Miracle-dz/UniFAR-FTUs huggingface dataset:
Effect of rosmarinic acid in motor dysfunction and life span in a mouse model of familial amyotrophic lateral sclerosis

Amyotrophic lateral sclerosis (ALS) is a late‐onset progressive neurodegenerative disease affecting motor neurons. About 2% of patients with the disease are associated with mutations in the gene encoding Cu/Zn superoxide dismutase (SOD1). The purpose of this study is to assess the effect of rosemary extract and its major constituents, rosmarinic acid (RA) and carnosic acid (CA), in human SOD1 G93A transgenic mice, which are well‐established mouse models for ALS. The present study demonstrates that intraperitoneal administration of rosemary extract or RA from the presymptomatic stage significantly delayed motor dysfunction in paw grip endurance tests, attenuated the degeneration of motor neurons, and extended the life span of ALS model mice. In addition, RA administration significantly improved the clinical score and suppressed body weight loss compared with a vehicle‐treated group. In conclusion, this study provides the first report that rosemary extract and, especially, RA have preventive effects in the mouse model of ALS. © 2009 Wiley‐Liss, Inc.
Chondroitinase ABC combined with neural stem/progenitor cell transplantation enhances graft cell migration and outgrowth of growth‐associated protein‐43‐positive fibers after rat spinal cord injury

We previously reported that the transplantation of neural stem/progenitor cells (NSPCs) can contribute to the repair of injured spinal cord in adult rats and monkeys. In some cases, however, most of the transplanted cells adhered to the cavity wall and failed to migrate and integrate into the host spinal cord. In this study we focused on chondroitin sulfate proteoglycan (CSPG), a known constituent of glial scars that is strongly expressed after spinal cord injury (SCI), as a putative inhibitor of NSPC migration in vivo. We hypothesized that the digestion of CSPG by chondroitinase ABC (C‐ABC) might promote the migration of transplanted cells and neurite outgrowth after SCI. An in vitro study revealed that the migration of NSPC‐derived cells was inhibited by CSPG and that this inhibitory effect was attenuated by C‐ABC pre‐treatment. Consistently, an in vivo study of C‐ABC treatment combined with NSPC transplantation into injured spinal cord revealed that C‐ABC pre‐treatment promoted the migration of the transplanted cells, whereas CSPG‐immunopositive scar tissue around the lesion cavity prevented their migration into the host spinal cord in the absence of C‐ABC pre‐treatment. Furthermore, this combined treatment significantly induced the outgrowth of a greater number of growth‐associated protein‐43‐positive fibers at the lesion epicentre, compared with NSPC transplantation alone. These findings suggested that the application of C‐ABC enhanced the benefits of NSPC transplantation for SCI by reducing the inhibitory effects of the glial scar, indicating that this combined treatment may be a promising strategy for the regeneration of injured spinal cord.
Development of coaxial shield via in silicon carrier for high frequency application

System-in-package (SiP) based on silicon carriers is a fast emerging technology that offers system design flexibility and integration of heterogeneous technologies. One of the key technologies enabler for silicon carrier is through wafer interconnects. The development of SiP will require the devices with different functionality operating at high frequency to be densely packed on the silicon substrate. However, silicon substrate is usually of low resistivity, when a high frequency signal is transmitted vertically through the substrate via, significant signal attenuation can occur that leads to substrate crosstalk and poor RF performance. In this paper, a novel coaxial shielded via in silicon carrier is presented for high frequency applications. Electrical modeling was carried out to obtain the required geometries for optimum performance. The coaxial shield via is able to suppress undesirable substrate crosstalk between vertical interconnects as well as provide excellent RF performance. The detailed fabrication process is also presented. A negative tone SU-8 photoresist is used as the dielectric for the coaxial shield via structure. A test vehicle is fabricated on 8-inch, 10 Omegamiddotcm resistivity silicon wafer with a target of achieving a transmission coefficient, S21 of greater than -0.5 dB at 40 GHz. SU-8 dielectric of approximately 112 mum thickness was deposited on the via sidewall of a 300 mum diameter through wafer via holes, and the via-holes filled with copper using bottom up electroplating approach to achieve a radius ratio, n of 4
FOLFIRINOX in Locally Advanced and Metastatic Pancreatic Cancer: A Single Centre Cohort Study

