Miracle-dz/UniFAR-FTUs huggingface dataset:
Medial and lateral perforant path evoked potentials are selectively modulated by pairing with glutamatergic activation of locus coeruleus in the dentate gyrus of the anesthetized rat

Norepinephrine (NE) in vitro produces long‐lasting potentiation of medial perforant path input and depression of lateral perforant path input to dentate gyrus in the rat. Similar, but highly transient, effects have been reported in vivo using paragigantocellular stimulation to release NE. The present study uses alternate stimulation of the medial perforant path and lateral olfactory tract (eliciting a lateral perforant path‐evoked potential) to examine the effects of glutamatergic activation of locus coeruleus (LC) on the two pathways for up to 3 h post‐LC activation. In the first experiment, the expected potentiation of the medial perforant path population spike in dentate gyrus was observed, but without accompanying depression of the lateral perforant path‐mediated evoked potential (lateral olfactory tract stimulation, 60 s ISI). In a second experiment, with more frequent pairing of input with NE release (10 s ISI), significant potentiation of lateral perforant path‐mediated input to dentate gyrus occurred, but potentiation of medial perforant path input was not seen. A third experiment with a 30 s ISI again produced potentiation of lateral perforant path‐mediated input without potentiation of the medial perforant path population spike. The size of effects with the 30 s ISI was intermediate between that seen with 10 s and 60 s ISI. Potentiation of lateral perforant path over medial perforant path input has previously been reported with acute nicotinic activation of the LC. This outcome also resembles heterosynaptic modulation previously reported with tetanic potentiation. The data argue for a competitive relationship between medial and lateral perforant path inputs to dentate gyrus and suggest pairing with increased NE produces a bias favoring one or the other pathway depending on parameters such as strength and frequency. NE potentiating effects on lateral perforant path input here may also have occurred in entorhinal cortex (EC) given the system‐wide NE release with LC activation. © 2011 Wiley Periodicals, Inc.
Rituximab, used alone or in combination, is superior to other treatment modalities in splenic marginal zone lymphoma

Splenic marginal zone lymphoma (SMZL) is a rare B‐cell malignancy, with no standard treatment other than splenectomy. Rituximab has shown encouraging results. We therefore retrospectively assessed 43 patients from two centres, who received rituximab, either alone or with chemotherapy. All patients responded, 34/43 (79%) achieving a complete response (CR), compared with 3/10 (30%) after chemotherapy without rituximab (P = 0·005). Of these 10 patients, 9 (90%) subsequently achieved a CR after rituximab (P = 0·02). Rituximab monotherapy appeared equally as effective as rituximab combination therapy (90% vs. 79% CR, P = 0·7) with significantly less toxicity (12·5% vs. 83%, P = 0·002). Splenectomized patients were more likely to obtain a CR with rituximab (16/16, 100%) than unsplenectomized patients (18/27, 67%, P = 0·008). Disease‐free survival (DFS) at 3 years was better after rituximab than after splenectomy alone [79% (95% confidence interval 60–89) vs. 29% (8–54), Hazard ratio (HR) 0·28 (0·12–0·68), P = 0·003] and better than after chemotherapy without rituximab [25% (4–55), HR 0·21 (0·08–0·51), P = 0·0004]. Survival at 3 years after rituximab was 98%. In summary, the CR and DFS rates after rituximab, given alone or with chemotherapy, were significantly better than after chemotherapy without rituximab in the same patients, with manageable toxicity. Rituximab, with or without splenectomy, should be considered for the treatment of SMZL.
In‐vitro response of erythroid progenitors from children with thalassaemia major to human growth hormone and insulin‐like growth factor I

OBJECTIVE Most short‐statured children with β‐thalassaemia major have markedly reduced levels of circulating insulin‐like growth factor I (IGF‐I). Both human growth hormone (hGH) and IGF‐I enhance the in‐vitro growth of erythroid progenitors, with hGH exerting its effects via paracrine production of IGF‐I. The aim of this study was to characterize further the hGH‐IGF‐l axis abnormalities in thalassaemia major by evaluating the erythroid potentiating effects of both peptides in cultures of thalassaemic and control erythroid progenitors.
Duodenal stump fistula after gastrectomy for gastric cancer: risk factors, prevention, and management

