Miracle-dz/UniFAR-FTUs huggingface dataset:
Toxicological and pharmacological properties of fenticonazole, a new topical antimycotic.

The acute oral and subchronic (6 weeks) topical toxicity of alpha-(2,4-dichlorophenyl)-beta,N-imidazolylethyl 4-phenylthiobenzyl ether nitrate (fenticonazole, Rec 15/1476) was studied in mice, rats, guinea pigs and beagle dogs. The acute oral LD50 in mice and rats was found to be 3000 mg/kg, while the i.p. acute toxicity was 1191 mg/kg in mice and between 309 and 440 mg/kg in rats. The acute oral LD50 in beagle dogs was 1000 mg/kg. Percutaneous subchronic (6 weeks) toxicity was evaluated in guinea pigs and beagle dogs. Both species of animals exhibited no toxic effect attributable to the treatment with fenticonazole and no histopathologic changes were attributed to the drug treatment. Fenticonazole did not affect numerous pharmacological and physiological parameters (blood pressure, heart rate, pulmonary ventilation, nor did it interfere with the activity of histamine, adrenaline, noradrenaline and acetylcholine). It does not possess analgesic or antiinflammatory activity at high doses (100 mg/kg p.o.). In mice it exhibits a slight CNS depressant activity, milder than that of miconazole.
Early effects of 12-O-tetradecanoyl-phorbol-13-acetate on the incorporation of tritiated precursor into DNA and the thickness of the interfollicular epidermis, and their relation to tumor promotion in mouse skin.

The macroscopic and histological changes induced in mouse skin by various doses of 12- O -tetradecanoyl-phorbol-13-acetate (TPA) were studied; its tumorigenic and tumorpromoting activity were tested, and the changes induced in the thickness of interfollicular epidermis (IFE) and in the rate of incorporation of thymidine-methyl-3H into skin DNA were measured. TPA in the dose range of 0.016 to 0.0016 emole shows marked promoting activity, while 0.00016 emole does not, thus suggesting a threshold for promoting activity between 0.0016 and 0.00016 emole. Doses of 0.08 and 0.16 emole of TPA induce marked necrosis and ulceration of the skin and are therefore unsuitable for studies of tumor-promoting activity. The changes in the rate of incorporation of thymidine-methyl-3H into DNA and the thickness of IFE are dose dependent in degree and duration. A single application of TPA induces initially an inhibition in the incorporation of thymidine-methyl-3H into DNA, followed by marked stimulation in the rate of incorporation and returning to control levels thereafter. Following a second application of TPA, 168 hr after the first, the initial inhibition of thymidine-methyl-3H incorporation into DNA is not observed, and the onset of the increase in the rate of incorporation is earlier and its peak is higher. A single application of TPA induces a marked increase in the thickness of IFE, but this reverts to the control level between 120 and 168 hr later. After a second application, the increase in the thickness of IFE is 1.5 to 2.0 times higher, and the peak of thickness is reached earlier than after a single application, suggesting that the first application of TPA potentiates the effects of subsequent applications. There is a correlation between the increase in thickness of IFE and skin tumor promotion with 0.016 and 0.0016 emole of TPA. However, 0.00016 emole of TPA induces a significant increase in the thickness of IFE and in the rate of incorporation of thymidine-methyl-3H into DNA but does not show promoting activity, indicating that the threshold for epidermal hyperplasia is different from that for promoting activity and suggesting that hyperplastic action and promoting action are independent phenomena.
The Rad51 Paralog Rad51B Promotes Homologous Recombinational Repair

