Miracle-dz/UniFAR-FTUs huggingface dataset:
Análisis de las mutaciones más frecuentes del gen BRCA1 (185delAG y 5382insC) en mujeres con cáncer de mama en Bucaramanga, Colombia

Introduccion. El cancer de mama es un problema de salud publica a nivel mundial y en Santander es la primera causa de morbimortalidad por cancer en mujeres. Todo cancer se considera una enfermedad genetica y las mutaciones en los genes BRCA confieren un riesgo de 60% a 80% para el cancer de mama. Este estudio consistio en buscar las dos mutaciones BRCA1 mas frecuentes segun la base de datos Breast Cancer Core Information. Objetivo. Determinar la presencia de mutaciones especificas (185delAG, exon 2, y 5382insC, exon 20) en el gen BRCA1 en mujeres con cancer de mama heredo-familiar, atendidas en los diferentes servicios de oncologia de Bucaramanga, Colombia. Materiales y metodos. La muestra incluyo 30 pacientes, de las cuales se obtuvo un consentimiento informado, un cuestionario dirigido y sangre venosa para los estudios moleculares. El analisis molecular se realizo mediante PCR-mismatch, para introducir o eliminar sitios de restriccion, y digestion enzimatica (HinfI o DdeI). Resultados. No se detectaron dos de las mutaciones mas frecuentes en el gen BRCA1 en las 30 pacientes estudiadas. Conclusion. Se requieren mas estudios en la region que abarquen la tamizacion de la totalidad del gen BRCA1, para hacer una mayor contribucion al conocimiento de la epidemiologia molecular del cancer de mama en Bucaramanga, Santander, Colombia.
Novel Developments in the Use of Antimetabolites

Antimetabolites are the most widely used and most efficacious group of anticancer drugs. Antimetabolites are also the oldest rationally designed anticancer drugs, targeted against RNA and DNA, and can, therefore, be considered as the first generation of targeted drugs. Unfortunately, resistance often develops, leading to the design of new antimetabolites, which either have a novel mechanism of action, bypass resistance or in combination enhance the effect of other drugs, such as another antimetabolite, other DNA, or protein kinase targeted anticancer drugs. Several novel antimetabolites are in clinical development. The cytidine-analog fluorocyclopentenylcytosine (RX-3117) is active in gemcitabine-resistant tumors and is activated by uridine-cytidine-kinase, can be incorporated into RNA and DNA and can downregulate DNA-methyltransferase-1. TAS-114 is a new generation dUTPase inhibitor. dUTPase normally prevents incorporation of dUTP and of the 5FU-nucleotide FdUTP into DNA. However, inhibition of dUTPase will enhance their incorporation, thereby increasing thymine-less cell-death. The formulation TAS-102 (trifluorothymidine and thymidine-phosphorylase-inhibitor) acts by incorporation into DNA and has shown efficacy in tumors progressing on 5FU therapy. Gemcitabine and cytarabine prodrugs were tested in model systems and have entered clinical evaluation. The elaidic-acid prodrugs of gemcitabine (CP-4126, CO101) and cytarabine (elacytarabine) failed in randomized Phase III studies. Two other gemcitabine prodrugs LY2334737 (gemcitabine with a valproic acid at the 5′-position) and NUC1031 (a 5′-arylphosphoamidate prodrug, with a side-chain at the 5′-phosphate) are in early clinical development. In summary, several novel antimetabolites show promise in clinical development, either because of a novel mechanism of action, or clever combination or by innovative prodrug design.
Neuroimaging study in subjects at high risk of psychosis revealed by the Rorschach test and first-episode schizophrenia

