Selection of wrist posture in conditions of motor ambiguity.
In our everyday motor interactions with objects, we often encounter situations where the features of an object are determinate (i.e., not perceptually ambiguous), but the mapping between those features and appropriate movement patterns is indeterminate, resulting in a lack of any clear preference for one posture over another. We call this indeterminacy in stimulus-response mapping 'motor ambiguity'. Here, we use a grasping task to investigate the decision mechanisms that mediate the basic behavior of selecting one wrist posture over another in conditions of motor ambiguity. Using one of two possible wrist postures, participants grasped a dowel that was presented at various orientations. At most orientations, there was a clear preference for one wrist posture over the other. Within a small range of orientations, however, participants were variable in their posture selection due to the fact that the dowel was ambiguous with respect to the hand posture it afforded. We observed longer reaction times (RT) during 'ambiguous' trials than during the 'unambiguous' trials. In two subsequent experiments, we explored the effects of foreknowledge and trial history on the selection of wrist posture. We found that foreknowledge led to shorter RT unless the previous trial involved selecting a posture in the ambiguous region, in which case foreknowledge gave no RT advantage. These results are discussed within the context of existing models of sensorimotor decision making.


A Prevalence Study of Psychosocial Distress in Adolescents and Young Adults With Cancer.
Psychosocial distress is common among cancer patients. Significant associations between coping and social support with distress and quality of life in adult cancer patients have been identified before, but little is known about the interrelationships between distress, medical coping, and social support in adolescents and young adults (AYAs). The aims of this study are to investigate the prevalence of psychological distress in Chinese AYAs with cancer and examine the associations among distress, anxiety and depression, medical coping, and social support in the same population. A total of 610 AYA patients were recruited for this study; 551 patients completed the Chinese version of the National Comprehensive Cancer Network Distress Thermometer (DT), the Hospital Anxiety and Depression Scale, the Medical Coping Modes Questionnaire, and the Social Support Rating Scale. The prevalence of psychological distress was 89.1% in Chinese AYAs with cancer. The DT scores were the highest in the 21- to 25-year-old patients; the DT scores were positively correlated with anxiety and depression (P < .01) but negatively correlated with medical coping and social support (P < .01). The prevalence of psychological distress in AYA cancer patients was higher than that in the general cancer population. Medical coping and social support can lower the prevalence of psychological distress in AYA cancer patients. Findings suggest the need for evidence-based intervention strategies to enhance medical coping and social support in AYA cancer patients. Nurses are crucial to implementing psychological interventions in AYA cancer patients.


Beta 1-adrenergic selectivity of the new cardiotonic agent denopamine in its stimulating effects on adenylate cyclase.
Effects of the new selectively beta 1-adrenergic cardiotonic drug denopamine (TA-064), (-)-(R)-1-(p-hydroxyphenyl)-2-[(3,4-dimethoxyphenethyl)amino]ethanol, on the adenylate cyclase-adenosine-3',5'-monophosphate (c-AMP) system of various tissues and cells in rats and guinea pigs were investigated in comparison with those of isoproterenol. Denopamine at concentrations above 10(-6) M stimulated lipolysis in vitro, and, above 10(-5) M, elevated the c-AMP level in isolated rat fat cells. The c-AMP level of guinea-pig heart ventricular muscle was also elevated when the heart was perfused with 3 X 10(-6) M denopamine or when slices of ventricular muscle were incubated with 10(-6) M denopamine. These changes were abolished in the presence of beta-adrenergic antagonists. Incubation with denopamine did not cause substantial elevation of c-AMP levels in rat reticulocytes and diaphragm. Denopamine activated adenylate cyclase of the rat cell membranes in a concentration-dependent manner. Although dose dependence was less apparent, denopamine also activated adenylate cyclase of the membrane fraction from guinea pig cardiac muscle, but it hardly activated the same enzyme from rat reticulocytes. Isoproterenol, on the other hand, showed marked concentration-dependent activation of adenylate cyclase in all these preparations. Denopamine did not inhibit c-AMP phosphodiesterase of both particulate and supernatant fractions of guinea-pig cardiac muscle. The stimulation of lipolysis by denopamine was observed even when elevation of the c-AMP level was not detected, while the stimulation of lipolysis by isoproterenol was always accompanied with an elevation of c-AMP. When guinea-pig hearts were perfused with 3 X 10(-6) M denopamine or 10(-7) M isoproterenol, their cardiotonic effects were of the same magnitude whereas the degree of c-AMP elevation in the ventricular tissue by denopamine was significantly less than that by isoproterenol. It was concluded that stimulation of the adenylate cyclase-c-AMP system by denopamine was restricted to the tissues whose receptors were predominantly of the beta 1-type, and that the elevation of c-AMP levels in these tissues by denopamine was less marked than by isoproterenol, suggesting that the stimulation of lipolysis and heart by denopamine may be mediated by a special pool of c-AMP or some other unknown factor(s).


Heteroagglomeration of oxide nanoparticles with algal cells: effects of particle type, ionic strength and pH.
Discharged oxide nanoparticles (NPs) have been shown toxic to unicellular algae, yet the research on heteroagglomeration between NPs and cells as an important precondition of the toxicity is scarce. This study for the first time investigated heteroagglomerations between various NPs and algal cells (Chlorella pyrenoidosa) and analyzed influencing factors including pH and ionic strength (IS) through cosettling experiment, transmission electron microscopic (TEM) observation, and Derjaguin–Landau–Verwey–Overbeek (DLVO) calculation. The examined NPs included anatase and rutile TiO2, microporous and spherical SiO2, and α-form and β-form Al2O3. The results of cosettling experiments coincided well with the TEM observations, whereas the DLVO theory could only partly explain the NP–cell heteroagglomerations. The NP–cell heteroagglomeration for rutile TiO2 and β-form Al2O3 was weak and insensitive to pH or IS. Preferential heteroagglomeration occurred at low pH or high IS for microporous SiO2, while marked heteroagglomeration only occurred under the neutral and low IS condition for anatase TiO2. The heteroagglomeration for spherical SiO2 was insensitive to pH but increased with increasing IS, while the heteroagglomeration for α-form Al2O3 occurred at low pH and irrelevant to IS. The work will shed new light on the bionano interfacial interaction and help to understand biological effects of NPs.


How to avoid and manage complications in aorto-iliac interventions.
Although less invasive than the open surgical alternatives by far, endovascular surgery is not free of complications. In a systematic review of endovascular treatment of extensive aorto-iliac occlusive disease mortality ranged from 1.2% to 6.7%. Complications were reported in 3% to 45% of the patients. In this article we give a systematic overview of the most frequent complications of endovascular aorto-iliac interventions, including suggestions how to manage and how to avoid them. Careful case selection, a high level of expertise of the operator and continuous monitoring of outcome are factors that can help to reduce complications, but also the alternative of open and laparoscopic surgery should kept in mind. The lowest complication rate will result from a treatment tailored on the individual patient and the available local experience.


Comparison of results from different laboratories in measuring 8-oxo-2'-deoxyguanosine in synthetic oligonucleotides.
The European Standards Committee on Oxidative DNA Damage (ESCODD) was set up in 1997 to resolve methodological problems and to reach agreement on the basal level of 8-oxo-2'-deoxyguanosine (8-oxodG) in biological samples. In the present ESCODD trial 6 samples of 8-oxodG-containing oligonucleotides with different ratios of 8-oxodG/2'-deoxyadenosine (dAdo) were sent to 25 laboratories throughout Europe. The methods used were HPLC with electrochemical detection (amperometric or coulometric), GC-MS or LC-MS-MS. The LC-MS-MS and the coulometric HPLC analyses gave 8-oxodG concentrations within 53 and 73% of expected values, respectively, whereas the amperometric HPLC and GC-MS consistently overestimated the 8-oxodG concentration by several fold. As the oligonucleotides contained no 2'-deoxyguanosine (dGuo), this was not due to artificial oxidation. On the contrary, in most cases the concentrations of dAdo and thymidine (dThd), used as estimates for non-oxidised DNA bases were underestimated, though a few laboratories overestimated the lowest concentration samples containing 8 and 20 microM, respectively. In one-third of the reported results, the ratio of 8-oxodG/10(5) dAdo was within 25% of the calculated value in the oligonucleotide samples and in half of the results the coefficient of variation in duplicate samples was less than 10%. The coefficients of variation were higher for the dAdo concentrations than for 8-oxodG. Our findings strongly indicate that careful quality control must be applied to the analytical procedures for 8-oxodG and very importantly also to the procedures for non-modified 2'-deoxyribonucleosides. We recommend the use of synthetic oligonucleotides for this purpose.


Regulation of Apoptosis by Enteroviruses.
Enterovirus infection can cause a variety of diseases and severely impair the health of humans, animals, poultry, and other organisms. To resist viral infection, host organisms clear infected cells and viruses via apoptosis. However, throughout their long-term competition with host cells, enteroviruses have evolved a series of mechanisms to regulate the balance of apoptosis in order to replicate and proliferate. In the early stage of infection, enteroviruses mainly inhibit apoptosis by regulating the PI3K/Akt pathway and the autophagy pathway and by impairing cell sensors, thereby delaying viral replication. In the late stage of infection, enteroviruses mainly regulate apoptotic pathways and the host translation process via various viral proteins, ultimately inducing apoptosis. This paper discusses the means by which these two phenomena are balanced in enteroviruses to produce virus-favoring conditions - in a temporal sequence or through competition with each other. This information is important for further elucidation of the relevant mechanisms of acute infection by enteroviruses and other members of the picornavirus family.


[Matrix metalloproteinase-9 (MMP-9) activity in cerebrospinal fluid of amyotrophic lateral sclerosis patients].
Matrix metalloproteinase-9 (MMP-9) is a member of the family of zinc-dependent endopeptidases that degrade extracellular matrix proteins. It can be activated by serine proteinases or by superoxide radicals. The motor neurons in amyotrophic lateral sclerosis patients express significantly higher levels of MMP-9, suggesting a role in neurodegeneration. The aim of the study was to investigate MMP-9 in cerebrospinal fluid from amyotrophic lateral sclerosis patients. MMP-9 was measured by enzyme-linked immunosorbent assay ELISA in cerebrospinal fluid from 24 amyotrophic lateral sclerosis patients and 15 controls. The mean amyotrophic lateral sclerosis duration was 18 months. According to Munsat ALS Health State Scale, the patients were divided into four groups: mild, moderate, severe, terminal. The patients were also divided into groups with shorter (below 12 months) and longer (above 12 months) duration of the disease. MMP-9 level was insignificantly lower in the cerebrospinal fluid from amyotrophic lateral sclerosis patients compared with controls. MMP-9 level showed a tendency to decrease with clinical status worsening, however this correlation was not statistically significant. The difference between MMP-9 level in the cerebrospinal fluid between the groups of patients with shorter and longer duration of amyotrophic lateral sclerosis was not significant.