ABSTRACT The highly conserved Saccharomyces cerevisiae Rad51 protein plays a central role in both mitotic and meiotic homologous DNA recombination. Seven members of the Rad51 family have been identified in vertebrate cells, including Rad51, Dmc1, and five Rad51-related proteins referred to as Rad51 paralogs, which share 20 to 30% sequence identity with Rad51. In chicken B lymphocyte DT40 cells, we generated a mutant with RAD51B/RAD51L1, a member of the Rad51 family, knocked out. RAD51B−/− cells are viable, although spontaneous chromosomal aberrations kill about 20% of the cells in each cell cycle. Rad51B deficiency impairs homologous recombinational repair (HRR), as measured by targeted integration, sister chromatid exchange, and intragenic recombination at the immunoglobulin locus. RAD51B−/− cells are quite sensitive to the cross-linking agents cisplatin and mitomycin C and mildly sensitive to γ-rays. The formation of damage-induced Rad51 nuclear foci is much reduced in RAD51B−/−cells, suggesting that Rad51B promotes the assembly of Rad51 nucleoprotein filaments during HRR. These findings show that Rad51B is important for repairing various types of DNA lesions and maintaining chromosome integrity.
A clinicopathological study of interface dermatitis.

BACKGROUND Interface dermatitis (ID) refers to a pattern of skin reaction characterized by an inflammatory infiltrate that appears to obscure the dermo-epidermal junction when observed at low power examination and referred to as lichenoid tissue reaction. A wide range of inflammatory skin diseases exhibits interface change with considerable overlap of histological features. The aim of the present study was to study the clinical features and microscopic features of ID. MATERIALS AND METHODS The material for the present study consisted of skin biopsy samples collected from patients attending the outpatient Department of Dermatology. The study was conducted for a period of 3 years from 2007 to 2010. During this period, a total of 125 cases was studied. RESULTS In the present study, a total of 125 cases of ID was studied which presented clinically as papulosquamous disorders. Majority of the cases of ID were seen in women (57.6%). Majority of ID were lichen planus (LP) and its variants (63.2%). Clinicopathological concordance was seen in 109 cases (87.2%) and discordance in 16 cases (12.8%). CONCLUSION The mere presence of an interface lichenoid inflammatory reaction should not be the sole criterion for the diagnosis of LP or one of its many variants, as now seems to be the case. A clinicopathologic correlation is absolutely essential for a conclusive diagnosis of ID.
Thymidylate synthase and methylenetetrahydrofolate reductase gene polymorphism in normal tissue as predictors of fluorouracil sensitivity.

PURPOSE To analyze thymidylate synthase (TS) and methylenetetrahydrofolate reductase (MTHFR) gene polymorphism with respect to fluorouracil (FU) sensitivity. PATIENTS AND METHODS The study included a retrospective analysis of 88 patients with metastatic colorectal cancer and a prospective trial with 51 patients also with measurable metastases. All patients were treated with FU and leucovorin. The analysis of gene polymorphism was performed on normal intestinal tissue and lymphocytes. RESULTS The response rate was significantly higher in patients with TS 3R/3R or MTHFR 677 TT gene polymorphism compared with the other groups. The difference of response rate translated to a difference in time to progression. Similar results were observed in the retrospective analysis and the prospective confirmatory trial. CONCLUSION The analysis of gene polymorphism allows delineation of a group of patients (30%) with a response rate to a single drug of approximately 50%. This information should be used in the design of tailored treatment.
Cataract surgery has evolved from intracapsular cataract extraction ( ICCE ) to extracapsular cataract extraction ( ECCE ) and now Factors Associated with Complications and Postoperative Visual Outcome in Cataract Patients : A Study of 1632 Cases

Purpose: Cataract surgery is the most common intraocular surgery performed all over the world and it has advanced technically in the recent years. As in all surgeries, complications are unavoidable. A retrospective study was done to identify the factors associated with complications of surgery and visual outcome. Methods: A retrospective cohort study of 1632 cataract surgeries performed between 2007 and 2010 was done from the data obtained from cataract registry of the National Eye Database. Demographic features, ocular and systemic comorbidites, grade of surgeon and duration of surgery, type of aneathesia, intraoperative and postoperative complications and the type of intraocular lenses use were recorded. Best corrected visual acuities preoperatively and postoperatively were compared. Results: Mean age of patients was 66.9 years with equal gender distribution. Majority had age related cataracts. Phacoemulsification was done faster than other surgeries, especially by specialist surgeons. History of previous ocular surgery and operations under general anesthesia were associated with greater complications. Phacoemulsification was associated with less complications and better visual outcome. The age and aetiology of cataract did not affect complications. Malays, absence of ocular comorbidities, left eye and eyes operated under local anaesthetia were more likely to have good visual improvement. The gender and age, cause of cataract, systemic comorbidities and grade of surgeon operating did not affect the visual improvement. Intraoperative and postoperative complications did not affect the visual improvement. Conclusion: Phacoemulsification with acryllic lenses had good visual outcome. Duration of surgery, grade of surgeon and complications did not affect visual outcome.
Targeting of a lysosomal membrane protein: a tyrosine‐containing endocytosis signal in the cytoplasmic tail of lysosomal acid phosphatase is necessary and sufficient for targeting to lysosomes.

