Screening diagnosis and staging of esophageal cancer.
In geographic areas where there is a high risk of esophageal cancer, analysis of cells obtained from the esophagus has been used effectively to detect early lesions. This has been demonstrated on a large scale in studies from China. Using abrasive balloon cytology techniques, 75% of the cancers detected were early lesions, where the 5-year survival after resection was in the range of 90%. Endoscopic followup studies indicate that dysplastic changes in the esophageal mucosa are a common precursor to malignancy. In many cases, the time course from dysplasia to carcinoma in situ to early invasive cancer may take place over many years, allowing a reasonable amount of time for screening. In low-incidence areas, such as the United States, most esophageal cancers are related to the excessive use of tobacco and alcohol. These factors are too common and the incidence of the disease too low, however, to justify screening on this basis. There are smaller groups at higher risk where selective screening by endoscopy with cytology and biopsy is recommended, usually every 1 to 3 years. These include patients with longstanding achalasia, lye strictures, and Plummer- Vinson syndrome. Patients with cancers of the head and neck region and patients with celiac disease may also be considered to be at increased risk. Tylosis is a rare inherited disease with a very high risk of esophageal cancer. There is an increased incidence of adenocarcinoma of the esophagus with Barrett's epithelium, and once identified such patients should be kept under endoscopic surveillance. The finding of severe dysplasia in any of these groups would indicate a shorter screening interval. Most patients with symptoms referable to the esophagus are first tested by barium esophagram. If negative, with persistent symptoms or if a suspicious lesion is identified, endoscopy with cytology and biopsy is recommended. Staging of the cancer is based on the size of the cancer both longitudinally and circumferentially and the presence of extraesophageal spread. At the present time, CT is the best noninvasive method for judging the extent of the cancer. Performance and nutritional status are also determinants of prognosis and should be considered in planning treatment.


Double-donor surrogacy and the intention to parent.
Assisted reproduction often involves biological contributions by third parties such as egg/sperm donors, mitochondrial DNA donors, and surrogate mothers. However, these arrangements are also characterised by a biological relationship between the child and at least one intending parent. For example, one or both intending parents might use their own eggs/sperm in surrogacy, or an intending mother might conceive using donor sperm or gestate a donor embryo. What happens when this relationship is absent, as in the case of 'double-donor surrogacy' arrangements (DDS)? Here, a child is conceived using both donor eggs and sperm, carried by a surrogate, and raised by the commissioning parents. In this paper, I critically examine proposals to allow DDS in the United Kingdom, and the intentionalist justification for treating this practice distinctly (morally and legally speaking) from private adoption. I argue that the intentionalist approach cannot plausibly justify such a distinction and that other approaches to moral parenthood are also unlikely to succeed.


Global Research Activity on Health System Preparedness Against Viral Infectious Disease Outbreaks.
The present study aimed to give an overview of research publications on health system preparedness against viral infectious disease outbreaks. A bibliometric method was implemented from 2001 to 2020. The studied pathogens were dengue, Ebola, influenza, Zika, Middle East respiratory syndrome (MERS), Severe acute respiratory syndrome (SARS), and coronavirus disease 2019 (COVID-19). The search query returned 501 documents. The growth of publications showed a sharp peak in 2020 for COVID-19 and 3 small peaks in 2006, 2009, and 2015 for SARS, influenza, and Ebola, respectively. Of the retrieved documents, 208 (41.5%) were on influenza, 164 (32.7%) were on COVID-19, and 83 (16.6%) were on Ebola. Countries in the region of the Americas (n = 221; 44.1%) returned the majority of the documents, while countries in Latin America and the African region returned the least. The United States (n = 197; 39.3%) had a leading role in this field. The US Centers for Disease Control and Prevention (n = 51; 10.2%) ranked first, followed by the Johns Hopkins University (n = 16; 3.2%). The Disaster Medicine and Public Health Preparedness journal (n = 21; 4.2%) ranked first. International research collaboration was relatively inadequate. Research on preparedness against infectious diseases was episodic. Research collaboration needs to be prioritized for countries with a history of fatal outbreaks.


Excision of a mediastinal parathyroid gland with use of video-assisted thoracoscopy, intraoperative 99mTc-sestamibi scanning, and intraoperative monitoring of intact parathyroid hormone.
To report the complementary use of video-assisted thoracoscopic surgery (VATS) and intraoperative 99mTc-sestamibi scanning for persistent secondary hyperparathyroidism due to a mediastinal supernumerary parathyroid gland. We describe a patient with recurrent secondary hyperparathyroidism attributable to a mediastinal parathyroid gland who underwent parathyroidectomy with use of VATS, intraoperative 99mTc-sestamibi scanning (gamma probe), and intraoperative monitoring of intact parathyroid hormone (iPTH). A 32-year-old man with chronic renal failure who had undergone a 4-gland parathyroidectomy with autotransplantation 14 years previously presented with symptomatic hypercalcemia. A preoperative single-photon emission computed tomographic (SPECT) sestamibi scan revealed a focus of mediastinal uptake, suggestive of an intrathymic gland. The patient underwent a cervical exploration, and the previously reimplanted parathyroid gland and the thymus were resected. iPTH levels failed to normalize, and the operation was terminated. A repeated SPECT scan again revealed an area of mediastinal uptake. Computed tomographic scan of the chest showed a mediastinal gland adjacent to the aortic arch. VATS and intra-operative sestamibi scanning aided in localization of the ectopic parathyroid gland. After removal of the hyperplastic gland, iPTH levels decreased appropriately. In reoperative parathyroidectomy involving mediastinal glands, VATS, complemented by gamma probe localization and iPTH monitoring, may be used to minimize the operative dissection needed to cure hyperparathyroidism.


[Quality research and the difficulties involved therein].
After an evaluation of the current situation of research in our country and establishing the concept and requisites of what is considered "quality research", this article will analyze the difficulties in carrying it out (lack of appreciation of research activity and consequent lack of necessary support and insufficient funding, lack of training for researchers, lack of continuity, among others), while trying to provide possible solutions to these problems. The important role of university hospitals will play as the backbone of translational research, coordinating research and medical practice, is also considered, together with the need to reorganize these institutions for this transcendent mission. The driving forces behind research activity in our discipline and the characteristics of radiological research are analyzed, postulating the need to return to the basics (simple, practical patient-centered research, as opposed to research based on technology) and pointing out the interest in the integration of recently constituted European organisms to promote multicenter research in medical imaging (EIBIR: European Institute for Biomedical Imaging Research).


Bone disorders in chronic liver disease.
Osteomalacia rarely occurs in adult patients with chronic liver disease despite a low serum vitamin D level being reported in up to two-thirds of patients with cirrhosis. In contrast, osteoporosis, which increases the risk of vertebral fractures, occurs in 12%-55% of patients with cirrhosis. Although the prevalence is probably falling, as shown by a fall from 57%-26% in patients with biliary disease requiring liver transplantation over the last 2 decades, it still accounts for significant patient morbidity. Bone density also falls in the first 3 months after liver transplantation, and pretransplant fractures are predictive of posttransplant fractures. Many of the known risk factors for postmenopausal osteoporosis exist in the cirrhotic population, such as excess alcohol intake, steroid use, poor nutrition, and hypogonadism. There is also an increased risk of osteoporosis in patients without cirrhosis, particularly those with hemochromatosis and biliary disease. The diagnosis is made with bone density measurements. The effective treatment is largely based on evidence from postmenopausal osteoporosis as there have been only a few small clinical trials of patients with chronic liver disease. Bisphosphonates are the mainstay of treatment; they have been shown to be effective in biliary disease and are well tolerated.


Lewis Acid Probe for Basicity of Sulfide Electrolytes Investigated by 11B Solid-State NMR.
Sulfide-based solid-state lithium-ion batteries (SSLIB) have attracted a lot of interest globally in the past few years for their high safety and high energy density over the traditional lithium-ion batteries. However, sulfide electrolytes (SEs) are moisture-sensitive which pose significant challenges in the material preparation and cell manufacturing. To the best of our knowledge, there is no tool available to probe the types and the strength of the basic sites in sulfide electrolytes, which is crucial for understanding the moisture stability of sulfide electrolytes. Herein, we propose a new spectral probe with the Lewis base indicator BBr3 to probe the strength of Lewis basic sites on various sulfide electrolytes by 11B solid-state NMR spectroscopy (11B-NMR). The active sulfur sites and the corresponding strength of the sulfide electrolytes are successfully evaluated by the proposed Lewis base probe. The probed strength of the active sulfur sites of a sulfide electrolyte is consistent with the results of DFT (density functional theory) calculation and correlated with the H2S generation rate when the electrolyte was exposed in moisture atmosphere. This work paves a new way to investigate the basicity and moisture stability of the sulfide electrolytes.


Using amine-functionalized magnetite hollow nanospheres (AMHNs) as adsorbents for heavy metal ions.
In this paper, the amine-functionalized magnetite hollow nanospheres (AMHNs), prepared through a facile one-pot synthesis, were used as heavy metal ion adsorbents, whose morphology and physicochemical features were exploring by transmission electron microscopy, vibrating sample magnetometer, X-ray diffraction and Fourier-transform infrared analyses. Its adsorption performances for Pb2+, Cu2+, Zn2+, Ni2+ and Cd2+ were studied in detail. The adsorption increased with the increase of initial pH value of the solution and could be obviously affected by ionic strength. Also, the adsorption kinetics and isotherms were studied. The adsorption processes for Pb2+, Cu2+, Zn2+, Ni2+ and Cd2+ could all reach equilibrium in 60 min and be described well by the Langmuir thermodynamics model. The saturated adsorption capacities for Pb2+, Cu2+, Zn2+, Ni2+ and Cd2+ were 0.66, 0.47, 0.45, 0.38 and 0.26 mmol/g, respectively. In addition, the competitive adsorption showed the AMHNs had higher affinity to Pb2+ than to other heavy metal ions.


Interactive effects of predator and prey harvest on ecological resilience of rocky reefs.
A major goal of ecosystem-based fisheries management is to prevent fishery-induced shifts in community states. This requires an understanding of ecological resilience: the ability of an ecosystem to return to the same state following a perturbation, which can strongly depend on species interactions across trophic levels. We use a structured model of a temperate rocky reef to explore how multi-trophic level fisheries impact ecological resilience. Increasing fishing mortality of prey (urchins) has a minor effect on equilibrium biomass of kelp, urchins, and spiny lobster predators, but increases resilience by reducing the range of predator harvest rates at which alternative stable states are possible. Size-structured predation on urchins acts as the feedback maintaining each state. Our results demonstrate that the resilience of ecosystems strongly depends on the interactive effects of predator and prey harvest in multi-trophic level fisheries, which are common in marine ecosystems but are unaccounted for by traditional management.


