Miracle-dz/UniFAR-FTUs huggingface dataset:
Clinical / Scientific Notes

Katja Thomas, MD Thorsten Schultheiss, MD Tjalf Ziemssen, MD, PhD NEUROBORRELIOSIS DURING NATALIZUMAB TREATMENT IN MULTIPLE SCLEROSIS We present a case of acute neuroborreliosis in the setting of long-term treatment with natalizumab. A 33-year-old man was diagnosed with relapsing-remitting multiple sclerosis (MS) in 1999. Following failure of various immunomodulatory treatments including interferon and immunoglobulin, he was treated with mitoxantrone from May 2000 to August 2004. Due to persistently high disease activity, he was also treated with cyclophosphamide (December 2005–April 2006) and then azathioprine (April–June 2006), which were both discontinued due to adverse effects. After the patient scored 6.5 on the Expanded Disability Status Scale and had 2 relapses in 2006, we initiated natalizumab therapy (300 mg monthly, starting September 2006). The patient improved significantly in ambulation and the relapse rate slowed as well. In 2010, JC virus serology was positive. In July 2011 (60th natalizumab infusion), the patient complained of progressive bilateral neuropathic pain in his arms. Subsequent brain MRI results were similar to those from 2006, demonstrating multiple partly confluent supratentorial and infratentorial lesions. Despite methylprednisolone treatment, the patient’s clinical status worsened. We also noted generalized myalgia, fever, progressive diplopia, paresthesia, and hyperpathia in both legs and neck without an obvious central or peripheral origin. Again, MRI including cervical spinal cord was unchanged. CSF analysis revealed elevated lymphocyte count (189 MPt/L with increased activated immunoglobulin [Ig] and CD191 B cells; figure, A and B). CXCL13, tumor necrosis factor–a, and interleukin-6 peaked in CSF at time of symptom presentation (figure, C and D). In addition, intrathecal protein, IgG, and IgM concentrations were elevated (figure, E). Blood– brain barrier breakdown was evident due to increased CSF/serum IgG gradient and albumin ratio (figure, F). Virologic and bacteriologic analyses were negative. Although CSF was negative for BorreliaDNA according to PCR analysis, Borrelia-specific antibodies against IgM and IgG in serum and CSF confirmed acute neuroborreliosis (figure, G). Retrospectively, the patient reported a tick bite 5 weeks before onset of symptoms. Antibiotic treatment (ceftriaxone 2 g/day) was started IV and administered for 14 days. Neuropathic pain and diplopia remitted soon after. Follow-up CSF analysis showed gradually decreasing pathologic parameters (figure, A). Natalizumab infusions were not interrupted during diagnostic workup and subsequent ceftriaxone treatment and the patient continues to have monthly treatment. VLA-4 saturation and concentrations in CSF and serum were stable in 2010 through the ceftriaxone treatment period (figure, H).
Light and electron microscopic analysis of two divisions of the suprachiasmatic nucleus in the young and aged rat

The suprachiasmatic nucleus (SCN) is a principal controller of mammalian circadian rhythms. However, in spite of documented disturbance of biological rhythms in old animals, few significant age‐related changes have been observed in this nucleus. This study examined age‐related differences in SCN volume, neuronal number, density, and ultra‐structural features in the entire rat SCN and in its two divisions, the denser ventromedial (compacta) and less dense dorsolateral (dissipata). Light and electron microscopic morphometric techniques were utilized in weanlings (21–28 days), young adults (3–6 mo), and aged (30–36 mo) animals.
Coping With Pediatric Cancer

Pediatric cancer patients and their families face significant physical, emotional, and psychosocial challenges. Few studies have investigated how children manage these challenges and how parents may help in the process. This qualitative study aimed to explore common cancer-related stressors for children and to examine child coping and parental assistance in coping with these stressors during treatment. Fifteen children undergoing cancer treatment and their parents participated in semistructured interviews. Four themes emerged capturing cancer-related stressors: cancer treatment/side effects, distressing emotions, disruption in daily routines, and social challenges. Six themes emerged regarding child coping strategies that were classified within an approach/avoidance coping framework. Approach coping strategies included the following: cognitive restructuring, relaxation, practical strategies, seeking social support, and emotional expression. Distraction was the only avoidant coping strategy. Parents tended to encourage approach coping strategies (eg, cognitive restructuring, social support). Within families, few coping strategies were reported (child: M = 1.47, SD = 0.99; parent: M = 3.33, SD = 1.18), suggesting that early family-based interventions teaching coping techniques for cancer-related stressors may be beneficial.
THE RELATIONSHIP BETWEEN MAGNITUDE OF CEREBRAL ACTIVATION AND INTENSITY OF EMOTIONAL AROUSAL

