Raising Awareness of Pre-Exposure Prophylaxis (PrEP) among Women in New York City: Community and Provider Perspectives.
This study explored the knowledge, attitudes, and perceived facilitators and barriers to adoption of HIV pre-exposure prophylaxis (PrEP) among black women and Latinas in the Bronx, NY. Data were collected in focus group discussions (FGDs) held separately with staff (n = 21) and black and Latina female clients aged 18 to 50 (n = 23) of four organizations providing health and social services. Participants were also asked to give feedback about four action messages regarding PrEP for a social marketing campaign. Transcripts were analyzed by two researchers using grounded theory. We found that the majority of clients (74%) and staff (57%) had not heard about PrEP before participating in the FGDs. Following brief educational messaging about PrEP, participants identified potential facilitators and barriers to PrEP uptake among women, and expressed enthusiasm for more widespread efforts to raise awareness about PrEP as an HIV prevention option. Participants preferred an action message that was brief, referred to PrEP as a pill, and did not mention condoms or STD testing. These findings demonstrate the need to raise awareness about PrEP among women and build the capacity of women-serving organizations to educate, screen, and refer or provide PrEP services.


Changes of the phenolic compounds and antioxidant activities in germinated adlay seeds.
Over the years, germinated adlay products have been used as both food source and folk medicine. This study investigated the changes of total phenolic content (TPC), total flavonoid content (TFC), antioxidant activities, and phenolic acid profiles of adlay seed during germination. Results revealed that phenolic compounds and antioxidant activities varied with the germination stages. Germination significantly increased the free form phenolic and flavonoid contents by 112.5% and 168.3%, respectively. However, both of the bound form phenolic and flavonoid contents significantly decreased after germination. Phenolic acid compositions were quantified via HPLC analysis, and the levels of vanillic, p-coumaric, caffeic, hydroxybenzoic and protocatechuic acids in the free phenolic extracts were found to be significantly increased. The improvement of the free and total phenolic and flavonoid contents by the germination process led to a significant enhancement of the antioxidant activities (evaluated by the ABTS, FRAP and ORAC assays). The TPC showed the highest correlation with ORAC values (r = 0.9979). Germinated adlay had higher free and total phenolic and flavonoid contents, and antioxidant activities than ungerminated adlay. This study indicates that germinated adlay could be a promising functional food, more suitable for human consumption. © 2017 Society of Chemical Industry.


Tbx3 impinges on the p53 pathway to suppress apoptosis, facilitate cell transformation and block myogenic differentiation.
Tbx3 is a member of the T-box family of transcription factors. Mutations in Tbx3 cause ulnar-mammary syndrome, an autosomal dominant disorder characterized by upper limb defects, apocrine-gland defects including mammary hypoplasia, and tooth, hair and genital defects. In cell culture, Tbx3 and its close relative Tbx2 are capable of immortalizing mouse embryo fibroblasts. We show that expression of Tbx3 together with Myc or oncogenic Ras (H-Ras(Val17)) leads to efficient transformation of mouse embryo fibroblasts. Oncogene cooperation by Tbx3 correlates with an ability of Tbx3 to suppress the induction of p19ARF and p53 that is typically caused by overexpression Myc and Ras, and to protect against Myc-induced apoptosis. Whereas Tbx3 is capable of interfering with apoptosis caused by excessive Myc levels, a Tbx3 mutant lacking its C-terminal repression domain shows no anti-apoptotic activity and fails to repress levels of p19ARF or p53. Consistent with an ability to suppress p53 pathway function, we find that Tbx3, but not a Tbx3 C-terminal mutant, efficiently blocks myogenic differentiation of C2C12 myoblasts. Our results support the idea that deregulation and/or excessive levels of Tbx3 may have oncogenic potential in vivo.


Calcium (hydrogen-1-malate) hexahydrate on Echeveria gibbiflora leaves and its effect on sperm cells.
Echeveria gibbiflora is a plant widely used for its contraceptive activity in traditional Mexican medicine. Data on calcium crystals in plants are not outstanding. In the case of the Echeveria gibbiflora leaves, however, its quality, quantity, and salt type are quite surprising; one striking result of its X-ray crystallographic data shows the presence of calcium bis (hydrogen-1-malate) hexahydrate [2(C4H5O(5)1), Ca(1)2+, 6(H2O1)]. This highly soluble compound might explain the rapid shape changes of calcium crystals. Because SEM-EDS analysis shows that calcium malate crystals were obtained in a highly pure state and the immobilization and agglutination pattern that OBACE show on human and bull spermatozoa are not found even when high concentrations of calcium bis (hydrogen-1-malate) hexahydrate salt are present it is not feasible to involucrate molecules as calcium malate as part of the OBACE contraceptive activity.


Survival analysis in public health research.
This paper reviews the common statistical techniques employed to analyze survival data in public health research. Due to the presence of censoring, the data are not amenable to the usual method of analysis. The improvement in statistical computing and wide accessibility of personal computers led to the rapid development and popularity of nonparametric over parametric procedures. The former required less stringent conditions. But, if the assumptions for parametric methods hold, the resulting estimates have smaller standard errors and are easier to interpret. Nonparametric techniques include the Kaplan-Meier method for estimating the survival function and the Cox proportional hazards model to identify risk factors and to obtain adjusted risk ratios. In cases where the assumption of proportional hazards is not tenable, the data can be stratified and a model fitted with different baseline functions in each stratum. Parametric modeling such as the accelerated failure time model also may be used. Hazard functions for the exponential, Weibull, gamma, Gompertz, lognormal, and log-logistic distributions are described. Examples from published literature are given to illustrate the various methods. The paper is intended for public health professionals who are interested in survival data analysis.


Podiatric medical abnormalities in a random population sample 40 years or older in Spain.
Podiatric medical abnormalities are highly prevalent, yet few random population studies exist that determine the presence of pathologic abnormalities in the feet, despite their importance. The aim of this study was to determine the prevalence of podiatric medical abnormalities in a random sample population 40 years or older. An observational study was conducted of a random sample population (n = 1,002) located in A Coruña, Spain. Anthropometric variables, comorbidity (Charlson score), quality of life (36-item Short-Form Health Survey), and podiatric medical examination findings were studied. A descriptive analysis and multivariate logistic regression were performed. The most common diseases were claw toes (69.7%), hallux valgus (38%), and hallux extensus (15.8%), which increased with age and female sex. The most frequent metatarsal formula was index minus (40.9%), followed by index plus minus (35.0%). The most frequent digital formula was Egyptian foot (57.1%), followed by Greek foot (31.4%). In this study, although the presence of podiatric medical abnormalities reduced the probability of enjoying a better quality of life, it did not do so significantly. After taking into account age, sex, comorbidity, body mass index (BMI), and the presence of podiatric medical abnormalities, the variables with an independent effect that modified the physical component of quality of life were sex (female), comorbidity, and BMI. There was a high prevalence of podiatric medical abnormalities, which increased with age and female sex. Comorbidity, BMI, and sex modified quality of life independently of podiatric medical abnormalities.


Successful ambulatory treatment of Hodgkin's disease in Iranian children based on German-Austrian DAL-HD 85-90: single institutional results.
Hodgkin's disease (HD) accounts for 7.5% of childhood malignancies in Iran. In order to minimize chemotherapy toxicity and avoid eventual hospitalization and psychological and financial burdens we have applied since 1988, for the first time in Iran, a treatment regimen based on subsequently revised DAL-HD 85-90 and later GPOH-HD 95 protocols. During the period 1988-2004, 40 children with HD received DAL/GPOH-HD-adapted treatment; 25 males (62.5%) and 15 females (37.5%) (male/female ratio 1.7; age 4-14 years, mean 8.8). Clinical evaluation and staging was performed in all patients. Constitutional symptoms: 24 patients were asymptomatic (A; 60%) and 16 had constitutional complaints (B; 40%). Staging was as follows: stage I; seven (17.5%); II, 11 (27.5%); III, 11 (27.5%); and IV, 11 (27.5%). Histopathology: 22 patients had mixed cellularity (MC; 55%), 13 nodular sclerosis (32.5%), four lymphocyte predominance (LP; 10%) and one patient lymphocyte depletion (2.5%). Stage IA and IIA patients (n = 15) received either OPA x2 (vincristine, prednisolone, doxorubicin) or OPPA x2 or OPEA x2 (vincristine, prednisolone, procarbazine and doxorubicin), the latter receiving etoposide instead of procarbazine, and applied to males. Stages IIB, IIIA/B and IV received OPPA x2, followed by CO(P)P x4 (cyclophosphamide, vincristine, prednisolone in alternate courses and procarbazine). Twenty nine patients (72.5%) received radiotherapy (20-25 Gy); four to the involved field (stage I), 25 to the upper mantel (stage II and also III with either residual or mediastinal mass) and three additionally to spleen and para-aortic lymph nodes. Eleven patients received only chemotherapy. All patients achieved complete remission (CR). Relapse occurred in eight patients (20%); seven stage IV (MC) and one stage IA (LP) with progression to IIIB. Salvage chemotherapy consisted of MOPP/ABVD hybrid; six patients achieved a second sustained remission and three patients died: two due to relapse and progressive disease and the third one in CR, owing to thrombocytopenic hemorrhage and foudroyant pneumonia. The achieved overall and event-free survival was 88.1% and 75.4%, respectively. Aside from minor acute toxicities, three patients demonstrated azoospermia at the age of 18 years and one of these patients suffered non-Hodgkin lymphoma as a second malignancy. HD occurred as a second malignancy in two patients with acute lymphoblastic leukemia. Both received appropriate treatment and are over 10 years in CR. The DAL/GPOH-HD-based treatment approach proved to achieve long-term sustained cure even in children with advanced HD disease. The essentially outpatient diagnosis and treatment modus did not compromise the disease outcome, and was well tolerated and accepted by the patients and their parents. The employed drugs are easily available and affordable. This treatment approach is suitable for ambulatory use in developing countries. However, male infertility remains the major obstacle to procarbazine and cyclophosphamide use.


Inadvertent Debridement of the Medial Patellofemoral Ligament Following Arthroscopic Knee Surgery for Infection: A Case Report.
Arthroscopic debridement of the knee is usually considered a safe procedure. There are no case reports of medial patellofemoral ligament (MPFL) injury leading to habitual dislocation of the patella following this procedure in the literature. A 35-year-old male presented with complaints of habitual dislocation of the left patella, which he noticed after multiple arthroscopic surgeries of the left knee performed elsewhere. He had a history of septic arthritis of the knee following anterior cruciate ligament reconstruction, for which he underwent arthroscopic debridement of the knee twice. After a detailed evaluation, we noticed MPFL medial patellofemoral ligament injury. The MPFL medial patellofemoral ligament injury occurred as a result of extensive resection of the medial joint capsule while operating for septic arthritis. This rare grave surgical complication emphasizes the care one should take during arthroscopic debridement of the knee.


