Miracle-dz/UniFAR-FTUs huggingface dataset:
Effects of melagatran, a novel direct thrombin inhibitor, during experimental septic shock

Sepsis and endotoxaemia initiate the generation of thrombin, which is responsible for the conversion of fibrinogen to fibrin, platelet aggregation and acts as an inflammatory mediator affecting numerous types of cells, including myocardial, smooth muscle and endothelial cells. Human Gram-negative septic shock, frequently seen in intensive care units, is a condition with high mortality. This condition can be replicated in the endotoxaemic pig. As many of the toxic effects of sepsis are due to thrombin generation, it was of interest to study, using this porcine experimental septic shock model, whether inhibition of thrombin could alleviate the effects of endotoxaemia. For this purpose melagatran, a direct synthetic thrombin inhibitor with a molecular weight of 429 Da, was employed. Melagatran does not significantly interact with any other enzymes in the coagulation cascade or fibrinolytic enzymes aside from thrombin. Furthermore, melagatran does not require endogenous co-factors such as antithrombin or heparin co-Factor II for its antithrombin effect, which is important, as these inhibitors are often consumed in septic patients. We have shown that melagatran exerts a beneficial effect on renal function, as evaluated by plasma creatinine and urinary output, during experimental septic shock. These effects were most pronounced during the later phase of the experimental period, after the infusion of melagatran had been discontinued. Prevention of intrarenal coagulation may be attributable to this finding. In addition, melagatran had beneficial effects on systemic haemodynamics (left ventricular stroke work index, pulmonary capillary wedge pressure and systemic vascular resistance index) in endotoxaemic pigs. This result may be explained by the ability of melagatran to inhibit thrombin, thereby counteracting thrombin’s cellular effects. Thus, it can be seen, using this experimental model of septic shock, that melagatran may help to alleviate some of the damaging effects of endotoxaemia, although more research is required to test this further.
Neuropsychological Sequelae of Ethylene Glycol Intoxication: A Case Study

Ingestion of Ethylene glycol (EG) can result in a clinical syndrome marked by renal, cardiopulmonary, and neurological dysfunction. We present a case study addressing EG intoxication with neurological, radiological, and neuropsychological findings several days to weeks after initial ingestion and again at follow-up six months later. In our case study, CT scans of the head on days one and two post EG ingestion were essentially normal, as was a brain MRI six months later. An MRI of the brain on day five revealed nonspecific cerebellar white matter abnormalities. Neuropsychological assessment at three to four weeks post admission indicated global cognitive impairment with particular deficits in attention, processing speed, constructional ability, language, and memory retrieval. Results at six months follow-up indicated partial improvement in overall cognitive functioning with remaining deficits in processing speed, naming, and constructional ability. These findings suggest that EG intoxication is capable of causing lasting neuropsychological sequelae despite evidence of relatively normal neuroradiologic findings.
BCL‐2 IMMUNOREACTIVITY INCREASES WITH SEVERITY OF CIN: A STUDY OF NORMAL CERVICAL EPITHELIA, CIN, AND CERVICAL CARCINOMA

The presence of the BCL‐2 protein, a marker for inhibition of programmed cell death, was studied in a series of routinely processed cervical tissues, consisting of normal endocervical (n=40) and ectocervical epithelium (n=27), squamous metaplastic epithelium (n=30), CIN (cervical intraepithelial neoplasia) lesions (n=32), and cervical carcinomas (n=13). BCL‐2 was strongly expressed in the basal cell compartment of normal ectocervical squamous epithelium and in nearly all reserve cells, while in endocervical columnar cells it was moderately expressed. In immature squamous metaplastic epithelium, BCL‐2 expression varied. Half of the cases showed only basal cell staining, while the other half showed staining also in suprabasal layers. BCL‐2 could be detected in all premalignant lesions, showing a striking increase in the number of positive cells with increasing severity of CIN, in combination with a mild increase in staining intensity. All adenocarcinomas were positive (n=5), while five of eight squamous cell carcinomas expressed BCL‐2. Based on these results, it is hypothesized that both the larger number of cells staining with BCL‐2 in higher grades of CIN and the increase in staining intensity imply an increasing protection of these neoplastic conditions against programmed cell death. This protection facilitates not only continuing proliferation, but also the induction of genetic instability in dysplastic epithelial cells; it may thus reflect the greater capacity of the more severe CIN lesions to evolve into cervical carcinoma.
Clinical and microbiological effects of systemic azithromycin in adjunct to nonsurgical periodontal therapy in treatment of Aggregatibacter actinomycetemcomitans associated periodontitis: a randomized placebo-controlled clinical trial.

