Miracle-dz/UniFAR-FTUs huggingface dataset:
Falls Sustained During Inpatient Rehabilitation After Lower Limb Amputation: Prevalence and Predictors

Pauley T, Devlin M, Heslin K: Falls sustained during inpatient rehabilitation after lower limb amputation: Prevalence and predictors. Am J Phys Med Rehabil 2006;85:521–532. Objective:The purpose of this study is to identify risk factors for falling and fall-related injury among a group of inpatients undergoing rehabilitation after major lower limb amputation. Design:Retrospective cohort. Results:Out of 1267 patients, 260 (20.5%) fell at least once. There were a total of 374 falls, 67 (17.9%) of which resulted in one or more injuries. Adjusted odds ratios (OR) and 95% confidence intervals (CI) were calculated for factors significantly associated with falling, including age of ≥71 yrs (OR = 1.40, 95% CI = 1.02–1.89), lengths of stay of 22–35 days (OR = 2.97, 95% CI = 1.14–7.72) or >5 wks (OR = 6.07, 95% CI = 2.34–15.71), four or more comorbidities (OR = 1.93, 95% CI = 1.09–3.41), cognitive impairment (OR = 1.68, 95% CI = 1.02–2.78), two or more as-needed medications (OR = 1.81, 95% CI = 1.02–3.21), benzodiazepines (OR = 2.22, 95% CI = 1.24–3.96), and opiates (OR = 5.76, 95% CI = 3.29–10.09). Factors significantly associated with fall-related injuries included bilateral amputation (OR = 3.68, 95% CI = 1.49–9.05) and falls during the day shift (OR = 2.63, 95% CI = 1.24–5.57). Conclusions:One in five patients with lower limb amputation will likely experience at least one fall during inpatient rehabilitation, with 18% sustaining an injury. Ongoing research is required to develop appropriate intervention strategies to ameliorate the risk of falling during inpatient rehabilitation.
Practice guideline update summary: Botulinum neurotoxin for the treatment of blepharospasm, cervical dystonia, adult spasticity, and headache

Objective: To update the 2008 American Academy of Neurology (AAN) guidelines regarding botulinum neurotoxin for blepharospasm, cervical dystonia (CD), headache, and adult spasticity. Methods: We searched the literature for relevant articles and classified them using 2004 AAN criteria. Results and recommendations: Blepharospasm: OnabotulinumtoxinA (onaBoNT-A) and incobotulinumtoxinA (incoBoNT-A) are probably effective and should be considered (Level B). AbobotulinumtoxinA (aboBoNT-A) is possibly effective and may be considered (Level C). CD: AboBoNT-A and rimabotulinumtoxinB (rimaBoNT-B) are established as effective and should be offered (Level A), and onaBoNT-A and incoBoNT-A are probably effective and should be considered (Level B). Adult spasticity: AboBoNT-A, incoBoNT-A, and onaBoNT-A are established as effective and should be offered (Level A), and rimaBoNT-B is probably effective and should be considered (Level B), for upper limb spasticity. AboBoNT-A and onaBoNT-A are established as effective and should be offered (Level A) for lower-limb spasticity. Headache: OnaBoNT-A is established as effective and should be offered to increase headache-free days (Level A) and is probably effective and should be considered to improve health-related quality of life (Level B) in chronic migraine. OnaBoNT-A is established as ineffective and should not be offered for episodic migraine (Level A) and is probably ineffective for chronic tension-type headaches (Level B).
Perceived Self-Control is Related to Mental Distress in Patients Entering Substance Use Disorder Treatment

ABSTRACT Background: Levels of mental distress are high in patients with substance use disorders (SUD) and investigation of correlates may broaden our understanding of this comorbidity. Objectives: We investigated self-reported symptoms of mental distress among individuals entering either outpatient opioid maintenance treatment (OMT) or other inpatient SUD treatment and related factors, with a particular focus on perceived self-control. Methods: A cross-sectional study including substance users (n = 548; mean age 34 years; 27% women) entering treatment at 21 different treatment-centers across Norway, interviewed between December 2012 and April 2015. Symptoms of mental distress were assessed with Global Symptom Index (GSI) score. Adjusted relative risk ratios (RRR) with 95% confidence intervals (CI) were estimated through multinomial logistic regression. Results: More than half of the participants in both treatment groups reported mental distress (GSI) above clinical cut-off. The use of alcohol and exposure to violence were associated with increased likelihood of high GSI for both patient groups. Also, lower perceived self-control was related to high GSI in both treatment groups. Conclusion: Symptoms of mental distress were equally common among patients entering OMT and those entering other inpatient SUD treatment, even if the patients differed on a number of clinical characteristics. Use of alcohol and exposure to violence were associated with more mental distress in both groups. Perceived self-control also appeared to be important when explaining symptoms of mental distress among these SUD patients.
Endothelin receptors in human coronary artery and aorta