Room-temperature polariton parametric scattering driven by a one-dimensional polariton condensate.
We demonstrate a novel way to realize room-temperature polariton parametric scattering in a one-dimensional ZnO microcavity. The polariton parametric scattering is driven by a polariton condensate, with a balanced polariton pair generated at the adjacent polariton mode. This parametric scattering is experimentally investigated by the angle-resolved photoluminescence spectroscopy technique under different pump powers and it is well described by the rate equation of interacting bosons. The direct relation between the intensity of the scattered polariton signal and that of the polariton reservoir is acquired under nonresonant excitation, exhibiting the explicit nonlinear characteristic of this room-temperature polariton parametric process.


Increased amnionic fluid alpha-fetoprotein due to a holoacardium amorphous twin.
Amnionic fluid alpha-fetoprotein measurement was employed as a screening test for neural tube defects in a pregnancy only at risk due to advanced maternal age. The alpha-fetoprotein concentration was elevated more than 10 standard deviations above the mean and was found to be caused by a holoacardium amorphous twin. A normal female fetus was also present. Various causes of elevated alpha-fetoprotein concentration in amnionic fluid are discussed.


The Brainstem Tau Cytoskeletal Pathology of Alzheimer's Disease: A Brief Historical Overview and Description of its Anatomical Distribution Pattern, Evolutional Features, Pathogenetic and Clinical Relevance.
The human brainstem is involved in the regulation of the sleep/waking cycle and normal sleep architectonics and is crucial for the performance of a variety of somatomotor, vital autonomic, oculomotor, vestibular, auditory, ingestive and somatosensory functions. It harbors the origins of the ascending dopaminergic, cholinergic, noradrenergic, serotonergic systems, as well the home base of the descending serotonergic system. In contrast to the cerebral cortex the affection of the brainstem in Alzheimer's disease (AD) by the neurofibrillary or tau cytoskeletal pathology was recognized only approximately fourty years ago in initial brainstem studies. Detailed pathoanatomical investigations of silver stained or tau immunostained brainstem tissue sections revealed nerve cell loss and prominent ADrelated cytoskeletal changes in the raphe nuclei, locus coeruleus, and in the compact parts of the substantia nigra and pedunculopontine nucleus. An additional conspicuous AD-related cytoskeletal pathology was also detected in the auditory brainstem system of AD patients (i.e. inferior colliculus, superior olive, dorsal cochlear nucleus), in the oculomotor brainstem network (i.e. rostral interstitial nucleus of the medial longitudinal fascicle, Edinger-Westphal nucleus, reticulotegmental nucleus of pons), autonomic system (i.e. central and periaqueductal grays, parabrachial nuclei, gigantocellular reticular nucleus, dorsal motor vagal and solitary nuclei, intermediate reticular zone). The alterations in these brainstem nuclei offered for the first time adequate explanations for a variety of less understood disease symptoms of AD patients: Parkinsonian extrapyramidal motor signs, depression, hallucinations, dysfunctions of the sleep/wake cycle, changes in sleeping patterns, attentional deficits, exaggerated pupil dilatation, autonomic dysfunctions, impairments of horizontal and vertical saccades, dysfunctional smooth pursuits. The very early occurrence of the AD-related cytoskeletal pathology in some of these brainstem nuclei points to a major and strategic role of the brainstem in the induction and brain spread of the AD-related cytoskeletal pathology.


Public health campaigns and their effect on stroke knowledge in a high-risk urban population: A five-year study.
Background The level of knowledge of stroke risk factors and stroke symptoms within a population may determine their ability to recognize and ultimately react to a stroke. Independent agencies have addressed this through extensive awareness campaigns. The aim of this study was to determine the change in baseline knowledge of stroke risk factors, symptoms, and source of stroke knowledge in a high-risk Toronto population between 2010 and 2015. Methods Questionnaires were distributed to adults presenting to cardiovascular clinics at the University of Toronto in Toronto, Canada. In 2010 and 2015, a total of 207 and 818 individuals, respectively, participated in the study. Participants were identified as stroke literate if they identified (1) at least one stroke risk factor and (2) at least one stroke symptom. Results A total of 198 (95.6%) and 791 (96.7%) participants, respectively, completed the questionnaire in 2010 and 2015. The most frequently identified risk factors for stroke in 2010 and 2015 were, respectively, smoking (58.1%) and hypertension (49.0%). The most common stroke symptom identified was trouble speaking (56.6%) in 2010 and weakness, numbness or paralysis (67.1%) in 2015. Approximately equal percentages of respondents were able to identify ≥1 risk factor (80.3% vs. 83.1%, p = 0.34) and ≥1 symptom (90.9% vs. 88.7%, p = 0.38). Overall, the proportion of respondents who were able to correctly list ≥1 stroke risk factors and stroke symptoms was similar in both groups.(76.8% vs. 75.5%, p = 0.70). The most commonly reported stroke information resource was television (61.1% vs. 67.6%, p = 0.09). Conclusion Stroke literacy has remained stable in this selected high-risk population despite large investments in public campaigns over recent years. However, the baseline remains high over the study period. Evaluation of previous campaigns and development of targeted advertisements using more commonly used media sources offer opportunities to enhance education.


[Conceptualizing and Measuring the Quality of Adaptive Learning Support in Kindergarten Using Mathematical Board Games. A Study in Germany and Switzerland].
Good adaptive support by educational professionals is crucial for pre-school children's mathematical learning. Thus there is a need for appropriate instruments to evaluate the quality of the planning, implementation, and reflection process for mathematical learning opportunities in kindergarten. Existing instruments tend to focus on micro-adaptive learning support (MI-ALS), which considers the interaction between the professionals and the children. The quality of macro-adaptive learning support (MA-ALS), the teachers' planning of and reflection on learning opportunities, has yet to be comprehensively investigated. MA-ALS is important for the acquisition of subject-related (mathematical) competence, an aspect of kindergarten education that is gaining in importance in the pre-school curricula of many countries.The quality of mathematical learning support in kindergarten is conceptualized by differentiating between the quality of MA-ALS and MI-ALS. MI-ALS is also divided into general support (group management, emotional warmth) and subject-related support (learning stimulation, subject-specific language). A rating tool for analyzing the quality of mathematical learning support is presented and its psychometric quality is assessed. The tool is then used to analyze the teaching quality in two guided play situations (recorded) and two interviews each with 145 education professionals in Germany and Switzerland. A confirmatory factor analysis (CFA) confirms the validity of the distinction between group management, emotional warmth and subject-related support. The relationship between the level of MI-ALS and MA-ALS, the training of the teachers (academic vs non-academic), and the educational context (Germany vs Switzerland) is examined. The results corroborate the importance of including planning and reflection as a dimension of learning support quality.


Visible-Light-Induced Dearomatization of Indoles/Pyrroles with Vinylcyclopropanes: Expedient Synthesis of Structurally Diverse Polycyclic Indolines/Pyrrolines.
Visible-light-induced cycloaddition reactions initiated via energy-transfer processes have recently evolved as powerful methods for the construction of strained cyclic molecules that are not easily accessed using known ground-state synthetic methods. Particularly, the reactions initiated by the excitation of aromatic rings provide an alternative solution to the direct transformations of aromatic feedstocks under the scheme of dearomatization. Vinylcyclopropanes (VCPs) are well-known reagents in radical clock experiments, working as a probe to detect transient radical intermediates. However, the synthetic applications in this regard still remain limited due to uncontrollable selectivities. Herein, we report visible-light-induced dearomatization of indole- or pyrrole-tethered VCPs, in which several competitive reaction pathways, including [5 + 2], [2 + 2], interrupted [5 + 2], and [5 + 4] cycloadditions, can be well regulated by engineering substrate structures and tuning reaction conditions. The reaction mechanism has been explored by combined experimental and computational investigations. These reactions provide a convenient method to synthesize structurally diverse polycyclic molecules with high efficiency and good selectivity.


Diffusion-weighted imaging to differentiate metastatic from non-metastatic retropharyngeal lymph nodes in nasopharyngeal carcinoma.
To evaluate the diagnostic value of diffusion-weighted MRI for differentiating metastatic from non-metastatic retropharyngeal lymph nodes (RLNs) in patients with nasopharyngeal carcinoma (NPC). Untreated patients with NPC (n = 145) were scanned with both morphological MRI and diffusion-weighted imaging (DWI). RLNs (n = 335) were classified as metastatic on the basis of response to therapy as assessed on follow-up MRI. Morphological (short- and long-axial diameters) and functional [mean apparent diffusion coefficient (ADC) and minimum ADC values] parameters of the RLNs were derived from DWI and compared between metastatic and non-metastatic groups. A receiver operating characteristic curve and the area under the curve were used to evaluate the effectiveness of individual criteria and to generate threshold values to diagnose RLN metastases. Statistically significant differences between metastatic and non-metastatic RLNs were found for all four parameters derived from DWI (p < 0.001). At threshold values, accuracies of the ADC-based criteria (0.938 and 0.965 for mean and minimum ADC values, respectively) were greater than that of size-based criteria (0.838 and 0.809 for short- and long-axial diameters). The minimum ADC value at the threshold of 0.89 × 10(-3) mm(2) s(-1) was the most effective of all parameters in differentiating metastatic from non-metastatic RLNs with the sensitivity of 95.7%, specificity of 95.1% and accuracy of 96.5%. DWI is feasible for differentiating metastatic RLNs from non-metastatic nodes in patients with NPC with high accuracy, and the minimum ADC derived from DWI could serve as a standard clinical marker for disease status.


Beta-endorphin, ACTH, and catecholamine responses in chronic autonomic failure.
Plasma epinephrine (EPI), norepinephrine (NE), beta-endorphin, and corticotropin (ACTH) responses were measured during insulin-induced hypoglycemia in normal subjects and in patients with either multiple system atrophy (MSA) or idiopathic orthostatic hypotension (IOH). In normal subjects, there was a striking rise in EPI, NE, beta-endorphin, and ACTH following the nadir of hypoglycemia. Both beta-endorphin and ACTH responses were significantly lower than normal in patients with MSA, in contrast to normal levels in IOH patients. No correlation was observed between the degree of adrenergic insufficiency and the beta-endorphin and ACTH responses. The normal peptide responses in IOH are consistent with involvement limited to the peripheral sympathetic nervous system, whereas lesions in the central nervous system in MSA interfere with release of beta-endorphin and ACTH in response to hypoglycemia. The strong correlation between beta-endorphin and ACTH levels is consistent with their common origin. Peripheral adrenergic activity is not essential for beta-endorphin and ACTH release in humans.


