Miracle-dz/UniFAR-FTUs huggingface dataset:
Correlation of long term phenotypic and clinical outcomes following limbal epithelial transplantation cultivated on amniotic membrane in rabbits

Aim: To determine the epithelial phenotype in rabbits with total limbal stem cell deficiency (LSCD) after reconstruction with autologous limbal epithelial stem cells ex vivo expanded on rabbit amniotic membrane (AM). Methods: Left eyes of 52 rabbits were rendered total LSCD, verified by impression cytology. The fibrovascular pannus of each cornea was removed. Group I (n = 10) received rabbit AM transplantation alone, while groups II–IV (n = 42) underwent transplantation of LSC cultured on rabbit AM (LSC-AM) from a small limbal biopsy taken from the right eye. Clinical outcome was graded as “success,” “partial success,” or “failure” depending on the corneal smoothness and avascularity. Epithelial phenotype was determined by immunostaining and graded as “corneal (K),” “conjunctival (J),” or “mixed (M)” depending on expression of K3 and Muc5AC. Results: After 1 year follow up, group I showed 100% failure and groups II–IV showed 26% success (p<0.001). Clinical failure correlated with J phenotype p = 0.001), while clinical success correlated with K phenotype p = 0.01). When the phenotypic outcome was used for comparison, J phenotype was significantly high in group I (p = 0.003), while K phenotype was significantly high in groups II–IV (p<0.05). Conclusion: There is a strong correlation between clinical success and resultant corneal epithelial phenotype. Ex vivo expanded LSC can successfully reconstruct corneal surfaces with unilateral total LSCD.
Disease Beyond the Arch: A Systematic Review of Middle Aortic Syndrome in Childhood.

BACKGROUND Middle aortic syndrome (MAS) is a rare clinical entity in childhood, characterized by a severe narrowing of the distal thoracic and/or abdominal aorta, and associated with significant morbidity and mortality. MAS remains a relatively poorly defined disease. This paper systematically reviews the current knowledge on MAS with respect to etiology, clinical impact, and therapeutic options. METHODS A systematic search of 3 databases (Embase, MEDLINE, and Cochrane Central Register of Controlled Trials) yielded 1,252 abstracts that were screened based on eligibility criteria resulting in 184 full-text articles with 630 reported cases of childhood MAS. Data extracted included patient characteristics, clinical presentation, vascular phenotype, management, and outcomes. RESULTS Most cases of MAS are idiopathic (64%), 15% are associated with Mendelian disorders, and 17% are related to inflammatory diseases. Extra-aortic involvement including renal (70%), superior mesenteric (30%), and celiac (22%) arteries is common, especially among those with associated Mendelian disorders. Inferior mesenteric artery involvement is almost never reported. The majority of cases (72%) undergo endovascular or surgical management with residual hypertension reported in 34% of cases, requiring medication or reintervention. Clinical manifestations and extent of extra-aortic involvement are lacking. CONCLUSIONS MAS presents with significant involvement of visceral arteries with over two thirds of cases having renal artery stenosis, and one third with superior mesenteric artery stenosis. The extent of disease is worse among those with genetic and inflammatory conditions. Further studies are needed to better understand etiology, long-term effectiveness of treatment, and to determine the optimal management of this potentially devastating condition.
Aquatic toxicity of nanosilver colloids to different trophic organisms: Contributions of particles and free silver ion

The wide uses of nanosilver (nAg) have resulted in concerns regarding ecotoxicity to aquatic organisms. Some previous studies have found that the toxicity of nAg is due to the nanoparticles themselves, while others have found that ionic silver (Ag+) released by nAg particles plays an important role. In the present study, the authors quantitatively evaluated the relative contribution of nAg particles and Ag+ to the toxicity to three aquatic organisms of different trophic levels, including an algal species (Raphidocelis subcapitata), a cladoceran species (Chydorus sphaericus), and a freshwater fish larva (Danio rerio). A bare and a polyvinylpyrrolidone (PVP)–coated nAg as well as a monodispersed nAg with a dispersant (DIS‐nAg) were examined. The toxicity of the nAg in the form of colloids decreased in the order DIS‐nAg > PVP‐nAg > Bare‐nAg for all three trophic aquatic organisms (in terms of median effect concentration). The DIS‐nAg had the highest and Bare‐nAg the lowest concentration of free Ag+, implying that free Ag+ cannot be neglected in explaining the toxicity of nAg colloids. Furthermore, the contribution of free Ag+ to the toxicity of nAg colloids for R. subcapitata was the highest but for D. rerio the lowest, implying that the organisms tested have different accumulation abilities for Ag+ or nAg particles. Environ. Toxicol. Chem. 2012; 31: 2408–2413. © 2012 SETAC
Clinical evaluation of an advanced category antihaemophilic factor prepared using a plasma/albumin‐free method: pharmacokinetics, efficacy, and safety in previously treated patients with haemophilia A 1