Introduction: FOLFIRINOX is emerging as new standard of care for fit patients with locally advanced pancreatic cancer (LAPC) and metastatic pancreatic cancer (MPC). However, some of the physicians are reluctant to use FOLFIRINOX due to high toxicity rates reported in earlier studies. We reviewed our experience with FOLFIRINOX in LAPC and MPC, focussing on dose adjustments, toxicity and efficacy. Methods: We reviewed all patients with LAPC or MPC treated with FOLFIRINOX in our institution between April 2011 and December 2015. Unresectability (stage III and IV) was determined by the institution's multidisciplinary team for pancreatic cancer. Results: Fifty patients (18 LAPC and 32 MPC) were enrolled, with a median age of 55 years (IQR 49-66) and WHO performance status of 0/1. FOLFIRINOX was given as first-line treatment in 82% of patients. Dose modifications were applied in 90% of patients. The median number of completed cycles was 8 (IQR 5-9). Grade 3-4 toxicity occurred in 52% and grade 5 toxicity in 2%. The response rate was 25% (12% in LAPC, 32% in MPC). Median overall survival and progression-free survival were 14.8 and 10.3 months in LAPC, and 9.0 and 5.9 months in MPC, respectively. Overall 1- and 2-year survival was 65% and 10% in LAPC and 40% and 5% in MPC. Within the LAPC group, 6 patients (33%) underwent local ablative therapy and 1 patient (6%) a resection, leading to a median survival of 21.8 months. Conclusion: FOLFIRINOX treatment with nearly routine dose modification was associated with acceptable toxicity rates, relatively high response rates and an encouraging overall survival.
Antithyroid drug-induced aplastic anemia.

BACKGROUND Antithyroid drugs have been used for more than 50 years for the management of hyperthyroidism. Most patients tolerate treatment well but some may develop life threatening side effects such as agranulocytosis and aplastic anemia (AA). We review all cases of antithyroid drug induced AA and describe, as illustrative cases, two women with Graves' disease who developed AA after 8 and 24 weeks of carbimazole (CBM) and methimazole (MMI) treatment respectively. PATIENT FINDINGS AND SUMMARY To date, at least 34 cases of aplastic anemia (AA) due to antithyroid drugs [(1 with CMZ, 31 with MMI, and 2 with propylthiouracil (PTU)] have been published, not including the two patients described here. In addition, at least another 14 patients in whom AA developed after treatment with antithyroid drugs (11 with CMZ, and 3 with MMI) have been reported in Yellow Card Scheme data analysis. Patients with AA usually exhibit sudden onset of symptoms after a relative short time of exposure to the drugs, and all have concomitant agranulocytosis. Most have a rapid recovery following discontinuation of the drug and supportive treatment. Although only two antithyroid drug induced AA deaths have been published, the mortality rate was higher in the Yellow Card Scheme data analysis. CONCLUSIONS Aplastic anemia associated with antithyroid drug treatment is rarer than antithyroid drug associated agranulocytosis. The prognosis of patients with antithyroid drug induced AA is good overall, but may not be as favorable as that of antithyroid drug induced isolated agranulocytosis.
Shifting breast cancer trends in the United States.

PURPOSE United States breast cancer incidence rates declined during the years 1999 to 2003, and then reached a plateau. These recent trends are impressive and may indicate an end to decades of increasing incidence. METHODS To put emerging incidence trends into a broader context, we examined age incidence patterns (frequency and rates) during five decades. We used age density plots, two-component mixture models, and age-period-cohort (APC) models to analyze changes in the United States breast cancer population over time. RESULTS The National Cancer Institute's Connecticut Historical Database and Surveillance, Epidemiology, and End Results program collected 600,000+ in situ and invasive female breast cancers during the years 1950 to 2003. Before widespread screening mammography in the early 1980s, breast cancer age-at-onset distributions were bimodal, with dominant peak frequency (or mode) near age 50 years and smaller mode near age 70 years. With widespread screening mammography, bimodal age distributions shifted to predominant older ages at diagnosis. From 2000 to 2003, the bimodal age distribution returned to dominant younger ages at onset, similar to patterns before mammography screening. APC models confirmed statistically significant calendar-period (screening) effects before and after 1983 to 1987. CONCLUSION Breast cancer in the general United States population has a bimodal age at onset distribution, with modal ages near 50 and 70 years. Amid a background of previously increasing and recently decreasing incidence rates, breast cancer populations shifted from younger to older ages at diagnosis, and then back again. These dynamic fluctuations between early-onset and late-onset breast cancer types probably reflect a complex interaction between age-related biologic, risk factor, and screening phenomena.
Tracheostomy: may the truth be out there?

