Miracle-dz/UniFAR-FTUs huggingface dataset:
Evaluation of the Morphological Effects of TDT 067 (Terbinafine in Transfersome) and Conventional Terbinafine on Dermatophyte Hyphae In Vitro and In Vivo

ABSTRACT TDT 067 is a novel, carrier-based dosage form of terbinafine in Transfersome (1.5%) formulated for topical delivery of terbinafine to the nail, nail bed, and surrounding tissue. We examined the effects of TDT 067 and conventional terbinafine on the morphology of dermatophytes. Trichophyton rubrum hyphae were exposed to TDT 067 or terbinafine (15 mg/ml) and examined under white light, scanning electron microscopy (SEM), and transmission electron microscopy (TEM). Subungual debris from patients treated with TDT 067 in a clinical trial was also examined. Exposure of T. rubrum hyphae to TDT 067 led to rapid and extensive ultrastructural changes. Hyphal distortion was evident as early as 4 h after exposure to TDT 067. After 24 h, there was complete disruption of hyphal structure with few intact hyphae remaining. Exposure to terbinafine resulted in morphological alterations similar to those seen with TDT 067; however, the effects of TDT 067 were more extensive, whereas a portion of hyphae remained intact after 24 h of exposure to terbinafine. Lipid droplets were observed under TEM following 30 min of exposure to TDT 067, which after 24 h had filled the intracellular space. These effects were confirmed in vivo in subungual debris from patients with onychomycosis who received topical treatment with TDT 067. The Transfersome in TDT 067 may potentiate the action of terbinafine by delivering terbinafine more effectively to its site of action inside the fungus. Our in vivo data confirm that TDT 067 can enter fungus in the nail bed of patients with onychomycosis and exert its antifungal effects.
Cerebral Oxygen Saturation-Time Threshold for Hypoxic-Ischemic Injury in Piglets

BACKGROUND: Detection of cerebral hypoxia-ischemia (H-I) and prevention of brain injury remains problematic in critically ill neonates. Near-infrared spectroscopy (NIRS), a noninvasive bedside technology could fill this role, although NIRS cerebral O2 saturation (ScO2) viability-time thresholds for brain injury have not been determined. We investigated the relationship between H-I duration at ScO2 35%, a viability threshold which causes neurophysiological impairment, to neurological outcome. METHODS: Forty-six fentanyl-midazolam anesthetized piglets were equipped with NIRS and cerebral function monitor (CFM) to record ScO2 and electrocortical activity (ECA). After carotid occlusion, inspired O2 was adjusted to produce H-I (ScO2 35% with decreased ECA) for 1, 2, 3, 4, 6 or 8 h in different groups, followed by survival to assess neurological outcome by behavioral and histological examination. RESULTS: For H-I lasting 1 or 2 h, ECA and ScO2 during reperfusion rapidly returned to normal and neurological outcomes were normal. For H-I more than 2–3 h, ECA was significantly decreased and ScO2 was significantly increased during reperfusion, suggesting continued depression of tissue O2 metabolism. As H-I increased beyond 2 h, the incidence of neurological injury increased linearly, approximately 15% per h. CONCLUSION: A viability-time threshold for H-I injury is ScO2 of 35% for 2–3 h, heralded by abnormalities in NIRS and CFM during reperfusion. These findings suggest that NIRS and CFM might be used together to predict neurological outcome, and illustrate that there is a several hour window of opportunity during H-I to prevent neurological injury.
Prevalence of newly isolated, cytopathic small round virus (Aichi strain) in Japan

Cytopathic small round virus (Aichi strain), isolated from a patient with oyster-associated gastroenteritis, showed no reaction in the polymerase chain reaction method for enteroviruses or in the enzyme-linked immunosorbent assay (ELISA) for the five serotypes of astroviruses. Our ELISA was sensitive in detecting the Aichi strain antigen in stool samples, but there was no reaction in this ELISA with any non-Aichi strains of enteric viruses, with such origins as enterovirus, rotavirus, Norwalk virus, calicivirus, or astrovirus. In the ELISA, 13 of 47 stool samples from adult patients in five of nine oyster-associated gastroenteritis outbreaks were positive, but only 1 of 397 pediatric stool samples in Aichi Prefecture was positive. The prevalence rate for Aichi strain antibody was found to be 7.2% for persons aged 7 months to 4 years. The prevalence rate for antibody to Aichi strain increased with age, to about 80% in persons 35 years old. On the basis of the results of the present study, it was hypothesized that Aichi strain could be a new type of small round virus that mainly produces diarrhea in patients in the 15- to 34-year-old age group, 50 to 76% of whom possess neutralizing antibody.
A review of laparoscopic uterine suspension procedures for uterine preservation