Summary. The efficacy and safety of an advanced category recombinant antihaemophilic factor produced by a plasma‐ and albumin‐free method (rAHF‐PFM) was studied in 111 previously treated subjects with haemophilia A. The study comprised a randomized, double‐blinded, crossover pharmacokinetic comparison of rAHF‐PFM and RECOMBINATE rAHF (R‐FVIII); prophylaxis (three to four times per week with 25–40 IU kg−1 rAHF‐PFM) for at least 75 exposure days; and treatment of episodic haemorrhagic events. Median age was 18 years, 96% of subjects had baseline factor VIII <1%, and 108 received study drug. Bioequivalence, based on area under the plasma concentration vs. time curve and adjusted in vivo recovery, was demonstrated for rAHF‐PFM and R‐FVIII. Mean (±SD) half‐life for rAHF‐PFM was 12.0 ± 4.3 h. Among 510 bleeding events, 473 (93%) were managed with one or two infusions of rAHF‐PFM and 439 (86%) had efficacy ratings of excellent or good. Subjects who were less adherent to the prophylactic regimen had a higher bleeding rate (9.9 episodes subject−1 year−1) than subjects who were more adherent (4.4 episodes subject−1 year−1; P < 0.03). One subject developed a low titre, non‐persistent inhibitor (2.0 BU) after 26 exposure days. These data demonstrate that rAHF‐PFM is bioequivalent to R‐FVIII, and suggest that rAHF‐PFM is efficacious and safe, without increased immunogenicity, for the treatment of haemophilia A.
Gene–environment interactions and the response to exercise

Many of the symptoms of heart failure (breathlessness and fatigue) are not primarily due to reduced cardiac output, but relate to an impairment of peripheral muscle performance and metabolic efficiency. With regular training it is possible to increase skeletal muscle performance through improvements in muscle efficiency. Recent data suggest that such improvements may be modulated by local tissue renin‐angiotensin systems and, in particular, by the local activity of angiotensin‐converting enzyme (ACE). These findings might explain the remarkable benefits of ACE inhibition in the treatment of heart failure.
Archivos de narrativa y matrices folklóricas: oralidad, escritura y génesis

Resumen Revisito una aproximacion al relato folklorico, a partir de un archivo de narrativa folklorica riojana. El enfoque teorico combina aportes de la critica genetica con la teoria informatica del hipertexto. El archivo incluye versiones orales reunidas en investigaciones de campo (1985-1999), alrededor de la matriz “La dama fantasma”, con elementos del motivo folklorico E 322.3. 3.1 “The vanishing hitchhiker”. Comprende tambien recreaciones escriturarias, filmicas y registros virtuales. El trabajo se encuadra en una investigacion sobre “Archivos de Narrativa Tradicional Argentina”, que revisa criterios de archivacion de narrativa tradicional, de la Encuesta Folklorica de 1921 a 2005.
The impact of platelets on the progression of traumatic intracranial hemorrhage.

