Phenotype and Treatment of Breast Cancer in HIV-Positive and -Negative Women in Cape Town, South Africa.
An estimated 5.9 million people in South Africa are infected with HIV. Because antiretroviral therapy has made infection with HIV a treatable, chronic condition, HIV-infected individuals are now surviving to middle and older age. We investigated the implications of HIV status for breast cancer in South Africa. We compared clinical and demographic characteristics of women newly diagnosed with a first primary breast cancer at Tygerberg Hospital, Cape Town, South Africa, from January 2010 to December 2011 by HIV status. We then compared HIV-positive patients with HIV-negative controls, matched 2:1 on age and ethnicity, with respect to chemotherapy regimens, toxicities, completion of systemic chemotherapy, and changes in CD4 cell count. Of 586 women with breast cancer, 31 (5.3%) were HIV positive, 420 (71.7%) were HIV negative, and 135 (23%) were untested for HIV. Women with HIV were younger than other women (P < .001). The groups did not differ in regard to stage at presentation, histologic subtype, tumor grade, nodal involvement, or hormone receptor positivity. More than 84% of patients who initiated systemic chemotherapy, regardless of HIV status, completed it without serious toxicity. Among HIV-positive patients receiving chemotherapy, the mean baseline CD4 cell count was 477 cells/µL (standard deviation, 160 cells/µL), and the mean nadir was 333 cells/µL (standard deviation, 166 cells/µL). HIV-infected women were younger at breast cancer diagnosis than HIV-negative women but otherwise similar in phenotype and completion of chemotherapy. Longer term follow-up is needed to evaluate the effects of HIV, antiretroviral therapy, and chemotherapy on the survival and quality of life of patients with breast cancer.


Frequency and predisposing factors for interfractional rectal displacement requiring repeated precaution in prostate cancer patients treated with image-guided intensity-modulated radiation therapy.
To investigate the frequency and characteristics of interfractional rectal displacement in patients with prostate cancer treated with image-guided intensity-modulated radiation therapy (IG-IMRT) using helical tomotherapy. Data for a total of 256 patients were analyzed. Megavoltage computed tomography (MVCT) images were acquired before radiation therapy and interfractional rectal displacement was assessed with soft-tissue matching by comparing treatment planning images within 9,445 fractions. Anterior rectal region displacement larger than 5 mm, requiring repeated precaution, was defined as the action level of rectal displacement (ARD). ARD was identified in 676 (7.2%) out of 9,445 fractions and at least once in 75% (190/256) of patients. Univariate analysis identified three predisposing factors for ARD: body mass index (BMI), rectal volume and prostate volume. Multivariate logistic regression analysis revealed that lower BMI and large rectal volume were statistically significant predictors of ARD. The highest incidence of ARD (13.6% and 9.1%) was found during the initial two weeks of treatment (first five and next five fractions), after which the incidence decreased to 5.96% (p<0.0001). ARD was identified in 7.9% of fractions and in 74.8% of patients and was most likely to occur in patients with a low BMI and/or large rectal volume. ARD occurred predominantly during the initial two weeks of treatment and became less likely over time.


End-to-Side vs. Free Graft Nerve Reconstruction-Experimental Study on Rats.
The long history of regeneration nerve research indicates many clinical problems with surgical reconstruction to be resolved. One of the promising surgical techniques in specific clinical conditions is end-to-side neurorrhaphy (ETS), described and then repeated with different efficiency in the 1990s of the twentieth century. There are no reliable data on the quality of recipient nerve regeneration, possible donor nerve damage, and epineural window technique necessary to be performed. This research attempts to evaluate the possible regeneration after end-to-side neurorrhaphy, its quality, potential donor nerve damage, and the influence of epineural windows on regeneration efficiency. Forty-five female Wistar rats were divided into three equal groups, and various surgical technics were applied: A-ETS without epineural window, B-ETS with epineural window, and C-free graft reconstruction. The right peroneal nerve was operated on, and the tibial nerve was selected as a donor. After 24 weeks, the regeneration was evaluated by (1) footprint analysis every two weeks with PFI (peroneal nerve function index), TFI (tibial nerve function index), and SFI (sciatic nerve function index) calculations; (2) the amplitude and latency measurements of motor evoked potentials parameters recorded on both sides of the peroneal and tibial nerves when electroneurography with direct sciatic nerve electrical stimulation and indirect magnetic stimulation were applied; (3) histomorphometry with digital conversion of a transverse semithin nerve section, with axon count, fibers diameter, and calculation of axon area with a semiautomated method were performed. There was no statistically significant difference between the groups investigated in all the parameters. The functional indexes stabilized after eight weeks (PFI) and six weeks (TFI and SFI) and were positively time related. The lower amplitude of tibial nerve potential in groups A and B was proven compared to the non-operated side. Neurophysiological parameters of the peroneal nerve did not differ significantly. Histomorphometry revealed significantly lower diameter and area of axons in operated peroneal nerves compared to non-operated nerves. The axon count was at a normal level in every group. Tibial nerve parameters did not differ from non-operated values. Regeneration of the peroneal nerve after ETS was ascertained to be at the same level as in the case of free graft reconstruction. Peroneal nerves after ETS and free graft reconstruction were ascertained to have a lower diameter and area than non-operated ones. The technique of an epineural window does not influence the regeneration result of the peroneal nerve. The tibial nerve motor evoked potentials were characterized by lower amplitudes in ETS groups, which could indicate axonal impairment.


Influence of maternal diabetes on serum leptinemic and insulinemic status of the offspring: a case study of selected patients in a tertiary care hospital in Bangladesh.
Leptin is now known to be an important hormone affecting intrauterine fetal growth. Since growth of fetus is also affected by the glycemic status of the mother. Serum leptin of infant is influenced by the maternal diabetic state. Investigation of cord blood leptin in babies of DM (Diabetes Mellitus) and GDM (Gestational Diabetes Mellitus) mothers (controlled blood glucose levels) may provide some indication about involvement of genetic factor in the development of leptin abnormalities in fetus. The study was taken to investigate whether cord blood insulin, c-peptide and leptin levels correlate with birth weight in offspring of DM mother. Blood was drawn from umbilical cord of 30 babies from GDM mothers (GDM-babies), 45 babies from Type 2 DM Mothers (DM-babies), and 30 babies from ND (Nondiabetic) mothers (ND-babies) of term pregnancy. Weight, blood glucose, placenta, serum leptin and c-peptide of the babies were measured. Birth weight of GDM and DM babies were significantly higher compared to ND-babies. Glucose level in GDM babies was significantly higher than ND and DM babies. Leptin levels in GDM babies were significantly higher than that of ND and DM babies. Serum c-peptide in GDM babies was significantly higher than DM and ND babies. However, there was no significant difference in leptin-glucose ratio among the three groups. Irrespective of degree of hyperglycemia leptin is a major determinant of fetal growth. DM mother produces different insulinemic and leptinemic responses in the fetus indicating a possible genetic involvement.


Binary electroosmotic-pump nanoflow gradient generator for miniaturized high-performance liquid chromatography.
High-performance liquid chromatography (HPLC) plays an important role in biotechnology, and a majority of chromatographic separations use gradient elution. While gradient generators can be built in different formats, binary pumps or quaternary pumps are most frequently used for gradient generator constructions. We have recently developed a high-pressure electroosmotic pump (EOP); the pump can be manufactured at a cost of a few hundred dollars. However, it is challenging to use this pump to deliver a gradient eluent directly. In this study, we first improve the monolith preparation by applying a pressure to the monomer solution during polymerization. We assemble a binary EOP gradient generator and discuss the relationship between the gradient profile and voltage applied to the EOP. We demonstrate the feasibility of the binary EOP gradient generator for generating a smooth and reproducible nanoflow gradient. After integration of the gradient generator into a miniaturized HPLC system, we use the HPLC system for separating peptide mixtures from trypsin-digested proteins. The performance comparison between the above miniaturized HPLC system and an Agilent 1200 HPLC system exhibits comparable efficiencies, resolutions, and peak capacities.


[Neutrophils induce the maturation and activation of immature dendritic cells during adaptive immune responses].
To investigate whether polymorphonuclear neutrophilic leucocyte (PMN) can induce the maturation and activation of immature dendritic cells, thus promoting the Th1 immunity to microbial pathogens in vitro. PMN isolated from mouse bone marrow were stimulated by lipopolysaccharide (LPS), and were cultured with immature DC (imDCs) isolated from mouse bone marrow for 18 hours. Then the analysis of DC surface markers CD40 and CD86 was done by flow cytometry, and ELISA was used to detect the levels of TNF-alpha and IL-12. Purified DC cocultured with LPS-PMN (PMN-DC) and imDC were incubated with fluorescein isothiocyanate conjugated OVA (FITC-OVA), and the phagocytic capacity of PMN-DC and imDC was assessed by flow cytometry. Splenic CD4(+) T cells from DO11.10 x C57BL/6 F1 hybrid mice were obtained, and then cultured with PMN-DC or imDC in the presence of OVA (323 - 339). The cells were double stained with anti-CD4-PE and 7-amino-actinomycin D. The cellular data were acquired for 56s with a flow cytometer and the assay of IFN-gamma and IL-4 was done by intracellular staining. LPS-PMN induced strong up-regulation of CD40 and CD86, and this capacity was remarkably inhibited after being neutralized by anti-TNF-alpha monoclonal antibody. LPS-PMN also stimulated imDCs to produce IL-12 and TNF-alpha. PMN-DCs demonstrated decreased phagocytic capacity compared with that of imDCs. Furthermore, the PMN-DC induced considerable DO11.10 T cell proliferation, and stimulated DO11.10 T cell to produce a large amount of IFN-gamma, but a relatively low amount of IL-4. LPS-PMN can induce the maturation and activation of imDCs, including the cytokine secretion, specific antigen presentation and Th1 differentiation, thus promoting the type I immunity to microbial pathogens.