OBJECTIVE This study aimed to evaluate clinical and microbiological effects of systemic azithromycin (AZM) in adjunct to nonsurgical periodontal therapy (NSPT; or scaling root planing - SRP) in treatment of Aggregatibacter actinomycetemcomitans associated periodontitis (AAAP). METHODS AND MATERIALS Seventy individuals with moderate to severe periodontitis and subgingival detection of A. actinomycetemcomitans were randomly allocated to two groups. Thirty-five individuals were allocated to full mouth SRP+AZM (500 mg oral delivery (OD) × 3 days) while 35 individuals were allocated to SRP+Placebo (OD × 3 days) group. The clinical variables evaluated were probing depth (PD), clinical attachment level (CAL), gingival index (GI), plaque index (PI), and percent bleeding on probing sites (%BOP), while microbiologic variables included percentage of subjects positive for A. actinomycetemcomitans at baseline, 3, 6, and 12 months. RESULTS The AZM group showed statistically significant reduction in mean PD (2.91 ± 0.88 mm) as compared to placebo (1.51 ± 0.98 mm) (P < 0.001), while CAL gain was significant in the AZM group (2.71 ± 1.15 mm) as compared to the placebo group (1.71 ± 1.29 mm) (P < 0.001). There was also a statistically significant reduction in the number of subjects positive for A. actinomycetemcomitans in the AZM group (P < 0.0001). CONCLUSION Azithromycin was found to significantly improve the clinical and microbiological parameters in AAAP individuals.
Preliminary In Vivo Evaluation of a Nanofiltered Factor IX Concentrate

1. Mannucci PM. Clinical evaluation of viral safety of coagulation factor VIII and IX concentrates. Vox Sang 1993; 64:197-203. 2. Kreuz W, Auerswald G, Brückmann C, Zieger B, Linde R, Funk M, Auberger K, Sutor AH, Rasshofer R, Roggendorf M. Prevention of hepatitis C virus in­ fection in children with haemophilia A and B and von Willebrand’s disease. Thromb Haemost 1992; 67 (1): 184. 3. Kudesia G, Chapman S, Makris M, Preston FE. Need for second-generation anti-HCV testing in haemophilia. Lancet 1992; 339: 501-2. 4. Zaaijer HL, Cuypers HTM, Reesink HW, Lelie PN, Vrielink H, van der Poel CL. New immunoblot resolves indeterminate results for antibody to hepatitis C virus. Transfusion 1994, 34:184. 5. Gerritzen A, Schneweis K, Scholt B, Brackmann H, Kaiser R, Oldenburg I. Acute hepatitis C in hemophiliacs due to “virus-inactivated” clotting factor concentrates. Thromb Haemost 1992; 68 (6): 781. 6. Schulman S, Lindgren A, Petrini P, Allander T. Transmission of hepatitis C with pasteurised factor VIII. Lancet 1992; 340: 305-6. 7. Mannucci P, Schimpf K, Brettler D, Ciavarella N, Colombo M, Haschke F, Lechner K, Lusher J, Weissbach G, and the International Study Group. Low risk for hepatitis C in hemophiliacs given a high-purity, pasteurized factor VIII concentrate. Ann Int Med 1990; 113: 27-32. 8. Pollmann H, Richter H. Prevalence of hepatitis and HIV in a group of hemo­ philiacs. Ann Hematol 1994; 68: 128.
RESEARCH ON SPOKEN LANGUAGE PROCESSING Progress Report No . 23 ( 1999 ) Indiana University New Directions in Pediatric Cochlear Implantation

Cochlear implantation has been an approved surgical intervention for children (2-18 years) with profound deafness for nearly 10 years. The last decade has brought technological advances in cochlear implant designs with concomitant improvements in patient performance and subsequent broadening of cochlear implant candidacy. Although average performance levels clearly establish the efficacy of pediatric cochlear implantation, individual communication abilities vary widely. This, controversy exists regarding the appropriate expansion of evolving technology into new patient populations. In this chapter, we review current implant technology, patient selection criteria and performance results for pediatric cochlear implant recipients and consider the challenges inherent in the broadening of cochlear implant candidacy.
Classifications in Brief: Laboratory Risk Indicator for Necrotizing Fasciitis Score.