Purpose of review The most appropriate surgical approach for uterine preservation still remains the subject of ongoing controversy. Uterine suspension procedures can be performed abdominally, vaginally, or laparoscopically. This article focuses on the three different laparoscopic approaches of uterine suspension for uterine preservation: suspension to the round ligaments; suspension to the uterosacral ligaments; and suspension to the anterior ligament of the sacral promontory. This article reviews the published studies in the literature, analyzes the results, discusses the differences, and compares the different laparoscopic techniques. Recent findings A review of the literature reveals a paucity of research studies and publications on laparoscopic uterine suspension procedures. All the published studies are small, retrospective case series or case studies. Laparoscopic ventrosuspension using the round ligaments for uterine prolapse has a reported success rate of less than 50%. The ventrosuspension procedure has a very limited role and should not be employed. In comparison, laparoscopic uterine suspension procedures have a reported success rate ranging between 81 and 100%. The newest surgical technique is the laparoscopic sacral colpohysteropexy and there is only one reported case series on this procedure. The reported success rate for the sacral colpohysteropexy is 100%. Summary The first surgical option for uterine preservation is uterine suspension to the uterosacral ligaments. If the uterosacral ligaments cannot be identified or the uterosacral ligaments are weak and unusable, then laparoscopic sacral colpohysteropexy is a reliable second option. Uterine suspension to the round ligaments has an unacceptably high failure rate and is not an effective, durable alternative.
Cycle biogéochimique du mercure dans l'environnement, développements analytiques et spéciation en milieu estuarien

La premiere partie de ce travail porte sur le developpement de nouveaux concepts pour l'analyse de speciation du mercure dans les matrices environnementales. L'utilisation de l'extraction chimique assistee sous champ micro-ondes permet la preparation rapide des echantillons biologiques ou solides tout en preservant l'integrite moleculaire des formes chimiques a analyser. L'etape de determination est realisee par des techniques couplees en ligne faisant intervenir le piegeage cryogenique et la spectrometrie atomique, apres derivation en phase aqueuse par generation d'hydrure ou ethylation des composes du mercure (mercure inorganique, methyle-mercure). Une procedure de controle qualite et assurance a permis de verifier que ces methodes sont justes et precises. Le deuxieme volet de ce travail a permis d'appliquer ces methodes analytiques a l'etude du cycle biogeochimique du mercure dans les milieux estuariens dans le cadre d'un programme europeen (projet biogest). L'etude d'une carotte, realisee dans des sediments fluides (creme de vase) de l'estuaire de la gironde, demontre que le developpement de ces formations sedimentaires entraine la mobilisation du mercure dissous dans la colonne d'eau et contribue a la methylation du mercure dans cet estuaire. Les resultats obtenus sur la speciation et la distribution du mercure dans les phases dissoute et particulaire de trois estuaires europeens macrotidaux (gironde, rhin, escaut) etablissent que le regime hydrodynamique et le temps de residence des particules de ces systemes controlent la disponibilite chimique, et donc les processus de transfert et de transformation du mercure. Ces processus engendrent une production significative de methyle-mercure dans les estuaires macrotidaux qui peut avoir des repercussions sur les ecosystemes marins cotiers.
Cytoskeletal Changes in Oocytes and Early Embryos During in vitro Fertilization Process in Mice