Prediction of Emperor-Hawaii seamount locations from a revised model of global plate motion and mantle flow.
The bend in the Hawaiian-Emperor seamount chain is a prominent feature usually attributed to a change in Pacific plate motion approximately 47 Myr ago. However, global plate motion reconstructions fail to predict the bend. Here we show how the geometry of the Hawaiian-Emperor chain and other hotspot tracks can be explained when we combine global plate motions with intraplate deformation and movement of hotspot plumes through distortion by global mantle flow. Global mantle flow models predict a southward motion of the Hawaiian hotspot. This, in combination with a plate motion reconstruction connecting Pacific and African plates through Antarctica, predicts the Hawaiian track correctly since the date of the bend, but predicts the chain to be too far west before it. But if a reconstruction through Australia and Lord Howe rise is used instead, the track is predicted correctly back to 65 Myr ago, including the bend. The difference between the two predictions indicates the effect of intraplate deformation not yet recognized or else not recorded on the ocean floor. The remaining misfit before 65 Myr ago can be attributed to additional intraplate deformation of similar magnitude.


Reduced frontal asymmetry of delta waves during all-night sleep in schizophrenia.
Delta wave deficits during sleep have been observed in patients with schizophrenia. Decreased slow-wave sleep is reported to be associated with negative symptoms. Frontal lobe dysfunction is also believed to underlie negative symptoms of schizophrenia. This study was designed to identify functional abnormalities in schizophrenia manifested on patients' electroencephalograms. Polysomnograph examinations were performed in 12 healthy male volunteers and 11 male outpatients with schizophrenia. We investigated the laterality of frontal cortical delta waves in patients with schizophrenia and in healthy control subjects. Laterality of frontal cortex delta wave counts during all-night sleep was investigated by computer analysis. Total delta wave counts were lower in patients with schizophrenia than in control subjects. Control subjects showed significantly higher delta wave counts in the right frontal cortex than in the left. This asymmetry was not observed in patients with schizophrenia. These findings suggest that reduced right frontal delta wave dominance is involved in the pathophysiology of schizophrenia.


Optical breakdown of solids by few-cycle laser pulses.
We show that a broadly accepted criterion of laser-induced breakdown in solids, defining the laser-breakdown threshold in terms of the laser fluence or laser intensity needed to generate a certain fraction of the critical electron density rc within the laser pulse, fails in the case of high-intensity few-cycle laser pulses. Such laser pulses can give rise to subcycle oscillations of electron density ρ with peak ρ values well above ρc even when the total energy of the laser pulse is too low to induce a laser damage of material. The central idea of our approach is that, instead of the ρ = ρ c ratio, the laser-breakdown threshold connects to the total laser energy coupled to the electron subsystem and subsequently transferred to the crystal lattice. With this approach, as we show in this work, predictions of the physical model start to converge to the available experimental data.


Duodenal hematoma caused by endoscopic hemostatic procedures (sclerotherapy).
Endoscopic hemostatic procedures such as local injection of epinephrine are commonly used for the treatment of bleeding ulcers. Although the risks are usually considered to be minimal, there are reports describing that duodenal intramural hematomas may develop as a complication after endoscopy especially in patients susceptible to hemorrhage such as those with anticoagulants therapy or blood dyscrasia.


Gender disparities in the experience, effects and reporting of electronic aggression among secondary school students in Nigeria.
Electronic aggression is the use of electronic communication technologies to harass others. It is a problem among adolescents and young people worldwide. There is a dearth of information on this problem in developing countries in spite of the increasing use of electronic media technology in these countries. To explore gender differences in the prevalence, effects and reporting of electronic aggression among secondary school students in Oyo state, Nigeria. A cross-sectional study was conducted using mixed methods (a quantitative survey of 653 students and 18 in-depth interviews with victims and/or perpetrators). Survey students were selected using multi-stage sampling and in-depth interviewees were selected purposively. History of electronic aggression (as a perpetrator and/or victim) in the 3 months preceding the study was obtained. Respondents also provided information on the effects of the last incident of bullying on them and whether or not they reported this incident. 25.8% of males and 22.1% of females had perpetrated electronic aggression, while 42.7% of females were victims compared to 36.8% of males. More females (58.1%) than males (40.3%) perpetrated electronic aggression via phone calls and more males (33.8%) than females (22.6%) perpetrated electronic aggression via chatrooms. 45.4% of male victims and 39.4% of female victims felt angry following the last cyberbully incident. Findings from the in-depth interviewees corroborated the survey findings and a male victim reported feeling very sad and even tried to stay away from school following repeated episodes of electronic aggression. More female (59.1%) than male (42.7%) victims reported the incident to someone (p=0.035). Incidents of electronic aggression were common and the experiences of male and female students were comparable, although more female victims reported the incidents they had experienced. Victims, especially males, should be encouraged to report incidents so that the relevant authorities can institute interventions to address the problem.


Alternative 5' exons either provide or deny an initiator methionine codon to the same alpha-tubulin coding region.
The primary structures of two overlapping novel alpha-tubulin cDNA clones isolated from a Macaca fascicularis testis cDNA library and the corresponding human gene are presented. Although the general structure of the human gene conforms to that of previously described mammalian alpha-tubulin genes, there is a surprising difference: the ATG initiator codon is conspicuously absent. The macaque testis cDNA similarly lacks the initiator methionine, but otherwise encodes a variant alpha-tubulin isotype precisely conserved in the human gene. RNA blot analysis in the macaque, using a 3' untranslated region probe, revealed the existence of two additional related transcripts expressed in every tissue examined except the adult testis. Sequence comparisons indicate that the 2.0 kb testis transcript and one of the additional transcripts result from differential transcription of the same gene. The two transcripts differ only at the 5' end as a result of the recruitment of different 5' exons. Curiously, the 5' exon utilized outside the testis encodes an initiator methionine in the expected location.


Low admittance rate after ambulatory laparoscopic surgery.
Reducing intra-abdominal pressure from 12 mmHg to 6-8 mmHg during laparoscopy may reduce pain after minor laparoscopic procedures. We hypothesised that post-operative pain following ambulatory laparoscopic surgery was a limiting factor for day surgery. The primary aim of the study was to analyse risk factors for hospital admittance following laparoscopic ambulatory surgery. In this explorative prospective uncontrolled study, patients were included consecutively from 1 June 2013 to 31 March 2015 in an ambulatory setting using a standardised anaesthetic and post-operative multimodal analgesic regimen. Patients underwent the following three surgical procedures: laparoscoscopic cholecystectomy and laparoscopic inguinal and umbilical hernia repair. In the post-anaesthesia care unit, pain was repeatedly recorded using a visual analogue scale. The need for intravenously administered on-demand sufentanil was registered. The main reason for admittance to hospital was registered in a structured questionnaire. A total of 1,212 consecutive patients were included. Post-operative pain was the main reason for admittance in 14 patients, and 97% of all patients were discharged after a median of 5 h post-operatively (range: 0.4-5.0 h). In patients undergoing ambulatory laparoscopic surgery using a perioperative multimodal analgesic regimen, pain was the limiting factor for discharge in 1% of patients operated in an ambulatory set-up. none. Danish Data Protection Agency: 2012-58-0004, Danish Health Authority: 3-3013-1435/1, Clinicaltrial.gov: NCT02782832.


Job strain and health-related quality of life in a national sample.
Studies of the health effects of job strain have focused on morbidity and mortality as outcomes. This is the first study to examine the relationship of job strain to more comprehensive health status measures that encompass health-related quality of life. In a national cross-sectional survey, 1319 working men and women, aged 18 through 64 years, completed a modified version of the Job Content Questionnaire that classified workers' jobs into four categories: high strain, passive, low strain, and active. Subjects also completed the Medical Outcomes Study Short-Form Health Survey and a health distress scale. Logistic regression analyses were employed that controlled for age, race/ethnicity, gender, and education. Both work and nonwork variables were included. Job strain was significantly associated with five of nine components of health-related quality of life: physical functioning, role functioning related to physical health, vitality, social functioning, and mental health. Job strain made a modest yet statistically significant contribution beyond the effects of chronic illness and psychosocial variables. The results provide justification for further investigating the role of job strain as an independent risk factor for health-related quality of life.


A novel Dutch mutation in UNC13D reveals an essential role of the C2B domain in munc13-4 function.
UNC13D, encoding the protein munc13-4, is essential in intracellular trafficking and exocytosis of lytic granules. Mutations in this gene are associated with familial hemophagocytic lymphohistiocytosis type 3 (FHL3), a genetically heterogeneous, rare autosomal recessive immune disorder. How mutations affect function of munc13-4 is poorly understood. Since 2006 we genetically identified seven FHL patients with mutations in UNC13D. Here, we report for the first time a c.2695C>T (p.Arg899X) mutation in exon 28 of UNC13D in three young unrelated Dutch patients. The mutation causes a premature stop codon and encodes munc13-4(1-899), which lacks the C-terminal C2 domain. Genealogical research and haplotyping of the patient families demonstrated that a single ancestral founder introduced the mutation in the Netherlands. We then characterized the mutant protein phenotypically in cell biological and immunological assays. Munc13-4(1-899) was correctly targeted to CD63-positive secretory lysosomes, although its stability was reduced and dynamic turnover on the granule membrane became uncoupled from receptor signaling. In accord, and in contrast to wild-type munc13-4, ectopically expressed mutant failed to rescue degranulation in cells with silenced endogenous munc13-4. The functional and clinical data showed that this novel Dutch founder mutation leads to severe early onset of FHL3 due to misfolding and degradation of munc13-4(1-899).


Intracytoplasmic sperm injection may increase the risk of imprinting defects.
In germ cells and the early embryo, the mammalian genome undergoes widespread epigenetic reprogramming. Animal studies suggest that this process is vulnerable to external factors. We report two children who were conceived by intracytoplasmic sperm injection (ICSI) and who developed Angelman syndrome. Molecular studies, including DNA methylation and microsatellite and quantitative Southern blot analysis, revealed a sporadic imprinting defect in both patients. We discuss the possibility that ICSI may interfere with the establishment of the maternal imprint in the oocyte or pre-embryo.


Fatal case of intracerebral hemorrhage during gamma knife treatment for metastases.
This case report presents a patient suffering acute fatal intracranial-intratumoral hemorrhage during a gamma knife treatment session. Acute hemorrhage during a radiosurgery session is extremely rare and a plausible cause for this case is discussed along with a literature review of previously reported incidents. The patient was a 71-year-old male presenting with three large intracranial lesions and an underlying primary renal cell carcinoma malignancy. Because of a severe kyphotic deformity resulting from ankylosing spondylitis, the patient was placed in a moderate Trendelenburg position to allow his head to fit into the gamma knife unit during the radiosurgery session. The two left-sided lesions were to be treated with 20 Gy to the 50% isodose line, and the right-sided lesion with 16 Gy to the 40% isodose line. Anesthesia was available throughout the treatment session to aid with pain control. The gamma knife treatment was aborted because the patient suffered a generalized seizure while in the unit. Immediate head CT of the patient revealed large acute hemorrhages into all three intracranial masses. This proved to be a fatal complication. It is likely that this positioning contributed to the hemorrhage. The clinical history of this patient is provided as well as a review of the literature on acute intracranial hemorrhage associated with radiosurgical therapy.