1 ETA and ETB‐selective and non‐selective ligands were used to define the endothelin receptors in the media (vascular smooth muscle layer) of human aorta and coronary artery. Saturation experiments with iodinated endothelin‐1 (ET‐1), endothelin‐2 and sarafotoxin 6b (S6b) identified high affinity binding sites in aorta (KD [125I]‐ET‐1 0.33±0.02nM (n=9), KD [125I]‐ET‐2 1.04±0.23 nM (n=5), KD [125I]‐S6b 0.15±0.01 nM (n=9 ±s.e.mean)) and coronary artery (KD [125I]‐ET‐1 0.43±0.10nM, KD [125I]‐ET‐2 0.71±0.17 nM, KD [125I]‐S6b 0.27±0.03 nM (n=3 ±s.e.mean)). Hill coefficients (nH) approached unity in each case. 2 No specific binding was detectable with [125I]‐ET‐3 (4 pM‐4 nM) in aorta. Unlabelled ET‐3 competed monophasically with [125I]‐ET‐1 in aorta (KD 8.21±1.62 nM, compared to unlabelled ET‐1 KD, 0.60±0.20 nM) (n= 3 ±s.e.mean). In coronary artery, the KD and Bmax values calculated from [125I]‐ET‐3 saturation experiments were 2.13±1.39nM and 20.6±12.9 fmol mg−1 protein, respectively (n=3 ±s.e.mean). 3 ETA antagonists competed monophasically for [125I]‐ET‐1 (100 pM) binding sites with nanomolar or subnanomolar affinity in the aorta (KD BQ123, 0.47±0.13nM; KD FR139317, 0.40±0.10nM; KD PD151242, 2.09±0.48 nM) and coronary artery (KD FR139317, 0.41±0.13 nM; KD PD151242, 3.60±0.74nM) (n=3 ±s.e.mean). However, two site fits were preferred on analysis of competition experiments with ETB‐selective agonists versus [125I]‐ET‐1 in coronary artery (BQ3020: KDETA 0.96±0.14)μm, KD ETB 1.34±1.08nM and sarafotoxin 6c: KD ETA 1.15±0.14 μm, KD ETB 1.77±0.72nM) (n=3 ±s.e.mean). The selectivity of the agonists for ETB receptors (700 fold) was lower than reported in other species. 4 Sarafotoxin 6b (2 pM‐2 μm) completely inhibited [125I]‐ET‐1 (100 pM) binding in aorta (KD 1.36±0.22nM) (n=3 ±s.e.mean). The non‐peptide compounds Ro462005 and bosentan, competed with [125I]‐ET‐1 binding in coronary artery with KD values of 0.19±0.04 μm and 2.94±0.95 nM, respectively (n=3 ±s.e.mean). 5 Inhibition of [125I]‐ET‐2 and [125I]‐S6b binding by FR139317 was similar to the inhibition of [125I]‐ET‐1 binding in both arteries, being monophasic with KD values in the same range. 6 ETA receptors in coronary artery media were detected by [125I]‐PD151242 (KD 0.23±0.04 nM, Bmax 10.1±1.2 fmol mg−1 protein) (n=3 ±s.e.mean). [125I]‐BQ3020, an ETB‐selective radioligand, indicated the presence of a smaller population of ETB receptors in this tissue (KD 0.60±0.31 nM, Bmax 4.5±2.1 fmol mg−1 protein) (n=3 ±s.e.mean). 7 Autoradiography with [125I]‐PD151242 and [125I]‐BQ3020 confirmed the predominance of ETA receptors in the media of both arteries. 8 The results of this study indicate that ETA receptors predominate in the vascular smooth muscle of human cardiac arteries, with a small and variable population of ETB receptors detectable in the coronary artery.
Effects of opium addiction on some serum factors in addicts with non‐insulin‐dependent diabetes mellitus