The cytoskeleton plays crucial roles in the development and fertilization of germ cells and in the early embryo development. The growth, maturation and fertilization of oocytes require an active movement and a correct localization of cellular organelles. This is performed by the re‐organization of microtubules and actin filaments. Therefore, the aim of the present study was to determine the changes in cytoskeleton during in vitro fertilization process using appropriate immunofluorescence techniques. While the chromatin content was found to be scattered throughout the nucleus during the oocyte maturation period, it was seen only around nucleolus following the completion of the maturation. Microtubules, during oocyte maturation, were regularly distributed throughout the ooplasm which was then localized in the subcortical region of oocytes. Similarly microfilaments were scattered throughout the ooplasm during the oocyte maturation period whereas they were seen in the subcortical region around the polar body and above the meiotic spindle throughout the late developmental stages. In conclusion, those changes occurred in microtubules and microfilaments might be closely related to the re‐organization of the genetic material during the oocyte maturation and early embryo development.
Predictors of Primary Care Physician Practice Location in Underserved Urban or Rural Areas in the United States: A Systematic Literature Review

Purpose The authors conducted a systematic review of the medical literature to determine the factors most strongly associated with localizing primary care physicians (PCPs) in underserved urban or rural areas of the United States. Method In November 2015, the authors searched databases (MEDLINE, ERIC, SCOPUS) and Google Scholar to identify published peer-reviewed studies that focused on PCPs and reported practice location outcomes that included U.S. underserved urban or rural areas. Studies focusing on practice intentions, nonphysicians, patient panel composition, or retention/turnover were excluded. They screened 4,130 titles and reviewed 284 full-text articles. Results Seventy-two observational or case–control studies met inclusion criteria. These were categorized into four broad themes aligned with prior literature: 19 studies focused on physician characteristics, 13 on financial factors, 20 on medical school curricula/programs, and 20 on graduate medical education (GME) programs. Studies found significant relationships between physician race/ethnicity and language and practice in underserved areas. Multiple studies demonstrated significant associations between financial factors (e.g., debt or incentives) and underserved or rural practice, independent of preexisting trainee characteristics. There was also evidence that medical school and GME programs were effective in training PCPs who locate in underserved areas. Conclusions Both financial incentives and special training programs could be used to support trainees with the personal characteristics associated with practicing in underserved or rural areas. Expanding and replicating medical school curricula and programs proven to produce clinicians who practice in underserved urban or rural areas should be a strategic investment for medical education and future research.
Indirect estimation of the area density of Atg8 on the phagophore

Atg8 is a ubiquitin-like protein that controls the expansion of the phagophore during autophagosome formation. It is recruited to the phagophore during the expansion stage and released upon the completion of the autophagosome. One possible model explaining the function of Atg8 is that it acts as an adaptor of a coat complex. Here, we tested the coat-adaptor model by estimating the area density of Atg8 molecules on the phagophore. We developed a computational process to simulate the random sectioning of vesicles heterogeneous in size. This method can be applied to estimate the original sizes of intracellular vesicles from sizes of their random sections obtained through transmission electron microscopy. Using this method, we found that the estimated area density of Atg8 is comparable with that of proteins that form the COPII coat.
Mantle cell lymphoma: state-of-the-art management and future perspective

Mantle cell lymphoma (MCL) is a unique subtype of B-cell non-Hodgkin lymphomas (NHL) characterized in almost all cases by the chromosomal translocation t(11;14)(q13;q32) and nuclear cyclin D1 overexpression. Most patients present with advanced stage disease, often with extranodal dissemination, and typically pursue an aggressive clinical course. Recent improvement has been achieved by the successful introduction of monoclonal antibodies and dose-intensified approaches including autologous stem cell transplantation strategies. However, with the exception of allogeneic hematopoietic stem cell transplantation, current treatment approaches are not curative and the corresponding survival curve is characterized by a relatively steep and continuous decline, with a median survival of about 4 years and <15% long-term survivors. Despite its rarity, MCL is of particular clinical and scientific interest by providing a paradigm for neoplasms with dysregulated control of cell cycle machinery and impaired apoptotic pathways. Recently gained insights into underlying pathobiology unravel numerous promising molecular targeting strategies, however their introduction into clinical practice and current treatment algorithms remains a challenge. This article will provide relevant information for decision making in clinical practice and give a perspective on upcoming management strategies.
Pitx2a Binds to Human Papillomavirus Type 18 E6 Protein and Inhibits E6-mediated P53 Degradation in HeLa Cells*