Lysosomal acid phosphatase (LAP) is synthesized as a transmembrane protein with a short carboxy‐terminal cytoplasmic tail of 19 amino acids, and processed to a soluble protein after transport to lysosomes. Deletion of the membrane spanning domain and the cytoplasmic tail converts LAP to a secretory protein, while deletion of the cytoplasmic tail as well as substitution of tyrosine 413 within the cytoplasmic tail against phenylalanine causes accumulation at the cell surface. A chimeric polypeptide, in which the cytoplasmic tail of LAP was fused to the ectoplasmic and transmembrane domain of hemagglutinin is rapidly internalized and tyrosine 413 of the LAP tail is essential for internalization of the fusion protein. A chimeric polypeptide, in which the membrane spanning domain and cytoplasmic tail of LAP are fused to the ectoplasmic domain of the Mr 46 kd mannose 6‐phosphate receptor, is rapidly transported to lysosomes, whereas wild type receptor is not transported to lysosomes. We conclude that a tyrosine containing endocytosis signal in the cytoplasmic tail of LAP is necessary and sufficient for targeting to lysosomes.
SURGICAL MANAGEMENT OF CAROTID BODY TUMOURS: A 24‐YEAR SURGICAL EXPERIENCE

Background: Carotid body tumours (CBT) are rare tumours, best treated by complete surgical resection. However, there is no uniform agreement on the method of resection. The aim of this study was to review our 24 years’ experience of meticulous subadventitial excision of CBT.
Opinion/Editorial and Review of Recent Literature: Where Ultrasound has yet to Make a Difference in Regional Anesthesia

In recent years, ultrasound (US) guidance for peripheral nerve blocks (PNBs) has enjoyed a meteoric rise in popularity and use. The attraction of US guidance is clear. One can see a needle approach a target nerve in real time and avoid contacting undesirable targets such as vascular structures. The improved proximity to the target nerve could potentially allow for lesser quantities of local anesthetics to be used, thereby potentially reducing the risk of local anesthetic toxicity. Onset times could theoretically be reduced. Finally, success rates could be greatly increased over those performed with anatomic landmarks and peripheral nerve stimulation (NS), while affording greater overall safety. On first review, these claims seem to overwhelmingly favor the use of US-based PNB techniques. However, not all would agree with claims made by US enthusiasts.
Lipoprotein (a) and risk of cardiovascular disease--a systematic review and meta analysis of prospective studies.

