Dependency

Haemorrhoidal disease is identified by declension of the inflamed and bleeding of vascular tissues of the anal canal. Traditionally, haemorrhoids are associated with chronic constipation and the most common symptoms are irritation in anus region, pain and discomfort, swelling around anus, tender lumps around the anus and rectal bleeding (depending upon the grade of haemorrhoid). Among the several conventional treatment procedures (commonly mentioned as, rubber band litigation, sclerotherapy and electrotherapy), laser haemorrhoidoplasty is an out-patient and less-invasive laparoscopic procedure...

RATIONALE: Patients with schizophrenia with second-generation antipsychotics (SGAs) treatment have shown an increased risk of bone fragility and susceptibility to fracture; however, it is still unclear whether this risk is derived from the effect of antipsychotics on balance of bone metabolism. OBJECTIVES: We investigated the changes of two bone turnover biomarkers (BTMs) concentrations in people with schizophrenia receiving SGAs: procollagen type I aminoterminal propeptide (PINP) and C-terminal telopeptide of type I collagen (CTX-1) as BTMs of osteogenesis and bone resorption, respectively, to explore how antipsychotics contribute to bone fragility...

PURPOSE: It has long been thought that the carcinogenic effect of radiation resulted from the induction of oncogenic mutations which then led to an increase in the proportion of cancer-bearing individuals. However, even as early as the 1960s, there were indications that the carcinogenic effect of radiation might result from the induction of an earlier onset of cancer. Recently, the former notion was challenged by its inability to explain time-dependent decline of the relative risk following an exposure to radiation, and a parallel shift of mouse survival curves toward younger ages following an exposure to radiation...

BACKGROUND: Autoimmune inner ear disease (AIED) manifests with recurrent fluctuating sensorineural hearing loss and vestibular symptoms. Treatment includes steroids and a variety of immunosuppressants. Despite adequate treatment, sensorineural hearing loss can be progressive to the point of deafness. In these patients, a cochlear implant (CI) is indicated. We present the case of a 25-year-old male who underwent cochlear implantation in the left ear. After implantation we noticed brisk variations in impedances which were related to application of the previously prescribed tumor necrosis alpha (TNFα) inhibitor adalimumab...

PURPOSE: Von Hippel-Lindau (VHL) disease is an autosomal-dominantly inherited tumor predisposition syndrome. One of the most common tumors are central nervous system (CNS) hemangioblastomas. Recommendations on the initiation and continuation of the screening and surveillance program for CNS tumors in pediatric VHL patients are based on small case series and thus low evidence level. To derive more robust screening recommendations, we report on the largest monocentric pediatric cohort of VHL patients...

PURPOSE: Physical activity has the potential to reduce the risk of diabetes after cancer diagnosis. However, current evidence supporting its effects is limited. This study aims to examine the associations between changes in physical activity and subsequent risk of diabetes among cancer survivors. METHODS: A total of 264,250 cancer survivors (mean age 56.7 (12.5) years, 44.2% males) without a prior history of diabetes were assessed for adherence to physical activity both before and after their diagnosis...

Perylenequinones (PQs) from bambusicolous Shiraia fungi serve as excellent photosensitizers for photodynamic therapy. However, the lower yield of PQ production in mycelium cultures is an important bottleneck for their clinical application. Light has long been recognized as a pivotal regulatory signal for fungal secondary metabolite biosynthesis. In this study, we explored the role of nitric oxide (NO) in the growth and PQ biosynthesis in mycelium cultures of Shiraia sp. S9 exposed to red light. The continuous irradiation with red light (627 nm, 200 lx) suppressed fungal conidiation, promoted hyphal branching, and elicited a notable increase in PQ accumulation...

PURPOSE: Colon cancer is a prevalent cancer globally, representing approximately 10% of all cancer cases and accounting for 10% of all cancer-related deaths. Therefore, finding new therapeutic methods with high efficiency will be very valuable. Cromolyn (C), a common anti-allergic and mast cell membrane stabilizing drug, has recently shown valuable anti-cancer effects in several studies. This study was designed to investigate the anti-cancer activity of cromolyn on colon cancer in vitro and in vivo and to determine values such as selectivity index and survival effect...

BACKGROUND: The primary aim of this study was to longitudinally examine the impact of DM on physical performance measures including Gait Speed and Chair Stand tests over 8 years of follow up in people with or at risk of knee osteoarthritis (OA). DESIGN: A prospective longitudinal study. SETTING: Multisite community based. POPULATION: This study included participants with or at risk of knee OA aged from 45 to 79 years from the Osteoarthritis Initiative from baseline to 96 months follow-up...

The aberrant activation of fibroblast growth factor receptor (FGFR) acts as a potent driver of multiple types of human cancers. Despite the development of several conventional small-molecular FGFR inhibitors, their clinical efficacy is largely compromised due to low selectivity and side effects. Here, we report the selective FGFR1/2-targeting proteolysis targeting chimeric (PROTAC), BR-cpd7 that displays significant isoform specificity to FGFR1/2 with DC50 values around 10 nM, while sparing FGFR3. The following mechanistic investigation reveals the reduced FGFR signaling, through which BR-cpd7 induces cell cycle arrest and consequently blocks the proliferation of multiple FGFR1/2-dependent tumor cells...

