Miracle-dz/UniFAR-FTUs huggingface dataset:
Omni-focal refractive focus correction technology as a substitute for bi/multi-focal intraocular lenses, contact lenses, and spectacles

We present novel technology for extension in depth of focus of imaging lenses for use in ophthalmic lenses correcting myopia, hyperopia with regular/irregular astigmatism and presbyopia. This technology produces continuous focus without appreciable loss of energy. It is incorporated as a coating or engraving on the surface for spectacles, contact or intraocular lenses. It was fabricated and tested in simulations and in clinical trials. From the various testing this technology seems to provide a satisfactory single-lens solution. Obtained performance is apparently better than those of existing multi/bifocal lenses and it is modular enough to provide solution to various ophthalmic applications.
Alzheimer's disease and dementing disorders: Practices and experiences of rural physicians

This paper presents information on rural primary care physicians' diagnoses, the procedures used, treatment recommendations, as well as reported advantages and disadvantages ofpracticing in a rural setting and managing patients with Alzheimer's disease and dementing disorders. A total of 102 primary care physicians in rural Illinois counties were interviewed (response rate = 72.3 percent). There was considerable variability in physicians' responses to the causes of dementia syndrome and the procedures used in making a diagnosis. When questioned in an open-ended format about possible causes of dementing disorders, physicians mostfrequently mentioned Alzheimer's disease (80 percent), multi-infarct dementia (56percent), and drug toxicity (53 percent). “Non-specific” causes were also mentioned, including arteriosclerosis (36 percent), organic brain syndrome (27 percent), and old age (25 percent). Laboratory tests and CT scans were most often used in the diagnostic process. Less than 10 percent of the physicians used more formal, cognitive screening tests like the Mini-Mental State Exam. Less than one-half of the physicians had previously recommended nursing home placement in the management of their dementia patients. Physician age, practice type (solo/group) and specialty (internal/family medicine) were associated with some of the physicians' responses regarding dementia causes and procedures used in diagnosis. The rural setting was viewed as inadequate with regard to laboratory facilities and supportpersonnel as well as problematic in requiring long distance travel for consultation. On the other hand, the rural community provided an advantage over the urban in opportunities for support and cooperation forfamilies andfriends to assist in managing the care ofdementia disorder patients. Alzheimer's disease and other dementias present the problem of uncertainty at many levels including medical, patient outcome, and family management issues. In the rural setting, the physician often represents the entire health professions community. It is imperative that rural physicians be prepared to both diagnose and, in turn, manage the complex and difficultsituation created by dementia syndrome.
Measuring the youth bullying experience: a systematic review of the psychometric properties of available instruments.

BACKGROUND Bullying is a significant problem in schools and measuring this concept remains problematic. The purposes of this study were to (1) identify the published self-report measures developed to assess youth bullying; (2) evaluate their psychometric properties and instrument characteristics; and (3) evaluate the quality of identified psychometric papers evaluating youth bullying measures. METHODS A systematic review of the literature was conducted using 4 electronic databases. Data extraction and appraisal of identified instruments were completed using a standardized method and Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. RESULTS Thirty-one articles describing 27 self-report instruments were evaluated in our analysis. Quality assessments ranged from 18% to 91%, with 6 papers reaching or exceeding a quality score of 75%. Limited evidence supporting the reliability, validity, and responsiveness of existing youth bullying measures was identified. CONCLUSIONS Evidence supporting the psychometric soundness of the instruments identified was limited. Many measures were in early development and additional evaluation is necessary to validate their psychometric properties. A pool of instruments possesses acceptable initial psychometric dependability for selected assessment purposes. These findings have significant implications for assessing youth bullying and designing and evaluating school-based interventions.
A Setup for Administering TMS to Medial and Lateral Cortical Areas During Whole-Brain fMRI Recording

