Miracle-dz/UniFAR-FTUs huggingface dataset:
The p53 homolog p63 modulates acute and chronic damage in irradiated salivary glands

Head and neck cancer is diagnosed in more than 50,000 Americans each year, resulting in roughly 11,000 deaths. For this disease, a typical therapeutic regimen involves cisplatin, a radiosensitizer, given alongside targeted irradiation. While technological advances such as IMRT have been useful in sparing normal tissues from radiotherapy, the salivary glands occupy much of the head and neck and surround several lymph nodes, and thus, non-diseased salivary glands are often damaged. This causes reduced salivary output, damaged oral mucosa, dysphagia, malnutrition and tooth decay. Often, these side-effects are so severe that patients discontinue treatment, however, in many cases, salivary gland damage is permanent, and treatment options are palliative. Specifically, muscarinic-cholinergic agonists are used to enhance secretion from remaining salivary cells, although due to non-specific action, these drugs have a number of ill-effects. It is clear that therapies are needed to prevent radiation-induced salivary gland damage, as well as to restore glandular function in patients who are already suffering. Previous work from our group has shown that salivary gland dysfunction results from loss of acinar cells to radiation-induced apoptosis. Importantly, a single intravenous dose of IGF1 can prevent apoptosis and preserve salivary output when given immediately prior to irradiation. Because of its broad effects, however, IGF1 may never be a viable clinical option. Instead, our goal is to identify signaling events that mediate the radioprotective effects of IGF1 downstream of Akt. Because radiation-induced apoptosis in salivary glands is p53-dependent, we assessed the contributions of the p53 homologs
Comparison of Polymerization Shrinkage, Physical Properties, and Marginal Adaptation of Flowable and Restorative Bulk Fill Resin-Based Composites.

PURPOSE The purpose of this study was to compare the marginal adaptation of two flowable bulk fill resin-based composites (FB-RBCs), two restorative bulk fill resin-based composites (RB-RBCs), and one regular incremental-fill RBC in MOD cavities in vitro. Additionally, the influence of linear polymerization shrinkage, shrinkage force, flexural modulus, and bottom/top surface hardness ratio on the marginal adaptation was evaluated. METHODS A Class II MOD cavity was prepared in 40 extracted sound lower molars. In group 1 (control group), the preparation was filled with Filtek Z350 (Z3, 3M ESPE, St Paul, MN, USA) using the incremental filling technique. The FB-RBCs, SDR (SD, group 2) (Dentsply Caulk, Milford, DE, USA) and Venus Bulk Fill (VB, group 3) (Heraeus Kulzer, Dormagen, Germany), were placed in the core portion of the cavity first, and Z350 was filled in the remaining cavity. The RB-RBCs, Tetric N-Ceram Bulkfill (TB, group 4) (Ivoclar Vivadent, Schaan, Liechtenstein) and SonicFill (SF, Group 5) (Kerr, West Collins, Orange, CA, USA), were bulk filled into the preparation. Images of the magnified marginal area were captured under 100× magnification before and after thermomechanical loading, and the percentage ratio of the imperfect margin (%IMwhole) was calculated. Gaps, cracks in the enamel layer, and chipping of composite, enamel, or dentin were all considered to be imperfect margins. Linear polymerization shrinkage, polymerization shrinkage force, flexural strength, flexural modulus, and bottom/top surface hardness ratio of were measured. Eight specimens were allocated for each material for each test. One-way analysis of variance with the Scheffé test was used to compare the groups at a 95% confidence level. RESULTS Before thermomechanical loading, %IMwhole was in the order of group 3 ≤ groups 2 and 5 ≤ groups 1 and 4 (p=0.011), whereas after loading, it was in the order of group 4 ≤ group 5 ≤ group 1 ≤ groups 2 and 3 (p<0.001). The order of materials were Z3 < TB and SF < SD and VB (p<0.001) in polymerization shrinkage; SF ≤ TB ≤ Z3 < SD < VB (p<0.001) in polymerization shrinkage force; VB < SD < TB ≤ Z3 ≤ SF (p<0.001) in flexural modulus; SD, VB, and TB < Z3 and SF (p<0.001) in flexural strtength; and SF< Z3 < TB < VB and SD (p<0.001) in bottom/top surface hardness ratio. The Pearson correlation constant between %IMwhole and polymerization shrinkage, shrinkage force, elastic modulus, and bottom/top surface hardness ratio was 0.697, 0.708, -0.373, and 0.353, respectively, after thermomechanical loading. CONCLUSION Within the limitations of this study, RB-RBCs showed better marginal adaptation than FB- RBCs. The lower level of polymerization shrinkage and polymerization shrinkage stress in RB-RBCs seems to contribute to this finding because it would induce less polymerization shrinkage force at the margin. FB-RBCs with lower flexural modulus may not provide an effective buffer to occlusal stress when they are capped with regular RBCs.
Exercise and the heart: the Good, the Bad, and the Ugly