Low pathogenic avian influenza (H9N2) in chicken: Evaluation of an ancestral H9-MVA vaccine.
Modified Vaccinia Ankara (MVA) has proven its efficacy as a recombinant vector vaccine for numerous pathogens including influenza virus. The present study aimed at evaluating a recombinant MVA candidate vaccine against low pathogenic avian influenza virus subtype H9N2 in the chicken model. As the high genetic and antigenic diversity of H9N2 viruses increases vaccine design complexity, one strategy to widen the range of vaccine coverage is to use an ancestor sequence. We therefore generated a recombinant MVA encoding for the gene sequence of an ancestral hemagglutinin H9 protein (a computationally derived amino acid sequence of the node of the H9N2 G1 lineage strains was obtained using the ANCESCON program). We analyzed the genetics and the growth properties of the MVA vector virus confirming suitability for use under biosafety level 1 and tested its efficacy when applied either as an intra-muscular (IM) or an oral vaccine in specific pathogen free chickens challenged with A/chicken/Tunisia/12/2010(H9N2). Two control groups were studied in parallel (unvaccinated and inoculated birds; unvaccinated and non-inoculated birds). IM vaccinated birds seroconverted as early as four days post vaccination and neutralizing antibodies were detected against A/chicken/Tunisia/12/2010(H9N2) in all the birds before challenge. The role of local mucosal immunity is unclear here as no antibodies were detected in eye drop or aerosol vaccinated birds. Clinical signs were not detected in any of the infected birds even in absence of vaccination. Virus replication was observed in both vaccinated and unvaccinated chickens, suggesting the MVA-ancestral H9 vaccine may not stop virus spread in the field. However vaccinated birds showed less histological damage, fewer influenza-positive cells and shorter virus shedding than their unvaccinated counterparts.


Isolation and identification of the dominant Lactobacillus in gut and faeces of pigs using carbohydrate fermentation and 16S rDNA analysis.
The gut contents and faeces of 9 adult pigs and 387 colonies growing on MRS culture (selective for Lactobacillus) were sampled to isolate and identify Lactobacillus species present. The results showed that the number of bacteria growing on MRS culture increased from the anterior to posterior of the gut and decreased in the faeces (e.g., stomach, 4.04 x 10(5) cfu/g; small intestine, 9.77 x 10(7) cfu/g; large intestine 3.85 x 10(11) cfu/g; faeces, 1.22 x 10(11) cfu/g). Fifty-two lactobacilli-like colonies were selected from 387 on the basis of their size and Gram staining, and used for the fermentation of 11 carbohydrates, from which 12 lactobacilli were selected for 16S rDNA analysis. The result showed that Lactobacillus ruminis was the dominant Lactobacillus in the stomach, small intestine, large intestine and faeces of pigs. The identification of most strains estimated by their 16S rDNA was 98-99% accurate.


Aberrant methylation of the CHFR gene is frequently detected in non-invasive colorectal cancer.
Aberrant methylation of the CHFR gene associated with gene silencing has been reported in several primary tumors. In order to define the role of CHFR in the tumorigenic pathway of the colorectum, the methylation of CHFR was examined in tumors from colorectal cancer patients. Ninety-eight colorectal cancer patients were examined using a methylation-specific PCR (MSP) for CHFR CpG island in primary tumors. An aberrant methylation of the CHFR gene was detected in 25 out of 98 (26%) primary colorectal cancers. No methylation was detected in the corresponding normal tissue specimens. This finding suggested that an aberrant methylation of the CHFR gene occurs frequently in colorectal cancers. After a methylation analysis of all samples, the clinicopathological data were correlated with these results. A significant difference was found in the tumor (p = 0.035), thus, indicating that in early colorectal cancer the CHFR gene was more frequently methylated than in advanced cases. These findings suggest that CHFR might act as a tumor suppressor in at least some colorectal cancers and that CHFR methylation might, therefore, be a particular phenomenon of early colorectal cancer.


Ingestion of the pods of Enterolobium contortisiliquum causes hepatogenous photosensitization in cattle.
Enterolobium contortisiliquum (Leg. Mimosoidae) is reported as a poisonous plant related to photosensitization and photodermatitis, digestive disturbs and abortion. To date, the clinical and pathological features of photosensitization has not been reproduced or only reproduced associated with very mild presentations. The objective of this study was to reproduce in cattle the clinicopathological features of photosensitization associated with the ingestion of the pods of E. contortisiliquum. The pods were harvested from a property with a history of an ongoing outbreak of photosensitization and abortion in cattle. Six 24-month-old steers were cannulated and used in the experiment, two of them served as negative controls. E. contortisiliquum pods were administered to four steers through ruminal cannula. In the first phase of the experiment, daily doses of 30 g/kg/body weight (bw) and 20 g/kg/bw were administered to Bovines 1 and 2 respectively, for three consecutive days. In the second phase, starting four days after the last daily feeding of the pods, these two bovines were challenged with the same doses of the pods for three consecutive days and another two steers (Bovines 3 and 4) were fed 15 g/kg/bw each for three consecutive days. In the two phases, the steers developed signs compatible with ruminal acidosis which were more severe during the second phase. Three and five days after the administration of the pods, two steers presented photodermatitis characterized by hyperemia and edema on the skin of the dorsum of the neck, of the shaved skin around the cannula, of muzzle and ear. Lesions evolved to dermal necrosis with sloughing and subsequent scar retraction and dermal thickening. Ulceration of mucosae exposed to sunlight was also observed. All the steers which received the pods had significant elevations in the serum activities of gamma-glutamyl transferase (GGT) and aspartate aminotransferase (AST). The levels of GGT and AST remained elevated for up to 12 days after the administration of the pods was discontinued. Histopathological hepatic changes detected by liver biopsies were hepatocellular swelling and randomly scattered individual hepatocellular necrosis. The current study presents solid experimental evidence that the ingestion of E. contortisiliquum definitely induces the classical lesions of hepatogenous photosensitization in cattle.


Changes in eating habits following total and frontolateral laryngectomy.
Swallowing is a continuous dynamic process, characterized by complex stages, that involves structures of the oral cavity, pharynx, larynx and esophagus. It can be divided into three phases: oral, pharyngeal and esophageal. Dysphagia is characterized by difficulty with, or the inability to swallow food of normal consistencies. To investigate the presence of swallowing difficulties and modifications made to the consistency of the food consumed in cases of total and partial laryngectomy, with or without subsequent radiotherapy, among patients who had not been diagnosed as having dysphagia. Descriptive study. Voice Clinic of São Paulo Hospital, Universidade Federal de São Paulo/Escola Paulista de Medicina, São Paulo, Brazil. 36 laryngectomy patients: 25 total and 11 frontolateral cases, were studied. A survey consisting of a 23-item questionnaire was applied by a single professional. Among those interviewed, 44% reported having modified the consistency of the food consumed (56% of the total and 20% of the partial frontolateral laryngectomy cases). It was not possible to investigate the influence of radiotherapy on the groups in this study, because the partial frontolateral laryngectomy cases were not exposed to radiotherapy. There was a higher incidence of complaints of swallowing difficulties in total laryngectomy cases (p < 0.027) than in partial frontolateral cases. However, there was no relationship between the surgery and weight loss. We also noted the patients' other problems regarding the eating process, as well as the compensation that they made for such problems. Research has shown an association between laryngectomy and swallowing difficulties, although there have been no reports of associated changes in eating habits among laryngectomized patients. This study showed that difficulty in swallowing is not rare in total and frontolateral laryngectomy cases. Such patients, even those who did not complain of dysphagia, also had minor difficulties while eating, and had to make some adaptations to their meals.


Diagnosis and Treatment of Metastatic Disease to the Pancreas.
Introduction: Metastatic disease to the pancreas is a rare entity from all malignant pancreatic masses. Its diagnosis is very challenging, but with the introduction of endoscopic ultrasound (EUS)-fine needle aspiration (FNA), now there is a feasible way to make an accurate histopathological and definitive diagnosis. Materials and Methods: This is a retrospective review of 11 patients with metastasis to the pancreas diagnosed with EUS-FNA in a tertiary referral center over a period of 3 years. We describe our institutional experience in diagnosing metastatic disease to the pancreas through EUS-FNA. Results: Between January 2015 and June 2018, 115 patients were diagnosed with pancreatic malignancy by EUS-FNA and only 11 (10%) with metastatic disease to the pancreas. Most common primary malignancy was renal cell carcinoma, followed by colon carcinoma, squamous/small cell carcinoma of the lung, and urothelial carcinoma. Five of 11 patients presented as a solitary pancreatic mass on initial imaging without any evidence of primary or metastatic disease elsewhere. Conclusions: In our experience, metastatic disease to the pancreas can represent up to 10% of solid pancreatic masses, which is lower compared to the reported incidence in previous literature. Our findings reveal that early identification and diagnosis help patient management and limit surgical morbidity and mortality.


The secretion, components, and properties of saliva.
Saliva has one of the most difficult roles to perform in the body. It must facilitate the taste and detection of foods nutritious to the body but also defend the mucosa from infection by the ever-present microbiota present in the mouth. It achieves these roles by having a complex composition and versatile physical properties. The protein and ion components make a solution that is 99% water into a viscoelastic solution capable of many roles, such as acting as a lubricant and an antimicrobial, preventing the dissolution of teeth, aiding digestion, and facilitating taste. This review describes the neural regulation of salivary secretion in terms of fluid, protein, and ion secretion. It then describes some of the components and physical properties of saliva and attempts to relate them to the functions that saliva must perform.


Results of dynamic hip-screw osteosynthesis for intracapsular fractures of the femoral neck.
Dynamic hip-screw osteosynthesis was carried out in 121 patients with fractures of the proximal femur and intracapsular fractures of the femoral neck. Five patients died (4%). The mean age of the 121 patients was 66.4 years, in the subcapital fracture group of 48 patients, the mean age was 58 years. In the 48 patients, treated for an intracapsular femoral neck fracture, good functional results were achieved in 36 patients (75%). Partial femoral head necrosis was seen in six patients. Fast and proper anatomic reduction and dynamic fixation with a central positioned hip-screw (sliding nail) for intracapsular femoral neck fractures, result in good fracture healing with a low incidence of segmental femoral head necrosis.