Binding of high risk human papillomavirus (HPV) E6 protein to E6-associated protein (E6AP), a cellular ubiquitin-protein ligase, enables E6AP to ubiquitinate p53, leading to p53 degradation in cervical cancer cells such as HeLa cells. Here we report that Pitx2a, a bicoid-type homeodomain transcription factor, can bind to HPV E6 protein and inhibit E6/E6AP-mediated p53 degradation. Deletion of the Pitx2a homeodomain abrogates its ability to bind to HPV E6 protein and to induce p53 accumulation in HeLa cells, suggesting that the homeodomain of Pitx2a is essential for inhibition of E6/E6AP-mediated p53 degradation. Recombinant Pitx2a can also block E6/E6AP-mediated p53 degradation in vitro, indicating that this function of Pitx2a is independent of its transcription activity. Pitx2a does not regulate Hdm2-mediated p53 degradation, because Pitx2a does not affect p53 protein levels in HPV-negative cells, such as HCT116, U2OS, and C33A cells. In addition, Pitx2a-induced p53 is transcriptionally active and maintains its specific DNA binding activity in HeLa cells. Taken together, these findings suggest that, by binding to E6, Pitx2a interferes with E6/E6AP-mediated p53 degradation, leading to the accumulation of functional p53 protein in HeLa cells.
Echinococcus granulosus in northern Queensland. 2. Ecological determinants of infection in beef cattle.

OBJECTIVE To provide information on possible ecological determinants of infection with Echinococcus granulosus in a beef pastoral area of northern Queensland. PROCEDURE An ecological study was carried out on the prevalence and viability of infection with Echinococcus granulosus in definitive and potential intermediate hosts, and their predator prey relationships. Seven adjacent extensive beef properties 100 km south of Townsville, that included areas of savannah, open woodland and dense closed scrub, were selected for the study. Infection with E granulosus in dingoes was determined at post mortem, and in domestic dogs by examining duodenal mucus after purging with arecoline hydrobromide. Cattle, wild pigs and macropods were examined at post mortem for viable hydatid cysts. The diet of dingoes was investigated by identifying the hair of prey species found in their stomach and colon, and that of domestic dogs by questioning their owners. RESULTS Prevalence of hydatidosis in adult cattle ranged from 41% in animals from properties with large areas of dense closed scrub, to 3% on properties with little or no scrub. Hydatid cysts were found in 21.8% of black-striped wallabies (Macropus dorsalis), 9.4% of feral pigs, 1.5% of wallaroos (Macropus robustus), and 1.4% of eastern grey kangaroos (Macropus giganteus). No rufous rat kangaroos (Aepyprymnus rufescens) or swamp wallabies (Wallabia bicolor) were infected. Most cysts in macropods were viable, whereas in pigs about half were viable and in cattle only 0.7% contained viable protoscoleces. Infection with E granulosus was detected in 76% of dingoes, whereas no infection was detected in domestic dogs in the study area. CONCLUSIONS It was concluded that the sylvatic cycle of E granulosus in the study area was maintained mainly through predation of black-striped wallabies by dingoes, and that the verges of dense scrub were the main nidus of infection.
The relationship between amniotic fluid matrix metalloproteinase-8 and funisitis.

OBJECTIVE The fetal inflammatory response syndrome is a multisystem disorder associated with impending preterm delivery and adverse neonatal outcome. Inflammation of the umbilical cord--funisitis--is the histologic counterpart of fetal inflammatory response syndrome and has been associated with an increased risk for the development of cerebral palsy. Neutrophils found in the amniotic cavity are of fetal origin. Therefore, neutrophil secretory products may be an index of the fetal inflammatory response syndrome. To test this hypothesis, we examined the relationship between levels of amniotic fluid matrix metalloproteinase-8 and funisitis. STUDY DESIGN The relationship between the presence of funisitis and concentrations of amniotic fluid matrix metalloproteinase-8 was examined in 255 consecutive patients who delivered preterm singleton neonates (gestational age, <36 weeks) within 72 hours of amniocentesis. Amniotic fluid was cultured for aerobic and anaerobic bacteria and for mycoplasmas. Funisitis was diagnosed in the presence of neutrophil infiltration into the umbilical vessel walls or Wharton jelly. Matrix metalloproteinase-8 was measured by use of a specific immunoassay. Nonparametric statistics were used for analysis. RESULTS Funisitis was present in 23% (59/255) of cases. Patients with funisitis had a significantly higher median concentration of amniotic fluid matrix metalloproteinase-8 than those without funisitis (median, 433.7 ng/mL [range, 1.5-3836.8 ng/mL] vs median, 1.9 ng/mL [range, <0.3-4202.7 ng/mL]; P <.001). The diagnostic indices of matrix metalloproteinase-8 (cutoff, 23 ng/mL) in the identification of funisitis were: sensitivity of 90% (53/59), specificity of 78% (153/196), positive predictive value of 55% (53/96), and negative predictive value of 96% (153/159). CONCLUSIONS There is a strong association between increased levels of amniotic fluid matrix metalloproteinase-8 and funisitis. We propose that determination of amniotic fluid matrix metalloproteinase-8 concentrations may assist the assessment of the fetal inflammatory status, thereby eliminating the need for fetal blood sampling.
Prospective evaluation of radiation‐induced skin toxicity in a race/ethnically diverse breast cancer population

