Miracle-dz/UniFAR-FTUs huggingface dataset:
Disease-Modifying Therapy in Multiple Sclerosis: Strategies For Optimizing Management

BACKGROUND–The objective for this article is to highlight several challenges faced by patients and providers in the utilization of disease-modifying agent (DMA) therapy in multiple sclerosis (MS) and to offer practical management strategies that can effectively mitigate or even prevent limiting adverse reactions and enhance treatment compliance. REVIEW SUMMARY–Our discussion will be limited to the use of interferon &bgr;1a (Avonex, Rebif), interferon &bgr;1b (Betaseron), and glatiramer acetate (Copoxane) as these are the primary agents used in the United States for primary disease-modifying therapy in relapsing forms of MS. Some of the recommendations contained herein are derived from evidence-based studies, while others are contingent upon our collective clinical experiences. At the University of Texas Southwestern Medical Center at Dallas and Texas Neurology in Dallas we actively follow approximately 5000 MS patients. The majority of our patients with relapsing-remitting MS (RRMS) or secondary progressive MS (SPMS) are treated with one of the currently available DMAs. Our experience with these patients, and the challenges they face in continuing long-term treatment, constitutes the basis of our proposed treatment strategies. As part of this effort we formulated an assessment and intervention instrument that can be used in the clinic and by telephone to enhance compliance and minimize adverse events. CONCLUSION–A comprehensive treatment approach to the utilization of disease-modifying therapy in MS can serve to optimize the management of our patients and effectively meet the challenges that arise during the course of treatment.
Cross-Validation of Levenson's Psychopathy Scale in a Sample of Federal Female Inmates

Levenson, Kiehl, and Fitzpatrick's Self-Report Psychopathy Scale (LSRPS) is evaluated to determine the factor structure and concurrent validity of the instrument among 430 federal female inmates. Confirmatory factor analysis fails to validate the expected 2-factor structure. Subsequent exploratory factor analysis reveals a 3-factor structure (egocentric, antisocial, and callous), where each factor accounts for significant variance in scores on several theoretically relevant measures. Higher scores on the antisocial factor of the LSRPS are associated with a history of varied psychopathological and negative legal outcomes, suggesting evidence of concurrent validity. However, the egocentric and callous factors do not seem to measure precisely the same construct as the primary psychopathy factor from the Levenson et al. study. The 3-factor structure proposed here has been proposed by other researchers and found in other samples of psychopathy in female inmates. Implications for both research and clinical practice using the LSRPS with female inmates are discussed.
Continuous up-regulation of heat shock proteins in larvae, but not adults, of a polar insect

Antarctica's terrestrial environment is a challenge to which very few animals have adapted. The largest, free-living animal to inhabit the continent year-round is a flightless midge, Belgica antarctica. Larval midges survive the lengthy austral winter encased in ice, and when the ice melts in summer, the larvae complete their 2-yr life cycle, and the wingless adults form mating aggregations while subjected to surprisingly high substrate temperatures. Here we report a dichotomy in survival strategies exploited by this insect at different stages of its life cycle. Larvae constitutively up-regulate their heat shock proteins (small hsp, hsp70, and hsp90) and maintain a high inherent tolerance to temperature stress. High or low temperature exposure does not further up-regulate these genes nor does it further enhance thermotolerance. Such “preemptive” synthesis of hsps is sufficient to prevent irreversible protein aggregation in response to a variety of common environmental stresses. Conversely, adults exhibit no constitutive up-regulation of their hsps and have a lower intrinsic tolerance to high temperatures, but their hsps can be thermally activated, resulting in enhanced thermotolerance. Thus, the midge larvae, but not the adults, have adopted the unusual strategy of expressing hsps continuously, possibly to facilitate proper protein folding in a cold habitat that is more thermally stable than that of the adults but a habitat subjected frequently to freeze-thaw episodes and bouts of pH, anoxic, and osmotic stress.
Intrathecal ziconotide in the treatment of refractory pain in patients with cancer or AIDS: a randomized controlled trial.