The aim of this study was to determine the effect of opium on biochemical parameters in addicts with non‐insulin‐dependent diabetes mellitus (NIDDM). Twenty‐three males and 26 females between 35 and 65 years of age, with NIDDM, addicted to opium, were selected as the case group. Twenty‐three males and 26 females with NIDDM and no opium addiction served as controls. Fasting glucose, glycated haemoglobin (HbA1c), total cholesterol, high density lipoproteins ‐ cholesterol (HDL‐c), triglycerides (TGs), sodium (Na + ), potassium (K + ), calcium (Ca2+), iron (Fe2+), total iron binding capacity (TIBC), serum total protein, albumin, alanine aminotransferase (ALT), aspartate aminotransferase (AST), uric acid and urea were measured in the serum of the two groups. Serum protein electrophoresis was also carried out. Compared to the control group, in addicted males with NIDDM, HbA1c, K + and Fe2+ were higher, and serum total protein, ALT and HDL‐c were lower. No significant difference was observed between other factors. Albumin was lower in addicts, but no significant difference was observed between the albumin/globulin ratios. In addicted females with NIDDM, serum total protein, TIBC, ALT and AST were lower compared to non‐addicts. Cholesterol tends to be lower in diabetic addicted males, HbA1c in addicted females and uric acid in addicted males was higher compared to non‐addicted diabetics. Their differences, however, were not significant. According to our results, smoking opium increases serum glucose and decreases HDL‐c, and thus adds to metabolic disorders in NIDDM patients. It also increases potassium and Fe2+ in males and decreases TIBC in females, and could therefore potentially interfere with water and iron metabolism.
Decreased expression of tumour suppressor Bax‐interacting factor‐1 (Bif‐1), a Bax activator, in gastric carcinomas

Aims: Evasion of apoptosis is one of the hallmarks of cancer. Bax‐interacting factor‐1 (Bif‐1) interacts with both Bax and Bak that are essential for the intrinsic pathway of apoptosis, and enhances apoptosis. The aim of this study was to explore whether alteration of Bif‐1 expression might be a characteristic of gastric cancer. Methods: We analysed the expression of Bif‐1 protein in 60 gastric adenocarcinomas by immunohistochemistry using a tissue microarray approach. Results: In normal gastric mucosal cells, surface and glandular epithelial cells strongly expressed Bif‐1. While Bif‐1 expression was detected in 24 cases (40%) of the gastric carcinomas, there was no Bif‐1 immunostaining in the remaining 36 cancers. Even in the 24 cases with positive Bif‐1 immunostainings, 10 cancers showed decreased intensity of immunostaining compared with the normal mucosal epithelial cells. Conclusion: The decreased expression of Bif‐1 in malignant gastric epithelial cells compared with the normal mucosal cells suggests that loss of Bif‐1 expression may play a role in gastric tumorigenesis, possibly by inhibiting the apoptosis mediated by Bif‐1.
Interaction between amount and pattern of training in the induction of intermediate- and long-term memory for sensitization in aplysia.

In Aplysia, three distinct phases of memory for sensitization can be dissociated based on their temporal and molecular features. A single training trial induces short-term memory (STM, lasting <30 min), whereas five trials delivered at 15-min intervals induces both intermediate-term memory (ITM, lasting >90 min) and long-term memory (LTM, lasting >24 h). Here, we explore the interaction of amount and pattern of training in establishing ITM and LTM by examining memory for sensitization after different numbers of trials (each trial = one tail shock) and different patterns of training (massed vs. spaced). Under spaced training patterns, two trials produced STM exclusively, whereas four or five trials each produced both ITM and LTM. Three spaced trials failed to induce LTM but did produce an early decaying form of ITM (E-ITM) that was significantly shorter and weaker in magnitude than the late-decaying ITM (L-ITM) observed after four to five trials. In addition, E-ITM was induced after three trials with both massed and spaced patterns of training. However, L-ITM and LTM after four to five trials require spaced training: Four or five massed trials failed to induce LTM and produced only E-ITM. Collectively, our results indicate that in addition to three identified phases of memory for sensitization--STM, ITM, and LTM--a unique temporal profile of memory, E-ITM, is revealed by varying either the amount or pattern of training.
Diet-induced co-variation between architectural and physicochemical plasticity in an extended phenotype

ABSTRACT The adaptive benefits of extended phenotypic plasticity are imprecisely defined due to a paucity of experiments examining traits that are manipulable and measurable across environments. Spider webs are often used as models to explore the adaptive benefits of variations in extended phenotypes across environments. Nonetheless, our understanding of the adaptive nature of the plastic responses of spider webs is impeded when web architectures and silk physicochemical properties appear to co-vary. An opportunity to examine this co-variation is presented by modifying prey items while measuring web architectures and silk physiochemical properties. Here, we performed two experiments to assess the nature of the association between web architectures and gluey silk properties when the orb web spider Argiope keyserlingi was fed a diet that varied in either mass and energy or prey size and feeding frequency. We found web architectures and gluey silk physicochemical properties to co-vary across treatments in both experiments. Specifically, web capture area co-varied with gluey droplet morphometrics, thread stickiness and salt concentrations when prey mass and energy were manipulated, and spiral spacing co-varied with gluey silk salt concentrations when prey size and feeding frequency were manipulated. We explained our results as A. keyserlingi plastically shifting its foraging strategy as multiple prey parameters simultaneously varied. We confirmed and extended previous work by showing that spiders use a variety of prey cues to concurrently adjust web and silk traits across different feeding regimes. Summary: Multiple prey cues induce spiders to alter web architecture and silk properties to plastically switching foraging strategies.
Dynamics of the SetCD-Regulated Integration and Excision of Genomic Islands Mobilized by Integrating Conjugative Elements of the SXT/R391 Family

