High and specific diversity of protists in the deep-sea basins dominated by diplonemids, kinetoplastids, ciliates and foraminiferans.
Heterotrophic protists (unicellular eukaryotes) form a major link from bacteria and algae to higher trophic levels in the sunlit ocean. Their role on the deep seafloor, however, is only fragmentarily understood, despite their potential key function for global carbon cycling. Using the approach of combined DNA metabarcoding and cultivation-based surveys of 11 deep-sea regions, we show that protist communities, mostly overlooked in current deep-sea foodweb models, are highly specific, locally diverse and have little overlap to pelagic communities. Besides traditionally considered foraminiferans, tiny protists including diplonemids, kinetoplastids and ciliates were genetically highly diverse considerably exceeding the diversity of metazoans. Deep-sea protists, including many parasitic species, represent thus one of the most diverse biodiversity compartments of the Earth system, forming an essential link to metazoans.


GPNMB mitigates Alzheimer's disease and enhances autophagy via suppressing the mTOR signal.
Alzheimer's disease (AD) is a common neurodegenerative disease which is characterized by amyloid beta (Aβ) accumulation. We found that glycoprotein NMB (GPNMB) was highly expressed in the brain of APP/PS1 mice, a mouse model of AD. However, its role in AD remains unclear. In this study, we aimed to explore the function of GPNMB in AD. The expression of GPNMB in the brain was detected by immunofluorescence and western blot. In addition, the role of GPNMB in AD was explored through gain-of-function. Autophagy, which is beneficial to Aβ clearance, was evaluated by transmission electron microscope and immunofluorescence with beclin-1. Furthermore, 3-MA, an autophagy inhibitor, was employed to evidence whether GPNMB reduced the level of Aβ through autophagy. We found that over-expression of GPNMB improved AD-like behaviors in APP/PS1 mice and reduced Aβ deposition. Further study showed that GPNMB enhanced autophagy, reduced microglial cells and inhibited the activation of the mTOR signal. Additionally, treatment with 3-MA abolished the beneficial effect of GPNMB on Aβ clearance. This study revealed that the high level of GPNMB in AD brain may help Aβ clearance and improve AD-like behaviors through enhancing autophagy via suppressing the mTOR signal. This beneficial role of GPNMB provides us novel strategies for the prevention and treatment of AD.


Size distribution, directional source contributions and pollution status of PM from Chengdu, China during a long-term sampling campaign.
Long-term and synchronous monitoring of PM10 and PM2.5 was conducted in Chengdu in China from 2007 to 2013. The levels, variations, compositions and size distributions were investigated. The sources were quantified by two-way and three-way receptor models (PMF2, ME2-2way and ME2-3way). Consistent results were found: the primary source categories contributed 63.4% (PMF2), 64.8% (ME2-2way) and 66.8% (ME2-3way) to PM10, and contributed 60.9% (PMF2), 65.5% (ME2-2way) and 61.0% (ME2-3way) to PM2.5. Secondary sources contributed 31.8% (PMF2), 32.9% (ME2-2way) and 31.7% (ME2-3way) to PM10, and 35.0% (PMF2), 33.8% (ME2-2way) and 36.0% (ME2-3way) to PM2.5. The size distribution of source categories was estimated better by the ME2-3way method. The three-way model can simultaneously consider chemical species, temporal variability and PM sizes, while a two-way model independently computes datasets of different sizes. A method called source directional apportionment (SDA) was employed to quantify the contributions from various directions for each source category. Crustal dust from east-north-east (ENE) contributed the highest to both PM10 (12.7%) and PM2.5 (9.7%) in Chengdu, followed by the crustal dust from south-east (SE) for PM10 (9.8%) and secondary nitrate & secondary organic carbon from ENE for PM2.5 (9.6%). Source contributions from different directions are associated with meteorological conditions, source locations and emission patterns during the sampling period. These findings and methods provide useful tools to better understand PM pollution status and to develop effective pollution control strategies.


Choroidal vascularity index: an enhanced depth optical coherence tomography-based parameter to determine vascular status in patients with proliferative and non-proliferative macular telangiectasia.
The pathogenesis of subretinal neovascularization (SRNV) due to macular telengiectasia (MacTel 2) has not fully elucidated. This optical coherence tomography (OCT)-based method can provide better understanding of the pathogenesis of SRNV due to MacTel 2. To evaluate the choroidal vascular index (CVI) through optical coherence tomography (OCT) on eyes with proliferative macular telangiectasia type 2 (MacTel 2) or non-proliferative MacTel 2, and in healthy individuals. Macular enhanced depth imaging OCT scans on 42 eyes of 21 patients with non-proliferative MacTel 2, on 32 eyes of 20 patients with proliferative MacTel 2, and on 38 eyes of 32 control patients were analyzed by adjusting for age-gender-axial length. Proliferative MacTel 2 was diagnosed when subretinal neovascularization (SRNV) was simultaneously observed in the non-proliferative phase. Binarization methods of ImageJ software were used to analyze images, and total choroid area (TCA), luminal area (LA) and stromal area (SA) were obtained. CVI was characterized as the ratio of LA to TCA. The mean TCA and SA were significantly higher in group 1 and group 2 when compared with group 3 (3.36 ± 0.29 mm2 vs. 3.27 ± 0.76 mm2 vs. 2.49 ± 0.24 mm2, p < 0.001; 1.15 ± 0.31 mm2 vs. 1.10 ± 0.69 mm2 vs. 0.35 ± 0.23 mm2, respectively; p < 0.001). Although LA was relatively higher in group 1 and group 2 than group 3, no statistically significant difference was observed (2.22 ± 0.14 mm2 vs. 2.17 ± 0.15 mm2 vs. 2.13 ± 0.21 mm2) (p = 0.088). CVI was significantly lower in group 1 than other groups (0.65 ± 0.01 vs 0.67 ± 0.02 vs 0.68 ± 0.02) (p < 0.001). As an OCT screening method, CVI may be used to assess the vascular status of the choroid on the eyes which are naive for or were exposed to SRNV secondary to MacTel 2, and to elucidate the pathogenesis of this disease.