Purpose A duodenal stump fistula is one of the most severe complications after gastrectomy for gastric cancer. We aimed to analyze the risk factors for this problem, and to identify the methods used for its prevention and management. Methods We retrospectively reviewed the clinical data of 716 consecutive patients who underwent curative gastrectomy with a duodenal stump for gastric cancer between 2008 and 2013. Results A duodenal stump fistula occurred in 16 patients (2.2%) and there were 2 deaths in this group. Univariate analysis revealed age >60 years (odds ratio [OR], 3.09; 95% confidence interval [CI], 0.99–9.66), multiple comorbidities (OR, 4.23; 95% CI, 1.50–11.92), clinical T stage (OR, 2.91; 95% CI, 1.045-8.10), and gastric outlet obstruction (OR, 8.64; 95% CI, 2.61–28.61) to be significant factors for developing a duodenal stump fistula. Multivariate analysis identified multiple comorbidities (OR, 3.92; 95% CI, 1.30–11.80) and gastric outlet obstruction (OR, 5.62; 95% CI, 1.45–21.71) as predictors of this complication. Conclusion Multiple comorbidities and gastric outlet obstruction were the main risk factors for a duodenal stump fistula. Therefore, preventive methods and aggressive management should be applied for patients at high risk.
Ultrabroadband and Flattened Dispersion in Aluminum Nitride Slot Waveguides

Aluminum nitride (AlN) is an emerging platform for a wide range of on-chip applications. One promising feature is that both the second- and third-order nonlinearities are available in crystalline AlN waveguides. We design an AlN slot waveguide with a flat and low dispersion over an ultrawide spectral range from near-infrared to mid-infrared. A dual-slot structure is designed and the flattened group velocity dispersion within −13 and +11 ps/(nm·km) over 2000-nm-wide bandwidth with three zero dispersion wavelengths is achieved. The impacts of the structural parameters are analyzed in detail and the phase-matching condition in four-wave mixing process is investigated as well. A 3-dB conversion bandwidth of 1200 nm and −28-dB conversion efficiency are predicted in a 1-cm-long horizontal dual-slot AlN waveguide with the pump power of 2 W.
Plasma Na-K Atpase Inhibitor Activity and Intracellular Ions during Hemodialysis

We have investigated the relationship between plasma Na-K ATPase inhibitor activity (EDLS) and intracellular ions in 37 uremic hemodialysed hypertensive patients, and in 20 normotensive non uremic controls (NC). As compared with the NC population, significantly enhanced values for erythrocyte (RBC) Na, Ca, platelet cytosolic Ca and EDLS were observed in all the uremic patients tested just before a dialysis session, as well as a decrease in RBC Ca ATPase and in the platelet pH. In uremia, significant correlations have been noted between RBC Na and platelet Ca (r = 0.6) or systolic BP (r = 0.45); between platelet Ca and systolic blood pressure (r = 0.8) or diastolic BP (r = 0.5) and between EDLS and RBC Na, Ca or platelet Ca (r = 0.5). Anti-hypertensive treatment has no influence on these parameters. During dialysis, a significant decrease has been noted in RBC Na, Ca, platelet Ca, SBP (only in untreated patients) and EDLS and an increase in RBC Ca ATPase and platelet pH. These modifications are significantly correlated with the weight change.
Combined Peritoneal Dialysis and Hemodialysis: Our Experience Compared to Others