BACKGROUND Several studies have investigated the role of Lipoprotein (a) as a risk factor for cardiovascular disease (CVD) and have produced controversial results. DATA SOURCES We conducted a systematic literature review in the databases MEDLINE, EMBASE, and COCHRANE aimed at retrieving prospective studies that investigated the prognostic value of Lipoprotein (a) concentrations on cardiovascular risk and mortality. METHODS From each study we extracted estimates of risk ratios (RR) with respect to the risk of CVD (endpoints: all coronary heart disease (CHD) events pooled, major coronary events, myocardial infarction, stroke) and all cause mortality. Study specific risk ratios were standardised to contrast the top third with the bottom third of the study specific Lipoprotein (a) distribution. Pooled summary estimates were calculated by using fixed and random effects meta analysis techniques, in total and stratified by study design and study population. RESULTS For the present meta analysis we selected 67 prospective studies including 181,683 individuals. Synthesising data from 37 studies that reported estimates for the endpoint 'CHD events' resulted in a RR of 1.57 (95% CI: 1.41 to 1.75, p < 0.001). For this endpoint subgroup analyses by design and population showed significant estimates: population based cohort studies: n = 15 studies, RR = 1.48 (95% CI: 1.26 to 1.74, p < 0.001), cohort studies including patients with previous disease: total: n = 11 studies, RR = 1.67 (95% CI: 1.28 to 2.17, p < 0.001), with CHD: n = 6 studies, RR = 2.37 (95% CI: 1.41 to 3.97, p = 0.001), nested case control studies: n = 11 studies, RR = 1.64 (95% CI: 1.47 to 1.83, p < 0.001). We did not find any significant effect on risk of stroke (n = 16 studies, RR = 1.10 (95% CI: 0.97 to 1.25, p = 0.137)) and mortality (n = 9 studies, RR = 1.12 (95% CI: 0.94 to 1.33, p = 0.200)). CONCLUSIONS This meta analysis of prospective studies shows a clear association between elevated Lipoprotein (a) levels and increased risk of CHD. This effect is substantially higher in individuals with previous CHD. Our systematic review showed no evidence of an effect on stroke and all cause mortality.
Gastric biopsies: the gap between evidence-based medicine and daily practice in the management of gastric Helicobacter pylori infection.

BACKGROUND Many consider histology to be the gold standard for Helicobacter pylori detection. Because the number and distribution of H pylori organisms vary, particularly in patients taking proton pump inhibitors (PPIs), the American Gastroenterological Association recommends discontinuing PPIs two weeks before endoscopy, and taking biopsies from both the body and antrum. OBJECTIVE To assess the influence of clinical practice on the histopathological detection of H pylori infection. METHODS Electronic patient records were evaluated for the sites of gastric sampling and PPI use at endoscopy. One hundred fifty cases with biopsies taken from both antrum and body were randomly selected for pathological re-review with special stains. The gastric regions sampled, H pylori distribution and influence of clinical factors on pathological interpretation were assessed. RESULTS Between 2005 and 2010, 10,268 biopsies were taken to detect H pylori. Only one region was sampled in 60% of patients (antrum 47%, body 13%). Re-review of biopsies taken from both antrum and body indicated that the correct regions were sampled in only 85 (57%) patients. Of these, 54 were H pylori positive and 96 were H pylori negative. H pylori was present in the antrum in only 15% of the patients and body only in 21%. Of 96 H pylori-negative patients, two were reinterpreted as positive. Forty-seven per cent of patients were taking PPIs at endoscopy, contributing to both false-negative and false-positive diagnoses. CONCLUSION Despite national and international guidelines for managing H pylori infection, the American Gastroenterological Association guidelines are infrequently adhered to, with PPIs frequently contributing to false diagnosis; sampling one region only increases the likelihood of missing active infection by at least 15%.
Crave-Out: A Distraction/Motivation Mobile Game to Assist in Smoking Cessation