Cranial facet joint violations by percutaneously placed pedicle screws adjacent to a minimally invasive lumbar spinal fusion.
Protecting cranial facet joint is a modifiable risk factor that may decrease the incidence of adjacent segment disease after lumbar spinal fusion. Percutaneously instrumented screws may more frequently violate cranial facet joints because of the potential limitation of screw entry site selection. To our knowledge, however, there is no study that has evaluated the cranial facet joint violations adjacent to minimally invasive lumbar fusion related to percutaneously placed pedicle screws. We investigated the incidence and relating factors of cranial facet joint violations by percutaneous pedicle screws. A retrospective study of prospectively collecting data. The sample comprises 184 pedicle screws percutaneously placed at the cranial fusion segments in 92 patients who underwent minimally invasive lumbar spinal fusion. The facet joint violations adjacent to a cranial fusion segment were examined on the postoperative computed tomography (CT) scans. Two independent observers retrospectively examined all the postoperative CT images. A facet joint was considered violated if any of the following situations were encountered: pedicle screw clearly within the facet joint; pedicle screw head clearly within the facet joint; and pedicle screw and/or screw head within 1 mm from or abutting the facet joint, without clear joint involvement. The incidence of the violations was 50% (46/92) of all patients and 31.5% (58/184) of all screws, which were significantly higher than the previously reported rates with the traditional open procedure (50% vs. 23.5% of all patients, p<.001; 31.5% vs. 15.2% of all screws, p<.001). The violations occurred approximately 3.3 times more frequently at the most cranial pedicle screws of L5 pedicle than at the other pedicles (70.8% vs. 42.6%, odds ratio [OR]=3.3, p=.021). Logistic regression analysis revealed a significant trend toward reducing the incidence of the violations as increasing the year of surgery (OR=0.7, p=.008). The incidence showed no significant relationships with patients' age, gender, body mass index, preoperative diagnosis, the number of fused segments, or the side of screw placement. Our data raise a concern about the higher incidence of cranial facet joint violations by percutaneously placed pedicle screws than that previously reported rates by traditionally instrumented screws. Furthermore, more care should be taken to avoid cranial facet joint violations when the surgeon is a novice to percutaneous pedicle screw placement and/or minimally invasive fusion surgery is considered at the L5-S1 segment.


Discovery of 3-aryl substituted benzoxaboroles as broad-spectrum inhibitors of serine- and metallo-β-lactamases.
The production of β-lactamases represents the main cause of resistance to clinically important β-lactam antibiotics. Boron containing compounds have been demonstrated as promising broad-spectrum β-lactamase inhibitors to combat β-lactam resistance. Here we report a series of 3-aryl substituted benzoxaborole derivatives, which manifested broad-spectrum inhibition to representative serine-β-lactamases (SBLs) and metallo-β-lactamases (MBLs). The most potent inhibitor 9f displayed an IC50 value of 86 nM to KPC-2 SBL and micromolar inhibitory activity towards other tested enzymes. Cell-based assays further revealed that 9f was able to significantly reduce the MICs of meropenem in clinically isolated KPC-2-producing bacterial strains and it showed no apparent toxicity in HEK293T cells.


