Prior transurethral resection does not increase morbidity following real-time ultrasound-guided prostate seed implantation.
Patients with localized prostate cancer who had a prior open prostatectomy or transurethral resection of the prostate (TURP) for benign prostatic hyperplasia (BPH) may be at risk for greater morbidity when treated with brachytherapy. This analysis examines the morbidity following brachytherapy using the real-time method to determine if patients with a history of TURP are at increase risk for developing complications. An ultrasound-guided transperineal interactive prostate seed was implanted in 419 patients with T1-T2 prostate cancer. All patients were implanted using a peripheral weighting of sources (75%) with the interior sources placed at least 5 mm from the urethra. The patients were divided into two groups: group 1 consisted of 376 patients (89.7%) without a prior TURP, and group 2 consisted of 43 patients (10.3%) who had a TURP prior to their implant. The mean age, prostate-specific antigen level, Gleason score, clinical stage, prostate volume, isotope implanted, and number of patients treated with neoadjuvant hormone therapy were comparable for both groups. Median follow-up for group 1 was 12 months and for group 2 was 18 months. No patients suffered from radiation-related proctitis or cystitis in either group of patients. Two patients in group 2 implanted with iodine 125 and who had a history of two prior TURPs developed mild superficial urethral necrosis (SUN). The actuarial freedom from developing superficial urethral necrosis at 4 years was 84% in patients with a history of prior TURP. There were no episodes of SUN in group 1 and no cases of incontinence reported in either group of patients. The actuarial rate of potency was 78% at 2 years. Whereas other techniques of seed implantation report incontinence in patients who had a prior open prostatectomy or TURP, the real-time method combined with peripheral loading avoids this complication.


Reduced-intensity allogeneic hematopoietic stem cell transplantation for relapsed multiple myeloma.
Despite recent advances, multiple myeloma (MM) remains incurable, and most patients eventually develop progressive disease. Allogeneic hematopoietic stem cell transplantation (allo-HSCT) offers a potentially curative option in 10%-20% of patients with relapsed or refractory disease. We evaluated the outcome of patients undergoing allo-HSCT with reduced-intensity conditioning (RIC) for relapsed and/or refractory MM at our institution. The study cohort included 51 patients with heavily pretreated, relapsed MM who underwent RIC allo-HSCT between 1996 and 2006. The median time from diagnosis to allo-HSCT was 34 months, and median follow-up in surviving patients was 27 months (range, 3-98 months). Cumulative transplantation-related mortality at 1 year was 25%. Progression-free survival (PFS) and overall survival (OS) at 2 years were 19% and 32%, respectively. The incidences of grade II-IV acute and chronic graft-versus-host disease were 27% and 47%, respectively. At the time of this analysis, 12 patients (24%) were alive, 7 of whom (14%) were in remission for up to 6 years after allo-HSCT. A lower beta2 microglobulin level (<3.3) and previous autologous HSCT were predictive of lower nonrelapse mortality and longer PFS and OS. Our findings indicate that allo-HSCT with RIC is associated with acceptable toxicity and durable remission and survival in relapsed or refractory MM. The use of RIC allo-HSCT earlier in the course of the disease may offer the greatest benefit.


What does tuberculin reactivity after bacille Calmette-Guérin vaccination tell us?
The effect of bacille Calmette-Guérin (BCG) vaccination on tuberculin reactivity is briefly reviewed. BCG vaccination will almost invariably result in tuberculin conversion with a positive tuberculin skin test developing 4-8 weeks after vaccination. However, these tuberculin reactions will wane-rapidly in all individuals who receive the vaccine in the neonatal period and more slowly in those who are vaccinated at an older age such as during the primary-school years. Of BCG vaccine recipients whose initial tuberculin skin test is negative, 10%-25% will have a positive tuberculin skin test if they are retested within 1-4 weeks-the so-called "booster phenomenon. " There is no relationship between tuberculin reactivity after BCG vaccination and the protective efficacy of the vaccine against development of active tuberculosis. Therefore, the ideal BCG vaccine would produce a scar at the site of injection to identify individuals who have been vaccinated but would have no effect on tuberculin reactivity.


Review of Canadian trials of adjuvant endocrine therapy for breast cancer.
Adjuvant ovarian ablation delays recurrence and prolongs survival in premenopausal patients with breast cancer, but the differences fall short of statistical significance; this effect is enhanced to statistically significant differences by low-dose prednisone. Adjuvant tamoxifen has delayed recurrence in post-menopausal patients with steroid receptor-positive tumors and positive axillary nodes, but, to date, has not affected survival.


Decision aids to help older people make health decisions: a systematic review and meta-analysis.
Decision aids have been overall successful in improving the quality of health decision making. However, it is unclear whether the impact of the results of using decision aids also apply to older people (aged 65+). We sought to systematically review randomized controlled trials (RCTs) and clinical controlled trials (CCTs) evaluating the efficacy of decision aids as compared to usual care or alternative intervention(s) for older adults facing treatment, screening or care decisions. A systematic search of (1) a Cochrane review of decision aids and (2) MEDLINE, Embase, PsycINFO, Cochrane library central registry of studies and Cinahl. We included published RCTs/CCTs of interventions designed to improve shared decision making (SDM) by older adults (aged 65+) and RCTs/CCTs that analysed the effect of the intervention in a subgroup with a mean age of 65+. Based on the International Patient Decision aid Standards (IPDAS), the primary outcomes were attributes of the decision and the decision process. Other behavioral, health, and health system effects were considered as secondary outcomes. If data could be pooled, a meta-analysis was conducted. Data for which meta-analysis was not possible were synthesized qualitatively. The search strategy yielded 11,034 references. After abstract and full text screening, 22 papers were included. Decision aids performed better than control resp. usual care interventions by increasing knowledge and accurate risk perception in older people (decision attributes). With regard to decision process attributes, decision aids resulted in lower decisional conflict and more patient participation. This review shows promising results on the effectiveness of decision aids for older adults. Decision aids improve older adults' knowledge, increase their risk perception, decrease decisional conflict and seem to enhance participation in SDM. It must however be noted that the body of literature on the effectiveness of decision aids for older adults is still in its infancy. Only one decision aid was specifically developed for older adults, and the mean age in most studies was between 65 and 70, indicating that the oldest-old were not included. Future research should expand on the design, application and evaluation of decision aids for older, more vulnerable adults.


Understanding comorbidity of anxiety disorders with antisocial behavior: findings from two large community surveys.
Although a positive association between antisocial behavior and anxiety disorders may seem clinically counterintuitive, some previous studies have in fact found a higher co-occurrence of anxiety disorders and antisocial behavior than in the general population. We investigated the relationship between anxiety disorders and antisocial behavior in two contemporaneous community surveys (National Comorbidity Survey, Ontario Health Survey). A significant association was found between any DSM-III-R anxiety disorder diagnosis and any DSM-III-R antisocial diagnosis (National Comorbidity Survey, odds ratio = 3.05, p <.01; Ontario Health Survey, odds ratio = 2.37, p <.01). This association remained significant after controlling for sociodemographics, depression, and alcohol and drug use disorders. Posttraumatic stress disorder and social phobia complex subtype (i.e., multiple social fears) produced the largest odds ratios. People with comorbid anxiety and antisocial diagnoses displayed high levels of distress, neuroticism, and disability, and poor quality of life. Clinicians and health policy makers need to be aware of the co-occurrence of anxiety disorders and antisocial behavior.


Incidence and clinical manifestations of rheumatic fever: a 6 year community-based survey.
Most data on the incidence of rheumatic fever come from hospital records. We presumed that there may be cases of RF that do not require hospitalization, especially in countries with high quality community health care. To explore the incidence and characteristics of RF using community-based data. A retrospective descriptive study was conducted among the members (more than 450,000) of the Clalit Health Services, Central district, during 2000-2005. The electronic medical files of members up to 40 years old with a diagnosis of RF in hospital discharge letters or during community clinic visits were retrieved. Patients with a first episode of RF according to the modified Jones criteria were included. There were 44 patients with a first episode of RF. All patients were under the age of 29. The annual incidence among patients aged 0-30 years was 3.2:100,000; the highest incidence was among children aged 5-14 years (7.5:100,000), and in males the incidence was 2.26 times higher than in females. The incidence was higher among patients from large families, of non-Jewish ethnicity, and from rural areas. Twenty-five percent of the patients were both diagnosed and treated in an ambulatory care setting. Although the incidence of RF in the western world and in Israel is low, the disease still occurs and mainly affects children. Any future estimates of disease incidence should take into account that RF is becoming an ambulatorily treated disease.


Diversity and evolution of TIR-domain-containing proteins in bivalves and Metazoa: New insights from comparative genomics.
The Toll/interleukin-1 receptor (TIR) domain has a fundamental role in the innate defence response of plants, vertebrate and invertebrate animals. Mostly found in the cytosolic side of membrane-bound receptor proteins, it mediates the intracellular signalling upon pathogen recognition via heterotypic interactions. Although a number of TIR-domain-containing (TIR-DC) proteins have been characterized in vertebrates, their evolutionary relationships and functional role in protostomes are still largely unknown. Due to the high abundance and diversity of TIR-DC proteins in bivalve molluscs, we investigated this class of marine invertebrates as a case study. The analysis of the available genomic and transcriptomic data allowed the identification of over 400 full-length sequences and their classification in protein families based on sequence homology and domain organization. In addition to TLRs and MyD88 adaptors, bivalves possess a surprisingly large repertoire of intracellular TIR-DC proteins, which are conserved across a broad range of metazoan taxa. Overall, we report the expansion and diversification of TIR-DC proteins in several invertebrate lineages and the identification of many novel protein families possibly involved in both immune-related signalling and embryonic development.


Beneficial effects of nitric oxide breathing in adult patients with sickle cell crisis.
Pain from vaso-occlusive crisis (VOC) is the major cause of hospitalization in patients with sickle cell disease (SCD). The beneficial therapeutic effects of inhaled nitric oxide (NO) on the pathophysiology of SCD have been reported. A double-blind, randomized, placebo-controlled clinical trial was conducted to determine whether NO breathing reduces acute VOC pain in adult patients and to study the safety of inhaled NO. Twenty-three patients experiencing acute VOC were enrolled. After randomization but before treatment, five were found to not meet final eligibility criteria. Nine patients were assigned to inhaled NO (80 ppm) and nine to placebo (21% O2). Primary outcome was the mean change in pain scores after 4 hr of inhalation, measured on a 10-cm visual analog scale (VAS). Both groups had similar baseline VAS pain scores but inhaled NO significantly reduced pain scores compared with placebo (P 5 0.02) at the end of NO inhalation. Secondary outcome was parenteral morphine use at baseline, 4, and 6 hr. Parenteral morphine use was lower in the inhaled NO group, but the difference was not statistically significant.Safety assessments included systolic blood pressure measurements,pulse oximetry readings, concentration of delivered nitrogen dioxide, and concentration of methemoglobin (metHb). None of these NO toxicities was observed.