A study of provider-caregiver communication in paediatric ambulatory care.
Provider-caregiver communication is a key ingredient in quality health care and patient safety, and effective communication has been shown to affect compliance and outcomes. To identify and compare communication issues among three paediatric outpatient clinics. In this prospective, qualitative study, a questionnaire was used to survey physicians, nurse practitioners and caregivers at three different infectious diseases clinics. There was a statistically significant preponderance of families in the tuberculosis clinic for whom English was not the mother tongue and who were not fluent in English. Patients in the HIV clinic were less likely to be at their first appointment than were patients attending the other clinics. Patients in the general clinic were less likely to have been seen by the same physician on the previous visit. Parents from all three clinics were satisfied with the care they received, with communication and with rapport with their child. There was a trend toward parents in the tuberculosis clinic being happier with their clinic visit and less likely to complain about the wait time. Language proficiency and lack of continuity of provider care were identified as potential risks for patient safety in the ambulatory setting. Further studies are necessary to identify language and cultural issues that may affect patient care in a tertiary paediatric hospital servicing a multiethnic population.


A Novel Open-Framework Copper Borovanadate with Enhanced Catalytic Performance for Oxidation of Benzylic C-H Bond.
A novel open-framework copper borovanadate, with a 6-connected topological net and 1D 8-membered ring channels, has been obtained for the first time. The compound not only exhibits a unique -B3 O7 (OH)-Cu-B(OH)3 linkage and features the largest ratio between TM2+ (Cu2+ ) and the borovanadate anion, but also possesses enhanced catalytic performance, high recyclability, and stability during the oxidation of benzylic C-H bonds.


Enteroendocrine Cells: Chemosensors in the Intestinal Epithelium.
The enteroendocrine system orchestrates how the body responds to the ingestion of foods, employing a diversity of hormones to fine-tune a wide range of physiological responses both within and outside the gut. Recent interest in gut hormones has surged with the realization that they modulate glucose tolerance and food intake through a variety of mechanisms, and such hormones are therefore excellent therapeutic candidates for the treatment of diabetes and obesity. Characterizing the roles and functions of different enteroendocrine cells is an essential step in understanding the physiology, pathophysiology, and therapeutics of the gut-brain-pancreas axis.


[Histamine release from human leukocytes by human recombinant interleukin-3].
Human recombinant interleukin-3 (hrIL-3) released histamine from human leukocytes in vitro. The histamine release by hrIL-3 significantly correlated with those by anti-IgE, thrombin, and f-met. peptide, but not by A23187. Histamine release by hrIL-3 was a Ca2(+)-dependent reaction, as was that by anti-IgE, although the time course of histamine release by hrIL-3 was slower than that by anti-IgE. Pre-treatment of leukocytes with hrIL-3 decreased the histamine release by hrIL-3 itself, but enhanced the histamine releases by anti-IgE, f-met. peptide, thrombin and A23187. These results suggested that the mechanism of hrIL-3-induced histamine release was different from those of anti-IgE, f-met. peptide, thrombin, and A23187. There was no significant difference between hrIL-3-induced histamine release of leukocytes from asthmatics and healthy controls.


Pushing the envelope: Evaluating speech rhythm with different envelope extraction techniques.
The amplitude of the speech signal varies over time, and the speech envelope is an attempt to characterise this variation in the form of an acoustic feature. Although tacitly assumed, the similarity between the speech envelope-derived time series and that of phonetic objects (e.g., vowels) remains empirically unestablished. The current paper, therefore, evaluates several speech envelope extraction techniques, such as the Hilbert transform, by comparing different acoustic landmarks (e.g., peaks in the speech envelope) with manual phonetic annotation in a naturalistic and diverse dataset. Joint speech tasks are also introduced to determine which acoustic landmarks are most closely coordinated when voices are aligned. Finally, the acoustic landmarks are evaluated as predictors for the temporal characterisation of speaking style using classification tasks. The landmark that performed most closely to annotated vowel onsets was peaks in the first derivative of a human audition-informed envelope, consistent with converging evidence from neural and behavioural data. However, differences also emerged based on language and speaking style. Overall, the results show that both the choice of speech envelope extraction technique and the form of speech under study affect how sensitive an engineered feature is at capturing aspects of speech rhythm, such as the timing of vowels.


Tuberculous uveitis.
Tuberculous uveitis is an underdiagnosed form of uveitis. Absence of pulmonary signs and symptoms does not rule out the disease. In an era of reduced immunity from human immunodeficiency virus and acquired immunodeficiency syndrome, the disease is becoming more prevalent. This review discusses the common manifestations of tuberculous uveitis, pointing out helpful diagnostic criteria in suspicious cases of uveitis. Physicians need to be aware that ocular manifestations of tuberculosis may be independent of systemic disease.


Long-term effects of hormone replacement therapy on symptoms of angina pectoris, quality of life and compliance in women with coronary artery disease.
The aim of the present study was to evaluate the effects of HRT on symptoms of angina pectoris, quality of life and factors of importance for compliance in women with ischemic heart disease. Sixty postmenopausal women with coronary artery disease were randomized into three groups: one group received transdermal 17 beta-estradiol at a dose of 50 micrograms per 24 h alone for 18 days followed by 10 days of combined treatment with medroxyprogesterone acetate (MPA) 5 mg orally; the second group received placebo and the third group received conjugated estrogens orally for 18 days followed by a combined treatment with MPA for 10 days. Clinical evaluations were performed at baseline, after 3, 6 and 12 months. The investigations included gynecological history. occurrence of climacteric symptoms, quality of life evaluation, cardiac history and symptoms of angina pectoris. Forty-six women (77%) completed the study during 1 year. The following cardiac events occurred in the women who completed the study: one patient was hospitalized because of congestive heart failure (patch), two patients because of angina pectoris, one patient because of coronary bypass operation (CEE) and three patients underwent balloon dilatation (placebo), all three on CEE. Among the 14 women who discontinued, two patients had TIA (patch), one experienced palpitations (CEE) and one woman died from myocardial infarction (placebo). Overall improvement in mood and cognitive functions were reported in all three treatment groups. HRT does not seem to have negative effects on symptoms of angina pectoris and seems to increase quality of life in older women with coronary heart disease. It also seems safe from the cardiovascular point of view.


Effect of manual hyperinflation on haemodynamics in an animal model.
Manual hyperinflation is a physiotherapy technique that improves static compliance and mobilizes secretions, but has the potential to alter haemodynamic function. The aim of the present study was to investigate the effects of manual hyperinflation on haemodynamic function in a healthy animal model, without the usual confounding effects inherent in an heterogeneous intensive care population. The study used a within-subjects design, in an animal research theatre. Nine healthy sheep (eight Border Leicester, one Merino, mean weight 39.5 kg, standard deviation (SD) 1.6 kg) completed the study. The sheep were induced (thiopentane 15-20 ml), intubated, ventilated and surgically instrumented for an arterial line and pulmonary artery catheter. Anaesthesia was maintained by 1.5% halothane/oxygen. Manual hyperinflation was delivered for two minutes with a Mapleson C circuit, using a peak inspiratory pressure of 35 cmH2O and an inspiratory:expiratory ratio of 2:1. Mean tidal volume during manual hyperinflation was 294% (SD 22%) of the ventilator tidal volume. A paired Student's t-test demonstrated that cardiac output (thermodilution method) decreased significantly (p < 0.05) and systemic vascular resistance increased significantly (p < 0.01) after manual hyperinflation. A repeated-measures analysis of variance (ANOVA) and a least-significant difference pairwise comparison revealed that mean arterial pressure and pulse pressure decreased significantly during (p < 0.01) and increased significantly (mean arterial pressure, p < 0.05 and mean pulse pressure p < 0.001) after the technique. Pulmonary artery pressure also increased significantly during manual hyperinflation (p < 0.01). There were no significant effects on right atrial pressure, pulmonary artery occlusion pressure or heart rate. Significant haemodynamic changes occurred in this animal model. The increased intrathoracic pressure, applied for an increased period during inspiration, decreased cardiac output with compensatory vasoconstriction evident by the increased systemic vascular resistance and mean arterial pressure. The results suggest that there may be a decrease in cardiac output after increased positive pressure in subjects with normal cardiac and respiratory function.


Aggregates of quadrupolar dyes: giant two-photon absorption from biexciton states.
A model for aggregates of quadrupolar (DAD or ADA) molecules is presented that relaxes the dipolar approximation for intermolecular electrostatic interactions. New effects, including the appearance of bound biexcitons in clusters of nonpolar molecules, are predicted with interesting and unforeseen consequences on the material properties. Specifically, we show that the large two-photon absorption cross-section, typical of quadrupolar chromophores, can be further amplified by orders of magnitude as a result of aggregation.


ChatGPT in the higher education environment: perspectives from the theory of high order thinking skills.
ChatGPT is a form of technological progress in the 5.0 era. The use of ChatGPT has begun to penetrate all fields of science, including the field of education. Students use ChatGPT to help them complete their assignments in the university environment. Apart from providing many benefits, ChatGPT also has many dangers threatening students. One of the dangers for students who rely too much on ChatGPT is a decrease in higher-order thinking skills.


A finite mixture model for X-chromosome association with an emphasis on microbiome data analysis.
Analysis of the X chromosome has been largely neglected in genetic studies mainly because of complex underlying biological mechanisms. On the other hand, the study of human microbiome data (typically over-dispersed counts with an excess of zeros) has generated great interest recently because of advancements in next-generation sequencing technologies. We propose a novel approach to infer the association between host genetic variants in the X-chromosome and microbiome data. The method accounts for random X-chromosome inactivation (XCI), skewed (or nonrandom) XCI (XCI-S), and escape of XCI (XCI-E). The inference is performed through a finite mixture model (FMM), in which an indicator variable denoting the "true" biological mechanism is treated as missing data. An expectation-maximization algorithm on zero-inflated and two-part models is implemented to estimate genetic effects. We investigate the performance of the FMM along with strategies that assume XCI and XCI-E mechanisms for all subjects compared with alternative approaches. Briefly, an XCI mechanism codes males' genotypes as homozygous females, whereas under XCI-E, males are treated as heterozygous females. By comprehensive simulations, we evaluate tests of the hypothesis under a computationally efficient score statistic. In summary, the FMM renders reduced bias and commensurate power compared to XCI, XCI-E, and alternative strategies while maintaining adequate Type 1 error control. The proposed method has far-reaching applications. In particular, we illustrate its usage on a large-scale human microbiome study, the Genetic, Environmental and Microbial (GEM) project, to test for the genetic association on the X chromosome.