Background Smoking is still the number one preventable cause of death. Cravings—an intense desire or longing for a cigarette—are a major contributor to quit attempt failure. New tools to help smokers’ manage their cravings are needed. Objective To present a case study of the development process and testing of a distraction/motivation game (Crave-Out) to help manage cravings. Methods We used a phased approach: in Phase 1 (alpha testing), we tested and refined the game concept, using a Web-based prototype. In Phase 2 (beta testing), we evaluated the distraction/motivation potential of the mobile game prototype, using a prepost design. After varying duration of abstinence, smokers completed the Questionnaire of Smoking Urge-Brief (QSU-Brief) measurement before and after playing Crave-Out. Paired t tests were used to compare pregame and postgame QSU-Brief levels. To test dissemination potential, we released the game on the Apple iTunes App Store and tracked downloads between December 22, 2011, and May 5, 2014. Results Our concept refinement resulted in a multilevel, pattern memory challenge game, with each level increasing in difficulty. Smokers could play the game as long as they wanted. At the end of each level, smokers were provided clear goals for the next level and rewards (positive reinforcement using motivational tokens that represented a benefit of quitting smoking). Negative reinforcement was removed in alpha testing as smokers felt it reminded them of smoking. Measurement of QSU-Brief (N=30) resulted in a pregame mean of 3.24 (SD 1.65) and postgame mean of 2.99 (SD 1.40) with an overall decrease of 0.25 in cravings (not statistically significant). In a subset analysis, the QSU-Brief decrease was significant for smokers abstinent for more than 48 hours (N=5) with a pregame mean of 2.84 (SD 1.16) and a postgame mean of 2.0 (SD 0.94; change=0.84; P =.03). Between December 22, 2011, and May 29, 2014, the game was downloaded 3372 times from the App-Store, with 1526 smokers visiting the online resource www.decide2quit. org linked to the game. Conclusions Overall, playing the game resulted in small, but nonsignificant decreases in cravings, with changes greater for those had already quit for more than 48 hours. Lessons learned can inform further development. Future research could incorporate mHealth games in multicomponent cessation interventions. Trial Registration Clinicaltrials.gov NCT00797628; https://clinicaltrials.gov/ct2/show/NCT00797628 (Archived by WebCite at http://www.webcitation.org/6hbJr6LWG)
Contact-induced grammaticalization: Evidence from bilingual acquisition

It is widely acknowledged that developments in bilingual individuals parallel, and ultimately underlie, those taking place in the course of contact-induced change. In this paper we address the poorly understood relationship between the individual and community-level processes, focusing on the process of grammaticalization in circumstances of language contact and the corresponding developmental processes in bilingual acquisition. The phenomena chosen for discussion are drawn from Singapore Colloquial English (SCE) and from the Hong Kong Bilingual Corpus (Yip & Matthews 2000, 2007). Parallel developments in SCE and bilingual acquisition are analysed as cases of contact-induced grammaticalization as defined by Heine and Kuteva (2003; 2005), with some modifications. The emergence of already as a marker of aspect presents a case of ‘ordinary’ contact-induced grammaticalization, while the development of grammatical functions of give represents a case of replica grammaticalization. One implication of these findings is that bilingual first language acquisition is a possible route for substrate influence, both in general and specifically in the development of contact languages such as pidgins and creoles.
Effects of Topical Glutathione Treatment in Rat Ischemic Wound Model

Oxidative stress secondary to ischemia can cause physiopathologic changes that adversely affect wound healing. In this experimental study, we hypothesized that the topical use of esterified glutathione, a well-known antioxidant, can minimize the effects of oxidative stress by an increase in intracellular glutathione and accelerate wound healing by increasing the contraction capacity of fibroblasts and preventing keratinocytes from apoptosis in a rat ischemic wound model. Experimental models were divided into 3 groups as treatment, control, and healthy. Bipedicled flaps were elevated from the dorsum of the rats, and 6-mm punch wounds were created at the end of the first day when the ischemia is most apparent. Wounds were followed histopathologically and immunohistochemically, and matrix metalloproteinase (MMP)-1 and tissue inhibitors of metalloproteinase (TIMP-1) levels were measured by ELISA. Samples were collected at 0, 5, 8, 10, and 12 days. Histopathologic evaluation revealed significant extracellular matrix deposition and reepithelization every fifth day in treatment and healthy groups when compared with control group. Immunohistochemical evaluation revealed increased apoptosis in basal keratinocytes in the control group when compared with the other groups. The evaluation of the samples collected at 5 and 8 days revealed increased MMP-1 levels in treatment and control groups, but the increase in TIMP-1 levels was more significant than MMP-1 levels in treatment group. MMP-1/TIMP-1 ratio was significantly low in the treatment group. Our results showed that topical GSH treatment can reduce oxidative stress, and the reestablishment of the MMP-1/TIMP-1 ratio gives way to adequate and regular extracellular matrix production and reepithelization. It is concluded that esterified GSH, which is experimentally shown to be effective in ischemic wound healing, can be used clinically in ischemic wounds.