Affinity maturation of recombinant antibodies using E. coli mutator cells.
Phage libraries can display repertoires of antibodies which are greater in number than the mammalian immune response. However, the selected antibodies often have low binding affinity to their target antigen or hapten (KD below 10(-6) M), which is characteristic of the primary immune repertoire. There is a need for procedures to mimic somatic hypermutation through antigen driven affinity maturation, thereby increasing the affinity of selected immunoglobulins. To investigate the effectiveness of mutation and affinity selection of recombinant antibody genes with mutator E. coli cells, incorporating phage-display strategies. Unique human scFvs were selected from a naive Fd-phage library. These genes were mutated by propagation in mutD5 mutator E. coli cells (mutD5-FIT) which were competent for Fd (M13) based phagemid transfections and generated point mutations (transversions and transitions) in the scFv genes. Individual phage-displayed scFvs were affinity selected from the mutation library and were assayed as soluble scFvs by ELISA and BIAcore for binding to antigen. The in vivo mutation of phage-displayed scFvs in E. coli mutD5-FIT, combined with affinity selection against antigen, produced scFv molecules with improved binding activity. The point mutations which resulted in single amino acid substitutions frequently produced ten fold increases in apparent binding affinity. Structural comparisons revealed that these point mutations were in framework regions (adjacent to the CDRs) and within the CDRs. In one case the apparent affinity of an anti-glycophorin scFv after mutation in the VL framework region close to CDR3 increased by 10(3). However, this increase in apparent affinity was accompanied by an increased propensity to dimerise and form aggregates. A strategy for the rapid affinity maturation of scFv and Fab antibody fragments has been developed which utilises mutator strains of E. coli and incorporates phage display of antibody repertoires (libraries).


The Longevity-Frailty Hypothesis: Evidence from COVID-19 Death Rates in Europe.
By the end of spring (31 May), the COVID-19 death rate was remarkably unevenly distributed across the countries in Europe. While the risk of COVID-19 mortality is known to increase with age, age-specific COVID-19 death rates across Europe were similarly unevenly distributed. To explain these mortality distributions, we present a simple model where more favorable survival environments promote longevity and the accumulation of health frailty among the elderly while less favorable survival environments induce a mortality selection process that results in lower health frailty. Because the age-related conditions of frailty render the elderly less resistant to SARS-CoV-2, pre-existing survival environments may be non-obviously positively related to the COVID-19 death rate. To quantify the survival environment parameter of our model, we leveraged historic cohort- and period-based age-specific probabilities of death and life expectancies at age 65 across Europe. All variables are significantly correlated with indicators of frailty like elderly dependence on others for personal and household care for a subset of European countries. With respect to COVID-19 death rates, we find significant positive relationships between our survival indicators and COVID-19 death rates across Europe, a result that is robust to statistical control for the capacity of a healthcare system to treat and survive infected persons, the timing and stringency of non-pharmaceutical interventions, population density, age structure, case rates and the volume of inbound international travelers, among other factors. To address possible concerns over reporting heterogeneity across countries, we show that results are robust to the substitution of our response variable for a measure of cumulative excess mortality. Also consistent with the intuition of our model, we also show a strong negative association between age-specific COVID-19 death rates and pre-existing all-cause age-specific mortality rates for a subset of European countries. Overall, results support the notion that variation in pre-existing frailty, resulting from heterogeneous survival environments, partially accounts for striking differences in COVID-19 death during the first wave of the pandemic.


Shoulder demands in manual wheelchair users across a spectrum of activities.
Investigate shoulder joint kinetics over a range of daily activity and mobility tasks associated with manual wheelchair propulsion to characterize demands placed on the shoulder during the daily activity of manual wheelchair users. Case series. Twelve individuals who were experienced manual wheelchair users. Upper extremity kinematics and handrim wheelchair kinetics were measured over level propulsion, ramp propulsion, start and stop over level terrain, and a weight relief maneuver. Shoulder intersegmental forces and moments were calculated from inverse dynamics for all conditions. Weight relief resulted in significantly higher forces and ramp propulsion resulted in significantly higher moments than the other conditions. Surprisingly, the start condition resulted in large intersegmental moments about the shoulder equivalent with that of the ramp propulsion, while the demand imparted by the stop condition was shown to be equivalent to level propulsion across all forces and moments. This study provides characterization of daily living and mobility activities associated with manual wheelchair propulsion not previously reported and identifies activities that result in higher shoulder kinetics when compared to standard level propulsion.


Noninvasive in vivo spectroscopic nanorod-contrast photoacoustic mapping of sentinel lymph nodes.
Sentinel lymph node (SLN) biopsy has increasingly become important in axillary staging of breast cancer patients since SLN biopsy alleviates the postoperative complications of previously practiced axillary lymph node dissections. Nevertheless, the procedures of SLN biopsy using blue dye and radioactive substance are still intraoperative, and the latter methods are also ionizing. In this pilot study, we have proposed noninvasive in vivo spectroscopic photoacoustic (PA) SLN mapping using gold nanorods as lymph node tracers in a rat model. Gold nanorods have biocompatibility, high optical absorption, and easily tuned surface plasmon resonance peak wavelength.