Laser resurfacing for dermal photoaging.
The skin is a highly organized system composed of resident cells, extracellular matrix, blood vessels, and circulating cells that all work together to maintain cutaneous integrity. Environmental insults, particularly sunlight, act to alter the skin permanently, producing visibly undesirable effects. By wounding the skin or inducing a healing response with minimal wounding, the repair process can be activated to return the skin to a more normal condition. Owing to the complexity of the healing response, even the most well-studied and precise laser system can result in unpredicted results when used to treat photo-damaged skin. Through continued research into the normal functioning of skin, the alterations brought about by chronic photodamage, and the repair process, an integrated approach to treatment of photoaging will evolve. Agents such as alpha-hydroxy acids, retinoids, and growth factors that impact the healing response can be combined with various lasers to optimize improvement of photo-damaged skin, while minimizing the adverse consequences of treatment.


Microbeam synchrotron imaging of hairs from ancient Egyptian mummies.
Developments in microfocus synchrotron techniques have led to new results regarding the long-term alteration of archaeological samples of biological origin. Here, ancient hair samples from two Egyptian mummies have been analyzed using a conjunction of structural and elemental synchrotron methods. In this favored context of conservation, structural analysis revealed a remarkable preservation of keratin supramolecular organization at any observed length scale. Bulk keratin structure has therefore not been modified significantly over 2000 years. However, infrared spectroscopy indicated a partial disorganization of keratins close to the hair surface through polypeptide bond breakage. Elemental mapping showed a strongly heterogeneous distribution which can be related to mummification and cosmetic treatments.


Delineating FOXG1 syndrome: From congenital microcephaly to hyperkinetic encephalopathy.
To provide new insights into the FOXG1-related clinical and imaging phenotypes and refine the phenotype-genotype correlation in FOXG1 syndrome. We analyzed the clinical and imaging phenotypes of a cohort of 45 patients with a pathogenic or likely pathogenic FOXG1 variant and performed phenotype-genotype correlations. A total of 37 FOXG1 different heterozygous mutations were identified, of which 18 are novel. We described a broad spectrum of neurodevelopmental phenotypes, characterized by severe postnatal microcephaly and developmental delay accompanied by a hyperkinetic movement disorder, stereotypes and sleep disorders, and epileptic seizures. Our data highlighted 3 patterns of gyration, including frontal pachygyria in younger patients (26.7%), moderate simplified gyration (24.4%) and mildly simplified or normal gyration (48.9%), corpus callosum hypogenesis mostly in its frontal part, combined with moderate-to-severe myelination delay that improved and normalized with age. Frameshift and nonsense mutations in the N-terminus of FOXG1, which are the most common mutation types, show the most severe clinical features and MRI anomalies. However, patients with recurrent frameshift mutations c.460dupG and c.256dupC had variable clinical and imaging presentations. These findings have implications for genetic counseling, providing evidence that N-terminal mutations and large deletions lead to more severe FOXG1 syndrome, although genotype-phenotype correlations are not necessarily straightforward in recurrent mutations. Together, these analyses support the view that FOXG1 syndrome is a specific disorder characterized by frontal pachygyria and delayed myelination in its most severe form and hypogenetic corpus callosum in its milder form.


Post-acute effects of SARS-CoV-2 infection in individuals not requiring hospital admission: a Danish population-based cohort study.
Individuals admitted to hospital for COVID-19 might have persisting symptoms (so-called long COVID) and delayed complications after discharge. However, little is known regarding the risk for those not admitted to hospital. We therefore examined prescription drug and health-care use after SARS-CoV-2 infection not requiring hospital admission. This was a population-based cohort study using the Danish prescription, patient, and health insurance registries. All individuals with a positive or negative RT-PCR test for SARS-CoV-2 in Denmark between Feb 27 and May 31, 2020, were eligible for inclusion. Outcomes of interest were delayed acute complications, chronic disease, hospital visits due to persisting symptoms, and prescription drug use. We used data from non-hospitalised SARS-CoV-2-positive and matched SARS-CoV-2-negative individuals from 2 weeks to 6 months after a SARS-CoV-2 test to obtain propensity score-weighted risk differences (RDs) and risk ratios (RRs) for initiation of 14 drug groups and 27 hospital diagnoses indicative of potential post-acute effects. We also calculated prior event rate ratio-adjusted rate ratios of overall health-care use. This study is registered in the EU Electronic Register of Post-Authorisation Studies (EUPAS37658). 10 498 eligible individuals tested positive for SARS-CoV-2 in Denmark from Feb 27 to May 31, 2020, of whom 8983 (85·6%) were alive and not admitted to hospital 2 weeks after their positive test. The matched SARS-CoV-2-negative reference population not admitted to hospital consisted of 80 894 individuals. Compared with SARS-CoV-2-negative individuals, SARS-CoV-2-positive individuals were not at an increased risk of initiating new drugs (RD <0·1%) except bronchodilating agents, specifically short-acting β2-agonists (117 [1·7%] of 6935 positive individuals vs 743 [1·3%] of 57 206 negative individuals; RD +0·4% [95% CI 0·1-0·7]; RR 1·32 [1·09-1·60]) and triptans (33 [0·4%] of 8292 vs 198 [0·3%] of 72 828; RD +0·1% [0·0-0·3]; RR 1·55 [1·07-2·25]). There was an increased risk of receiving hospital diagnoses of dyspnoea (103 [1·2%] of 8676 vs 499 [0·7%] of 76 728; RD +0·6% [0·4-0·8]; RR 2·00 [1·62-2·48]) and venous thromboembolism (20 [0·2%] of 8785 vs 110 [0·1%] of 78 872; RD +0·1% [0·0-0·2]; RR 1·77 [1·09-2·86]) for SARS-CoV-2-positive individuals compared with negative individuals, but no increased risk of other diagnoses. Prior event rate ratio-adjusted rate ratios of overall general practitioner visits (1·18 [95% CI 1·15-1·22]) and outpatient hospital visits (1·10 [1·05-1·16]), but not hospital admission, showed increases among SARS-CoV-2-positive individuals compared with SARS-CoV-2-negative individuals. The absolute risk of severe post-acute complications after SARS-CoV-2 infection not requiring hospital admission is low. However, increases in visits to general practitioners and outpatient hospital visits could indicate COVID-19 sequelae. None.


Biosynthesis of silver nanoparticles from Trichoderma species.
A total of 75 isolates belonging to five different species of Trichoderma viz., T. asperellum, T. harzianum, T. longibrachiatum, T. pseudokoningii and T. virens were screened for the production of silver nanoparticles. Although all the isolates produced nanoparticles, T. virens VN-11 could produce maximum nanoparticles as evident from the UV-Vis study. The highest Plasmon band was observed at 420 nm at every 24 h that attained maximum intensity at 120 h (0.543). The high resolution transmission electron microscopy (HRTEM) further provided the morphology of the nanoparticles. These nanoparticles were found single or aggregated with round and uniform in shape and 8-60 nm in size. The nitrate reductase activity of VN-11 was found to be 150 nmol/h/mL which confirmed the production of silver nanoparticles through reduction of Ag+ to Ag0.


Identification of serum microRNAs predicting the response of esophageal squamous-cell carcinoma to nivolumab.
Nivolumab, a programmed cell death protein 1 (PD-1) inhibitor, showed promising activity for the treatment of advanced esophageal squamous-cell carcinoma in a phase II study (ONO-4538-07; JapicCTI-No.142422). We explored serum microRNA (miRNA) candidate predictive markers of the response to nivolumab. In the phase II study, 19 patients received nivolumab (3 mg/kg IV Q2W) at National Cancer Center Hospital. The expression of 2565 serum miRNAs before and during treatment was analyzed using a 3D-Gene Human miRNA Oligo Chip (Toray Industries, Inc.). Immune-related response evaluation criteria used to evaluate response and miRNA expression were compared between responders and non-responders. The top 20 miRNAs by accuracy in receiver operating characteristic curve analysis were identified by leave-one-out cross-validation, and those with the area under curve values > 0.8, cross-validated accuracy > 0.8, and a 0.5 difference in the average log2 expression level between responders and non-responders were further analyzed. Of the 19 patients, five responded to nivolumab. We identified miRNAs related to the response to nivolumab, including one detected in the serum before treatment (miR-1233-5p; AUC = 0.895) and three present after treatment (miR-6885-5p, miR-4698 and miR-128-2-5p; AUC = 0.93, 0.97 and 0.93, respectively). Candidate miRNAs capable of predicting the response to nivolumab were identified in the serum of patients with advanced esophageal squamous-cell carcinoma in ONO-4538-07.


Population dynamics of a dual Pseudomonas putida-Pseudomonas fluorescens biofilm in a capillary bioreactor.
Most biofilm studies employ single species, yet in nature biofilms exist as mixed cultures, with inevitable effects on growth and development of each species present. To investigate how related species of bacteria interact in biofilms, two Pseudomonas spp., Pseudomonas fluorescens and Pseudomonas putida, were cultured in capillary bioreactors and their growth measured by confocal microscopy and cell counting. When inoculated in pure culture, both bacteria formed healthy biofilms within 72 h with uniform coverage of the surface. However, when the bioreactors were inoculated with both bacteria simultaneously, P. putida was completely dominant after 48 h. Even when the inoculation by P. putida was delayed for 24 h, P. fluorescens was eliminated from the capillary within 48 h. It is proposed that production of the lipopeptide putisolvin by P. putida is the likely reason for the reduction of P. fluorescens. Putisolvin biosynthesis in the dual-species biofilm was confirmed by mass spectrometry.