Modulation of antibody-mediated glomerular injury in vivo by bacterial lipopolysaccharide, tumor necrosis factor, and IL-1.
We have investigated the effects of LPS, human rTNF (hrTNF) and human rIL-1 beta (hrIL-1 beta) pretreatment on the intensity of antibody-mediated injury in vivo by using a passive model of anti-glomerular basement membrane (GBM) antibody-mediated nephritis in rats. The experiments show that all three pretreatments exacerbate injury in this model whether judged by albuminuria or the prevalence of glomerular capillary thrombi. The effect on albuminuria was dose dependent with all three treatments. The lowest effective dose of LPS was 0.025 microgram while those for hrTNF and hrIL-1 beta were 0.4 microgram and 0.5 microgram, respectively. All three pretreatments also increased the prevalence of glomerular capillary thrombi which were rare in rats injected with anti-GBM antibodies without pretreatment. LPS pretreatment appeared to be more effective in causing glomerular capillary thrombi than hrTNF or hrIL-1 beta and this was reflected in the correlations between albuminuria and the proportion of glomeruli with capillary thrombi. This relation was linear for all three pretreatments but the slope was appreciably greater for rats pretreated with LPS (0.37) when compared with results from rats given either hrTNF (0.22) or hrIL-1 beta (0.29). Pretreatment of nephritic rats with both cytokines increased the slope to 0.42 demonstrating a synergistic effect. The synergism of hrTNF with hrIL-1 beta was also demonstrated by the effective doses needed to induce albuminuria which was evident in rats treated with 0.05 microgram of IL-1 beta and 0.4 microgram of TNF. Neither the cytokines nor LPS caused clinical, morphologic, or biochemical evidence of renal toxicity when given alone in the dose used here but they did cause a transient increase in the number of neutrophils marginated in glomerular capillaries. Pretreatment of rats with LPS or cytokines increased the glomerular neutrophil influx after anti-GBM antibodies by roughly sixfold. Our experiments show that TNF and IL-1 can increase the severity of glomerular injury in nephritis; they may be important in modulating glomerular injury clinically.


Layer-by-Layers of Polymeric Micelles as a Biomimetic Drug-Releasing Network.
Mucin networks are lubricous biofunctional coats formed through the continuous deposition of mucin glycoproteins. Previously, we demonstrated the synthesis of a mucin mimic using biotinylated-filomicelles crosslinked via streptavidin using a layer-by-layer approach. These networks recreate the fibrous nature of mucin and can serve as a drug-releasing network. In this work, the ability to vary the network properties by blending filomicelles with spherical micelles is demonstrated. In addition, the deposition of a dense polymer coating on the mucin network was shown to act as a barrier to control diffusion and improved the structural stability under simulated oral chemical conditions. These biomimetic coatings can be utilized as a delivery system, providing a tunable drug release for oral applications.


Epidemiological study of tick infestation in buffalo of various regions of district Khairpur, Pakistan.
The aim of this study was to determine the epidemiological infestation and identification of Ixodidae and Argasidae ticks species in buffalo of different parts of district Khairpur, Pakistan. A total of 720 Water buffaloes from three tehsils (subdivisions) were selected randomly and examined from organized and unorganized dairy farms for tick infestation in district Khairpur, Pakistan. This epidemiological survey was conducted during April to September 2015. The overall mean population and preferred site of tick attachment to infested animals, in Gambat, Sobhodero, and Kot Diji tehsils, were observed on different body parts. The primary body area of infestation by ticks (head, thorax, abdomen, udder, and tail) ranged from highest in tail and udder part compared to lowest in the abdomen, head, and thorax. In all study areas, the infestation was higher (p<0.05) in tail and udder than other parts of the body. In all the study areas, the overall highest population was found in the month of July. In addition, we first time identify four new species of ticks (Hyalomma anatolicum, H. anatolicum excavatum, Hyalomma Ixodes excavatum, and Ixodes ricinus) in district Khairpur, Pakistan. Results of this study provide additional information of epidemiological tick infestation, and will be helpful for evolving effective control policy for the management of tick infestation in study district.


Sociodemographic, physical, mental and social factors in the cessation of breastfeeding before 6 months: a systematic review.
The World Health Organization recommends exclusive breastfeeding as the main source of nutrition for infants during their first 6 months of life. However, despite this well-known recommendation, not all mothers breastfeed, whether partly or fully, during this time. The aim of this systematic literature review was to compile evidence regarding sociodemographic, physical, mental and social factors that influence breastfeeding mothers to stop breastfeeding before the infant reaches 6 months. A systematic search was conducted in four databases. Studies with quantitative research were included. Totally, 186 abstracts were read, 83 seemed relevant but 18 were found to be duplicates. Finally, 27 articles met the inclusion criteria and were included. The quality assessment was carried out with a quality assessment template from the Swedish Council on Technology and Assessment, and the grading of the result was carried out according to GRADE. The association of breastfeeding cessation between the mother's young age, low level of education, return to work within 12-week postpartum, caesarean birth and inadequate milk supply was found to have a low level of evidence. The link found between depressions among the mothers with the cessation of breastfeeding was found to have a very low level of evidence. Sociodemographic factors appeared to have caused cessation of breastfeeding in some of the included articles. The preventive work should focus on how to improve the knowledge of healthcare professionals and targeted interventions must address mothers who are at risk of ceasing breastfeeding before the recommended time.


Comparison of ceftibuten transport across Caco-2 cells and rat jejunum mounted on modified Ussing chambers.
Ceftibuten uptake into Caco-2 cells and intestinal brush border membrane vesicles is mediated by the dipeptide transport system (PEPT1). The apical to basolateral transport characteristics of ceftibuten across Caco-2 cells and rat jejunum mounted on a modified Ussing chamber was examined. Mannitol was used as a paracellular marker along with trans-epithelial electrical resistance (TEER) for monitoring tight junction permeability. Transport across Caco-2 cells and rat jejunum mounted on a modified Ussing chamber was linear across the concentration range 0.25-10 mM. The net flux of mannitol and ceftibuten was higher across rat jejunum compared with Caco-2 cells. At a donor concentration of 0.25 mM, ceftibuten transport across Caco-2 cells was found to be pH dependent. Glycyl proline, a dipeptide, and 2,4- dinitrophenol, an energy poison, caused a reduction in the permeability of 0.25 mM ceftibuten across Caco-2 cells. Benzoic acid and adipic acid also inhibited transcellular transport of ceftibuten. At a donor concentration of 0.25 mM, passive paracellular transport accounts for about 60% and the active carrier mediated mechanism accounts for about 40% of ceftibuten transport across Caco-2 cells. None of the inhibitors however, had a significant effect on ceftibuten transport across rat jejunum mounted on a modified Ussing chamber at a donor concentration of 0.25 mM. In the concentration range 0.25-10 mM, ceftibuten is predominantly transported by paracellular mechanisms across rat jejunum and a mixture of active and passive transport across Caco-2 cells.


Characterization of a monoclonal antibody specific to California serogroup orthobunyaviruses and development as a chimeric immunoglobulin M-positive control in human diagnostics.
California serogroup viruses (CSGVs) of medical importance in the United States include La Crosse virus, Jamestown Canyon virus (JCV), California encephalitis virus, and snowshoe hare virus. Current diagnosis of CSGVs relies heavily on serologic techniques for detecting immunoglobulin M (IgM), an indication of a recent CSGV infection. However, human-positive control sera reactive to viruses in the serogroup are scarce because detection of recent infections is rare. Here, we describe the development of new murine monoclonal antibodies (MAbs) reactive to CSGVs and the engineering of a human-murine chimeric antibody by combining the variable regions of the broadly CSGV cross-reactive murine MAb, 3-3B6/2-3B2 and the constant region of the human IgM. MAb 3-3B6/2-3B2 recognizes a tertiary epitope on the Gn/Gc heterodimer, and epitopes important in JCV neutralization were mapped to the Gc glycoprotein. This engineered human IgM constitutively expressed in a HEK-293 stable cell line can replace human-positive control sera in diagnostic serological techniques such as IgM antibody capture enzyme-linked immunosorbent assay (MAC-ELISA). Compared to the parent murine MAbs, the human-chimeric IgM antibody had identical serological activity to CSGVs in ELISA and demonstrated equivalent reactivity compared to human immune sera in the MAC-ELISA.IMPORTANCEOrthobunyaviruses in the California serogroup cause severe neurological disease in children and adults. While these viruses are known to circulate widely in North America, their occurrence is rare. Serological testing for CSGVs is hindered by the limited availability and volumes of human-positive specimens needed as controls in serologic assays. Here, we described the development of a murine monoclonal antibody cross-reactive to CSGVs engineered to contain the variable regions of the murine antibody on the backbone of human IgM. The chimeric IgM produced from the stably expressing HEK293 cell line was evaluated for use as a surrogate human-positive control in a serologic diagnostic test.


Relaxed skin tension line-oriented keystone-designed perforator island flaps considering the facial aesthetic unit concept for the coverage of small to moderate facial defects.
A variety of reconstructive options including skin grafts, loco-regional flaps, and free flaps exist for the coverage of facial defects. Each technique has advantages and disadvantages. In this study, we present our experience with relaxed skin tension line (RSTL)-oriented, keystone-designed perforator island flap (KDPIF) reconstructions, in consideration of the facial aesthetic unit concept for coverage of small to moderate facial defects.Between May 2016 and February 2018, 17 patients (11 men and 6 women), with an average age of 63.53 years (range: 37-83 years) underwent KDPIF reconstructions to cover facial defects. We performed the KDPIF reconstructions in consideration of the RSTLs and facial aesthetic unit concept. We retrospectively reviewed the defect causes, locations, and sizes, and flap sizes, types, and survivals, as well as the complications. Cosmetic outcomes were evaluated using the Harris 4-stage scale from 3 independent plastic surgeons' point of view, and postoperative satisfactory surveys from all patients.All defects were successfully covered with KDPIF. The defect sizes varied from 1.5 × 1.5 cm to 3 × 3.5 cm. The flap sizes varied from 1.5 × 3 cm to 3 × 5.5 cm. All flaps fully survived and there were no postoperative complications. The average subjective patient satisfaction score was 8.29 (range: 7-10) and the objective cosmetic outcomes were favorable (fair, good, or excellent).Considering its simplicity and safety, the KDPIF is a good reconstruction option with few complications and high reproducibility. The RSTL-oriented KDPIF reconstruction is a good reconstructive option for covering small to moderate facial defects with superior aesthetic outcomes.