Association between lumbosacral transitional vertebrae and spinal pathologies based on T2 whole-spine sagittal magnetic resonance imaging.
To assess the association between 4, 5, or 6 lumbar spine vertebrae and the presence of lumbar spinal pathologies. We reviewed all MRI reports and images performed between August 1st, 2018 and July 31st, 2019. Lumbar spine pathologies such as disc herniation, lytic spondylolisthesis, and spinal stenosis were recorded. The reviewer studied the T2 sagittal screening of the entire spine and counted down manually from C2 to T12 on the assumption that there are seven cervical and twelve dorsal vertebrae. We then recorded whether there were four, five, or six lumbar vertebrae. Our work incorporated a total of 1985 patients for whom T2-weighted entire spine sagittal MR images were obtainable. The study cohort's average age was 52.2 ± 15.9 years, comprising 944 males and 1041 females. One hundred and thirty-three patients (6.7%) had 4 lumbar-type vertebrae; 1799 (90.6%) had 5 lumbar-type vertebrae; and 53 (2.7%) had 6 lumbar-type vertebrae. There was a statistically significant difference between the rates of 6 lumbar-type vertebrae in males versus females (p < 0.05). There was a statistically significant difference with more spinal stenosis patients in the 6 lumbar-type vertebrae compared to the 4 or 5 lumbar-type vertebrae groups (p < 0.001). Our study shows that spinal stenosis is significantly more common in patients with 6 lumbar-type vertebrae.


Laparoscopic repair of a migrated adjustable gastric band connecting tube with colonic erosion.
Laparoscopic adjustable gastric bands are a popular and effective surgical option to treat morbid obesity. The overall complication rate is 10-20% and the most common complication is of 'slippage'. Although other complications such as gastric band migration and erosion have been reported, the phenomenon of a migrated gastric band connecting tube eroding into the colon (after port removal) is seldom reported in the literature. In this article we describe such a case of an incidentally found colonic erosion on colonoscopy and describe the subsequent laparoscopic repair, as well as a review of the literature.


Health Education about Lifestyle-Related Risk Factors in Gynecological and Obstetric Care: A Qualitative Study of Healthcare Providers' Views in Germany.
Lifestyle-related risk factors (LRRFs) during pregnancy and lactation are associated with a range of health problems. However, previous studies have shown a large knowledge gap among pregnant women regarding the effects of LRRFs. This study aimed to investigate the role of health education about LRRFs during pregnancy and lactation in gynecological and obstetric care from healthcare providers' (HCPs) point of view. To explore the views of healthcare providers, a qualitative study was performed. In 2019, 22 in-depth interviews were conducted with a purposive sample of 9 gynecologists and 13 midwives. Participants came from different inpatient and outpatient care settings and from rural, urban, and socially deprived areas in southern Germany. All the interviews were tape-recorded and transcribed verbatim. A combined inductive and deductive approach was applied for data analysis. Interviews with HCPs showed that they were aware of the possible impacts of LRRFs during pregnancy and lactation. They noted the importance of action, specifically among women with low socioeconomic status (SES), migrants, and women with a concerning medical history or other specific needs. However, the interviews showed that, at present, there is no standardized practice of educating patients on LRRFs in routine care. This was attributed to a lack of guidelines and time, unfavorable regulations, and undefined responsibilities. The priority of health education is lower in inpatient healthcare settings as compared to outpatient healthcare settings. HCPs apply a demand-driven healthcare approach, focusing on a woman's medical history, needs, and personal circumstances. HCPs voiced the importance of implementing pre-conception education across different healthcare settings, garnering support from other health organizations, and setting out clearly defined responsibilities among HCPs. This qualitative study explored HCPs' perspectives on health education about LRRFs during pregnancy and lactation. The results from this study emphasize the need for a central strategy for health education about LRRFs during pregnancy and lactation in gynecological and obstetric care.


Mutant PIK3CA licenses TRAIL and CD95L to induce non-apoptotic caspase-8-mediated ROCK activation.
Constitutively active PI3K catalytic subunit alpha (PIK3CA) interfered with apoptosis induction downstream of death receptor-signaling complex formation allowing robust caspase-8 activation without triggering the execution steps of apoptosis. In mutant PIK3CA-expressing cells, tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) and CD95L stimulated nuclear factor kappaB (NFkappaB) activation, invasion, and transition to an amoeboid-like morphology. NFkappaB activation and adoption of amoeboid shape were inhibited by caspase-8 knockdown or FLIP-S expression, but only the cell morphology alterations required caspase-8 activity. Furthermore, we identified caspase-8-mediated, caspase-3-independent cleavage of the protein kinase rho-associated, coiled-coil containing protein kinase 1 as a novel mechanism for acquiring amoeboid shape and enhanced invasiveness in response to TRAIL and CD95L. Taken together, we provide evidence that mutated PIK3CA converts the 'tumor surveillance' activity of cancer cell-expressed death receptors and caspase-8 toward tumor promotion.


The preparation and characterization of a cell-free system from Saccharomyces cerevisiae that translates natural messenger ribonucleic acid.
A cell-free protein-synthesizing system has been prepared from Saccharomyces cerevisiae by differential centrifugation of lysed spheroplasts. The preparation, a modified 100,000 x g supernatant fraction, contains ribosomes and monosomes, ribosomal subunits, translation factors, and aminoacyl-tRNA synthetases, but no polysomes. After removal of small amounts of remaining mRNA with micrococcal nuclease, protein synthesis is stringently dependent on the addition of mRNA, as well as amino acids and an energy-generating system. The 5'-cap analogue, 7-methylguanosine 5'-phosphate, inhibits translation of several natural mRNAs, but has no effect on chain elongation. Incubation of the polysome-free extract with natural mRNA leads to the formation of protein-synthesizing polysomes and eventually, to the release of protein; the molecular weight of the protein synthesized in the presence of BMV (brome mosaic virus) RNA is consistent with that of BMV coat protein.