Integrated genomic and BMI analysis for type 2 diabetes risk assessment.
Type 2 Diabetes (T2D) is a chronic disease arising from the development of insulin absence or resistance within the body, and a complex interplay of environmental and genetic factors. The incidence of T2D has increased throughout the last few decades, together with the occurrence of the obesity epidemic. The consideration of variants identified by Genome Wide Association Studies (GWAS) into risk assessment models for T2D could aid in the identification of at-risk patients who could benefit from preventive medicine. In this study, we build several risk assessment models, evaluated with two different classification approaches (Logistic Regression and Neural Networks), to measure the effect of including genetic information in the prediction of T2D. We used data from to the Original and the Offspring cohorts of the Framingham Heart Study, which provides phenotypic and genetic information for 5245 subjects (4306 controls and 939 cases). Models were built by using several covariates: gender, exposure time, cohort, body mass index (BMI), and 65 SNPs associated to T2D. We fitted Logistic Regressions and Bayesian Regularized Neural Networks and then assessed their predictive ability by using a ten-fold cross validation. We found that the inclusion of genetic information into the risk assessment models increased the predictive ability by 2%, when compared to the baseline model. Furthermore, the models that included BMI at the onset of diabetes as a possible effector, gave an improvement of 6% in the area under the curve derived from the ROC analysis. The highest AUC achieved (0.75) belonged to the model that included BMI, and a genetic score based on the 65 established T2D-associated SNPs. Finally, the inclusion of SNPs and BMI raised predictive ability in all models as expected; however, results from the AUC in Neural Networks and Logistic Regression did not differ significantly in their prediction accuracy.


Changes in disease burden in Poland between 1990-2017 in comparison with other Central European countries: A systematic analysis for the Global Burden of Disease Study 2017.
Systematic collection of mortality/morbidity data over time is crucial for monitoring trends in population health, developing health policies, assessing the impact of health programs. In Poland, a comprehensive analysis describing trends in disease burden for major conditions has never been published. The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) provides data on the burden of over 300 diseases in 195 countries since 1990. We used the GBD database to undertake an assessment of disease burden in Poland, evaluate changes in population health between 1990-2017, and compare Poland with other Central European (CE) countries. The results of GBD 2017 for 1990 and 2017 for Poland and CE were used to assess rates and trends in years of life lost (YLLs), years lived with disability (YLDs), disability-adjusted life years (DALYs). Data came from cause-of-death registration systems, population health surveys, disease registries, hospitalization databases, and the scientific literature. Analytical approaches have been used to adjust for missing data, errors in cause-of-death certification, and differences in data collection methodology. Main estimation strategies were ensemble modelling for mortality and Bayesian meta-regression for disability. Between 1990-2017, age-standardized YLL rates for all causes declined in Poland by 46.0% (95% UI: 43.7-48.2), YLD rates declined by 4.0% (4.2-4.9), DALY rates by 31.7% (29.2-34.4). For both YLLs and YLDs, greater relative declines were observed for females. There was a large decrease in communicable, maternal, neonatal, and nutritional disease DALYs (48.2%; 46.3-50.4). DALYs due to non-communicable diseases (NCDs) decreased slightly (2.0%; 0.1-4.6). In 2017, Poland performed better than CE as a whole (ranked fourth for YLLs, sixth for YLDs, and fifth for DALYs) and achieved greater reductions in YLLs and DALYs than most CE countries. In 2017 and 1990, the leading cause of YLLs and DALYs in Poland and CE was ischaemic heart disease (IHD), and the leading cause of YLDs was low back pain. In 2017, the top 20 causes of YLLs and YLDs in Poland and CE were the same, although in different order. In Poland, age-standardized DALYs from neonatal causes, other cardiovascular and circulatory diseases, and road injuries declined substantially between 1990-2017, while alcohol use disorders and chronic liver diseases increased. The highest observed-to-expected ratios were seen for alcohol use disorders for YLLs, neonatal sepsis for YLDs, and falls for DALYs (3.21, 2.65, and 2.03, respectively). There was relatively little geographical variation in premature death and disability in CE in 2017, although some between-country differences existed. Health in Poland has been improving since 1990; in 2017 Poland outperformed CE as a whole for YLLs, YLDs, and DALYs. While the health gap between Poland and Western Europe has diminished, it remains substantial. The shift to NCDs and chronic disability, together with marked between-gender health inequalities, poses a challenge for the Polish health-care system. IHD is still the leading cause of disease burden in Poland, but DALYs from IHD are declining. To further reduce disease burden, an integrated response focused on NCDs and population groups with disproportionally high burden is needed.


Foreign bodies in the pediatric age: the experience of an Italian tertiary care hospital.
Foreign bodies in pediatric age represent an extremely frequent pathological condition and can undergo fearsome complications. Within the ENT area, foreign bodies in the pediatric age can be found in various districts such as external auditory canal, nasal passages, oral cavity, pharynx, larynx and trachea. They can be various and shape; generally, the main ones are buttons, beads, small parts of toys, caps of pens, pebbles, fragments of food bolus and others. As described in the literature, the main localizations are the external auditory canal and nasal cavities. Laryngeal and tracheal localization is infrequent but can be fatal. The aspiration of foreign bodies, mainly small parts of toys, occurs more frequently under three years age and mainly-especially in males. The experience of the ENT Department of the San Camillo-Forlanini Hospital in Rome, in the period between January 2007 and December 2018, consists a total of 1443 patients, aged between 0 and 14, who arrived in the emergency room with a foreign body diagnosis; of these, 613 (42.5%) were found with foreign body in the external auditory canal, 458 (31.7%) in nasal fossa, 298 (20.5%) in pharynx, 64 (4.4%) in oropharynx, and 10 (0.7%) in larynx and trachea. Treatment was in 1255 (87%) removal in the emergency room and home discharge, 79 (5.4%) with outpatient discharge, 40 (2.7%) need for hospitalization and surgery, 64 (4.4 %) refusal of hospitalization and 1 case (0.07%) died in the emergency room.


Understanding interpretive errors in radiologists learning computed tomography colonography.
To determine if interpretive errors in the course of learning CT colonography are secondary to failures in detection or in characterization and determine the types of lesions frequently missed. Fifteen radiologists completed an electronic CTC training module consisting of two parts: 1) a teaching file demonstrating the varied appearances of polyps, cancers, and pitfalls in interpreting exams; and 2) a test of 50 complete CTC datasets. Following review of each test case, radiologists were asked to indicate if and where a polyp was visualized. The module then showed each neoplasm (if any) located within the dataset. For false negative examinations, radiologists indicated if the lesion was not seen, was seen but interpreted as colonic wall or fold, or was seen but interpreted as stool or fluid. The average sensitivity for sessile, pedunculated, and flat polyps for these novice readers was 76%, 63%, and 32%, respectively. Average sensitivity for all morphologies of cancers (annular, polypoid, flat) was high (93%, 85%, 95%), with 8/11 missed cancers being secondary to failure in detection. The most frequently missed cancer was an annular constricting tumor (5/11). Overall, 55% (73/132) of errors were failures of detection and 45% (59/132) were errors in characterization. Radiologists learning CT colonography had slightly more errors of detection than characterization, but this difference was not statistically significant. Flat and pedunculated polyps and annular constricting cancers were the most frequently missed morphologies. Examples of these abnormalities should be emphasized in CTC training programs.


Immunity Impairment as a Result of Neurohormonal Disorders.
An important principle of psychoneuroimmunologic interaction is that immunocytes act as if they were mobile sensitive organs for the central nervous system, producing local and systemic neuropeptides and immunological transmitters with appropriate stimulation. They inform the brain of local damage and mobilize the neuroendocrine system for protection. Their list is long and continues to grow. It includes: somatostatin, vasoactive intestinal peptide, thyroid stimulating hormone, human chorionic gonadotropin, follicle stimulating hormone, luteinizing hormone and other neurotransmitters and hormones, having immunomodulating properties. This may indicate to close interaction between the immune and neuroendocrine systems, which may be involved into the disease process. A bright example of this may be a disease that has not been closely studied in our country, but is widespread throughout the world. This is the chronic fatigue syndrome, at the base of which lie disturbances of the central nervous, endocrine and immune systems. The idea that the chronic fatigue syndrome is a disturbance of the production of cytokines is related to a number of disturbances in the T system of immunity. It was found back in 1987-1988 that there is an increase in the level of HLA DR and IL-2 receptors and an increase in the ratio CD4/CD8 in patients suffering from this syndrome.


Twisted Light-Enhanced Photovoltaic Effect.
Twisted light carries a defined orbital angular momentum (OAM) that can enhance forbidden transitions in atoms and even semiconductors. Such attributes can possibly lead to enhancements of the material's photogenerated carriers through improved absorption of incident light photons. The interaction of twisted light and photovoltaic material is, thus, worth studying as more efficient photovoltaic cells are essential these days due to the need for reliable and sustainable energy sources. Two-dimensional (2D) MoS2, with its favorable optoelectronic properties, is a good platform to investigate the effects of twisted light on the photon absorption efficiency of the interacting material. This work, therefore, used twisted light as the exciting light source onto a MoS2 photovoltaic device. We observed that while incrementing the incident light's quantized OAM at fixed optical power, there are apparent improvements in the device's open-circuit voltage (VOC) and short-circuit current (ISC), implying enhancements of the photoresponse. We attribute these enhancements to the OAM of light that has facilitated improved optical absorption efficiency in MoS2. This study proposes a way of unlocking the potentials of 2D-MoS2 and envisions the employment of light's OAM for future energy device applications.


Comparison of logistic EuroSCORE and EuroSCORE II in predicting operative mortality of 1125 total arterial operations.
The purpose of this study was to compare effectiveness of the 1999 logistic EuroSCORE (LES) and of the 2012 EuroSCORE II (ESII) in a real-world patient population of 1125 patients undergoing total arterial grafting (TAG) coronary artery bypass graft (CABG) surgery. The performance of the two risk scores was compared using (i) discrimination (accuracy of discriminating non-survivors from survivors), (ii) calibration (assessment of agreement between the predicted/observed outcomes) and (iii) agreement between the two scores. By averaging medians of LES and ESII and then sub-division into 10 equal groups, actual operative mortality rate was compared with the median LES and ESII within each risk group, the difference plotted against the average risk score (as in a Bland and Altman plot), and using the traditional risk groupings for EuroSCORE of low (0-2.99), medium (3-5.99) and high risk (6.0 and above), the reclassification rate of ESII was compared with that of LES. In 1125 consecutive total arterial CABG patients, demographics included: mean age 64.6 years, 79% males, 35% diabetic patients, 57% urgent/emergent patients, 37% off-pump and 77% bilateral mammary grafting. Overall operative mortality was 3.2% (36 patients). Comparison of the LES and ESII showed (i) good discrimination for both LES and ESII (area under the curve for LES was 0.85 and for ESII was 0.87); (ii) neither score was well calibrated: LES tended to overestimate and ESII underestimated risk. In general, the ESII provided a better estimate of risk in lower risk patients and LES was better for the highest risk group. (iii) In terms of agreement, in the lower four risk groups the risk was overestimated by both scores, in five of the higher six risk groups ESII underestimated risk and LES overestimated risk, and in the highest risk group LES was very close (17.2 cf. 17.7) compared with ESII (5.6 cf. 17.7). In addition, ESII downgraded risk in 96.8% of survivors and in 97.2% of non-survivors. In 1125 consecutive TAG CABG patients, neither LES nor ESII performed well enough to be used as a consistent risk stratification tool; LES overestimated risk but was highly accurate for the highest of 10 risk groups and ESII consistently underestimated risk in all patients.