The dynamic nuclear envelope: resilience in health and dysfunction in disease.
The canonical appearance of the nucleus depends on constant adaptation and remodeling of the nuclear envelope in response to changing biomechanical forces and metabolic demands. Dynamic events at the nuclear envelope play a vital role in supporting key nuclear functions as well as conferring plasticity to this organelle. Moreover, imbalance of these dynamic processes is emerging as a central feature of disease etiology. This review focuses on recent advances that shed light on the myriad events at the nuclear envelope that contribute to resilience and flexibility in nuclear architecture.


Performance of 4 definitions of childhood elevated blood pressure in predicting subclinical cardiovascular outcomes in adulthood.
We aimed to compare the ability of the pediatric blood pressure (BP) standards issued by the US Fourth Report, the recently proposed US, Chinese, and international standards to predict adult hypertension and subclinical cardiovascular disease (CVD). 2296 children were randomly selected from Beijing at baseline. The follow-up survey was conducted among 1177 adults. Subclinical adult CVD was assessed using the carotid-femoral pulse wave velocity (cfPWV), carotid intima-media thickness (CIMT), and left ventricular mass index (LVMI). The prevalence of pediatric elevated BP was significantly higher according to the Chinese standards vs the Fourth Report, the updated US standards, and the international standards (18.7% vs 14.2%, 17.5%, and 18.0%, respectively; all Ps < .001). Children identified as elevated BP using any of the 4 standards were more likely to have adult hypertension, high cfPWV, and high LVMI than children without elevated BP. However, only the Chinese and updated US standards can predict the increased risk of adult high CIMT. Our results indicated that the Chinese standards performed equally or better compared with 3 other standards in predicting adult hypertension and subclinical CVD.


Mineral adequacy of vegetarian diets.
The bioavailability of a number of minerals may be altered by the special characteristics of vegetarian diets. Concern has centered on both inadequate and high dietary levels of specific minerals as well as reduced bioavailability because of a variety of dietary components. The possibility that plant-based diets may compromise mineral status is briefly reviewed for the following minerals: zinc, calcium, iron, manganese, selenium, and copper.


Perturbation of deep autoencoder weights for model compression and classification of tabular data.
Fully connected deep neural networks (DNN) often include redundant weights leading to overfitting and high memory requirements. Additionally, in tabular data classification, DNNs are challenged by the often superior performance of traditional machine learning models. This paper proposes periodic perturbations (prune and regrow) of DNN weights, especially at the self-supervised pre-training stage of deep autoencoders. The proposed weight perturbation strategy outperforms dropout learning or weight regularization (L1 or L2) for four out of six tabular data sets in downstream classification tasks. Unlike dropout learning, the proposed weight perturbation routine additionally achieves 15% to 40% sparsity across six tabular data sets, resulting in compressed pretrained models. The proposed pretrained model compression improves the accuracy of downstream classification, unlike traditional weight pruning methods that trade off performance for model compression. Our experiments reveal that a pretrained deep autoencoder with weight perturbation can outperform traditional machine learning in tabular data classification, whereas baseline fully-connected DNNs yield the worst classification accuracy. However, traditional machine learning models are superior to any deep model when a tabular data set contains uncorrelated variables. Therefore, the performance of deep models with tabular data is contingent on the types and statistics of constituent variables.


Pharmacopsychiatry and iatrogenic Parkinsonism.
Through the study of the pharmacological and clinical actions of chlozapine, a new drug used in psychiatry, we are questioning one of the traditional statements on the therapeutic action of antipsychotics: the affirmation that those must have, concomitantly, antipsychotic action and intense extrapyramidal effects (drug-induced parkinsonism). Combining our own investigations and those of other authors, the generally accepted concepts on the possible biochemical mechanisms involved in the etiology of endogenous psychosis are criticized. Although there is evidence of alterations of the dopaminergic system in schizophrenia and also changes due to the action of neuroleptics, we cannot reject, given the dissociation of effects obtained with chlozapine, the possibility that the repercussion on the nigrostriatal dopaminergic system be only one of the many probably mechanisms of action of psychotropic drugs. Thus, such anatomical and neurochemical systems could be involved only in a secondary manner in the biochemical alterations typical of schizophrenia.


The choosing of sleeping position in the overnight aggregation by the solitary bees Amegilla florea urens in Iriomote Island of Japan.
In addition to the process of joining the sleeping aggregation, the choice of sleeping position is an important night-time behaviour of small diurnal insects because of the increased risk for predator attacks as well as bad weather. The aggregation behaviour of the solitary bee Amegilla florea urens was investigated to elucidate the choice of sleeping position on substrates. Male and female constructed single-sex aggregations on hanging leaves during May and June, respectively. Most individuals tended to form aggregations with other individuals while few individuals slept alone. During the aggregation forming, both the number of individuals that tried to join the aggregation and the completion time of aggregation increased with the number of sleeping individuals, whereas the success rate of joining was unaffected. The sleeping positions of subsequent arrivals on the substrates were higher than those of the first arrivals in female aggregations. Therefore, the first female to arrive tended to be located near the bottom of a hanging substrate. Dissecting sleeping females showed that they contained mature oocytes, indicating that sexually mature individuals formed aggregations. In male aggregations, however, we could not find a clear relationship between the position on substrates and the arrival sequence. We suggest that the purpose for sleeping in aggregations might be a dilution effect for nocturnal predation and that the females that finished both nesting and foraging quickly could choose the optimal positions in the aggregation when they arrived on the sleeping substrates.


Total Usual Intake of Shortfall Nutrients Varies With Poverty Among US Adults.
To examine shortfall nutrient intakes (ie, calcium, folate, potassium, magnesium, and vitamins A, C, D, and E) by poverty-to-income ratio (PIR). National Health and Nutrition Examination Survey 2011-2012, a nationally representative, cross-sectional survey. US adults with complete data on poverty status and diet were included (n = 4,524). The National Cancer Institute method was used to estimate total usual micronutrient intakes from foods, beverages, medications, and dietary supplements reported on 2 24-hour dietary recalls using measurement error correction. Calcium, folate, potassium, magnesium, and vitamins A, C, D, and E across 3 PIR categories: <130%, 130% to 350%, and ≥350%. Mean intakes of folate, vitamin C, and vitamin D were significantly greater in men, and magnesium in women, across all PIR categories. Except for calcium in men and vitamin C in women, the highest PIR category had significantly higher mean total usual intakes of all remaining shortfall micronutrients. Importantly, men and women in the highest PIR category (≥350%) were significantly less likely to have intakes below the Estimated Average Requirement across all micronutrients compared with those in the lower PIR categories. Even with dietary supplements, large proportions of US adults have micronutrient intakes below the Estimated Average Requirement. Adults at the highest adjusted income have higher micronutrient intakes and lower risk of inadequacy than those with lower incomes.


Idiopathic endomyocardial fibrosis in a Western European: a case report.
Endomyocardial fibrosis (EMF) is a rare cause of restrictive cardiomyopathy, mainly found in tropical/subtropical country. Endomyocardial fibrosis causes severe congestive symptoms and may lead to end-stage heart failure. A French Caucasian 44-year-old man without noticeable medical history and who had never travelled outside of France was hospitalized for a first episode of acute heart failure revealing an atypical appearance of the left ventricle. Cardiac magnetic resonance (CMR) identified EMF, but investigations did not identify any aetiology (no eosinophilia). Despite optimal management of chronic heart failure, functional class declined rapidly resulting in several hospitalizations for heart failure. The patient finally underwent an elective heart transplantation with good results at 6-month follow-up. Endomyocardial fibrosis exact physiopathology remains unclear, although association with eosinophilia has been reported. Diagnosis is challenging and is based on multi-modal imagery with a central role of CMR. There is no consensus on optimal management, medical therapy having poor outcomes and rate of peri-operative complications being high. Heart transplantation should be considered for eligible patients.


[Influence on extratumoral organ activities of tumor-affinity samarium-153 preparations].
Possibilities to exercise an influence on the biodistribution of a tumor-affine 153Sm-preparation, samarium-153-nitrilotriacetate (NTA), were tested. Animals experiments on tumor-bearing mice after additional application of EDTMP (ethylenediamine tetramethylene phosphonate) for the reduction of extratumorale liver-radioactivity and yttrium chloride for the reduction of unwanted underground radioactivity in bone were carried out. Furthermore, the combination of both measurements was tested. The biodistribution of 153Sm-NTA showed a rather low tumor-radioactivity of app. 0.72%/g. The additional EDTMP-application caused a dose-dependent decrease of the underground-radioactivity in liver especially if given 2 h in advance or simultaneously. The additional application of the stable yttrium salt reduced the bone radioactivity on simultaneous increase of liver- and spleen-radioactivity and practically unchanged tumor-radioactivity. The combined use of EDTMP together with the bone-affine metal salt led to a reduction of liver radioactivity on simultaneous reduction of bone radioactivity. The background radioactivity can be reduced on unchanged tumor-radioactivity by combined Na-EDTMP/YCl3-application. The present results do not allow a therapeutic exploitation because of the low tumor accumulation.


Learning Algorithm for Boltzmann Machines With Additive Weight and Bias Noise.
This brief presents analytical results on the effect of additive weight/bias noise on a Boltzmann machine (BM), in which the unit output is in {-1, 1} instead of {0, 1}. With such noise, it is found that the state distribution is yet another Boltzmann distribution but the temperature factor is elevated. Thus, the desired gradient ascent learning algorithm is derived, and the corresponding learning procedure is developed. This learning procedure is compared with the learning procedure applied to train a BM with noise. It is found that these two procedures are identical. Therefore, the learning algorithm for noise-free BMs is suitable for implementing as an online learning algorithm for an analog circuit-implemented BM, even if the variances of the additive weight noise and bias noise are unknown.