Removal of humic substances from surface waters with recycled fluidized bed sand.
Recycled bed sand from a power plant's fluidized bed reactor was used to remove humic substances (HSs) from surface water samples. The performance of sand samples screened into different size fractions together with unscreened sand was evaluated in removing HSs by performing shaking and column experiments, and by monitoring the quality of the treated water samples in terms of pH, conductivity, chemical oxygen demand (COD), and colour. At the beginning of the column experiments, the used sand fractions removed HSs with over 80% efficiency. However, as the experiments proceeded, the removal efficiency rapidly decreased, reaching a steady state during which a column filled with small-particle-size screened sand removed 20-25% of the COD and colour at a 2.2 kg/h flow speed, and 25-35% of the COD and 30-35% of the colour at a slow 0.5 kg/h flow speed. With unscreened sand, the corresponding COD and colour removal efficiencies were 10-20% (COD) and 10-18% (colour) for fast column experiments, and 22-27% for COD and 25-30% for colour during slow column experiments. Elemental analysis revealed that recycled fluidized bed sand contained several cationic compounds known to form complexes with HSs. Especially calcium together with aluminium and iron are potential candidates for removing colour and COD from the water samples.HighlightsRecycled fluidized bed sand could be used as a low-cost adsorbent material for removing HSs from surface water samplesEspecially the COD and colour of the water samples could be reduced by the sand treatmentsFluidized bed sand contained several cationic compounds forming complexes with HSsNo significant amounts of heavy metals were leached during the sand treatments.


EPR characterisation of the triplet state in photosystem II reaction centers with singly reduced primary acceptor Q(A).
The triplet states of photosystem II core particles from spinach were studied using time-resolved cw EPR technique at different reduction states of the iron--quinone complex of the reaction center primary electron acceptor. With doubly reduced primary acceptor, the well-known photosystem II triplet state characterised by zero-field splitting parameters |D|=0.0286 cm(-1), |E|=0.0044 cm(-1) was detected. When the primary acceptor was singly reduced either chemically or photochemically, a triplet state of a different spectral shape was observed, bearing the same D and E values and characteristic spin polarization pattern arising from RC radical pair recombination. The latter triplet state was strongly temperature dependent disappearing at T=100 K, and had a much faster decay than the former one. Based on its properties, this triplet state was also ascribed to the photosystem II reaction center. A sequence of electron-transfer events in the reaction centers is proposed that explains the dependence of the triplet state properties on the reduction state of the iron--quinone primary acceptor complex.


One-shot optimization of multiple enzyme parameters: Tailoring glucose oxidase for pH and electron mediators.
Enzymes are biological catalysts with many industrial applications, but natural enzymes are usually unsuitable for industrial processes because they are not optimized for the process conditions. The properties of enzymes can be improved by directed evolution, which involves multiple rounds of mutagenesis and screening. By using mathematical models to predict the structure-activity relationship of an enzyme, and by defining the optimal combination of mutations in silico, we can significantly reduce the number of bench experiments needed, and hence the time and investment required to develop an optimized product. Here, we applied our innovative sequence-activity relationship methodology (innov'SAR) to improve glucose oxidase activity in the presence of different mediators across a range of pH values. Using this machine learning approach, a predictive model was developed and the optimal combination of mutations was determined, leading to a glucose oxidase mutant (P1) with greater specificity for the mediators ferrocene-methanol (12-fold) and nitrosoaniline (8-fold), compared to the wild-type enzyme, and better performance in three pH-adjusted buffers. The kcat /KM ratio of P1 increased by up to 121 folds compared to the wild type enzyme at pH 5.5 in the presence of ferrocene methanol.


Effects of anti-tumour necrosis factor-alpha therapy on the quality of life in Crohn's disease.
Infusion of anti-tumour necrosis factor-alpha appears to be highly effective in patients with Crohn's disease. To assess the effect of infliximab on the quality of life in patients with active or fistulizing disease, as measured by the inflammatory bowel disease questionnaire, and to examine the impact on its four dimensions. An observational study was conducted in 65 patients. An infusion of 5 mg/kg infliximab was given at week 0 in patients with active disease and at week 0, 2 and 6 in fistulizing disease. Changes from baseline in the total and dimensional inflammatory bowel disease questionnaire scores were calculated and compared between the patient groups. Potential predictors of change in the quality of life were identified. In the active disease group, at week 4, the mean total and dimensional inflammatory bowel disease questionnaire scores improved compared to baseline (P < 0.001). In the fistulizing group, at week 6, all scores changed from baseline (P < 0.05). Improvement in the total inflammatory bowel disease questionnaire score correlated well with the improvement of the Crohn's disease activity index. Systemic and social scores improved more than bowel and emotional scores. Inflammatory Crohn's disease and a young age at diagnosis were predictors for a better response to infliximab therapy. Infliximab therapy improves all dimensions of the quality of life in patients with Crohn's disease.