BACKGROUND The purpose of this study was to analyze the association of the initial platelet count with mortality and progression of intracranial hemorrhage (ICH) in blunt traumatic brain injured (TBI) patients. METHODS All blunt trauma patients with severe TBI admitted from January 2006 to December 2007 were retrospectively identified. Patients with a chest, abdomen, or extremity AIS score >3 were excluded to minimize the impact of concomitant injuries on the outcomes of the patients. All brain computed tomography scans were reviewed to analyze ICH progression. Discrete platelet cutoff values were entered into a multiple regression model to detect critical thresholds associated with ICH progression and mortality. RESULTS Of 626 TBI patients, 310 (49.5%) had a minimum of two brain computed tomography scans and were able to have ICH progression evaluated. Patients with platelets <175,000/mm3 had a significantly increased risk for ICH progression (OR [95% CI]: 2.09 [1.07-4.37]; adjusted p = 0.043). ICH progression was associated with increased need for craniotomy (OR [95% CI]: 3.27 [1.28-8.33]; adjusted p = 0.013) and mortality (OR [95% CI]: 3.41 [1.11-10.53]; adjusted p = 0.033). A platelet count <100,000/m3 was an independent predictor for mortality (OR [95% CI]: 9.5 [1.3-71.4]; adjusted p = 0.029). CONCLUSION A platelet count <100,000/mm3 is associated with a ninefold adjusted risk of death, and a platelet count <175,000/mm3 is a significant predictor of ICH progression. The impact of early correction of the admission platelet count warrants further validation.
Candida albicans-Induced DC Activation Partially Restricts HIV Amplification in DCs and Increases DC to T-Cell Spread of HIV

Dendritic cells (DCs) are central to the innate and adaptive responses needed to control pathogens, yet HIV exploits DCs to promote infection. The influence of other pathogens on DC-HIV interplay has not been extensively studied. We used Candida albicans (Candida) as a model pathogen which elicits innate DC responses that are likely important in controlling Candida by healthy immune systems. HIV did not impede Candida-specific DC activation. Candida-induced CD80 and CD83 upregulation was greater in DCs that had captured HIV, coinciding with increased amplification in presence of T cells and reduced but persistent low-level DC infection. In contrast, HIV-infected DCs matured normally in response to Candida, but this did not shut down HIV replication in DCs, and again Candida augmented HIV amplification in DC-T-cell mixtures. HIV-infected DCs secreted more IL-10 and IL-1β earlier than uninfected DCs and initially induced a higher frequency of CD4+CD25+FoxP3+ T-regulatory cells in response to Candida. Elevated early IL-10 production in cocultures was evident only when azidothymidine (AZT) was included to limit T-regulatory cell infection and destruction. Therefore, HIV manipulates the DC's innate and adaptive responses to Candida to further augment HIV spread, ultimately destroying the cells needed to limit candidiasis.
Can the interleukin-6 response to endotoxin be predicted? Studies of the influence of a promoter polymorphism of the interleukin-6 gene, gender, the density of the endotoxin receptor CD14, and inflammatory cytokines.

OBJECTIVES To evaluate whether the -174 G/C promoter polymorphism of the interleukin-6 gene, gender, the monocyte density of the endotoxin receptor CD14, or the inflammatory cytokines tumor necrosis factor-alpha or interleukin-1beta influence the interleukin-6 response of whole blood to endotoxin. DESIGN Analysis of interleukin-6 release from endotoxin-stimulated human whole blood. SETTING Medical research laboratory. PATIENTS Healthy human blood donors. INTERVENTIONS None. MEASUREMENTS AND MAIN RESULTS The interleukin-6 -174 G/C and the tumor necrosis factor -308 G/A promoter polymorphisms were determined by real-time polymerase chain reaction assay by using specific fluorescence labeled hybridization probes. Monocyte CD14 expression was assessed by flow cytometry. After incubation of whole blood with endotoxin, plasma concentrations of interleukin-6, tumor necrosis factor-alpha, and interleukin-1beta were measured by means of chemiluminescence. The interleukin-6 concentrations were lower (p = .005) in individuals who were CG heterozygotes compared with individuals homozygous for the C or the G. The difference between C and G homozygotes was not significant (p = .67). The interleukin-6 response was enhanced in men compared with women (p = .015). There was no correlation between interleukin-6 concentrations and monocyte CD14 density. Interleukin-6 concentrations correlated with the concentrations of tumor necrosis factor-alpha (r = .59, p = .01) and interleukin-1beta (r = .47, p = .01). There was no linkage between the tumor necrosis factor -308 and the interleukin-6 -174 polymorphisms. CONCLUSIONS The interleukin-6 response to endotoxin was influenced by gender and correlated with the concentrations of more proximal cytokine tumor necrosis factor-alpha and interleukin-1beta. The interleukin-6 -174 G/C promoter polymorphism can only partly predict the interleukin-6 response of human whole blood to endotoxin stimulation, and the results were different from previous reporter gene assays that reported higher interleukin-6 concentrations for the G allele. Tumor necrosis factor -308 G homozygotes produce the lowest tumor necrosis factor concentrations. The number of tumor necrosis factor -308 G homozygotes was not higher among interleukin-6 -174 heterozygotes, and thus this cannot account for their significantly smaller interleukin-6 production.
LPL gene mutation as the cause of severe hypertriglyceridemia in the course of ketoacidosis in a patient with newly diagnosed type 1 diabetes mellitus.