Glycolipid transfer protein expression is affected by glycosphingolipid synthesis.
Members of the glycolipid transfer protein superfamily (GLTP) are found from animals and fungi to plants and red micro-alga. Eukaryotes that encode the glucosylceramide synthase responsible for the synthesis of glucosylceramide, the precursor for most glycosphingolipids, also produce GLTPs. Cells that does not synthesize glucosylceramide neither express GLTPs. Based on this genetic relationship there must be a strong correlation between the synthesis of glucosylceramide and GLTPs. To regulate the levels of glycolipids we have used inhibitors of intracellular trafficking, glycosphingolipid synthesis and degradation, and small interfering RNA to down-regulate the activity of glucosylceramide synthase activity. We found that GLTP expression, both at the mRNA and protein levels, is elevated in cells that accumulate glucosylceramide. Monensin and brefeldin A block intracellular vesicular transport mechanisms. Brefeldin A treatment leads to accumulation of newly synthesized glucosylceramide, galactosylceramide and lactosylceramide in a fused endoplasmic reticulum-Golgi complex. On the other hand, inhibiting glycosphingolipid degradation with conduritol-B-epoxide, that generates glucosylceramide accumulation in the lysosomes, did not affect the levels of GLTP. However, glycosphingolipid synthesis inhibitors like PDMP, NB-DNJ and myriocin, all decreased glucosylceramide and GLTP below normal levels. We also found that an 80% loss of glucosylceramide due to glucosylceramide synthase knockdown resulted in a significant reduction in the expression of GLTP. We show here that interfering with membrane trafficking events and simple neutral glycosphingolipid synthesis will affect the expression of GLTP. We postulate that a change in the glucosylceramide balance causes a response in the GLTP expression, and put forward that GLTP might play a role in lipid directing and sensing of glucosylceramide at the ER-Golgi interface.


Pharmacokinetics and biodistribution of the camptothecin-polymer conjugate IT-101 in rats and tumor-bearing mice.
IT-101 is a camptothecin-polymer conjugate prepared by linking camptothecin (CPT) to a hydrophilic, cyclodextrin-based, linear polymer through ester bonds. In previous studies, these polymer conjugates with high molecular weights (ca 90 kDa) have shown significant antitumor effects against human colon carcinoma xenografts. The pharmacokinetics of IT-101 in plasma of rats and its biodistribution in nude mice bearing human LS174T colon carcinoma tumors is reported here. Sprague-Dawley rats were injected intravenously with three different doses of IT-101. Serial plasma samples were analyzed for polymer-bound and unconjugated CPT by high-performance liquid chromatography (HPLC). Concentration vs time data were modeled using non-compartmentalized methods and compared to CPT alone injected intravenously at an equivalent dose. Tumor-bearing mice were injected intravenously with IT-101 and intraperitoneally with CPT alone, and sacrificed after 24 and 48 h, and serum, heart, liver, spleen, lungs and tumor collected. Tissue samples were extracted and analyzed for polymer-bound and unconjugated CPT by HPLC. Plasma concentrations and the area under the curve for polymer-bound CPT are approximately 100-fold higher than those of unconjugated CPT or CPT alone, injected intravenously at an equivalent dose. The plasma half-life of IT-101 ranges from 17 -20 h and is significantly greater than that of CPT alone (1.3 h). When CPT is conjugated to polymer, the biodistribution pattern of CPT is different from that taken alone. At 24 h post injection, the total CPT per gram of tissue is the highest in tumor tissue when compared to all other tissues tested. Tumor concentrations of active CPT released from the conjugate are more than 160-fold higher when administered as a polymer conjugate rather than as CPT alone. The studies presented here indicate that intravenous administration of IT-101, a cyclodextrin based polymer-CPT conjugate, gives prolonged plasma half-life and enhanced distribution to tumor tissue when compared to CPT alone. The data also show that active CPT is released from the conjugate within the tumor for an extended period of time. These effects likely play a significant role in the enhanced antitumor activity of IT-101 when compared to CPT alone or irinotecan.


American historical archeology: methods and results.
For historical archeology to be effective, research methods must be employed that ensure that both archeological and historical data be synthesized in a constructive manner. An example from Flowerdew Hundred, a Virginia plantation, illustrates such an approach. Collections from eighteen sites(1619 to 1720) were studied and dated by the inside bore diameters of pipestem fragments from clay smoking pipes. The sites grouped into three distinct categories, each with a different date. The latest group of sites (1680 to 1720) contained Colono ware, a slave produced pottery; none of the earlier sites did, although there were blacks at Flowerdew Hundred as early as 1619. On the basis of studies of probate data and other primary historical sources, it is suggested that this pattern of Colono ware occurrence is due to a change in the social and residential status of blacks during the century and that only when they lived separately from the masters did they make this type of pottery.


Collaborative mental health care for the homeless: the role of psychiatry in positive housing and mental health outcomes.
Factors associated with positive outcomes for homeless men referred to a shelter-based collaborative mental health care team were examined. A chart review of 73 clients referred over 12 months was completed. Two outcome measures were examined, clinical status and housing status, 6 months after their referral to the program. Among the referred clients, the prevalence of severe and persistent mental illness and substance use disorders was 76.5% and 48.5%, respectively. At 6 months, 24 clients (35.3%) had improved clinically, and 33 (48.5%) were housed. Logistic regression identified 2 factors associated with clinical improvement: the number of visits with a psychiatrist and treatment adherence. The same 2 factors were associated with higher odds of housing, and presence of substance use disorder was associated with lower odds of housing at 6-month follow-up. Care by a mental health specialist is positively associated with improved outcomes. Strategies to improve treatment adherence, access to mental health specialists, and innovative approaches to treatment of substance use disorders should be considered for this population. Having a psychiatrist as a member of a shelter-based collaborative care team is one possible way of addressing the complex physical and mental health needs of homeless individuals.


Spectral reflectance and emittance of particulate materials. 1: theory.
The infrared spectral reflectance of a semi-infinite medium composed of irregular particles of different materials is calculated in terms of the sizes, shapes, and complex refractive indices of the particles. For particles larger than the wavelength, the scattering and absorption are computed mainly by geometrical optics but with important wave-optical corrections for the additional absorption caused by edges and asperities, which are represented by dipoles distributed over the surface of the particle. For particles smaller than the wavelength, a Lorentz-Lorenz model is used to derive the average complex index of the medium, the particles being treated as ellipsoids with a wide range of shapes. The average scattering of an individual ellipsoidal particle is then found from the relative refractive index of the particle with respect to the Lorentz-Lorenz medium. For both large and small particles the single-particle scattering is represented by six discrete beams. Calculation of the reflectance is then facilitated by a radiative transfer method that also involves six beams. For particles of intermediate size a suitable formula bridging the results for large and small particles is found to be satisfactory.


Product delivery in the developing world: options, opportunities and threats.
While many developed countries are moving to recombinant coagulation factors as their preferred modality for delivering haemophilia care, the cost of these products currently impedes their access by developing countries. A number of options are available to these countries for the provision of plasma-derived therapeutic products. The decreasing market for plasma-derived coagulation factors in the developed world is leading to the generation of a surplus of these products and an ability to offer them outside their traditional markets if prices are affordable. Current indications are that the commercial fractionation industry of the developed world has an excess capacity in both available plasma and fractionation plants. It would seem that accessing this capacity might have attractions for the developing world. Countries wedded to achieving self-sufficiency in haemophilia products may elect to develop a strategy for fractionating domestically sourced plasma. This may be achieved by the generation of a capacity to fractionate within the country or by contracting the fractionation to an external agency overseas. However, reliance on domestic plasma should not be allowed to impede access to sufficient and safe coagulation products. Irrespective of the route chosen, products need to attain satisfactory compliance to standards for safety, quality and efficacy. This is best done through alignment of the products with the requirements of credible regulatory agencies. While the approval of the mainstream regulators of the developed world affords considerable assurance regarding product quality, the increasing efforts made by fractionation agencies in the developing world to attain best practice is commendable and augurs well for the enhancement of haemophilia care in these countries.


The return trip effect: why the return trip often seems to take less time.
Three studies confirm the existence of the return trip effect: The return trip often seems shorter than the initial trip, even though the distance traveled and the actual time spent traveling are identical. A pretest shows that people indeed experience a return trip effect regularly, and the effect was found on a bus trip (Study 1), a bicycle trip (Study 2), and when participants watched a video of someone else traveling (Study 3). The return trip effect also existed when another, equidistant route was taken on the return trip, showing that it is not familiarity with the route that causes this effect. Rather, it seems that a violation of expectations causes this effect.