Reliability of the lateral angle of the internal auditory canal for sex determination of subadult skeletal remains.
When creating a basic biological profile, determining the sex of subadult skeletal remains is always problematic and several methods for sex determination have been proposed over time. The lateral angle of the internal auditory canal has been described as a good sex predictor in adults, and here we test its reliability for sex determination of subadults. The reliability of this method was assessed on a sample of 47 Portuguese known sex and age skeletons representing individuals from birth to 15 years of age. The lateral angle was measured on-screen using the Adobe Photoshop CS2(®) software, from photographs of bissected lateral angle casts. The measurements were performed by three different researchers in order to evaluate intra- and inter-observer variation. Our results demonstrate reasonable repeatability and replicability of the on-screen measurements. We used a 45° sectioning point to allocate individuals in the sample according to sex and attained 62.9% accuracy in sex determination using the lateral angle. When broken down by age, the least accuracy was observed for the 6-15 years-old group (54.5%) and the greatest accuracy was achieved for the 2-5 years-old (75.0%), but still low overall. The use of a sample-specific sectioning point did not improve the results. Although sexual dimorphism is statistically significant between female and male subadults, the lateral angle failed to consistently discriminate individuals according to sex.


Blunt cardiac trauma: atrioventricular valve disruption and ventricular septal defect.
Nonpenetrating cardiac trauma resulting in cardiac chamber or valvar rupture is uncommon, requiring a high degree of suspicion for diagnosis. A case involving avulsion of the tricuspid and mitral papillary muscles with resultant interventricular septal rupture is reported. This case illustrates the importance of transesophageal echocardiography in the rapid diagnosis of blunt cardiac trauma. Surgical treatment of this condition is also discussed.


Prenatal Origins of ASD: The When, What, and How of ASD Development.
Autism spectrum disorder (ASD) is a largely heritable, multistage prenatal disorder that impacts a child's ability to perceive and react to social information. Most ASD risk genes are expressed prenatally in many ASD-relevant brain regions and fall into two categories: broadly expressed regulatory genes that are expressed in the brain and other organs, and brain-specific genes. In trimesters one to three (Epoch-1), one set of broadly expressed (the majority) and brain-specific risk genes disrupts cell proliferation, neurogenesis, migration, and cell fate, while in trimester three and early postnatally (Epoch-2) another set (the majority being brain specific) disrupts neurite outgrowth, synaptogenesis, and the 'wiring' of the cortex. A proposed model is that upstream, highly interconnected regulatory ASD gene mutations disrupt transcriptional programs or signaling pathways resulting in dysregulation of downstream processes such as proliferation, neurogenesis, synaptogenesis, and neural activity. Dysregulation of signaling pathways is correlated with ASD social symptom severity. Since the majority of ASD risk genes are broadly expressed, many ASD individuals may benefit by being treated as having a broader medical disorder. An important future direction is the noninvasive study of ASD cell biology.


Chinese hamster ovarian cells transfected with human parathyroid hormone-related protein cDNA cause hypercalcemia in nude mice.
Parathyroid hormone-related protein (PTH-rP) has been implicated as a causative factor in the humoral hypercalcemia of malignancy. Animal models of hypercalcemia of malignancy that have traditionally utilized human or animal tumors or injections or infusions of hypercalcemic factors have limitations that may prevent exact delineation of the biologic effects of tumor-produced PTH-rP. To assess the effects of tumor-produced PTH-rP in vivo, we have transfected Chinese hamster ovarian (CHO) cells with cDNA encoding human preproPTH-rP-(1-141) which then stably express only PTH-rP. We inoculated these tumor cells into nude mice, and compared tumor-bearing nude mice with similar tumor-bearing nude mice inoculated with non-transfected CHO cells using standard parameters of calcium homeostasis. The nude mice carrying tumors expressing PTH-rP became hypercalcemic over 12 to 18 days. Blood ionized calcium values correlated positively with plasma PTH-rP concentration and tumor volume. Plasma PTH-rP concentrations in hypercalcemic mice were similar to those reported in humans with hypercalcemia of malignancy. Bone histology and histomorphometry from hypercalcemic nude mice demonstrated increased bone resorption when compared with mice bearing nontransfected CHO tumors. We have produced an animal model of tumor-produced PTH-rP by transfecting CHO cells with the cDNA for PTH-rP and inoculating these tumor cells into nude mice. Hypercalcemia in this model is mediated in part by the effects of PTH-rP to increase osteoclastic bone resorption. The model is advantageous because PTH-rP alone is secreted in a prolonged, constitutive fashion with pharmacokinetics similar to naturally occurring tumors. It should prove to be a useful model to study the effects of tumor-produced PTH-rP in vivo.


