Miracle-dz/UniFAR-FTUs huggingface dataset:
Health care access and glycemic control in youth and young adults with type 1 and type 2 diabetes in South Carolina

Affordability and geographic accessibility are key health care access characteristics. We used data from 481 youth and young adults (YYA) with diabetes (389 type 1, 92 type 2) to understand the association between health care access and glycemic control as measured by HbA1c values. In multivariate models, YYA with state or federal health insurance had HbA1c percentage values 0.68 higher (P = 0.0025) than the privately insured, and those without insurance 1.34 higher (P < 0.0001). Not having a routine diabetes care provider was associated with a 0.51 higher HbA1c (P = 0.048) compared to having specialist care, but HbA1c did not differ significantly (P = 0.069) between primary vs specialty care. Distance to utilized provider was not associated with HbA1c among YYA with a provider (P = 0.11). These findings underscore the central role of health insurance and indicate a need to better understand the root causes of poorer glycemic control in YYA with state/federal insurance.
Effects of Phantom Electrode Stimulation on Vocal Production in Cochlear Implant Users.

OBJECTIVES Cochlear implant (CI) users suffer from a range of speech impairments, such as stuttering and vocal control of pitch and intensity. Though little research has focused on the role of auditory feedback in the speech of CI users, these speech impairments could be due in part to limited access to low-frequency cues inherent in CI-mediated listening. Phantom electrode stimulation (PES) represents a novel application of current steering that extends access to low frequencies for CI recipients. It is important to note that PES transmits frequencies below 300 Hz, whereas Baseline does not. The objective of this study was to explore the effects of PES on multiple frequency-related characteristics of voice production. DESIGN Eight postlingually deafened, adult Advanced Bionics CI users underwent a series of vocal production tests including Tone Repetition, Vowel Sound Production, Passage Reading, and Picture Description. Participants completed all of these tests twice: once with PES and once using their program used for everyday listening (Baseline). An additional test, Automatic Modulation, was included to measure acute effects of PES and was completed only once. This test involved switching between PES and Baseline at specific time intervals in real time as participants read a series of short sentences. Finally, a subjective Vocal Effort measurement was also included. RESULTS In Tone Repetition, the fundamental frequencies (F0) of tones produced using PES and the size of musical intervals produced using PES were significantly more accurate (closer to the target) compared with Baseline in specific gender, target tone range, and target tone type testing conditions. In the Vowel Sound Production task, vowel formant profiles produced using PES were closer to that of the general population compared with those produced using Baseline. The Passage Reading and Picture Description task results suggest that PES reduces measures of pitch variability (F0 standard deviation and range) in natural speech production. No significant results were found in comparisons of PES and Baseline in the Automatic Modulation task nor in the Vocal Effort task. CONCLUSIONS The findings of this study suggest that usage of PES increases accuracy of pitch matching in repeated sung tones and frequency intervals, possibly due to more accurate F0 representation. The results also suggest that PES partially normalizes the vowel formant profiles of select vowel sounds. PES seems to decrease pitch variability of natural speech and appears to have limited acute effects on natural speech production, though this finding may be due in part to paradigm limitations. On average, subjective ratings of vocal effort were unaffected by the usage of PES versus Baseline.
Constipation in the elderly: investigation and management

Diagnosis of constipation is usually based on clinical criteria, in other words, the Rome III criteria, or from colorectal transit times determined radiographically. Depending on the definitions used, chronic constipation affects 2–28% of the general population and the prevalence increases with age. Constipation is usually classified as functional (idiopathic) or as secondary to diseases, conditions or to medications. In the elderly population, constipation is often associated with Parkinson’s disease, stroke or rectocele and prolapse. Treatment of constipation is initiated after a thorough history and physical exam. A number of tests are available but in most patients without alarm symptoms treatment is instituted after a physical examination and relevant blood samples. Basic treatment consists of appropriate daily habits, oral laxatives or suppositories, and mini enema. In more severe cases irrigation with enemas can be used. Surgical treatment is restricted to highly selected patients.
Acid sphingomyelinase deficiency protects mitochondria and improves function recovery after brain injury