CONTEXT Ziconotide (formerly SNX-111) selectively blocks N-type voltage-sensitive calcium channels and may be effective in patients with pain that is refractory to opioid therapy or those with intolerable opioid-related adverse effects. OBJECTIVE To assess the safety and efficacy of intrathecal ziconotide in patients with pain that is refractory to conventional treatment. DESIGN, SETTING, AND PATIENTS Double-blind, placebo-controlled, randomized trial conducted from March 12, 1996, to July 11, 1998, at 32 study centers in the United States, Australia, and the Netherlands. Patients were 111 individuals ages 24 to 85 years with cancer or AIDS and a mean Visual Analog Scale of Pain Intensity (VASPI) score of 50 mm or greater. Patients were randomly assigned in a 2:1 ratio to receive ziconotide or placebo treatment. INTERVENTIONS Intrathecal ziconotide was titrated over 5 to 6 days, followed by a 5-day maintenance phase for responders and crossover of nonresponders to the opposite treatment group. MAIN OUTCOME MEASURE Mean percentage change in VASPI score from baseline to the end of the initial titration period. RESULTS Of the evaluable population, 67 (98.5%) of 68 patients receiving ziconotide and 38 (95%) of 40 patients receiving placebo were taking opioids at baseline (median morphine equivalent dosage of 300 mg/d for the ziconotide group and 600 mg/d for the placebo group; P =.63, based on mean values), and 36 had used intrathecal morphine. Mean (SD) VASPI scores were 73.6 (1.8) mm in the ziconotide group and 77.9 (2.3) mm in the placebo group (P =.18). Mean VASPI scores improved 53.1% (95% confidence interval [CI], 44.0%-62.2%) in the ziconotide group and 18.1% (95% CI, 4.8%-31.4%) in the placebo group (P<.001), with no loss of efficacy of ziconotide in the maintenance phase. Pain relief was moderate to complete in 52.9% of patients in the ziconotide group compared with 17.5% in the placebo group (P<.001). Five patients receiving ziconotide achieved complete pain relief, and 50.0% of patients receiving ziconotide responded to therapy compared with 17.5% of those receiving placebo (P =.001). CONCLUSION Intrathecal ziconotide provided clinically and statistically significant analgesia in patients with pain from cancer or AIDS.
Role of the Parathyroid Hormone Type 1 Receptor (PTH1R) as a Mechanosensor in Osteocyte Survival

Osteocytes have a major role in the control of bone remodeling. Mechanical stimulation decreases osteocyte apoptosis and promotes bone accrual, whereas skeletal unloading is deleterious in both respects. PTH1R ablation or overexpression in osteocytes in mice produces trabecular bone loss or increases bone mass, respectively. The latter effect was related to a decreased osteocyte apoptosis. Here, the putative role of PTH1R activation in osteocyte protection conferred by mechanical stimulation was assessed. Osteocytic MLO‐Y4 cells were subjected to mechanical stimuli represented by hypotonic shock (216 mOsm/kg) or pulsatile fluid flow (8 Hz, 10 dynes/cm2) for a short pulse (10 min), with or without PTH1R antagonists or after transfection with specific PTHrP or PTH1R siRNA. These mechanical stimuli prevented cell death induced within 6 hours by etoposide (50 μM), related to PTHrP overexpression; and this effect was abolished by the calcium antagonist verapamil (1 μM), a phospholipase C (PLC) inhibitor (U73122; 10 μM), and a PKA activation inhibitor, Rp‐cAMPS (25 μM), in these cells. Each mechanical stimulus also rapidly induced β‐catenin stabilization and nuclear ERK translocation, which were inhibited by the PTH1R antagonist PTHrP(7–34) (1 μM), or PTH1R siRNA, and mimicked by PTHrP(1–36) (100 nM). Mechanical stretching by hypotonic shock did not affect cAMP production but rapidly (<1 min) stimulated Cai2+ transients in PTH1R‐overexpressing HEK‐293 cells and in MLO‐Y4 cells, in which calcium signaling was unaffected by the presence of a PTHrP antiserum or PTHrP siRNA but inhibited by knocking down PTH1R. These novel findings indicate that PTH1R is an important component of mechanical signal transduction in osteocytic MLO‐Y4 cells, and that PTH1R activation by PTHrP‐independent and dependent mechanisms has a relevant role in the prosurvival action of mechanical stimulus in these cells. © 2014 American Society for Bone and Mineral Research © 2014 American Society for Bone and Mineral Research
Twins in Jos Nigeria: a seven-year retrospective study.