Objective: There is increasing evidence of neuroanatomical pathology in schizophrenia, but it is unclear whether changes exist prior to disease onset. This study aimed to examine whether changes exist prior to disease onset, especially in the temporal lobes. Methods: T1-weighted and diffusion tensor magnetic resonance imaging were performed on 9 first-episode schizophrenia patients, 10 patients who were at high risk of schizophrenia and 10 healthy controls. Voxel-based analysis using the normalised images of cortical volume data was examined, and the fractional anisotropy value at three component fibres of the temporal lobes, inferior longitudinal fasciculus, superior longitudinal fasciculus (SLF) and cingulum hippocampal part was compared among the three groups. Results: There were statistically significant volume differences at the bilateral temporal lobe between the healthy subjects and high-risk group. Between the schizophrenic group and healthy subjects, statistically significant volume differences were detected at the bilateral temporal lobes and anterior cingulate cortex. The fractional anisotropy values of the SLF in the schizophrenic and high-risk groups were significantly lower than in the healthy subjects. Conclusion: Our findings indicate that some brain alterations may progress in patients at psychosis pre-onset, possibly because of disrupted developmental mechanisms, and these pathological changes may be predictive of functional outcome.
Insurance Payer Status and Race Explains Much of the Variability in Colorectal Cancer Survival

Health care inequalities exist for patients with colon cancer. We hypothesize that factors such as payers and medical comorbidities may explain much of this inequality. Methods: Patients with colon cancer in the NCDB from 2003-2010 were identified in this study. Results: 541,649 patients were identified. Median age and survival were 68.6 years and 62.5 months. A majority of them (80.2%) were non-Hispanic white (NHW). African American (AA) and Hispanic (HS) patients were more likely to have medicaid (MD) or be uninsured (UI) and reside in counties with lower socio-economic status (SES). From univariate analysis, it was found that private insurance (PI) had superior survival (98.7 months) compared to MD (46.0 months), medicare (MC) (50.4 months) and UI (54.4 months). Survival was highest for HS (70.9 months) followed by NHW (63.2 months) and AA (53.0 months). Also, survival was linked to comorbidity index (CI), SES, chemotherapy, gender and surgical resection. On multivariate analysis, it was found that male (RR 1.11), SES, surgery (RR 2.29), chemotherapy (RR 1.96), CI, and stage were associated with survival. Race was a predictor of survival, with a survival advantage for HS (RR 0.87) and others (0.87) compared to NHW (1) and AA (1.2). Insurance status was strongly linked to survival. Compared to PI all other groups had poorer survival: MC RR 1.11; MD RR 1.44; and NI RR 1.42. Conclusions: Inequality in outcomes for colon cancer patients is strongly associated with race and underinsurance.
Coordinating Data Monitoring Committees and Adaptive Clinical Trial Designs

There is a growing interest in employing adaptive clinical trial designs in drug development. Adaptation is usually based on accumulative efficacy data alone. This article examines issues that can arise when an independent data monitoring committee must interface their safety concerns when adaptive changes based on efficacy are taking place. Several types of adaptive changes are examined and the degree of complexity that safety concerns might introduce is discussed. Recommendations are made for sponsor-data monitoring committee communications when the latter has safety concerns that make a particular kind of adaptation inadvisable. Recommendations are made for making adaptive change decisions, minimizing bias, and training DMC and sponsor staff for participation in adaptive design trials.
Association between CYP1A2 gene single nucleotide polymorphisms and clinical responses to clozapine in patients with treatment-resistant schizophrenia

Objectives Despite clozapine's superior clinical efficacy in treatment-resistant schizophrenia (TRS), its adverse effects, need for periodic leukocyte monitoring, cost and variable clinical outcomes mandate a clinical need to predict its treatment response. Although cytochrome P450 1A2 (CYP1A2) is the principal determinant of metabolism of clozapine, the role of CYP1A2 gene in the clinical response to clozapine is uncertain. Hence, we investigated its association with treatment responses and adverse events of clozapine in TRS. Methods We evaluated four single nucleotide polymorphisms (SNP) in the CYP1A2 gene, clinical responses and serum clozapine levels in 101 consecutive patients with TRS on stable doses of clozapine. We defined clozapine response a priori and investigated allelic and genotypic associations. We assessed the socio-demographic and clinical profiles, premorbid adjustment, traumatic life events, cognition and disability of the participants, using standard assessment schedules for appropriate multivariate analyses. Results Our results revealed that CYP1A2 gene SNP (*1C, *1D, *1E and *1F) were not associated with clozapine treatment response, adverse effects, serum clozapine levels or with disability (p values > 0.10). Conclusion As CYP1A2 gene SNP do not help to predict the clinical response to clozapine, routine screening for them prior to start clozapine is currently unwarranted. We suggest future longitudinal genome-wide association studies investigating clinical and pharmacogenetic variables together.
Low-energy laser stimulates tooth movement velocity via expression of RANK and RANKL.

