showed significantly increased Fas-ligand mRNA levels (p < 0.001) and apoptotic cell death in neovessels (p < 0.001) compared to no-therapy corneas. AAV5 delivered 2.69 × 107 copies of DCN and 2.31 × 107 copies of PEDF genes per µg of DNA. AAV5 vector and delivered DCN and PEDF genes found tolerable to the rabbit eyes and caused no significant toxicity to the cornea. CONCLUSION: The combination AAV5-DCN and AAV5-PEDF topical gene therapy effectively reduces corneal fibrosis and CNV with high tolerability in vivo in rabbits. Additional studies are warranted.