INTRODUCTION A retrospective analysis of twin pregnancy was carried out between 1st January 1992 and 31st December 1998 to determine the incidence, epidemiological variables perinatal and maternal outcome of twin pregnancy in the institution. MATERIAL AND METHODS The case notes of the 413 twin pregnancy, 6 triplets and 1 quadruplet delivered during the period, and the labour records of all the deliveries were analyzed. Statistical analysis was with chi-squared test. The level of significance was set at 5%. RESULTS The incidence of twin pregnancy was 28/1000, triplet 0.4/1000 and quadruplet 0.07/1000. The age range of the twin mothers was 15-47 years with a mean of 28 +/- 5.4 years. The parity range was 0-14 years with a mean of 3.3 +/- 2.6. Rising maternal age and parity were associated with twinning rate. The mean fetal weight was 2.21 +/- 0.66 kg. There was no statistical significant difference in weight between the 1st and 2nd twins. Male babies however weighed heavier (p < 0.02) than the female infants. The incidence of low birth weight babies (< 2500 g) was 58.7% with a perinatal mortality rate of 278.4/1000. The perinatal outcome was worst for the very low birth weight babies (< 1500), 817.5/1000 8.5% of twin mothers had a retained 2nd twin. The perinatal outcome of the 27 unbooked mothers who delivered their 1st twin at home was (12) 44.4/1000, compared to the rate of 12.5/1000 (1) in 8 booked mothers, who delivered the 1st twin in the hospital. Among the 771 babies who were alive at the time of presentation in the labour ward, delivery by caesarean section had a better perinatal outcome (6.8%), compared to spontaneous vaginal delivery (13.1%) and assisted breech delivery (21.4%). The unbooked twin mothers had a perinatal mortality rate of 318.7/1000 compared to booked mothers 82.3/1000. The overall perinatal mortality rate was 186.4/1000. The clinical causes of death were prematurity 74.6%, retained 2nd twin 7.3%, antepartum haemorrhage 6.1%, severe pregnancy induced hypertension/eclampsia 3.0%, birth asphyxia 2.4%, congenital malformation 1.8%. The incidence of postpartum haemorrhage was 3% and there was no maternal mortality in the series. The institution will need to put in place adequate resuscitating facilities and manpower to manage the low birth weight infants so as to reduce the current high perinatal wastage.
Classification of breast cancer histopathology images using texture feature analysis

In this paper, we propose a method for classification of histopathological images using texture features. The images are first segmented as epithelial lining surrounding the lumen for breast histopathology images using spatio-color-texture graph segmentation method. The features such as Gray Level Co-occurrence Matrix (GLCM), Graph Run Length Matrix (GRLM) features, and Euler number are extracted. The linear discriminant analyzer (LDA) is used to classify breast histology images. The performance of LDA classifier is compared with k-NN and SVM classifiers. The experiments and quantitative analysis shows that LDA classifier outperforms over others with 100% and 80% correct classification rate for the non-malignant Vs malignant breast histopathology images respectively.
Negative Selection by IgM Superantigen Defines a B Cell Central Tolerance Compartment and Reveals Mutations Allowing Escape

To analyze B lymphocyte central tolerance in a polyclonal immune system, mice were engineered to express a superantigen reactive to IgM of allotype b (IgMb). IgMb/b mice carrying superantigen were severely B cell lymphopenic, but small numbers of B cells matured. Their sera contained low levels of IgG and occasionally high levels of IgA. In bone marrow, immature B cells were normal in number, but internalized IgM and had a unique gene expression profile, compared with those expressing high levels of surface IgM, including elevated recombinase activator gene expression. A comparable B cell population was defined in wild-type bone marrows, with an abundance suggesting that at steady state ∼20% of normal developing B cells are constantly encountering autoantigens in situ. In superantigen-expressing mice, as well as in mice carrying the 3H9 anti-DNA IgH transgene, or 3H9 H along with mutation in the murine κ-deleting element RS, IgM internalization was correlated with CD19 downmodulation. CD19low bone marrow cells from 3H9;RS−/− mice were enriched in L chains that promote DNA binding. Our results suggest that central tolerance and attendant L chain receptor editing affect a large fraction of normal developing B cells. IgHa/b mice carrying the superantigen had a ∼50% loss in follicular B cell numbers, suggesting that escape from central tolerance by receptor editing from one IgH allele to another was not a major mechanism. IgMb superantigen hosts reconstituted with experimental bone marrow were demonstrated to be useful in revealing pathways involved in central tolerance.
Population-based survey methods to quantify associations between human rights violations and health outcomes among internally displaced persons in eastern Burma