Parkin protein expression and its impact on survival of patients with advanced colorectal cancer.
Features of colorectal cancer such as natural history, molecular, chromosomal, and epigenetic alterations have been well described. However, there is still a lack of accurate prognostic markers, which is evident by the lower overall survival rates of patients with advanced cancer. Although alterations in parkin protein expression have been described in colorectal cancer, the functional significance of this protein remains unknown. The present study aimed to investigate the involvement of parkin expression in colorectal adenocarcinoma development and progression by evaluating the association between its expression, clinicopathological parameters, and expression of known proteins involved in colorectal cancer. Tissue microarrays consisting of 73 tumor and 64 normal tissue samples were generated to examine parkin expression and localization by immunohistochemistry. A positive correlation of parkin and APC expression was observed in the superficial, intermediate, and profound regions of all cases (ρ = 0.37; P = 0.001). Parkin expression was also significantly associated with tumors in men (P = 0.049), those of the mucinous subtype (P = 0.028), and of advanced stage (III + IV, P = 0.041). In addition, increased parkin expression was observed in the invasive front tumor region (P = 0.013). More importantly, a positive correlation was found between parkin expression and the overall survival of patients with advanced colorectal cancer (P = 0.019). Multivariate analysis showed that parkin expression was independent of any of the clinicopathological parameters evaluated in relation to patient survival. These results suggest that parkin expression status can be used as a potential independent prognostic marker of survival in advanced colorectal cancer.


Inhibition of plant amine oxidases by a novel series of diamine derivatives.
A series of N,N'-bis(2-pyridinylmethyl)diamines was synthesized and characterized for their inhibition effects towards plant copper-containing amine oxidase (EC 126.96.36.199) and polyamine oxidase (EC 22.214.171.124), which mediate the catabolic regulation of cellular polyamines. Even though these enzymes catalyze related reactions and, among others, act upon two common substrates (spermidine and spermine), their molecular and kinetic properties are different. They also show a different spectrum of inhibitors. It is therefore of interest to look for compounds providing a dual inhibition (i.e. inhibiting both enzymes with the same inhibition potency), which would be useful in physiological studies involving modulations of polyamine catabolism. The synthesized diamine derivatives comprised from two to eight carbon atoms in the alkyl spacer chain. Kinetic measurements with pea (Pisum sativum) diamine oxidase and oat (Avena sativa) polyamine oxidase demonstrated reversible binding of the compounds at the active sites of the enzymes as they were almost exclusively competitive inhibitors with K(i) values ranging from 10(-5) to 10(-3)M. In case of oat polyamine oxidase, the K(i) values were significantly influenced by the number of methylene groups in the inhibitor molecule. The measured inhibition data are discussed with respect to enzyme structure. For that reason, the oat enzyme was analyzed by de novo peptide sequencing using mass spectrometry and shown to be homologous to polyamine oxidases from barley (isoform 1) and maize. We conclude that some of the studied N,N'-bis(2-pyridinylmethyl)diamines might have a potential to be starting structures in design of metabolic modulators targeted to both types of amine oxidases.


Engagement of community health workers to improve immunization coverage through addressing inequities and enhancing data quality and use is a feasible and effective approach: An implementation study in Uganda.
Uganda, like many other developing countries, faces the challenges of unreliable estimates for its immunization target population. Strengthening immunization data quality and its use for improving immunization program performance are critical steps toward improving coverage and equity of immunization programs. The goal of this study was to determine the effectiveness of using community health workers (CHWs) to obtain quality and reliable data that can be used for planning and evidence-based response actions. An implementation study in which 5 health facilities were stratified and randomized in two groups to (i) receive a package of interventions including monthly health unit immunization data audit meetings, and defaulter tracking and linkage and (ii) to serve as a control group was conducted between July and September 2020. Immunization coverage of infants in both arms was determined by a review of records three months before and after the study interventions. In addition, key informant and in-depth interviews were conducted among facility-based health workers and CHWs respectively, at the endline to explore the feasibility of the interventions. Overall, a total of 2,048 children under one year eligible for immunization were registered in Bukabooli sub-county by CHWs as compared to the estimated district population of 1,889 children representing a moderate variance of 8.4%. The study further showed that it is feasible to use CHWs to track and link defaulters to points of immunization services as more than two-thirds (68%) of the children defaulting returned for catch-up immunization services. At the endline, immunization coverage for the Oral Polio Vaccine third dose; Rotavirus vaccine second dose; Pneumococcal Conjugate Vaccine third dose increased in both the intervention and control health facilities. There was a decrease in coverage for the Measles-Rubella vaccine decreased in the intervention health facilities and a decrease in Bacillus Calmette-Guérin vaccine coverage in the control facilities. Difference in difference analysis demonstrated that the intervention caused a significant 35.1% increase in coverage of Bacillus Calmette-Guérin vaccine (CI 9.00-61.19; p<0.05)). The intervention facilities had a 17.9% increase in DTP3 coverage compared to the control facilities (CI: 1.69-34.1) while for MR, OPV3, and Rota2 antigens, there was no significant effect of the intervention. The use of CHWs to obtain reliable population estimates is feasible and can be useful in areas with consistently poor immunization coverage to estimate the target population. Facilitating monthly health unit immunization data audit meetings to identify, track, and link defaulters to immunization services is effective in increasing immunization coverage and equity.


[The effect of cerebrocrast and nicardipine on the blood supply and metabolism of the brain in cats with intracranial hemorrhage].
Intravenous cerebrocrast, 1 g/kg/min, and nicardipine, 0.5 g/kg/min, given to cats during 60 min one day after cerebral hemorrhage were found to produce an improvement of cerebral blood supply and oxygen consumption along with a moderate fall of blood pressure. The favourable effect of cerebrocrast on brain oxygen and carbohydrate metabolism was mediated by increased brain blood supply. As compared to cerebrocrast, nicardipine induced a more prolonged antihypertensive response and more pronounced effects on cerebral tissue metabolism, by substantially decreasing brain lactate production.


Residue conservation information for generating near-native structures in protein-protein docking.
Protein-protein docking algorithms typically generate large numbers of possible complex structures with only a few of them resembling the native structure. Recently (Duan et al., Protein Sci, 14:316-218, 2005), it was observed that the surface density of conserved residue positions is high at the interface regions of interacting protein surfaces, except for antibody-antigen complexes, where a lesser number of conserved positions than average is observed at the interface regions. Using this observation, we identified putative interacting regions on the surface of interacting partners and significantly improved docking results by assigning top ranks to near-native complex structures. In this paper, we combine the residue conservation information with a widely used shape complementarity algorithm to generate candidate complex structures with a higher percentage of near-native structures (hits). What is new in this work is that the conservation information is used early in the generation stage and not only in the ranking stage of the docking algorithm. This results in a significantly larger number of generated hits and an improved predictive ability in identifying the native structure of protein-protein complexes. We report on results from 48 well-characterized protein complexes, which have enough residue conservation information from the same 59 benchmark complexes used in our previous work. We compute conservation indices of residue positions on the surfaces of interacting proteins using available homologous sequences from UNIPROT and calculate the solvent accessible surface area. We combine this information with shape-complementarity scores to generate candidate protein-protein complex structures. When compared with pure shape-complementarity algorithms, performed by FTDock, our method results in significantly more hits, with the improvement being over 100% in many instances. We demonstrate that residue conservation information is useful not only in refinement and scoring of docking solutions, but also helpful in enrichment of near-native-structures during the generation of candidate geometries of complex structures.


Relationship between genetic polymorphism of MTHFR C677T and lower extremities deep venous thrombosis.
To investigate the association between the polymorphism of methylenetetrahydrofolate reductase (MTHFR) gene and the formation of lower extremities deep venous thrombosis, and to evaluate the etiology of deep venous thrombosis. Polymorphisms of the 677th site C/T in MTHFR gene for 101 patients with lower extremities deep venous thrombosis (DVT group) and 120 healthy subjects (control group) were detected by polymerase chain reaction with sequence-specific primers. Genotype and allelic frequencies were compared between the two groups. Genotype frequencies of CC, CT and TT in MTHFR C677 T were 41.58, 25.74 and 32.67% in DVT group, and 58.33, 23.33 and 18.33% in control group, respectively. There was a significant difference in TT genotype frequency between the two groups (P <0.05). The frequency of MTHFR 677TT genotype may be correlated with the morbility of DVT.


Framing the transit: expeditionary culture and identities in Lieutenant E.J.W. Noble's caricatures of the 1874 transit of Venus expedition to Honolulu.
Making use of a source previously unknown to historians, this article sheds new light on the British expedition to the Sandwich Islands to observe the 1874 transit of Venus. This source, a series of caricature drawings that follow the expedition from departure to return, gives insight into expeditionary culture and the experience of a previously unremarked member of this astronomical expedition, Evelyn J.W. Noble, a career officer of the Royal Marine Artillery. It also reveals overlapping military, scientific and masculine identities, developed in dialogue with, and often deliberately subverting, more public accounts. The article explores this unique source as a product of naval, imperial and expeditionary cultures; as a contribution to the wide textual and visual culture that surrounded the transit expeditions; and as a series of drawings that united the expedition members through the use of humour and irony, by differentiating the group from others they encountered, and by reflecting or rejecting ideas about the nature of scientific work and personae. The artist represented himself not as a serving officer but as part of a (mostly) united group, dedicated to but humorously self-deprecating about their contribution to the scientific effort.


Species-sorting may explain an apparent minimal effect of immigration on freshwater bacterial community dynamics.
Long distance atmospheric transport of bacterial cells is often implied as a driver of the apparent cosmopolitan distribution of bacterial taxa. Surprisingly, efforts to measure immigration in bacterial communities are rare. An 8-week time series of within-lake bacterial community composition and atmospheric deposition rates and composition were used to estimate the influence of immigration on bacterial community dynamics in two north temperate lakes. Characterization of bacterial community dynamics using automated ribosomal intergenic spacer analysis suggested moderate overlap in composition between the lakes and atmospherically deposited cells. However, taxa that appeared to be delivered by atmospheric deposition had a relatively minor influence on lake bacterial community dynamics. The weak influence of immigrating bacterial taxa suggests that a species-sorting concept best describes aquatic bacterial metacommunity dynamics.