Corneal Epithelial Thickness Mapping in the Diagnosis of Ocular Surface Disorders Involving the Corneal Epithelium: A Comparative Study.
The purpose of this study was to analyze the role of corneal epithelial thickness (ET) mapping provided by spectral domain optical coherence tomography in the diagnosis of ocular surface disorders (OSDs) involving the corneal epithelium. This was a retrospective comparative study. Institutional settings are as follows. Study population includes 303 eyes with an OSD and 55 normal eyes (controls). Observation procedures include spectral domain optical coherence tomography with epithelial mapping in the central 6 mm. Main outcome measures include ET map classification (normal, doughnut, spoke-wheel, localized/diffuse, and thinning/thickening patterns) and ET data and statistics (minimum, maximum, and SD). A quantitative threshold was determined with receiver operating curves to distinguish pathological from normal corneas. Sensitivity and specificity of classification and quantitative data were calculated using all eyes to assess the ability to distinguish corneas with a given corneal disorder from other conditions. Classification of full agreement between 3 readers was obtained in 75.4% to 99.4% of cases. Main OSD features were keratoconus (135 eyes), doughnut pattern (sensitivity/specificity = 56/94%), and max-min ET ≥ 13 μm (84/43%); limbal deficiency (56 eyes), spoke-wheel pattern (66/98%), and max-min ET ≥ 14 μm (91/59%); epithelial basement membrane dystrophy (55 eyes), inferior thickening pattern (55/92%), and central ET > 56 μm (53/81%); dry eye (21 eyes), superior thinning pattern (67/88%), and minimal ET ≤ 44 μm (86/48%); pterygium (10 eyes), nasal thickening pattern (100/86%), and nasal ET > 56 μm (80/71%); and in situ carcinoma (11 eyes), max ET > 60 μm (91/60%), and ET SD >5 μm (100/58%). The epithelial map pattern recognition combined with quantitative analysis of ET is relevant for the diagnosis of OSDs and for distinguishing various OSDs from each other. Deep learning analysis of big data could lead to the fully automated diagnosis of these disorders.


Effect of verapamil on renal vasoconstriction induced by angiotensin II, norepinephrine or renal nerve stimulation in anesthetized dogs.
The effect of verapamil on the decrease in renal blood flow (RBF) induced by angiotensin II (Ang II), norepinephrine (NE) or renal nerve stimulation (RNS) was examined in pentobarbital-anesthetized dogs. The injection into the renal artery of Ang II (0.01-0.1 micrograms), or NE (0.1-1.0 micrograms), or RNS (1-10 Hz) decreased RBF in a dose- or frequency-dependent manner. The renal arterial infusion of verapamil (30 micrograms/min followed by 100 micrograms/min) brought about a sustained increase in RBF and inhibition of renal vasoconstriction induced by Ang II or NE, but not by RNS, when the extent of vasoconstriction was estimated in terms of absolute changes in RBF. We also observed that the inhibitory effect of verapamil on Ang II-induced vasoconstriction was greater than on NE-induced constriction, as estimated from the % change in RBF. These results indicate that in canine renal vasculature, verapamil exerts different inhibitory effects on the vasoconstriction induced by Ang II, NE or RNS.


Indomethacin and its effect on renal function and urinary kallikrein excretion in premature infants with patent ductus arteriosus.
In the course of a double-blind trial of intravenous indomethacin therapy in premature infants with patent ductus arteriosus, renal function and urinary kallikrein were studied in 21 infants following one dose of either saline placebo or indomethacin. Ten infants were assigned to the control group and 11 were in the indomethacin group. Significantly lower urine output, fraction excretion of sodium, fraction excretion of chloride, and urinary kallikrein were noted by 45%, 59%, 63%, and 51%, respectively, in the indomethacin group as compared to the control group. There was a concomitant decrease in serum sodium concentration (P less than .05) at 24 hours following indomethacin therapy. No significant difference in glomerular filtration rate was seen between the control group and the indomethacin-treated infants.


No Epstein Barr and cytomegalovirus DNA found in salivary gland tumours.
A series of 219 (106 malignant and 113 benign) salivary gland tumours was investigated by in situ hybridisation (ISH) to detect Epstein-Barr-virus (EBV) and cytomegalovirus (CMV) DNA. Normal salivary gland did not show hybridisation signals for these viruses. Tumours presenting hybridisation signals in ductal and myoepithelial cells and 17 Warthin's tumours were further studied by PCR, but none of these tumours contained EBV or CMV DNA. Our series did not contain lymphoepithelial carcinomas, which are EBV-associated tumours. The results suggest that factors other than EBV or CMV are involved in carcinogenesis of primary salivary gland tumours.


Management of thoracic aneurysm.
A review of the literature on the management of thoracic aneurysm is presented. These patients have various comorbid conditions and need thorough work-ups. Aneurysms can be classified according to shapes and locations. Various methods to maintain hemodynamic stability with adequate end-organ perfusion are presented. The success of the operation depends upon preoperative anticipation and preparation for adequate organ perfusion and hemodynamic stability along with good communication between the anesthesiologist and the surgical team.


Frailty status at admission to hospital predicts multiple adverse outcomes.
frailty is proposed as a summative measure of health status and marker of individual vulnerability. We aimed to investigate the discriminative capacity of a frailty index (FI) derived from interRAI Comprehensive Geriatric Assessment for Acute Care (AC) in relation to multiple adverse inpatient outcomes. in this prospective cohort study, an FI was derived for 1,418 patients ≥70 years across 11 hospitals in Australia. The interRAI-AC was administered at admission and discharge by trained nurses, who also screened patients daily for geriatric syndromes. in adjusted logistic regression models an increase of 0.1 in FI was significantly associated with increased likelihood of length of stay >28 days (odds ratio [OR]: 1.29 [1.10-1.52]), new discharge to residential aged care (OR: 1.31 [1.10-1.57]), in-hospital falls (OR: 1.29 [1.10-1.50]), delirium (OR: 2.34 [2.08-2.63]), pressure ulcer incidence (OR: 1.51 [1.23-1.87]) and inpatient mortality (OR: 2.01 [1.66-2.42]). For each of these adverse outcomes, the cut-point at which optimal sensitivity and specificity occurred was for an FI > 0.40. Specificity was higher than sensitivity with positive predictive values of 7-52% and negative predictive values of 88-98%. FI-AC was not significantly associated with readmissions to hospital. the interRAI-AC can be used to derive a single score that predicts multiple adverse outcomes in older inpatients. A score of ≤0.40 can well discriminate patients who are unlikely to die or experience a geriatric syndrome. Whether the FI-AC can result in management decisions that improve outcomes requires further study.


Regulation of GABAB receptors by histamine and neuronal activity in the isolated spinal cord of neonatal opossum in culture.
The aim of these experiments has been to analyse the properties of receptors for the transmitter gamma-aminobutyric acid (GABA) in developing mammalian nervous system. Changes in responses of GABAB receptors have been measured after alterations of the chemical environment and the level of electrical activity. We have previously shown that when the central nervous system (CNS) of the new-born opossum, Monodelphis domestica, is cultured for three to five days in the presence of histidine, inhibition by baclofen, a GABAB agonist, disappears (Stewart et al. 1991). We have now investigated whether histidine acts indirectly by way of conversion to histamine. As with histidine, culture with 150 microM histamine for five days virtually abolished the inhibition by baclofen. The effects of histidine, as well as histamine, were blocked by mepyramine, a histamine H1-receptor antagonist, and by ranitidine, an H2-antagonist. Tetrodotoxin (TTX), which blocks all electrical activity, protected preparations from the action of histidine but not histamine. Our results suggest that histidine is converted to histamine, which reduces the efficacy of GABAB agonists. We conclude that, in the developing mammalian CNS, transmitter levels and electrical activity can selectively influence the properties of receptors.


Enhanced neurofibrillary tangle formation, cerebral atrophy, and cognitive deficits induced by repetitive mild brain injury in a transgenic tauopathy mouse model.
Traumatic brain injury (TBI) is a risk factors for Alzheimer's disease (AD), and repetitive TBI (rTBI) may culminate in dementia pugilistica (DP), a syndrome characterized by progressive dementia, parkinsonism, and the hallmark brain lesions of AD, including neurofibrillary tangles (NFTs), formed by abnormal tau filaments and senile plaques (SPs) composed of Abeta fibrils. Previous study showed that mild rTBI (mrTBI) accelerated the deposition of Abeta in the brains of transgenic (Tg) mice (Tg2576) that over-express human Abeta precursor proteins with the familial AD Swedish mutations (APP695swe) and model of AD-like amyloidosis. Here, we report studies of the effects of mrTBI on AD-like tau pathologies in Tg mice expressing the shortest human tau isoform (T44) subjected to mrTBI, causing brain concussion without structural brain damage to simulate injuries linked to DP. Twelve-month-old Tg T44 (n = 18) and wild-type (WT; n = 24) mice were subjected to mrTBI (four times a day, 1 day per week, for 4 weeks; n = 24) or sham treatment (n = 18). Histopathological analysis of mice at 9 months after mrTBI revealed that one of the Tg T44 mice showed extensive telencephalic NFT and cerebral atrophy. Although statistical analysis of neurobehavioral tests at 6 months after mrTBI did not show any significant difference in any of groups of mice, the Tg T44 mouse with extensive NFT had an exceptionally low neurobehavioral score. The reasons for the augmentation of tau pathologies in only one T44 tau Tg mouse subjected to mrTBI remain to be elucidated.