Mastopexy with autologous augmentation after massive weight loss: the intercostal artery perforator (ICAP) flap.
The reconstruction of breast and upper-body deformities in massive weight loss (MWL) patients presents specific challenges to the plastic surgeon. In addition to significant breast ptosis and loss of breast volume, bariatric patients also have excessive lateral axillary and posterior truncal tissue that may require dermolipectomy for correction. A wise-pattern mastopexy was designed with a pedicled fasciocutaneous flap based on the intercostal artery perforators (ICAP) to correct breast ptosis, to restore breast volume, and to eliminate redundant upper truncal tissue. Five MWL patients underwent mastopexy with ICAP flap augmentation. All patients had stable and esthetically pleasing results 1, 3, and 6 months postoperatively. There were no complications of infection, wound dehiscence, seroma, or hematoma. Furthermore, there was no evidence of flap loss or tissue necrosis. Mastopexy with autologous augmentation using the ICAP flap was found to be a reliable method of breast reconstruction in the MWL patient.


Is high-intensity focused ultrasound (HIFU) an option for neoadjuvant therapy for borderline resectable pancreatic cancer patients? - a systematic review.
Pancreatic cancer is with the poorest prognosis of all common cancers worldwide. Despite the advances in treatment the results are poor throughout the different methods. Pancreatic resection still yields the best outcome. However only a quarter of the patients present at operable stage. HIFU is a noninvasive technique that can be used to treat pancreatic cancer. The aim of this review is to perform a systematic review on the data about the resection rate after HIFU ablation in patients with borderline resectable pancreatic cancer (BRPC) and the impact of this technique over the oncological results. The PubMed and Wanfang databases were searched using keywords: pancreatic cancer, HIFU ablation and high-intensity focused ultrasound. All found articles were reviewed. The systematic review was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) standard guidelines. This study was financially supported by 2019 'Kuan-Ren Elite' Program of 2nd Affiliated Hospital of Chongqing Medical University, China (Grant no. KY2019G019). The English database search showed 109 papers, of which 3 met the inclusion criteria. The Wanfang database resulted in 110 papers; however, none met the inclusion criteria of the review. From the included studies 97 patients underwent neoadjuvant HIFU ablation ± chemotherapy. Thirty-four patients reached resection (35.1%). In two patients, residual tumor (R) classification was not reported. R0 resection rate in all reported patients is 30.5% (29/95). R1 resection rate is 3.2% (3/95). HIFU is found to be safe and feasible in locally advanced and metastatic pancreatic cancer with proven downstaging and downsizing effects. Further research on role of HIFU ablation as a neoadjuvant treatment for borderline resectable pancreatic cancer is needed.


Postpubertal cryptorchidism: review and evaluation of the fertility.
We assessed the fertility of 91 patients affected by unilateral cryptorchidism who were subjected to postpubertal orchidopexy in the last 15 years. All cases were clinically examined, evaluated by semen analysis and Doppler ultrasound of the spermatic artery. Twenty-two patients underwent testicular biopsy. The results indicate that orchidopexy is not the best treatment for postpubertal cryptorchid patients. After orchidopexy, 83.5% of patients were azoospermic or oligospermic, with or without asthenospermia.


What do we really know about ADHD in college students?
Research on ADHD in college students began in the 1990s and has been steadily increasing in recent years. Because young adults with ADHD who attend college have experienced greater academic success during high school than many peers with the disorder, which is likely to be associated with better overall functioning, the degree to which they experience similar patterns of adjustment difficulties was not initially known. Accumulating research suggests that college students with ADHD experience less academic success and greater psychological and emotional difficulties than other students and use alcohol and drugs at higher rates. However, conclusions to be drawn from this research are limited by the use of small samples that may not be representative of the wider population of students with ADHD, and a lack of diagnostic rigor in identifying students with ADHD to be included in such research. Studies of the effectiveness of psychosocial treatments, medication treatment, and academic accommodations are extremely limited or nonexistent. Issues particularly germane to college students include feigning ADHD and the misuse and diversion of stimulant medication. Given that at least 25 % of college students with disabilities are diagnosed with ADHD, methodologically sound investigations are clearly needed in order to better understand the impact of ADHD on college students' adjustment and to develop and implement interventions that can enhance students' success.


Gait transition cost in humans.
The energetics of locomotion depend largely on speed, gait and body size. Gait selection for a given speed appears partly, but perhaps not wholly, related to metabolic cost. One cost normally omitted from considerations of locomotion efficiency is the metabolic cost of the transition between gaits. We present the first direct assessment of the metabolic cost for the walk-run/run-walk transition in humans. The average increase in metabolic cost for a step involving a transition is 1.75 times that of a mean non-transition step at a speed where metabolic power requirements are identical for walking and running. Despite this substantial increase in cost for the transition step, the metabolic cost of gait transition is unlikely to have a strong bearing on the process of gait selection as the cost of using a metabolically inappropriate gait, even for only a few steps, will dominate.


Blood Triglycerides Levels and Dietary Carbohydrate Indices in Healthy Koreans.
Previous studies have obtained conflicting findings regarding possible associations between indices measuring carbohydrate intake and dyslipidemia, which is an established risk factor of coronary heart disease. In the present study, we examined cross-sectional associations between carbohydrate indices, including the dietary glycemic index (GI), glycemic load (GL), total amount of carbohydrates, and the percentage of energy from carbohydrates, and a range of blood lipid parameters. This study included 1530 participants (554 men and 976 women) from 246 families within the Healthy Twin Study. We analyzed the associations using a generalized linear mixed model to control for familial relationships. Levels of the Apo B were inversely associated with dietary GI, GL, and the amount of carbohydrate intake for men, but these relationships were not significant when fat-adjusted values of the carbohydrate indices were used. Triglyceride levels were positively associated with dietary GI and GL in women, and this pattern was more notable in overweight participants (body mass index [BMI] ≥25 kg/m(2)). However, total, low-density lipoprotein and high-density lipoprotein cholesterol levels were not significantly related with carbohydrate intake overall. Of the blood lipid parameters we investigated, only triglyceride levels were positively related with dietary carbohydrate indices among women participants in the Healthy Twin Study, with an interactive role observed for BMI. However, these associations were not observed in men, suggesting that the association between blood lipid levels and carbohydrate intake depends on the type of lipid, specific carbohydrate indices, gender, and BMI.


Mini review: Targeting below-ground plant performance to improve nitrogen use efficiency (NUE) in barley.
Nitrogen (N) fertilizer is one of the major inputs for grain crops including barley and its usage is increasing globally. However, N use efficiency (NUE) is low in cereal crops, leading to higher production costs, unfulfilled grain yield potential and environmental hazards. N uptake is initiated from plant root tips but a very limited number of studies have been conducted on roots relevant to NUE specifically. In this review, we used barley, the fourth most important cereal crop, as the primary study plant to investigate this topic. We first highlighted the recent progress and study gaps in genetic analysis results, primarily, the genome-wide association study (GWAS) regarding both biological and statistical considerations. In addition, different factors contributing to NUE are discussed in terms of root morphological and anatomical traits, as well as physiological mechanisms such as N transporter activities and hormonal regulation.


Characterization of a cluster of oncogenic mutations in E6 of a human papillomavirus 83 variant isolated from a high-grade squamous intraepithelial lesion.
We previously isolated human papillomavirus 83 (HPV83m) from a cervical smear. Sequence analysis of E6 and E7 proteins highlighted five mutations located in the second putative zinc-finger region of E6 (E6m), an important domain for protein-protein or protein-DNA interactions. Here, we show that E6m of HPV83m can trigger human primary cell proliferation and anchorage-independent growth properties, similarly to E6 of HPV16, a high-risk HPV (HR-HPV). Interestingly, we demonstrate that, in contrast to E6 of HPV16, E6m corrupts neither p53 stability nor telomerase activity, but acts as a specific modulator of the transcriptional machinery. By studying E6m reversion mutants, we confirmed the importance of the second zinc-finger domain in triggering the observed upregulation of cell growth and of the transcriptional machinery. Reversion of these mutations in E6m (to yield strain E6r) fully abolished the oncogenic potential of E6m, transforming the phenotype of E6 from a high-risk to a low-risk phenotype. Importantly, our data define the importance of a cluster of mutations in the second zinc finger of E6m in increasing the oncogenic potential of HPV83.


Cochlear implantation requiring a retrofacial approach to the round window.
To describe three cases of cochlear implantation utilizing a retrofacial approach to the round window. Retrospective case review. Three patients with sensorineural hearing loss undergoing cochlear implantation. Cochlear implantation via a retrofacial approach to the round window. Three patients were noted to have inadequate visualization of the round window using a standard posterior tympanotomy at the time of their cochlear implant surgery. A retrofacial approach was performed to provide exposure of the round window to ensure correct placement of the electrode array. Intraoperative photos and postoperative imaging are demonstrated. When a laterally or anteriorly positioned facial nerve obscures visualization of the round window, a retrofacial approach is a possible route to visualize the round window.


[The diagnostic screening of acute leukemia using new technologies of automated blood analysis.]
The leukemia is a neoplastic clonal disease of hematopoietic system with primary affection of bone marrow. The modern technologies of automated blood analysis permit to implement a quick primary screening of pathological samples of blood suspicious for presence of blast cells. The application of various analysis techniques (optical, cytochemical, immune phenotypical) with the purpose of detecting blast cells demonstrates their different distribution at the graphics.