INTRODUCTION Severe hypertriglyceridemia is a condition associated with extremely high triglycerides (TG) plasma concentrations exceeding 1000mg/dl. This condition may result in mutations in genes encoding lipoprotein lipase (LPL), apolipoprotein C2 (APOC2) and apolipoprotein A5 (APOA5) characterized by an autosomal recessive inheritance pattern. AIM A case report of a patient in which clinical picture of type 1 diabetes mellitus (T1DM) was accompanied by diabetic ketoacidosis (DKA) and severe hypertriglyceridemia. CASE REPORT A 2.5-year-old boy was admitted to the hospital with ketoacidosis (pH - 7.0, BE - 20mmol/l, HCO3 10mmol/l), glucose level of 850mg%, hyponatremia (Na 100mmol/l) and hyperlipidemia (TG 13493 mg/dl, TC 734 mg/dl). The administered treatment resulted in nearly normal glycemic values and lipid disturbances normalization. This child was diagnosed with a heterozygous mutation of the LPL gene. Currently with an intensive insulin therapy and correct metabolic control of type 1 diabetes mellitus (T1DM), this patient maintains a normal lipid profile. CONCLUSION In patient with T1DM the diagnosis of severe hypertriglyceridemia in the course of ketoacidosis should be based on careful interpretation of laboratory tests results. Moreover genetic tests of the patient and his/her immediate relatives blood samples should be performed.
Objective Measurement of Fatigue Following Traumatic Brain Injury

ObjectivesTo quantify posttraumatic brain injury (post-TBI) mental fatigue objectively by documenting changes in performance on neuropsychological tests as a result of sustained mental effort and to examine the relationship between objectively measured mental fatigue and self-reported situational and day-to-day fatigue. ParticipantsThe study included 202 community-dwelling individuals with mild-severe TBI and 73 noninjured controls. MeasuresMeasures included Cambridge Neuropsychological Test Automated Battery, Global Fatigue Index, and situational fatigue rating. MethodSubjects were administered a 30-minute computerized neuropsychological test battery 3 times. The second and third administrations of the battery were separated by approximately 2 hours of interviews and administration of self-report measures. ResultsThe neuropsychological test scores were factor analyzed, yielding 3 subscales: speed, accuracy, and executive function. Situational fatigue and day-to-day fatigue were significantly higher in individual with TBI group than in individuals without TBI and were associated with speed subscale scores. Individuals with TBI evidenced a significant decline in performance on the accuracy subscale score. These declines in performance related to sustained mental effort were not associated with subjective fatigue in the TBI group. While practice effects on the speed and accuracy scores were observed in non–brain-injured individuals, they were not evidenced in individuals with TBI. ConclusionsFindings were largely consistent with previous literature and indicated that while subjective fatigue is associated with poor performance in individuals with TBI, it is not associated with objective decline in performance of mental tasks.
The Changing Role of Palliative Care in the ICU