Association of Prenatal Exposure to Maternal Drinking and Smoking With the Risk of Stillbirth.
Prenatal smoking is a known modifiable risk factor for stillbirth; however, the contribution of prenatal drinking or the combination of smoking and drinking is uncertain. To examine whether prenatal exposure to alcohol and tobacco cigarettes is associated with the risk of stillbirth. The Safe Passage Study was a longitudinal, prospective cohort study with data collection conducted between August 1, 2007, and January 31, 2015. Pregnant women from Cape Town, South Africa, and the Northern Plains region of the US were recruited and followed up throughout pregnancy. Data analysis was performed from November 1, 2018, to November 20, 2020. Maternal consumption of alcohol and tobacco cigarettes in the prenatal period. The main outcomes were stillbirth, defined as fetal death at 20 or more weeks' gestation, and late stillbirth, defined as fetal death at 28 or more weeks' gestation. Self-reported alcohol and tobacco cigarette consumption was captured at the recruitment interview and up to 3 scheduled visits during pregnancy. Participants were followed up during pregnancy to obtain delivery outcome. Of 11663 pregnancies (mean [SD] gestational age at enrollment, 18.6 [6.6] weeks) in 8506 women for whom the pregnancy outcome was known by 20 weeks' gestation or later and who did not terminate their pregnancies, there were 145 stillbirths (12.4 per 1000 pregnancies) and 82 late stillbirths (7.1 per 1000 pregnancies). A total of 59% of pregnancies were in women from South Africa, 59% were in multiracial women, 23% were in White women, 17% were in American Indian women, and 0.9% were in women of other races. A total of 8% were older than 35 years. In 51% of pregnancies, women reported no alcohol or tobacco cigarette exposure (risk of stillbirth, 4 per 1000 pregnancies). After the first trimester, 18% drank and smoked (risk of stillbirth, 15 per 1000 births), 9% drank only (risk of stillbirth, 10 per 1000 pregnancies), and 22% smoked only (risk of stillbirth, 8 per 1000 pregnancies). Compared with the reference group (pregnancies not prenatally exposed or without any exposure after the first trimester), the adjusted relative risk of late stillbirth was 2.78 (98.3% CI, 1.12-6.67) for pregnancies prenatally exposed to drinking and smoking, 2.22 (98.3% CI, 0.78-6.18) for pregnancies prenatally exposed to drinking only after the first trimester, and 1.60 (98.3% CI, 0.64-3.98) for pregnancies prenatally exposed to smoking only after the first trimester. The adjusted relative risk for all stillbirths was 1.75 (98.3% CI, 0.96-3.18) for dual exposure, 1.26 (98.3% CI, 0.58-2.74) for drinking only, and 1.27 (98.3% CI, 0.69-2.35) for smoking only compared with the reference group. These results suggest that combined drinking and smoking after the first trimester of pregnancy, compared with no exposure or quitting before the end of the first trimester, may be associated with a significantly increased risk of late stillbirth.


How is food variety conceptualised and measured as a diet quality indicator in developed settings? Protocol for a systematic scoping review.
Dietary diversity (DD) is a pillar of healthy eating guidance and can be used to assess diet quality. Despite being an established nutrition concept, many inconsistencies in its definition and measurement exist and meanings vary across the development spectrum. This protocol outlines a research trajectory, whereby a scoping review will be undertaken to illustrate and map the methodological approaches that have been utilised to measure diversity as a marker of diet quality in the general population. It seeks to determine the most common and less used methodological approaches to measure DD in the diet of healthy adults. Scoping review of peer-reviewed and grey literature from five bibliographic databases, supplemented by handsearching of reviews and reference lists. Search terms will include DD, food variety, mixed diet, balanced diet and food group variety. Eligible articles must include a measure for DD as an indicator of diet quality in the general population living in developed settings. Two independent reviewers will screen titles or abstracts, and read full-texts. Consensus will resolve any disagreements on study eligibility with a third reviewer consulted if needed. Data will be extracted using a standardised evidence table and analysed using a narrative synthesis approach. Data will be managed using Covidence. No ethics is required for this study using public documents. Results will be disseminated through peer-reviewed papers and scientific conferences. This scoping review will help to map, classify and assess the methodological approaches used in the nutrition literature to measure DD as a diet quality indicator. We anticipate a wide range of DD measures and expect to identify the most prevalent DD measures used to assess diet quality. Our findings will inform standardisation to improve future research on this nutritional concept.


Selective impairments of resting-state networks in minimal hepatic encephalopathy.
Minimal hepatic encephalopathy (MHE) is a neuro-cognitive dysfunction characterized by impairment in attention, vigilance and integrative functions, while the sensorimotor function was often unaffected. Little is known, so far, about the exact neuro-pathophysiological mechanisms of aberrant cognition function in this disease. To investigate how the brain function is changed in MHE, we applied a resting-state fMRI approach with independent component analysis (ICA) to assess the differences of resting-state networks (RSNs) between MHE patients and healthy controls. Fourteen MHE patients and 14 age-and sex-matched healthy subjects underwent resting-state fMRI scans. ICA was used to identify six RSNs [dorsal attention network (DAN), default mode network (DMN), visual network (VN), auditory network (AN), sensorimotor network (SMN), self-referential network (SRN)] in each subject. Group maps of each RSN were compared between the MHE and healthy control groups. Pearson correlation analysis was performed between the RSNs functional connectivity (FC) and venous blood ammonia levels, and neuropsychological tests scores for all patients. Compared with the healthy controls, MHE patients showed significantly decreased FC in DAN, both decreased and increased FC in DMN, AN and VN. No significant differences were found in SRN and SMN between two groups. A relationship between FC and blood ammonia levels/neuropsychological tests scores were found in specific regions of RSNs, including middle and medial frontal gyrus, inferior parietal lobule, as well as anterior and posterior cingulate cortex/precuneus. MHE patients have selective impairments of RSNs intrinsic functional connectivity, with aberrant functional connectivity in DAN, DMN, VN, AN, and spared SMN and SRN. Our fMRI study might supply a novel way to understand the neuropathophysiological mechanism of cognition function changes in MHE.


Stability of a binge drinking model with delay.
A more realistic binge drinking model with time delay is introduced. Time delay is used to represent the time lag of the immunity against drinking in our model. For the model without the time delay, using Routh-Hurwitz criterion, we obtain that the alcohol-free equilibrium is locally asymptotically stable if [Formula: see text]. We also obtain that the unique alcohol-present equilibrium is locally asymptotically stable if [Formula: see text]. For the model with time delay, the local stability of all the equilibria is derived. Furthermore, regardless of the time delay length, using comparison theorem and iteration technique, we obtain that the alcohol-free equilibrium is globally asymptotically stable under certain conditions. Numerical simulations are also conducted to illustrate and extend our analytic results.


Maternal plasma concentrations of angiogenic/antiangiogenic factors in the third trimester of pregnancy to identify the patient at risk for stillbirth at or near term and severe late preeclampsia.
To determine whether maternal plasma concentrations of placental growth factor (PlGF), soluble endoglin (sEng), and soluble vascular endothelial growth factor receptor-1 (sVEGFR-1) at 30-34 weeks of gestation can identify patients at risk for stillbirth, late preeclampsia, and delivery of small-for-gestational-age (SGA) neonates. A prospective cohort study included 1269 singleton pregnant women from whom blood samples were obtained at 30-34 weeks of gestation and who delivered at >34 weeks of gestation. Plasma concentrations of PlGF, sEng, and sVEGFR-1 were determined by enzyme-linked immunosorbent assay. The prevalence of late (>34 weeks of gestation) preeclampsia, severe late preeclampsia, stillbirth, and SGA was 3.2% (n = 40), 1.8% (n = 23), 0.4% (n = 5), and 8.5% (n = 108), respectively. A plasma concentration of PlGF/sEng <0.3 MoM was associated with severe late preeclampsia (adjusted odds ratio, 16); the addition of PlGF/sEng to clinical risk factors increased the area under the receiver-operating characteristic curve from 0.76 to 0.88 (P = .03). The ratio of PlGF/sEng or PlGF/sVEGFR-1 in the third trimester outperformed those obtained in the first or second trimester and uterine artery Doppler velocimetry at 20-25 weeks of gestation for the prediction of severe late preeclampsia (comparison of areas under the receiver-operating characteristic curve; each P ≤ .02). Both PlGF/sEng and PlGF/sVEGFR-1 ratios achieved a sensitivity of 74% with a fixed false-positive rate of 15% for the identification of severe late preeclampsia. A plasma concentration of PlGF/sVEGFR-1 <0.12 MoM at 30-34 weeks of gestation had a sensitivity of 80%, a specificity of 94%, and a likelihood ratio of a positive test of 14 for the identification of subsequent stillbirth. Similar findings (sensitivity 80%; specificity 93%) were observed in a separate case-control study. Risk assessment for stillbirth and severe late preeclampsia in the third trimester is possible with the determination of maternal plasma concentrations of angiogenic and antiangiogenic factors at 30-34 weeks of gestation.


Multiple auditory steady-state responses (MASTER): stimulus and recording parameters.
Steady-state responses evoked by simultaneously presented amplitude-modulated tones were measured by examining the spectral components in the recording that corresponded to the different modulation frequencies. When using modulation frequencies between 70 and 110 Hz and an intensity of 60 dB SPL, there were significant interactions between two stimuli when the carrier frequencies were closer than one half of an octave apart, with attenuation of the response to the lower carrier frequency. However, there were no significant decreases in response amplitude with four simultaneous stimuli provided the carrier frequencies differed by one octave or more. Higher intensities (70 dB SPL) resulted in greater interactions between the stimuli than when low intensities (35 dB SPL) were used. Modulation frequencies could be as closely spaced as 1.3 Hz without affecting the responses. Using broad-band noise as a carrier instead of a pure tone resulted in a significantly larger response when the stimuli were presented at the same sound pressure level. At modulation frequencies between 30 and 50 Hz, there were greater interactions between stimuli than at faster modulation frequencies. These results support the following recommendations for using multiple stimuli in evoked potential audiometry: (1) The multiple stimulus technique works well for steady state responses at frequencies between 70 and 110 Hz. (2) Up to four stimuli can be simultaneously presented to an ear without significant loss in amplitude of the response, provided the carrier frequencies are separated by an octave and the intensities are 60 dB SPL or less. (3) Bandpass noise might serve as a better carrier signal than pure tones.