Panic attacks in young adolescents.
The lifetime prevalence of interview-determined four-symptom panic attacks in 95 ninth graders was 11.6%. Those with panic attacks were significantly more depressed, were significantly more likely to have separated or divorced parents, and tended to be more likely to have tried cigarette smoking.


An improved method for perforated patch recordings using nystatin-fluorescein mixture.
This paper describes an improved method for solubilizing nystatin in an aqueous solution without the aid of organic solvents. The patch pipette was filled with a solution of nystatin and fluorescein sodium mixed in a molar ratio of 1:10. The success rate of perforated patch recordings was substantially improved, and the access resistance of 20-40 M omega was readily achieved.


The effect of light on forelimb regeneration in the newt.
The forelimb of the newt, Triturus (Notophthalamus) viridescens, was bilaterally amputated and the animals subjected to different photoperiods during the period of regeneration, namely (1) continuous light, (2) 15 hours of light/day and (3) total darkness. Animals exposed to continuous light reached the palette regeneration stage four to five days before those kept in total darkness with the 15 hours of light/day animals being intermediate. The difference in regeneration rate was first evident in the moderate early stage (blastema accumulation stage); it then increased during subsequent stages and the difference persisted during the observation period. In an attempt to determine whether the retina was the receptor of light affected, some animals were blinded at the time of amputation and subjected to continuous light. Their rate of regeneration was similar to sighted animals subjected to continuous light but greater than sighted animals in total darkness. The pineal is discussed as the likely mediator of the photo effect.


The effects of attention and adaptation duration on the motion aftereffect.
The motion aftereffect (MAE) is the perception of illusory motion following extended exposure to a moving stimulus. The MAE has been used to probe the role of attention in motion processing. Many studies have reported that MAEs are reduced if attention is diverted from the adaptation stimulus, but others have argued that motion adaptation is independent of attention. We explored several factors that might modulate the attention-adaptation relationship and therefore explain apparent inconsistencies, namely (a) adaptation duration, (b) motion type: translating versus complex, and (c) response bias. Participants viewed translating (Experiments 1a and 2) or rotating (Experiment 1b) random dot patterns while fixating a central letter stream. During adaptation, participants reported brief changes in the adaptor speed (attention-focused) or the presence of white vowels within the letter stream (attention-diverted). Trials consisted of multiple adaptation-test cycles, and the MAE was measured after each adaptation period. Across experiments, focused attention produced significantly larger MAEs than did diverted attention (15% change, Cohen's d = .41). Attention affected the MAE asymptote, rather than its accumulation rate, and had larger effects for translational than for complex motion. The effect of attention remained evident after controlling for response bias. Our results suggest that attention affects multiple levels of the motion-processing hierarchy: not only higher level motion processing, as seen with apparent motion, but also low-level motion processing, as evidenced by the MAE. (PsycINFO Database Record (c) 2018 APA, all rights reserved).


Apoferritin Nanocage for Brain Targeted Doxorubicin Delivery.
An ideal brain-targeted nanocarrier must be sufficiently potent to penetrate the blood-brain barrier (BBB) and sufficiently competent to target the cells of interest with adequate optimized physiochemical features and biocompatibility. However, it is an enormous challenge to the researchers to organize the above-mentioned properties into a single nanocarrier particle. New frontiers in nanomedicine are advancing the research of new biomaterials. Herein, we demonstrate a straightforward strategy for brain targeting by encapsulating doxorubicin (DOX) into a naturally available and unmodified apoferritin nanocage (DOX-loaded APO). APO can specifically bind to cells expressing transferrin receptor 1 (TfR1). Because of the high expression of TfR1 in both brain endothelial and glioma cells, DOX-loaded APO can cross the BBB and deliver drugs to the glioma with TfR1. Subsequent research demonstrated that the DOX-loaded APO had good physicochemical properties (particle size of 12.03 ± 0.42 nm, drug encapsulation efficiency of 81.8 ± 1.1%) and significant penetrating and targeting effects in the coculture model of bEnd.3 and C6 cells in vitro. In vivo imaging revealed that DOX-loaded APO accumulated specifically in brain tumor tissues. Additionally, in vivo tumor therapy experiments (at a dosage of 1 mg/kg DOX) demonstrated that a longer survival period was observed in mice that had been treated with DOX-loaded APO (30 days) compared with mice receiving free DOX solution (19 days).


Tumorablative conditioning regimen for haploidentical stem cell transplantation in 102 children with hematologic malignancies: a single-center experience.
Haploidentical hematopoietic stem cell transplantation (Haplo-HSCT) is widely carried out in China, and transplantation related complications decreased gradually with the transplant technology improving, and the overall survival(OS) increased year by year. However, relapse after transplantation is still one of the main causes of death in patients with hematological malignancy. In order to reduce the recurrence after HSCT, we set a tumorablative conditioning regimen (TAC ) regimen; the aim is as much as possible to eliminate the malignant clone to reduce the recurrence without increasing the conditioning toxicity. We retrospectively analyzed 102 cases of haplo-HSCT in our hospital from 2012 to 2017. Ninety-eight out of the 99 (99.0%) patients achieved primary engraftment. The 2-year OS and disease free survival (DFS) are 81.4% (83/102) and 77.45% (79/102). The cumulative incidence of leukemia relapse is 16.2% (16/99), Twenty-nine patients developed II-IV acute graft-versus-host disease (aGVHD) (29%) within 100 days and only nine patients have grade III-IV aGVHD (9%) in measurable 99 patients. The conditioning regimen was relatively well tolerated with limited regimen-related toxicity. The preliminary results show that TAC is safe and effective in haplo-HSCT of children with hematologic malignancies. This study will provide a clinical basis for the individualized conditioning regimen.


Comparison of gene expression profiles between Opisthorchis viverrini and non-Opisthorchis viverrini associated human intrahepatic cholangiocarcinoma.
Intrahepatic cholangiocarcinoma (ICC) is the second most common primary cancer in the liver, and its incidence is highest in the northeastern part of Thailand. ICCs in this region are known to be associated with infection with liver flukes, particularly Opisthorchis viverrini (OV), as well as nitrosamines from food. To clarify molecular mechanisms of ICC associated with or without liver flukes, we analyzed gene expression profiles of OV-associated ICCs from 20 Thai patients and compared their profiles with those of 20 Japanese ICCs that were not associated with OV, by means of laser microbeam microdissection and a cDNA microarray containing 27,648 genes. We identified 77 commonly upregulated genes and 325 commonly downregulated genes in the two ICC groups. Unsupervised hierarchical cluster analysis separated the 40 ICCs into two major branches almost completely according to the fluke status. The putative signature of OV-associated ICC exhibited elevated expression of genes involved in xenobiotic metabolism (UGT2B11, UGT1A10, CHST4, SULT1C1), whereas that of non-OV-associated ICC represented enhanced expression of genes related to growth factor signaling (TGFBI, PGF, IGFBP1, IGFBP3). Additional random permutation tests identified a total of 49 genes whose expression levels were significantly different between the two groups. We also identified genes associated with macroscopic type of ICCs. In conclusion, these data may not only contribute to clarification of common and OV-specific mechanisms underlying ICC, but also may serve as a starting point for the identification of novel diagnostic markers or therapeutic targets for the disease.


[Comparative angioarchitectonics of the kidneys of several rodents].
Studies have been made on kidney angioarchitectonics in 3 rodent species (allied taxonomically, but significantly different in their habitat) - the albino rat, the gerbil Meriones erythrourus and the aquatic rodent must-rat Ondatra zibetica - after the injection of the vessels with India ink and subsequent microphotometric analysis of unstained sections. The general pattern of vascular system of the kideny is similar in all the species studied. However, significant differences were found in vascularisation of the cortex and especially of the outer and inner medulla. In M. erythrourus, vascularisation of the papilla is approximately 2 1/2 times more intense than that of the cortex; large vascular bundles in the outer medulla are separated from both interbundle plexus and vascular system of the papilla; the glomeruli differ in their size; arterial sphincters are more numerous in the cortex. In O. zibetica, vascularisation of the papilla is somewhat 3 times less intense as compared to that of the cortex; medullar bundles are diffuse; the structure of the glomeruli is more uniform. With respect to its kidney angioarchitectonics, the albino rat occupies intermediate position. The observed differences are discussed in relation to ecological specialization of the species studied, indicating the important role of vascular system of the kidney in the formation of concentrating capacity of the latter.


Smoking in top-grossing movies--United States, 2010.
The National Cancer Institute has concluded that studies indicate a causal relationship between exposure to depictions of smoking in movies and youth smoking initiation. Adolescents in the top quartile of exposures to onscreen tobacco incidents have been found to be approximately twice as likely to begin smoking as those in the bottom quartile. The 2010 U.S. Department of Health and Human Services strategic plan to reduce tobacco use includes reducing youth exposure to onscreen smoking. To monitor tobacco use in movies, Thumbs Up! Thumbs Down! (TUTD), a project of Breathe California of Sacramento-Emigrant Trails, counts occurrences of tobacco incidents in U.S. top-grossing movies each year. This report updates a previous report with the latest TUTD findings. In 2010, the number of onscreen tobacco incidents in youth-rated (G, PG, or PG-13) movies continued a downward trend, decreasing 71.6% from 2,093 incidents in 2005 to 595 in 2010. Similarly, the average number of incidents per youth-rated movie decreased 66.2%, from 20.1 in 2005 to 6.8 in 2010. The degree of decline, however, varied substantially by motion picture company. The three companies with published policies designed to reduce tobacco use in their movies had an average decrease in tobacco incidents of 95.8%, compared with an average decrease of 41.7% among the three major motion picture companies and independents without policies. This finding indicates that an enforceable policy aimed at reducing tobacco use in youth-rated movies can lead to substantially fewer tobacco incidents in movies and help prevent adolescent initiation of smoking.