sessment in the critically ill. Crit Care Clinics 1995; 11:603–634 9. Konstantinides FN, Konstantinides NN, Li JC, et al: Urinary urea nitrogen: Too insensitive for calculating nitrogen balance studies in surgical clinical nutrition. J Parenter Enteral Nutr 1991; 15:189–193 10. Twyman D, Young AB, Ott L, et al: High protein enteral feedings: A means of achieving positive nitrogen balance in head injured patients. J Parenter Enteral Nutr 1985; 9:679–684
The Mental Health Consequences of Mass Shootings

Mass shooting episodes have increased over recent decades and received substantial media coverage. Despite the potentially widespread and increasing mental health impact of mass shootings, no efforts to our knowledge have been made to review the empirical literature on this topic. We identified 49 peer-reviewed articles, comprised of 27 independent samples in the aftermath of 15 mass shooting incidents. Based on our review, we concluded that mass shootings are associated with a variety of adverse psychological outcomes in survivors and members of affected communities. Less is known about the psychological effects of mass shootings on indirectly exposed populations; however, there is evidence that such events lead to at least short-term increases in fears and declines in perceived safety. A variety of risk factors for adverse psychological outcomes have been identified, including demographic and pre-incident characteristics (e.g., female gender and pre-incident psychological symptoms), event exposure (e.g., greater proximity to the attack and acquaintance with the deceased), and fewer psychosocial resources (e.g., emotion regulation difficulties and lower social support). Further research that draws on pre-incident and longitudinal data will yield important insights into the processes that exacerbate or sustain post-incident psychological symptoms over time and provide important information for crisis preparedness and post-incident mental health interventions.
High quality on-chip long annular Josephson junction clock source for digital Superconducting electronics

We have developed clock sources for rapid single flux quantum (RSFQ) digital circuits using high-quality long Josephson junction (LJJ) resonant oscillators of annular geometry. Being a topologically closed system and unperturbed by reflections from boundaries and collisions among the fluxons (flux quanta), the annular LJJ oscillator has demonstrated a high quality factor. The novel design of an annular junction clock that allows easier interface with RSFQ circuitry has been realized. Magnetic fluxons are inserted into an annular LJJ by local injection of current into the control line of the junction. This technique resolves the long-standing problem of achieving superior stability of the fluxon state for application as a clock source. The linewidth of the phase-locked clock source is measured as low as 24 Hz relative to a reference oscillator at 40 GHz. The cycle-to-cycle jitter was measured to be 9 fs at a frequency of 36 GHz, or 0.04% of the clock period which is in good agreement with theoretical estimation.
Analysis of Amaryllidaceae Alkaloids from Zephyranthes Robusta by GC-MS and Their Cholinesterase Activity

From the bulbs of Zephyranthes robusta Baker (Amaryllidaceae), seven known compounds, belonging to four structural types of Amaryllidaceae alkaloids, were identified and quantified by GC-MS. The alkaloid extract from the bulbs showed promising acetylcholinesterase and butyrylcholinesterase inhibitory activities against HuAChE (IC50 = 35.9 ± 3.5 μg/mL) and HuBuChE (IC50 = 190.9 ± 8.2 μg/mL).
Origin and Impact of Stigma and Discrimination in Schizophrenia - Patients' Perception: Mumbai Study