Mycoplasma pneumoniae as a causative agent of community-acquired pneumonia in children: clinical features and laboratory diagnosis.
Mycoplasma pneumoniae is a common cause of community-acquired pneumonia (CAP) in children. The aim of this study was to assess the prevalence of Mycoplasma pneumoniae infection in children with CAP and find clinical, radiological and laboratory features helpful to diagnose Mycoplasma pneumoniae pneumonia. Furthermore, we evaluated the value of serology, real-time PCR (RT-PCR) and culture for the accurate diagnosis of Mycoplasma pneumoniae pneumonia. The study included 166 children aged between 1 and 15 years with radiologically confirmed pneumonia. Throat swab specimens were cultured and assessed by RT-PCR for the presence of Mycoplasma pneumoniae. Mycoplasma pneumoniae-specific IgM and IgG antibodies were determined using ELISA in paired sera. Mycoplasma pneumoniae pneumonia was diagnosed in 14.5% CAP cases. Cough (p=0.029), headache (p=0.001) and wheezing (p=0.036) were more frequent in children with Mycoplasma pneumoniae pneumonia compared to children with pneumonia caused by other pathogens. Logistic regression analysis showed that headache (odds ratio [OR] =36.077, p=0.001) and wheezing (OR=5.681, p=0.003) were significantly associated with MP pneumonia. Neither radiological findings, nor common laboratory parameters distinguished Mycoplasma pneumoniae infection in children with CAP. Using IgG serology in paired sera as the gold standard, we found that sensitivity of IgM serology, RT-PCR and culture was equal (81.82%), while specificity values were 100%, 98.6% and 100% respectively. We observed that combination of IgM detection in acute-phase serum and RT-PCR was positive for 91.7% of cases with Mycoplasma pneumoniae infection. There are no characteristic radiological findings, or routine laboratory tests that would distinguish CAP caused by Mycoplasma pneumoniae from other CAP. It was found that clinical features such as headache and wheezing are indicative for Mycoplasma pneumoniae infection. Furthermore, it was found that during the acute phase of disease, detection of IgM antibodies in combination with RT-PCR allows for precise and reliable diagnosis of Mycoplasma pneumoniae infections in children.


PVsiRNAdb: a database for plant exclusive virus-derived small interfering RNAs.
Ribonucleic acids (RNA) interference mechanism has been proved to be an important regulator of both transcriptional and post-transcription controls of gene expression during biotic and abiotic stresses in plants. Virus-derived small interfering RNAs (vsiRNAs) are established components of the RNA silencing mechanism for incurring anti-viral resistance in plants. Some databases like siRNAdb, HIVsirDB and VIRsiRNAdb are available online pertaining to siRNAs as well as vsiRNAs generated during viral infection in humans; however, currently there is a lack of repository for plant exclusive vsiRNAs. We have developed `PVsiRNAdb (http://www.nipgr.res.in/PVsiRNAdb)', a manually curated plant-exclusive database harboring information related to vsiRNAs found in different virus-infected plants collected by exhaustive data mining of published literature so far. This database contains a total of 322 214 entries and 282 549 unique sequences of vsiRNAs. In PVsiRNAdb, detailed and comprehensive information is available for each vsiRNA sequence. Apart from the core information consisting of plant, tissue, virus name and vsiRNA sequence, additional information of each vsiRNAs (map position, length, coordinates, strand information and predicted structure) may be of high utility to the user. Different types of search and browse modules with three different tools namely BLAST, Smith-Waterman Align and Mapping are provided at PVsiRNAdb. Thus, this database being one of its kind will surely be of much use to molecular biologists for exploring the complex viral genetics and genomics, viral-host interactions and beneficial to the scientific community and can prove to be very advantageous in the field of agriculture for producing viral resistance transgenic crops.


The formation of NO+ from the reaction of N2(2+) with O2.
We have studied the potentially ionospherically significant reaction between N(2)2+ with O2 using position-sensitive coincidence spectroscopy. We observe both nondissociative and dissociative electron transfer reactions as well as two channels involving the formation of NO+. The NO+ product is formed together with either N+ and O in one bond-forming channel or O+ and N in the other bond-forming channel. Using the scattering diagrams derived from the coincidence data, it seems clear that both bond-forming reactions proceed via a collision complex [N2O2]2+. This collision complex then decays by loss of a neutral atom to form a daughter dication (NO2(2+) or N2O2+), which then decays by charge separation to yield the observed products.


[Glaucoma as primary optic neuropathy].
The appearance of the new concept of glaucomatous optic neuropathy directed to idea that high intraocular pressure and vascular insufficiency in the optic nerve head are only risk factors in the appearance of glaucoma. Glaucomatous optic neuropathy is the consequence of progressive loss of the retinal ganglion cells whose axons comprise the optic nerve. A great number of neurotrophic agents are under investigation with the view of preventing the dead of retinal ganglion cells. Induction of cell rescue mechanisms may be an alternate and efficient strategy for neuroprotection. The paper presents both actual data about the pathophysiological mechanisms of glaucoma (neurotrophin deprivation, excitotoxicity caused by glutamate, "ischemic cascade", apoptosis of retinal ganglion cells) and neuroprotective and neuroregenerative therapy and antiapoptotic agents.


Psychotropic Medication Prescribing for Youth at a Regional Autism Center.
Objectives: The Seattle Children's Autism Center (SCAC) serves youth throughout Washington state (WA). The authors examined (1) whether the ethnicity and race of patients seen at the SCAC aligned with the demographics reported in the WA census, and (2) whether psychotropic medication prescriptions were associated with patient factors, including age, sex, ethnicity, race, insurance, visit number, and diagnoses. Methods: The authors extracted demographic and prescription data from electronic medical records for all patients (3-21 years) seen at the SCAC in 2018 for psychiatric medication evaluation in the context of autism spectrum disorder (ASD) and/or other related neurodevelopmental disorder (n = 1112), and used binary logistic regression to ascertain the effects of patient factors on psychotropic prescriptions. Results: The SCAC study sample appeared to align well with the WA census. Older age and higher visit number were among the most significant factors associated with psychotropic prescriptions. Psychotropic prescriptions increased with age, across all categories, except attention-deficit/hyperactivity disorder medications. There were no sex differences in prescribing rates. There were differences in prescribing rates by ethnicity and race. There were also increased prescription rates among those with Medicaid insurance. Conclusion: These demographic differences in prescribing for youth with ASD provide more specificity than prior studies about sex, ethnic, racial, and insurance-related differences, and can serve as an impetus to examine the reasons for variance.


Antigen-specific T-cell factor in cell cooperation. Mapping within the I region of the H-2 complex and ability to cooperate across allogeneic barriers.
Further mapping of the mouse T-cell factor specific for poly(Try,Glu)-polyD-LAla--polyLys is reported. It is shown to be a product of the I-A subregion of the H-2 complex by the use of antisera either raised specifically against or made specific, by absorption, for different regions of the H-2 complex. The factor cooperates across allogeneic barriers, e.g., when factor produced by one strian is combined with bone marrow cells of other H-2 incompatible strains.


Anatomic Double-Bundle Anterior Cruciate Ligament Reconstruction Is Not Superior to Anatomic Single-Bundle Reconstruction at 10-Year Follow-up: A Randomized Clinical Trial.
The anatomic double-bundle (DB) technique is purported to be a superior technique due to its mimicking of the double-stranded anatomic formation of the anterior cruciate ligament (ACL). Previous studies with 2-, 5- and 10-year follow-up are conflicted as to whether this technique is superior to the previous gold standard method of ACL reconstruction, the anatomic single-bundle (SB) reconstruction. The aim of this prospective randomized study was to compare the outcomes of the anatomic DB technique and anatomic SB technique with independent drilling at 10 years after anterior cruciate ligament (ACL) reconstruction. We hypothesized that DB ACL reconstruction would result in a better outcome in terms of the pivot-shift test. Randomized controlled trial; Level of evidence, 1. A total of 105 patients (33 women, 72 men; median age, 27 years [range, 18-52 years]) were randomized and underwent ACL reconstruction (DB group: n = 53; SB group: n = 52). All reconstruction procedures were performed anatomically by identifying the ACL footprint, using the anteromedial portal for femoral tunnel drilling, and utilizing interference screws for tibial and femoral fixation. One blinded observer examined the patients both preoperatively and at follow-up (median, 120 months [range, 112-134 months]). Multiple subjective and objective clinical evaluations were used to assess the outcomes. Radiographic assessments of osteoarthritis were performed using the Ahlbäck, Kellgren-Lawrence, and Fairbank classification systems early postoperatively and at the final follow-up. Preoperatively, no differences were found between the study groups. Overall, 70 patients (67%; DB group: n = 39; SB group: n = 31) were available for analysis at 10-year follow-up. No significant difference could be shown between the groups in terms of the pivot-shift grade, knee laxity measurements using the KT-1000 arthrometer, manual Lachman grade, single-leg hop test result, range of motion measurements, Lysholm knee score, Tegner activity score, and Knee injury and Osteoarthritis Outcome Score (KOOS) score. Correspondingly, no differences were found between the groups regarding the presence of radiographic osteoarthritis at follow-up. Both groups improved at follow-up compared with preoperatively in terms of the pivot-shift grade, knee laxity measurements using the KT-1000 arthrometer, manual Lachman grade, Lysholm knee score, and KOOS score (P < .05 [highest P value for any comparison]). The anatomic DB technique was not superior to the anatomic SB technique with independent drilling at 10-year follow-up in regard to objective and subjective measurements. As such, one could argue that there is no need for the continued use of the anatomic DB technique in an unselected population.


[Highly-effective subtractive hybridization of cDNA].
A scheme for subtractive hybridization is described allowing for a 500-1000 fold enrichment of low abundant cDNA. The scheme is based on the previously described principle of normalization of an initial mixture of differently represented cDNAs in the single-stranded portion of a tracer after the first round of subtraction and the principle of a trapper excluding the fraction of the double-stranded cDNAs formed during the first round from the subsequent PCR-amplification. The technique is simple and makes unnecessary the separation of the tracer, driver and hybrids formed after the subtraction.


Prospective Comparison of Point-of-Care Device and Standard Analyzer for Monitoring of International Normalized Ratio in Outpatient Oral Anticoagulant Clinic.
Point-of-care testing (POCT) coagulometers are increasingly being used in the hospital setting and patients' self-testing. We determined the agreement of prothrombin time international normalized ratio (INR) results by POCT coagulometer and laboratory instrument through a comparative analysis and investigated whether the results of POCT coagulometer can reliably be used without being confirmed by standard laboratory analyzer. A total of 200 INR measurements by POCT coagulometer (CoaguChek XS Pro) and laboratory analyzer (Sysmex CS2000i) were compared using Passing-Bablok regression analysis and Bland-Altman plot. Agreement of the INR measurement was further analyzed in relation to dosing decision. The correlation of INR measurements between CoaguChek XS Pro and Sysmex CS2000i was excellent (correlation coefficient = 0.973). The overall mean difference was 0.21 INR ± 0.32 (range: 1.7-0.44). The mean difference was found to get increased as INR results increased and was 0.09 in the subtherapeutic range (≤1.9 INR), 0.29 INR in the therapeutic range (2.0-3.0 INR), while 0.4 INR in the supratherapeutic range (>3.0 INR). The overall agreement was excellent (κ = 0.916) and overall 11 (5.5%) of 200 INR measurements showed a difference in dosing decision between the 2 instruments. The positive bias of POC-INR is evident in the supratherapeutic range which could affect the dosing decision requiring confirmation with the laboratory INR measurement.