Optical characteristics of the canine prostate at 665 nm sensitized with tin etiopurpurin dichloride: need for real-time monitoring of photodynamic therapy.
Photodynamic therapy (PDT) is an emerging, minimally invasive therapy for prostate cancer that depends on the sequestration of a photosensitizing drug within targeted tissue. The photosensitizer is subsequently activated by light of a specific wavelength, resulting in destruction of the targeted tissue. Successful treatment requires knowledge of the optical properties of the target tissue, a critical element for therapy. Adult canines were injected with tin etiopurpurin dichloride (1.0 mg/kg) as a liposome emulsion vehicle in saline 24 hours prior to light treatment. Laser light was delivered to the prostate via a 400 microm optical fiber fitted with a 2.0 cm cylindrical diffuser and optical properties of the prostate were measured. In this study we determined the attenuation coefficient and critical fluence in the canine prostate. Our studies shown that the attenuation coefficient is not uniform but higher at the base (average for all animals 2.59 to 2.79 cm-1) than in the mid section or apex of the prostate (1.71 to 1.90 cm-1). Significant differences among dogs (0.11 to 12.70 cm-1) were found. In some cases we observed a fluctuation of the attenuation coefficient during treatment. We also established experimentally the minimum energy (1449 mJ/cm2) needed (critical fluence) to produce necrosis. Experimentally establishing the values of effective attenuation and critical fluence is necessary to predict the area of ablation during PDT and protect surrounding organs from over treatment. Based on our results it is evident that for PDT of the prostate to be successful the optical parameters of the prostate must be measured and monitored during treatment. We suggest that the optimum way of doing this is real-time computerized monitoring combined with simulation PDT.


Quantitation of ultraviolet-induced single-strand breaks using oligonucleotide chip.
A simple, accurate and robust methodology was established for the direct quantification of ultraviolet (UV)-induced single-strand break (SSB) using oligonucleotide chip. Oligonucleotide chips were fabricated by covalently anchoring the fluorescent-labeled ssDNAs onto silicon dioxide chip surfaces. Assuming that the possibility of more than one UV-induced SSB to be generated in a small oligonucleotide is extremely low, SSB formation was investigated quantifying the endpoint probe density by fluorescence measurement upon UV irradiation. The SSB yields obtained based on the highly sensitive laser-induced fluorometric determination of fluorophore-labeled oligonucleotides were found to coincide well with that predicted from a theoretical extrapolation of the results obtained for plasmid DNAs using conventional agarose gel electrophoresis. The developed method has the potential to serve as a high throughput, sample-thrifty, and time saving tool to realize more realistic, and direct quantification of radiation and chemical-induced strand breaks. It will be especially useful for determining the frequency of SSBs or lesions convertible to SSBs by specific cleaving reagents or enzymes.


Core hole processes in x-ray absorption and photoemission by resonant Auger-electron spectroscopy and first-principles theory.
Electron-core hole interactions are critical for proper interpretation of core-level spectroscopies commonly used as analytical tools in materials science. Here we utilize resonant Auger-electron spectroscopy to uniquely identify exciton, shake, and charge-transfer processes that result from the sudden creation of the core hole in both x-ray-absorption and photoemission spectra. These effects are captured for the transition-metal compounds SrTiO3 and MoS2 by fully ab initio, combined real-time cumulant, and Bethe-Salpeter equation approaches to account for core hole dynamics and screening. Atomic charges and excited-state electron-density fluctuations reflect materials' solid-state electronic structure, loss of translational symmetry around the core hole, and breakdown of the sudden approximation. They also demonstrate competition between long- and short-range screening in a solid.


Expression and phosphorylation of FOXO1 influences cell proliferation and apoptosis in the gastrointestinal stromal tumor cell line GIST-T1.
The mitogen-activated protein kinase (MAPK) and phosphatidylinositol 3-kinase (PI3K) pathways are activated during pathogenesis of gastrointestinal stromal tumors (GISTs). Forkhead box protein O1 (FOXO1) is a transcription factor regulated by the MAPK and PI3K pathways and is associated with multiple metabolic reactions. The present study aims to investigate the association of FOXO1 with cell proliferation and apoptosis in the cell line, GIST-T1. Cell counting kit-8 assay revealed that cell growth was inhibited by the PI3K inhibitor, LY294002, and/or MAPK inhibitor, UO126. Western blotting demonstrated that the expression of p-FOXO1 and B-cell lymphoma 2 (Bcl2) were significantly reduced, whereas the expression of Bcl-2-associated X protein was significantly increased following treatment with LY294002 and/or UO126 (all P<0.05). However, no significant change was revealed in the level of total FOXO1. Flow cytometry revealed that apoptosis was significantly increased by the pathway inhibitors (P<0.05). Specifically, the proportion of cells in the G1 phase was increased whereas the proportion in the S phase was reduced. The changes of protein expression and cell apoptosis were more evident in the LY294002 + UO126 group than in either single-inhibitor group. The results indicated that FOXO1 was able to affect cell proliferation, apoptosis and the cell cycle of GISTs. The regulation of FOXO1 was part of the PI3K and MAPK signaling network, while this regulation was mostly activated by phosphorylation of FOXO1.


Enhanced Autonomous Vehicle Positioning Using a Loosely Coupled INS/GNSS-Based Invariant-EKF Integration.
High-precision navigation solutions are a main requirement for autonomous vehicle (AV) applications. Global navigation satellite systems (GNSSs) are the prime source of navigation information for such applications. However, some places such as tunnels, underpasses, inside parking garages, and urban high-rise buildings suffer from GNSS signal degradation or unavailability. Therefore, another system is required to provide a continuous navigation solution, such as the inertial navigation system (INS). The vehicle's onboard inertial measuring unit (IMU) is the main INS input measurement source. However, the INS solution drifts over time due to IMU-associated errors and the mechanization process itself. Therefore, INS/GNSS integration is the proper solution for both systems' drawbacks. Traditionally, a linearized Kalman filter (LKF) such as the extended Kalman filter (EKF) is utilized as a navigation filter. The EKF deals only with the linearized errors and suppresses the higher orders using the Taylor expansion up to the first order. This paper introduces a loosely coupled INS/GNSS integration scheme using the invariant extended Kalman filter (IEKF). The IEKF state estimate is independent of the Jacobians that are derived in the EKF; instead, it uses the matrix Lie group. The proposed INS/GNSS integration using IEKF is applied to a real road trajectory for performance validation. The results show a significant enhancement when using the proposed system compared to the traditional INS/GNSS integrated system that uses EKF in both GNSS signal presence and blockage cases. The overall trajectory 2D-position RMS error reduced from 19.4 m to 3.3 m with 82.98% improvement and the 2D-position max error reduced from 73.9 m to 14.2 m with 80.78% improvement.


[Expression and localization of hnRNP A2/B1 during differentiation of human osteosarcoma MG-63 cells induced by HMBA].
The differentially expressed nuclear matrix proteins have great effects on canceration and regulation of cell differentiation. This study was to explore the existence and distribution of ribonucleoprotein hnRNP A2/B1 in nuclear matrix and its co-localization with Actin and Prohibitin in human osteosarcoma MG-63 cells before and after hexamethylene bisacetamide (HMBA) treatment. The nuclear matrix of MG-63 cells before and after treatment of HMBA were selectively extracted. The expression and localization of hnRNP A2/B1 in nuclear matrix were detected by 2-D PAGE, MALDI-TOF-MS, Western blot, and immunofluorescent staining. The co-localization of hnRNP A2/B1 with Actin and Prohibitin was observed under laser scanning confocal microscope (LSCM). hnRNP A2/B1 was detected in the component of nuclear matrix proteins of MG-63 cells by Western blot and immunogold staining and its expression was decreased after treatment of HMBA. hnRNP A2/B1 was located in the nuclear matrix, and its expression was weakened after HMBA treatment. hnRNP A2/B1 was co-localized with Actin or Prohibitin in MG-63 cells, while the co-localization relationship was weakened during differentiation of MG-63 cells. hnRNP A2/B1 is a kind of nuclear matrix protein, and localizes in the nuclear matrix. The distribution and expression of hnRNP A2/B1 and its co-localization with Actin and Prohibitin play important roles during the differentiation of MG-63 cells.


Redifferentiated Chondrocytes in Fibrin Gel for the Repair of Articular Cartilage Lesions.
Autologous chondrocyte implantation, which uses passaged chondrocytes, commonly leads to the formation of fibrocartilage. When chondrocytes are passaged to increase cell numbers, they lose their phenotype and ability to form hyaline cartilage. The use of transforming growth factor β (TGFβ) to redifferentiate passaged chondrocytes has been validated in vitro; however, it is unknown if redifferentiated chondrocytes will enhance defect repair when implanted in vivo. Furthermore, fibrin gel is used in orthopaedic surgery as a fixative and scaffold and could be an appropriate carrier to enhance retention of cells in the repair site. To investigate if passaged redifferentiated chondrocytes in fibrin gel have the ability to form cartilage tissue and if these redifferentiated cells will enhance the formation of hyaline cartilage in vivo when implanted into critical-size osteochondral defects. Controlled laboratory study. Rabbit and human chondrocytes were serially passaged twice in monolayer culture. Twice-passaged cells were used directly (dedifferentiated) or redifferentiated in high-density culture with TGFβ3. Dedifferentiated or redifferentiated cells were mixed with fibrin gel to form fibrin clots, which were cultured in vitro to assess the use of fibrin gel as a scaffold or implanted in vivo in a critical-size osteochondral defect in New Zealand White rabbit knee joints. Rabbits were sacrificed 6 weeks after implantation, and tissues were assessed histologically and by immunohistochemistry. Redifferentiation of passaged chondrocytes by means of 3-dimensional culture in the presence of TGFβ3 improved the formation of cartilaginous tissues in vitro, and culture in fibrin gel did not affect the cell phenotype. Implantation of dedifferentiated cells in vivo resulted in fibrocartilaginous repair tissues. Redifferentiated chondrocyte implants resulted in granulation tissues containing the hyaline cartilage marker collagen type 2. Redifferentiated chondrocytes will maintain their chondrogenic differentiation in fibrin clots. Implanted redifferentiated chondrocytes show a different reparative response than dedifferentiated chondrocytes and do not appear to enhance repair at an early time point. Another study of longer duration is required to assess tissue maturation over time. Redifferentiation of passaged chondrocytes with TGFβ3 before implantation does not improve defect repair in the first 6 weeks.


Hypokalemia-Induced Life-Threatening Arrhythmia in a Patient With Congestive Heart Failure.
Ventricular tachyarrhythmias are common in patients with heart failure. It is one of the important preventable causes of death in these patient populations. Hypokalemia is prevalent in patients with heart failure due to various reasons. Hypokalemia can trigger ventricular arrhythmias through different mechanisms. In this case report, we present a middle-aged man with congestive heart failure (CHF) and an automated intracardiac defibrillator (AICD) on multiple diuretic medications (unintended) who presented with acute chest pain. He was found to have severe hypokalemia, hyponatremia, and an acute kidney injury. Interrogation of the AICD revealed multiple episodes of ventricular fibrillation. The patient was managed by holding his diuretic medications, cautious volume repletion, and potassium replacement. Fortunately, the patient showed rapid clinical improvement and his plasma potassium level improved. On discharge, we reconciled the patient's medications to avoid the recurrence of hypokalemia from over-diuresis and arranged a close follow-up outpatient visit with his cardiologist.