Necrotizing fasciitis is a life-threatening infection that requires a multidisciplinary approach to management, often involving orthopaedic surgeons for surgical débridement. It was first defined by Meleney [15] in 1924, when he discovered beta-hemolytic Streptococcus in a series of 20 patients with necrotizing soft-tissue infections, appropriately termed hemolytic Streptococcus gangrene. In 1952, Wilson [23] renamed the disease necrotizing fasciitis based on consistently present necrotic fascial planes, and this is the currently used term. Since the original description, several classification systems have been used in patients with necrotizing fasciitis. These classifications have been based on anatomic location [13], causative organisms [9], depth of invasion [22], and surgical management of necrotizing fasciitis [2, 18]. However, these systems often address the clinical presentation and management of necrotizing fasciitis at a late stage, and thus, in our opinion, tend not to be useful in detecting early necrotizing fasciitis. In 2004, Wong et al. [25] proposed a new scoring system based on commonly acquired laboratory values that enabled the detection and differentiation of early necrotizing fasciitis from other soft-tissue infections. This is widely known as the Laboratory Risk Indicator for Necrotizing Fasciitis (LRINEC) score. Despite its original purpose, a retrospective cohort study has also demonstrated that LRINEC scores greater than or equal to 6 are associated with an increased risk of death or amputation [20]. However, although the LRINEC score was meant to improve the ability of clinicians to diagnose this lifeand limb-threatening condition early, studies have suggested that it is insufficiently sensitive for this purpose [1, 11]. Until, or unless, it is refined and demonstrated to be both reproducible and sensitive, clinicians probably should not use this score in practice without augmenting it with other diagnostic approaches, such as plain radiographs, CT, or MRI [1, 22].
Increase in hepatitis C virus incidence in HIV-1-infected patients followed up since primary infection

Background: An increase in the incidence of sexually transmitted infections and hepatitis C virus (HCV) infections in HIV-infected men who have sex with men (MSM) has recently been reported. Objective: To estimate HCV incidence and risk factors among HIV-1-infected patients followed up since primary HIV infection in the French PRIMO Cohort between 1996 and 2005. Patients and methods: All patients with at least 18 months of follow-up were studied. HCV antibody tests were performed on baseline plasma samples and repeated on the latest available sample when negative at baseline. Results: In total, 402 patients with a median follow-up of 36 (range 18–104) months were eligible. HCV seroconversion was observed in 6 patients (4 men and 2 women), corresponding to an HCV incidence rate of 4.3 per 1000 person-years. Incidence rates in men and women were 3.5 and 7.8 per 1000 person-years, respectively. The incidence rate was 1.2 per 1000 person-years before January 2003 and 8.3 per 1000 person-years after January 2003 (p = 0.06). The classic risk factors for HCV infection were found in women (intravenous drug use, and body piercing), whereas the only identified risk factor for HCV acquisition was unsafe sex in the four men. Conclusions: Increase in the incidence of acute HCV infection in recently HIV-infected patients confirms the shift in sexual behaviour in the recent years, especially in HIV-infected MSM. Repeated testing for HCV antibodies should be carried out in HCV-negative HIV-infected patients and specific recommendations about protected sex should be clearly provided.
Auditory–Motor Interactions for the Production of Native and Non-Native Speech

During speech production, auditory processing of self-generated speech is used to adjust subsequent articulations. The current study investigated how the proposed auditory–motor interactions are manifest at the neural level in native and non-native speakers of English who were overtly naming pictures of objects and reading their written names. Data were acquired with functional magnetic resonance imaging and analyzed with dynamic causal modeling. We found that (1) higher activity in articulatory regions caused activity in auditory regions to decrease (i.e., auditory suppression), and (2) higher activity in auditory regions caused activity in articulatory regions to increase (i.e., auditory feedback). In addition, we were able to demonstrate that (3) speaking in a non-native language involves more auditory feedback and less auditory suppression than speaking in a native language. The difference between native and non-native speakers was further supported by finding that, within non-native speakers, there was less auditory feedback for those with better verbal fluency. Consequently, the networks of more fluent non-native speakers looked more like those of native speakers. Together, these findings provide a foundation on which to explore auditory–motor interactions during speech production in other human populations, particularly those with speech difficulties.
To compare aneuploidy rates between ICSI and IVF Cases

