Miracle-dz/UniFAR-FTUs huggingface dataset:
VIM-1-Producing Pseudomonas mosselii Isolates in Italy, Predating Known VIM-Producing Index Strains

Acquired metallo-β-lactamases (MBLs) are emerging resistance determinants of great clinical concern. They are found in Enterobacteriaceae, Pseudomonas aeruginosa, and other Gram-negative nonfermenters, in which they can confer a very broad spectrum of β-lactam resistance, including the expanded-
Treatment of Early Acanthamoeba Keratitis With Alcohol-Assisted Epithelial Debridement

Purpose To study the safety and efficacy of treating early-stage Acanthamoeba keratitis (AK) with 20% alcohol-assisted epithelial debridement. Methods Four consecutive patients (2 wearing orthokeratology lenses and 2 wearing soft contact lenses) presented with pseudodendrites, radial keratoneuritis, and epithelial irregularities. Using a technique similar to laser-assisted subepithelial keratomileusis, we performed alcohol-assisted full-thickness debridement of the corneal epithelium and sent portions for smears, histopathologic and ultrastructural examinations, and culture for evidence of Acanthamoeba. Patients were then started on topical propamidine isethionate and 0.02% polyhexamethylene biguanide. Results Immediately after debridement, minimal underlying anterior stromal infiltrate or haze was seen. Dosages of antiamoebic agents were tapered as corneal defects reepithelialized (in 1–3 weeks) with no evidence of post-debridement corneal infection. At the final follow-up, 1 cornea was transparent and the other 3 corneas had very faint subepithelial haze. Cultures of all epithelial debridement specimens yielded Acanthamoeba trophozoites and cysts, and histopathologic and electron microscopic examinations revealed Acanthamoeba organisms within corneal epithelial layers. Conclusions Alcohol-assisted epithelial debridement facilitates detachment of the full-thickness corneal epithelial layer in a controlled manner and seems to be effective in the treatment of early-stage AK. Unlike the fragile fragmented specimens obtained by mechanical scraping without alcohol soaking, epithelial sheets detached easily and the architectures were well preserved, permitting histopathologic and ultrastructural examinations. Most importantly, 20% alcohol-assisted epithelial debridement did not prevent culturing of Acanthamoeba from the removed epithelial specimens.
Analysis of the ion binding sites of calmodulin by electrospray ionization mass spectrometry.

The binding of Ca2+ and Mg2+ to four calmodulins (SynCaM 1, SynCaM 8, SynCaM 12A, and SynCaM 18A) has been studied by ESI-MS. The mass spectra were recorded by dissolving the apoproteins in methanol/water (20/80, v/v) containing 1 mM CaCl2 or 1 mM MgCl2 and the pH adjusted to 6.0 with ammonia. The carrier solvent was methanol/water (20/80, v/v). In the case of Ca2+ complexation, ESI-MS reveals the presence of three kinds of sites: the first of high affinity corresponding to those determined using flow and equilibrium dialysis techniques and two others with lower affinities. These results clearly confirm the conclusion of Milos et al. [Milos, M. , Comte, M. , Schaer, J. J., & Cox, J. A. (1989) J. Inorg. Biochem. 36, 11-25] that there should exist between four and six auxiliary sites for Ca2+. Concerning the complexation of magnesium, the four proteins are able to bind two Mg2+ almost certainly on auxiliary cationic sites.
Temozolomide: a milestone in neuro-oncology and beyond?

Temozolomide (Temodal®, Temodar ), an imidazol derivative, is a second-generation alkylating agent. The orally available prodrug with the capacity of crossing the blood–brain barrier received accelerated US FDA approval in 1999. Three pivotal Phase II trials showed modest activity in the treatment of recurrent anaplastic astrocytoma glioblastoma. In 2005, the FDA and the European Agency for the Evaluation of Medicinal Products approved temozolomide for use in newly diagnosed glioblastoma, in conjunction with radiotherapy, based on an European Organisation for Research and Treatment of Cancer/National Cancer Institute of Canada Phase III trial. The adverse events associated with temozolomide are mild-to-moderate and generally predictable; the most serious are noncumulative and reversible myelosuppression and, in particular, thrombocytopenia, which occurs in less than 5% of patients. Continuous temozolomide administration is associated with profound CD4-selective lymphocytopenia. Molecular studies have suggested that the benefit of temozolomide chemotherapy is restricted to patients whose tumors have a methylated methylguanine methyltransferase gene promotor and are thus unable to repair some of the chemotherapy-induced DNA damage. Temozolomide is under investigation for other disease entities, in particular lower-grade glioma, brain metastases and melanoma.
Protective Effects of Vitamin E, Selenium and Zinc Supplementation on Hematological and Some Biochemical Parameters in Pregnant Rats Exposed to Cadmium