Draft Genome Sequences of Seven Streptococcus agalactiae Strains Isolated from Camelus dromedarius at the Horn of Africa.
We present draft whole-genome sequences of seven Streptococcus agalactiae strains isolated from Camelus dromedarius in Kenya and Somalia. These data are an extension to the group B Streptococcus (GBS) pangenome and might provide more insight into the underlying mechanisms of pathogenicity and antibiotic resistance of camel GBS.


Crystalline Supramolecular Gyroscope with a Water Molecule as an Ultrasmall Polar Rotator Modulated by Charge-Assisted Hydrogen Bonds.
A new strategy for the construction of crystalline molecular rotors is presented. The combination of a conformation-modifiable macrocyclic host and two cooperative guests affords one supramolecular gyroscope-like compound, (t-BuNH3)(18-crown-6)[ZnCl3(H2O)], in which the coordinated water molecule functions as an ultrasmall polar rotator, revealed by its significant dielectric relaxation and the molecular dynamics simulations. In addition, such a compound can reversibly undergo a polar-to-polar phase transition triggered by the changed conformation of the 18-crown-6 host, leading to a switchable on/off rotation of water molecule, well controlled by strength and direction of charge-assisted hydrogen bonds.


Crypticity in Biological Invasions.
Ecological effects of alien species can be dramatic, but management and prevention of negative impacts are often hindered by crypticity of the species or their ecological functions. Ecological functions can change dramatically over time, or manifest after long periods of an innocuous presence. Such cryptic processes may lead to an underestimation of long-term impacts and constrain management effectiveness. Here, we present a conceptual framework of crypticity in biological invasions. We identify the underlying mechanisms, provide evidence of their importance, and illustrate this phenomenon with case studies. This framework has potential to improve the recognition of the full risks and impacts of invasive species.


In house development of (99m)Tc-Rhenium sulfide colloidal nanoparticles for sentinel lymph node detection.
In this study, rhenium sulfide colloidal nanoparticles were developed as radiopharmaceutical for sentinel lymph node detection. We directly used rhenium sulfide as a starting material for the preparation of colloidal nanoparticles. UV-visible spectrophotometry was used for characterization of in house developed colloidal particles. The size distribution of radioactive particles was studied by using membrane filtration method. The percentage of radiolabeled colloidal nanoparticles was determined by paper chromatography (PC). The study also includes in vitro stability, protein binding in human blood and bioevaluation in a rabbit model. The results indicate that 77.27 ± 3.26 % particles of size less than 20nm (suitable for lymphoscintigraphy) were radiolabeled. (99m)Tc labeled rhenium sulfide labeling efficacy with the radiometal is 98.5 ± 0.5%, which remains considerably stable beyond 5h at room temperature. Furthermore, it was observed that 70.2 ± 1.3% radiolabeled colloid complex showed binding with the blood protein. Bioevaluation results show the remarkable achievement of our radiopharmaceutical. The in house prepared (99m)Tc labeled rhenium sulfide colloidal nanoparticles reached the sentinel node within 15 min of post injection. These results indicate that (99m)Tc labeled rhenium sulfide colloid nanoparticles kit produced by a novel procedure seems of significant potential as a feasible candidate for further development to be used in clinical practice.


Strategies for functional validation of genes involved in reproductive stages of orchids.
Plants in the largest family of angiosperms, Orchidaceae, are diverse in both specialized pollination and ecological strategies and provide a rich source for investigating evolutionary relationships and developmental biology. However, studies in orchids have been hindered by several challenges that include low transformation efficiency and long regeneration time. To overcome such obstacles, we selected a symptomless cymbidium mosaic virus (CymMV) isolate for constructing virus-induced gene-silencing vectors. The feasibility of the virus vectors was first assessed with use of an orchid phytoene desaturase gene. The vector was able to induce gene silencing in orchids; however, because of the slow growth of orchids, the commonly used phytoene desaturase gene was not a good visual marker in orchids. We inserted a 150-nucleotide unique region of a B-class MADS-box family gene, PeMADS6, into pCymMV-pro60. The transcription level of PeMADS6 in inoculated Phalaenopsis plants was reduced by up to 73%, but no effect was observed for other MADS-box family genes. In contrast, in Phalaenopsis plants inoculated with CymMV transcripts containing 500 nucleotides of PeMADS6, a conserved region among MADS-box genes, the transcription level of PeMADS6 and the B- and C-class MADS-box genes was reduced by up to 97.8% as compared with plants inoculated with the vector alone. Flower morphology was affected in the MADS-box family gene-silenced plants as well. This in vivo experiment demonstrates an efficient way to study genes involved in the reproductive stage of plants with a long life cycle.


[Effect of metanephric mesenchymal stem cells after renal ischemia reperfusion injury in mice].
To study the effect of metanephric mesenchymal stem cells (MMSCs ) after renal ischemia reperfusion injury (IRI). C57BL/6J male mice were divided into control group (n=5) and experimental group (n=30). The control group was given a sham operation, while in the experimental group, a model of renal IRI was established. The experimental group was further divided into two groups according to the material injected through the femoral vein: IRI group (injected with normal saline, 10 ml/kg) and cell therapy group (injected with normal saline containing 5×10(5) MMSCs, 10 ml/kg). Samples of blood and kidney tissues were collected from five mice from each group at 12 h, 24 h and 72 h after IRI. The serum creatinine (SCr) level was detected, and the results of kidney tissue pathological staining and Paller score of renal tubules were analyzed to assess the effect of MMSCs after renal IRI. In addition, the expression of microRNA-26a(miR-26a)in kidney tissues was detected by reverse transcriptase-polymerase chain reaction (RT-PCR) and compared among the groups. (1) In both IRI group and cell therapy group, the levels of SCr at 12 h, 24 h and 72 h after operation were all significantly higher than those of the control group, besides, the level of SCr at 24 h was significantly higher than that at 12 h and 72 h (all P<0.05). The levels of SCr at 12 h, 24 h and 72 h were of no significant differences between IRI group and cell therapy group(all P>0.05). (2)Paller scores of renal tubules at 12 h, 24 h and 72 h in both IRI group and cell therapy group were significantly higher than those in the control group, and the scores at 24 h were significantly higher than that at 72 h, while the latter were in turn higher than the scores at 12 h (all P<0.05). In the cell therapy group, Paller score of renal tubules at 24 h(57.2±6.3)was significantly lower than that in IRI group(70.8±14.8) (P<0.05). Histological examination showed renal tubular epithelial cell atrophy, swelling and protein cast in kidney tissues from IRI group at 24 h, compared with the control group and the cell therapy group at the same time.(3) In IRI group and cell therapy group, the levels of miR-26a in the kidney tissues at 12 h and 24 h were significantly lower than those of the control group (P<0.05). In the cell therapy group, the level of miR-26a in the kidney tissues at 24 h (0.416±0.139) and 72 h (1.152±0.239)were significantly higher than that in the IRI group(0.244±0.067, 0.855±0.038, both P<0.05). A negative correlation between the levels of miR-26a and SCr level were found (r=-0.5, P<0.05). MMSCs have a certain repairing effect on renal IRI, accompanied by an increase in miR-26a expression.


Observing reduction of 4-nitrobenzenthiol on gold nanoparticles in situ using surface-enhanced Raman spectroscopy.
In this article, reduction of 4-nitrobenzenthiol (4-NBT) on Au nanoparticles (NPs) was characterized using surface-enhanced Raman scattering (SERS). Plasmon-driven chemical transformation from 4-NBT dimering into p,p'-dimercaptoazobenzene (DMAB) has been investigated on the surface of Au NPs. The laser power-dependent SERS spectra of 4-NBT on the surface of Au substrates were studied, and show that the laser power has an influence on the SERS signals of 4-NBT on Au NPs and production of DMAB by a plasmon-driven surface-catalyzed chemical reaction tends to be much easier under relative high laser power. Furthermore, we have used simple and efficient Au substrates (gold NPs with a size around 45 nm) exhibiting both catalytic properties and SERS activities to monitor the catalytic reaction of surface catalytic reaction process with borohydride solution. The experiments prove that the nitro-to-amino group conversion could be completed by borohydride at ambient conditions on Au substrates. Illuminated with high laser power, 4-NBT molecules and already formed DMAB molecules are further reduced into 4-aminobenzenthiol (4-ABT) by the addition of borohydride, While with low laser power 4-NBT molecules are transformed into 4-ABT with DMAB as the intermediate, which proves Au NPs are a mild and promising catalyst. Our studies might be helpful in extending the understanding of chemical reactions of 4-NBT and related research as well as providing a new strategy synthesis of azo dyes and anilines.


Differences in survival between black and white patients with diabetic end-stage renal disease.
To evaluate whether the longer survival of blacks with diabetic end-stage renal disease (ESRD) relative to whites is due to racial differences in type of diabetes, comorbidity at ESRD onset, and ESRD treatment modality and to examine whether survival differences between blacks and whites occur only in certain population subgroups. The Michigan Kidney Registry was used to ascertain all blacks and whites (n = 594) with diabetic ESRD in southeastern Michigan, with ESRD onset at age < 65 years during 1974-1983. Patients were followed through 1988. Medical records were abstracted for type of diabetes, comorbidity at ESRD onset, and other factors. Median survival among insulin-dependent diabetes mellitus patients was 27 months in blacks and 17 months in whites, and among non-insulin-dependent diabetes mellitus patients was 30 months in blacks and 16 months in whites. After adjustment for confounding factors by Cox proportional hazards analysis, the death rate was 45% lower in blacks than in whites on dialysis (relative death rate [RDR] = 0.55, 95% confidence interval [CI] = 0.44-0.69), but was similar in blacks and whites with a renal transplant (RDR = 0.99, 95% CI = 0.64-1.52). Compared with dialysis, transplantation was associated with lower mortality in both races (white, RDR = 0.50, 95% CI = 0.36-0.70; blacks, RDR = 0.89, 95% CI = 0.60-1.34), although the effect was not statistically significant in blacks. Racial differences in survival did not vary by type of diabetes or any additional factor. Survival after ESRD onset is longer in blacks than in whites treated with dialysis, even after adjusting for comorbidity and other factors that affect survival. Survival does not differ by race among transplant patients.