OBJECTIVE Recent studies have demonstrated that low-energy laser irradiation stimulates bone formation in vitro and in vivo. However, very little is known about the effects of laser irradiation on osteoclastogenesis. The receptor activator of the nuclear factor-kB (RANK) / RANK ligand (RANKL) / osteoprotegerin (OPG) system is essential and sufficient for osteoclastogenesis. The present study was designed to examine the effects of low-energy laser irradiation on expressions of RANK, RANKL, and OPG during experimental tooth movement. DESIGN To induce experimental tooth movement in rats, 10 g of orthodontic force was applied to the molars. Next, a Ga-Al-As diode laser was used to irradiate the area around the moved tooth and the amount of tooth movement was measured for 7 days. Immunohistochemical staining with RANK, RANKL, and OPG was performed. Real time PCR was also performed to elucidate the expression of RANK in irradiated rat osteoclast precursor cells in vitro. RESULTS In the irradiation group, the amount of tooth movement was significantly greater than in the non-irradiation group by the end of the experimental period. Cells that showed positive immunoreactions to the primary antibodies of RANKL and RANK were significantly increased in the irradiation group on day 2 and 3, compared with the non-irradiation group. In contrast, the expression of OPG was not changed. Further, RANK expression in osteoclast precursor cells was detected at an early stage (day 2 and 3) in the irradiation group. CONCLUSION These findings suggest that low-energy laser irradiation stimulates the velocity of tooth movement via induction of RANK and RANKL.
Periodontal condition of the mandibular anterior dentition in patients with conventional and self-ligating brackets.

OBJECTIVES To explore whether the use of self-ligating brackets is associated with better values for periodontal indices because of the lack of elastomeric modules and concomitantly, reduced availability of retentive sites for microbial colonization and plaque accumulation. SETTING AND SAMPLE POPULATION Private practice of the first author. Patients were selected using the following inclusion criteria: age range 12-17 years, fixed appliances on both arches, aligned mandibular arch, and absence of oral habits and anterior crossbites. MATERIALS AND METHODS Prospective cohort investigation. Participants were grouped for bracket type, thus 50 patients formed the conventional bracket cohort and 50 patients the self-ligating bracket cohort. Both cohorts were followed with the purpose to examine periodontal status. Average length of follow-up was 18 months. This time period was considered adequate for a proportion of study participants to experience the outcome of interest. Outcome variables were plaque index, gingival index, calculus index, and probing depth for the two bracket cohorts. RESULTS No difference was found in the indices recorded between the two bracket cohorts studied. CONCLUSION Under the conditions as applied in this study, the self-ligating brackets do not have an advantage over conventional brackets with respect to the periodontal status of the mandibular anterior teeth.
Severe Hemorrhage in Chinese Children With Immune Thrombocytopenia

To better understand the clinical features, therapy, and clinical outcome of Chinese patients with immune thrombocytopenia (ITP) who suffered severe hemorrhage, we retrospectively analyzed 663 children with ITP diagnosed in our hospital during the last 10 years. Of the total 663 patients enrolled in our study, 520 were eligible for bleeding severity assessment, of which 20 children (3.8%) had severe bleeding, including intracranial hemorrhage (ICH) (n=9), gastrointestinal hemorrhage (n=6), massive epistaxis (n=3), urinary tract hemorrhage (n=1), and pulmonary hemorrhage (n=1). The age at diagnosis of severe hemorrhage ranged from 47 days to 14 years. Thirteen patients were newly diagnosed with ITP, 3 had persistent ITP, and 4 had chronic ITP. The latency between the onset of ITP and severe bleeding ranged from 6 hours to 10 years. The median platelet count at the time of severe hemorrhage was 6.5×109/L (range, 0 to 32×109/L). Most patients with severe hemorrhage were treated with intravenous immunoglobulin (90%), corticosteroids (65%), or both (60%). Two patients (10%) died because of ICH and pulmonary hemorrhage, respectively. Four patients (20%) recovered from thrombocytopenia. Our observation showed that severe hemorrhage is rare but can occur anywhere and at any time during the course of ITP. The majority of children with ITP in China should be observed rather than treated.
Is nickel allergy an occupational disease? Discussion of the occupational relevance of a type IV allergy to nickel (II) sulfate using case reports