Objectives: Palliative care is an interprofessional specialty as well as an approach to care by all clinicians caring for patients with serious and complex illness. Unlike hospice, palliative care is based not on prognosis but on need and is an essential component of comprehensive care for critically ill patients from the time of ICU admission. In this clinically focused article, we review evidence of opportunities to improve palliative care for critically ill adults, summarize strategies for ICU palliative care improvement, and identify resources to support implementation. Data Sources: We searched the MEDLINE database from inception through January 2014. We also searched the Reference Library of The Improving Palliative Care in the ICU Project website sponsored by the National Institutes of Health and the Center to Advance Palliative Care, which is updated monthly. We hand-searched reference lists and author files. Study Selection: Selected studies included all English-language articles concerning adult patients using the search terms "intensive care" or "critical care" with "palliative care," "supportive care," "end-of-life care," or "ethics. " Data Extraction: After examination of peer-reviewed original scientific articles, consensus statements, guidelines, and reviews resulting from our literature search, we made final selections based on author consensus. Data Synthesis: Existing evidence is organized to address: 1) opportunities to alleviate physical and emotional symptoms, improve communication, and provide support for patients and families; 2) models and specific interventions for improving ICU palliative care; 3) available resources for ICU palliative care improvement; and 4) ongoing challenges and targets for future research. Key domains of ICU palliative care have been defined and operationalized as measures of quality. There is increasing recognition that effective integration of palliative care during acute and chronic critical illness may help patients and families face challenges after discharge from intensive care. Conclusions: Palliative care is increasingly accepted as an essential component of comprehensive care for critically ill patients, regardless of diagnosis or prognosis. A variety of strategies to improve ICU palliative care appear to be effective, and resources including technical assistance and tools are available to support improvement efforts. As the longer-term impact of intensive care on those surviving acute critical illness is increasingly documented, palliative care can help prepare and support patients and families for challenges after ICU discharge. Further research is needed to inform efforts to integrate palliative care with intensive care more effectively and efficiently in and after the ICU and to document improvement using valid and responsive outcome measures.
Taking the edge off: why patients choose St. John's Wort.

BACKGROUND The number of visits to alternative medicine practitioners in this country is estimated at 425 million, which is more than the number of visits to allopathic primary care physicians in 1990. Patients' use of St. John's Wort (SJW) has followed this sweeping trend. The purpose of our study was to examine the reasons people choose to self-medicate with SJW instead of seeking care from a conventional health care provider. METHODS We used open-ended interviews with key questions to elicit information. Twenty-two current users of SJW (21 women; 20 white; mean age = 45 years) in a Southern city participated. All interviews were transcribed, and descriptive participant quotes were extracted by a research assistant. Quotes were reviewed for each key question for similarities and contextual themes. RESULTS Four dominant decision-making themes were consistently noted. These were: (1) Personal Health Care Values: subjects had a history of alternative medicine use and a belief in the need for personal control of health; (2) Mood: all SJW users reported a depressed mood and occasionally irritability, cognitive difficulties, social isolation, and hormonal mood changes; (3) Perceptions of Seriousness of Disease and Risks of Treatment: SJW users reported the self-diagnosis of "minor" depression, high risks of prescription drugs, and a perception of safety with herbal remedies; and (4) Accessibility Issues: subjects had barriers to and lack of knowledge of traditional health care providers and awareness of the ease of use and popularity of SJW. Also of note was the fact that some SJW users did not inform their primary care providers that they were taking the herb (6 of 22). Users reported moderate effectiveness and few side effects of SJW. CONCLUSIONS SJW users report depression, ease of access to alternative medicines, and a history of exposure to and belief in the safety of herbal remedies. Users saw little benefit to providing information about SJW to primary care physicians.
Macrocephaly in autism and other pervasive developmental disorders

To assess the prevalence of macrocephaly (head circumference ≥1.88 standard deviations above normative data for age and sex or >97th centile) in autism and other pervasive developmental disorders, 41 children with autism, and a comparison group of 21 children with tuberous sclerosis complex (TSC) or an unspecified seizure disorder were studied. Familiality of head circumference was also assessed from measurements of 133 first‐degree relatives. Significantly higher rates of macrocephaly were found in probands with autism (12.2%) and their first‐degree relatives (15.5%) when compared against a published normative sample. The incidence of macrocephaly in the comparison group of probands with TSC and seizure disorder (9.5%) and their first‐degree relatives (8.3%) was higher than normative data as well, although the relation between macrocephaly and autism was more pronounced. Head circumference and extreme scores reflecting macrocephaly were moderately heritable in the present sample (H2= 0.47). The increased prevalence of macrocephaly in relatives of children with autism compared with control children suggests that this characteristic may be a familial risk factor in the pathogenesis of autism.
Calcium transients studied under voltage‐clamp control in frog twitch muscle fibres

1. Intracellular calcium transients were recorded from frog twitch muscle fibres in response to voltage‐clamped depolarizing pulses, using arsenazo III as an intracellular calcium monitor. The object was to investigate the time‐ and voltage‐dependent characteristics of the coupling process between membrane depolarization and calcium release from the sarcoplasmic reticulum (s.r.)