2 Abstract: The aim of this study was to investigate the possible protective role of vitamin E (vit.E), zinc (Zn) and selenium (Se) as antioxidants against cadmium (Cd) toxicity in pregnant rats reflected via assessment of hematological and some biochemical parameters. Ninety pregnant rats were involved and randomly allocated into equally distributed (n=10) nine groups. The first group was kept as control group. While, the other eight groups were treated with 0.3 mg CdCl /kg b.wt for the first four groups (low dose cadmium) and 1.5 mg CdCl /kg 22 b.wt for the second four groups (high cadmium dose). Three of the low and 3 of the high doses exposed cadmium groups were treated with one of the following antioxidants: 10 mg vitamin E / animal, 2 mg zinc sulphate (ZnSO ) / kg b.wt. or 1.5 mg sodium selenite (NaSeO ), respectively. Blood samples were collected in 43 heparinized tubes and used for hematological studies and estimation of cadmium level. The plasma was separated to aliquots for evaluation of zinc level and glutathione peroxidase activity (GSH-Px). Exposure to both low and high Cd doses induced significant decrease in RBC's count, hemoglobin concentration and packed cell volume. In addition to significant hypozincemia was recorded. In high dose Cd exposed group glutathione peroxidase activity was significantly decreased. The whole blood of all cadmium exposed mothers rat was higher in cadmium compared to those of control group. Treatment with vit.E, Se and Zn increased significantly the erythrocytic parameters and Zn level and GSH-Px activity. Moreover, reduction of cadmium residual level in blood of mothers rat was evident. It could be concluded that treatment with vit. E, Se and Zn may have a protective effect specially at the low dose Cd exposure which is reflected on improving the blood parameters when compared with Cd treated group.
Risk factors for gastric cancer in South India.

INTRODUCTION Stomach cancer is the third most common cancer in South India. A higher incidence has been reported from certain states in northern India, where potential risk factors have been identified. Similar data is available only to a limited extent from southern India. The aim of this case-control study was to evaluate the effects of lifestyle habits and dietary factors on the risk of gastric cancer in South Indians. METHODS A hospital-based case-control study of matched pairs was conducted in Chennai, India, from 2002 to 2006 in a large tertiary care referral centre in South India. We studied 89 gastric cancer patients and 89 age- and gender-matched healthy controls of the same socioeconomic status. All subjects were interviewed face-to-face by a trained interviewer using a structured questionnaire to collect data about lifestyle habits, such as cigarette smoking, alcohol consumption, tobacco chewing and dietary factors, with special attention to known factors like salted fish, smoked and pickled foods as well as intake of vegetables and fruits. RESULTS The response rate was 100 percent. There were 64 male and 25 female patients. The male to female ratio was 2.6:1. The demographic characteristics were similar in the case and control populations. Less than ten percent of patients were below the age of 30 years. Approximately 50 percent were between 30 and 60 years of age, and the rest were over 60 years of age. Multivariate logistic regression models indicated that alcohol consumption (odds ratio [OR] 2.3, 95 percent confidence interval [CI] 1.1-4.9, p-value is 0.04) and consumption of pickled food (OR 1.8, 95 percent CI 1.2-3.9, p-value is 0.05) are independent risk factors for the development of gastric cancer. A protective effect of the consumption of pulses (OR 0.4, 95 percent CI 0.2-0.9, p-value is 0.05), showing a 55 percent reduction in risk, was also identified; this could be of use for possible control and prevention of this cancer. Tobacco chewing and cigarette smoking did not emerge as high risk factors for stomach cancer. CONCLUSION The study showed alcohol and pickled food consumption as independent risk factors for the development of gastric cancer, while consumption of pulses were protective. Cigarette smoking did not predict an increased risk of contracting the disease.
[Efficacy of gabapentin in the treatment of carpal tunnel syndrome].