Summary: Stimulating brain areas with transcranial magnetic stimulation (TMS) while concurrently and noninvasively recording brain activity changes through functional MRI enables a new range of investigations about causal interregional interactions in the human brain. However, standard head–coil arrangements for current methods for concurrent TMS-functional MRI somewhat restrict the cortical brain regions that can be targeted with TMS because space in typical MR head coils is limited. Another limitation for concurrent TMS-functional MRI approaches concerns the estimation of the precise stimulation site, which can limit the interpretation of the activity changes induced by TMS and increase the variability of the stimulation effects. Here, we present a novel approach using flexible MR receiver coils, allowing for stimulation of a large part of the cortex including more lateral areas. Furthermore, we present a fast and economical method to determine the precise location of the stimulation coil during scanning. This point-based registration method can accurately compute, during scanning, where TMS pulses are delivered. We validated this approach by stimulating medial (M1) and more lateral (dorsal part of the supramarginal gyrus) brain areas concurrently with functional MRI. Activation close to but not directly at the stimulated location and in distal areas connected to the targeted site was observed. This study provides a proof of concept that TMS of medial and lateral brain areas is feasible without significantly compromising brain coverage and that one can precisely determine the exact coil location inside the bore to verify targeting of brain areas.
Warburg meets autophagy: cancer-associated fibroblasts accelerate tumor growth and metastasis via oxidative stress, mitophagy, and aerobic glycolysis.

SIGNIFICANCE Here, we review certain recent advances in oxidative stress and tumor metabolism, which are related to understanding the contributions of the microenvironment in promoting tumor growth and metastasis. In the early 1920s, Otto Warburg, a Nobel Laureate, formulated a hypothesis to explain the "fundamental basis" of cancer, based on his observations that tumors displayed a metabolic shift toward glycolysis. In 1963, Christian de Duve, another Nobel Laureate, first coined the phrase auto-phagy, derived from the Greek words "auto" and "phagy," meaning "self" and "eating. " RECENT ADVANCES Now, we see that these two ideas (autophagy and aerobic glycolysis) physically converge in the tumor stroma. First, cancer cells secrete hydrogen peroxide. Then, as a consequence, oxidative stress in cancer-associated fibroblasts drives autophagy, mitophagy, and aerobic glycolysis. CRITICAL ISSUES This "parasitic" metabolic coupling converts the stroma into a "factory" for the local production of recycled and high-energy nutrients (such as L-lactate)-to fuel oxidative mitochondrial metabolism in cancer cells. We believe that Warburg and de Duve would be pleased with this new two-compartment model for understanding tumor metabolism. It adds a novel stromal twist to two very well-established cancer paradigms: aerobic glycolysis and autophagy. FUTURE DIRECTIONS Undoubtedly, these new metabolic models will foster the development of novel biomarkers, and corresponding therapies, to achieve the goal of personalized cancer medicine. Given the central role that oxidative stress plays in this process, new powerful antioxidants should be developed in the fight against cancer.
Lithium improves cell viability in psychosine‐treated MO3.13 human oligodendrocyte cell line via autophagy activation

Globoid cell leukodystrophy (GLD) is a rare, rapidly progressing childhood leukodystrophy triggered by deficit of the lysosomal enzyme galactosylceramidase (GALC) and characterized by the accumulation of galactosylsphingosine (psychosine; PSY) in the nervous system. PSY is a cytotoxic sphingolipid, which leads to widespread degeneration of oligodendrocytes and Schwann cells, causing demyelination. Here we report on autophagy in the human oligodendrocyte cell line MO3.13 treated with PSY and exploitation of Li as an autophagy modulator to rescue cell viability. We demonstrate that PSY causes upregulation of the autophagic flux at the level of autophagosome and autolysosome formation and LC3‐II expression. We show that pretreatment with Li, a drug clinically used to treat bipolar disorders, can further stimulate autophagy, improving cell tolerance to PSY. This Li protective effect is found not to be linked to reduction of PSY‐induced oxidative stress and might not stem from a reduction of PSY accumulation. These data provide novel information on the intracellular pathways activated during PSY‐induced toxicity and suggest the autophagy pathway as a promising novel therapeutic target for ameliorating the GLD phenotype. © 2016 Wiley Periodicals, Inc.
Graded fear generalization enhances the level of cfos‐positive neurons specifically in the basolateral amygdala