This review addresses three aspects of exercise impor- tant to the clinical cardiologist, including the thera- peutic use of exercise, the adaptations produced by chronic endurance exercise training, and the risks of vigorous exertion. Regular exercise is useful in reduc- ing atherosclerotic coronary heart disease (CHD) risk, treating selected CHD risk factors, managing CHD patients after an initial cardiac event, and in improv- ing effort tolerance in patients with angina pectoris, congestive heart failure, and claudication. Chronic endurance exercise training produces cardiovascular adaptations, including bradyarrhythmias, cardiac en- largement, and cardiac murmurs, which must be dif- ferentiated from those conditions that increase the cardiovascular risk of exercise. This risk in young sub- jects is due to congenital abnormalities and acquired cardiomyopathy, whereas cardiac complications in adults are largely due to atherosclerotic vascular dis- ease. Prevention of exercise-related cardiac events is difficult because of their rarity, and depends on selective preparticipation screening and the careful evaluation of symptomatic athletes before permitting their return to competition.
The Effect of 2 Injection Speeds on Local Anesthetic Discomfort During Inferior Alveolar Nerve Blocks.

This randomized double-blind crossover trial investigated the discomfort associated with 2 injection speeds, low (60 seconds) and slow (100 seconds), during inferior alveolar nerve block by using 1.8 mL of 2% lidocaine with 1 : 100,000 epinephrine. Three phases were considered: (a) mucosa perforation, (b) needle insertion, and (c) solution injection. Thirty-two healthy adult volunteers needing bilateral inferior alveolar nerve blocks at least 1 week apart were enrolled in the present study. The anesthetic procedure discomfort was recorded by volunteers on a 10-cm visual analog scale in each phase for both injection speeds. Comparison between the 2 anesthesia speeds in each phase was performed by paired t test. Results showed no statistically significant difference between injection speeds regarding perforation (P = .1016), needle placement (P = .0584), or speed injection (P = .1806). The discomfort in all phases was considered low. We concluded that the 2 injection speeds tested did not affect the volunteers' pain perception during inferior alveolar nerve blocks.
Surviving Prison: Exploring prison social life as a determinant of health

Prison social environments play an important role in the health of prisoners. How they respond to imprisonment is partially dependent upon how effectively they integrate into an institution’s social structure, learn to fit in with others and adapt to and cope with becoming detached from society, community and family ‐ hence, how they personally manage the transition from free society to a closed carceral community. This paper reports on findings of an ethnography conducted in an adult male training prison in England, which used participant observation, group interviewing, and one‐to‐one semi‐structured interviews with prisoners and prison officers. The research explored participants’ perceptions of imprisonment, particularly with regard to how they learned to adapt to and ‘survive’ in prison and their perceptions of how prison affected their mental, social and physical well‐being. It revealed that the social world of prison and a prisoner’s dislocation from society constitute two key areas of ‘deprivation’ that can have important health impacts.
Placental malperfusion in response to intrauterine inflammation and its connection to fetal sequelae