Type IV sensitization to nickel (II) sulfate is common in the general population. Nickel can be found in different metals leading to occupational exposition in industrial professions.The individual clinical relevance of nickel allergy can easily be identified but it can be difficult to assess if nickel allergy was acquired privately or occupationally. The problem if nickel allergy fulfills the criteria of an occupational skin disease is presented in three case reports. The occupational relevance of a type IV sensitization to nickel in a chemical laboratory assistant, a flight attendant and a cashier are discussed. Important conditions for acquiring nickel allergy are contact with nickel‐plated and nickel‐releasing materials, the kind of skin contact, the status of the epidermal barrier, and the individual working conditions with an increased bioavailability of nickel. In cases of type IV sensitization to nickel, the affected person cannot continue to work in metal plating or with contact to nickel‐plated metals.The causal relationship between the type IV sensitization to nickel and the occupation needs to be clarified in each individual case. In general, occupationally caused nickel allergy is rare and the occupational relevance of nickel allergy is often overestimated.
Acceptability and feasibility of early pregnancy termination by mifepristone-misoprostol. Results of a large multicenter trial in the United States. Mifepristone Clinical Trials Group.

OBJECTIVES To evaluate whether the regimen of oral mifepristone and misoprostol for medical abortion is acceptable to women and providers, in the United States, including physicians, nurses, and counselors, and whether proposed modifications of this regimen appear feasible for clinical practice. DESIGN A prospective study. SETTING Seventeen clinics in 15 states. PARTICIPANTS A total of 2121 women with pregnancies of 63 days or less in duration. INTERVENTIONS The administration of mifepristone, 600 mg, orally, followed after 2 days by the administration of misoprostol, 400 micrograms, orally. Clinical observation for 4 hours followed misoprostol administration. Two weeks later, at a checkup, women were questioned about the abortion experience. Providers also answered questions about acceptability and feasibility. MAIN OUTCOME MEASURES Patient reports of overall satisfaction with the abortion, the number of women who would choose medical abortion again if needed or recommend the method to others, the best and worst features of the method, and provider and patient assessments of home use. RESULTS The regimen was highly acceptable. Nearly all women (95.7%) would recommend it to others, 91.2% would choose it again, and 87.6% found it very or moderately satisfactory. Even among women for whom the method failed, 69.6% would try it again, 84.9% would recommend it to others, and 51.9% found it very or moderately satisfactory. The chance to avoid a surgical procedure was reported as the method's best feature. The most commonly cited worst features were the uncertainty and fear of side effects. Providers and women considered home use feasible and safe. CONCLUSIONS American women found abortion with the use of mifepristone and misoprostol acceptable. Even most with unsuccessful outcomes would select the regimen again and recommend it to others. Most providers and women thought that home use of misoprostol should be available for women who prefer it.
Systematic approach to hair loss in women

Diffuse hair loss is a common complaint and cause of significant emotional distress particularly in women. The best way to alleviate the anxiety is to effectively treat the hair loss. It is paramount to address the symptom systematically. In addition to its psychological impact, hair loss may be a manifestation of a more general medical problem. The diagnosis can be established with a detailed patient history focussing on chronology of events, examination of the scalp and pattern of hair loss, a pull test with examination of bulbs of shed hairs, trichoscopy, and few pertinent screening blood tests. In selected cases a scalp biopsy may be required. The most important differential diagnoses include acute and chronic telogen effluvium, female pattern hair loss, and diffuse alopecia areata. Occasionally, patients seeking advice are not necessarily losing hair. In the absence of convincing evidence of hair loss, they are suffering of psychogenic pseudoeffluvium, and thought should be given to an underlying psychological disorder. Once the diagnosis is established, treatment appropriate for that diagnosis is likely to control the hair loss. Finally, appropriate psychological support and education about the basics of the hair cycle, and why considerable patience is required for effective cosmetic recovery, are essential to help limit patient anxiety.
How Successful are We at Getting our Clients Back to Work? The Results of an Audit