An adaptable method using human mixed tissue ratiometric controls for benchmarking performance on gene expression microarrays in clinical laboratories.
Molecular biomarkers that are based on mRNA transcripts are being developed for the diagnosis and treatment of a number of diseases. DNA microarrays are one of the primary technologies being used to develop classifiers from gene expression data for clinically relevant outcomes. Microarray assays are highly multiplexed measures of comparative gene expression but have a limited dynamic range of measurement and show compression in fold change detection. To increase the clinical utility of microarrays, assay controls are needed that benchmark performance using metrics that are relevant to the analysis of genomic data generated with biological samples. Ratiometric controls were prepared from commercial sources of high quality RNA from human tissues with distinctly different expression profiles and mixed in defined ratios. The samples were processed using six different target labeling protocols and replicate datasets were generated on high density gene expression microarrays. The area under the curve from receiver operating characteristic plots was calculated to measure diagnostic performance. The reliable region of the dynamic range was derived from log(2) ratio deviation plots made for each dataset. Small but statistically significant differences in diagnostic performance were observed between standardized assays available from the array manufacturer and alternative methods for target generation. Assay performance using the reliable range of comparative measurement as a metric was improved by adjusting sample hybridization conditions for one commercial kit. Process improvement in microarray assay performance was demonstrated using samples prepared from commercially available materials and two metrics - diagnostic performance and the reliable range of measurement. These methods have advantages over approaches that use a limited set of external controls or correlations to reference sets, because they provide benchmark values that can be used by clinical laboratories to help optimize protocol conditions and laboratory proficiency with microarray assays.


Rapid procedure for the detection of acid and gas production by bacterial cultures.
A rapid miniaturized procedure, with a Microtiter plate and the Amojell-overlay technique, is described for the detection of acid and gas production by bacterial cultures.


Virome of Camellia japonica: Discovery of and Molecular Characterization of New Viruses of Different Taxa in Camellias.
Many species of the genus Camellia are native to China, and several species such as C. japonica have been cultivated as garden plants for over 1,000 years. Virus-like symptoms have been recorded for years. In this study, C. japonica plants with various leaf symptoms were observed in Jiangxi and Chongqing provinces. The species composition of potential viruses in the symptomatic plants was analyzed by next-generation sequencing of six libraries prepared from total RNAs of specimens from 10 trees. Five new viruses were discovered, and their genome sequences were determined. These viruses were tentatively named Camellia chlorotic ringspot viruses (CaCRSVs), Camellia yellow ringspot virus (CaYRSV), Camellia-associated badnavirus (CaBaV), and Camellia-associated marafivirus (CaMaV) based on comprehensive analyses. Among these viruses, CaYRSV, CaBaV, and CaMaV share similar genome organizations and clear sequence homology with known viruses in databases and could potentially be classified as new species of the genera Badnavirus, Idaeovirus, and Marafivirus, respectively. CaCRSVs comprise two distinct viruses, and each likely contains five genomic RNA segments that were found to be distantly related to viral RNAs of members in the genus Emaravirus (family Fimoviridae). The RNAs of CaCRSVs show conserved terminal sequences that differ markedly from those of emaraviral RNAs. These data, together with the phylogenetic analysis, suggest that the evolutionary status of CaCRSVs may represent a novel genus in the family Fimoviridae. In addition, two known viruses (geminivirus and blunervirus) and a mass of betaflexiviruses existing as heterogeneous mixtures were detected, and their roles in symptom formation were studied. Collectively, the information of the viral species and detection protocols that were developed can serve as a basis for better management of these viruses. Distinguishing the virus-related symptoms from genetic characteristics of C. japonica is also significant for breeding efforts.


Designing better adaptive sampling algorithms for ECG Holter systems.
Let psi be any adaptive sampling algorithm that can run in real time on a tapeless multichannel electrocardiogram (ECG) Holter system. Simple methods which can significantly improve psi's fidelity are described and their results are compared in this paper. It is shown that by adding some simple tests to psi, the signals reconstructed by psi can be improved as much as 5.45 dB. It is also shown that under the same data rate, a good data compressor with slowly sampled input ECG is preferable to a bad data compressor with highly sampled input ECG.


Screening for elevated levels of fear-avoidance beliefs regarding work or physical activities in people receiving outpatient therapy.
Screening people for elevated levels of fear-avoidance beliefs is uncommon, but elevated levels of fear could worsen outcomes. Developing short screening tools might reduce the data collection burden and facilitate screening, which could prompt further testing or management strategy modifications to improve outcomes. The purpose of this study was to develop efficient yet accurate screening methods for identifying elevated levels of fear-avoidance beliefs regarding work or physical activities in people receiving outpatient rehabilitation. A secondary analysis of data collected prospectively from people with a variety of common neuromusculoskeletal diagnoses was conducted. Intake Fear-Avoidance Beliefs Questionnaire (FABQ) data were collected from 17,804 people who had common neuromusculoskeletal conditions and were receiving outpatient rehabilitation in 121 clinics in 26 states (in the United States). Item response theory (IRT) methods were used to analyze the FABQ data, with particular emphasis on differential item functioning among clinically logical groups of subjects, and to identify screening items. The accuracy of screening items for identifying subjects with elevated levels of fear was assessed with receiver operating characteristic analyses. Three items for fear of physical activities and 10 items for fear of work activities represented unidimensional scales with adequate IRT model fit. Differential item functioning was negligible for variables known to affect functional status outcomes: sex, age, symptom acuity, surgical history, pain intensity, condition severity, and impairment. Items that provided maximum information at the median for the FABQ scales were selected as screening items to dichotomize subjects by high versus low levels of fear. The accuracy of the screening items was supported for both scales. This study represents a retrospective analysis, which should be replicated using prospective designs. Future prospective studies should assess the reliability and validity of using one FABQ item to screen people for high levels of fear-avoidance beliefs. The lack of differential item functioning in the FABQ scales in the sample tested in this study suggested that FABQ screening could be useful in routine clinical practice and allowed the development of single-item screening for fear-avoidance beliefs that accurately identified subjects with elevated levels of fear. Because screening was accurate and efficient, single IRT-based FABQ screening items are recommended to facilitate improved evaluation and care of heterogeneous populations of people receiving outpatient rehabilitation.


DsbL and DsbI form a specific dithiol oxidase system for periplasmic arylsulfate sulfotransferase in uropathogenic Escherichia coli.
Disulfide bond formation in the Escherichia coli periplasm requires the transfer of electrons from substrate proteins to DsbA, which is recycled as an oxidant by the membrane protein DsbB. The highly virulent, uropathogenic E. coli strain CFT073 contains a second, homologous pair of proteins, DsbL and DsbI, which are encoded in a tri-cistronic operon together with a periplasmic, uropathogen-specific arylsulfate sulfotransferase (ASST). We show that DsbL and DsbI form a functional redox pair, and that ASST is a substrate of DsbL/DsbI in vivo. DsbL is the most reactive oxidizing thioredoxin-like protein known to date. In contrast to DsbA, however, DsbL oxidizes reduced RNaseA with a much lower rate and prevents unspecific aggregation of reduced insulin. The 1.55 A resolution crystal structure of reduced DsbL provides insight into the reduced state of thioredoxin-like dithiol oxidases at high resolution, and reveals an unusual cluster of basic residues stabilizing the thiolate anion of the nucleophilic active-site cysteine. We propose that the DsbL/DsbI pair of uropathogenic E. coli was acquired as an additional, specific redox couple that guarantees biological activity of ASST.


Analysis of extrachromosomal Ac/Ds transposable elements.
The mechanism of transposition of the maize Ac/Ds elements is not well understood. The true transposition intermediates are not known and it has not been possible to distinguish between excision models involving 8-bp staggered cuts or 1-bp staggered cuts followed by hairpin formation. In this work, we have analyzed extrachromosomal excision products to gain insight into the excision mechanism. Plasmid rescue was used to demonstrate that Ds excision is associated with the formation of circular molecules. In addition, we present evidence for the formation of linear extrachromosomal species during Ds excision. Sequences found at the termini of circular and linear elements showed a broad range of nucleotide additions or deletions, suggesting that these species are not true intermediates. Additional nucleotides adjacent to the termini in extrachromosomal elements were compared to the sequence of the original donor site. This analysis showed that: (1) the first nucleotide adjacent to the transposon end was significantly more similar to the first nucleotide flanking the element in the donor site than to a random sequence and (2) the second and farther nucleotides did not resemble the donor site. The implications of these findings for excision models are discussed.


A computational method for simultaneous LQ optimal control design via piecewise constant output feedback.
The paper is concerned with simultaneous linear-quadratic (LQ) optimal control design for a set of LTI systems via piecewise constant output feedback. First, the discrete-time simultaneous LQ optimal control design problem is reduced to solving a set of coupled matrix inequalities and an iterative LMI algorithm is presented to compute the feedback gain. Then, simultaneous stabilization and simultaneous LQ optimal control design of a set of LTI continuous-time systems are considered via periodic piecewise constant feedback gain. It is shown that the design of a periodic piecewise constant feedback gain simultaneously minimizing a set of given continuous-time performance indexes can be reduced to that of a constant feedback gain minimizing a set of equivalent discrete-time performance indexes. Explicit formulas for computing the equivalent discrete-time systems and performance indexes are derived. Examples are used to demonstrate the effectiveness of the proposed method.


Primary Surgical Management of Laryngeal Neuroendocrine Neoplasms: A Single Institution Case Series.
Objective: Laryngeal neuroendocrine neoplasms (NENs) are rare diseases. A single institution retrospective study was done of the outcome of patients with laryngeal NENs who undergo primary surgery as the first treatment modality. Methods: Retrospective analysis of medical records of patients with laryngeal NENs between 2009 and 2018. Cases were classified by applying the 2022 World Health organization Classification of Head and Neck Tumors (5th edition). Results: Six patients were eligible at our tertiary center: 1 large cell neuroendocrine carcinoma (NEC), 3 small cell NEC, 1 neuroendocrine tumor grade 1, and 1 neuroendocrine tumor grade 2. All admitted patients received upfront surgeries, including 3 transoral CO2 laser surgeries and 3 total laryngectomies with or without elective neck dissection. Four patients underwent subsequent chemoradiotherapy. Although 3 patients had recurrent disease and distal metastasis, the overall survival was generally improved. Conclusion: According to our institutional experience, upfront surgery in the first-line setting of a multi-modality approach with adjuvant chemoradiotherapy plays a very important role in managing laryngeal NECs, and may confer additional survival benefit in some patients of the large cell carcinoma subgroup.