[Relationship between the structure and antioxidant activity of various betalains].
Antioxidant activities of nine betalains were studied on the model of linetol peroxidation. Betaxanthins were shown to have the highest antioxidant activity. The relationship between the chemical structure and antioxidant activity of betalains was examined.


Recombinant granulocyte/macrophage-colony stimulating factor in human and murine bone marrow transplantation.
Recombinant granulocyte/macrophage-colony stimulating factor (rGM-CSF) is a protein that mediates a broad range of biological activities including inducing proliferation of bone marrow progenitor cells and up-regulating the functional capabilities of neutrophils, monocytes, and macrophages. We have administered rGM-CSF in vivo in the context of allogeneic (murine) and autologous (human) bone marrow transplantation (BMT). In a murine allogeneic model of T-cell depletion constructed to favor graft failure/rejection of donor marrow, ex vivo treatment of marrow with rGM-CSF significantly promoted engraftment. However, when rGM-CSF was infused in vivo, engraftment was significantly impaired. We have initiated a phase I clinical trial of rGM-CSF in human autologous BMT for patients with acute lymphoblastic leukemia (ALL). rGM-CSF has been administered for 14-21 days in a dose escalation study (16-128 micrograms/M2/day). At high doses of rGM-CSF, neutrophil recovery has returned earlier and to higher levels than previously observed in historical controls. rGM-CSF related toxicity in this study has been mild.


Activation of factor XII in rat plasma: protection by benzamidine of the cofactor function of high molecular weight kininogen.
Factor XII has been assayed as kaolin-activated prekallikrein activator in rat citrated plasma pretreated with acetone (Briseid et al. 1978 & 1979; Briseid & Berstad 1979). In the present work benzamidine added during blood collection increased the extent of activation by a factor of 6. Rat high molecular weight kininogen (HMWK) added to acetone-treated citrated plasma likewise increased the activation, providing evidence of the protection by benzamidine of the cofactor function of HMWK. All cofactor capacity was retained after the removal of the kinin part of HMWK. Experiments carried out with plasminogen-free plasma showed that plasmin could hardly be the the factor responsible for the destruction of HMWK. The stoichiometric factor XII concentration-effect curve obtained by diluting acetone-treated rat plasma with acetone-treated human factor XII deficient plasma showed that factor XII is present in functional excess, the concentration of HMWK deciding the extent of activation. By diluting acetone-treated rat plasma with buffer, HMWK concentration-effect curves were obtained which were approximately linear over a range of 0.03-0.40 microgram (bradykinin equivalents) per ml kaolin incubate. No further activation of factor XII was obtained at 0.80 microgram/ml.


A novel mixed phospholipid functionalized monolithic column for early screening of drug induced phospholipidosis risk.
Drug-induced phospholipidosis (PLD) is characterized by the excessive accumulation of phospholipids, resulting in multilamellar vesicle structure within lysosomes. In the present study, a novel mixed phospholipid functionalized monolithic column was developed for the first time through a facile one-step co-polymerization approach. The phospholipid composition of the monolith can be adjusted quantitatively and accurately to mimic the mixed phospholipid environment of different biomembranes on a solid matrix. The mixed phospholipid functionalized monolith as a promising immobilized artificial membrane technique was used to study drug-phospholipid interaction. Scanning electron microscopy, elemental analysis, FT-IR spectra, ζ-potential analysis and micro-HPLC were carried out to characterize the physicochemical properties and separation performance of the monolith. Mechanism studies revealed that both hydrophobic and electrostatic interactions play an important role in the retention of analytes. The ratio of their contributions to retention can be easily manipulated by adjusting the composition of the mixed phospholipids, in order to better mimic the interaction between drugs and cell membrane. The obtained mixed phospholipid functionalized monolithic columns were applied to the screening of drug-induced PLD potency. Data from 79 drugs on the market demonstrated that the chromatographic hydrophobicity index referring to the mixed phospholipid functionalized monolith at pH 7.4 (CHI IAM7.4) for the selected drugs were highly correlated with the drug-induced PLD potency data obtained from other in vivo or in vitro assays. Moreover, the effect of the acidic phospholipid phosphatidylserine proportion on prediction accuracy was also investigated. The monolith containing 20% phosphatidylserine and 80% phosphatidylcholine exhibited the best prediction ability for the drug-induced PLD potency of the tested compounds. This research has led to the successful development of a novel and facile approach to prepare a mixed phospholipids functionalized monolith, which offers a reliable, cost-effective and high-throughput screening tool for early prediction of the PLD potency of drug candidates.


Endocytic Trafficking at the Mature Podocyte Slit Diaphragm.
Endocytic trafficking couples cell signaling with the cytoskeletal dynamics by organizing a crosstalk between protein networks in different subcellular compartments. Proteins residing in the plasma membrane are internalized and transported as cargo in endocytic vesicles (i.e., endocytosis). Subsequently, cargo proteins can be delivered to lysosomes for degradation or recycled back to the plasma membrane. The slit diaphragm is a modified tight junction connecting foot processes of the glomerular epithelial cells, podocytes. Signaling at the slit diaphragm plays a critical role in the kidney while its dysfunction leads to glomerular protein loss (proteinuria), manifesting as nephrotic syndrome, a rare condition with an estimated incidence of 2-4 new cases per 100,000 each year. Relatively little is known about the role of endocytic trafficking in podocyte signaling and maintenance of the slit diaphragm integrity. This review will focus on the role of endocytic trafficking at the mature podocyte slit diaphragm.


[Experiences with the preventive use of aminophylline (Euphylline) in apnea and periodic respiration in infants].
Sleep apnea and periodic breathing in infants are the result of a mild hypoxia and they are the requirement for SIDS. As a results of the modern medicine each 4.-5. death is the cause of SIDS during the first year of life. The positive effect of theophylline on apnea of prematurity is known since 1973. We have given theophylline (Euphyllin) from 1979 till 1986 to 198 premature infants with a birth weight below 2000 g for apnea prophylaxis orally in a doses of 9 mg/kg body weight per day distributed in 3 to 4 doses for a period of 1 to 4 months. Since then primary apnea in premature infants haven't any importance. Beside the home-monitoring we give theophylline for SIDS. In 1986 and 1987 1041 healthy term newborn infants received theophylline over a period of 6-8 weeks and more then 300 newborns until 6 months and more. There were no deaths from these infants form the cause of SIDS. Since 1987 all newborn infants with a pathological hypoxia-test as a screening test for the risk of SIDS received Euphyllin until normalization. With this method we have reduced evidently the death rate of SIDS in our district.


Effects of cetirizine on human eosinophil and neutrophil activation in vitro.
The ability of cetirizine, a novel antihistamine agent, to inhibit the in vivo activation of human eosinophils, neutrophils and monocytes has been investigated using C3b- and IgG-dependent rosette formation, cytotoxicity against opsonised parasitic larvae and adherence to plasma-coated glass (PCG). The drug inhibited platelet-activating factor (PAF)-induced enhancement of eosinophil and neutrophil IgG (Fc) and complement (C3b) rosettes with an IC50 of 2 x 10(-5) M. There was also comparable inhibition of PAF-dependent enhancement of eosinophil cytotoxicity (for complement-coated schistosomula of Schistosoma mansoni). Cetirizine inhibited PAF-induced eosinophil, but not neutrophil, hyperadherence to PCG. These data support the view that cetirizine may exert some of its anti-allergic effects by inhibiting the activation of human granulocytes and that it may also selectively inhibit PAF-induced eosinophil hyperadherence.


Evaluation of an Optimal Epidemiological Typing Scheme for Legionella pneumophila with Whole-Genome Sequence Data Using Validation Guidelines.
Sequence-based typing (SBT), analogous to multilocus sequence typing (MLST), is the current "gold standard" typing method for investigation of legionellosis outbreaks caused by Legionella pneumophila However, as common sequence types (STs) cause many infections, some investigations remain unresolved. In this study, various whole-genome sequencing (WGS)-based methods were evaluated according to published guidelines, including (i) a single nucleotide polymorphism (SNP)-based method, (ii) extended MLST using different numbers of genes, (iii) determination of gene presence or absence, and (iv) a kmer-based method. L. pneumophila serogroup 1 isolates (n = 106) from the standard "typing panel," previously used by the European Society for Clinical Microbiology Study Group on Legionella Infections (ESGLI), were tested together with another 229 isolates. Over 98% of isolates were considered typeable using the SNP- and kmer-based methods. Percentages of isolates with complete extended MLST profiles ranged from 99.1% (50 genes) to 86.8% (1,455 genes), while only 41.5% produced a full profile with the gene presence/absence scheme. Replicates demonstrated that all methods offer 100% reproducibility. Indices of discrimination range from 0.972 (ribosomal MLST) to 0.999 (SNP based), and all values were higher than that achieved with SBT (0.940). Epidemiological concordance is generally inversely related to discriminatory power. We propose that an extended MLST scheme with ∼50 genes provides optimal epidemiological concordance while substantially improving the discrimination offered by SBT and can be used as part of a hierarchical typing scheme that should maintain backwards compatibility and increase discrimination where necessary. This analysis will be useful for the ESGLI to design a scheme that has the potential to become the new gold standard typing method for L. pneumophila.


Targeting Smoothened Sensitizes Gastric Cancer to Chemotherapy in Experimental Models.
BACKGROUND The Hedgehog pathway receptor smoothened (SMO) has critical roles in tumor progression. However, whether SMO is a key factor regulating gastric cancer chemotherapy resistance is unknown. MATERIAL AND METHODS We investigated the potential functions of SMO in inducing gastric cancer paclitaxel resistance in clinical samples, gastric cancer cell lines (424GC and AGS), and subcutaneous syngeneic mouse models. RESULTS We found high SMO expression in paclitaxel-resistant gastric cancer clinical samples. Paclitaxel gastric cancer cells had higher SMO expression than in drug-sensitive cells. Upregulating SMO expression induced paclitaxel resistance in gastric cells lines via enhancing cell proliferation and inhibiting apoptosis. The combination of IPI-926, an inhibitor of SMO, with paclitaxel decreased cell viability of paclitaxel-resistant gastric cancer cells in vitro and controlled tumor growth in animal models. CONCLUSIONS The Hedgehog pathway receptor SMO is an important regulator of gastric cancer paclitaxel resistance and could be a target for sensitizing paclitaxel-resistant tumors.