The effect of linker length on binding affinity of a photoswitchable molecular glue for DNA.
Molecular glue for DNA is a small synthetic ligand that adheres two single-stranded DNAs to produce a double-stranded DNA. We previously devised a photoswitchable molecular glue (PMG) that uses external light stimuli to reversibly control DNA hybridization. To optimize the structure of PMG, we synthesized a series of PMGs and evaluated the effect of changing the methylene linker length on the binding affinity and photoresponse. From the comprehensive T(m) and CSI-TOF-MS measurements, a PMG possessing a three-methylene linker with carbamate linkage produced maximum binding affinity and photoswitching ability. These results indicate that a small difference in the linker can significantly affect PMG function. These findings are useful for designing new photoswitchable DNA-binding ligands.


Characterization of a Sex-Determining Region and Its Genomic Context via Statistical Estimates of Haplotype Frequencies in Daughters and Sons Sequenced in Pools.
Sex chromosomes are generally derived from a pair of autosomes that have acquired a locus controlling sex. Sex chromosomes may evolve reduced recombination around this locus and undergo a long process of molecular divergence. At that point, the original loci controlling sex may be difficult to pinpoint. This difficulty has affected many model species from mammals to birds to flies, which present highly diverged sex chromosomes. Identifying sex-controlling loci is easier in species with molecularly similar sex chromosomes. Here we aimed at pinpointing the sex-determining region (SDR) of Armadillidium vulgare, a terrestrial isopod with female heterogamety (ZW females and ZZ males) and whose sex chromosomes appear to show low genetic divergence. To locate the SDR, we assessed single-nucleotide polymorphism (SNP) allele frequencies in F1 daughters and sons sequenced in pools (pool-seq) in several families. We developed a Bayesian method that uses the SNP genotypes of individually sequenced parents and pool-seq data from F1 siblings to estimate the genetic distance between a given genomic region (contig) and the SDR. This allowed us to assign more than 43 Mb of contigs to sex chromosomes, and to demonstrate extensive recombination and very low divergence between these chromosomes. By taking advantage of multiple F1 families, we delineated a very short genomic region (∼65 kb) that presented no evidence of recombination with the SDR. In this short genomic region, the comparison of sequencing depths between sexes highlighted female-specific genes that have undergone recent duplication, and which may be involved in sex determination in A. vulgare.


The quest for a herpes simplex virus vaccine: background and recent developments.
Herpes simplex virus infections in humans range from localized skin infections of the oral, ocular and genital regions, to severe and often fatal disseminated infections of immunocompromised hosts. Following primary infection, the virus often becomes established in a latent form in the neurons of sensory ganglia and can reactivate to excrete virus asymptomatically or produce recrudescent lesions. This review describes some of the mechanisms involved in the immune response against HSV infections and examines the different strategies adopted to develop a vaccine against this seemingly intractable disease.


Nonpenetrating trabeculectomy with placement of a collagen drainage device.
Since the advent of trabeculectomy with antimetabolite therapy, there have been few changes in the surgical management of glaucoma. This is the first report of a new technique, nonpenetrating trabeculectomy with placement of a collagen drainage device. The procedure facilitates aqueous drainage without entering the human eye. Meticulous surgical dissection of the trabecular meshwork is required with creation of an external filtration tract and subscleral positioning of a collagen device to facilitate aqueous drainage. With this procedure, the surgeon can avoid common complications of glaucoma surgery such as synechias, overfiltration, hypotony, intraocular infection, uveal prolapse, and failed surgical blebs. The procedure and device have been used extensively in Russia.


Uncovering assets in Brazilian national parks.
Protected areas (PAs) are the cornerstone of global conservation policy and have expanded dramatically over the last century. Though unequivocally beneficial for biodiversity, gazetting land for protecting nature can also be seen as an 'opportunity cost' that some politicians are unwilling to pay. One of the most effective strategies to increase the political resilience of PAs in the face of such threats is to demonstrate their broader value to society. This is one of the objectives of the recently proposed 'PA asset framework'. The framework conceptualizes PAs as being composed of suites of biophysical, human, infrastructure, institutional and cultural assets that interact with individuals and institutions to generate different forms of tangible and intangible value. Here, we test the utility of the framework by conducting an asset-based analysis of Brazilian National Parks (NPs) at two different scales (NP system and NP unit). Assets were identified at the system level through a systematic review of 49 Management Plans (MPs) using a typology of PA asset classes as a tool for characterising the presence and state of assets in or associated with NPs. At the NP unit level, assets were identified through semi-structured interviews with local managers of the Chapada Diamantina National Park. Biophysical and infrastructure assets were the most represented asset classes at both scales. Our analysis successfully revealed: (i) which assets can be managed to generate wider forms of values at local scale (e.g. natural spectacles, iconic species, park volunteers) (ii) relational values between assets (e.g. trails and outdoor recreational features), and (iii) value generating practices (VGPs) to capture values from the interaction between different assets (i.e. restoration of degraded areas through voluntary programmes, etc.). We conclude by discussing how the PA asset framework can be operatively integrated into NP management to improve the future allocation of limited financial resources.