[Fatty acid composition of total lipids and phospholipids of membrane preparations of transport ATPases].
The fatty acid composition of total lipids and phospholipids of duck salt gland Na,K-ATPase (outer plasma membrane) and of rabbit skeletal muscle Ca-ATPase (intracellular membrane) was investigated. The bulk of Na,K-ATPase fatty acids is represented by palmitic (16:0), oleic (18:1), stearic (18:0) and arachidonic (20:4) acids. The duck salt gland is characterized by rather a high content of unsaturated fatty acids, especially of arachidonic acid. The unsaturation index of total-lipid fatty acids increases during purification of these preparations in the following order: homogenate greater than microsomal fraction greater than purified enzyme. The fatty acid composition of Na,K-ATPase total lipids and phospholipids reveals certain differences. Phospholipids contain more stearic and liholeic (18:2) acids than total lipids, but the level of arachidonic acid in them is twice as low. Besides, phospholipids were found to contain polyunsaturated docosohexaenic (22:6) acid. The bulk of fatty acids of rabbit skeletal muscle Ca-ATPase total lipids and phospholipids is represented by 16:0, 18:0, 18:1 and 18:2 acids. The content of polyunsaturated fatty acids in this preparation is much lower than in duck salt gland Na,K-ATPase. The fatty acid composition of total lipids and phospholipids in rabbit skeletal muscle Ca-ATPase differ insignificantly. The differences in the fatty acid composition of membrane preparations under study is conditioned mainly by the fractional composition of their lipids.


Utility of Tc99m-Mebrofenin hepato-biliary scintigraphy (HIDA scan) for the diagnosis of biliary atresia.
To determine the utility of Tc99m-Mebrofenin hepato-biliary scintigraphy (HIDA scan) for diagnosis of biliary atresia in patients with neonatal cholestasis. Our study involves the retrospective analysis of 46 patients with neonatal cholestasis who underwent HIDA scans at the Pediatric Hepatobiliary Clinic, BJ Wadia Hospital for Children from May 2005 to July 2007. Biliary atresia (BA) was diagnosed on the basis of intra-operative cholangiogram. Non-BA patients were included in the neonatal hepatitis (NH) group. All patients received phenobarbitone and ursodeoxycholic acid for 5 days, prior to the HIDA scan. The HIDA scan was evaluated on the basis of uptake of the radioactive tracer by the liver at 5 minutes after intravenous injection; retention of radioactive tracer within the liver at 24 hours after injection and visualization of excretion of tracer into the intestine upto 24 hours after administration. The results of the HIDA scans were analyzed and correlated with the final diagnosis, gender and age of the patients. Chi-square test was employed for statistical analysis. The age of presentation of our patients ranged from 5 days to 6 months. The male: female ratio was 37:9. Of the total 46 patients, 28 had BA and 18 had NH. All 28 (100%) patients diagnosed with BA showed persistent radiotracer in the liver at 24 hours whereas 17 (94.4%) of the 18 NH patients showed hepatic radiotracer retention (p = 0.207), the difference being statistically insignificant. Twenty two (78.6%) patients of BA showed no excretion of the radiotracer at 24 hours whereas only 7 (38.9%) of the NH group did not excrete the radiotracer (p = 0.007), which was statistically significant. Neither the sex nor the age of the child contributed to any difference on the hepatic retention (p = 0.618 and 0.235, respectively) or on the intestinal excretion (p = 0.307 and 0.9, respectively) of the radiotracer. HIDA scan is a useful tool for screening of biliary atresia in patients with neonatal cholestasis. Non excretion of the radioactive radiotracer into the intestines even after 24 hours of radiotracer administration can suggest biliary atresia in majority of patients.


Smoking related systemic and oral diseases.
This article reviewed smoking related systemic diseases and oral diseases. Smoking is related to lung cancer, cardiovascular diseases and many other systemic diseases. Cigarette smoke affects the oral cavity first, so it is evident that smoking has many negative influences on oral cavity, for example, staining of teeth and dental restorations, wound healing, reduction of the ability to smell and taste, and development of oral diseases such as oral cancer, periodontitis, smoker's palate, smoker's melanosis, hairy tongue, leukoplakia, oral candidiasis and implant survival rate. The article also discusses the relationship between smoking and dental caries in detail.


Pharmacological stimulation of metabotropic glutamate receptor type 4 in a rat model of Parkinson's disease and L-DOPA-induced dyskinesia: Comparison between a positive allosteric modulator and an orthosteric agonist.
Metabotropic glutamate receptor 4 (mGlu4) negatively modulates GABA and glutamate release in the 'indirect pathway' of the basal ganglia, and has thus been proposed as a potential target to treat motor symptoms in Parkinson's disease. Here, we present an extensive comparison of the behavioural effects produced by the mGlu4 positive allosteric modulator (PAM), VU0364770, and the mGlu4 orthosteric agonist, LSP1-2111, in rats with unilateral 6-OHDA lesions. The compounds' activity was initially assessed in a test of haloperidol-induced catalepsy in intact rats, and effective doses were then evaluated in the hemiparkinsonian animal model. Neither of the two compounds modified the development of dyskinetic behaviours elicited by chronic treatment with full doses of l-DOPA. When given together with l-DOPA to rats with already established dyskinesias, neither VU0364770 nor LSP1-2111 modified the abnormal involuntary movement scores. VU0364770 potentiated, however, the motor stimulant effect of a subthreshold l-DOPA dose in certain behavioural tests, whereas LSP1-2111 lacked this ability. Taken together, these results indicate that a pharmacological stimulation of mGlu4 lacks intrinsic antidyskinetic activity, but may have DOPA-sparing activity in Parkinson's disease. For the latter indication, mGlu4 PAMs appear to provide a better option than orthosteric agonists.


Transfer of rpl22 to the nucleus greatly preceded its loss from the chloroplast and involved the gain of an intron.
Most chloroplast and mitochondrial proteins are encoded by nuclear genes that once resided in the organellar genomes. Transfer of most of these genes appears to have occurred soon after the endosymbiotic origin of organelles, and so little is known about the process. Our efforts to understand how chloroplast genes are functionally transferred to the nuclear genome have led us to discover the most recent evolutionary gene transfer yet described. The gene rpl22, encoding chloroplast ribosomal protein CL22, is present in the chloroplast genome of all plants examined except legumes, while a functional copy of rpl22 is located in the nucleus of the legume pea. The nuclear rpl22 gene has acquired two additional domains relative to its chloroplast ancestor: an exon encoding a putative N-terminal transit peptide, followed by an intron which separates this first exon from the evolutionarily conserved, chloroplast-derived portion of the gene. This gene structure suggests that the transferred region may have acquired its transit peptide by a form of exon shuffling. Surprisingly, phylogenetic analysis shows that rpl22 was transferred to the nucleus in a common ancestor of all flowering plants, at least 100 million years preceding its loss from the legume chloroplast lineage.


Improving one-step scarless genome editing in Drosophila melanogaster by combining ovoD co-CRISPR selection with sgRNA target site masking.
The precise and rapid construction of alleles through CRISPR/Cas9-mediated genome engineering renders Drosophila melanogaster a powerful animal system for molecular structure-function analyses and human disease models. Application of the ovoD co-selection method offers expedited generation and enrichment of scarlessly edited alleles without the need for linked transformation markers, which specifically in the case of exon editing can impact allele usability. However, we found that knockin procedures by homology-directed repair (HDR) under ovoD co-selection resulted in low transformation efficiency. This is likely due to repeated rounds of Cas9 cleavage of HDR donor and/or engineered genomic locus DNA, as noted for other CRISPR/Cas9 editing strategies before, impeding the recovery of correctly edited alleles. Here we provide a one-step protocol to improve the generation of scarless alleles by ovoD -co-selection with single-guide RNA (sgRNA) binding site masking. Using this workflow, we constructed human disease alleles for two Drosophila genes, unc-13/CG2999 and armadillo/CG11579. We show and quantify how a known countermeasure, the insertion of silent point mutations into protospacer adjacent motif (PAM) or sgRNA homology regions, can potently suppress unintended sequence modifications during CRISPR/Cas9 genome editing of D. melanogaster under ovoD co-selection. This strongly increased the recovery frequency of disease alleles.


Control of Ion-Photoelectron Entanglement and Coherence Via Rabi Oscillations.
We report a theoretical investigation of photoionization by a pair of coherent, ultrashort, fundamental and second-harmonic extreme-ultraviolet pulses, where the photon energies are selected to yield the same photoelectron energy for ionization of two different subshells. This choice implies that the fundamental energy is equal to the difference in energy of the ionic states and that they are therefore coupled by the fundamental photon. By deriving analytical expressions using the essential-states approach, we show that this Rabi coupling creates coherence between the two photoelectron wave packets, which would otherwise be incoherent. We analyze how the coupling is affected by the parameters, such as relative phase, pulse width, delay between the two pulses, Rabi coupling strength, and photoelectron energy. Our discussion mostly considers Ne 2p and 2s photoionization, but it is generally valid for many other quantum systems where photoionization from two different shells is observed.


HLA-DR antigen expression in colorectal carcinomas: influence of expression by IFN-gamma in situ and its association with tumour progression.
The authors attempted to investigate the host's immune response against colorectal carcinoma through the expression of HLA-DR antigen on carcinoma cells (Ca) on normal epithelia immediately adjacent to carcinoma (AN) in relation to tumour progression. The expression of HLA-DR antigen on Ca and on normal epithelia, both on AN and those 5-10 cm removed from the carcinoma (RN), were examined immunohistochemically. mRNAs of cytokines, IFN-gamma and TNF-alpha, were detected by reverse transcription-polymerase chain reaction (RT-PCR) in both carcinoma and remote normal tissues. The expression of HLA-DR antigen on AN was significantly increased compared with RN. Patients with tumours showing HLA-DR staining both in Ca and AN were in less advanced Dukes' stages (Dukes' A or B) compared with those without the stain. Furthermore, the expression of HLA-DR antigen in normal mucosa coincided significantly with the existence of IFN-gamma mRNA. Detection in carcinoma tissues of IFN-gamma mRNA that leads to the induction of HLA-DR antigen on AN could be an indicator of a host's immune response to carcinoma. These in vivo observations might be clinically applicable to the prediction of patients' immune responsiveness to carcinomas.


Treatment Refusal in Arizona's Jail-Based Competency to Stand Trial Restoration Programs.
In 2003, Arizona began a jail-based restoration to competency program for detainees in its largest jail system in Phoenix. Today, jail-based competency programs have become the rule statewide to the degree that very few incompetent detainees are now referred to the Arizona State Hospital for restoration services. This article focuses on the topic of treatment refusal and the use of forced medications for detainees who are in these jail-based restoration programs. We describe Arizona's novel statewide jail-based programs, Arizona's statutory and case law approach to treatment refusal, and the restoration to competency programs in one large county jail that has no legal mechanism outside of civil commitment for the determination of whether forced treatment will be permitted. We conclude with a discussion of specific override procedures that might apply directly to incompetent detainees in a jail-based competency restoration program and whether the use of these procedures is prudent in a jail environment.