Studies of contact hypersensitivity induction in mice with optimal sensitizing doses of hapten.
To avoid unsuspected and unwanted consequences of excess hapten during epicutaneous sensitization, optimal sensitizing doses of dinitrofluorobenzene (DNFB) were determined for several ultraviolet B radiation (UVB)-resistant and UVB-susceptible strains of mice. Using these doses of hapten applied epicutaneously or injected intracutaneously into normal or UVB-exposed body wall skin, it was determined that four consecutive daily exposures to UVB prevented contact hypersensitivity induction in all mice when optimal sensitizing doses of DNFB were applied epicutaneously. By contrast, UVB-resistant, but not UVB-susceptible, mice developed contact hypersensitivity when an optimal sensitizing dose of DNFB was injected intracutaneously into UVB-irradiated skin. Moreover, whereas UVB-susceptible mice failed to develop contact hypersensitivity when an optimal sensitizing dose of DNFB was painted on skin exposed to a single dose of UVB, UVB-resistant mice did develop contact hypersensitivity under similar circumstances. Based on these results, it is concluded that 1) conventional doses of epicutaneously applied haptens induce contact hypersensitivity with the aid of antigen-presenting cells derived from both the epidermis and the dermis, 2) the phenomenon of UVB susceptibility is mediated by cells and molecules within the dermis when conventional doses of hapten and UVB radiation are employed, and 3) UVB susceptibility is mediated by cells and molecules within the epidermis when optimal sensitizing doses of hapten and a single exposure to UVB are employed.


PI3Kγ stimulates a high molecular weight form of myosin light chain kinase to promote myeloid cell adhesion and tumor inflammation.
Myeloid cells play key roles in cancer immune suppression and tumor progression. In response to tumor derived factors, circulating monocytes and granulocytes extravasate into the tumor parenchyma where they stimulate angiogenesis, immune suppression and tumor progression. Chemokines, cytokines and interleukins stimulate PI3Kγ-mediated Rap1 activation, leading to conformational changes in integrin α4β1 that promote myeloid cell extravasation and tumor inflammation Here we show that PI3Kγ activates a high molecular weight form of myosin light chain kinase, MLCK210, that promotes myosin-dependent Rap1 GTP loading, leading to integrin α4β1 activation. Genetic or pharmacological inhibition of MLCK210 suppresses integrin α4β1 activation, as well as tumor inflammation and progression. These results demonstrate a critical role for myeloid cell MLCK210 in tumor inflammation and serve as basis for the development of alternative approaches to develop immune oncology therapeutics.


Salicylic Acid-Based Organic Dyes Acting as the Photosensitizer for Solar Cells.
A D-π-A metal-free organic dye, featuring salicylic acid as a novel acceptor/anchoring unit, has been designed, synthesized and applied to dye-sensitized solar cell. The detailed photophysical, electrochemical, photovoltaic and sensitizing properties of the organic dye were investigated, in addition to the computational studies of the dye and dye-(TiO2)6 system. A solar cell device using this new organic dye as a sensitizer produced a solar to electric power conversion efficiency (PCE) of 3.49% (J(sc) = 6.69 mAcm-2, V(oc) = 0.74 V and ff = 0.70) under 100 mWcm(-2) simulated AM 1.5 G solar irradiation, demonstrating that the salicylic acid-based organic dye is a suitable alternative to currently used organometallic dyes.


A quasi-experimental study of the effects of the Erggi action model of musculoskeletal symptoms and VDU working conditions among university staff.
The aim of this study was to investigate musculoskeletal symptoms and working conditions of university workers with and without contact with an Erggi action model. A quasi-experimental and longitudinal field study design examined effects of the Erggi action model with 3 types of questionnaires filled by 1000 university workers. The statistical analyses used logistic regression. Subjects who had contact with the Erggi action model had a higher probability of weekly musculoskeletal symptoms impairing their work, perceived more possibilities to influence their musculoskeletal symptoms and had lower risk for sick leave compared to those without contact with the Erggi action model. The Erggi action model increases the probability of influencing workers' musculoskeletal symptoms, decreases the number of sick leave and increases awareness of musculoskeletal symptoms and working conditions.


Delta space plot analysis of cardiovascular coupling in vasovagal syncope during orthostatic challenge.
In this work, a graphical method to study cardiovascular coupling, called delta space plot analysis (DSPA), was introduced. The graphical representation is susceptible to be parameterized in shape and orientation. The usefulness of this technique was studied on cardiovascular data from patients with vasovagal syncope (VVS) and from controls. The study included 15 female patients diagnosed with VVS and 11 age-matched healthy female subjects. All subjects were enrolled in a head-up tilt (HUT) test, breathing normally, including 5 minutes of supine position (baseline) and 18 minutes of 70° orthostatic phase. The DSPA parameters were obtained at different times during the HUT test, i.e., at baseline, early (first 5 min) and late (10-15 min) orthostatic phases. In baseline there were no considerable differences between female controls and female patients. During the late orthostatic phase, parameters from DSPA showed highly significantly (p=0.000003) reduced cardiovascular coupling in patients. Findings indicated a loss of control on cardiovascular coupling in female patients susceptible to vasovagal syncope during orthostatic challenge. In addition, this study provided promising results for a new graphical method to investigate cardiovascular coupling.


Homeopathic products, not as innocent and safe as they seem? A case report.
Although homeopathic and other alternative products are very popular and are supposed to be safe and harmless they are not free of risks. We present the case of a 29-year-old woman who had to be treated for a state of extreme agitation after using speed, alcohol and homeopathic slimming droplets (LOCO X112). Toxicological analysis of these droplets revealed the presence of thyroid extract and diethylpropione, an amphetamine-like noradrenergic anorectic agent banned in Belgium. This case among other reports in the literature proves that homeopathic products are not as safe and harmless as they seem. Medical professionals as well as the public should be aware of this.


Anti-NMDA receptor encephalitis presenting with imaging findings and clinical features mimicking Rasmussen syndrome.
Antibody mediated anti-N-methyl-d-aspartate (NMDA) receptor encephalitis is a recently reported diagnosis of clinical importance. Recognition of the syndrome, especially in pediatric populations, is difficult and often undiagnosed and/or confused with neurological disorders with similar clinical features. We report a case of an 11 year old female with explosive-onset epilepsy and predominantly unilateral frontal lobe abnormalities on magnetic resonance imaging (MRI) and fluorodeoxyglucose positron emission tomography (FDG-PET) neuroimaging. A diagnosis of Rasmussen syndrome (RS) was considered. Cerebrospinal fluid analysis revealed strong positivity for NMDA receptor antibodies. Screening for occult ovarian teratoma with computed tomography (CT) and MRI initially did not demonstrate associated tumor. Treatment with steroids and plasma exchange improved her clinical course and subsequent MRI showed resolution. NMDA receptor encephalitis has variable neuroimaging manifestations, and can mimic other entities. We emphasize the clinical syndrome of NMDA receptor encephalitis and consideration of the diagnosis in evaluating a child with explosive-onset epilepsy, unilateral imaging abnormalities, and neurocognitive decline.


Age-related analysis of structural, biochemical and mechanical properties of the porcine mitral heart valve leaflets.
The aim of this study was to assess structural and biochemical differences in the extracellular matrix of the fetal and adult porcine mitral heart valves in relation to their mechanical characteristics. Using tensile tests it was demonstrated that the material properties of porcine mitral heart valves progressively change with age. The collagen content of the adult heart valve, as estimated by hydroxyproline assay, increases three times as compared with fetal heart valves. Transmission electron microscopy demonstrated that the diameter of collagen fibrils increased in adult heart valves compared with fetal heart valves. The level of collagen cross-linking is lower in the fetal heart valve than the adult heart valve. The reported age differences in the material properties of fetal and adult porcine heart valves were associated with increases in collagen content, the diameter of collagen fibrils and the level of collagen cross-linking. These data lay a foundation for systematic elucidation of the structural determinants of material properties of heart valves during embryonic and postnatal valvulogenesis. They are also essential to define the desirable level of tissue maturation in heart valve tissue engineering.


HER2 testing: a review of detection methodologies and their clinical performance.
The ERBB2 proto-oncogene, commonly referred to as the human epidermal growth factor receptor-2 (HER2) gene, encodes a 185 kd receptor tyrosine kinase. Overexpression of the protein leads to constitutive activity of the HER2 receptor and breast tumor development through enhanced cell proliferation, survival, motility and adhesion. Overabundance of the HER2 receptor, typically caused by amplification of the HER2 gene, is present in approximately 10-30% of invasive breast cancers, and is associated with an aggressive disease course and decreased disease-free and overall survival in node-positive patients. Tratuzumab, a humanized murine monoclonal antibody, offers a targeted treatment modality for tumors that over express the HER2 protein. Tratuzumab, shown to be effective and initially approved for treatment of metastatic breast cancer, has recently been shown to be very effective in the adjuvant setting. Thus, to offer prognostic information and to direct appropriate treatment it is important to provide accurate laboratory assessment of the status of HER2. This article provides an overview of the methods currently used to assess HER2.


Biosorption of Cr(VI) from water using biomass of Aeromonas hydrophila: central composite design for optimization of process variables.
The potential use of biomass of Aeromonas hydrophila for biosorption of chromium from aqueous solution was investigated. The variables (pH, initial Cr(VI) concentration, biomass dose, and temperature) affecting process were optimized by performing minimum number of experimental runs with the help of central composite design. The results predicted by design were found to be in good agreement (R2 = 99.1%) with those obtained by performing experiments. Multiple regression analysis shows that uptake decreases with increase in pH and biomass dose, whereas it increases with increase in temperature and concentration. The maximum removal of Cr(VI) predicted by contour and optimization plots was 184.943 mg/g at pH 1.5, initial Cr(VI) concentration 311.97 mg/L, temperature 60 degrees C, and biomass dose 1.0 g. The removal of Cr(VI) was governed by adsorption of Cr(VI) as well as its reduction into Cr(III), which further gets adsorbed. The sorption capacity of biomass was calculated from experimental data using Langmuir sorption model and was found to be 151.50 mg/g at 40 degrees C and pH 1.5, which is comparable to other biosorbents. In addition to this, Dubinin-Radushkevich model was applied, and it was found that nature of sorption was chemisorption.


Motivators and barriers to using patient experience reports for performance improvement.
Increasingly, patient experience surveys are available to provide performance feedback to physician groups. However, limited published literature addresses factors influencing use of these reports for performance improvement. To address this gap, we conducted semistructured interviews with leaders of Massachusetts physician groups. We asked about factors influencing groups' use of performance data and report characteristics. Motivating characteristics included having group leaders who emphasized a positive patient experience and prioritized patient retention; public reporting was not an important motivator for most groups. Full physician panels were perceived as a barrier to use of reports. Performance reports from a statewide public reporting collaborative were not sufficient for the majority of groups, with many seeking external reports. As policy makers create financial incentives to support performance improvement, assisting leaders to articulate the professional case for patient experience and enhancing the content and timing of performance reports may be important.