Because of changes in clinical practice, it became evident within a rehabilitation unit that there was a need to try to address employment issues with clients in a coordinated multiagency manner. A project was therefore set up in 2000 to develop guidelines in order to assist clients in returning to work. This article describes a retrospective audit, which was carried out in this rehabilitation unit for adults aged 16–65 years who had either a neurological or a rheumatoid problem. The guidelines were used to record and collect data on clients who were receiving occupational therapy between March 2000 and May 2001 and had expressed a wish to look at employment issues. Information from occupational therapy notes and a follow-up phone call to one client were also used to collect data. The audit highlighted several areas where the process had not been successful. However, it did show that when a coordinated multiagency team is involved, a successful return to work can be achieved.
When Doctors Deceive

It is true that doctors of other times and other cultures have held to a different standard of disclosure (Mitchell 2007). It is also true that doctors today employ a range of practices, such as reassurance, that may be considered deceptive to a degree. Foddy (2009), in the target article, takes inspiration from such relativism to argue that deceptive placebo use should be permitted, even embraced, as the transgression would be minimal and the benefit potentially substantial. I would draw different conclusions from these undoubted facts. I would conclude that deception is not a unitary concept, but one that varies enormously in scope and moral import between situations. And, as I will argue, that the kind of deception he advocates is of the greatest moral import, occurs in situations of the greatest impact, and is more likely to lead to disaster than benefit. ‘Deception’ embraces a wide range of behaviors, some of which, such as plant deception, it makes no sense to consider unethical. In our fellow humans we draw ready distinctions between the ‘make-believe’ of a novel or the stage magician who tells us, falsely, he has nothing up his sleeve, and anything we would consider wrong (Kanaan in press). The key to understanding these distinctions lies in the way the deception is formulated, but also in the conditions under which the ‘deception’ is practiced; in particular, in the expectations—the level of trust—of the participants in that situation (Chisholm and Feehan 1977). We know, beforehand, that the novel and the magician are not telling us the truth. Similarly, when a dinner guest tells us their meal was the finest they have ever had, we do not judge them too harshly—we would perhaps call it ‘tact’ or ‘flattery’, rather than ‘lying’—because our expectations are not to take such statements as being wholly sincere. Contrast the dinner party with the medical consultation, however. The public continues to trust doctors in general above all others (Manson and O’Neill 2007). And while we may take our doctor telling us “it’s nice to see you again” no differently than any other compliment, their telling us the nature of our problem and the treatment for it will typically occur under conditions of maximal trust. Such communication is akin to a promise, and its breach considered equivalently. There is no question but that we would consider deliberate deception under such circumstances to be lying (Kanaan in press). Foddy (2009) acknowledges there may be consequences from such a transgression, were it discovered, but I do not think he appreciates the damage that may occur from a fall
Introduction to the special issue, Integrative Neural Systems Underlying Vital Aerodigestive Tract Functions

This special issue is an outgrowth of the conference, ‘‘Integrative Neural Systems Underlying Vital Aerodigestive Tract Functions,’’ held in Madison, Wisconsin, June 17–19, 2010. The program included 3 plenary lectures, 4 keynote lectures, and 15 scientific papers. In addition, workgroup presentations, and panel discussions provided opportunities for general discussion and integration of information in a multidisciplinary context. This special issue is intended to disseminate major conclusions, potential directions for research, and unique approaches for consideration of application to clinical practice arising from the conference. The contributions assembled in this issue include 7 articles based on the plenary or keynote lectures, an invited perspective on laryngeal function, and a summary of workgroup discussions held at the conference. In this introductory article, names printed in upper case refer to articles in this special issue.