BACKGROUND AND OBJECTIVE To evaluate the analgesic efficacy and safety of gabapentin in the treatment of carpal tunnel syndrome (CTS), as well as the electromyographic (EMG) evolution after 6 months. PATIENTS AND METHOD A prospective study with a 6-month follow-up of patients with EMG diagnosis of primary CTS starting treatment with 1.800 mg/day of gabapentin. At baseline visit and after 6 months of treatment a complete clinical evaluation and an EMG study were performed. Adverse effects of gabapentin were also registered. RESULTS Twenty-five patients were included, mean age (standard deviation) 58.88 (7.69) years. After 6 months of treatment, a statistically significant reduction of pain (p = 0.001) and improvement of severity of symptoms (p = 0.008) were observed, although functional capacity did not change. EMG was performed in 19 patients at 6 months. Compared to baseline EMG: 52.6% patients showed no changes in EMG findings, while 5.3% patients showed improvement and in 26.3% the EMG was normal. Progression was only seen in 15.8% of patients after 6 months of treatment. In 28% of the patients gabapentin was stopped because of side effects. CONCLUSIONS In our series, gabapentin was effective in the reduction of pain and improvement of the severity of the symptoms. Results of EMG after 6 months of treatment showed no changes, with improvement and/or remission in 84.2% of the cases. The drug was safe and well tolerated.
Managing Clinical Knowledge for Health Care Improvement

Quality health care rests fundamentally on the achievements of biomedical research. All health outcomes are improved by sound science: health status can be turned around by transplantation when someone's life is in jeopardy due to a diseased organ; social functioning can be improved by shock wave lithotripsy that -leads to faster recovery; and satisfaction can beenhanced when children with moderate or severe asthma receive appropriate anti-inflammatory treatment. To improve the quality of health care that patients actually receive, both biomedical research production and especially its introduction into clinical practice need to be examined.
Impact of confounding by leukocyte composition on associations of leukocyte DNA methylation with common risk factors.

AIM One concern in epigenome-wide studies investigating leukocyte DNA methylation is that observed associations may at least partly reflect differences in leukocyte composition (LC) rather than changes in methylation. We estimated the magnitude of confounding by LC for common risk factors and diseases. MATERIALS & METHODS Variation of LC according to sex, race, age, smoking, alcohol consumption, BMI, cardiovascular fitness, hypertension, coronary heart disease and diabetes was analyzed using blood differentials from 4117 participants of NHANES. Furthermore, leukocyte DNA methylation levels of biomarkers of smoking, BMI, diabetes, age and sex were regressed on these outcomes in a sample of 989 participants of ESTHER, and regression coefficients with and without adjustment for estimated LC were compared. RESULTS Aside from race and ages below 25 years, none of the investigated factors had substantial impact on LC. Adjusted and unadjusted coefficients were virtually identical. CONCLUSION Confounding by LC might often be a minor issue.
Canadian multi‐institutional survey of immune tolerance therapy (ITT) – experience with the use of recombinant factor VIII for ITT

Summary. Immune tolerance therapy (ITT) is currently the most effective approach to eradicate inhibitors in patients with haemophilia A. Limited evidence suggests that the use of plasma‐derived factor VIII (pdFVIII) for ITT may be associated with a greater success rate than recombinant factor VIII (rFVIII). Analysis of ITT cases in Canada offered the opportunity to examine the success rate of using rFVIII for ITT, as rFVIII has been used almost exclusively for Canadian haemophilia A patients since 1994. The results of 32 patients from five haemophilia treatment centres were collated. Three patients continue on ITT. Of the 29 patients who completed ITT, 25 (86.2%) used rFVIII exclusively, and four used pdFVIII exclusively or pdFVIII followed by rFVIII. The initial FVIII dosing frequency was once per day in 72.4% of patients at an average dose of 98 U kg−1 (range 50–200). Eight patients (25%) received one or more adjuvant therapies. The median duration of ITT was 1.1 years (mean 1.5 years, range 9 days to 6 years). The overall success rate of the 29 patients who completed ITT was 79.3% (23/29), which is comparable with the results of immune tolerance registries. Our results suggest that the success rate of ITT using rFVIII is not inferior to the results with pdFVIII.
SPONGIFORM ENCEPHALOPATHY IN FREE-RANGING MULE DEER (ODOCOILEUS HEMIONUS), WHITE-TAILED DEER (ODOCOILEUS VIRGINIANUS) AND ROCKY MOUNTAIN ELK (CERVUS ELAPHUS NELSONI) IN NORTHCENTRAL COLORADO