ABSTRACT Mobilizable genomic islands (MGIs) are small genomic islands that are mobilizable by SXT/R391 integrating conjugative elements (ICEs) due to similar origins of transfer. Their site-specific integration and excision are catalyzed by the integrase that they encode, but their conjugative transfer entirely depends upon the conjugative machinery of SXT/R391 ICEs. In this study, we report the mechanisms that control the excision and integration processes of MGIs. We found that while the MGI-encoded integrase IntMGI is sufficient to promote MGI integration, efficient excision from the host chromosome requires the combined action of IntMGI and of a novel recombination directionality factor, RdfM. We determined that the genes encoding these proteins are activated by SetCD, the main transcriptional activators of SXT/R391 ICEs. Although they share the same regulators, we found that unlike rdfM, intMGI has a basal level of expression in the absence of SetCD. These findings explain how an MGI can integrate into the chromosome of a new host in the absence of a coresident ICE and shed new light on the cross talk that can occur between mobilizable and mobilizing elements that mobilize them, helping us to understand part of the rules that dictate horizontal transfer mechanisms.
Clinical Study on the Dose-Effect Relationship of a Nifuratel-Nystatin Combination in the Treatment of Vulvo-vaginal Infections

Summary Objective: The dose-effect relationship of nifuratel (CAS 4936-47-4) + nystatin (CAS 1400-61-9, CAS 34786-70-4) (Macmiror Complex ®) in topical treatment of vulvo-vaginitis was studied. Method: Sixty patients with Trichomoniasis and/or Candidiasis were randomized to: 1) nifuratel 125 mg/nystatin 50000 IU, 2) nifuratel 250 mg/nystatin 100000 IU, 3) nifuratel 500 mg/nystatin 200000 IU. Undistinguishable ovules were intravaginally applied qd for 10 days. The dose-effect relationship was assessed by ANCOVA. Result: After 5 days the microbiological cure rate occurred in 10 % of patients in the least dose, in 40 % in the middle dose and in 85 % in the highest dose group (P=0.000). After 10 days of treat-ment, the microbiological cure rate increased to 45 %, 84 %, and 95 %, respectively (P=0.007). Clinical signs and symptoms gradually disappeared in a doseand time-dependent manner. No relapse has been observed after 10 day-follow up on 46 patients. Conclusion: The results confirmed a linear relationship between nifuratel + nystatin dose and effect. The least effective dose was nifuratel 250 mg + nystatin 100,000 IU once daily for 5 days and the best dose in terms of risk/benefit ratio was nifuratel 500 mg + nystatin 200,000 IU once daily for 5 days.
Integral pharmacological management of bone mineral disorders in chronic kidney disease (part II): from treatment of phosphate imbalance to control of PTH and prevention of progression of cardiovascular calcification

ABSTRACT Introduction: Chronic kidney disease-mineral and bone disorders (CKD-MBD) are associated with costly complications and dismal hard-outcomes. Areas covered: In two comprehensive articles we review contemporary and future pharmacological options for treatment of phosphate (P) imbalance (part 1) and hyperparathyroidism (this part 2), taking into account CKD-accelerated cardiovascular calcification (CVC) processes. Expert opinion: Improvements in CKD-MBD require an integral approach, addressing all three components of the CKD-MBD triad. Here, initial guidance to control hyperparathyroidism is provided, taking into account the presence/absence of CVC. We include also measures for patients at risk of adynamic bone disease or suffering from calciphylaxis. Many epidemiological studies (relating to vitamin D) and thorough analyses of recent randomized clinical trials (of cinacalcet) point towards benefits of attempting to improve biochemical parameters while trying to, at least, avoid progression of CVC by more rational use of intestinal P-binders and low-dose vitamin D derivatives and/or calcimimetics. This approach does not seem to be far away from significantly improving hard-outcomes, at least in the dialysis population. The availability of new drugs and the performance of randomized clinical trials should ultimately lead to define earlier, clearer, and more cost-effective patient stratification and biochemical targets with consequent significant clinical improvements.
Has Higher Household Indebtedness Weakened Monetary Policy Transmission?