Purpose: Stigma and discrimination faced by patients with schizophrenia are the most important barriers to accessing care and can result in long treatment delays. Stigma is universal but the nature, source, and impact of stigma varies across cultures and regions. Thus, interventions need to be specific. This study assessed the perceptions of patients with schizophrenia regarding the stigma and discrimination they face in their lives. The main determinants and sources of stigma, as well as the nature of and forms of stigma were of interest. Methods: Opinions on various aspects of stigma were obtained using a semi-structured interview. One hundred patients with a diagnosis of schizophrenia, who were attending a psycho-education group in a hospital setting in Mumbai, India, were surveyed. Results: The stigma and discrimination linked to schizophrenia was found to have a significant impact on the lives of these individuals. From the patient perspective, a lack of knowledge, the nature of the illness itself, and behavioral symptoms were seen as the main reasons for stigma and discrimination. Common effects of stigma were low self-esteem and discrimination in family and work settings. Providing care and treatment was identified as the most common method of combating stigma. The availability of effective treatment was thought to be the most important method of reducing stigma, which will certainly aid in the access of mental health care for patients globally. Conclusions: The stigma associated with schizophrenia represents a challenge for effective mental health care. The solution for minimizing this stigma through anti-stigma programs is essential and necessitates the collection and analysis of complex information, particularly including patient perceptions. Implications: Dealing with stigma should be part of treatment and psycho-educational programs. Better treatment and rehabilitation for the illness and its symptoms is important, but so is educating members of the community, who are viewed as the primary source of stigma and discrimination.
The incidence of feco-oral parasites in street-food vendors in Buea, south-west region Cameroon.

BACKGROUND The street-food industry lacks legal recognition, it operates in unstable and precarious conditions, involving women and men with minimal or no knowledge of hygienic food handling practices. Infective eggs, bacteria, toxins and cysts of faecal orally transmissible parasites are common agents responsible for food contamination in developing countries. OBJECTIVE To determine the incidence of digestive faecal-oral parasites among street-food vendors in Buea, South-west region of Cameroon, METHODS From March to May 2009, physical and laboratory analysis of stool samples of 150 randomly selected street-food vendors, residing in four different zones in the municipality were carried out. Information on environmental and personal hygiene was also collected. RESULTS Results revealed that 56.7% of the sampled population was infected with faecal-oral parasites. The major faecal-oral parasites detected in stool samples were: Entamoeba coli (14.0%), Entamoeba histolytica (12.67%), Ascaris lumbricoides (11.33%), Ankylostoma duodenalis (10.67%). Childcare activities, lack of deworming, poor personal hygiene, poor sanitary and toilet facilities, were factors promoting the spread of faecal-oral infections. CONCLUSION Food vendors should be educated on personal hygiene and safe food handling measures. Regulatory procedures on environmental hygiene and regular medical and paramedical follow up of food vendors should be enforced.
The Emerging Role of IL‐10 in Pregnancy

I had a friend. In a cold winter in Villejuif, he convinced Nicole Kiger and me to immunize CBA/J mice with BALB/c spleen cells before mating them with DBA/2, and subsequently spent the weekend doing solid phase radioimmunoassays of maternal sera. This led to the first quick report, followed by two key papers in the CBA x DBA/2 murine abortion Furthermore, J.P. Kolb had noted an increase in placental weight after alloimmunization. This was rather more neglected by myself than one may in retrospect think, but Jean Pierre, inspired by my friend’s enthusiasm, went on with placental weights, while I went on for MLR and Nicole Kiger had some matings made in Nice. The results2 led my friend to propose that protection against abortion was rather due to immunostimulation than immunosuppression. That was the initial formulation of the immunotropism theory4 which we subsequently proved in a series of papers. As you can imagine from this starting anecdote, this presentation and this paper is dedicated to the memory of my friend, the late and missed T.G. Wegmann. The original immunotropism theory put more emphasis on the immunostimulatory role of T cells and T cell-derived cytokines than on immunosuppression, at least in its original form.4 Hence the first papers derived from such observations were more prone to link optimal placental growth with secretion of cytokines actins as growth factors for However, Tom had noticed that the data we had obtained in the CBA x DBA/2 model were strongly suggestive of a balance between what he called “the good cytokines,” i.e., anti-inflammatory ones, and the “bad guys,” namely the TNT and gamma interferon. Indeed, he knew that TNT is highly abortifacient, since Parand and Chedid” and we and others had observed that this is also the case for gamma interferon as well as I L ~ . ’ ~ ~ ~ The observation made by Raghupathy et al. regarding abnormally high levels of TNF in CBA x DBA/2 matir~gs’~. ’~ was coupled with observations made by himself and his group about IL-10 secretion in pregnancyI6 and led it to propose that
Purinergic regulation of cytosolic calcium and phosphoinositide metabolism in rat osteoblast‐like osteosarcoma cells