Exposure to intrauterine inflammation (IUI) is associated with short- and long-term adverse perinatal outcomes. However, little data exist on utilizing placenta to prognosticate fetal injury in this scenario. Our study aimed to utilize imaging modalities to evaluate mechanisms contributing to placental injury following IUI exposure and correlated it to concomitant fetal brain injury. CD1 pregnant dams underwent laparotomies and received intrauterine injections of either lipopolysaccharide (LPS; a model of IUI) or phosphate-buffered saline (PBS). In utero ultrasound Doppler velocimetry of uterine and umbilical arteries and magnetic resonance imaging (MRI) of placental volumes with confirmatory immunohistochemical (vimentin) and histochemistry (fibrin) analyses were performed. ELISA for thrombosis markers, fibrinogen and fibrin was performed to analyze thrombi in placenta. Fetal brain immunohistochemistry was performed to detect microglial activation (ionized calcium-binding adaptor molecule 1, Iba1). On ultrasound, LPS group demonstrated elevated resistance indices, pulsatility indices and a greater occurrence of absent end-diastolic flow in the umbilical and uterine arteries. In the fetus, there was an increased cardiac Tei indices in the LPS group. MRI revealed decreased volume of placenta in the LPS group associated with placental thinning and placental endothelial damage on immunohistochemistry. Decreased fibrinogen content and more thrombi staining in placenta exposed to maternal LPS indicated the hypercoagulability. Furthermore, the expression of Iba1was significantly associated with placental thickness (r = -0.7890, Pearson correlation coefficient). Our data indicate that IUI can trigger events leading to maternal placental malperfusion and fetal vessel resistance, as well as predispose the developing fetus to cardiac dysfunction and brain damage. Furthermore, our data suggest that prenatal ultrasound can be a real-time clinical tool for assessing fetal risk for adverse neurologic outcomes following the potential IUI exposure.
Outcome of Screening for Congenital Hypothyroidism in Mazandaran Province: From Diagnosis to Treatment

Background and purpose: Screening for congenital hypothyroidism in newborns is carried out with TSH measurement of blood samples from newborn heel in Mazandaran province since 2006. This paper reports the status of these children until the end of 2012. Materials and methods: The study was performed in 2013-2014 using current information. Babies with TSH levels greater than 5 mU / L were treated with levothyroxine for three years. If the drug was stopped abruptly or gradually in three years and normal TSH achieved the disease was regarded transient, otherwise the patients were considered for lifelong follow-up treatments. For data analysis SPSS V.16 was applied. Results: During this period, 269088 infants were screened. Among the cases 548 (54.4% male) were diagnosed with congenital hypothyroidism. The results showed that infants who were treated at each time interval were 43% of permanent and 57% transient hypothyroidism. Age at onset therapy in 95% of cases was before 60 days. The mean time to start treatment was 20.8 ± 10 days. No significant relationship was found between the sex and permanent or transient hypothyroidism. Conclusion: The screening program for congenital hypothyroidism is being performed successfully in Mazandaran province. In some cases, the dosage of drugs and infants' follow-up intervals varied even between physicians. Also, levothyroxine is either not prescribed according to the infant's weight or is recorded incorrectly. Follow-up procedures and the decision to discontinue treatment were not similar at 3 years of age of the subjects. Physicians should be informed for the strict implementation of the guidelines of the Ministry of Health. To obtain more accurate information cases of death or immigration should not be removed from the statistics.
Theoretical Analysis of the Faraday Effect in Carbon Nanotubes with Arbitrary Chirality

Using tight-binding model with nearest neighbour interactions, the optical properties of carbon nanotubes under the influence of an external magnetic field are analyzed. First, dipole matrix elements for two cases of light polarized parallel as well as perpendicular to the nanotube axis are analyzed. A close form analytic expression for dipole matrix is obtained for carbon nanotubes with arbitrary chirality in the case of light polarized parallel to the nanotube axis. Then the diagonal and off-diagonal elements of the frequency-dependent susceptibility in the presence of an axial magnetic field are investigated. The off-diagonal elements are applied to calculate the interband Faraday rotation and the Verdet constant. These effects should be clearly detectable under realistic conditions using weak magnetic fields.
Glyphosate, but not its metabolite AMPA, alters the honeybee gut microbiota

The honeybee (Apis mellifera) has to cope with multiple environmental stressors, especially pesticides. Among those, the herbicide glyphosate and its main metabolite, the aminomethylphosphonic acid (AMPA), are among the most abundant and ubiquitous contaminant in the environment. Through the foraging and storing of contaminated resources, honeybees are exposed to these xenobiotics. As ingested glyphosate and AMPA are directly in contact with the honeybee gut microbiota, we used quantitative PCR to test whether they could induce significant changes in the relative abundance of the major gut bacterial taxa. Glyphosate induced a strong decrease in Snodgrassella alvi, a partial decrease of a Gilliamella apicola and an increase in Lactobacillus spp. abundances. In vitro, glyphosate reduced the growth of S. alvi and G. apicola but not Lactobacillus kunkeei. Although being no bee killer, we confirmed that glyphosate can have sublethal effects on the honeybee microbiota. To test whether such imbalanced microbiota could favor pathogen development, honeybees were exposed to glyphosate and to spores of the intestinal parasite Nosema ceranae. Glyphosate did not significantly enhance the effect of the parasite infection. Concerning AMPA, while it could reduce the growth of G. apicola in vitro, it did not induce any significant change in the honeybee microbiota, suggesting that glyphosate is the active component modifying the gut communities.
Herpes simplex virus type 1 epidemiology in Latin America and the Caribbean: Systematic review and meta-analytics