There is considerable knowledge concerning the cerebral localization of positive and negative emotions; however, relatively little is known about the cerebral representation of subjective emotional intensity. Indeed, few studies to date seem to have been conducted on the cerebral effects of increased emotional intensity. The purpose of the present investigation was to investigate the relationship between the intensity of cerebral activation and emotional arousal using quantitative electroencephalography (QEEG). Participants were asked to recollect an angry memory while QEEG was recorded from 19 electrode sites arranged according to the International 10/20 System. Significant positive correlations were found between subjective intensity of angry memories and changes in low beta (13-21 Hz) and high beta (21-32 Hz) magnitude (µV) at the F8, T6, and O1 electrode sites among the male participants. Additionally, a significant positive correlation between emotion intensity and changes in high beta at the T6 electrode site was found among female participants. Results are discussed in terms of implications for emotional regulation and dysfunction.
Local voices on renewable energy projects: the performative role of the regulatory process for major offshore infrastructure in England and Wales

ABSTRACT There is currently a considerable emphasis on delivering major renewable energy infrastructure projects. Such projects will have impacts on local communities; some impacts may be perceived as positive but others will be viewed more negatively. Any just regulatory process for considering and permitting such infrastructure will need to heed the concerns that local communities voice. But what counts as a local voice? In this paper it is argued that the regulatory process plays a performative role, constructing what counts as a local voice. Furthermore, this has consequences for how regulatory deliberations proceed and the outcomes of regulatory processes. The empirical basis for this argument is a study of major offshore renewable energy infrastructure in England and Wales and the way that it is regulated through a specific regime – the Nationally Significant Infrastructure Projects (NSIPs) regime established by the Planning Act 2008. Through a detailed study of eight projects that have passed through the regime, the analysis unfolds the way that the voices of local residents, local businesses, local NGOs and local authorities are constructed in the key boundary object of the Examining Authority’s report; it then draws out the implications for the mitigation measures that are negotiated. The research suggests that what counts as a local voice is constrained by how the performative role of the NSIPs regulatory regime differentiates between interests and suggests that new ways of giving voice to local people are required.
Tolerability and Pulmonary Pharmacodynamic Effects During Treatment Initiation of Once‐Daily Oral Fingolimod in Subjects With Moderate Asthma

Fingolimod, a first‐in‐class sphingosine 1‐phosphate receptor modulator, is the first approved oral therapy for relapsing multiple sclerosis (MS). While treatment initiation of clinical dose of fingolimod (0.5 mg) does not affect pulmonary function, supra‐therapeutic doses (≥5.0 mg) increased airway resistance. The aim of this double‐blind, placebo‐controlled, parallel group, 10‐day study was to measure the effect of fingolimod on pulmonary function in otherwise healthy patients with moderate asthma. Subjects (n = 36) were randomized into four cohorts that received either fingolimod 0.5, 1.25, 2.5 mg, or placebo once daily for 10 days. Subjects in placebo and fingolimod 0.5 mg groups did not differ in FEV1AUEC0–6 h, FEF25–75% AUEC0–6 h, or in short‐acting beta (β) 2 agonists (SABA, rescue bronchodilator) use. Subjects on higher doses of fingolimod showed a mild reduction in FEV1AUEC0–6 h and FEF25–75%AUEC0–6 h and a significant sixfold increase in SABA use versus placebo. One subject had moderately severe, acute exacerbation of asthma after receiving the first dose of fingolimod 1.25 mg that quickly responded to inhaled SABA. The observed safety profile was consistent with previous reports. These results provide reassurance that moderately asthmatic MS individuals can start on fingolimod 0.5 mg therapy with minimal effects on pulmonary function and SABA use.
Rat Liver Foci and in Vitro Assays to Detect Initiating and Promoting Effects of Chlorinated Ethanes and Ethylenes a