Introduction: Intracytoplasmic sperm injection (ICSI) currently helps many couples with male infertility. However, ICSI procedure may cause asynchronous sperm decondensation. This could introduce a risk for aneuploidy. The ICSI technique also could cause damage to the second meiotic spindle during injection and cause significantly abnormal pairing of chromosomes when compared with In vitro fertilization (IVF). In this study, we have examined whether ICSI has a higher incidence of aneuploidy when compared with IVF. Material and Methods: A retrospective study was conducted on 36 individuals. Common numbers of chromosome abnormalities were detected using fluorescent in-situ hybridization (FISH). Seven probes were used to detect chromosome X, Y, 13, 16, 18, 21, and 22. Chi-square test was used for statistical analysis and presented as odd ratios with confidence intervals. Results: The age range was 26 through 44 (mean age 35.5) for IVF and 25 through 46 (mean age 35.8) for ICSI. From the 36 egg retrievals, 57 embryos were obtained from nine individuals using IVF and 183 embryos were obtained from 27 individuals using ICSI. For the IVF group, 37 of the 57 examined embryos were abnormal (65%), whereas 128 of 183 examined embryos were abnormal for the ICSI group (69.9%). Among the 57 embryos from the IVF cases, the number of absolute abnormal chromosomes were as follows: X&Y chromosomes: 4 (12.9%), chromosome 13: 9 (29%), chromosome 16: 7 (22.5%), chromosome 18: 6 (19.3%), chromosome 21: 8 (25.8%), chromosome 22: 10 (32.2%). For the ICSI embryos: X and Y chromosomes: 18 (14%), chromosome 13: 34 (26.5%), chromosome 16: 23 (18%), chromosome 18: 23 (18%), chromosome 21: 26 (20.3%), chromosome 22: 31 (24.2%). The odds ratios for the difference between IVF and ICSI for each chromosome were as follows: X&Y chromosomes: 1.53 (0.598-3.916), chromosome 13: 0.969 (0.443-2.122), chromosome 16: 0.709 (0.307-1.639), chromosome 18: 1.650 (0.650-4.188), chromosome 21: 0.777 (0.350-1.724), chromosome 22: 0.647 (0.311-1.348). Overall no significant difference between two insemination procedures was seen 0.948 (0.678-1.324). Conclusions: As a result; ICSI does not create a significantly higher aneuploidy number when compared with IVF as examined by FISH analysis of seven chromosome pairs.
The antidiabetic effect and pharmacokinetic properties of glipizide. Comparison of a single dose with divided dose regime.

In 13 patients with maturity-onset diabetes mellitus which did not respond to diet therapy alone, serum concentration of glipizide, blood glucose (B-G) concentration, serum immunoreactive insulin (S-IRI) and plasma glycerol (P-G) were monitored hourly over 12 hours after placebo, an initial dose of glipizide (5 mg p.o.) and long-term treatment with glipizide (range 7.5--20 mg, mean 10.4), which produced fasting B-G of less than 8 mmol/l. During the long-term treatment, glipizide was given in a random, cross-over pattern, either as a single dose in the morning or as a three-part divided dose regime, in the same total daily amount. The duration of the immediate effects of glipizide on B-G, S-IRI and S-IRI/B-G was 9, 4.5 and 6.5 hours, respectively. The mean apparent half-life of glipizide was 4.1 hours, the mean distribution volume 0.13 l/kg and the mean plasma clearance 0.023 l/kg x h. The area under the concentration curve from 7.30 a.m. to 7.30 p.m. was 15% higher after the single dose regime. The serum levels of glipizide at 10 hours were only 30% lower than after the three-part divided dose regime. There were no significant differences between the single and divided dose regimes as regards B-G, S-IRI and S-IRI/B-G, although the mean B-G for the 12-hour period was somewhat lower after the former than after the latter (7.0 against 8.7 mmol/l).
Human papillomavirus types in 115,789 HPV‐positive women: A meta‐analysis from cervical infection to cancer