[Skin reaction to OK-432 and its dosage for locoregional administration].
Establishment of optimal dosage of OK-432, a streptococcal preparation, was studied based on its skin test was studied. Locoregional immunotherapy using OK-432 was conducted for patients with malignant fluids. More OK-432 was administered to patients having a weaker skin reaction to OK-432 and less to those having a stronger one, corresponding to their redness diameter of skin reaction. There was a marked difference in OK-432-skin test among patients. Some patients with malignant fluids having small redness responded to the treatment after a large amount of OK-432, and others were well controlled by a smaller dosage of OK-432. It is suggested that OK-432-skin test may provide the optimal dosage for local treatment of malignant fluids.


Epidemiological Correlates of Substance Abuse Among In-Facility Clients of De-addiction and Rehabilitation Centres of District Dehradun: A Cross-Sectional Study.
Background The increasing production, distribution, promotion, and availability of substances contemporaneous with the changing values of society have resulted in rising substance abuse as an emerging public health concern in India. A prevalence of 32-37% has been reported for substance abuse in various studies conducted in Uttarakhand but there is a dearth of data on socio-epidemiological factors affecting substance abuse. Materials & methods A facility-based observational cross-sectional study was conducted in selected de-addiction and rehabilitation centers of district Dehradun. Data were collected using multistage systematic random sampling from clients admitted to the facility. Results The mean age of in-facility participants was 28 ± 8 years and most of them started taking drugs after the age of 18 years. The most common substance of abuse was alcohol (61.7%) followed by tobacco smoking (15.6%). Both 'peer pressure' and 'curiosity' play a major role in predisposition to substance use. Further, we found that age (p=0.002), and level of education (p <0.001) were important determinants for substance abuse. At the same time, among other factors, the influence of occupation notably did not have a statistically significant association. Conclusion Sensitization and capacity building of both providers and the community is integral to effective strategizing for the prevention and control of substance abuse. Regional studies including the current study can be of help in framing drug policies and management guidelines including prioritizing the importance of the establishment of de-addiction and rehabilitation centers at the district level.


Rehydration of crown fragment 1 year after reattachment: a case report.
The reattachment of the crown fragment to a fractured tooth is a conservative treatment that should be considered for patients with crown fractures of anterior teeth. This case report describes the reattachment of crown fragment that is discolored because of dehydration. After 1 month, the fragment had regained some of the original color and translucency. After 1 year, the reattached fragment had satisfying esthetics and excellent function. The reattachment of the crown fragment should be done even if the crown fragment is discolored.


Prosthetic liner wear in total hip replacement: a longitudinal 13-year study with computed tomography.
This case report follows a woman who had a total hip replacement in 1992 when she was 45 years old. Six serial computed tomography (CT) examinations over a period of 13 years provided information that allowed her revision surgery to be limited to liner replacement as opposed to replacement of the entire prosthesis. Additionally, they provided data that ruled out the presence of osteolysis and indeed none was found at surgery. In 2004, when the first CT was performed, the 3D distance the femoral head had penetrated into the cup was determined to be 2.6 mm. By 2017, femoral head penetration had progressed to 5.0 mm. The extracted liner showed wear at the thinnest part to be 5.5 mm, as measured with a micrometer. The use of modern CT techniques can identify problems, while still correctable without major surgery. Furthermore, the ability of CT to assess the direction of wear revealed that the liner wear changed from the cranial to dorsal direction.


Ontogenesis of learning: III. Variation in the rat's differential reflexive and learned responses to sound frequencies.
The ontogenesis of the rat's differential response to variation in sound frequency was investigated. Two behavioral procedures were employed: (a) a differential Pavlovian conditioning procedure that provided a means of inferring the pup's capacity to learn to respond differentially on the basis of sound frequency (e.g., 2000 Hz vs 900 Hz), and (b) a habituation-generalization task that indexed the capacity to discriminate different sound frequencies from the pup's reflexive behavior. Pups less than 17 days old failed to learn to respond differentially to a 2000-Hz vs 900-Hz tone (Experiment I, IIA, IIB, and III). In contrast, pups only 14 days old discriminated tones that differed by as little as 200 Hz when the reflex-habituation-generalization procedure was employed (Experiment IV). This suggests that the reflexive and learned behaviors, potentially controlled by sound frequency, are dissociated during ontogenesis, the former emerging prior to the latter. These data were interpreted within a neurobiological framework that related ontogenetic changes in behavioral capacity to a caudal-to-rostral maturational sequence in the ascending auditory system of the components that contribute to these capacities.


Effects of near-infrared LED therapy on experimental tooth replantation in rats.
Dental avulsion damages periodontal tissues and may induce dentoalveolar ankylosis and root resorption after replantation. The aim of this work was to evaluate the effects of light-emitting diode (LED) therapy after tooth replantation. The upper right incisors of 36 male Wistar rats were extracted and replanted after 15 min. The control group (Co, n = 18) was submitted to replantation and the LED group (n = 18) was submitted to replantation and LED therapy (940 nm, 4 J cm-2 ) for three consecutive days (0, 24, and 48 h). Six animals from each group were euthanized at 7, 14, and 21 days for histological analysis. The upper left incisors were used as a negative control. Data were compared using the Fisher exact test, considering P < 0.05. After 7 days, the Co (73.3%) and LED (72.2%) groups presented areas of periodontal ligament necrosis. However, periodontal ligament necrosis was more frequent in the LED group at 14 (70%, P < 0.05) and 21 days (43.2%, P < 0.05) in relation to the Co group (33 and 21.6%). Inflammatory cell infiltration was more frequent in the Co group at 7 days (100%) than the LED group (24.4%, P < 0.05), but increased in the LED group after 21 days (83.3%, P < 0.05). Bone necrosis was more frequent in the LED group after 14 (79%, P < 0.05) and 21 days (60%, P < 0.005) than in the Co group (45% and 20%). Bone repair was evident in the Co group at 14 days. All of the replanted teeth had pulp necrosis. The results suggest that the application of LED therapy up to 48 h after tooth replantation may delay periodontal ligament repair.


[Relationship between job stress contents, psychosocial factors and mental health status among university hospital nurses in Korea].
The present study was intended to assess the mental health of nurses working for university hospitals and to establish which factors determine their mental health. Self-administered questionnaires were given to 1,486 nurses employed in six participating hospitals located in Daejeon City and Chungnam Province between July 1st and August 31st, 2006. The questionnaire items included sociodemographic, job-related, and psychosocial factors, with job stress factors (JCQ) as independent variables and indices of mental health status (PWI, SDS and MFS) as dependent variables. For statistical analysis, the Chi-square test was used for categorical variables, with hierarchical multiple regression used for determining the factors effecting mental health. The influence of psychosocial and job-related factors on mental health status was assessed by covariance structure analysis. The statistical significance was set at p<0.05. The factors influencing mental health status among subject nurses included sociodemographic characteristics such as age, number of hours of sleep, number of hours of leisure, and subjective health status; job-related characteristics such as status, job satisfaction, job suitability, stresses such as demands of the job, autonomy, and coworker support; and psychosocial factors such as self-esteem, locus of control and type A behavior patterns. Psychosocial factors had the greatest impact on mental health. Covariance structure analysis determined that psychosocial factors affected job stress levels and mental health status, and that the lower job stress levels were associated with better mental health. Based on the study results, improvement of mental health status among nurses requires the development and application of programs to manage job stress factors and/or psychosocial factors as well as sociodemographic and job-related characteristics.


Among-site variability in the stochastic dynamics of East African coral reefs.
Coral reefs are dynamic systems whose composition is highly influenced by unpredictable biotic and abiotic factors. Understanding the spatial scale at which long-term predictions of reef composition can be made will be crucial for guiding conservation efforts. Using a 22-year time series of benthic composition data from 20 reefs on the Kenyan and Tanzanian coast, we developed Bayesian vector autoregressive state-space models for reef dynamics, incorporating among-site variability, and quantified their long-term behaviour. We estimated that if there were no among-site variability, the total long-term variability would be approximately one-third of its current value. Thus, our results showed that among-site variability contributes more to long-term variability in reef composition than does temporal variability. Individual sites were more predictable than previously thought, and predictions based on current snapshots are informative about long-term properties. Our approach allowed us to identify a subset of possible climate refugia sites with high conservation value, where the long-term probability of coral cover ≤0.1 (as a proportion of benthic cover of hard substrate) was very low. Analytical results show that this probability is most strongly influenced by among-site variability and by interactions among benthic components within sites. These findings suggest that conservation initiatives might be successful at the site scale as well as the regional scale.


Assessment of the survival and the clinical results of Stanmore total knee replacements.
We review 210 Stanmore knee replacements in 163 patients to assess the survival of the prostheses and the long-term results. The annual rate of failure reached a maximum of 4.6% in the fourth year after operation; thereafter it declined to reach zero by the eighth year. Between two and eight years after operation, 66.3% of the surviving knees were completely free of pain and 30.2% had mild retropatellar pain. Fixed flexion deformities present before operation were completely corrected in 73% of the knees, and varus or valgus deformities were invariably corrected. Stability was always restored to unstable knees and 80.8% of knees flexed to 90 degrees or more after replacement. Aseptic loosening (8.1%), prosthetic infection (4.3%) and femoral fracture (2.9%) led to 8.5% of the prostheses being revised or removed over eight years. Modifications in prosthetic design and operative techniques have been introduced to minimise such complications in the future.


Direct-aperture optimization applied to selection of beam orientations in intensity-modulated radiation therapy.
Direct-aperture optimization (DAO) was applied to iterative beam-orientation selection in intensity-modulated radiation therapy (IMRT), so as to ensure a realistic segmental treatment plan at each iteration. Nested optimization engines dealt separately with gantry angles, couch angles, collimator angles, segment shapes, segment weights and wedge angles. Each optimization engine performed a random search with successively narrowing step sizes. For optimization of segment shapes, the filtered backprojection (FBP) method was first used to determine desired fluence, the fluence map was segmented, and then constrained direct-aperture optimization was used thereafter. Segment shapes were fully optimized when a beam angle was perturbed, and minimally re-optimized otherwise. The algorithm was compared with a previously reported method using FBP alone at each orientation iteration. An example case consisting of a cylindrical phantom with a hemi-annular planning target volume (PTV) showed that for three-field plans, the method performed better than when using FBP alone, but for five or more fields, neither method provided much benefit over equally spaced beams. For a prostate case, improved bladder sparing was achieved through the use of the new algorithm. A plan for partial scalp treatment showed slightly improved PTV coverage and lower irradiated volume of brain with the new method compared to FBP alone. It is concluded that, although the method is computationally intensive and not suitable for searching large unconstrained regions of beam space, it can be used effectively in conjunction with prior class solutions to provide individually optimized IMRT treatment plans.