Downregulation of carboxylesterase contributes to cyflumetofen resistance in Tetranychus cinnabarinus (Boisduval).
Increased expression or point mutations of carboxyl/cholinesterases (CCEs) have been involved in many cases of insecticide and acaricide resistance. However, it has been only rarely documented that downregulation of CCE genes is associated with resistance, although many insecticides and acaricides need hydrolytic activation in vivo. Previously, expression analysis of a laboratory-selected cyflumetofen-resistant strain of Tetranychus cinnabarinus indicated that resistance was associated with increased expression of a CCE gene of TcCCE04, but also the downregulation of two CCE genes, TcCCE12 and TcCCE23. Synergism experiments revealed the importance of ester hydrolysis in cyflumetofen toxicity, because treatment with S,S,S-tributylphosphorotrithioate (DEF) caused strong inhibition of cyflumetofen hydrolysis, in both the susceptible and resistant strains. Moreover, silencing expression of TcCCE12 and TcCCE23 via RNAi further decreased the susceptibility of mites to cyflumetofen significantly, suggesting that downregulated CCE genes could be involved in cyflumetofen resistance. In addition, it was shown that recombinant TcCCE12 protein could hydrolyze cyflumetofen effectively. Decreased esterase activity via downregulation of specific CCE genes most likely contributes to cyflumetofen resistance by decreased activation of cyflumetofen to its active metabolite. Mixtures of cyflumetofen and esterase-inhibition acaricides (e.g. organophosphates or carbamates) should be avoided in field applications. © 2019 Society of Chemical Industry.


Prediction of location of a symptomatic early gestation based solely on clinical presentation.
To evaluate three strategies for diagnosis of women at risk for ectopic pregnancy based on information collected at initial presentation. Strength of association for risk factors, signs, and symptoms obtained at initial presentation of women with pain, bleeding, or both in a first-trimester pregnancy and a nondiagnostic ultrasound examination were calculated using a cohort of 2,026 women. Three models (logistic regression, a numeric scoring system, and a Classification and Regression Tree) were created to predict final outcome and tested on a second cohort of 1,634 women. Accuracy was assessed using 2x2 tables evaluating the decision of send home compared with do not send home (combination of monitor or intervene) and intervene compared with do not intervene (monitor or send home). Sensitivity, specificity, and predictive values were calculated. The ultimate diagnosis of women in the test population was 304 (18.6%) patients with an ectopic pregnancy, 834 (51.0%) with miscarriage, and 494 (30.2%) with an ongoing intrauterine pregnancy. A total of 95.9% of patients with ectopic pregnancy or miscarriage were correctly assigned to the strategy to monitor or intervene upon based on the scoring system, and 97.6% based on the Classification and Regression Tree. The specificity of the decision to send a patient home with a likely intrauterine pregnancy was greater than 95% for all three methods. The sensitivity of all strategies in the decision to intervene for an ectopic pregnancy was greater than 98%. A simplified scoring system based on five factors (age, ectopic history, bleeding, prior miscarriage, and human chorionic gonadotropin level) was as effective as a Classification and Regression Tree or logistic regression modes in predicting outcome of women at risk for ectopic pregnancy. Prediction of location of a symptomatic first-trimester pregnancy based on clinical symptoms and risk factors is possible, but must be used in conjunction with outpatient surveillance. II.


Antisite defects in layered multiferroic CuCr(0.9)In(0.1)P2S6.
The CuCr1-xInxP2S6 system represents a large family of metal chalcogenophosphates that are unique and promising candidates for 2D materials with functionalities such as ferroelectricity. In this work, we carried out detailed microstructural and chemical characterization of these compounds using aberration-corrected STEM, in order to understand the origin of these different ordering phenomena. Quantitative STEM-HAADF imaging and analysis identified the stacking order of an 8-layer thin flake, which leads to the identification of anti-site In(3+)(Cu(+)) doping. We believe that these findings will pave the way towards understanding the ferroic coupling phenomena in van der Waals lamellar compounds, as well as their potential applications in 2-D electronics.


Exploring Markers of Exhausted CD8 T Cells to Predict Response to Immune Checkpoint Inhibitor Therapy for Hepatocellular Carcinoma.
Reversal of CD8 T-cell exhaustion was considered a major antitumor mechanism of anti-programmed cell death-1 (PD-1)/ anti-programmed death ligand-1 (PD-L1)-based immune checkpoint inhibitor (ICI) therapy. The aim of this study was to identify markers of T-cell exhaustion that is best associated with ICI treatment efficacy for advanced hepatocellular carcinoma (HCC). Immune cell composition of archival tumor samples was analyzed by transcriptomic analysis and multiplex immunofluorescence staining. HCC patients with objective response after anti-PD-1/anti-PD-L1-based ICI therapy (n = 42) had higher expression of genes related to T-cell exhaustion. A 9-gene signature (LAG3, CD244, CCL5, CXCL9, CXCL13, MSR1, CSF3R, CYBB, and KLRK1) was defined, whose expression was higher in patients with response to ICI therapy, correlated with density of CD8+LAG3+ cells in tumor microenvironment, and independently predicted better progression-free and overall survival. This 9-gene signature had similar predictive values for patients who received single-agent or combination ICI therapy and was not associated with prognosis in HCC patients who received surgery, suggesting that it may outperform other T-cell signatures for predicting efficacy of ICI therapy for HCC. For HCC patients who underwent surgery for both the primary liver and metastatic lung tumors (n = 31), lung metastatic HCC was associated with a higher exhausted CD8 T-cell signature, consistent with prior observation that patients with lung metastatic HCC may have higher probability of response to ICI therapy. CD8 T-cell exhaustion in tumor microenvironment may predict better efficacy of ICI therapy for HCC.


Association of One-Step Nucleic Acid Amplification Detected Micrometastases with Tumour Biology and Adjuvant Chemotherapy.
One-step nucleic acid amplification (OSNA) is an intraoperative technique with a high sensitivity and specificity for sentinel node assessment. The aim of this study was to assess the impact of OSNA on micrometastases detection rates and use of adjuvant chemotherapy. A retrospective review of patients with sentinel node micrometastases over a five-year period was carried out and a comparison of micrometastases detection using OSNA and H&E techniques was made. Out of 1285 patients who underwent sentinel node (SLN) biopsy, 76 patients had micrometastases. Using H&E staining, 36 patients were detected with SLN micrometastases (9/year) in contrast to 40 patients in the OSNA year (40/year) (p < 0.0001), demonstrating a fourfold increase with the use of OSNA. In the OSNA group, there was also a proportional increase in Grade III, triple-negative, ER-negative, and HER-2-positive tumours being diagnosed with micrometastases. Also on interactive PREDICT tool, the number of patients with a predicted 10-year survival benefit of more than 3% with adjuvant chemotherapy increased from 52 to 70 percent. OSNA has resulted in an increased detection rate of micrometastases especially in patients with aggressive tumour biology. This increased the number of patients who had a predicted survival benefit from adjuvant chemotherapy.


Upper Respiratory Symptoms, Gut Health and Mucosal Immunity in Athletes.
Upper respiratory symptoms remain the most common illness in athletes. Upper respiratory symptoms during heavy training and competition may impair performance. Preventing illness is the primary reason for the use of supplements, such as probiotics and prebiotics, for maintaining or promoting gut health and immune function. While exercise-induced perturbations in the immune system may increase susceptibility to illness and infection, growing evidence indicates that upper respiratory symptoms are related to a breakdown in the homeostatic regulation of the mucosal immune system of the airways. Balancing protection of the respiratory tract with normal physiological functioning requires dynamic orchestration between a wide array of immune parameters. The intestinal microbiota regulates extra-intestinal immunity via the common mucosal immune system and new evidence implicates the microbiota of the nose, mouth and respiratory tract in upper respiratory symptoms. Omics' approaches now facilitate comprehensive profiling at the molecular and proteomic levels to reveal new pathways and molecules of immune regulation. New targets may provide for personalised nutritional and training interventions to maintain athlete health.


Effect of Monomers of 3-Hydroxyhexanoate on Properties of Copolymers Poly(3-Hydroxybutyrate-co 3-Hydroxyhexanoate).
The properties of poly(3-hydroxybutyrate-co-3-hydroxyhexanoate) P(3HB-co-3HHx) copolymers with different ratios of monomers synthesized by the wild-type strain Cupriavidus necator B-10646 on sugars, and an industrial sample from Kaneka synthesized by the recombinant strain C. necator NSDG-ΔfadB1 on soybean oil, were studied in a comparative aspect and in relation to poly(3-hydroxybutyrate) P(3HB). The copolymer samples, regardless of the synthesis conditions or the ratio of monomers, had reduced values of crystallinity degree (50-60%) and weight average molecular weight (415-520 kDa), and increased values of polydispersity (2.8-4.3) compared to P(3HB) (70-76%, 720 kDa, and 2.2). The industrial sample had differences in its thermal behavior, including a lower glass transition temperature (-2.4 °C), two peaks in its crystallization and melting regions, a lower melting point (Tmelt) (112/141 °C), and a more pronounced gap between Tmelt and the temperature of thermal degradation (Tdegr). The process, shape, and size of the spherulites formed during the isothermal crystallization of P(3HB) and P(3HB-co-3HHx) were generally similar, but differed in the maximum growth rate of the spherulites during exothermic crystallization, which was 3.5-3.7 μm/min for P(3HB), and 0.06-1.25 for the P(3HB-co-3HHx) samples. The results from studying the thermal properties and the crystallization mechanism of P(3HB-co-3HHx) copolymers are important for improving the technologies for processing polymer products from melts.


Using Metagenomics to Connect Microbial Community Biodiversity and Functions.
Microbes constitute about a third of the Earth's biomass and are composed by an enormous genetic diversity. In a majority of environments the microbial communities play crucial roles for the ecosystem functioning, where a drastic biodiversity alteration or loss could lead to negative effects on the environment and sustainability. A central goal in microbiome studies is to elucidate the relation between microbial diversity to functions. A better understanding of the relation diversity-function would increase the ability to manipulate that diversity to improve plant and animal health and also setting conservation priorities. The recent advances in genomic methodologies in microbial ecology have provide means to assess highly complex communities in detail, making possible the link between diversity and the functions performed by the microbes. In this work we first explore some advances in bioinformatics tools to connect the microbial community biodiversity to their potential metabolism and after present some examples of how this information can be useful for a better understanding of the microbial role in the environment.