We evaluated predictors of radiation‐induced skin toxicity in a prospective study of a tri‐racial/ethnic breast cancer population. We evaluated patient demographics, tumor characteristics, and treatment variables in the first 392 patients in a prospective study assessing radiation‐induced skin toxicity. Logistic regression analyses were conducted to evaluate potential predictors of skin toxicity. The study consists of 59 non‐Hispanic whites (NHW; 15%), 241 Hispanic Whites (HW; 62%), 79 black or African Americans (AA; 20%), and 13 others (3%). Overall, 48% developed grade 0–1 skin toxicity, 49.8% grade 2, and 2.2% grade 3 by the National Cancer Institute's Common Toxicity Criteria for Adverse Events (CTCAE) scale. Twenty‐one percent developed moist desquamation. In multivariate analysis, higher body mass index (BMI; OR = 2.09; 95%CI = 1.15, 3.82), higher disease stage (OR = 1.82; 95%CI = 1.06, 3.11), ER‐positive/PR‐negative status (OR = 2.74; 95%CI = 1.26, 5.98), and conventionally fractionated regimens (OR = 3.25; 95%CI = 1.76, 6.01) were significantly associated with higher skin toxicity grade after adjustment for age, race, ethnicity, ER status, and breast volume. BMI specifically predicted for moist desquamation, but not degree of erythema. In this racially and ethnically diverse cohort of breast cancer patients receiving radiation to the intact breast, risk factors including BMI, disease stage, and conventionally fractionated radiation predicted for higher skin toxicity grade, whereas age, race, ethnicity, and breast volume did not. BMI specifically predicted for moist desquamation, suggesting that preventive measures to address this particular outcome should be investigated.
Perioperative chemotherapy with docetaxel, cisplatin and capecitabine (DCX) in gastro-oesophageal adenocarcinoma: a phase II study of the Arbeitsgemeinschaft Internistische Onkologie (AIO){dagger}.

BACKGROUND This prospective multicentre phase II trial assessed the feasibility and efficacy of perioperative chemotherapy with docetaxel, cisplatin and capecitabine (DCX) in patients with gastro-oesophageal adenocarcinoma. METHODS Patients with curatively resectable adenocarcinoma of the stomach, the gastro-oesophageal junction or the lower third of the oesophagus were enrolled. Patients received docetaxel 75 mg/m(2) plus cisplatin 60 mg/m(2) (day 1), followed by oral capecitabine 1875 mg/m(2) divided into two doses (days 1-14) every 3 weeks. There were three cycles preoperatively and three cycles postoperatively. The primary end point was the R0 resection rate. RESULTS Fifty-one patients were recruited and assessed for feasibility and efficacy. 94.1% of patients received all three planned cycles preoperatively, and 52.9% received three cycles postoperatively. The R0 resection rate was 90.2%. 13.7% of patients showed complete pathological remission (pCR). Toxicity was acceptably tolerable. Without prophylactic granulocyte colony-stimulating factor administration, neutropenic fever developed in 21.5% of patients preoperatively (grade 3 or 4) and in 11.1% of patients postoperatively. CONCLUSIONS DCX is a safe and feasible perioperative regimen in the treatment of gastro-oesophageal adenocarcinoma with a high percentage of cycles delivered pre- and postoperatively, compared with standard practice. The high efficacy in terms of R0 resection rate and pCR is very promising.