Traumatic brain injury (TBI) is one of the leading causes of disability worldwide and a prominent risk factor for neurodegenerative diseases. The expansion of nervous tissue damage after the initial trauma involves a multifactorial cascade of events, including excitotoxicity, oxidative stress, inflammation, and deregulation of sphingolipid metabolism that further mitochondrial dysfunction and secondary brain damage. Here, we show that a posttranscriptional activation of an acid sphingomyelinase (ASM), a key enzyme of the sphingolipid recycling pathway, resulted in a selective increase of sphingosine in mitochondria during the first week post-TBI that was accompanied by reduced activity of mitochondrial cytochrome oxidase and activation of the Nod-like receptor protein 3 inflammasome. TBI-induced mitochondrial abnormalities were rescued in the brains of ASM KO mice, which demonstrated improved behavioral deficit recovery compared with WT mice. Furthermore, an elevated autophagy in an ASM-deficient brain at the baseline and during the development of secondary brain injury seems to foster the preservation of mitochondria and brain function after TBI. Of note, ASM deficiency attenuated the early stages of reactive astrogliosis progression in an injured brain. These findings highlight the crucial role of ASM in governing mitochondrial dysfunction and brain-function impairment, emphasizing the importance of sphingolipids in the neuroinflammatory response to TBI.
The Relationship Between Interocular Asymmetry of Visual Field Defects and Optic Nerve Head Blood Flow in Patients With Glaucoma

Purpose: To investigate the association between asymmetry of visual field (VF) defects and optic nerve head (ONH) blood flow in patients with glaucoma using laser speckle flowgraphy. Methods: In total, 170 eyes of 85 patients with primary open-angle glaucoma were included. Intraocular pressure, VF (Humphrey 24-2, SITA program), mean blur rate in the tissue area (MBR-T) of the ONH measured by laser speckle flowgraphy, axial length, circumpapillary retinal nerve fiber layer thickness (cpRNFLT), disc area, cup/disc area ratio, and parapapillary atrophy (PPA) area was measured in each eye. The paired eyes were divided into better and worse eyes according to the mean deviation (MD) of VF, and intereye differences of various parameters (better MD eye minus worse MD eye) were examined. Factors associated with MD difference, MBR-T difference, or cpRNFLT difference were investigated. Results: MD of the VF in better and worse eyes were −10.2±7.3 dB and −16.8±7.4 dB, respectively. In stepwise multiple regression analysis, MBR-T differences, cpRNFLT differences and sex (male) were significantly correlated with MD differences (&bgr;, 0.26, 0.21, 0.20; P=0.01, 0.04, 0.047, respectively). MD differences were significantly associated with MBR-T differences (&bgr;, 0.28; P=0.01). For cpRNFLT differences, differences in &bgr;-PPA area and MD differences were identified as significant factors (&bgr;, −0.26, 0.22; P=0.02, 0.04, respectively). Conclusions: Asymmetry of ONH blood flow is significantly associated with asymmetry of visual field defects in patients with glaucoma independently of cpRNFLT.
Focal adhesions are essential to drive zebrafish heart valve morphogenesis

Elucidating the morphogenetic events that shape vertebrate heart valves, complex structures that prevent retrograde blood flow, is critical to understanding valvular development and aberrations. Here, we used the zebrafish atrioventricular (AV) valve to investigate these events in real time and at single-cell resolution. We report the initial events of collective migration of AV endocardial cells (ECs) into the extracellular matrix (ECM), and their subsequent rearrangements to form the leaflets. We functionally characterize integrin-based focal adhesions (FAs), critical mediators of cell–ECM interactions, during valve morphogenesis. Using transgenes to block FA signaling specifically in AV ECs as well as loss-of-function approaches, we show that FA signaling mediated by Integrin &agr;5&bgr;1 and Talin1 promotes AV EC migration and overall shaping of the valve leaflets. Altogether, our investigation reveals the critical processes driving cardiac valve morphogenesis in vivo and establishes the zebrafish AV valve as a vertebrate model to study FA-regulated tissue morphogenesis.
Current concepts in cochlear ribbon synapse formation

In mammals, hair cells and spiral ganglion neurons (SGNs) in the cochlea together are sophisticated “sensorineural” structures that transduce auditory information from the outside world into the brain. Hair cells and SGNs are joined by glutamatergic ribbon‐type synapses composed of a molecular machinery rivaling in complexity the mechanoelectric transduction components found at the apical side of the hair cell. The cochlear hair cell ribbon synapse has received much attention lately because of recent and important findings related to its damage (sometimes termed “synaptopathy”) as a result of noise overexposure. During development, ribbon synapses between type I SGNs and inner hair cells form in the time window between birth and hearing onset and is a process coordinated with type I SGN myelination, spontaneous activity, synaptic pruning, and innervation by efferents. In this review, we highlight new findings regarding the diversity of type I SGNs and inner hair cell synapses, and the molecular mechanisms of selective hair cell targeting. Also discussed are cell adhesion molecules and protein constituents of the ribbon synapse, and how these factors participate in ribbon synapse formation. We also note interesting new insights into the morphological development of type II SGNs, and the potential for cochlear macrophages as important players in protecting SGNs. We also address recent studies demonstrating that the structural and physiological profiles of the type I SGNs do not reach full maturity until weeks after hearing onset, suggesting a protracted development that is likely modulated by activity.
Impact of Early Diabetic Ketoacidosis on the Developing Brain