Nine chlorinated aliphatics (CAs) were examined in a rat liver foci assay for tumor initiating and promoting activities. In this model, young adult male Osborne Mendel rats were first subjected to a partial hepatectomy, the test chemical was then administered at the maximum tolerated dose in the initiation or promotion phase in conjunction with diethylnitrosamine (DEN; 30 mg/kg b.w.) or phenobarbital (PB; 0.05 percent, w/w, in the diet), and gamma glutamyltranspeptidase (GGT) was used as a putative preneoplastic indicator. When administered in the promotion protocol after initiation with DEN, 1,1-dichloroethane, 1,1,2-trichloroethane (1,1,2-TCE), 1,1,2,2-tetrachloroethane (1,1,2,2-TTCE), tetrachloroethylene (TTCY), and hexachloroethane induced significant increases in GGT+-foci above control levels. 1,1,2,2-TTCE, TTCY, and 1,1,2-TCE also induced significant increases in GGT+-foci when administered in the promotion protocol without DEN initiation. Two variants of GGT+-foci were observed: the classical type associated with PB promotion, and the other, which was more diffuse, less intensely stained, resembling foci undergoing redifferentiation and associated with CAs. A number of CAs were also genotoxic in short-term in vitro tests. Taken together, the studies suggest that CAs may be complete carcinogens in vivo with weak initiating activity and stronger promoting activity.
Genotypes Associated with Virulence in Environmental Isolates of Vibrio cholerae

ABSTRACT Vibrio cholerae is an autochthonous inhabitant of riverine and estuarine environments and also is a facultative pathogen for humans. Genotyping can be useful in assessing the risk of contracting cholera, intestinal, or extraintestinal infections via drinking water and/or seafood. In this study, environmental isolates ofV. cholerae were examined for the presence of ctxA, hlyA, ompU, stn/sto, tcpA, tcpI, toxR, and zot genes, using multiplex PCR. Based on tcpA and hlyAgene comparisons, the strains could be grouped into Classical and El Tor biotypes. The toxR, hlyA, and ompU genes were present in 100, 98.6, and 87.0% of the V. choleraeisolates, respectively. The CTX genetic element and toxin-coregulated pilus El Tor (tcpA ET) gene were present in all toxigenicV. cholerae O1 and V. cholerae O139 strains examined in this study. Three of four nontoxigenic V. cholerae O1 strains contained tcpA ET. Interestingly, among the isolates of V. cholerae non-O1/non-O139, two hadtcpA Classical, nine contained tcpA El Tor, three showed homology with both biotype genes, and four carried thectxA gene. The stn/sto genes were present in 28.2% of the non-O1/non-O139 strains, in 10.5% of the toxigenicV. cholerae O1, and in 14.3% of the O139 serogroups. Except for stn/sto genes, all of the other genes studied occurred with high frequency in toxigenic V. cholerae O1 and O139 strains. Based on results of this study, surveillance of non-O1/non-O139 V. cholerae in the aquatic environment, combined with genotype monitoring using ctxA, stn/sto, andtcpA ET genes, could be valuable in human health risk assessment.
Enhancement of T-cell-mediated arthritis in mice by treatment with a monoclonal antibody against interleukin-4.

We investigated a role for interleukin-4 (IL-4) in T-cell-mediated arthritis by employing a monoclonal antibody against IL-4 (11B11 mAb). As a model of T-cell-mediated arthritis, antigen-induced arthritis (AIA) in mice was used. To induce AIA, mice were immunized with methylated bovine serum albumin (mBSA) (day 0). On day 14, the animals were intraarticularly injected with mBSA into the ankle joint. 11B11 mAb was daily injected i.p. for a period of 10 days, commencing on the day of immunization with mBSA. We found that treatment with 11B11 mAb significantly enhanced the severity of AIA. The enhanced arthritis was also observed in mice injected i.v. with lymphoid cells from mBSA-immunized mice, followed by the intraarticular challenge injection of mBSA. The enhancement of AIA by the anti-IL-4 mAb was associated with a significant increase in the proliferative response of lymphoid cells to mBSA in mice treated with the mAb. The secretion of IL-4 as well as IL-5 decreased in 11B11 mAb-treated mice, while the production of IFN-gamma and IL-2 increased following mAb treatment. Thus, the neutralization of IL-4 by an anti-IL-4 mAb appeared to enhance AIA, suggesting a role for IL-4 in downregulating T-cell-mediated joint inflammation.
Modelling the Australian J-Curve: An ARDL Cointegration Approach