The potential of the capillary electrophoresis techniques for quality control of biopharmaceuticals-a review.
CE is considered as a powerful technique in biopharmaceutical industry, owing to its inherent advantages such as high resolution, efficient separation, and its flexibility to couple with high-sensitive detecting methods. Present review provides a summary of the applications of CE-based methods in the quality control of biopharmaceuticals according to the papers published between 1994 and July 2014. This article is divided into the sections based on different CE modes applied in the analysis of biopharmaceuticals and gives detailed information about the employed experimental conditions. At the end some overall conclusions and perspectives are given.


Intrapulmonary percussive ventilation improves lung function in cystic fibrosis patients chronically colonized with Pseudomonas aeruginosa: a pilot cross-over study.
High levels of shear stress can prevent and disrupt Pseudomonas aeruginosa biofilm formation in vitro. Intrapulmonary percussive ventilation (IPV) could be used to introduce shear stress into the lungs of cystic fibrosis (CF) patients to disrupt biofilms in vivo. We performed a first-of-its-kind pilot clinical study to evaluate short-term IPV therapy at medium (200 bursts per minute, bpm) and high frequency (400 bpm) as compared to autogenic drainage (AD) on lung function and the behavior of P. aeruginosa in the CF lung in four patients who are chronically colonized by P. aeruginosa. A significant difference between the three treatment groups was observed for both the forced expiratory volume in 1 s (FEV1) and the forced vital capacity (FVC) (p < 0.05). More specifically, IPV at high frequency significantly increased FEV1 and FVC compared to AD (p < 0.05) and IPV at medium frequency (p < 0.001). IPV at high frequency enhanced the expression levels of P. aeruginosa planktonic marker genes, which was less pronounced with IPV at medium frequency or AD. In conclusion, IPV at high frequency could potentially alter the behavior of P. aeruginosa in the CF lung and improve lung function. The trail was retrospectively registered at the ISRCTN registry on 6 June 2013, under trial registration number ISRCTN75391385.


Determination of antibodies against human growth hormone using a direct immunoassay format and different electrochemical methods.
A direct immunoassay format with human growth hormone (hGH) immobilized on a self assembled monolayer modified surface plasmon resonance (SPR) chip was chosen to detect specific antibodies (anti-hGH) using different electrochemical techniques. Atomic force microscopy imaging and SPR were used as control methods for the evaluation and confirmation of the antigen-antibody complex formation. The applicability and sensitivity of candidate electrochemical techniques to develop an accurate and sensitive electrochemical immunosensor were investigated. Four electrochemical methods for anti-hGH determination - pulse amperometry (PA), cyclic voltammetry (CV), square wave voltammetry (SWV) and differential pulse voltammetry (DPV), were compared. Higher sensitivity of the developed immunosensor was observed using PA and CV: analytical signal registered using the PA method was 2.50 times higher in comparison with CV, 16.3 times higher in comparison with SWV and 24.5 times higher in comparison with the DPV method. In the case of PA detection method, the limit of detection was lower (75 nM) than that of the CV method (108 nM).


First isolation of West Nile virus in Brazil.
Serological evidence of West Nile virus (WNV) infection has been reported in different regions of Brazil from equine and human hosts but the virus had never been isolated in the country. We sought to identify the viral etiology of equine encephalitis in Espírito Santo state. We performed viral culture in C6/36 cells, molecular detection of WNV genome, histopathology and immunohistochemistry from horse cerebral tissue. We also carried out sequencing, phylogenetic analysis and molecular clock. Histopathologic analysis from horse cerebral tissue showed injury related to encephalitis and WNV infection was confirmed by immunohistochemistry. The virus was detected by reverse transcription quantitative polymerase chain reaction (RT-qPCR) from brain tissue and subsequently isolated in C6/36 cells. WNV full-length genome was sequenced showing the isolated strain belongs to lineage 1a. The molecular clock indicated that Brazilian WNV strain share the same common ancestor that were circulating in US during 2002-2005. Here we report the first isolation of WNV in Brazil from a horse with neurologic disease, which was clustered into lineage 1a with others US WNV strains isolated in beginning of 2000's decade.


Synovial chondromatosis of the temporomandibular joint: a case report.
Synovial chondromatosis is a rare benign condition. It most commonly affects the large joints. Presentation in the temporomandibular joint is rare. Our case was an incidental radiological finding and not diagnosed immediately, highlighting the ease with which conditions such as this can be missed, particularly in asymptomatic patients. Only 45% of patients with synovial chondromatosis show radiographic changes. Findings as significant as ours are unusual. An increased professional awareness of the radiological signs of synovial chondromatosis would be beneficial to improve diagnosis and prognosis for patients.


Kinetics of thermal decomposition of 4-carboxyl-2,6-dinitrobenzenediazonium ion (CDNBD).
The kinetics of thermal decomposition of 4-carboxyl-2,6-dinitrobenzenediazonium ion (CDNBD), an arenediazonium ion newly developed as a derivatizing reagent for drug analysis, are described. The arenediazonium ion, in an optimized concentrated sulfuric acid/orthophosphoric acid medium, was incubated for various time intervals at 30 degrees, 45 degrees, 55 degrees , 65 degrees , 75 degrees, and 85 degrees C. The amount of ion left after each time interval was quantified selectively by colorimetric assay at 490 nm, using mefenamic acid as a model diazo-coupling component. The rate constants for the decomposition were determined graphically. An Arrhenius plot was used to delineate the dependence of the rate constant on temperature and to predict the half-life at 25 degrees C and lower temperatures. The diazonium ion decomposed by first-order kinetics. The rate constants of decomposition, which increased progressively with temperature, were 3.18 +/- 0.41 x 10(-5), 1.19 +/- 0.07 x 10(-4), 4.87 +/- 0.15 x 10(-4), 12.88 +/- 0.73 x 10(-4), and 21.32 +/- 2.74 x 10(-4) (s(-1)) with corresponding half-lives of 363, 97.06, 23.72, 8.97, and 5.42 min at 30 degrees, 45 degrees, 55 degrees, 65 degrees, and 75 degrees C, respectively. CDNBD is highly stable in concentrated acid medium, with half-life values of about 10 h, 10 days, and 7.3 months at 25 degrees, 0 degrees, and -20 degrees C, respectively. The reagent stability profile shows that it could be readily adapted for routine applications in instrumental chemical analysis.


Preferences and choices of a child concerning the environment in a pediatric dental operatory.
The aim of this cross-sectional descriptive study was to determine children's preferences in a dental clinic so as to reduce anxiety during dental procedures. In this study survey methodology was used. A questionnaire was designed to evaluate the child's preference in a dental hospital so as to remove anxiety during a dental procedure. This study was carried out on 50 children aged 6-10 years. The children were randomly selected based on their first dental visit in a private dental college. A large number of children preferred listening to rhymes and watching cartoons while undergoing dental treatment. They also preferred the walls painted with cartoons, the dental chair full of toys, a scented environment, and the presence of their parents during the treatment. The results of this study will help the dental team decide on the appropriate design of the pediatric dental operatory room in order to provide a comfortable dental environment which will reduce anxiety in children and improve the quality of health care.


A light microscopic study of the gastro-entero-pancreatic endocrine cells of the mink (Mustela vison).
Endocrine cells in the stomach, intestine and pancreas of the mink were investigated, using silver impregnation and immunohistochemical methods, and the following results were obtained. The stomach of the mink possesses a well-developed acid-secreting region which occupies about 70% of the gastric mucosa. Half of Brunner's glands whose excretory duct empties in the most proximal duodenum are located in the duodenal submucosa with the remainder in the pyloric submucosa. The area covered by the glands is 7.5 mm long in rostrocaudal direction. Endocrine cells are numerous in Brunner's glands, in the pyloric gland region and in the duodenum, while they are few in the colorectum. Somatostatin-immunoreactive cells are distributed throughout the whole GEP system, while gastrin-immunoreactive cells are located mainly in the pyloric gland region. Secretin-, motilin- and neurotensin-immunoreactive cells are found in the duodenum, jejunoileum and lower jejunoileum, respectively. Glucagon-immunoreactive cells are located mainly in the pancreatic islet and are distributed scarcely in the fundic gland region. A few glucagon-immunoreactive cells are also found in the middle portion of the jejunoileum. In addition to the somatostatin-immunoreactive cells, argentaffin, glucagon- and glicentin-immunoreactive cells in the fundic gland region and argentaffin and gastrin-immunoreactive cells in the pyloric gland region extend cytoplasmic processes along the basement membrane. This suggests a paracrine secretion of these cell types. A few open type cells which are stained with Hellerström-Hellman's or Sevier-Munger's method or are reactive to the somatostatin antiserum are found in the fundic gland region. A possible relation between the present observation of the endocrine cells and the eating habits of the mink is discussed.


Spontaneous carotid dissection.
Carotid dissection is a rare occurrence but it is the main cause of stroke in individuals aged less than 45 years, and can be the etiology in up to 25% of strokes in young adults. We report a case with classic image of ying yang on vascular ultrasound, which was treated according to the best available medical evidence, yielding a favorable outcome.


GENETICS OF BRASSICA RAPA. 3. COSTS OF DISEASE RESISTANCE TO THREE FUNGAL PATHOGENS.
Genetic costs of resistance to pathogens may be an important factor maintaining heritable variation for resistance in natural populations. Pleiotropic fitness trade-offs occur when genetic resistance causes reduction in other components of fitness. Although costs of resistance have an important influence on plant-pathogen interactions, few previous studies have detected pleiotropic costs of resistance in the absence of confounding effects of linkage disequilibrium. To avoid this potential problem, we performed artificial selection experiments on resistance to two fungal pathogens, Leptosphaeria maculans, and Peronospora parasitica, and compared growth rates of resistant and susceptible genotypes of Brassica rapa in the absence of pathogens. Leptosphaeria resistance had no effect on growth rate, indicating cost-free defense. In contrast, Peronospora-resistant genotypes grow 6% slower than Peronospora-susceptible genotypes in pathogen-free environments, indicating a significant genetic fitness cost to Peronospora resistance. Such genetic trade-offs could maintain genetic variation in the wild. Another factor that might explain heritable variation for resistance is ecological trade-offs, in which genetic resistance to one species causes susceptibility to another. Such ecological trade-offs do not exist for the pathogens studied in this system.


Pancreatic ectasia in uremic macaques.
Pancreatic ectasia (PE) is a common incidental finding in people dying from uremia. It has been described as dilatation of acini, inspissation of secretions, and proliferation of ductal cells. PE occurred in 17 macaques, 11 of which were known to have been uremic. The lesion was studied by light and electronmicroscopy and histochemistry and by construction of a three-dimensional model of a dilated acinar ductal system from serial semithick Epon sections. Atrophic acinar cells interspersed with clumps of centroacinar cells lined all portions of the system. There was no evidence of ductular proliferation. Fibrillar material was present in the dilated acinar lumens and associated with epithelial cells and leukocytes, but no blockage of the system was demonstrated. The lesion is similar to those induced by a variety of experimental procedures and to the pancreatic lesions of cystic fibrosis.