Membrane expression of decay-accelerating factor on neutrophils from normal individuals and patients with paroxysmal nocturnal hemoglobinuria.
Decay-accelerating factor (DAF), a complement-regulating glycoprotein, was found to be a maturational protein for normal neutrophils, and a remarkable correlation was found between the DAF level and alkaline phosphatase activity in neutrophils. We studied the relationship between the amount of DAF on the membrane and cell maturity in total nucleated bone marrow (BM) cells, mature BM and peripheral blood (PB) neutrophils from normal subjects, and patients with paroxysmal nocturnal hemoglobinuria (PNH) using a fluorescence-activated cell sorter with anti-DAF monoclonal antibodies. Percentage distributions of differentiating neutrophils from normal total nucleated BM cells showed that the proportion of immature cells (myeloblasts plus promyelocytes) decreased, while that of mature ones (bands plus segmented forms) increased as the fluorescence intensity increased. For PB neutrophils, no apparent correlation was found between DAF expression and cell maturity. This may have resulted from margination of the fully matured neutrophils with a high amount of DAF. In PNH patients who have low levels of DAF, this study showed that DAF expression in their neutrophils differs from that in normal subjects, and abnormalities occur in PNH cells from a very early stem-cell stage.


[Ergoferon and oseltamivir in treatment of influenza: results of multicentre randomized comparative clinical trial].
The narrow range of choice and virus resistance to the most common drugs require search and introduction of new drugs with proven efficacy and safety for the treatment of influenza. Ergoferon is a new combined medicine containing release active antibodies to interferon-gamma (anti-IFNgamma), CD4-coreceptor and histamine. The formulation influences various links of antiviral defense and provides antiinflammatory effect. The efficacy of the drug is related to its production process during which multiple reduction of the initial concentration of every component leads to release of special release activity. Previous experimental studies showed that anti-IFNgamma had antiviral activity against pandemic influenza virus A (H1N1) 2009 comparable to that ofoseltamivir (suppression of virus replication in the lung tissue, increase of the lifespan and reduction of the laboratory animals mortality). The aim of the multicentre randomized clinical trial was to compare (versus oseltamivir) the efficacy and safety of ergoferon in the treatment of influenza in adults. 213 patients with flu-like symptoms were examined in 8 medical centres of Russia during two epidemiological seasons (2010-11 and 2011-12). The inclusion criteria were: the first 48 hours after the onset; fever > or =37.8 degrees C, at least one common symptom and at least one respiratory symptom. Influenza was confirmed in 52 patients by QuickVue rapid diagnosis. 23 patients received ergoferon according to the treatment scheme and 29 received oseltamivir (daily dose 150 mg). Duration of the treatment was 5 days. The patients were followed up for 7 days. The primary endpoint was the percentage of the patients with the body temperature normalization for 2-5 days of the treatment. The maximum efficacy of ergoferon was observed on the second day of the treatment: almost half (48%) of the initially febrile patients had normal body temperature (versus 28% in the patients treated with oseltamivir). The comparison of the two groups of the patients by the morning and evening measurements of the body temperature every five days of the treatment by Cochran-Mantel-Haenszel revealed a significant difference between the two groups (chi2 = 7.1; p = 0.008). The average duration of the fever in the group of ergoferon was 2.3 +/- 1.2 days, in the group of oseltamivir--2.6 +/- 1.3 days (the efficacy of oseltamivir in the present study was comparable with the previously published data). The percentage of the patients treated with antipyretics because of hyperthermia on the second day of the treatment lowered 3 times and amounted to 17% (versus 41% in the oseltamivir group). The severity of common and respiratory symptoms (nose/throat/chest) significantly decreased on the third day of the treatment in both groups, the majority of the patients had either minimum severity or no signs of influenza. The clinical improvement was associated with positive changes in the life quality. No cases of the disease aggravation were recorded. Complications requiring antibiotic treatment or hospitalization were not observed during the followup. There were no adverse events recorded due to the drug use. No deviations in the laboratory indices were stated. Ergoferon is a new safe drug for the treatment of influenza. Its clinical efficacy was comparable to that of oseltamivir. The therapeutic effects of the drug were evident from: significant reduction of the disease severity, duration of febricity and general toxicity and respiratory flu symptoms, lower percentage of the patients with fever for 2 days. The febrile period in most of the patients did not exceed 2 days.


Buparlisib , an oral pan-PI3K inhibitor for the treatment of breast cancer.
Deregulation of the phosphatidylinositol-3-kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) intracellular signaling pathway is common in breast cancer (BC) and has been found to be potentially implicated in resistance to endocrine and anti-HER2 therapies. Targeting the PI3K/Akt/mTOR pathway may remove this inhibition and restore sensitivity to these compounds. Buparlisib (BKM120) is a potent oral pan-class I PI3K inhibitor that is being extensively evaluated in multiple tumor types. This review briefly summarizes the pharmacodynamics and pharmacokinetics of buparlisib, focusing on preclinical and clinical data in BC and on ongoing randomized trials. Overall, buparlisib is a safe and tolerable drug and, despite its peculiar toxicity profile, it is suitable for studies in combination with other anticancer agents in BC. Early-phase clinical trials in BC have provided evidence of antitumor activity. Several trials are being conducted in all the biological subsets of BC, including combinations with endocrine therapy, anti-HER2 agents, PARP-inhibitors and chemotherapy. While clinical results are eagerly awaited, biological material suitable for both genomic and non-genomic analyses is being collected. The authors expect an intense investigation of the potential biomarkers that explain response or resistance to buparlisib and inspire strategies to rationally explore the therapeutic potential of this drug.


Liposome-based cationic adjuvant formulations (CAF): past, present, and future.
The use of liposomes as vaccine adjuvants has been investigated extensively over the last few decades. In particular, cationic liposomal adjuvants have drawn attention, with dimethyldioctadecylammonium (DDA) liposomes as a prominent candidate. However, cationic liposomes are, in general, not sufficiently immunostimulatory, which is why the combination of liposomes with immunostimulators has arisen as a strategy in the development of novel adjuvant systems in recent years. One such adjuvant system is CAF01. In this review, we summarize the immunological properties making CAF01 a promising versatile adjuvant system, which was developed to mediate protection against tuberculosis (TB) but, in addition, has shown promising protective efficacy against other infectious diseases requiring different immunological profiles. Further, we describe the stabilization properties that make CAF01 suitable in vaccine formulation for the developing world, which in addition to vaccine efficacy, are important prerequisites for any novel TB vaccine to reach global implementation. The encouraging nonclinical data led to a preclinical vaccine toxicology study of the TB model vaccine, Ag85B-ESAT-6/CAF01, that concluded that CAF01 has a satisfactory safety profile to advance the vaccine into phase I clinical trials, which are scheduled to start in 2009.


A prospective comparison of clinical examination, MRI, bone SPECT, and arthroscopy to detect meniscal tears.
Recent studies have shown that SPECT bone scintigraphy is valuable to detect meniscal tears of the knee. This has not been formally assessed in a prospective study, and no substantive study has compared bone SPECT with other noninvasive diagnostic methods. One hundred consecutive patients referred to an orthopedic surgeon with undiagnosed knee pain were assessed by clinical examination, MRI, SPECT bone scintigraphy, and arthroscopy. The MRI and SPECT bone scan findings were reported blinded to other information. Using arthroscopy as a gold standard, both MRI and SPECT showed high diagnostic ability to detect meniscal tears, with respective sensitivity rate, specificity rates, and positive and negative predictive accuracies of 80%, 71%, 84%, and 71% for MRI and 84%, 80%, 88%, and 76% for SPECT. Some meniscal tears were detected by MRI alone (n = 5) or SPECT alone (n = 8). SPECT bone scintigraphy is a suitable alternative to MRI to detect meniscal tears. The comparable diagnostic ability of SPECT bone scintigraphy implies that it can be used successfully when MRI is unavailable or unsuitable.


Gastrointestinal manifestations of cow's milk protein allergy during the first year of life.
Cow's milk protein sensitive enteropathy (CMPSE) is a common condition in the first year of life. Clinically CMPSE usually presents with symptoms like vomiting, chronic diarrhea, mucous bloody diarrhea and hematemesis. More unusual symptoms associated with CMPSE are infantile colic, gastroesophageal reflux and chronic constipation. The objective of this study was to assess the gastrointestinal manifestations and allergic march in CMPSE patients. The authors reviewed the records of 10 CMPSE patients observed by the Gastrointestinal Unit at King Chulalongkorn Memorial Hospital from 1997-2001 including patient characteristics, laboratory investigations, endoscopy and follow-up outcome. Of 10 CMPSE patients, the median age of CMPSE onset was 3.5 months. The gastrointestinal manifestations were hematemesis (n = 6), mucous bloody diarrhea (n = 3) and chronic watery diarrhea (n = 2). Exclusively breast-fed infants seemed to have more delayed onset of symptoms than those who were not. Anemia (n = 3), high serum IgE (n = 4) and positive skin prick test for cow's milk (n = 5) were found. Neither peripheral eosinophilia nor hypoalbuminemia was found. Endoscopy revealed acute and chronic gastritis. Treatment was successful by changing to soy or extensive hydrolysate formula with mean duration of cow's milk intolerance of 24 months. In 2-year follow-up, three of ten patients who had high serum IgE level developed allergic rhinitis and eczema. CMPSE can be manifested in various symptoms. Exclusive breast feeding for more than 4 months can postpone the onset of CMPSE. Serum IgE or specific IgE level to cow's milk protein may identify the atopic career of CMPSE individuals.


Identification and isolation of actin from Neurospora crassa.
Crude cell extracts of Neurospora crassa contained an abundant protein that was identified as actin by a number of criteria. The protein, either in cell extracts or in pure form, co-migrated with rabbit skeletal muscle actin in polyacrylamide gels. The N. crassa actin was purified by DEAE-cellulose and DNAase I-Sepharose chromatography and had the expected property of inhibiting DNAase I activity. Although N. crassa actin could polymerize and depolymerize, purification based entirely on this characteristic was ineffective. The actin was susceptible to proteolytic degradation, and under certain conditions, a breakdown product of defined size was observed.