Fear is an important emotional reaction in response to threatening stimuli and is important for survival. However, when fear occurs in inappropriate circumstances, it can lead to pathological conditions including an increased vulnerability for developing anxiety disorders such as posttraumatic stress disorder (PTSD). Patients with PTSD generalize fear to contexts or to environments that are not associated with the trauma. We sought to explore if increasing the level of dissimilarity relative to the context in which mice learn fear results in changes in the level of fear responding to the new context. We also determined with this procedure if the number of cells expressing the immediate early gene cfos changes with the corresponding level of expressed fear within brain regions known to be important in modulating fear, including the basolateral amygdala (BLA) and hippocampus. Our results indicate that mice that were tested in increasingly different contexts showed significantly different levels of fear responses. Freezing level was higher in the context most similar to the acquisition context than the one that was highly different. The level of cfos within the BLA, but not hippocampus, was also significantly different between the test contexts, with higher levels in the somewhat similar compared with the most different context. Overall, these results highlight the BLA as a critical region in the node of fear circuitry for modulating fear generalization. © 2016 Wiley Periodicals, Inc.
Suicides not in contact with mental health services: Risk indicators and determinants of referral

Background: Three quarters of UK suicides were not in contact with mental health services one year before dying. The characteristics of this group of suicides have not been adequately explored. Aim: Identify risk factors in no-contact suicides and explain non-referral to Mental Health Services (MHS). Method: Ongoing, observational, retrospective survey of all suicides in West Kent (population 988,027) over 5 years. No contact suicides are compared with MHS suicides through standard questionnaires completed by consultant psychiatrists, and general practitioners, and by examining coroners' records. Results: No contact suicides were significantly more likely to be male, employed, living with others and not diagnosed with a mental disorder. They have a significantly lesser frequency of previous self-harm. Their suicide risk is retrospectively estimated to be lower. 50.5% of all suicides were either not registered, had no general practitioner contact, or were last seen 13 weeks or more before suicide. These characteristics can explain non referral to specialist services. Conclusion: No-contact suicides take place to a considerable extent outside the current limitations of primary health and social care systems. Many have a different risk factor profile, and are similar to people who do not seek medical help in the first place. Declaration of interest: None.
From blast to bench: A translational mini‐review of posttraumatic headache

Current events within the military and professional sports have resulted in an increased recognition of the long‐term and debilitating consequences of traumatic brain injury. Mild traumatic brain injury accounts for the majority of head injuries, and posttraumatic headache is the most common adverse effect. It is estimated that between 30% to 90% of traumatic brain injuries result in posttraumatic headache, and for a significant number of people this headache disorder can continue for up to and over a year post injury. Often, the most severe and chronic posttraumatic headache has a migraine‐like phenotype and is difficult to resolve. In this review we discuss the preclinical findings from animal models of posttraumatic headache. We also describe potential mechanisms by which traumatic brain injury leads to chronic posttraumatic headache, including neuroinflammatory mediators and migraine‐associated neuropeptides. There are surprisingly few preclinical studies that have investigated overlapping mechanisms between posttraumatic headache and migraine, especially considering the prevalence and debilitating nature of posttraumatic headache. Given this context, posttraumatic headache is a field with many emerging opportunities for growth. The frequency of posttraumatic headache in the general and military population is rising, and further preclinical research is required to understand, ameliorate, and treat this disabling disorder. © 2017 Wiley Periodicals, Inc.
Surgical Options in Chronic Obstructive Pulmonary Disease