Between March 1981 and June 1995, a neurological disease characterized histologically by spongiform encephalopathy was diagnosed in 49 free-ranging cervids from northcentral Colorado (USA). Mule deer (Odocoileus hemionus) were the primary species affected and accounted for 41 (84%) of the 49 cases, but six Rocky Mountain elk (Cervus elaphus nelsoni) and two white-tailed deer (Odocoileus virginianus) were also affected. Clinical signs included emaciation, excessive salivation, behavioral changes, ataxia, and weakness. Emaciation with total loss of subcutaneous and abdominal adipose tissue and serous atrophy of remaining fat depots were the only consistent gross findings. Spongiform encephalopathy characterized by microcavitation of gray matter, intraneuronal vacuolation and neuronal degeneration was observed microscopically in all cases. Scrapie-associated prion protein or an antigenically indistinguishable protein was demonstrated in brains from 26 affected animals, 10 using an immunohistochemical staining procedure, nine using electron microscopy, and seven using Western blot. Clinical signs, gross and microscopic lesions and ancillary test findings in affected deer and elk were indistinguishable from those reported in chronic wasting disease of captive cervids. Prevalence estimates, transmissibility, host range, distribution, origins, and management implications of spongiform encephalopathy in free-ranging deer and elk remain undetermined.
Lipoprotein(a) in clinical practice: New perspectives from basic and translational science

Abstract Elevated plasma concentrations of lipoprotein(a) (Lp(a)) are a causal risk factor for coronary heart disease (CHD) and calcific aortic valve stenosis (CAVS). Genetic, epidemiological and in vitro data provide strong evidence for a pathogenic role for Lp(a) in the progression of atherothrombotic disease. Despite these advancements and a race to develop new Lp(a) lowering therapies, there are still many unanswered and emerging questions about the metabolism and pathophysiology of Lp(a). New studies have drawn attention to Lp(a) as a contributor to novel pathogenic processes, yet the mechanisms underlying the contribution of Lp(a) to CVD remain enigmatic. New therapeutics show promise in lowering plasma Lp(a) levels, although the complete mechanisms of Lp(a) lowering are not fully understood. Specific agents targeted to apolipoprotein(a) (apo(a)), namely antisense oligonucleotide therapy, demonstrate potential to decrease Lp(a) to levels below the 30–50 mg/dL (75–150 nmol/L) CVD risk threshold. This therapeutic approach should aid in assessing the benefit of lowering Lp(a) in a clinical setting.
Cryptococcal Ventricular-Peritoneal Shunt Infection: Clinical and Epidemiological Evaluation of Two Closely Associated Cases

Abstract Objective: To determine the cause of meningitis associated with Cryptococcus neoformans in two patients with recent ventricular-peritoneal (VP) shunt placement. Design: A retrospective review of materials, records, and concurrent cases of VP shunt procedures. Isolates of C neoformans from each patient were submitted for analysis by colony morphology, biochemical testing, and karyotyping by pulsed-field electrophoresis. Setting: Two 400-bed community hospitals. Patients: Two immunocompetent patients presented with symptoms of progressive hydrocephalus in August 1991. Each received a VP shunt on the same day by the same surgeon using materials from a common vendor and hospital. Results: Both patients presented within six to eight weeks with symptoms of fever, headache, rash, and cultures of cerebrospinal fluid (CSF) that yielded C neoformans. Each patient recovered after therapy with amphotericin B and flucytosine followed by several months of fluconazole, although one required replacement of the VP shunt for cure. Review of each patient's history and CSF characteristics at the time of shunt placement suggested re-activation of a pre-existing infection. Isolates of C neoformans from each patient were submitted for analysis by colony morphology, biochemical testing, and karyotyping by pulsed-field electrophoresis. Each isolate was found to be unique by chromosomal karyotyping. Conclusions: Our data and previous reports suggest that cryptococcal VP shunt infections appear to be a complication of shunts placed in previously infected persons rather than noso-transmission of cryptococcus during placement.
Switching atypical antipsychotics: a review