This study analyses the existence of the J-curve phenomenon in Australia using quarterly data over the period 1970-2016. The Autoregressive Distributed Lag (ARDL) cointegration and error correction methodology are used to examine the short-run and long-run impact of real exchange rate on Australia’s trade balance. The empirical findings support the J-curve effect in which real currency depreciations exert a negative effect on trade balance in the long-run. In addition, domestic income plays an important role in improving trade balance in the long-run. This result is also robust to alternative cointegration methods. Furthermore, we segment currency appreciations and depreciations to determine whether any asymmetries are present in the real exchange rate by utilising the non-linear version of the ARDL approach. While this method still supports the J-curve effect, no asymmetric responses are found in the real exchange rate in the long-run. However, asymmetries are present in the short-run in which real depreciations improve Australia’s trade balance.
Identification of Rat Cysteine-Rich Secretory Protein 4 (Crisp4) as the Ortholog to Human CRISP1 and Mouse Crisp4

Abstract Cysteine-rich secretory proteins (CRISPs) are present in a diverse population of organisms and are defined by 16 conserved cysteine residues spanning a plant pathogenesis related-1 and a C-terminal cysteine-rich domain. To date, the diversification of mammalian CRISPs is evidenced by the existence of two, three, and four paralogous genes in the rat, human, and mouse, respectively. The current study identifies a third rat Crisp paralog we term Crisp4. The gene for Crisp4 is on rat chromosome 9 within 1 Mb of both the Crisp1 and Crisp2 genes. The full-length transcript for this gene was cloned from rat epididymal RNA and encodes a protein that shares 69% and 91% similarity with human CRISP1 and mouse CRISP4, respectively. Expression of rat Crisp4 is most abundant in the epididymis, with the highest levels of transcription observed in the caput and corpus epididymis. In contrast, rat CRISP4 protein is most abundant in the corpus and cauda regions of the epididymis. Rat CRISP4 protein is also present in caudal sperm extracts, appearing as a detergent-soluble form at the predicted MWR (26 kDa). Our data identify rat Crisp4 as the true ortholog to human CRISP1 and mouse Crisp4, and demonstrate its interaction with spermatozoa in the epididymis.
Synergistic effect of targeting the epidermal growth factor receptor and hyaluronan synthesis in oesophageal squamous cell carcinoma cells

Worldwide, oesophageal cancer is the eighth most common cancer and has a very poor survival rate. In order to identify new tolerable treatment options for oesophageal squamous cell carcinoma (ESCC), erlotinib was tested with moderate efficacy in phase I and II studies. As 4‐methylumbelliferone (4‐MU), an hyaluronan (HA) synthesis inhibitor showed anti‐cancer effects in vitro, and in ESCC xenograft tumours, we investigated whether the anti‐cancer effects of erlotinib could be augmented by combining it with 4‐MU.
Contact Transscleral Cyclophotocoagulation with Diode Laser in Refractory Glaucoma

Objective To evaluate the clinical effectiveness of contact transscleral cyclophotocoagulation (CTCP) with diode laser. Design and Patients Forty-eight seeing eyes and 20 blind and painful eyes of 68 patients suffering from refractory glaucoma were treated using a diode laser (EOS3000, Laser Science) coupled with a 400-μm optic fiber ending in a 3-mm focusing tip. Sixteen to twenty 3.9-J (2.6 W x 1.5 to 2.5 s) laser spots were placed over 360°, 1.5 mm from the corneolimbal junction. Results In the seeing-eye group, the follow-up was 20.7 ± 8.14 months, pre- and posttreat-ment lOPs were 37.1 ± 11.27 and 19.5 ± 8.73 mmHg respectively (p < 0.0001), and success (IOP > 2 and < 21 mmHg) was 70.8%. No significant visual acuity change was found in the successful eyes, whereas a significant visual acuity reduction was found in the unsuccessful cases (p=0.03). In the blind-eye group, the follow-up was 20.5 ± 8.54 months, pre- and post-treatment lOPs were 50.7 ± 15.05 and 20.6 ± 13.99 mmHg respectively (p < 0.0001), and success (remission of pain) was 100%. As for complications, one seeing eye developed a spontaneously-resolved vitreous hemorrhage and one seeing and one blind eye became hypotonic, though no phthysis was observed. No conjunctival or lens damage was detected, and no scleral thinning was revealed by ultrasound biomicroscopy. No case of sympathetic ophthalmia was found. Conclusions Diode laser can be successfully employed for CTCP in refractory glaucoma.
An independent and prospective comparison of two commercial fibrosis marker panels (HCV FibroSURE and FIBROSpect II) during albinterferon alfa‐2b combination therapy for chronic hepatitis C