Anti-PF4/heparin antibodies associated with repeated hemofiltration-filter clotting: a retrospective study.
Heparin-induced thrombocytopenia is an immune-mediated adverse drug reaction that is associated with a procoagulant state and both arterial and venous thrombosis. After observing two cases of repeated hemofiltration-filter clotting associated with high anti-PF4/heparin antibody concentrations, we systematically measured the anti-PF4/heparin antibody concentration in all cases of unexpected and repeated hemofiltration-filter clotting during continuous veno-venous hemofiltration (CVVH). The aim of this study was to identify factors associated with positive anti-PF4/heparin antibody in the case of repeated hemofiltration-filter clotting. We reviewed the charts of all patients who had an anti-PF4/heparin antibody assay performed for repeated hemofiltration-filter clotting between November 2004 and May 2006 in our surgical intensive care unit. We used an enzyme-linked immunoabsorbent assay (heparin-platelet factor 4-induced antibody) with an optical density (OD) of greater than 1 IU considered positive. During the study period, anti-PF4/heparin antibody assay was performed in 28 out of 87 patients receiving CVVH. Seven patients were positive for anti-PF4/heparin antibodies (OD 2.00 [1.36 to 2.22] IU) and 21 were antibody-negative (OD 0.20 [0.10 to 0.32] IU). Baseline characteristics, platelet counts, and activated partial thromboplastin time ratios were not different between the two groups. CVVH duration was significantly decreased in antibody-positive patients (5.0 [2.5 to 7.5] versus 12.0 [7.5 to 24.0] hours; P = 0.007) as was CVVH efficiency (urea reduction ratio 17% [10% to 37%] versus 44% [30% to 52%]; P = 0.04) on heparin infusion. Anti-PF4/heparin antibody concentration was inversely correlated with CVVH duration. The receiver operating characteristic curve showed that a 6-hour cutoff was the best CVVH session duration to predict a positive antibody test (sensitivity 71%, specificity 85%, and area under the curve 0.83). CVVH duration (32 [22 to 37] hours; P < 0.05) and urea reduction (55% [36% to 68%]; P < 0.03) were restored by danaparoid sodium infusion. Repeated hemofiltration-filter clotting in less than 6 hours was often associated with the presence of anti-PF4/heparin antibodies, regardless of the platelet count. In antibody-positive patients, replacement of heparin by danaparoid sodium allowed the restoration of CVVH duration and efficiency.


Elder Mistreatment among Chinese and Korean Immigrants: The Roles of Sociocultural Contexts on Perceptions and Help-Seeking Behaviors.
The purpose of this study was to identify dimensions of elder mistreatment in Chinese and Korean immigrant communities and to increase sociocultural understanding of such mistreatment by elucidating the complexities of abuse embedded in unique social and cultural contexts. In-depth interviews were conducted with 20 local professionals working primarily in Asian elderly advocacy, and six focus group discussions were conducted involving 60 community members in the San Francisco Bay area. Five dimensions of elder mistreatment were identified: psychological abuse, neglect by a trusted person, financial exploitation, physical abuse, and sexual abuse. In general, fewer Korean community member participants reported having observed physical or financial abuse than Chinese groups, but they reported greater knowledge of situations involving psychological abuse, neglect by a trusted person, and sexual abuse. The contexts of cultural influences and immigration and acculturation were salient themes that shaped participants' subjective perceptions and beliefs about elder abuse and hence help-seeking behaviors.


Differentiating Botulinum Neurotoxin-Producing Clostridia with a Simple, Multiplex PCR Assay.
Diverse members of the genus Clostridium produce botulinum neurotoxins (BoNTs), which cause a flaccid paralysis known as botulism. While multiple species of clostridia produce BoNTs, the majority of human botulism cases have been attributed to Clostridium botulinum groups I and II. Recent comparative genomic studies have demonstrated the genomic diversity within these BoNT-producing species. This report introduces a multiplex PCR assay for differentiating members of C. botulinum group I, C. sporogenes, and two major subgroups within C. botulinum group II. Coding region sequences unique to each of the four species/subgroups were identified by in silico analyses of thousands of genome assemblies, and PCR primers were designed to amplify each marker. The resulting multiplex PCR assay correctly assigned 41 tested isolates to the appropriate species or subgroup. A separate PCR assay to determine the presence of the ntnh gene (a gene associated with the botulinum neurotoxin gene cluster) was developed and validated. The ntnh gene PCR assay provides information about the presence or absence of the botulinum neurotoxin gene cluster and the type of gene cluster present (ha positive [ha+] or orfX+). The increased availability of whole-genome sequence data and comparative genomic tools enabled the design of these assays, which provide valuable information for characterizing BoNT-producing clostridia. The PCR assays are rapid, inexpensive tests that can be applied to a variety of sample types to assign isolates to species/subgroups and to detect clostridia with botulinum neurotoxin gene (bont) clusters.IMPORTANCE Diverse clostridia produce the botulinum neurotoxin, one of the most potent known neurotoxins. In this study, a multiplex PCR assay was developed to differentiate clostridia that are most commonly isolated in connection with human botulism cases: C. botulinum group I, C. sporogenes, and two major subgroups within C. botulinum group II. Since BoNT-producing and nontoxigenic isolates can be found in each species, a PCR assay to determine the presence of the ntnh gene, which is a universally present component of bont gene clusters, and to provide information about the type (ha+ or orfX+) of bont gene cluster present in a sample was also developed. The PCR assays provide simple, rapid, and inexpensive tools for screening uncharacterized isolates from clinical or environmental samples. The information provided by these assays can inform epidemiological studies, aid with identifying mixtures of isolates and unknown isolates in culture collections, and confirm the presence of bacteria of interest.


Multiple biochemical markers in patients with gynecologic malignancies.
Plasma levels of carcinoembryonic antigen (CEA), alpha-fetoprotein (AFP), and human chorionic gonadotropin (hCG) were measured in 253 patients with gynecologic malignancies and in 317 patients with benign gynecologic diseases. Plasma concentrations of each of these antigens were elevated in a significantly (p less than 0.001) greater number of patients with invasive gynecologic cancers than in the control population. Carcinoembryonic antigen was the most commonly elevated marker, followed by AFP and hCG. Prior to therapy, over 85% of patients with ovarian or cervical cancer had elevated plasma levels of one or more antigens. Specifically, CEA was most often elevated in patients with mucinous adenocarcinomas of the ovary and endocervix. Alpha-fetoprotein was most often increased in patients with germ cell or stromal tumors of the ovary and in patients with large-cell nonkeratinizing cervical cancers. In contrast, hCG concentrations were highest in patients with serious cystadenocarcinomas of the ovary and in patients with keratinizing squamous cell carcinomas of the cervix. Plasma antigen levels were directly related to tumor differentiation and stage of disease, and generally returned to normal eight to 12 weeks following therapy. Effective plasma and tumor antigen screening during initial evaluation of patients with gynecologic tumors should help to identify the most appropriate antigen for immunodetection procedures and for serial plasma determinations following therapy.


Treatment of severe hyperlipidemia: six years' experience with low-density lipoprotein apheresis.
In total, 30 patients suffering from familial hypercholesterolemia, resistant to diet and lipid-lowering drugs, were treated for up to 6 years (3.6 + or - 1.6; range, 0.2-6.8 years) with low-density lipoprotein (LDL) apheresis. Three different systems were used; the dextran sulfate adsorption system (Kaneka) for 27 of 30 patients, the immunoadsorption system from Baxter for 2 of 30 patients, and the immunoadsorption system with special lipoprotein(a) (Lp[a]) columns from Lipopak for one patient. Prior to the LDL apheresis, 23 of 30 patients suffered from coronary heart disease. Twenty of 23 patients suffered intermittently from symptoms of angina, excertional dyspnea, and claudication. With LDL apheresis, reductions of 47% for total cholesterol, 49% for LDL, 26% for Lp(a), and 40% for triglycerides were reached. Severe side effects such as shock or allergic reactions were very rare (0.55%). In the course of treatment with LDL apheresis, an improvement in general well-being and increased performance were experienced in 27 of 30 patients. A reduction of nitrate medication between 60 and 100% was observed in 17 of 23 patients. The present data clearly demonstrate that treatment with LDL apheresis in patients suffering from severe familial hyperlipidemia, resistant to maximum conservative therapy, is very effective and safe even over long periods of time.


Kawasaki Disease Presenting as Acute Intestinal Obstruction.
Kawasaki disease (KD) is an acute febrile illness of childhood associated with vasculitis of medium-sized arteries especially the coronary arteries. Typical clinical features involving the skin, mucous surfaces, etc., occur sequentially over a few days. We report a rare presentation of KD as a surgical abdomen in a 2-year-old boy. Awareness of this presentation is important as it can otherwise lead to a delay in starting potentially life-saving intervention like intravenous immunoglobulins for cardiac complications kept cryptic by the manifest acute abdomen.


Hyponatremia and Renal Venous Congestion in Heart Failure Patients.
The interrelationship between the heart and kidneys has a great importance in the homeostasis of the cardiovascular system. Heart failure patients present intrarenal arterial hypoperfusion and intrarenal venous congestion due to reduced left ventricle ejection fraction, which triggers numerous neurohormonal factors. The aim of this study was to investigate intrarenal vascularization (arterial and venous), as well as the links between it and systemic congestion and, on the other side, with the mortality in patients with heart failure. Material and Methods. This cross-sectional study was performed on a group of 44 patients with heart failure in different stages of evolution and 44 healthy subjects, matched for age and gender, as controls. Serum natremia, NT-proBNP, and creatinine analyses were performed in all patients and controls. Renal and cardiac ultrasonography was done in all patients and controls, recording intrarenal arterial resistive index (RRI), intrarenal venous flow (IRVF) pattern, renal venous stasis index (RVSI), and left ventricular ejection fraction (LVEF). Data are recorded and presented as mean ± standard deviation. Statistical analyses were performed using the Student t-test, ANOVA test, and the Pearson correlation. Differences were considered statistically significant at the value of p < 0.05. Hyponatremia was identified in 47.72% of the HF patients. This study revealed correlations between serum natremia and LVEF, NT-proBNP, serum creatinine, interlobar venous RVSI (p < 0.00001), and interlobar artery RRI (p ≤ 0.002). Hyponatremia and renal venous congestion represent negative prognostic factors in HF patients. In HF patients, hyponatremia was correlated with cardiac dysfunction and intrarenal venous congestion. Hyponatremia and renal venous congestion represented negative prognostic factors in HF patients.


Improved distance analysis in RNA using network-editing techniques for overcoming errors due to spin diffusion.
Multispin magnetization transfer, or spin diffusion, is a significant source of error in NOESY-derived distance measurements for the determination of nucleic acid solution structures. The BD-NOESY and CBD-NOESY experiments, which allow the measurement of interproton distances with greatly reduced contributions from spin diffusion, have been adapted to structural analysis in RNA oligonucleotides. The techniques are applied to a lead-dependent ribozyme (LZ2). We demonstrate the measurement of both aromatic proton-aromatic proton NOEs free of spin diffusion involving the intervening ribose moieties and aromatic proton-ribose proton NOEs free of the efficient cross-relaxation within the ribose ring. In LZ2, the accuracy and precision of the resulting distances are significantly improved. We also find that, by allowing the use of longer mixing times with greater sensitivity, the experimental attenuation of spin diffusion in RNA increases the distance range of interactions that can be analyzed. This effect permits measurement of important long-range distances in LZ2 that are not accessible with standard techniques. Thus, these techniques allow the simultaneous optimization of the number, accuracy, and precision of distance constraints used for RNA structure determinations.