Emphysema poses a considerable burden on healthcare resources. In economic terms, the cost of chronic obstructive pulmonary disease (COPD) in the United States alone has been estimated to exceed $30 billion in direct and indirect costs. Despite ever-changing pharmacologic advances, we have yet to make a significant impact on disease progression using a purely medical approach. However, several surgical procedures, some developed over 50 years ago, have demonstrated therapeutic benefit in treating patients with COPD. There are currently 3 surgical options for advanced COPD: bullectomy, lung volume reduction surgery (LVRS), and transplantation. There are also several novel minimally invasive bronchoscopic therapies that are currently being studied. One or more of these options may best suit a particular patient based on their underlying disease. This review helps healthcare practitioners understand how emphysema impacts pulmonary function and reviews surgical methods that may improve this disease state. The goal is to help guide physicians and caregivers to the most appropriate therapy for each individual patient.
Hospice Methods to Measure and Analyze Nursing‐sensitive Patient Outcomes

A tool was developed to measure outcomes for patients who were imminently dying when admitted to both inpatient and home care hospice settings. The specific area of concern to the hospice team was the dignity experienced by the patient and family during the dying process. The study took place over 2 years, from 2000 to 2002. The nursing-sensitive patient outcomes were selected from those developed by the University of Iowa College of Nursing. Ten outcome indicators were selected. Each indicator was given descriptors that were ranked on a scale from 1 to 5. The four most frequently measured outcomes improved significantly from time of admission until death. The Dignified Dying Outcome Tool provided a means for better understanding the care being provided to imminently dying patients as well as a measure for nursing staff to determine the outcomes of their interventions.
Disruption of endothelial cell mitochondrial bioenergetics in lambs with increased pulmonary blood flow.

AIMS The mitochondrial dysfunction in our lamb model of congenital heart disease with increased pulmonary blood flow (PBF) (Shunt) is associated with disrupted carnitine metabolism. Our recent studies have also shown that asymmetric dimethylarginine (ADMA) levels are increased in Shunt lambs and ADMA increases the nitration of mitochondrial proteins in lamb pulmonary arterial endothelial cells (PAEC) in a nitric oxide synthase (NOS)-dependent manner. Thus, we determined whether there was a mechanistic link between endothelial nitric oxide synthase (eNOS), ADMA, and the disruption of carnitine homeostasis in PAEC. RESULTS Exposure of PAEC to ADMA induced the redistribution of eNOS to the mitochondria, resulting in an increase in carnitine acetyl transferase (CrAT) nitration and decreased CrAT activity. The resulting increase in acyl-carnitine levels resulted in mitochondrial dysfunction and the disruption of mitochondrial bioenergetics. Since the addition of L-arginine prevented these pathologic changes, we examined the effect of L-arginine supplementation on carnitine homeostasis, mitochondrial function, and nitric oxide (NO) signaling in Shunt lambs. We found that the treatment of Shunt lambs with L-arginine prevented the ADMA-mediated mitochondrial redistribution of eNOS, the nitration-mediated inhibition of CrAT, and maintained carnitine homeostasis. In turn, adenosine-5'-triphosphate levels and eNOS/heat shock protein 90 interactions were preserved, and this decreased NOS uncoupling and enhanced NO generation. INNOVATION Our data link alterations in cellular L-arginine metabolism with the disruption of mitochondrial bioenergetics and implicate altered carnitine homeostasis as a key player in this process. CONCLUSION L-arginine supplementation may be a useful therapy to prevent the mitochondrial dysfunction involved in the pulmonary vascular alterations secondary to increased PBF.
Antioxidants for the treatment of patients with severe angioproliferative pulmonary hypertension?