Cell migration is controlled by the coordinated action of cell adhesion, cytoskeletal dynamics, contractility and cell extrinsic cues. Integrins are the main adhesion receptors to ligands of the extracellular matrix (ECM), linking the actin cytoskeleton to the ECM and enabling cells to sense matrix rigidity and mount a directional cell migration response to stiffness gradients. Most models studied show preferred migration of single cells or cell clusters towards increasing rigidity. This is referred to as durotaxis, and since its initial discovery in 2000, technical advances and elegant computational models have provided molecular level details of stiffness sensing in cell migration...

INTRODUCTION: This study aimed to evaluate the accuracy in terms of trueness and precision of 3 different liquid crystal display (LCD) printers with different cost levels. METHODS: Three LCD 3-dimensional (3D) printers were categorized into tiers 1-3 on the basis of cost level. The printers' accuracies were assessed in terms of trueness and precision. For this research, 10 standard tessellation language (STL) reference files were used. For trueness, each STL file was printed once with each 3D printer...

PURPOSE: To examine the distortion of the linear quadratic (LQ) model of in vitro cytogenetic dose response over an extended range of γ-ray doses by analyzing the available literature data, and to establish the dose ranges, in which the LQ dose response curve (DRC) can be most accurately fitted for biological dosimetry. MATERIALS AND METHODS: Data on yields of dicentrics (Dic) or dicentrics plus centric rings (Dic + CR) induced in vitro in human lymphocytes by acute γ-rays were extracted from 108 open sources...

One central question in the scientific and philosophical study of consciousness is regarding the scope of human consciousness. There is a lively debate as to whether high-level information integration is necessarily dependent on consciousness. This study presents a new form of unconscious integration based on the facingness between two individuals. Using a breaking continuous flash suppression paradigm, Experiments 1-3 found that two facing human heads got a privilege in breaking into awareness compared to nonfacing pairs...

Elemental models of associative learning typically employ a common prediction-error term. Following a conditioning trial, they predict that the change in the strength of an association between a cue and an outcome is dependent upon how well the outcome was predicted. When multiple cues are present, they each contribute to that prediction. The same rule applies both to increases in associative strength during excitatory conditioning and the loss of associative strength during extinction. In five experiments using an allergy prediction task, we tested the involvement of a common error term in the extinction of causal learning...

The congruency effect in Stroop-like tasks-a popular measure of distraction-is smaller after incongruent relative to congruent trials. However, it is unclear whether this congruency sequence effect (CSE)-a popular index of coping with distraction-reflects adjustments of control after congruent trials, incongruent trials, or both. The episodic retrieval account of the CSE posits adjustments of control after both congruent and incongruent trials. In this account, retrieving a memory of the previous trial's congruency (i...

Sirtuin 2 (SIRT2) is a class III histone deacetylase that is highly conserved from bacteria to mammals. We prepared and characterized the wild-type (WT) and mutant forms of the histone deacetylase (HDAC) domain of human SIRT2 (hSIRT2) using various biophysical methods and evaluated their deacetylation activity. We found that WT hSIRT2 HDAC (residues 52-357) forms a homodimer in a concentration-dependent manner with a dimer-monomer dissociation constant of 8.3 ± 0.5 μM, which was determined by mass spectrometry...

Background: Monomethyl auristatin E (MMAE) has been used as a payload for several Food and Drug Administration (FDA) approved antibody-drug conjugates (ADCs). It is known that MMAE is released from the ADC following binding, internalization and proteolytic degradation in target tissues. A striking discrepancy in systemic MMAE levels has been observed across species with 50-fold higher MMAE levels in human than that in rodents when normalized by ADC dose with unknown mechanism. Hypothesis and purpose: Multiple factors could affect systemic MMAE levels such as production and elimination of unconjugated MMAE following ADC dosing...

Allergic airway inflammation results from uncontrolled immune responses to environmental Ags. Although it is well established that allergic immune responses exhibit a high degree of diversity, driven by primary effector cell types such as eosinophils, neutrophils, or CD4 T cells with distinct effector signatures, the mechanisms responsible for such pathogenesis remain elusive. Foxp3+ regulatory T cells (Tregs) are essential immune regulators during chronic inflammation, including allergic airway inflammation...

Singlet dioxygen has been widely applied in different disciplines such as medicine (photodynamic therapy or blood sterilization), remediation (wastewater treatment) or industrial processes (fine chemicals synthesis). Particularly, it can be conveniently generated by energy transfer between a photosensitizer's triplet state and triplet dioxygen upon irradiation with visible light. Among the best photosensitizers, substituted zinc(II) phthalocyanines are prominent due to their excellent photophysical properties, which can be tuned by structural modifications, such as halogen- and chalcogen-atom substitution...