Summary. Noninvasive markers that accurately follow changes in fibrosis may provide alternatives to liver biopsy for assessment of histological endpoints of antiviral therapy in chronic hepatitis C (CHC). This study compared two commercially available serum marker panels (HCV FibroSURE™ and FIBROSpect II®) during interferon‐based therapy. Ninety‐five interferon‐naïve patients with genotype 1 CHC were enrolled in a phase 2b, active‐controlled study of albinterferon alfa‐2b/ribavirin for 48 weeks. Proprietary and simple biochemical marker panels were independently evaluated in serum before and during the study. Baseline liver biopsies were evaluated for METAVIR fibrosis by a single pathologist. Index scores were obtained for HCV FibroSURE (n = 84) and FIBROSpect II (n = 95); mean biopsy length: 17.8 ± 8.0 mm. For detecting fibrosis stages 2–4 (prevalence 23% [22/95] and 21% [18/84]), HCV FibroSURE and FIBROSpect II indicated high sensitivity (1.00 and 0.95, respectively), lower but comparable specificity (0.61 and 0.66, respectively), and a good area under the receiver operating characteristic curve (0.89 and 0.90, respectively). Simple indices had high indeterminate rates (31–40%) at baseline. Patients with a sustained virological response had lower baseline scores than nonresponders, and reduced median percent changes in index scores for HCV FibroSURE (−20.0%vs 2.9%; P = 0.14) and FIBROS Spect II (−6.8%vs 18.4%; P = 0.05). The panels demonstrated comparable performance characteristics for differentiating mild from moderate–severe stage disease in CHC. Lower index scores at baseline that continue to decline likely reflect reduced fibrogenesis activity in patients with successful antiviral responses to therapy.
Galinsosides A and B, bioactive flavanone glucosides from Galinsoga parviflora

Galinsosides A (1) and B (2), new flavanone glucosides together with two known flavanones, 7,3′,4′-trihydroxyflavanone (3) and 3,5,7,3′,4′-pentahydroxyflavanone (4) have been isolated from an ethyl acetate- soluble fraction of Galinsoga parviflora. Their structures were assigned on the basis of spectral studies. Compound 1 showed significant antioxidant and urease inhibitory activity while compound 2 was moderately active. On the other hand, 2 showed inhibitory potential against α-glucosidase.
Groundwater Arsenic Contamination, Its Health Impact and Mitigation Program in Nepal

Abstract About 47% of Nepal's total population is living in Terai region and 90% of them are relying on groundwater as their major source of drinking water. About 200,000 shallow tubewells have been installed by different agencies in 20 Terai districts, serving 11 million people. Recently, arsenic contamination of groundwater has been recognized as a public health problem in Nepal. This has sensitized government, national and international nongovernment organizations working on water quality sector to carry out water quality assessment for arsenic in the affected communities. So far, 15,000 tubewells has been tested where 23% samples exceeded World Health Organization guideline value of 10 µg/L and 5% exceeded “Nepal Interim Arsenic Guideline” of 50 µg/L. It is estimated that around 0.5 million people in Terai are living at risk of arsenic poisoning (>50 µg/L). Some recent studies have reported the prevalence of dermatosis related to arsenicosis from 1.3 to 5.1% and the accumulation of arsenic in biological samples like hair and nail much higher than the acceptable level. Though some steps are being taken by government and private organizations to combat the problem, it has not been able to cover all the affected communities. Nepal still needs more research work on arsenic occurrence and effects and mitigation programs simultaneously.
The In Vitro Effects of a Novel Vascular Protectant, AGI-1067, on Platelet Aggregation and Major Receptor Expression in Subjects With Multiple Risk Factors for Vascular Disease

Oxidation-sensitive signals are important in platelet activation. The novel, phenolic, intracellular and extra-cellular antioxidant AGI-1067 inhibits the expression of a number of proinflammatory genes involved in atherosclerosis. The effect of AGI-1067 on human platelets was evaluated. Blood obtained from 20 aspirin-naïve volunteers with multiple risk factors for vascular disease was preincubated with escalating concentrations of AGI-1067 for the assessment of its ex vivo effects on platelet aggregation and expression of major surface receptors flow cytometry, evaluated by flow cytometry. AGI-1067 resulted in significant inhibition of a variety of activation-dependent platelet biomarkers in healthy volunteers, including adenosine diphosphate-induced platelet aggregation and decreased surface platelet expression of glycoprotein IIb/IIIa antigen, activity with PAC-1 antibody, and glycoprotein Ib (CD42b). The effect of AGI-1067 differs from other known antiplatelet agents, suggesting opportunities for therapeutic combination. These data need to be confirmed in subjects receiving orally dosed AGI-1067 to be clinically relevant.