Genotyping may improve risk stratification of high‐risk (HR) human papillomavirus (HPV)‐positive women in cervical screening programs; however, prospective data comparing the natural history and carcinogenic potential of individual HR types remain limited. A meta‐analysis of cross‐sectional HR HPV‐type distribution in 115,789 HPV‐positive women was performed, including 33,154 normal cytology, 6,810 atypical squamous cells of undetermined significance (ASCUS), 13,480 low‐grade squamous intraepithelial lesions (LSIL) and 6,616 high‐grade SIL (HSIL) diagnosed cytologically, 8,106 cervical intraepithelial neoplasia grade 1 (CIN1), 4,068 CIN2 and 10,753 CIN3 diagnosed histologically and 36,374 invasive cervical cancers (ICCs) from 423 PCR‐based studies worldwide. No strong differences in HPV‐type distribution were apparent between normal cytology, ASCUS, LSIL or CIN1. However, HPV16 positivity increased steeply from normal/ASCUS/LSIL/CIN1 (20–28%), through CIN2/HSIL (40/47%) to CIN3/ICC (58/63%). HPV16, 18 and 45 accounted for a greater or equal proportion of HPV infections in ICC compared to normal cytology (ICC:normal ratios = 3.07, 1.87 and 1.10, respectively) and to CIN3 (ICC:CIN3 ratios = 1.08, 2.11 and 1.47, respectively). Other HR types accounted for important proportions of HPV‐positive CIN2 and CIN3, but their contribution dropped in ICC, with ICC:normal ratios ranging from 0.94 for HPV33 down to 0.16 for HPV51. ICC:normal ratios were particularly high for HPV45 in Africa (1.85) and South/Central America (1.79) and for HPV58 in Eastern Asia (1.36). ASCUS and LSIL appear proxies of HPV infection rather than cancer precursors, and even CIN3 is not entirely representative of the types causing ICC. HPV16 in particular, but also HPV18 and 45, warrant special attention in HPV‐based screening programs.
Cross-sectional relationships between sedentary behavior and frailty in older adults.

BACKGROUND The aim of this study was to analyze the association between frailty and sedentary behavior and to examine the discriminative ability of sedentary behavior in screening frailty in older adults. METHODS This was a cross-sectional study based on data from an epidemiologic population-based household survey involving 316 community-dwelling older adults (≥60 years) of both sexes (173 women and 143 men). The frailty was measured from an adapted version of the criteria proposed by Fried et al. in 2001, which is based on the presence of three or more of the following components: shrinking, weakness, poor endurance/exhaustion, slowness and low activity. Sedentary behavior was determined by the International Physical Activity Questionnaire (long version). RESULTS The prevalence of frailty was 23.8%, and the average time in sedentary behavior was 6.1±3.2 h/day. Sedentary behavior was independently and positively associated with frailty (PR=1.10; 95% CI: 1.02-1.19; P=0.013). The ROC curve showed that the sedentary behavior could discriminate frail older adults (AUC=0.66; 95% CI: 0.61-0.72), and the best cutoff point was 7 h/day (sensitivity =54% and specificity =75%). CONCLUSIONS Frailty is strongly associated with sedentary behavior. Sedentary behavior can be a potential marker in screening of frailty in community-dwelling older adults. Our findings suggest that reducing the time with sedentary behavior and increasing the time with physical activity may prevent frailty syndrome.
Cognitive Functioning in Elderly Persons with Type 2 Diabetes and Metabolic Syndrome: the Hoorn Study

Background/Aims: Type 2 diabetes mellitus (DM2) is associated with mild decrements in cognitive functioning, particularly in the elderly. It is often preceded by a ‘prediabetic stage’, characterized by the co-occurrence of insulin resistance and vascular risk factors, usually referred to as the metabolic syndrome. Cognitive decrements may already develop in these early stages. Methods: Cognitive functioning was compared cross-sectionally between DM2 patients (n = 64), patients with metabolic syndrome but without DM2 (n = 83) and control subjects (n = 100) participating in the prospective population-based Hoorn study. Participants performed an extensive neuropsychological examination. Vascular and metabolic determinants were recorded. Results: Both the DM2 group and the metabolic syndrome group performed worse than controls on the domains of information processing speed and attention and executive functioning (mean differences in z-scores 0.2–0.3, all p < 0.05). There were no significant differences in performance between the DM2 and metabolic syndrome group. None of the individual risk factors of the metabolic syndrome, measured at either the present or the previous examination, was a key determinant of cognitive functioning. Conclusion: These results show that DM2-associated cognitive decline may develop in early stages of the disease, possibly in relation to risk factors clustered in the metabolic syndrome.