SIGNIFICANCE Pathobiological mechanisms that contribute to pulmonary vasoconstriction, lung vascular remodeling, and the development of right heart failure include the generation of reactive oxygen and nitrogen species and the response of lung vascular and cardiac cells to these molecules. We review the information regarding oxidant stress balanced by antioxidant mechanisms and the role of oxidants and antioxidants in hypoxic pulmonary hypertension and their potential role in an animal model of severe pulmonary arterial hypertension (PAH). RECENT ADVANCES In human lung tissue from patients with idiopathic PAH, we find reduced superoxide dismutase activity and high expression of the oxidant stress markers nitrotyrosine and 8-OH-guanosine. In the Sugen 5416/chronic hypoxia model of PAH, lung tissue expression of nitrotyrosine and hemeoxygenase 1 (HO-1) is substantial, while HO-1 expression in the failing right ventricle is decreased. This model, based on administration of the VEGF receptor blocker Sugen 5416 and chronic hypoxia (Su/Hx), reproduces many of the characteristic features of severe angioobliterative human PAH. Treatment of Su/Hx rats with protandim, which nuclear factor erythroid-2 related factor (Nrf2)-dependently upregulates the expression of genes encoding antioxidant enzymes, protects against right heart failure without affecting angioobliterative PAH. CRITICAL ISSUES In human severe PAH, patient survival is determined by the function of the stressed right ventricle; investigation of oxidative and nitrosative stresses and their potential contribution to right heart failure is necessary. FUTURE DIRECTIONS Antioxidant therapeutic strategies may be of benefit in the setting of human severe PAH. Whether antioxidant strategies affect lung vascular remodeling and/or prevent right heart failure remains to be examined.
Comparison of stool microbiota compositions, stool alpha1‐antitrypsin and calprotectin concentrations, and diarrhoeal morbidity of Indonesian infants fed breast milk or probiotic/prebiotic‐supplemented formula

The composition of faecal microbiota of babies is known to be influenced by diet. Faecal calprotectin and α1‐antitrypsin concentrations may be associated with mucosal permeability and inflammation. We aimed to assess whether there was any difference after consumption of a probiotic/prebiotic formula on faecal microbiota composition, calprotectin and α1‐antitrypsin levels, and diarrhoea in comparison with breast milk‐fed Indonesian infants.
Occurrence of Metarhizium spp. in Central Brazilian soils

The biodiversity of entomopathogenic fungi in tropical ecosystems is still little investigated, and the objective of this study was to isolate and identify fungi of the entomopathogenic genus Metarhizium (Hypocreales: Clavicipitaceae) present in undisturbed soils of the Central Brazilian Cerrado. A total of 107 Metarhizium isolates was obtained from soils collected from Cerrado sites in the state of Goiás; gene sequences from 63 of these were obtained and compared. Among these, one was confirmed to be M. anisopliae sensu stricto; 53 were very closely allied to M. anisopliae but require more extensive genetic characterization to determine if they might represent a new taxon in the M. anisopliae species complex. Eight of these Cerrado isolates were referable to M. robertsii, and the remaining isolate is the first South American (and Southern Hemisphere) collection of M. flavoviride var. pemphigi. These findings underline the need for better characterization of the diversity of these widely distributed fungi in Brazil.
The Utility and Recent Advances in Self-Monitoring of Blood Glucose in Type 1 Diabetes

ABSTRACT Self-monitoring of blood glucose (SMBG) is a fundamental and effective principle in the management of type 1 diabetes mellitus (T1DM). SMBG is a precise and accurate clinical tool in the treatment of glycemia and facilitates tight glycemic control. Recent studies have shown that frequent SMBG improves metabolic control and can detect and predict hypoglycemia. The Diabetes Control and Complications Trial demonstrated that SMBG is a key component in achieving tight glycemic control and is associated with improvement in complications of diabetes. Despite the recommendations and benefits of frequent SMBG, it continues to be an underutilized tool, though adherence rates are steadily improving. Recent advances in glucose meters and SMBG data processing have revolutionized the clinical applicability of SMBG. However, several barriers to frequent SMBG have been identified and need to be addressed in order to realize the full potential of SMBG in patients with T1DM. In this review, we provide an overview .