Job innovation for direct caregivers in the care of persons with mental retardation. A system of personal caregiving.
Professionals in different branches of the health care sector increasingly advocate a more flexible, individually-tailored type of care. To fit in with this trend, the Job Innovation Model was developed in The Netherlands. This model involves the systematic introduction of a system of personal caregiving. The purpose of the present study, using a pre-test-post-test quasi-experimental design, was to evaluate the effects of the implementation of the Job Innovation Model on the work and work perception of direct caregivers in the care of persons with mental retardation. Caregivers in the experimental group were found to have adopted the principles of the Job Innovation Model to a greater extent than their colleagues in the control group, and as a result, the experimental group started to work more methodically and perceived greater clarity in their work. In addition, a trend was observed towards greater job satisfaction among caregivers as a result of the introduction of the new model. No changes were found concerning burnout.


Pap1-mediated regulation of thioredoxin gene from Schizosaccharomyces pombe.
The genomic DNA encoding thioredoxin (TRX) was previously isolated from the fission yeast Schizosaccharomyces pombe. In this investigation, regulation of the S. pombe TRX gene was studied in lacZ translational fusions. The synthesis of beta-galactosidase from the fusion plasmid pYKT24 was significantly enhanced by treatments with cadmium chloride, zinc chloride, and high temperatures. Synthesis of beta-galactosidase from the fusion plasmid was significantly decreased by higher concentrations (5 microM, 10 microM) of mercuric chloride, whereas it was enhanced by its lower concentration (1 microM). Diamide affected the synthesis of beta-galactosidase in the same manner with mercuric chloride. However, high osmolarity had no effect on the beta-galactosidase synthesis from the fusion plasmid pYKT24. Various fusion plasmids were constructed to carry serially deleted upstream regions of the TRX gene. Pap1 mediates the regulation of the S. pombe TRX gene. The upstream region, between 987 and 1,270 bp from the translational initiation point, is responsible for the regulation.


Sevelamer decreases systemic inflammation in parallel to a reduction in endotoxemia.
Uremic toxins play a pivotal role in the development of systemic complications of chronic kidney disease (CKD), which are largely mediated by the activation of the immune system. Triggers of inflammation in CKD are largely unknown and strategies aiming to reduce circulating ligands that could start the inflammatory response are potentially important. In the present study, we investigated the impact of sevelamer hydrochloride treatment in reducing endotoxemia and inflammation in a group of hemodialysis (HD) patients. HD patients, who were converted from calcium carbonate treatment to sevelamer according to KDOQI guidelines, were included and prospectively followed for 6 months. Systemic inflammation was evaluated by serum ultra-high-sensitivity C-reactive protein (hsCRP) using an automated immunoturbidimetric assay. Endotoxin was measured using Limulus amebocyte lysate chromogenic endpoint assay. All the analyses were performed immediately before conversion and after 6 months of treatment. After the exclusion of patients discontinuing the treatment, 20 patients (mean dialysis time 12 +/- 4 months on HD, age 52 +/- 2 years, 38% males, 11% diabetics) were included in the analysis. No significant changes were observed in Ca, P and PTH levels, while a reduction in cholesterol levels was seen. Plasma concentration of hsCRP and endotoxin significantly decreased after 6 months of conversion to sevelamer compared with baseline. We conclude that sevelamer treatment leads to a decrease in hsCRP levels, which was accompanied by a parallel decrease in endotoxemia, suggesting that endotoxemia may contribute to the systemic inflammation in HD patients, which was partially reduced by the use of sevelamer.


[Ureteral rupture when changing a suprapubic vesical catheter].
We describe, for the first time, a rupture of the ureter caused by changing a suprapubic vesical catheter. The guide wire passed into the ostium of the left ureter during the procedure, and the catheter was pushed over the wire into the left ureter blocking it. The lesion was diagnosed by intravenous pyelography. A pigtail stent was placed in the left ureter.


Pharmacokinetics of flucloxacillin and its metabolites in patients with renal failure: Impact on liver toxicity .
The antimicrobial agent flucloxacillin is a potential cause of drug-induced liver disease, but the underlying mechanisms for toxicity have not been fully elucidated. As in-vitro and in-vivo findings suggest that biotransformation products contribute to hepatotoxicity, the purpose of this study was to characterize formation and accumulation of its metabolites in patients with renal failure. Twelve intensive care patients undergoing continuous venovenous hemofiltration received 4.0 g flucloxacillin as single and repeated infusion. Blood and dialysate samples were collected and analyzed for flucloxacillin and its metabolites by HPLC. The overall amounts of the flucloxacillin metabolites 5'-hydroxymethylflucloxacillin (5-OH-FX), 5'-hydroxymethylflucloxacillin-penicilloic acid (5-OH-PA), and flucloxacillin-penicilloic acid (FX-PA) produced varied considerably between patients, and accounted for 3.62 - 35.9% of total flucloxacillin concentration (flucloxacillin + metabolites) in the plasma. Clearance rates and sieving coefficients for 5-OH-FX and FX-PA were comparable to that of the parent drug, although removal of 5-OH-PA was decreased. Using an isolated perfused rat liver model we demonstrated that 5-OH-FX reached concentrations in the bile (240.5 ± 84.2 nmoles/mL) that were sufficient to exert cytotoxic effects, unlike either of the two penicilloic acids. Based on data from perfused rat livers, high biliary concentrations of 5-OH-FX might also be observed in our patients explaining why LDH, bilirubin, and alkaline phosphatase were elevated in up to 8/12 patients after repeated infusion of flucloxacillin. Liver toxicity of flucloxacillin might therefore be observed in patients with renal impairment after continuously elevated 5-OH-FX levels. .


Parallel responses of human epidermal keratinocytes to inorganic SbIII and AsIII.
SbIII and AsIII are known to exhibit similar chemical properties, but the degree of similarity in their effects on biological systems merits further exploration. Present work compares the responses of human epidermal keratinocytes, a known target cell type for arsenite-induced carcinogenicity, to these metalloids after treatment for a week at environmentally relevant concentrations. Previous work with these cells has shown that arsenite and antimonite have parallel effects in suppressing differentiation, altering levels of several critical enzymes and maintaining colony forming ability. More globally, protein profiling now reveals parallels in SbIII and AsIII effects. The more sensitive technique of transcriptional profiling also shows considerable parallels. Thus, gene expression changes were almost entirely in the same directions for the two treatments, although the degree of change was sometimes significantly different. Inspection of the changes revealed that RYR1 and LRIG1 were among the genes strongly suppressed, consistent with reduced calcium-dependent differentiation and maintenance of EGF-dependent proliferative potential. Moreover, levels of miRNAs in the cells were altered in parallel, with nearly 90% of the 198 most highly expressed ones being suppressed. Among these was miR-203, which is known to decrease proliferative potential. Finally, both SbIII and AsIII were seen to attenuate bone morphogenetic protein 6 induction of dual specificity phosphatases 2 and 14, consistent with maintaining epidermal growth factor receptor signaling. These findings raise the question whether SbIII, like AsIII, could act as a human skin carcinogen.


Acute action of choriogonadotropin on Leydig tumor cells: induction of a higher affinity benzodiazepine-binding site related to steroid biosynthesis.
We previously demonstrated that the mitochondrial peripheral-type benzodiazepine receptor (PBR) is coupled to hormone-activated steroidogenesis by regulating the intramitochondrial cholesterol transport, the rate-determining step of steroid biosynthesis. In the present study we examined whether PBR is the site of hormone action using the hCG-responsive MA-10 mouse Leydig tumor cell line as a model system. Within 15 sec of the addition of hCG to Leydig cells a 3-fold cAMP-dependent increase in PBR binding was observed. This rapid increase returned to basal levels within 60 sec. No effect was observed after 1 min in the continued presence of hCG. Scatchard analysis revealed that in addition to the known high affinity (5.0 nM) benzodiazepine-binding site, a second, hormone-induced, higher affinity (0.2 nM) benzodiazepine-binding site appeared. We then examined whether in such a short time frame steroid synthesis occurs. Fifteen-second incubation of MA-10 cells with the inhibitor of cholesterol metabolism aminoglutethimide together with hCG also resulted in an increased rate of pregnenolone formation by their isolated mitochondria that were washed and incubated in aminoglutethimide-free buffer. The dose response of benzodiazepine binding to hCG closely parallels the increase in steroid formation by the mitochondria of stimulated cells. Addition of the selective inhibitor of cAMP-dependent protein kinase, H-89, completely blocked hormone-induced PBR binding and steroid formation, whereas addition of the inactive analog H-85 was without any effect. The addition of flunitrazepam, a benzodiazepine previously shown to inhibit the trophic hormone action on steroidogenesis, completely abolished the hCG-induced rapid stimulation of steroid synthesis. These results demonstrate that in MA-10 cells, the most rapid effect described thus far of hCG and cAMP, is the transient induction of a higher affinity benzodiazepine-binding site, which occurs concomitantly with an increase in the rate of steroid formation. This, in turn, suggests that these hormones alter PBR to activate cholesterol delivery to the inner mitochondrial membrane and subsequent steroid formation.


New understanding of the damage of SARS-CoV-2 infection outside the respiratory system.
Since early December 2019, a number of pneumonia cases associated with unknown coronavirus infection were identified in Wuhan, China, and many additional cases were identified in other regions of China and in other countries within 3 months. Currently, more than 80,000 cases have been diagnosed in China, including more than 3000 deaths. The epidemic is spreading to the rest of the world, posing a grave challenge to prevention and control. On February 12, 2020, the International Committee on Taxonomy of Viruses and the World Health Organization officially named the novel coronavirus and associated pneumonia as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and coronavirus disease 2019 (COVID-19), respectively. According to the recent research on SARS-CoV-2, the virus mainly infects the respiratory system but may cause damage to other systems. In this paper, we will systematically review the pathogenic features, transmission routes, and infection mechanisms of SARS-CoV-2, as well as any adverse effects on the digestive system, urogenital system, central nervous system, and circulatory system, in order to provide a theoretical and clinical basis for the diagnosis, classification, treatment, and prognosis assessment of SARS-CoV-2 infection.