Writer's cramp: a controlled trial of habit reversal treatment.
In uncontrolled studies, several behavioural methods, including habit reversal, were said to be useful in writer's cramp. In this controlled study, 23 subjects with writer's cramp recruited from a neurology clinic were randomly allocated to five sessions over four weeks of either habit reversal training or a control treatment of relaxation training. Three subjects dropped out. Twenty patients (9 habit reversers, 11 controls) completed the trial up to three months follow-up. Outcome measures included observation of writing within the session, assessment of writing tasks completed at home, and blind ratings by an independent assessor. The results showed that habit reversal was no better than relaxation. Taking both treatments together, patients improved to three months follow-up on seven of nine measures, but remained substantially handicapped.


Delayed onset and diminished magnitude of rotavirus activity--United States, November 2007-May 2008.
Rotavirus is the leading cause of severe acute gastroenteritis among infants and young children, accounting for an estimated 527,000 deaths among children aged <5 years worldwide in 2004 (1,2). In the United States, rotavirus causes few deaths (20-60) each year, but remains a substantial cause of morbidity among children, resulting in approximately 55,000--70,000 hospitalizations, 205,000-272,000 emergency department (ED) visits, and 410,000 physician office visits. In the continental United States, rotavirus activity follows a distinct winter-spring seasonal pattern. In winter months, approximately 50% of hospitalizations and ED visits and 30% of outpatient visits for acute gastroenteritis among U.S. children aged <3 years are caused by rotavirus. To prevent rotavirus disease, in February 2006, a human-bovine rotavirus vaccine, RotaTeq (Merck & Co., Inc., Whitehouse Station, New Jersey), was recommended for routine use among U.S. infants . To summarize rotavirus activity through May 3, during the current 2007-08 season, CDC analyzed data from the National Respiratory and Enteric Virus Surveillance System (NREVSS) and the New Vaccine Surveillance Network (NVSN). The results indicated that, when compared with the 15 previous seasons spanning 1991-2006, rotavirus activity during the current season appeared delayed in onset by 2-4 months and diminished in magnitude by >50%. Additional surveillance and epidemiologic studies are needed to confirm the impact of rotavirus vaccination on the 2007-08 season and to monitor the impact of the vaccine on the incidence and epidemiology of rotavirus during future seasons.


Community Violence Exposure, Sleep Disruption, and Insulin Resistance in Low-Income Urban Adolescents.
Exposure to violence, which is experienced at disproportionally higher levels by black versus white youth, is associated with disruptions in sleep and elevated cardiovascular risk. Further, poor sleep hygiene is associated with insulin resistance. However, research to date examining disruptions in sleep and cardiovascular risk in African-American adolescents has not taken the impact of exposure to violence into account, nor considered how gender might affect patterns of association. The present study addressed this gap by testing a path model linking exposure to community violence, sleep disruption, and insulin resistance in a sample of African-American adolescents and evaluating model fit across gender. African-American adolescents (N = 107; 56% female; Mage = 14.29, SD = 1.17) completed structured interviews at home and provided a blood sample after fasting overnight. The model fit connecting exposure to violence with sleep disruption and insulin resistance, adjusting for depressive symptoms and body mass index z score, was excellent. Multiple group analysis indicated gender differences in model fit. Path analysis revealed significant positive associations between exposure to violence and sleep disruption and sleep disruption and insulin resistance for females but not males. These data indicate that low-income, urban African-American female adolescents who witness violence and experience sleep disruptions may already be at elevated risk for health problems compared with their male counterparts. Additional research should attempt to replicate and explicate the underlying reasons for the gender differences observed here, with the goal of improving health and disrupting the path leading to health disparities.


Porphyrinoid f-Element Complexes.
Porphyrin and related pyrrole-containing macrocycles, collectively porphyrinoids, are versatile ligands that allow access to a multitude of coordination modes. Judicious modification of the porphyrin core as well as the pendant substituents has extended the coordination chemistry of porphyrinoids to include systems that are able to stabilize f-block element complexes with possible utility. This review focuses on our group's efforts to prepare expanded porphyrin and porphyrinogen ligands that can serve as tools to study and apply f-element metal coordination chemistry: it covers the background of the topic, selected syntheses, and application of these species in the chemical and medical sciences.


Steroid sulfatase and filaggrin mutations in a boy with severe ichthyosis, elevated serum IgE level and moyamoya syndrome.
X-linked ichthyosis (XLI) is a relatively common, recessive condition caused by mutations in the steroid sulfatase (STS) gene. Common loss-of-function mutations in the filaggrin gene (FLG) cause ichthyosis vulgaris and predispose individuals to atopic eczema. We report a case of a 6-year-old boy who presented with unusually severe XLI, an increased serum immunoglobulin E level (2120IU/ml) and moyamoya angiopathy. Whole-exome sequencing identified a gross deletion encompassing the STS in Xp22.31 and the p.K4022X FLG mutation. The deletion is at least 1.6Mb in size in the proband, based on real-time quantitative polymerase chain reaction results. No other genetic mutations related to ichthyosis, moyamoya or hyper-immunoglobulin E syndrome were detected. Furthermore, his mother's brothers suffered from mild XLI and only had a deletion encompassing the STS. Additionally, his father and older sister suffered from mild ichthyosis vulgaris and had the p.K4022X FLG mutation. We report the first case of XLI with concurrent moyamoya syndrome. Moreover, an IgE-mediated immune response may have triggered the moyamoya signaling cascade in this patient with ichthyosis. Furthermore, our study strengthens the hypothesis that filaggrin defects can synergize with an STS deficiency to exacerbate the ichthyosis phenotype in an ethnically diverse population.


In vivo versus in vitro oviductal glycoprotein (OGP) association with the zona pellucida (ZP) in the hamster and baboon.
The goal of this study was to determine if differences exist between in vivo vs. in vitro OGP association with the ZP and to quantitate those differences. Ovarian oocytes were harvested 12.5 or 27 hr post-hCG from hyperstimulated hamsters or baboons, respectively. Hamster and baboon ovarian oocytes were incubated in vitro in media +/- homologous OGP (100 or 200 microg/100 microl) or in some studies with 100 microl oviductal fluid for 3, 6, or 24 hr at 37 degrees C. Some of the baboon ovarian oocytes were transferred immediately after harvesting to the ampulla of both oviducts using a tom cat catheter and retrieved after a 3 hr in situ incubation. Hamster oviductal oocytes were collected 3, 6, and 24 hr following ovulation. After incubation or oocyte retrieval from the oviduct, cumulus cells were removed, oocytes were washed extensively and binding of OGP to the ZP was examined by immunofluorescence. Fluorescence intensity was quantified using densitometric scanning of photographic negatives with the background of each negative as an internal control. In all studies, OGP association with the ZP was significantly greater in vivo than in vitro (P < 0.05). In vitro OGP association with the ZP did not significantly increase with incubation time or OGP concentration; however, a small nonsignificant increase in OGP association with the ZP in the oviduct was detected over time. Differences did not appear to be due to depletion of OGP from the in vitro incubation media, since Western blot analysis of the media showed that OGP was still present. Although OGP concentration in vivo is unknown, Western blots showed similar intensity comparing 100 microg of OGP media and oviductal fluid. Immunolocalization of OGP using laser confocal microscopy showed regional differences in OGP binding. The outer half of the zona pellucida had significantly more OGP bound than the inner half on oviductal oocytes. No regional differences were detected for in vitro incubated oocytes. In conclusion, OGP association with the ZP is greater in vivo vs. in vitro, suggesting that one must be cautious in designing and evaluating in vitro studies of OGP function.


Exploring the structural requirements in multiple chemical scaffolds for the selective inhibition of Plasmodium falciparum calcium-dependent protein kinase-1 (PfCDPK-1) by 3D-pharmacophore modelling, and docking studies.
Current research on antimalarial protein kinases has provided an opportunity to design kinase-based antimalarial drugs. We have developed a common feature-based pharmacophore model from a set of multiple chemical scaffolds including derivatives of 3,6-imidazopyridazines, pyrazolo[2,3-d]pyrimidines and imidazo[1,5-a]pyrazines, in order to incorporate the maximum structural diversity information in the model for the Plasmodium falciparum calcium-dependent protein kinase-1 (PfCDPK-1) target. The best pharmacophore model (Hypo-1) with the essential features of two hydrogen bond donors (HBD), one hydrophobic aromatic (HYAr) and one ring aromatic (RA) showed the classification accuracies of 86.27%, 78.43% and 100.00% in labelling the training and test set (test set-1 and test set-2) compounds into more active and less active classes. In order to identify the crucial interaction between multiple scaffold ligands and the target protein, we first developed the homology model using a template structure of P. bergheii (PbCDPK1; PDB ID: 3Q5I), and thereafter performed the docking studies. The residues such as Lys85, Phe147, Tyr148, Leu198, Val211, and Asp212 were found to be the most important interacting residues for possessing PfCDPK-1 inhibitory activity.


[Changes in proteoglycans in human articular cartilage in relation to age].
The authors investigated in articular cartilage the presence and amount of the free fragment of the protein nucleus of the proteoglycan monomer containing the area of the bond with hyaluronic acid (HABR) and the presence of the small dermatan sulfate proteoglycan in relation to age. The articular cartilage of older subjects contains a much higher ratio of the protein fragment with functional HABR, as compared with young adult tissue. The more ready extractability of this fragment suggests an impaired bond between the proteoglycan monomer and hyaluronic acid. The ratio of the small dermatan sulfate proteoglycan is significantly reduced in the articular cartilage of older subjects. In the articular cartilage of a very old person (87 years) this proteoglycan was not detected or its content is at the borderline of detection of the methods used.