Background: Case reports of human rights violations have focused on individuals’ experiences. Population-based quantification of associations between rights indicators and health outcomes is rare and has not been documented in eastern Burma. Objective: We describe the association between mortality and morbidity and the household-level experience of human rights violations among internally displaced persons in eastern Burma. Methods: Mobile health workers in conflict zones of eastern Burma conducted 1834 retrospective household surveys in 2004. Workers recorded data on vital events, mid-upper arm circumference of young children, malaria parasitaemia status of respondents and household experience of various human rights violations during the previous 12 months. Results: Under-5 mortality was 218 (95% confidence interval 135 to 301) per 1000 live births. Almost one-third of households reported forced labour (32.6%). Forced displacement (8.9% of households) was associated with increased child mortality (odds ratio = 2.80), child malnutrition (odds ratio = 3.22) and landmine injury (odds ratio = 3.89). Theft or destruction of the food supply (reported by 25.2% of households) was associated with increased crude mortality (odds ratio = 1.58), malaria parasitaemia (odds ratio = 1.82), child malnutrition (odds ratio = 1.94) and landmine injury (odds ratio = 4.55). Multiple rights violations (14.4% of households) increased the risk of child (incidence rate ratio = 2.18) and crude (incidence rate ratio = 1.75) mortality and the odds of landmine injury (odds ratio = 19.8). Child mortality risk was increased more than fivefold (incidence rate ratio = 5.23) among families reporting three or more rights violations. Conclusions: Widespread human rights violations in conflict zones in eastern Burma are associated with significantly increased morbidity and mortality. Population-level associations can be quantified using standard epidemiological methods. This approach requires further validation and refinement elsewhere.
Zinc supplementation at the time of ethanol exposure ameliorates teratogenicity in mice.

BACKGROUND We have previously demonstrated that ethanol teratogenicity in mice is related to the maternal expression of metallothionein (MT), a zinc (Zn)-binding protein. Ethanol induces maternal liver MT, which causes plasma Zn concentrations to decrease as Zn moves into the liver. During pregnancy it is suggested that this change decreases fetal Zn supply and contributes to abnormal development. Here we investigated whether maternal Zn supplementation at the time of ethanol exposure reduces teratogenicity. METHODS Mice were injected with 25% ethanol (0.015 ml/g intraperitoneally at 0 and 4 hr) and ZnSO4 (2.5 microg Zn/g subcutaneously at 0 hr) and were killed over 16 hr to ascertain changes in plasma Zn. Plasma Zn concentrations peaked at 2 hr, where levels were 5-fold normal and then returned toward normal over 14 hr. Pregnant mice were treated in a similar manner on gestation day 8 with saline, saline + Zn, ethanol + Zn, or ethanol alone, and fetal abnormalities were assessed on gestation day 18. RESULTS External abnormalities were most prevalent in offspring from dams treated with ethanol. Zn treatment at the time of ethanol exposure reduced the incidence of fetal abnormalities to basal levels. Litters from dams treated with ethanol + Zn contained more fetuses and fewer fetal resorption sites compared with those from ethanol-treated dams. CONCLUSIONS These findings demonstrate that Zn supplementation at the time of ethanol exposure significantly negates the deleterious effects of ethanol on the fetus.
A critical analysis of New Zealand's family policies under the National-led Government 2008-2014

3 Introduction . 5 Chapter One: The Policy Problem . 7 Policy Problem Challenges . 8 Ageing Population . 10 Gender Equality . 11 Child Welfare . 13 Comparative Perspectives . 15 Conclusion . 23 Chapter Two: Possible Policy Responses . 26 Outline of Analytic Framework . 26 Recommendation from Literature on Best Practice . 27 Paid Leave/Flexible Employment . 27 Childcare . 30 Tax Credits/Financial Incentives. 31 Policy Responses Other Countries Have Used . 32 Norway . 32 Sweden . 33 France . 34 Germany . 36 Australia . 37 Conclusion . 39 Chapter Three: Analysis of New Zealands Policies . 41 Parental/Maternity Leave Policy . 41 Flexible Employment Policy . 47 Childcare Policy . 49 Tax Credits/Financial Assistance Policy . 52 Welfare Policy . 57 Conclusion . 63 References . 68 List of Figures Figure 1.1 Employment rate of Women of different ages with and without children, selected European Countries.15 Figure 1.2 Potential impact of various policy reforms on total fertility rates.16 Figure 1.3 The Economic crisis has had a large impact on the employment rates in many countries.18 Figure 1.4 Fertility rates across the OECD are typically below replacement level with a moderate decline since the crisis.20
Ocular injuries in blast victims.