[Preparation and application of anti-ouabain IgY antibody].
To prepare highly specific anti-ouabain polyclonal antibody for detecting endogenous ouabain in tissues. Ouabain-BSA compound was used to immunize hens, and the eggs were collected one week after the first immunization. The IgY antibodies in the egg yolk were separated and purified by PEG-6000 Method, and analyzed by 12% SDS-PAGE and enzyme-linked immunosorbent assay (ELISA) for titration. The IgY antibodies obtained were applied subsequently in ELISA and immunohistochemistry. The IgY titer increased rapidly after the second immunization, with the highest titer of 1:10240 that lasted for at least 4 weeks. Competitive ELISA for IgY detection showed an average intraassay coefficient of variation (CV) of 2.03% and an inter-assay CV of 2.34%. Immunohistochemistry visualized the location of the endogenous ouabain mainly in the cytoplasm of the zona reticularis of rat adrenal cortex. Immunization of hens allows efficient preparation of IgY antibody which can be used in routine immunoassays.


Antenatal corticosteroids for late-preterm infants: a decision-analytic and economic analysis.
Objectives. Antenatal corticosteroids (ACS) are not routinely administered to patients at risk for delivery between 34 and 36 6/7 weeks. Our objective was to determine whether ACS are cost-effective for late-preterm infants at risk for imminent preterm delivery. We hypothesized that the preferred strategy <36 weeks would include ACS while the preferred strategy ≥36 weeks would not. Methods. We performed decision-analytic and cost-effectiveness analyses to determine whether ACS was cost-effective at 34, 35, and 36 weeks. We conducted a literature review to determine probability, utility, and cost estimates absent of patient-level data. Base-case cost-effectiveness analysis, univariable sensitivity analysis, and Monte Carlo simulation were performed. A threshold of $100,000/QALY was considered cost-effective. Results. The incremental cost-effectiveness ratio favored the administration of a full course of ACS at 34, 35, and 36 weeks ($62,888.25/QALY, $64,425.67/QALY, and $64,793.71/QALY, resp.). A partial course of ACS was not cost-effective. While ACS was the consistently dominant strategy for acute respiratory outcomes, all models were sensitive to changes in variables associated with chronic respiratory disease. Conclusions. Our findings suggest that the administration of ACS to patients at risk of imminent delivery 34-36 weeks could significantly reduce the cost and acute morbidity associated with late-preterm birth.


A Novel Fc-Engineered Anti-HER2 Bispecific Antibody With Enhanced Antitumor Activity.
Human epidermal growth factor receptor 2 (HER2) overexpression has been demonstrated in a variety of cancers. Targeted therapy with anti-HER2 monoclonal antibodies (mAbs) has been approved as a therapeutic modality. Despite the efficacy of mAbs in tumor treatment, many patients do not benefit from this therapeutic platform. Fragment crystallizable (Fc) engineering is a common approach to improve the efficacy of therapeutic mAbs. Five Fc-engineered mAbs have so far been approved by FDA. We have recently developed an anti-HER2 bispecific mAb, BiHT, constructed from variable domains of trastuzumab, and our novel humanized anti-HER2 mAb, hersintuzumab. BiHT displayed promising antitumor activity as potently as the combination of the parental mAbs. Here, we aimed to modify the Fc of BiHT to improve its therapeutic efficacy. The Fc-engineered BiHT (MBiHT) bound to recombinant HER2 and its subdomains with an affinity similar to BiHT. It also recognized native HER2 on different cell lines, inhibited their proliferation, downregulated HER2 expression, and suppressed downstream signaling pathways similar to BiHT. Compared with BiHT, MBiHT displayed enhanced antibody-dependent cellular cytotoxicity activity against various tumor cell lines. It also inhibited the growth of ovarian xenograft tumors in nude mice more potently than BiHT. Our findings suggest that MBiHT could be a potent therapeutic candidate for the treatment of HER2-overexpressing cancer types.


Immunogenicity and safety of intradermal influenza vaccine in immunocompromized patients: a meta-analysis of randomized controlled trials.
The primary influenza prevention strategy is focused on annual vaccination according to the categories identified in the various countries as being at greatest risk of complications. Many studies were conducted in order to demonstrate that intradermal (ID) vaccine formulation represents a promising alternative to conventional intramuscular (IM) formulation, especially in subjects with an impaired immune system. However, there is no consensus whether the efficacy and safety of ID is equivalent to IM in these subjects. Therefore, we performed a meta-analysis of Randomized Controlled Trials (RCT) to compare the immunogenicity and safety of ID and IM influenza vaccines in subjects with a depleted immune system. We conducted a search strategy of medical literature published until November 2014 in order to identify RCTs that evaluated the immunogenicity and safety of ID compared with IM influenza vaccines in immunocompromized patients. We identified a total of 269 citations through research in electronic databases and scanning reference lists. Of these, 6 articles were included in the meta-analysis, for a total of 673 subjects. The seroprotection rate induced by the ID vaccine is comparable to that elicited by the IM vaccine. The overall RR was 1.00 (95 % CI = 0.91 -1.10) for A/H1N1 strain, 1.00 (95 % CI = 0.90-1.12) for A/H3N2 and 0.99 (95 % CI = 0.84 -1.16) for B strain. No significant differences in the occurrence of systemic reactions were detected (17.7 % in the ID group vs 18.2 % in the IM group) with a pooled RR = 1.00 (95 % CI = 0.67 -1.51), whereas ID administration caused significantly more injection site reactions with a mean frequency of 46 % in the ID group compared to 22 % in the IM group, with a pooled RR = 1.89 (95 % CI = 1.40 -2.57). The ID influenza vaccine has shown a similar immunogenicity and safety to the IM influenza vaccine in immunocompromized patients, and it may be a valid option to increase compliance to influenza vaccination in these populations.


Evaluations of home care interventions for frail older persons using the interRAI Home Care instrument: a systematic review of the literature.
This systematic review describes the use of the interRAI Home Care (interRAI HC) instrument, an internationally validated comprehensive geriatric assessment, as a base for the evaluation of home care projects. Because of the evidence base of the instrument and its widespread use, researchers can make a thorough evaluation of projects and interventions in home care and can also have insight in international comparisons. The aim of this systematic review is to identify research that evaluates interventions in the home care setting using this comprehensive geriatric assessment and to describe these evaluations and report the results of the use of this instrument. Two independent reviewers constructed a comprehensive list of Medical Subject Headings, which was designed for 5 explicit categories: (1) interventions; (2) evaluation; (3) home care; (4) interRAI HC; and (5) older person. A systematic literature search was then performed in the main electronic databases Web of Science, EMBASE, MEDLINE, Cochrane, PsycInfo, and CINAHL for the years 1990 to 2013. Home care. Studies were described and the following information was extracted from the articles: mean age and proportion of gender of participants; sample size; location of the study; goal of the study; main findings; main limitations; and results of the evaluation of the interRAI HC instrument. A total of 349 articles were identified. Eighteen studies met our inclusion criteria describing 18 interventions in home care evaluated with the interRAI HC instrument. This systematic review can help researchers to plan evaluation of interventions in home care. The interRAI HC instrument proves to be a comprehensive tool to measure outcomes and can serve as an evaluation instrument for interventions. It can also be used as an intervention itself, when caregivers use the tool and its outcome measures to implement a care plan.


Parallel Polarization Illumination with a Multifocal Axicon Metalens for Improved Polarization Imaging.
Polarization imaging is an important branch of the microscopy technique that can provide additional information and enhanced contrast. The illumination system of a polarization microscope enables many different polarizations but makes the setup bulky, complicated, and slow. Here, we design and fabricate an ultrathin planar axicon metalens that also enables parallel illumination with different polarizations. Our results reveal a diffraction-limited size and high degree of linear polarization. To verify our approach, we accurately map the polarization angle of an aluminum grating, which is used as a polarizer. Furthermore, we demonstrate that elliptical polarization can be generated without additional design. A single metalens has the same capabilities as a conventional illumination module containing a polarizer, compensator, and rotation-stage/optical modulator. In addition, our device has the potential to enable rapid super-resolution polarization imaging. The new method could be useful in many applications and areas, including, e.g., materials research and biomedicine.


Velopharyngeal nomenclature: incompetence, inadequacy, insufficiency, and dysfunction.
Different usages of the terms velopharyngeal incompetence, velopharyngeal inadequacy, velopharyngeal insufficiency, and velopharyngeal dysfunction that are commonly found in the literature are reviewed. It is advocated that one should not attempt to use any of the terms to distinguish between neuromotor or structural causes for behavioral dysfunction. Although the terms can be used as synonyms, this is not always the case. When terms are used differently, it is important to make the specific usage clear from context.


Chromosome-length genome assembly and linkage map of a critically endangered Australian bird: the helmeted honeyeater.
The helmeted honeyeater (Lichenostomus melanops cassidix) is a Critically Endangered bird endemic to Victoria, Australia. To aid its conservation, the population is the subject of genetic rescue. To understand, monitor, and modulate the effects of genetic rescue on the helmeted honeyeater genome, a chromosome-length genome and a high-density linkage map are required. We used a combination of Illumina, Oxford Nanopore, and Hi-C sequencing technologies to assemble a chromosome-length genome of the helmeted honeyeater, comprising 906 scaffolds, with length of 1.1 Gb and scaffold N50 of 63.8 Mb. Annotation comprised 57,181 gene models. Using a pedigree of 257 birds and 53,111 single-nucleotide polymorphisms, we obtained high-density linkage and recombination maps for 25 autosomes and Z chromosome. The total sex-averaged linkage map was 1,347 cM long, with the male map being 6.7% longer than the female map. Recombination maps revealed sexually dimorphic recombination rates (overall higher in males), with average recombination rate of 1.8 cM/Mb. Comparative analyses revealed high synteny of the helmeted honeyeater genome with that of 3 passerine species (e.g., 32 Hi-C scaffolds mapped to 30 zebra finch autosomes and Z chromosome). The genome assembly and linkage map suggest that the helmeted honeyeater exhibits a fission of chromosome 1A into 2 chromosomes relative to zebra finch. PSMC analysis showed a ∼15-fold decline in effective population size to ∼60,000 from mid- to late Pleistocene. The annotated chromosome-length genome and high-density linkage map provide rich resources for evolutionary studies and will be fundamental in guiding conservation efforts for the helmeted honeyeater.