Background: Atypical antipsychotics are increasingly used in the treatment of diverse psychiatric disorders; however, there is little information on the ‘why, when, and how’ of switching between the different atypical antipsychotics currently available. Objective: To review the data on switching and atypical antipsychotics. Methods: A literature search was initially conducted using the key words followed by a search of relevant articles including conference abstracts; relevant pharmaceutical companies were also contacted. Results: Clinical trial data are limited in terms of parameters measured, and case reports describe specific problems. Few studies are based on real world populations of psychiatric patients over the long-term. Careful patient and drug selections matched to a carefully supervised and appropriate cross titration based upon the pharmacodynamic and pharmacokinetic properties of all of the drugs involved is important to avoid potential complications such as re-emergence or worsening of psychosis and withdrawal, rebound, and emergent phenomena including new or uncovered side-effects. Psychoeducation and involvement of patients and caregivers in the process are also necessary for a successful switch. Conclusion: Despite the prevalence of switching in real world clinical practice, there is a paucity of data to guide clinicians with respect to effective and safe strategies. There are no criteria defining a successful switch. With the increasing range and formulations of atypical antipsychotics available, there is a rationale for their early use to avoid the practical problems associated with switching from conventional antipsychotics as well as the opportunity to maintain patients on an optimal atypical antipsychotic monotherapy.
A Role for Androgens in Epithelial Proliferation and Formation of Glands in the Mouse Uterus

The endometrium consists of stromal and epithelial compartments (luminal and glandular) with distinct functions in the regulation of uterine homeostasis. Ovarian sex steroids, namely 17β-estradiol and progesterone, play essential roles in modulating uterine cell proliferation, stromal-epithelial cross-talk and differentiation in preparation for pregnancy. The effect of androgens on uterine function remains poorly understood. The current study investigated the effect of the non-aromatizable androgen dihydrotestosterone (DHT) on mouse endometrial function. Ovx female mice were given a single sc injection (short treatment) or 7 daily injections (long treatment) of vehicle alone (5% ethanol, 0.4% methylcellulose) or vehicle with the addition of 0.2 mg DHT (n=8/group) and a single injection of bromodeoxyuridine 2 hours prior to tissue recovery. Treatment with DHT increased uterine weight, the area of the endometrial compartment and immunoexpression of the androgen receptor in the luminal and glandular epithelium. Treatment-dependent proliferation of epithelial cells was identified by immunostaining for MKi67 and bromodeoxyuridine. Real-time PCR identified significant DHT-dependent changes in the concentrations of mRNAs encoded by genes implicated in the regulation of the cell cycle (Wee1, Ccnd1, Rb1) and stromal-epithelial interactions (Wnt4, Wnt5a, Wnt7a, Cdh1, Vcl, Igf1, Prl8, Prlr) as well as a striking effect on the number of endometrial glands. This study has revealed a novel role for androgens in regulating uterine function with an effect on the glandular compartment of the endometrium. This previously unrecognized role for androgens has implications for our understanding of the role of androgens in regulation of endometrial function and fertility in women.
Relative contribution of iron burden, HFE mutations, and insulin resistance to fibrosis in nonalcoholic fatty liver

The mechanism(s) determining the progression from fatty liver to steatohepatitis is currently unknown. Our goal was to define the relative impact of iron overload, genetic mutations of HFE, and insulin resistance on the severity of liver fibrosis in a population of subjects with nonalcoholic fatty liver disease (NAFLD) who had low prevalence of obesity and no overt symptoms of diabetes. In a cohort of 263 prospectively enrolled patients with NAFLD, 7.4% of patients had signs of peripheral iron overload and 9% had signs of hepatic iron overload, but 21.1% had hyperferritinemia. The prevalence of C282Y and H63D HFE mutations was similar to the general population and mutations were not associated with iron overload. Although subjects were on average only moderately overweight, insulin sensitivity, measured both in the fasting state and in response to oral glucose, was lower. Univariate analysis demonstrated that the presence of severe fibrosis was independently associated with older age, female sex, overweight, aspartate/alanine aminotransferase ratio, serum ferritin level, fasting glucose and insulin levels, decreased insulin sensitivity, and with histologic features (degree of necroinflammation and steatosis). After adjustment for body mass index (BMI), age, sex, and degree of steatosis, ferritin levels (odds ratio [OR] = 1.77; 95% CI = 1.21‐ 2.58; P = .0032) and the oral glucose insulin sensitivity (OR = 0.53; CI = 0.33‐0.87; P = .0113) were independent predictors of severe fibrosis. In conclusion, the current study indicates that insulin resistance is a major, independent risk factor for advanced fibrosis in patients with NAFLD. Increased ferritin levels are markers of severe histologic damage, but not of iron overload. Iron burden and HFE mutations do not contribute significantly to hepatic fibrosis in the majority of patients with NAFLD. (HEPATOLOGY 2004;39:179–187.)