OBJECTIVE This study examined whether a history of diabetic ketoacidosis (DKA) is associated with changes in longitudinal cognitive and brain development in young children with type 1 diabetes. RESEARCH DESIGN AND METHODS Cognitive and brain imaging data were analyzed from 144 children with type 1 diabetes, ages 4 to <10 years, who participated in an observational study of the Diabetes Research in Children Network (DirecNet). Participants were grouped according to history of DKA severity (none/mild or moderate/severe). Each participant had unsedated MRI scans and cognitive testing at baseline and 18 months. RESULTS In 48 of 51 subjects, the DKA event occurred at the time of onset, at an average of 2.9 years before study entry. The moderate/severe DKA group gained more total and regional white and gray matter volume over the observed 18 months compared with the none/mild group. When matched by age at time of enrollment and average HbA1c during the 18-month interval, participants who had a history of moderate/severe DKA compared with none/mild DKA were observed to have significantly lower Full Scale Intelligence Quotient scores and cognitive performance on the Detectability and Commission subtests of the Conners’ Continuous Performance Test II and the Dot Locations subtest of the Children’s Memory Scale. CONCLUSIONS A single episode of moderate/severe DKA in young children at diagnosis is associated with lower cognitive scores and altered brain growth. Further studies are needed to assess whether earlier diagnosis of type 1 diabetes and prevention of DKA may reduce the long-term effect of ketoacidosis on the developing brain.
Autoimmunity and immunodeficiency at the crossroad: autoimmune disorders as the presenting feature of selective IgM deficiency

Selective immunoglobulin M deficiency (sIgMD) is an immunodeficiency with undefined pathogenesis and commonly presenting with recurrent infections. 1 The European Society for Immunodeficiencies Registry defines sIgMD as a serum IgM level repeatedly below 2 SD of normal with normal levels of serum IgA, IgG and IgG subclasses, normal vaccination responses, absence of T-cell defects and absence of causative external factors. Rarely it can also be associated with autoimmune diseases. 2–7 Here we describe a patient with primary sIgMD; who presented with multiple autoimmune diseases without a history of recurrent infections and we provide a short literature review on sIgMD and autoimmune diseases.
Bifidobacterium Breve A1 Supplementation Improved Cognitive Decline in Older Adults with Mild Cognitive Impairment: An Open-Label, Single-Arm Study

ObjectivesWe previously reported the therapeutic potential of Bifidobacterium breve A1 (B. breve A1) for preventing cognitive impairment in Alzheimer’s disease model mice, which suggested that supplementation of the probiotics could be an effective therapeutic strategy for managing cognitive function in mild cognitive impairment (MCI). Design and SettingsWe conducted an open-label, single-arm study to examine the effects of 24-week supplementation of B. breve A1 on elderly with MCI in Aki Orthopedics Rehabilitation Clinic in Japan.Participants27 participants were screened by their Mini Mental State Examination (MMSE) scores.MeasurementsCognitive function was assessed using MMSE and Digit Symbol Substitution Test (DSST) at baseline and every 8 weeks. Mental condition and quality of life for gastrointestinal symptoms were measured using the Profile of Mood States 2nd Edition (POMS2), and the Gastrointestinal Symptom Rating Scale (GSRS). ResultsOf the 27 participants enrolled, 19 completed the study. MMSE scores were significantly increased during the intervention by mixed model Dunnett’s test and Wilcoxon signed-rank tests (+1.7, P < 0.01). POMS2 and GSRS scores were significantly improved during intervention when analyzed by Wilcoxon signed-rank tests.ConclusionThe present study showed that oral supplementation of B. breve A1 in participants with MCI improved cognitive function, thus suggesting the potential of B. breve A1 for improving cognitive function and maintaining quality of life of the elderly. Further randomized, double-blind placebo-controlled studies are worth conducting to examine the beneficial effect of B. breve A1.
Diamond Anvil Cell Partitioning Experiments for Accretion and Core Formation: Testing the Limitations of Electron Microprobe Analysis