Objectives To investigate the epidemiology of herpes simplex virus type 1 (HSV-1) in Latin America and the Caribbean. Methods Systematic review and meta-analytics guided by the Cochrane Collaboration Handbook and reported following the PRISMA guidelines. Results Thirty-three relevant reports were identified including 35 overall (and 95 stratified) seroprevalence measures, and five and nine proportions of virus isolation in genital ulcer disease (GUD) and in genital herpes, respectively. Pooled mean seroprevalence was 57.2% (95% CI: 49.7–64.6%) among children and 88.4% (95% CI: 85.2–91.2%) among adults. Pooled mean seroprevalence was lowest at 49.7% (95% CI: 42.8–56.6%) in those aged ≤10, followed by 77.8% (95% CI: 67.9–84.8%) in those aged 10–20, 82.8% (95% CI: 73.1–90.8%) in those aged 20–30, 92.5% (95% CI: 89.4–95.1%) in those aged 30–40, and 94.2% (95% CI: 92.7–95.5%) in those aged ≥40. Age was the strongest source of heterogeneity in seroprevalence, explaining 54% of variation. Evidence was found for seroprevalence decline over time. Pooled mean proportion of HSV-1 isolation was 0.9% (95% CI: 0.0–3.6%) in GUD and 10.9% (95% CI: 4.4–19.4%) in genital herpes. Conclusions HSV-1 is a widely prevalent infection in this region, but its epidemiology may be slowly transitioning, with still limited contribution for HSV-1 in genital herpes.
Epidemiological and clinical features of Kawasaki disease in Spain over 5 years and risk factors for aneurysm development. (2011-2016): KAWA-RACE study group

Background Kawasaki disease (KD) is an acute self-limited systemic vasculitis of unknown etiology affecting mainly children less than 5 years of age. Risk factors for cardiac involvement and resistance to treatment are insufficiently studied in non-Japanese children. Objective This study aimed to investigate the epidemiology, clinical features and risk factors for resistance to treatment and coronary artery lesions (CAL) in KD in Spain. Methods Retrospective study (May 2011-June 2016) of all patients less than 16 years of age diagnosed with KD included in KAWA-RACE network (84 Spanish hospitals). Results A total of 625 cases were analyzed, 63% were males, 79% under 5 year-olds and 16.8% younger than 12 months. On echocardiographic examination CAL were the most frequent findings (23%) being ectasia the most common (12%). Coronary aneurysms were diagnosed in 9.6%, reaching 20% in infants under 12 months (p<0.001). A total of 97% of the patients received intravenous immunoglobulin (IVIG) with a median number of days from fever onset to IVIG administration of 7.2. A second dose was given to 15.7% and steroids to 14.5% patients. Only 1.4% patients received infliximab. No deaths were reported. A multivariate analysis identified anemia, hypoalbuminemia, hyponatremia, higher creatinine and procalcitonin as independent risk factors for treatment failure and length under 103 cm, hemoglobin < 10.2 mg/dL, platelets > 900,000 cells/mm3, maximum temperature < 39.5°C, total duration of fever > 10 days and fever before treatment ≥ 8 days as independent risk factors for developing coronary aneurysms. Conclusions In our population, children under 12 months develop coronary aneurysms more frequently and children with KD with anemia and leukocytosis have high risk of cardiac involvement. Adding steroids early should be considered in those patients, especially if the treatment is not started before 8 days of fever. A score applicable to non-Japanese children able to predict the risk of aneurysm development and IVIG resistance is necessary.
Total cholesterol variability and risk of atrial fibrillation: A nationwide population-based cohort study