We have shown that ATP increases cytosolic Ca2+ in UMR‐106 cells through P2‐purinergic receptor stimulation (Calcif Tissue Int 45:251‐254). This response was further characterized using cells loaded with indo‐1/AM or prelabeled with [3H]inositol. ATP elicited a rapid transient increase in Ca2+ from 148 to 540 nM, followed by a biphasic decline (first rapid and then slower) to basal within 1 minute and then a late slow rise to 200 nM by 4 minutes. ADP also elicited a rapid transient increase, but this was followed by a second smaller transient and a later, slow increase above basal Ca2+. These transient increases in Ca2+ induced by ATP and ADP were dose dependent, detected at 10−6 M ATP and 10−7 M ADP, and saturated at 10−4 M with both nucleotides. The maximum increase in Ca2+ was 20% greater with ATP than ADP. EGTA chelation of extracellular Ca2+ abolished the biphasicity of the ATP‐induced Ca2+ transient, the second ADP‐induced transient, and all late slower increases in Ca2+. Desmethoxyverapamil pretreatment attenuated the biphasicity of the ATP‐induced transient and the second peak elicited by ADP. Elevated extracellular Ca2+ (5 mM) prevented the return to the basal level that normally follows the ATP‐induced Ca2+ transient and amplified the sustained increase in Ca2+ but had little effect on the response to ADP. IP3 and IP4 increased rapidly after addition of ATP, with I(1,4,5)P3 increasing before I(1,3,4)P3. These data indicate that P2‐purinergic stimulation of UMR‐106 cells causes three consecutive responses in cytosolic Ca2+: (1) a transient increase due to IP3‐mediated mobilization of intracellular Ca2+; (2) a transient increase due in part to influx, probably associated with a Ca2+ channel; and (3) a later sustained increase that requires extracellular calcium.
Contribution of the Serine 129 of Histone H2A to Chromatin Structure

ABSTRACT Phosphorylation of a yeast histone H2A at C-terminal serine 129 has a central role in double-strand break repair. Mimicking H2A phosphorylation by replacement of serine 129 with glutamic acid (hta1-S129E) suggested that phosphorylation destabilizes chromatin structures and thereby facilitates the access of repair proteins. Here we have tested chromatin structures in hta1-S129 mutants and in a C-terminal tail deletion strain. We show that hta1-S129E affects neither nucleosome positioning in minichromosomes and genomic loci nor supercoiling of minichromosomes. Moreover, hta1-S129E has no effect on chromatin stability measured by conventional nuclease digestion, nor does it affect DNA accessibility and repair of UV-induced DNA lesions by nucleotide excision repair and photolyase in vivo. Similarly, deletion of the C-terminal tail has no effect on nucleosome positioning and stability. These data argue against a general role for the C-terminal tail in chromatin organization and suggest that phosphorylated H2A, γ-H2AX in higher eukaryotes, acts by recruitment of repair components rather than by destabilizing chromatin structures.
The Effectiveness of Group Psychological Intervention in Enhancing Perceptions of Control following Spinal Cord Injury

Objective: This research investigated the effects of a structured psychological intervention, delivered during hospital rehabilitation, on the perceptions of control in people with spinal cord injury (SCI). Method: A longitudinal study was designed to assess perceptions of control (using an objective measure of locus of control) in SCI persons who participated in specialised group cognitive-behavioural therapy (CBT) during hospital rehabilitation. The treatment SCI group's responses on locus of control were compared with a control group of SCI persons who only received traditional rehabilitation services during their hospitalisation. Results and Conclusions: Mean locus of control scores were not high (i.e. external) for both groups and there were no overall group differences on locus of control responses across time in comparison to the control group. However, subjects in both groups who initially perceived life as externally controlled were extracted to form subgroups. The members of the subgroup who received CBT were significantly more likely to feel in control of themselves 2 years post injury compared to similar persons in the control group. Furthermore, an external locus of control was significantly but mildly associated with depressive mood 2 years after the injury. This research suggests that the provision of a structured psychological program in the rehabilitation stage will be beneficial for many SCI persons who feel that they have little control over their lives.