False-positive results released by direct-to-consumer genetic tests highlight the importance of clinical confirmation testing for appropriate patient care.
There is increasing demand from the public for direct-to-consumer (DTC) genetic tests, and the US Food and Drug Administration limits the type of health-related claims DTC tests can market. Some DTC companies provide raw genotyping data to customers if requested, and these raw data may include variants occurring in genes recommended by the American College of Medical Genetics and Genomics to be reported as incidental/secondary findings. The purpose of this study was to review the outcome of requests for clinical confirmation of DTC results that were received by our laboratory and to analyze variant classification concordance. We identified 49 patient samples received for further testing that had previously identified genetic variants reported in DTC raw data. For each case identified, information pertaining to the outcome of clinical confirmation testing as well as classification of the DTC variant was collected and analyzed. Our analyses indicated that 40% of variants in a variety of genes reported in DTC raw data were false positives. In addition, some variants designated with the "increased risk" classification in DTC raw data or by a third-party interpretation service were classified as benign at Ambry Genetics as well as several other clinical laboratories, and are noted to be common variants in publicly available population frequency databases. Our results demonstrate the importance of confirming DTC raw data variants in a clinical laboratory that is well versed in both complex variant detection and classification.


Clinical characteristics and cognitive function in bipolar disorder patients with different onset symptom.
In recent years, studies on the clinical features and cognitive impairment of patients with different first-episode types of bipolar disorder have received increasing attention. The patients with bipolar disorder may present with different symptoms at first onset. The aim of this study is to assess the cognitive functions of a patient's index episode of bipolar disorder, depression or mania, on risk factors of effecting on cognitive functions. One hundred sixty eight patients with bipolar disorder diagnosed for the first time were enrolled in the study. All patients were divided into two groups according to their index episode of bipolar disorder, either depression or mania. Seventy three patients of the cohort had an index episode mania and 95 patients had initial symptoms of depression. Demographic and clinical disease characteristic data of all enrolled patients were collected. Meanwhile, 75 healthy controls were included. Demographic data of controls were collected. The cognitive functions of all patients and controls were detected by continuous performance test (CPT), digital span test (DST) and Wisconsin card sorting test (WCST). The main cognitive functions data were compared among the mania group, depression group and control group. The relevant risk factors affecting cognitive function were analyzed. (1) Most patients with bipolar disorder had an index episode depression (56.55% vs. 43.45%). Compared with the depression group, the mania group had later age of onset [(24.01 ± 4.254) vs. (22.25 ± 6.472), t = 2. 122, p = 0.035]. The education level of patient groups was lower than control group (p < 0.001). (2) The healthy control group's DST, WCST and CPT scores were better than the patient groups (All p < 0.05). The mania group's DST (forward, reverse, sum), WCST (total responses, completed classifications, correct responses, incorrect responses, percentage of correct responses, completed the number of responses required for classification, the percentage of conceptualization level, the number of persistent responses, non-persistent errors), CPT (2 digit score, 3 digit score, 4 digit score) was better than the depression group (p < 0.05). (3) In mania group, correlation analysis showed that all CPT parameter, inverse digit span, and the sum of DST was negatively correlated with the education level (All p < 0.05). The CPT-4 digit score was negatively correlated with onset age (p < 0.05). In the WCST, the number of correct responses, the percentage of correct responses and the percentage of conceptualization level were positively correlated with the BRMS score (All p < 0.05). The number of false responses and persistent responses were negatively correlated with the BRMS score (All p < 0.05). The number of persistent errors and percentage of persistent errors was positively correlated with education years (All p < 0.05). In depression group, there was a positive correlation between inverse digit span and the education level (p < 0.05). In our study, there were cognitive impairments in attention, memory, and executive function of patients with different onset syndromes of bipolar disorder. Compared with the mania group, the degree of cognitive impairments in bipolar patients with the depressive episode was more severe. The risk factors affecting cognitive impairments included the age of onset, education level, number of hospitalizations and severity of illness.


Human amniotic membrane and prostaglandin biosynthesis.
The human amnion has become a significant tissue for metabolism of chemical substances with biologic activities, such as steroid hormones and prostaglandins. In this paper our studies on the biosynthesis of prostaglandins in human amnion focused on the role of prostaglandins in initiating and maintaining labor. First of all, the source of prostaglandins released in amniotic fluid was investigated. The amnion was demonstrated to possess the highest activity of generating prostaglandins among amnion, chorion laeve, and decidua vera, obtained after normal vaginal delivery. Subsequently, the bioconversion of arachidonic acid into prostaglandins and related compounds using the homogenate of human amnion was carried out without the addition of cofactors in the incubation mixture to show the natural spectrum of various types of PGs formed. PGE2 was revealed to be a main product of the amnion; its conversion rate was 5% of incubated radioactivity. Other compounds catalyzed by cyclooxygenase were PGF2 alpha (0.2%), TXB2 (0.3%), and HHT (1-2%), whereas 15-HETE (2-3%) and a mixture of 9, 11, 12-HETE (1-2%) were formed by lipoxygenase in the amnion. And third, the activity to produce PGE2 in the amnion obtained at normal vaginal delivery was greater than that obtained at cesarean section prior to the onset of labor. Thus, these results suggested that the amnion played a significant role in prostaglandin biosynthesis in uterine tissues. To provide a better understanding of the metabolism of arachidonic acid in the amnion as regards initiation and maintenance of labor, we discuss prostaglandin biosynthesis in the amnion and the mechanism of arachidonic acid release.


How green is my operation theater?
To ascertain the awareness regarding global warming and the anesthesia practices contributing to it in the city of Delhi. A questionnaire was circulated amongst the qualified anesthesiologists (consultants and senior residents) in the city of Delhi. The initial contact was made through e-mail and the questionnaire was required to be filled and returned electronically. The questionnaire was also made available online at http://sites.google.com/site/surveydelhi. After 1 month, the forms were distributed physically. Assuming that at least 50% of the approximately 1200 practising anesthesiologists would be able to recognize the greenhouse gases correctly, the target number of responses was 150 with 99% confidence limit. Of the 831 anesthesiologists contacted, only 184 responded. Ninety-eight percent were aware of the greenhouse effect, but only 15.8% (29) could correctly identify all the greenhouse gases. However, 47.28% (87) could identify nitrous oxide and inhalational agents as a cause of greenhouse effect. Ninety percent of the respondents use circle system and 87% use low flows frequently. Ninety-three percent (171) of respondents routinely use nitrous oxide, and 32.1% (59) would, however, not use air even if made available. Seventy-nine percent (145) advocated total intravenous anesthesia as an alternative to reduce the menace. Only 22% were motivated enough to respond to the survey. More than half of these anesthesiologists were not aware about the anesthetic agents contributing to the greenhouse effect. However, their clinical practices inadvertently do not add to the environmental pollution.


Stiffness after total knee arthroplasty.
Stiffness after total knee arthroplasty (TKA) adversely affects outcome and impacts patient function. Various risk factors for stiffness after TKA have been identified, including reduced preoperative knee range of motion, history of prior knee surgery, etiology of arthritis, incorrect positioning or oversizing of components, and incorrect gap balancing. Mechanical and associated causes, such as infection, arthrofibrosis, complex regional pain syndrome, and heterotopic ossification, secondary gain issues have also been identified. Management of stiffness following TKA can be challenging. The condition needs to be assessed and treated in a staged manner. A nonsurgical approach is the first step. Manipulation under anesthesia may be considered within the first 3 months after the index TKA, if physical therapy fails to improve the range of motion. Beyond this point, consideration should be given to surgical intervention such as lysis of adhesions, either arthroscopically or by open arthrotomy. If the cause of stiffness is deemed to be surgical error, such as component malpositioning, revision arthroplasty is indicated. The purpose of this article is to evaluate the various aspects of management of stiffness after TKA.


Electron cotunneling into a Kondo lattice.
Motivated by recent experimental interest in tunneling into heavy-electron materials, we present a theory for electron tunneling into a Kondo lattice. The passage of an electron into a Kondo lattice is accompanied by a simultaneous spin flip of the localized moments via cotunneling mechanism. We compute the tunneling current with the large-N mean field theory. In the absence of disorder, differential tunneling conductance exhibits two peaks separated by the hybridization gap. Disorder effects lead to the smearing of the gap resulting in a Fano line shape.


Fractional Quantum Hall States in Bilayer Graphene Probed by Transconductance Fluctuations.
We have investigated fractional quantum Hall (QH) states in Bernal-stacked bilayer graphene using transconductance fluctuation measurements. A variety of odd-denominator fractional QH states with νQH → νQH + 2 symmetry, as previously reported, are observed. However, surprising is that also particle-hole symmetric states are clearly resolved in the same measurement set. We attribute their emergence to the reversal of orbital states in the octet level scheme induced by a strong local charge imbalance, which can be captured by the transconductance fluctuations. Also the even-denominator fractional QH state at filling -1/2 is observed. However, contrary to a previous study on a suspended graphene layer [ Ki et al. Nano Lett. 2014, 14 , 2135 ], the particle-hole symmetric state at filling 1/2 is detected as well. These observations suggest that the stability of both odd and even denominator fractional QH states is very sensitive to local transverse electric fields in bilayer graphene.


Removal of fluoride from wastewater using HCl-treated activated alumina in a ribbed hydrocyclone separator.
Excessive fluoride concentration in wastewater is a major health concern worldwide. The main objective of wastewater treatment is to allow industrial effluents to be disposed of without danger to the human health and the natural environment. In this current study, experiments have been conducted to remove fluoride from aqueous solution using alumina and HCl (Hydrochloric acid) treated activated alumina in a continuous mode. A spiral rib was introduced in the cylindrical part of the conventional hydrocyclone to increase the performance, and the new hydrocyclone is dubbed as ribbed hydrocyclone. Experiments were carried out to analyze the performance of the ribbed hydrocyclone and compared the results with the conventional hydrocyclone of the same dimension. The efficiency of conventional and ribbed hydrocyclone at a slurry flow rate of 50 LPM (liter per minute) for the solid concentration of 1.4 wt% were 80% and 93.5% respectively. The cut size d50 of the conventional and ribbed hydrocyclone was 18 µm and 13 µm respectively at a slurry velocity of 50 LPM. Fluoride removal efficiency using alumina and HCl-treated alumina was also investigated in a continuous mode by the ribbed hydrocyclone. Maximum fluoride removal efficiency was 49.5%, and 80% for alumina and HCl-treated alumina for the initial concentration of 10 mg/L at a slurry flow rate of 50 LPM.