Objective To determine the clinical experience of using combined-modality [simultaneous hemodialysis (HD) and peritoneal dialysis (PD)] treatment in patients with end-stage renal disease. Design We reviewed data on 4 patients from our center that were treated with “combined-mode therapy. ” We then conducted a retrospective survey by sending questionnaires to nephrologists in the US and Canada by mail and by posting the survey on the Internet. Data queried included number of patients on combined modality, solute clearances, albumin levels pre and post combined therapy, reasons for using combined therapy, duration and success of combined therapy, and reimbursement issues. Setting and Participants Ours is a tertiary-care center. Patients that were not doing well on PD alone were put on combined modality of treatment between 1992 and 1998. Main Outcome Measures Clinical improvement in the indication for which the participant was started on combined modality. Results In response to the survey, data on 27 patients were collected. These data were combined with data on 4 patients from our unit that had previously been treated with combined HD and PD. Most patients were reported to have more than one clinical reason for changing from PD to combined therapy. The main clinical reason for offering combined treatments was inadequate solute clearance (34%), followed by ultrafiltration problems (16%) and neuropathy (11%). Mean duration of time followed on combined treatment was 8.5 ± 0.12 months. Most patients tolerated combined treatment well and were reported to show improvement in the clinical reasons for which they needed the combined modality. Dual access and reimbursement issues were not a problem. There was no single method used for calculating total (HD, PD, and residual renal) solute clearance. No universal total solute clearance goal was reported. Conclusion Hemodialysis and PD are not mutually exclusive. They can be used in combination to achieve targeted solute clearances, to improve certain clinical conditions, and to control volume and blood pressure in a subset of patients. Further evaluation is needed to better establish the long-term outcomes of using combined modality. Total solute clearance goals and methods for determining total solute clearance need to be standardized.
In vivo 31P MRS detection of an alkaline inorganic phosphate pool with short T1 in human resting skeletal muscle

Non‐invasive determination of mitochondrial content is an important objective in clinical and sports medicine. 31P MRS approaches to obtain information on this parameter at low field strength typically require in‐magnet exercise. Direct observation of the intra‐mitochondrial inorganic phosphate (Pi) pool in resting muscle would constitute an alternative, simpler method. In this study, we exploited the higher spectral resolution and signal‐to‐noise at 7T to investigate the MR visibility of this metabolite pool. 31P in vivo MR spectra of the resting soleus (SOL) muscle were obtained with 1H MR image‐guided surface coil localization (six volunteers) and of the SOL and tibialis anterior (TA) muscle using 2D CSI (five volunteers). A resonance at a frequency 0.38 ppm downfield from the cytosolic Pi resonance (Pi1; pH 7.0 ± 0.04) was reproducibly detected in the SOL muscle in all subjects and conditionally attributed to the intra‐mitochondrial Pi pool (Pi2; pH 7.3 ± 0.07). In the SOL muscle, the Pi2/Pi1 ratio was 1.6 times higher compared to the TA muscle in the same individual. Localized 3D CSI results showed that the Pi2 peak was present in voxels well away from blood vessels. Determination of the T1 of the two Pi pools in a single individual using adiabatic excitation of the spectral region around 5 ppm yielded estimates of 4.3 ± 0.4 s vs 1.4 ± 0.5 s for Pi1 and Pi2, respectively. Together, these results suggest that the intra‐mitochondrial Pi pool in resting human skeletal muscle may be visible with 31P MRS at high field. Copyright © 2010 John Wiley & Sons, Ltd.
Gene structure of CYP2C8 and extrahepatic distribution of the human CYP2Cs

Extrahepatic tissue distribution of the mRNAs for the four human CYP2Cs (2C8, 2C9, 2C18, and 2C19) was examined in kidney, testes, adrenal gland, prostate, brain, uterus, mammary gland, ovary, lung, and duodenum. CYP2C mRNAs were detected by RT‐PCR using specific primers for each individual CYP2C. CYP2C8 mRNA was detected in the kidney, adrenal gland, brain, uterus, mammary gland, ovary, and duodenum. CYP2C9 mRNA was detected in the kidney, testes, adrenal gland, prostate, ovary, and duodenum. CYP2C18 mRNA was found only in the brain, uterus, mammary gland, kidney, and duodenum and CYP2C19 mRNA was found only in the duodenum. Immunoblot analysis of small intestinal microsomes detected both 2C9 and 2C19 proteins. In addition, genomic clones for CYP2C8 were sequenced, and long‐distance PCR was performed to determine the complete gene structure. CYP2C8 spanned a 31 kb region. Comparative analysis of the 2.4 kb upstream region of CYP2C8 with CYP2C9 revealed two previously unidentified transcription factors sites, C/EBP and HPF‐1, and the latter might be involved in hepatic expression. Although CYP2C8 has been shown to be phenobarbital inducible, neither a barbiturate‐responsive regulatory sequence (a Barbie box) nor a phenobarbital‐responsive enhancer module (PBREM) was found within the upstream region analyzed. © 1999 John Wiley & Sons, Inc. J Biochem Toxicol 13: 289–295, 1999
Microsomal Prostaglandin E Synthase-1 Facilitates an Intercellular Interaction between CD4+ T Cells through IL-1β Autocrine Function in Experimental Autoimmune Encephalomyelitis