Abstract Metal–silicate partitioning studies performed in high-pressure, laser-heated diamond anvil cells (DAC) are commonly used to explore element distribution during planetary-scale core–mantle differentiation. The small run-products contain suitable areas for analysis commonly less than tens of microns in diameter and a few microns thick. Because high spatial resolution is required, quantitative chemical analyses of the quenched phases is usually performed by electron probe microanalysis (EPMA). Here, EPMA is being used at its spatial limits, and sample thickness and secondary fluorescence effects must be accounted for. By using simulations and synthetic samples, we assess the validity of these measurements, and find that in most studies DAC sample wafers are sufficiently thick to be characterized at 15 kVacc. Fluorescence from metal-hosted elements will, however, contaminate silicate measurements, and this becomes problematic if the concentration contrast between the two phases is in excess of 100. Element partitioning experiments are potentially compromised; we recommend simulating fluorescence and applying a data correction, if required, to such DAC studies. Other spurious analyses may originate from sources external to the sample, as exemplified by 0.5 to >1 wt% of Cu arising from continuum fluorescence of the Cu TEM grid the sample is typically mounted on.
The effect of multiple nutrients on plasma parathyroid hormone level in healthy individuals

Abstract Although the effect of isolated nutrients on plasma parathyroid hormone (PTH) is somewhat familiar, the effect of multiple nutrients on plasma PTH level has not yet been studied. The aim of this study was to identify groups of food items that are associated with the plasma PTH level in healthy individuals. This cross-sectional study enrolled 1180 healthy individuals from Croatia with plasma PTH levels inside the referent values. A food frequency questionnaire containing 58 food items was completed to evaluate the dietary intake. We used principal component analysis to reduce food items into dietary groups, followed by linear regression analysis to test the association between dietary groups and the level of PTH. The results indicate that different sorts of vegetables (p = .006), sausages, salami, mushrooms, eggs (p = .033), as well as white bread (p = .009) are associated with the increase, while bran bread (p = .009) is associated with the decreased plasma PTH level.
Acute and Chronic Effects of Cigarette Smoking on sRAGE

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Pharmacotherapeutic strategies for treating pancreatic cancer: advances and challenges

ABSTRACT Introduction: Despite many efforts to improve the outcome of pancreatic ductal adenocarcinoma (PDAC), its prognosis remains poor, which is mostly related to late diagnosis and drug resistance. Improving systemic therapy is considered the major challenge in improving the outcome of this disease. Areas covered: This review covers novel chemotherapy and targeted agents in the treatment of PDAC, with a focus on advanced stage disease. Expert opinion: Current frontline therapies used in the treatment of patients with PDAC with favorable performance status are gemcitabine (GEM) and nab-paclitaxel or 5-fluorouracil, leucovorin, irinotecan, and oxaliplatin (FOLFIRINOX). PDAC has a number of genetic mutations that may explain its biological behavior, such as KRAS, p53 and CDK2NA, which occur in more than 90% of cases. Unfortunately, to this day, a specific targeting agent to any of those frequent gene mutations is lacking. Emerging areas of targeted therapies include the DNA repair, stroma, metabolism, and stem cells. Immunotherapy with either vaccines or immune checkpoint inhibitors has not produced any significant improvements in outcome of PDAC. Incorporating different approaches in therapy, including conventional, immunological, and others, is key in offering patients with the best possible care.
The preoperative single dose dexamethasone effect to pro-and anti-inflammatory cytokine during orthopedic surgery

Background: The efficacy of glucocorticoids like dexamethasone in reducing postoperative pain has been investigated and showed that a single dose of dexamethasone significantly analgesia has advantages in terms of reduction in pain intensity, opioid requirements, rescue analgesia, and did not increase the incidence of infection and impaired wound healing. The aim of this study was to evaluate the effects of preoperative single dose of intravenous dexamethasone to the dynamics of pro- and anti-inflammatory cytokine in orthopedic surgery perioperative period. Materials and Methods: Thirty patients were studied and randomly into two groups: 15 patients received 8 mg dexamethasone intravenous preoperatively and perioperative analgesia with paracetamol and patient-controlled analgesia (PCA) morphine (dexamethasone group) and 15 patients received perioperative analgesia paracetamol and PCA morphine only (control group). Blood samples were taken at the time before anesthesia, immediately postsurgery, 4 h and 24 h after surgery to measure plasma levels of interleukin 6 (IL-6) and IL-10. We recorded the pain intensity and morphine requirement in 4 h and 24 h after surgery. Results: IL-6 levels in the dexamethasone group did not increased from immediately after surgery to 24 h after surgery but increased in the control group (P < 0.05). There is no difference of IL-10 levels in both groups at all measurement time. Rest and moving pain intensity from time to time in the two groups did not differ except the rest pain at 24 h postoperative (P < 0.05). Morphine requirement in the dexamethasone group was lower in the 24 h after surgery than the control group. Conclusion: The addition of dexamethasone preoperatively on the combination of paracetamol and morphine did not change plasma levels of IL-6 and IL-10 cytokines Dexamethasone provides sufficient analgesia and decrease postoperative opioid requirement.