A 3-Year-Old Girl with Recurrent Infections and Autoimmunity due to a STAT1 Gain-of-Function Mutation: The Expanding Clinical Presentation of Primary Immunodeficiencies.
We report a 3-year-old Peruvian girl, born to non-consanguineous parents. At the age of 8 months, she had a severe pneumonia complicated with empyema that required thoracic drainage and mechanical ventilation. Although no microorganisms were isolated, the patient recovered with broad-spectrum antibiotics. Since that date, she has presented multiple episodes of pneumonia and recurrent episodes of bronchospasm. At 1 year 5 months of age, the patient began with recurrent episodes of oropharyngeal, vaginal, and skin candidiasis, which improved transiently after using oral azole drugs. At 2.5 years of age, she was admitted with lupus-like syndrome, including serositis, hemolytic anemia, thrombocytopenia, and positive antinuclear (1:80) and dsDNA (1:10) autoantibodies. Available immunologic testing was not contributory. Imaging studies revealed bilateral ethmoidal sinusitis and mild hepatomegaly. Bone marrow analysis did not showed evidence of leukemia or myelodysplasia, while renal biopsy concluded mild mesangial proliferation. Genetic studies revealed a pathogenic heterozygous signal transducer and activator of transcription 1 gain-of-function mutation (WT/P293L). The clinical status and lung function of the patient has worsened progressively. She has not achieved an optimal response to therapy, including high-dose intravenous immunoglobulin, GM-CSF, prophylactic antibiotics and antifungal drugs, so we plan to perform hematopoietic stem cell transplantation.


Urinary metabolites of tetrahydronorharmane in the rat.
The metabolism of THN in the rat was studied in vivo by use of 14C-radiolabelled compound. Structures of major urinary metabolites were determined by exact spectral data. Their concentrations were measured by liquid scintillation counting. It was found that THN is submitted to endogenous transformation, and that the excreted derivatives form three groups of similar concentration: unchanged substance, hydroxylated/conjugated compounds, and aromatic metabolites. Structures and proposed pathways are summed up in the diagram on the following page.


Kawasaki disease: novel insights into etiology and genetic susceptibility.
Kawasaki disease (KD) is a vasculitis of young childhood that particularly affects the coronary arteries. Molecular analysis of the oligoclonal IgA response in acute KD led to production of synthetic KD antibodies. These antibodies identify intracytoplasmic inclusion bodies in acute KD tissues. Light and electron microscopic studies indicate that the inclusion bodies are consistent with aggregates of viral proteins and RNA. Advances in molecular genetic analysis and completion of the Human Genome Project have sparked a worldwide effort to identify genes associated with KD. A polymorphism of one such gene, ITPKC, a negative regulator of T cell activation, confers susceptibility to KD in Japanese populations and increases the risk of developing coronary artery abnormalities in both Japanese and U.S. children. Identification of the etiologic agent and of genes conferring KD susceptibility are the best means of improving diagnosis and therapy and enabling prevention of this important disorder of childhood.


Factors that improve the preservation of nephron morphology during cold storage.
Light and electron microscopy were used to evaluate the nephron morphology of rat kidneys that were perfused and stored at 0 to 2 degrees C. for up to 48 hours in preservation solutions which (1) contained different osmotic agents, (2) were adjusted to different levels of osmolality, and (3) which had different ionic compositions (e.g., intracellular-like, extracellular-like). Storage in an enriched phosphate-buffered isotonic culture medium that contained very little effective osmotic agent (i.e., medium 199) results in significant necrosis of glomeruli and uriniferous tubules with 12 to 24 hours. Storage in Collins solution that has an intracellular-like ionic composition and that contains dextrose as an osmotic agent results in significantly better preservation of kidney nephrons. When the dextrose in Collins solution is replaced with mannitol or sucrose, there is dramatic improvement in the preservation of glomeruli and uriniferous tubules. Overall, sucrose appears to be the most effective osmotic agent in preventing degeneration of the nephron during cold storage. Further improvement in nephron preservation is seen when the osmolality of Collins solution is raised (i.e., 400 to 600 mOsmoles) by adding more of the osmotic agents. Finally, storage in simple sodium phosphate-buffered solutions containing either dextrose, mannitol, or sucrose results in the same quality of morphologic preservation as seen with Collins intracellular-like solutions containing similar amounts of these osmotic agents. It appears, therefore, that the selection of an effective osmotic agent (e.g., sucrose) and making the preservation solution hypertonic with this osmotic agent are of primary importance in preserving nephron morphologic integrity during cold storage. The presence of an intracellular-like ionic composition in the preservation solution, however, does not appear to influence morphologic preservation. The effects of the above variables on the ultrastructural morphology of different segments of the uriniferous tubules and the renal corpuscles are described and illustrated.


[Clinical rationale for the efficiency of using the domestic antioxidant agent Histochrome].
The objective of the study was to evaluate the efficacy of the Russian drug Histochrome in the treatment of 554 children at different ages who had intraocular hemorrhages of various degrees and sites in relation to the route and time of its administration. Histochrome therapy was shown to reduce the time of resorption of hyphemas and hemophthalmos by two times and retinal hemorrhages to 2 weeks. There was a positive effect in increasing visual acuity by 0.2 or more in 70.3% of cases.


Pyridine-NHC: effective ligand in Pd-catalyzed cyclopropanation of esters with substituted allyl carbonates.
By consideration of the mechanism of Pd-catalyzed cyclopropanation and allylation, NHC-pyridine compounds were adopted as the ligand in Pd-catalyzed cyclopropanation of esters and monosubstituted allylic reagents. The corresponding cyclopropanes were afforded as major products in moderate to good yields with high cyclopropane/allylation selectivity.


Effect of the ATP-binding cassette drug transporters ABCB1, ABCG2, and ABCC2 on erlotinib hydrochloride (Tarceva) disposition in in vitro and in vivo pharmacokinetic studies employing Bcrp1-/-/Mdr1a/1b-/- (triple-knockout) and wild-type mice.
We tested whether erlotinib hydrochloride (Tarceva, OSI-774), an orally active epidermal growth factor receptor tyrosine kinase inhibitor, is a substrate for the ATP-binding cassette drug transporters P-glycoprotein (P-gp; MDR1, ABCB1), breast cancer resistance protein (BCRP; ABCG2), and multidrug resistance protein 2 (MRP2; ABCC2) in vitro and whether P-gp and BCRP affect the oral pharmacokinetics of erlotinib hydrochloride in vivo. In vitro cell survival, drug transport, accumulation, and efflux of erlotinib were done using Madin-Darby canine kidney II [MDCKII; wild-type (WT), MDR1, Bcrp1, and MRP2] and LLCPK (WT and MDR1) cells and monolayers as well as the IGROV1 and the derived human BCRP-overexpressing T8 cell lines. In vivo, the pharmacokinetics of erlotinib after p.o. and i.p. administration was studied in Bcrp1/Mdr1a/1b(-/-) (triple-knockout) and WT mice. In vitro, erlotinib was actively transported by P-gp and BCRP/Bcrp1. No active transport of erlotinib by MRP2 was observed. In vivo, systemic exposure (P = 0.01) as well as bioavailability of erlotinib after oral administration (5 mg/kg) were statistically significantly increased in Bcrp1/Mdr1a/1b(-/-) knockout mice (60.4%) compared with WT mice (40.0%; P = 0.02). Erlotinib is transported efficiently by P-gp and BCRP/Bcrp1 in vitro. In vivo, absence of P-gp and Bcrp1 significantly affected the oral bioavailability of erlotinib. Possible clinical consequences for drug-drug and drug-herb interactions in patients in the gut between P-gp/BCRP-inhibiting substrates and oral erlotinib need to be addressed.


Infant mental health promotion and the discourse of risk.
The field of infant mental health promotion has rapidly developed in academia, health policy and practice. Although there are roots in earlier childhood health and welfare movements, recent developments in infant mental health promotion are distinct and different. This article examines the development and practice of infant mental health promotion in South Australia. A regional, intersectoral forum with a focus on families and young children was used as a case study. In-depth interviews with forum members were analysed using a governmentality lens. Participants identified a range of risks to the healthy development of the infant. The study suggests that the construction of risk acts as a technique of governing, providing the rationale for intervention for the child, the mother and the public's good. It places responsibility on parents to self-govern. Although the influence of broader social contexts is acknowledged, the problematisation of mothering as risk shifts the focus to individual capacity, rather than encompassing the systems and social conditions that support healthy relationships. This research suggests that the representations of risk are a pervasive and potent influence that can act to undermine health promotion efforts that seek to empower and enable people to have more control over their own health.


Health risk assessment on N-nitrosodimethylamine in drinking water and food in major cities of China with disability-adjusted life years (DALYs).
In this study, a health risk assessment of N-nitrosodimethylamine (NDMA) in drinking water and food was conducted using disability-adjusted life years (DALYs) in major cities of China. Considering the numerous non-detected values found in drinking water samples, a zero-inflated model was employed to obtain a more precise NDMA concentration distribution function in drinking water. With exogenous chronic daily intake of 1.20 × 10-6 mg/(kg*d), the lifetime cancer risk and disability-adjusted life years of NDMA are 4.01 × 10-5 and 5.52 × 10-6 per person-year (ppy). The disease burden attributable to water sources accounts for nearly 9.94% of total exogenous intake. The contribution rate of vegetables is the largest, followed by cereals, milk products, fish and shrimp, and meat. Taking endogenous sources into consideration, the contribution rates of drinking water and food sources decrease to 0.08% and 0.69%. This study provides a scientific basis for making policy decisions on NDMA pollution management.


Darwin to DNA, molecules to morphology: the end of classical population genetics and the road ahead.
Molecular reductionism has permeated all of biology and because of successive new technical breakthroughs it has succeeded in unraveling the structural details of genes and genomes. The molecular revolution has reached its reductionist limit, i.e., the study of component parts in isolation, and is ready to come full circle through genomics, proteomics, and gene expression studies back to the phenotype and bring evolutionary biology to confront the Darwinian paradigm, the relationship between gene, organism, and environment. Classical experimental population genetics, dealing with genetic polymorphism and estimation of selection coefficients on a gene-by-gene basis, is coming to an end and a new era of interdisciplinary and interactive biology focusing on dynamic relationships among gene, organism, and environment has begun. In the new population genetics, there will be a shift in focus from single genes to gene networks, from gene-structure to gene-regulation, from additivity to epistasis, and from simple phenotypes to gene-interaction networks and the evolution of complex and modular systems.