Attitudes, Beliefs, and Current Practices Carried Out by Family Physicians in Spain Regarding the Prevention of Road Injuries in Older Adults: A Nationwide Cross-Sectional Study.
The activities related to the prevention of crash injuries in older adults (PCIOA) performed by Family Physicians (FPs) have been scarcely studied. Our aim was to estimate the frequency of PCIOA activities performed by FPs in Spain and its association with attitudes and beliefs regarding this health problem. We conducted a cross-sectional study in a nationwide sample of 1888 FPs working in Primary Health Care Services, recruited from October 2016 to October 2018. Participants completed a validated, self-administered questionnaire. Study variables included three scores related to current practices (General Practices, General Advice and Health Advice), several scores related to attitudes (General, Drawbacks and Legal), demographic and workplace characteristics. To obtain the adjusted coefficients and their 95% confidence intervals, we applied mixed effects multi-level linear regression models and the likelihood-ratio test to compare multi-level and one-level models. The frequency of PCIOA activities reported by FPs in Spain was low. The General Practices Score was 0.22/1, the General Advice Score was 1.82/4, the Health Advice Score was 2.61/4, and the General Attitudes Score was 3.08/4. The importance given to road crashes in the elderly obtained 7.16/10, the role that FPs should play in the PCIOA obtained 6.73/10, and the current perceived role obtained 3.95/10. The General Attitudes Score and the importance that FPs give themselves in the PCIOA were associated with the three Current Practices Scores. The frequency of activities related to the PCIOA that FPs usually carry out in Spain is far below desirable standards. The average level of attitudes and beliefs about the PCIOA of the FPs working in Spain seems adequate. The variables of the most pronounced FPs associated with the prevention of traffic accidents in older drivers were age over 50 years, female sex and foreign nationality.


A randomised controlled trial of routine versus restrictive use of episiotomy at operative vaginal delivery: a multicentre pilot study.
To compare the maternal and neonatal outcomes of operative vaginal delivery in relation to the use of episiotomy. Pilot randomised controlled trial (RCT). Two urban maternity units in Scotland and England. Nulliparous women anticipating a singleton cephalic vaginal delivery were recruited in the antenatal period. If an operative vaginal delivery was required in the second stage of labour, women were randomised to either routine (in all cases) or restrictive (only if tearing apparent) use of episiotomy. The primary outcome was anal sphincter tearing (third or fourth degree). Secondary outcomes included postpartum haemorrhage (PPH), neonatal trauma and pelvic floor symptoms up until 10 days postpartum. In a group of 317 women requiring operative vaginal delivery, 200 were randomised: 99 to routine use of episiotomy and 101 to restrictive use. There were small differences in the rates of anal sphincter tears (8.1% routine versus 10.9% restrictive, OR 0.72, 95% CI 0.28-1.87) and primary PPH (36.4% routine versus 26.7% restrictive, OR 1.57, 95% CI 0.86-2.86). Neonatal trauma was similar between the two groups (45.5% routine versus 43.6% restrictive, OR 1.08, 95% CI 0.62-1.89), as was prolonged catheterisation, urinary incontinence, faecal incontinence, perineal infection and prolonged hospital admission. This pilot study does not provide conclusive evidence that a policy of routine episiotomy is better or worse than a restrictive policy. A definitive RCT is feasible but will require a large sample size to inform clinical practice.


Concepts and mechanisms of generalized central nervous system arousal.
A concept of generalized arousal of the CNS is presented and given an operational definition that leads to quantitative physical measures. Because this primitive arousal function underlies all motivated behavioral responses, cognitive functions, and emotional expression, disorders of generalized arousal can be associated with a large number of problems in medicine and public health, including vegetative states, attentional disorders, depression, occupational hazards, and problems with sleep and anesthesia. Some of its known mechanisms are briefly reviewed, at the levels of neuroanatomy, neurophysiology, and functional genomics. Generalized arousal contributes to the excitement and the activation of behaviors during specific arousal states. Data are summarized for four genomic/neurochemical systems through which changes in generalized arousal could affect sexual arousal, two of which heighten, and the other two of which reduce arousal.


Transradial approach for transcatheter arterial chemoembolization in patients with hepatocellular carcinoma: comparison with conventional transfemoral approach.
We evaluated the clinical usefulness and safety of transradial approach for transcatheter arterial chemoembolization (TACE) in patients with hepatocellular carcinoma (HCC) compared with that of conventional transfemoral approach. The two groups (radial group, n = 177; femoral group, n = 150) of cases were retrospectively compared with regard to the successful rate of angiography or TACE, time required for catheterizaiton and complications. Hepatic angiography and TACE were completed in 174 (98.3%) of 177 cases in the radial group. There was no intergroup difference of time required for catheterization. Minor complications (dull pain, numbness) occurred in 8 (4.6%) patients in the radial group, and there were lower complications in the radial group compared to the femoral group. TACE by our new transradial approach was found to have therapeutic efficacy with lower complications comparable to that of the conventional transfemoral approach.


Accessing the scientific literature. The reality of virtual scholarship.
The age-honored practice of plowing through the Index Medicus in a good medical library to meander through citations for treasured finds is an anachronism. Today, clinicians have the astonishing capacity to bring to bear existing knowledge almost effortlessly. Virtual scholarship makes available up-to-date medical citations and their abstracts. There can be access around the clock on any topic in the office, at the bedside, or from home. Computerized searches of the medical literature promote directed continuing education and may enhance clinical care of patients.


The orthopedic and renal manifestations of idiopathic carpal tarsal osteolysis.
Idiopathic carpal tarsal osteolysis (ICTO) is a rare congenital disorder that results in the destruction and resorption of bone, leading to severe functional deficits and cosmetic deformities. This report includes a literature review describing the orthopedic and renal manifestations of ICTO. An additional case report of ICTO with atypical features is included.


Polymorphism of the HLA-DMA and DMB genes in rheumatoid arthritis.
To determine whether the HLA-DMA and DMB genes, whose encoded molecules are involved in HLA class II-restricted antigen presentation, contribute to the genetic susceptibility to rheumatoid arthritis (RA). One hundred ninety-one RA patients, 147 control subjects, and 218 HLA-DRB1 genotype-matched control subjects were oligotyped for DMA and DMB genes. DMA*0103 and DMB*0104 were significantly increased in the RA patients compared with the randomly selected and the matched controls, thus indicating a direct influence of the DM genes. After stratification of the patients and matched controls according to DRB1 genotypes, only DMA*0103 was increased in the RA patients with DRB1*01, as well as in the patients negative for the RA-susceptibility DR alleles. Our results suggest that DMA*0103 could play an additional role in the genetic susceptibility to RA.


Fibroadenoma of the anogenital region.
Fibroadenoma of the anogenital region is a rare tumour histologically similar to fibroadenoma of the breast. Morphological and immunophenotypic features of a case with pseudoangiomatous stromal hyperplasia are presented here.


Interfacing clinical practice and error prevention.
Medication error is a major source of preventable harm to patients in hospitals and is an area in which, it is suggested, information technology will have a positive impact. This paper presents findings from part of a study that examined current information utilisation patterns during nursing medication rounds. Nursing working patterns in medication administration are poorly understood despite being one of the most likely sources of medication error. Methods used were drawn from principles of Human Computer Interaction (HCI), using a semi-structured observational tool for analysing system requirements and data elements. Results from this study indicated that clinical and contextual factors impact on nursing patterns of information handling in many ways, including documentation quality, location of information sources and current patterns of computer utilization. Numerous extraneous interruptions also impact on the ability of nurses to assimilate and use clinical information effectively. These results were used to develop a conceptual framework for interfacing error prevention in clinical practice. These insights into the human factors that are the reality of clinical practice allow us to design and develop effective information technology systems to help prevent nursing medication administration errors.


Solvent molecules in an epitaxially grown scaffold of star-shaped nanographenes.
A scanning tunneling microscopy (STM) study of a star-shaped hexa-peri-hexabenzocoronene (HBC-star) derivative at solid-solution interfaces is presented. The star-shape of the molecules provides voids at their periphery which can be filled by smaller molecules. The use of solvents with different affinities to fill the voids allows for the fine-tuning of the structure of self-assembled architectures of HBC-stars. This concept is demonstrated by the use of solvents of different polarity and size, which leads to the formation of complex, epitaxial architectures at the interface. For small polar solvent molecules, a surprising decrease of the tunneling barrier is observed. The self-assembled architecture may serve as a useful model system for studying the dependence of electron tunneling on order, mobility, and polarity of adsorbates.


A holistic approach to managing a patient with heart failure.
Despite varied and complex therapeutic strategies for managing patients with heart failure, the prognosis may remain poor in certain groups. Recognition that patients with heart failure frequently require input from many care groups formed the basis of The British Society of Heart Failure Annual Autumn Meeting in London (UK), in November 2012, entitled: 'Heart failure: a multidisciplinary approach'. Experts in cardiology, cardiac surgery, general practice, care of the elderly, palliative care and cardiac imaging shared their knowledge and expertise. The 2-day symposium was attended by over 500 participants from the UK, Europe and North America, and hosted physicians, nurses, scientists, trainees and representatives from the industry, as well as patient and community groups. The symposium, accredited by the Royal College of Physicians and the Royal College of Nursing, focused on the multidisciplinary approach to heart failure, in particular, current therapeutic advances, cardiac remodeling, palliative care, atrial fibrillation, heart rate-lowering therapies, management of acute heart failure and the management of patients with mitral regurgitation and heart failure.


Preparedness for caregiving and preparedness for death: Associations and modifiable thereafter factors among family caregivers of patients with advanced cancer in specialized home care.
The purpose of this study was to (1) explore associations between preparedness for caregiving and preparedness for death among family caregivers of patients with advanced cancer and (2) explore modifiable preparedness factors, such as communication and support. Data was derived from a baseline questionnaire collected in specialized home care. The questionnaire included socio-demographics, the Preparedness for Caregiving Scale, and single items addressing preparedness for death, received support and communication about incurable illness. Data was analyzed using descriptive statistics and Spearman correlations. Altogether 39 family caregivers participated. A significant association was found between preparedness for caregiving and preparedness for death. Received support and communication about the illness was associated with higher levels of preparedness for caregiving and death. This study contributes to evidence on the association between preparedness for caregiving and death, but also that communication and support employed by healthcare professionals could improve family caregiver preparedness and wellbeing.