Background Long-term variability of cardiometabolic risk factors have been suggested as the risk factors for cardiovascular disease and mortality. However, the effect of long-term variability of total cholesterol (TC) on incident atrial fibrillation (AF) has not been examined. Methods and findings We explored whether visit-to-visit TC variability are associated with the risk of incident AF in 160,165 Korean adults, using the population-based Korean National Health Insurance Service–Health Screening Cohort (NHIS-HEALS) database, over a median duration of 8.4 years. TC variability was measured as coefficients of variance (TC-CV), standard deviation (TC-SD), and variability independent of the mean (TC-VIM). Kaplan–Meier analysis demonstrated a decreased disease-free probability in the highest quartile group of TC variability compared to that in the other groups. In the multivariate Cox proportional hazard analysis, the risk of AF increased significantly in the highest quartile group of TC variability. After multivariate adjustment for confounding variables including mean TC levels, the hazard ratio for incident AF was 1.15 (95% confidence interval 1.05–1.25; P = 0.0035) when comparing the highest with the lowest TC variability quartile (TC-CV). These relationships were consistent with TC variability defined using TC-SD or TC-VIM. Subgroup analyses, including age, sex, body mass index, and cardiometabolic disorders, showed similar results. Conclusions The present study is the first to demonstrate that high TC variability was associated with an increased risk of AF.
A cluster randomised, double-blind pilot and feasibility trial of an active behavioural physiotherapy intervention for acute whiplash-associated disorder (WAD)II

Whiplash-associated disorder (WAD) causes substantial social and economic burden, with ≥70% patients classified as WADII (neck complaint and musculoskeletal sign(s)). Effective management in the acute stage is required to prevent development of chronicity; an issue for 60% of patients. An Active Behavioural Physiotherapy Intervention (ABPI) was developed to address both physical and psychological components of WAD. The ABPI is a novel complex intervention designed through a rigorous sequential multiphase project to prevent transition of acute WAD to chronicity. An external pilot and feasibility cluster randomised double-blind (assessor, participants) parallel two-arm clinical trial was conducted in the UK private sector. The trial compared ABPI versus standard physiotherapy to evaluate trial procedures and feasibility of the ABPI for managing acute WADII in preparation for a future definitive trial. Six private physiotherapy clinics were recruited and cluster randomised using a computer-generated randomisation sequence. Twenty-eight (20 ABPI, 8 standard physiotherapy) participants [median age 38.00 (IQR = 21.50) years] were recruited. Data were analysed descriptively with a priori establishment of success criteria. Ninety-five percent of participants in the ABPI arm fully recovered (Neck Disability Index ≤4, compared to 17% in the standard physiotherapy arm); required fewer treatment sessions; and demonstrated greater improvement in all outcome measures (pain intensity, Cervical Range of Motion, Pressure Pain Threshold, EuroQol-5 Dimensions) except for the Impact of Events Scale and Fear Avoidance Beliefs Questionnaire. The findings support the potential value of the ABPI, and that an adequately powered definitive trial to evaluate effectiveness (clinical, cost) is feasible with minor modifications to procedures.
Poor outcomes in recurrent tuberculosis: More than just drug resistance?

Background Approximately 11% of people reported to have tuberculosis (TB) have previously received treatment. Clinical outcomes are consistently poor on retreatment regimens, however reasons for this are unclear. This study aimed to explore factors which may contribute to unsuccessful outcomes in retreatment TB. Methods and findings A prospective cohort of consecutive patients starting WHO Category II retreatment regimen was recruited at a central hospital in Malawi. Participants were evaluated at baseline, after completion of the intensive phase at 2-months, and at the end of the 8-month treatment course. Patients were assessed for respiratory co-morbidity; anaemia; renal impairment; diabetes; Anti-retroviral (ART) failure; and drug toxicity. Amongst 158 patients entering TB care at the point of a recurrent episode, only 92 (58%) had a microbiologically confirmed diagnosis. The prevalence of drug resistance was low (9.6%). Of the 158 patients, 131 (83%) were HIV-positive, of whom 96 (73%) were on ART. Of 63 patients on ART >1 year, 24 (38%) had ART failure. Chronic lung disease was found in 88% on CT thorax, including scarring (80%), bronchiectasis (61%), COPD (22%), and destroyed lung (19%). Spirometry revealed restrictive deficit in 60%, and obstructive deficit in 7% of patients. Anaemia and renal impairment were common (34% and 45% respectively). Ototoxicity developed in 32%, and nephrotoxicity in 15%. 40% of patients reported peripheral neuropathy. Liver injury developed in 4%. Conclusions If outcomes are to be improved in retreatment TB, there is an urgent need to address the impact of other co-morbid medical conditions including chronic lung disease, HIV and ART failure.