Anti-angiogenic therapy increases intratumoral adenovirus distribution by inducing collagen degradation.
Conditionally replicating adenoviruses (CRAd) are a promising class of gene therapy agents that can overcome already known glioblastoma (GBM) resistance mechanisms but have limited distribution upon direct intratumoral (i.t.) injection. Collagen bundles in the extracellular matrix (ECM) have an important role in inhibiting virus distribution. In fact, ECM pre-treatment with collagenases improves virus distributions to tumor cells. Matrix metalloproteinases (MMPs) are an endogenous class of collagenases secreted by tumor cells whose function can be altered by different drugs including anti-angiogenic agents, such as bevacizumab. In this study we hypothesized that upregulation of MMP activity during anti-angiogenic therapy can improve CRAd-S-pk7 distribution in GBM. We find that MMP-2 activity in human U251 GBM xenografts increases (*P=0.03) and collagen IV content decreases (*P=0.01) during vascular endothelial growth factor (VEGF-A) antibody neutralization. After proving that collagen IV inhibits CRAd-S-pk7 distribution in U251 xenografts (Spearman rho=-0.38; **P=0.003), we show that VEGF-blocking antibody treatment followed by CRAd-S-pk7 i.t. injection reduces U251 tumor growth more than each individual agent alone (***P<0.0001). Our data propose a novel approach to improve virus distribution in tumors by relying on the early effects of anti-angiogenic therapy.


Light-harvesting complex II protein CP29 binds to photosystem I of Chlamydomonas reinhardtii under State 2 conditions.
The State 1 to State 2 transition in the photosynthetic membranes of plants and green algae involves the functional coupling of phosphorylated light-harvesting complexes of photosystem II (LHCII) to photosystem I (PSI). We present evidence suggesting that in Chlamydomonas reinhardtii this coupling may be aided by a hyper-phosphorylated form of the LHCII-like CP29 protein (Lhcbm4). MS analysis of CP29 showed that Thr6, Thr16 and Thr32, and Ser102 are phosphorylated in State 2, whereas in State 1-exposed cells only phosphorylation of Thr6 and Thr32 could be detected. The LHCI-PSI supercomplex isolated from the alga in State 2 was found to contain strongly associated CP29 in phosphorylated form. Electron microscopy suggests that the binding site for this highly phosphorylated CP29 is close to the PsaH protein. It is therefore postulated that redox-dependent multiple phosphorylation of CP29 in green algae is an integral part of the State transition process in which the structural changes of CP29, induced by reversible phosphorylation, determine the affinity of LHCII for either of the two photosystems.


Which is the best IVF/ICSI protocol to be used in poor responders receiving growth hormone as an adjuvant treatment? A prospective randomized trial.
This open label randomized study aims to define the best protocol to be used with growth hormone in poor responders, with comparison performed to delineate which protocol offers the best cycle outcomes. Two-hundred eighty-seven poor responders were included. The patients were randomly allocated into four groups receiving growth hormone (GH) as an adjuvant therapy added to either long or short agonist protocol, miniflare or antagonist protocols. The short/GH gave significantly lower mean number of oocytes when compared with the long/GH, antagonist/GH and miniflare/GH (4 ± 1.69 versus 5.06 ± 1.83, 4.95 + / = 1.90 and4.98 ± 2.51, respectively p = 0.005). Considering the number of fertilized oocytes, the long/GH showed significantly higher levels than short/GH and antagonist/GH (3.73 ± 1.47 versus 3.02 ± 1.52 and 2.89 ± 1.14, respectively). The main drawback is that it required significantly higher HMG dose and longer duration of stimulation. The long/GH was superior when compared with the three protocols regarding the number of oocytes retrieved and fertilized. But, when considering the clinical pregnancy rates, there was a difference in favor of the long/GH but not reaching a statistically significant value (ClinicalTrials.gov Identifier: NCT01897324).


[A Practical Approach to the Management of Patients with Gastrointestinal Cancer during the Novel Coronavirus Disease 2019(COVID-19)Pandemic-What Can Medical Oncologists Do?]
The SARS-CoV-2 was first identified in December 2019 in Wuhan, China. Since then, the ongoing COVID-19 pandemic has drastically changed the healthcare system, including cancer treatments worldwide. Since March 2020 in Japan, cancer patients faced a crisis; they suffered from delays or restrictions in cancer treatment during the initial outbreak. At present, we can perform cancer treatment as usual. Most of the treatments depend on continuous infection control by cancer patients and their families. However, the need to recognize cancer treatment management during the COVID-19 pandemic is crucial. Cancer treatment practice, purpose, risk factors, and the evidence during clinical trials should be comprehensively evaluated and adapted for each patient. Moreover, there is a need to discuss care planning between healthcare professionals, patients, and their families in advance. The COVID-19 vaccine could be essential for cancer patients. In this article, we review cancer treatment points for implementing whole-person care, including advanced care planning for patients with gastrointestinal malignancies, during the COVID-19 pandemic.


A cluster of mutations within a short triplet repeat in the C1 inhibitor gene.
Mutations in the C1 inhibitor gene that result in low functional levels of C1 inhibitor protein cause hereditary angioneurotic edema. This disease is characterized by episodic edema leading to considerable morbidity and death. Among 60 unreported kindred with the disease, four patients were discovered to have mutations clustered within a 12-bp segment of exon 5 from nucleotide 8449 to nucleotide 8460. This short segment of DNA contains three direct repeats of the triplet CAA and is immediately preceded by a similar adenosine-rich sequence (CAAGAACAC). These triplet repeats make this region susceptible to mutation by a slipped mispairing mechanism. There are two other short triplet repeat elements in the coding region for this gene, but they have not become mutated in any kindred examined. This suggests that the apparent enhanced mutation rate in this region of exon 5 may be influenced by DNA structural characteristics.


Gene transfer device utilizing micron-spiked electrodes produced by the self-organization phenomenon of Fe-alloy.
In the diffusional phase transformation of two-phase alloys, the new phase precipitates form the matrix phase at specific temperatures, followed by the formation of a mixed microstructure comprising the precipitate and the matrix. It has been found that by specific chemical-etching treatment, the precipitate in Fe-25Cr-6Ni alloy projects substantially and clusters at the surface. The configuration of the precipitate has an extremely high aspect ratio: it is several microns in width and several tens of microns in length (known as micron-spiked). This study targets the development of a gene transfer device with a micro-spike produced based on the self-organization phenomenon of the Fe-25Cr-6Ni alloy. With this spike-projected device, we tried to efficiently transfer plasmid DNA into adherent cells by electric pulse-triggered gene transfer using a plasmid-loaded electrode (electroporation-based reverse transfection). The spiked structure was applied to a substrate of the device to allow efficient gene transfer into adherent cells, although the general substrate was flat and had a smooth surface. The results suggest that this unique spike-projected device has potential applications in gene transfer devices for the analysis of the human genome in the post-genome period.


Comparative potencies of 3,4-methylenedioxymethamphetamine (MDMA) analogues as inhibitors of [3H]noradrenaline and [3H]5-HT transport in mammalian cell lines.
Illegal 'ecstasy' tablets frequently contain 3,4-methylenedioxymethamphetamine (MDMA)-like compounds of unknown pharmacological activity. Since monoamine transporters are one of the primary targets of MDMA action in the brain, a number of MDMA analogues have been tested for their ability to inhibit [3H]noradrenaline uptake into rat PC12 cells expressing the noradrenaline transporter (NET) and [3H]5-HT uptake into HEK293 cells stably transfected with the 5-HT transporter (SERT). Concentration-response curves for the following compounds at both NET and SERT were determined under saturating substrate conditions: 4-hydroxy-3-methoxyamphetamine (HMA), 4-hydroxy-3-methoxymethamphetamine (HMMA), 3,4-methylenedioxy-N-hydroxyamphetamine (MDOH), 2,5-dimethoxy-4-bromophenylethylamine (2CB), 3,4-dimethoxymethamphetamine (DMMA), 3,4-methylenedioxyphenyl-2-butanamine (BDB), 3,4-methylenedioxyphenyl-N-methyl-2-butanamine (MBDB) and 2,3-methylenedioxymethamphetamine (2,3-MDMA). 2,3-MDMA was significantly less potent than MDMA at SERT, but equipotent with MDMA at NET. 2CB and BDB were both significantly less potent than MDMA at NET, but equipotent with MDMA at SERT. MBDB, DMMA, MDOH and the MDMA metabolites HMA and HMMA, were all significantly less potent than MDMA at both NET and SERT. This study provides an important insight into the structural requirements of MDMA analogue affinity at both NET and SERT. It is anticipated that these results will facilitate understanding of the likely pharmacological actions of structural analogues of MDMA.


Rapid reversal of left ventricular enlargement after percutaneous closure of pulmonary sequestration in a newborn with prune belly syndrome.
In this article, we describe a newborn with Prune belly syndrome who presented with left ventricular dilation due to an extensive intralobar sequestration of the left lung. Pulmonary sequestration was combined with congenital cystic adenomatoid malformation and also had coarctation of the aorta. Percutaneous closure of the anomalous aberrant artery feeding the sequestrated lung and balloon angioplasty for coarctation resulted in prompt regression of the left ventricular enlargement in the catheterization lab.


Transmission through a scalar wave three-dimensional electromagnetic metamaterial and the implication for polarization control.
An interweaving-conductor metamaterial (ICM) is a metamaterial composed of multiple, interlocking, conducting networks. It exhibits unusual optical properties in the low-frequency linear-dispersion regime. In particular, two-network ICM supports only one, non-dispersive mode in the low frequency range, and is best described as an effective medium supporting a scalar wave in full three dimensions. We explore the light transmission properties of such a metamaterial, and the implications of a scalar wave medium for polarization control. Polarizers and polarization rotators with subwavelength sizes are numerically demonstrated.


[A rare cause of negative explora tory laparotomy in severe blunt trauma].
We report the case of a young man involved in a high velocity road traffic accident. He presented with multiple injuries and a shock. This shock was suspected to be caused by an intra-abdominal bleeding and an exploratory laparotomy was performed. The procedure did not identify any intra-abdominal bleeding and the source of bleeding was found lately: an intramuscular active bleeding in the dorsal and lumbar muscular compartments. This case was discussed in our local mortality and morbidity meeting.