OBJECTIVE To study the type and severity of ocular injuries in blast victims. METHODS It was a descriptive case series. The study was conducted at the Department of Ophthalmology, Khyber Teaching Hospital and Iqbal Eye Clinic Peshawar from March 2010 to May 2011. Detailed history was taken and complete ocular examination was done. B-scan was done to know about any posterior segment pathology (when required). Digital X-ray orbit and/or computed tomography were done to rule out intraocular foreign body. The treatment and follow up varied according to the type and extent of eye injury. RESULTS Total number of patients were 79, 78 (98.73%) males and 1 (1.26%) female. Mean age of patients was 23.43 +/- 10.67 years. Ocular injury was unilateral in 50 (63.29%) and bilateral in 29 (36.70%) patients. Forty-one (37.96%) eyes had closed globe injury and 67 (62.03%) had open globe injury. The most common type of injury was corneal/scleral perforation (48.14%) followed by vitreous haemorrhage (38.88%) and traumatic cataract (30.55%). The most commonly performed surgery was corneal/scleral repair (in 33 eyes). Final best corrected visual acuity (BCVA) improved in 56 (51.85%) eyes, remained unchanged in 49 (45.37%) eyes and worsened in 03 (2.77%) eyes. CONCLUSION Blast related ocular injuries are becoming increasingly common. In severely injured eyes the visual prognosis remains poor despite development of advanced microsurgical techniques and better methods of visual rehabilitation.
Animal Models of Complement-Mediated Hypersensitivity Reactions to Liposomes and Other Lipid-Based Nanoparticles

Intravenous injection of some liposomal drugs, diagnostic agents, micelles and other lipid-based nanoparticles can cause acute hypersensitivity reactions (HSRs) in a high percentage (up to 45%) of patients, with hemodynamic, respiratory and cutaneous manifestations. The phenomenon can be explained with activation of the complement (C) system on the surface of lipid particles, leading to anaphylatoxin (C5a and C3a) liberation and subsequent release reactions of mast cells, basophils and possibly other inflammatory cells in blood. These reactions can be reproduced and studied in pigs, dogs and rats, animal models which differ from each other in sensitivity and spectrum of symptoms. In the most sensitive pig model, a few miligrams of liposome (phospholipid) can cause anaphylactoid shock, characterized by pulmonary hypertension, systemic hypotension, decreased cardiac output and major cardiac arrhythmias. Pigs also display cutaneous symptoms, such as flushing and rash. The sensitivity of dogs to hemodynamic changes is close to that of pigs, but unlike pigs, dogs also react to micellar lipids (such as Cremophor EL) and their response includes pronounced blood cell and vegetative neural changes (e.g., leukopenia followed by leukocytosis, thrombocytopenia, fluid excretions). Rats are relatively insensitive inasmuch as hypotension, their most prominent response to liposomes, is induced only by one or two orders of magnitude higher phospholipid doses (based on body weight) compared to the reactogenic dose in pigs and dogs. It is suggested that the porcine and dog models are applicable for measuring and predicting the (pseudo)allergic activity of particulate “nanodrugs”.
Radiation doses of patients and urologists during percutaneous nephrolithotomy

Renal stones can be treated either by extracorporeal shock wave lithotripsy (ESWL) or percutaneous nephrolithotomy (PCNL). Increasing use of fluoroscopic exposure for access and to detect stone location during PCNL make the measurement of patient and staff doses important. The main objective of this work was to assess patient and urologist doses for the PCNL examination. We used the tube output technique for determination of patient doses (n = 20) and lithium fluoride thermoluminescent dosimeter (TLD) chips for urologist dose measurements. The TLD technique was also used for some patient dose measurements (n = 7) for comparison with the tube output technique. Mean entrance skin doses of 191 and 117 mGy were measured by the tube output technique for anterior–posterior (AP) and right anterior oblique (RAO) 30°/left anterior oblique (LAO) 30° projections, respectively. The mean urologist doses for eye, finger and collar were measured as 26, 33.5 and 48 µGy per procedure, respectively. The mean effective dose per procedure for the urologist was 12.7 µSv. None of the individual skin dose results approach deterministic levels.
Involvement of the first transmembrane segment of human α2‐adrenoceptors in the subtype‐selective binding of chlorpromazine, spiperone and spiroxatrine

BACKGROUND AND PURPOSE Some large antagonist ligands (ARC239, chlorpromazine, prazosin, spiperone, spiroxatrine) bind to the human α2A‐adrenoceptor with 10‐ to 100‐fold lower affinity than to the α2B‐ and α2C‐adrenoceptor subtypes. Previous mutagenesis studies have not explained this subtype selectivity.