Has monetary policy in advanced economies been less effective since the global financial crisis because of deteriorating household balance sheets? This paper examines the question using household data from the United States. It compares the responsiveness of household consumption to monetary policy shocks in the pre- and post-crisis periods, relating changes in monetary transmission to changes in household indebtedness and liquidity. The results show that the responsiveness of household consumption has diminished since the crisis. However, household balance sheets are not the culprit. Households with higher debt levels and lower shares of liquid assets are the most responsive to monetary policy, and the share of these households in the population grew. Other factors, such as economic uncertainty, appear to have played a bigger role in the decline of householdsâ responsiveness to monetary policy.
Playing to the Crowd: Musicians, Audiences, and the Intimate Work of Connection

Making music is a surprisingly limited component of what is required to be a music artist, particularly an independent artist. For Zoë Keating, one of the musicians Nancy K. Baym interviewed for her book Playing to the Crowd: Musicians, Audiences, and the Intimate Work of Connection, her work involves not only composition and performing as a cellist but also engaging continuously with her fans on social media and “offering her audience her self” (p. 5) through sharing personal stories about her young family and engaging in discussion online. This activity is part of what Baym characterizes as relational labor: “the ongoing, affective, material and cognitive work of communicating with people over time to create structures that support continued work” (p. 19). Distinct from affective or emotional labor, this concept, which is one of the most significant contributions of the book, encapsulates the continual processes of interpersonal connection within a realm in which sociality and commerce are particularly interwoven.
Evolving Insights in the Pathogenesis and Therapy of Cutaneous T‐cell lymphoma (Mycosis Fungoides and Sezary Syndrome)

Cutaneous T‐cell lymphomas (CTCL) are a heterogeneous group of malignancies derived from skin‐homing T cells. The most common forms of CTCL are Mycosis Fungoides (MF) and Sezary Syndrome (SS). Accurate diagnosis remains a challenge due to the heterogeneity of presentation and the lack of highly characteristic immunophenotypical and genetic markers. Over the past decade molecular studies have improved our understanding of the biology of CTCL. The identification of gene expression differences between normal and malignant T‐cells has led to promising new diagnostic and prognostic biomarkers that now need validation to be incorporated into clinical practice. These biomarkers may also provide insight into the mechanism of development of CTCL. Additionally, treatment options have expanded with the approval of new agents, such as histone deacetylase inhibitors. A better understanding of the cell biology, immunology and genetics underlying the development and progression of CTCL will allow the design of more rational treatment strategies for these malignancies. This review summarizes the clinical epidemiology, staging and natural history of MF and SS; discusses the immunopathogenesis of MF and the functional role of the malignant T‐cells; and reviews the latest advances in MF and SS treatment.
Munc18a Does Not Alter Fusion Rates Mediated by Neuronal SNAREs, Synaptotagmin, and Complexin*

Background: Munc18-1 is an important factor for synaptic transmitter release, but its molecular mechanism remains an enigma. Results: Munc18a does not affect fusion kinetics. It can sequester syntaxin-1A molecules from the syntaxin-1A·SNAP-25 t-SNARE complex. Conclusion: Munc18a has no effect on complete fusion in conjunction with synaptotagmin-1, complexin-1, and neuronal SNAREs. Significance: This work provides new insights into Munc18-1 and its interactions with other synaptic proteins. Sec1/Munc18 (SM) proteins are essential for membrane trafficking, but their molecular mechanism remains unclear. Using a single vesicle-vesicle content-mixing assay with reconstituted neuronal SNAREs, synaptotagmin-1, and complexin-1, we show that the neuronal SM protein Munc18a/nSec1 has no effect on the intrinsic kinetics of both spontaneous fusion and Ca2+-triggered fusion between vesicles that mimic synaptic vesicles and the plasma membrane. However, wild type Munc18a reduced vesicle association ∼50% when the vesicles bearing the t-SNAREs syntaxin-1A and SNAP-25 were preincubated with Munc18 for 30 min. Single molecule experiments with labeled SNAP-25 indicate that the reduction of vesicle association is a consequence of sequestration of syntaxin-1A by Munc18a and subsequent release of SNAP-25 (i.e. Munc18a captures syntaxin-1A via its high affinity interaction). Moreover, a phosphorylation mimic mutant of Munc18a with reduced affinity to syntaxin-1A results in less reduction of vesicle association. In summary, Munc18a does not directly affect fusion, although it has an effect on the t-SNARE complex, depending on the presence of other factors and experimental conditions. Our results suggest that Munc18a primarily acts at the prefusion stage.