Microsomal prostaglandin synthetase-1 (mPGES-1) is an inducible terminal enzyme that produces prostaglandin E2 (PGE2). In our previous study, we investigated the role of mPGES-1 in the inflammation and demyelination observed in experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis, using mPGES-1-deficient (mPGES-1−/−) and wild-type (wt) mice. We found that mPGES-1 facilitated inflammation, demyelination, and paralysis and was induced in vascular endothelial cells and macrophages and microglia around inflammatory foci. Here, we investigated the role of interleukin-1β (IL-1β) in the intercellular mechanism stimulated by mPGES-1 in EAE spinal cords in the presence of inflammation. We found that the area invaded by CD4-positive (CD4+) T cells was extensive, and that PGE2 receptors EP1–4 were more induced in activated CD4+ T cells of wt mice than in those of mPGES-1−/− mice. Moreover, IL-1β and IL-1 receptor 1 (IL-1r1) were produced by 65% and 48% of CD4+ T cells in wt mice and by 44% and 27% of CD4+ T cells in mPGES-1−/− mice. Furthermore, interleukin-17 (IL-17) was released from the activated CD4+ T cells. Therefore, mPGES-1 stimulates an intercellular interaction between CD4+ T cells by upregulating the autocrine function of IL-1β in activated CD4+ T cells, which release IL-17 to facilitate axonal and myelin damage in EAE mice.
Tissue engineered biological augmentation for tendon healing: a systematic review.

INTRODUCTION Tendon injuries give rise to significant morbidity. In the last few decades, several techniques have been increasingly used to optimize tendon healing. SOURCES OF DATA We performed a comprehensive search of PubMed, Medline, Cochrane, CINAHL and Embase databases using various combinations of the commercial names of each scaffold and the keywords 'tendon', 'rotator cuff', 'supraspinatus tendon', 'Achilles tendon', 'growth factors', 'cytokines', 'gene therapy', 'tissue engineering', 'mesenchymal' and 'stem cells' over the years 1966-2009. All articles relevant to the subject were retrieved, and their bibliographies were hand searched for further references in the context to tissue-engineered biological augmentation for tendon healing. AREAS OF AGREEMENT Several new techniques are available for tissue-engineered biological augmentation for tendon healing, growth factors, gene therapy and mesenchimal stem cells. AREAS OF CONTROVERSY Data are lacking to allow definitive conclusions on the use of these techniques for routine management of tendon ailments. GROWING POINTS The emerging field of tissue engineering holds the promise to use new techniques for tendon augmentation and repair. Preliminary studies support the idea that these techniques can provide an alternative for tendon augmentation with great therapeutic potential. AREAS TIMELY FOR DEVELOPING RESEARCH The optimization strategies discussed in this article are currently at an early stage of development. Although these emerging technologies may develop into substantial clinical treatment options, their full impact needs to be critically evaluated in a scientific fashion.
Communication aid provision and use among children and adolescents developing aided communication: an international survey

Abstract A fundamental requirement of a supportive language development for young children who need aided communication is that an aided communication system is made available and its use is supported. There is limited information about the age at which children are typically provided with a communication aid or about how aided communication is used in everyday situations. Using questionnaire-based interview data, this study investigated (a) the pattern of provision of communication aids to 84 children and adolescents, (b) parents’ and professionals’ evaluation of the quality of communication across contexts, and (c) availability and use of aided communication in these contexts. The age at which the participants received their first aided system varied considerably across the group; however, most were considerably older than the age at which children with typical development usually begin to speak. Parents and professionals rated most everyday situations as good communication situations but reported that the participants did not have their main form of expressive language available in many of these situations, or did not use it much. Parents rated their child’s education in relation to aided language positively, but many professionals indicated that they had limited knowledge about the participant’s use of aided communication outside of the school environment, or about the parents’ attitudes. The study gives insights into the language learning situation of children and adolescents who develop aided communication.
Extended report: nail disease in psoriatic arthritis--clinically important, potentially treatable and often overlooked.