A Case Study in the Use of Primary Literature in the Context of Authentic Learning Pedagogy in the Undergraduate Neuroscience Classroom.
Providing opportunities for undergraduate science students to develop causal reasoning skills and the ability to think like research scientists is a crucial part of their preparation for professional practice as a scientist and/or a clinician. This has led many to question whether the traditional academic in-class lecture still has a functional role in today's undergraduate science education. Here, we performed a case study to attempt to maximize the use of in-class time to create a more authentic learning opportunity for undergraduate neuroscience students in our institution, the majority of whom go on to be research active scientists. We hypothesised that using seminal research papers as a teaching tool in a flipped classroom setting would model for neuroscience students what it means to think like a research scientist, would provide an opportunity for them to develop their causal reasoning skills and allow them to become more comfortable with the nature of professional practice (i.e., research) in the context of the discipline. We describe the design and implementation of this teaching approach to undergraduate final year neuroscience students, and evaluate their perception of it. We provide evidence that this approach models for the students what it means to reason like a research scientist, and discuss the implications of these findings for future practice. We propose that these findings will help add to the educational experience of all Neuroscience students whether they are on pre-med or on a research track.


Stroke in childhood.
Essential facts About 400 children a year have a stroke in the UK. Many are left with severe disability. While there have been improvements in diagnosis and treatment in recent years, the condition is still not as well recognised as stroke in adults. Experts believe that greater awareness among parents and healthcare professionals could lead to speedier diagnosis and minimise risk of severe long-term health problems.


Tracheal septum: real or virtual?
Tracheal septum has never been reported in human beings, though it's a common occurrence in few lower vertebrates. We are presenting a case of thick tracheal secretion that appeared as a midline tracheal septum and prompted the clinician to go for bronchoscopy.


Divergence preceding island formation among Aegean insular populations of the freshwater snail genus Pseudorientalia (Caenogastropoda: Truncatelloidea).
Freshwater snails that inhabit islands are excellent model organisms for testing relationships between geological events and phylogeography, especially in the Aegean region. Although many Aegean islands were searched in the present study, species of the genus Pseudorientalia were only found on Lesvos, Samos, and Chios. Phylogenetic relationships between specimens living on these three islands were analysed using COI and 16S rRNA molecular markers and morphological data. A high level of diversity was found between islands. Genetic distances between clades showed differences high enough for the samples from different islands to be considered distinct species (p-distance: 0.105-0.133). These results are also supported by obvious morphological differences in shell morphology between islands. The mean divergence time between the Lesvos clade and Samos/Chios clade was 24.13 ± 3.30 Mya; between the Samos and Chios clades the divergence time was 14.80 ± 1.11 Mya. Our data suggest that high divergence may have occurred between Pseudorientalia populations during the Upper and Middle Miocene, when the Aegean region was part of a united landmass. It is possible that the observed highly divergent Pseudorientalia clades are relicts of high regional diversity that existed in the past.


Assessment of Anticancer Drug Effects on Pancreatic Cancer Cells under Glucose-Depleted Conditions Using Intracellular and Extracellular Amino Acid Metabolomics.
Previously, we developed a method to evaluate states of cells treated with anticancer drugs via the comprehensive analysis of amino acids, termed amino acid metabolomics. In the present study, we evaluated the effects of the anticancer drugs, gemcitabine hydrochloride and pyrvinium pamoate, on the proliferation of a pancreatic cancer cell line (PANC-1) under hypoglycemic conditions using amino acid metabolomics. Intracellular and extracellular amino acid profiles of PANC-1 were determined by hydrophilic interaction chromatography-tandem mass spectrometry with simple pretreatment. Changes to the drugs' anticancer effects resulting from glucose starvation conditions were presented in score plots obtained from principal component analyses. In particular, the analysis of intracellular amino acids was found to be the superior approach because the results allowed a clearer assessment of the cell state. Further, orthogonal partial least squares discriminant analysis was performed to search for amino acid candidates that discriminate with anticancer drug-treated PANC-1 cells. We identified several amino acids that might be able to distinguish the drug-treated group from the control group. These results might provide a better understanding of the mechanisms underlying cell responses such as drug resistance or austerity. The present study is the first to evaluate the efficacy of anticancer drugs under glucose starvation based on the analysis of the variation of extracellular and intracellular amino acid profiles in vitro.


The Motivation-Facilitation Model of Sexual Offending.
In this article, I describe the motivation-facilitation model of sexual offending, which identifies the traits of paraphilia, high sex drive, and intense mating effort as primary motivations for sexual offenses, as well as trait (e.g., antisocial personality) and state (e.g., intoxication) factors that can facilitate acting on these motivations when opportunities exist. Originally developed to explain contact sexual offending against children, the motivation-facilitation model was subsequently extended as an explanation for child pornography offending and for online solicitations of young adolescents. Here, I argue it has the potential to be expanded to explain other forms of sexual offending, including sexual assaults of adults and noncontact offenses involving exhibitionism or voyeurism. In this review, I critically examine the evidence for and against the model, discuss its limitations, and identify critical gaps for future research.


Decreased spermatogenesis as the result of an induced autoimmune reaction directed against the gonadotropin receptors in male rats.
The presence of luteinizing hormone (LH) and testosterone is considered critical for the maintenance of spermatogenesis in the rat. However, the role and importance of follicle-stimulating hormone (FSH) in the initiation and maintenance of spermatogenesis has been a subject of debate for some time. The objective of this study was to examine the role of FSH and LH in vivo in the developing and adult rat by inducing an autoimmune reaction against the receptors to these gonadotropins. Sperm numbers were reduced in animals immunized against either the FSH or LH receptor (FSHR/LHR). In animals immunized against both FSHR and LHR there was also a significant reduction in sperm number although spermatogenesis was never completely ablated. These results were seen in male rats immunized either prepubertally (18 days of age) or as adults (80 days of age). To examine the requirements for FSH in early postnatal-testicular development, pregnant females were also immunized against either FSHR, LHR, or both of the receptors, and the male offspring were examined at 30 days of age. Again, germ-cell number was decreased with the greatest effect in those pups whose mothers were immunized against both FSHR and LHR. Radioligand-receptor-binding assays revealed that the antibody produced in the rats against FSHR was able to compete with FSH for binding sites in receptor-membrane preparations. Therefore, the mechanism of disruption of spermatogenesis is probably due to suppression of hormone to receptor binding. The results of this study support a role for FSH in spermatogenesis not only during neonatal and early postnatal development but also in the adult animal.


Perceiving Partners to Endorse Benevolent Sexism Attenuates Highly Anxious Women's Negative Reactions to Conflict.
Benevolent sexism prescribes that men are dependent on women in relationships and should cherish their partners. The current research examined whether perceiving male partners to endorse benevolent sexism attenuates highly anxious women's negative reactions to relationship conflict. Greater attachment anxiety was associated with greater distress and insecurity during couples' conflict discussions (Study 1), during daily conflict with intimate partners (Study 2), and when recalling experiences of relationship conflict (Study 3). However, this heightened distress and insecurity was attenuated when women (but not men) perceived their partner to strongly endorse benevolent sexism (Studies 1-3) and thus believed their partner could be relied upon to remain invested (Study 3B). These novel results illustrate that perceiving partners to endorse benevolent sexism alleviates anxious women's insecure reactions to relationship threat by conveying partner's continued reliability. Implications of these security-enhancing effects are considered in light of the role benevolent sexism plays in sustaining gender inequality.


Fructose-fed rats are protected against ischemia/reperfusion injury.
This study examines the relationship between insulin resistance (IR) induced by fructose feeding (FF) and susceptibility to myocardial ischemia/reperfusion injury (MI/R). Six-week-old male Sprague-Dawley rats were randomized into control (CON; n = 59) or FF (n = 58) groups. After 4 weeks, rats were further randomized into one of the following groups: placebo, ischemic preconditioning (IPC), 5-hydroxydecanoic acid (5-HD) (10 mg/kg), or 5-HD + IPC. Moreover, to determine the role of fructose, a second model of IR (Zucker obese) and rats fed fructose diet for 3 days (FF-3) were also subjected to MI/R. In all experiments, rats were subjected to 30 min of myocardial ischemia and 4 h of reperfusion. In rats randomized to placebo, infarct size was significantly reduced by FF (24 +/- 5%) compared with CON (54 +/- 1%, p < 0.05). Pretreatment with 5-HD did not alter the infarct size in CON (45 +/- 5%) but inhibited the protection afforded by FF (53 +/- 7%). IPC reduced the infarct size to an equivalent level in both groups, whereas 5-HD administration prior to IPC blunted the IPC effect. In Zucker obese rats, infarct size was significantly larger (57 +/- 4%) compared with lean controls (37 +/- 4%, p < 0.05). In FF-3 rats, infarct size was also decreased (20 +/- 2%, p < 0.01) compared with CON. This study suggests that fructose feeding affords protection against MI/R that is related to or mimics preconditioning. This protection is not consistent with other models of IR and is likely related to the fructose diet itself.


Synchronous development of HCC and CCC in the same subsegment of the liver in a patient with type C liver cirrhosis.
As a result of having undergone computed tomography (CT), a 75-year-old woman with type-C liver cirrhosiswas shown to have two tumors on the ventral and dorsal sides of subsegment 3 (S3). The tumor on the ventral side was diagnosed as a classic hepatocellular carcinoma (HCC), while that on the dorsal side was considered atypical for a HCC. Although the indocyanine green (ICG) findings indicated poor hepatic reserve, the prothrombin time (PT) was relatively good. An operation was performed in February 2007; however, this resulted in exploratory laparotomy. Dynamic CT performed 12 mo after the operation revealed that the tumor on the dorsal side of S3 had apparently increased. The marginal portion of the tumor was shown to be in the early and parenchymal phases, while the internal portion was found to have grown only slightly in the delayed phase. We diagnosed this tumor as a cholangiocellular carcinoma (CCC). S3 subsegmentectomy was performed in April 2008. The tumor on the ventral side was pathologically diagnosed as a moderately differentiated HCC, and that on the dorsal side was diagnosed as a CCC. We can therefore report a rare case of synchronous development of HCC and CCC in the same subsegment of the liver in a patient with type-C liver cirrhosis. We also add a literature review for all the reported cases published in Japan and around the world, and summarize the features of double cancer exhibiting both HCC and CCC.


Combining a clinical ladder and performance appraisal system as a reward strategy: the EXCEL clinical ladder program.
In response to the dramatic changes occurring in health care today and a desire to reward professional nurses for clinical behaviors that would be valued in the future, Bergan Mercy Medical Center (BMMC) has developed an innovative clinical ladder/performance appraisal system. The BMMC EXCEL Clinical Ladder program, which is based on the developmental model of Patricia Benner, is a competency-based system that uniquely combines a clinical ladder and performance appraisal system. The program is clinically focused and contains optional components in which registered nurses (RNs) can receive additional credit for participation in professional growth and leadership activities. Nurses document examples of their practice through nursing narratives that describe actual clinical situations. The development and implementation processes, challenges encountered, and recommendations for alternative approaches to the implementation of such a unique system are discussed.


Neurophamacology of yawning.
Yawning is a common behavioral event that is observed in humans, as well as other mammals, birds and reptiles. In humans, yawning often occurs just before bed and upon waking up, and is also associated with tedious or boring situations. Although the physiologic roles of yawning have yet to be fully elucidated, the past 50 years of research has led to a much greater understanding of the neuropharmacologic regulation of yawning. While many of the early studies concluded that yawning was primarily driven by changes in cholinergic neurotransmission, we now know that numerous neurotransmitters and neurohormones are involved in the mediation of yawning, including acetylcholine, dopamine, glutamate, serotonin, oxytocin, GABA, opioids, adrenergics, nitric oxide, as well as the proopiomelanocortin-derived peptides ACTH and alpha-MSH. Furthermore, antagonist interaction studies have clearly defined at least 3 distinct neural pathways involved in the induction of yawning, as well as the hierarchical order through which these different neurotransmitter systems interact to regulate yawning. The following sections will discuss the state of knowledge for each of the major neurotransmitters and neurohormones involved in the regulation of yawning, their interactions with one another, and their place in the hierarchical organization of yawning.


Acidosis promotes invasiveness of breast cancer cells through ROS-AKT-NF-κB pathway.
It is well known that acidic microenvironment promotes tumorigenesis, however, the underlying mechanism remains largely unknown. In the present study, we show that acidosis promotes invasiveness of breast cancer cells through a series of signaling events. First, our study indicates that NF-κB is a key factor for acidosis-induced cell invasion. Acidosis activates NF-κB without affecting STAT3 activity; knockdown of NF-κB p65 abrogates the acidosis-induced invasion activity. Next, we show that the activation of NF-κB is mediated through phosphorylation and degradation of IκBα; and phosphorylation and nuclear translocation of p65. Upstream to NF-κB signaling, AKT is activated under acidic conditions. Moreover, acidosis induces generation of reactive oxygen species (ROS) which can be suppressed by ROS scavengers, reversing the acidosis-induced activation of AKT and NF-κB, and invasiveness. As a negative regulator of AKT, PTEN is oxidized and inactivated by the acidosis-induced ROS. Finally, inhibition of NADPH oxidase (NOX) suppresses acidosis-induced ROS production, suggesting involvement of NOX in acidosis-induced signaling cascade. Of considerable interest, acidosis-induced ROS production and activation of AKT and NF-κB can be only detected in cancer cells, but not in non-malignant cells. Together, these results demonstrate a cancer specific acidosis-induced signaling cascade in breast cancer cells, leading to cell invasion.


Extrachromosomal DNA (ecDNA) in cancer: mechanisms, functions, and clinical implications.
Extrachromosomal DNA (ecDNA) is circular DNA that plays an important role in the development and heterogeneity of cancer. The rapid evolution of methods to detect ecDNA, including microscopic and sequencing approaches, has greatly enhanced our knowledge of the role of ecDNA in cancer development and evolution. Here, we review the molecular characteristics, functions, mechanisms of formation, and detection methods of ecDNA, with a focus on the potential clinical implications of ecDNA in cancer. Specifically, we consider the role of ecDNA in acquired drug resistance, as a diagnostic and prognostic biomarker, and as a therapeutic target in the context of cancer. As the pathological and clinical significance of ecDNA continues to be explored, it is anticipated that ecDNA will have broad applications in the diagnosis, prognosis, and treatment of patients with cancer.


Herbal ephedra/caffeine for weight loss: a 6-month randomized safety and efficacy trial.
To examine long-term safety and efficacy for weight loss of an herbal Ma Huang and Kola nut supplement (90/192 mg/day ephedrine alkaloids/caffeine). Six-month randomized, double-blind placebo controlled trial. A total of 167 subjects (body mass index (BMI) 31.8+/-4.1 kg/m(2)) randomized to placebo (n=84) or herbal treatment (n=83) at two outpatient weight control research units. Primary outcome measurements were changes in blood pressure, heart function and body weight. Secondary variables included body composition and metabolic changes. By last observation carried forward analysis, herbal vs placebo treatment decreased body weight (-5.3+/-5.0 vs. -2.6+/-3.2 kg, P<0.001), body fat (-4.3+/-3.3 vs. -2.7+/-2.8 kg, P=0.020) and LDL-cholesterol (-8+/-20 vs. 0+/-17 mg/dl, P=0.013), and increased HDL-cholesterol (+2.7+/-5.7 vs. -0.3+/-6.7 mg/dl, P=0.004). Herbal treatment produced small changes in blood pressure variables (+3 to -5 mm Hg, P< or =0.05), and increased heart rate (4+/-9 vs. -3+/-9 bpm, P<0.001), but cardiac arrhythmias were not increased (P>0.05). By self-report, dry mouth (P<0.01), heartburn (P<0.05), and insomnia (P<0.01) were increased and diarrhea decreased (P<0.05). Irritability, nausea, chest pain and palpitations did not differ, nor did numbers of subjects who withdrew. In this 6-month placebo-controlled trial, herbal ephedra/caffeine (90/192 mg/day) promoted body weight and body fat reduction and improved blood lipids without significant adverse events.


Production of monozygotic (identical) horse twins by embryo micromanipulation.
The blastomeres of 192- to 8-cell embryos recovered surgically 1-3 days after ovulation from 23 Pony mares were mechanically separated and inserted, in various combinations, into evacuated pig zonae pellucidae to make 27 'half' and 17 'quarter' micromanipulated embryos. These were embedded in agar and cultured in vivo in the ligated oviducts of ewes for 3.5-5 days to allow development to the late morula/early blastocyst stage. Subsequent surgical or non-surgical transfer of 13 'half' and 17 'quarter' embryos to mares resulted in 10 established pregnancies, including 2 monozygotic pairs. Surgical transfer to mares that had not been recently used as donors of embryos was more successful (10/20) than surgical or non-surgical transfer to recently operated mares (0/10).


Spatial heterogeneity of autoinducer regulation systems.
Autoinducer signals enable coordinated behaviour of bacterial populations, a phenomenon originally described as quorum sensing. Autoinducer systems are often controlled by environmental substances as nutrients or secondary metabolites (signals) from neighbouring organisms. In cell aggregates and biofilms gradients of signals and environmental substances emerge. Mathematical modelling is used to analyse the functioning of the system. We find that the autoinducer regulation network generates spatially heterogeneous behaviour, up to a kind of multicellularity-like division of work, especially under nutrient-controlled conditions. A hybrid push/pull concept is proposed to explain the ecological function. The analysis allows to explain hitherto seemingly contradicting experimental findings.


Effect of nilvadipine on high-voltage activated Ca2+ channels in rat CNS neurons.
The effect of nilvadipine, a dihydropyridine derivative, on high-voltage activated (HVA) Ca2+ channels was investigated in freshly dissociated rat frontal cortical neurons. The cortical neurons were observed to have five pharmacologically distinct HVA Ca2+ channel subtypes consisting of the L-, N-, P-, O- and R-types. Nilvadipine selectively inhibited the L-type Ca2+ channel current which comprised 23% of the total HVA Ca2+ channel current. A reversible inhibitory effect of nilvadipine on the L-type Ca2+ channel current was also observed in a concentration-dependent fashion without affecting the current-voltage relationship. The half-maximum inhibitory concentration was 3 x 10(-8) M. These results suggest that the inhibitory effect of nilvadipine on the neuronal Ca2+ influx, in combination with the cerebral vasodilatory action, may prevent neuronal damage during brain ischemia.


[Osteocalcin in chronic alcoholism].
In order to investigate the mechanism by which the inorganic content of the bone is reduced in chronic alcoholism, the authors assayed osteocalcin in 60 chronic alcoholics. The level was significantly lower than in control subjects. There was no significant difference between levels in cirrhotics and in non-cirrhotic alcoholics. There was a negative correlation between osteocalcin and gamma GT levels. There was no correlation between osteocalcin and blood calcium, blood phosphorus, ALAT, ASAT, alkaline phosphatase, 5'-nucleotidase, albumin or bilirubin levels, or with the prothrombin time. These results suggest a direct impact of alcohol on the osteoblast.


Magnetic iron oxide nanoparticles as drug carriers: clinical relevance.
Significant preclinical and clinical research has explored the use of magnetic iron oxide nanoparticles (MNPs) for medical theranostics. Herein, we provide an overview of the optimal 'design-to-perform' MNPs used in cancer therapeutics, specifically focusing on magnetic hyperthermia, magnetic drug targeting, and targeting delivery. An account of the progress made in the clinic using MNPs is then analyzed. We place special emphasis on past and present magnetic nanoformulations used in clinical settings or yet to be clinically approved. Regrettably, as of now, no MNP drug delivery system is employed in the clinic. Thus, identifying current limitations, misconceptions and challenges will definitely impact the clinical success of MNP delivery theranostic systems and their promising future potential in medicine.


Leukemia in Olmsted County, Minnesota, 1965--1974.
Extending a study of the period 1935-1964, we determined the incidence rates of leukemia in Olmsted County during the decade 1965-1974. In this decade, the overall crude annual incidence rate was 9.5 per 100,000. The ratio of males to females was 2.4 to 1; and the incidence rate was significantly higher among males than among females, especially in the older age groups. Adjusted for age and sex, the mean annual incidence rate among males (17.3) was significantly higher than rates reported previously from other areas (ranging from 10.7 to 13); and it had increased significantly during the 40 years 1935-1974 in Olmsted County. The increase was most prominent in males aged 50 and over, and was detectable only in the subgroup with acute myelocytic leukemia. The observed number of farmers (8) was significantly higher than expected (2.8).