OBJECTIVES To examine the relationship between the severity of nail disease and characteristics of psoriatic arthritis (PsA). We also wished to assess the clinical management of nail disease in patients with PsA. METHODS We studied 69 patients with PsA at two visits. On the first visit, a rheumatology assessment of joint, skin and nail disease was made. On the second visit, a detailed dermatology assessment of skin and nails was made. Nail disease was analysed using a 20-nail psoriasis nail severity score (PNSS). RESULTS There were 57 (83%) patients with clinical evidence of psoriatic nail disease. Although 66 (96%) patients had been treated for skin disease, only one (1%) had received any treatment for nail disease. Severe nail disease measured by the PNSS correlated with severe skin psoriasis as indicated by the percentage of body surface area affected by psoriasis (r = 0.34, P = 0.004) and physician global assessment of psoriasis (r = 0.45, P<0.001). Patients with distal interphalangeal (DIP) joint disease had higher PNSS scores (P = 0.03). The PNSS was also associated with unremitting and progressive arthritis (P<0.001), and correlated with Stanford health assessment questionnaire (HAQ) (r = 0.34, P = 0.004), depression (r = 0.39, P<0.001) and anxiety (r = 0.34, P = 0.004) scores. Compared with dermatology assessment, the rheumatology examination of nail disease had a positive predictive value of 84% and negative predictive value of 83%. CONCLUSIONS In patients with PsA, the severity of nail disease correlates with indicators of severity of both skin and joint disease. Although rheumatologists can adequately screen for nail disease, the management of this aspect of PsA is often overlooked.
Laparoscopic Cholecystectomy in the Elderly: An Experience at a Tertiary Care Hospital in Western Nepal

Background The incidence of gallstone increases with increasing age. No studies have been reported in the elderly population with laparoscopic cholecystectomy from developing nations. The aim of this study was to compare perioperative outcomes of laparoscopic cholecystectomy between the elderly (≥60 years old) and the young (<60 years old). Methods From July 2015 to June 2016, a retrospective review of medical records of 78 elderly patients (≥60 years old) and 164 young patients (<60 years old) who underwent laparoscopic cholecystectomy was done. The patients' demographics and perioperative outcomes were analyzed. Results Median ages were 65 years (range: 60–80) and 45 years (range: 21–59) for the elderly group and the young group. The majority of patients were female (62.8 and 72%). There were no significant differences in the conversion rate (9 and 7.9%, P = 0.78), postoperative complications (17.9 and 14.6%, P = 0.50), and length of stay in the hospital (4 days for both groups, P = 0.35) between the two groups. There was no mortality in either of the groups. Conclusion Our results of laparoscopic cholecystectomy in elderly patients are comparable with those in young patients. Therefore, laparoscopic cholecystectomy is safe even in the elderly population.
Pain behind bars: the epidemiology of pain in older jail inmates in a county jail.

BACKGROUND The number of older jail inmates in poor health is increasing rapidly. Among older adults, pain is common and leads to greater acute care use. In jail, pain management is complicated by concerns about misuse and diversion. A lack of data about the prevalence and management of pain in older jail inmates limits our ability to develop optimal palliative care strategies for this population. OBJECTIVE To describe the prevalence of and factors associated with pain and analgesic use in a population of older jail inmates. DESIGN Cross-sectional study. χ(2) tests assessed association between characteristics, pain, and analgesic use. SETTING/SUBJECTS Two hundred ten jail inmates age 55 or older. MEASUREMENTS "Severe frequent pain" defined as "severe or very severe" pain experienced "frequently or constantly" using the validated Memorial Symptom Assessment Scale. Medical conditions, substance use, and analgesic treatment determined through self-report and jail medical records. RESULTS Participants' mean age was 59 years; 69% had multimorbidity; 75% reported any pain; 39% reported severe frequent pain. Report of severe frequent pain was associated with multimorbidity, functional impairment, and pre-jail acute care use (p<0.05), but not with substance use (57% versus 56%, p=0.89). Within a week of their interview, most participants with severe frequent pain had received an analgesic (87%) and many received an opioid (70%). CONCLUSION High rates of pain in a rapidly growing population of older jail inmates with multimorbidity and functional impairment suggest that jails are an important site for assessing symptom burden and developing appropriate palliative care interventions.