The angiogenic potentials of the cephalic mesoderm and the origin of brain and head blood vessels.
We have used two molecular markers to label blood vessel endothelial cells and their precursors in the early avian embryo. One marker, called Quek1, is the avian homologue of the mammalian VEGF receptor flk-1 and the other is the MB1/QH1 monoclonal antibody. Quek1 is expressed in a subset of mesodermal cells from the gastrulation stage. Quek1 positive cells later form blood vessel endothelial cells and express the MB1/QH1 antigen which is specific for endothelial and hemopoietic cells of the quail species. These two markers allowed us first to show that the cephalic paraxial mesoderm has angiogenic potentials which are much more extended than its trunk counterpart (the somites). Secondly, the origin of the endothelial cells lining the craniofacial and head blood vessels was mapped on the 3-somite stage cephalic mesoderm via the quail-chick chimera technique, in which well defined mesodermal territories are exchanged between stage-matched embryos of both species in a strictly isotopic manner. We found that the anterior region of the cephalic paraxial mesoderm is largely recruited to provide the forebrain and the upper face with their vasculature. This means that large volumes of tissues are vascularized by a discrete region of the cephalic mesoderm, the fate of which is otherwise to give rise to muscles. The widespread expansion of the angiogenic cells arising from the anterior paraxial mesoderm must be related to the high growth rate of the anterior region of the neural primordium, yielding the telencephalon and of the neural crest-derived facial structures which are themselves devoid of angiogenic potencies.(ABSTRACT TRUNCATED AT 250 WORDS)


Time dependent pharmacokinetics of pembrolizumab in patients with solid tumor and its correlation with best overall response.
Pembrolizumab is a monoclonal antibody that targets the programmed death-1 receptor to induce immune-mediated clearance (CL) of tumor cells. Originally approved by the US Food and Drug Administration in 2014 for treating patients with unresectable or metastatic melanoma, pembrolizumab is now also used to treat patients with non-small-cell lung cancer, classical Hodgkin lymphoma, head and neck cancer, and urothelial cancer. This paper describes the recently identified feature of pembrolizumab pharmacokinetics, the time-dependent or time-varying CL. Overall results indicate that CL decreases over the treatment period of a typical patient in a pattern well described by a sigmoidal function of time with three parameters: the maximum proportion change in CL from baseline (approximately Imax or exactly eImax - 1), the time to reach Imax/2 (TI50), and a Hill coefficient. Best overall response per response evaluation criteria in solid tumor category was found to be associated with the magnitude of Imax.


A new lethal sclerosing bone dysplasia.
A neonate is described with a lethal sclerosing bone dysplasia associated with prenatal fractures and craniofacial abnormalities including microcephaly, exophthalmos, hypoplastic nose and mid-face, small jaw and nodular hyperplasia of the gums. Parental consanguinity suggests that an autosomal recessive mutation is the likely aetiology.


Phenotypic drift in metastatic progression of breast cancer: A case report with histologically heterogeneous lesions that are clonally related.
Breast cancer metastasis to the stomach is rare; invasive lobular carcinoma has a predilection to spread to the gastrointestinal system and is morphologically similar to primary diffuse gastric carcinoma. This case highlights heterogeneous metastatic progression and that documentation of heterogeneity is important for informing future treatment strategies and prognostication.


Factors Influencing Intravitreal Bevacizumab and Triamcinolone Treatment in Patients with Diabetic Macular Edema.
To evaluate factors associated with response to intravitreal bevacizumab (IVB) and intravitreal triamcinolone acetonide (IVTA) in diabetic macular edema (DME). Ninety-one eyes of 88 patients diagnosed with DME were enrolled in this retrospective chart review. Group 1 included eyes that showed good response to IVB. Group 2 included eyes that did not respond to IVB but responded to IVTA. Group 3 included eyes that responded to neither. Clinical factors, HbA1c, and optical coherence tomography (OCT) findings including patterns of macular edema were compared among the 3 groups. A total of 44, 27, and 20 eyes were included in groups 1, 2, and 3, respectively. HbA1c was higher in group 3 than in the other groups. Proportion of full (combination of all patterns) type edema was higher in group 3 than in the other 2 groups. In group 1, the proportion of sponge-like diffuse retinal thickening type was higher and cystoid macular edema type was lower than in the other groups. The degree of diabetic control and morphologic subtypes with OCT should be considered to better predict the prognosis after treatment in DME.


Synergistic cytotoxicity, inhibition of signal transduction pathways and pharmacogenetics of sorafenib and gemcitabine in human NSCLC cell lines.
Lung cancer is one of the most lethal tumors and, although standard chemotherapy produces clinical response, there has been little improvement in prognosis. Therefore, research effort has focused on target-specific agents, such as sorafenib, which blocks both the RAF/MEK/ERK signalling pathways and receptors involved in neovascularization and tumor progression, including VEGFR-2 and c-Kit. We investigated whether sorafenib would be synergistic with gemcitabine against NSCLC cell lines. Human lung cancer cells A549, CALU-1, CALU-6, H23 and HCC 827 were treated with sorafenib and gemcitabine, alone or in combination, and the cytotoxicity was assessed with CellTiter 96 Non-radioactive cell proliferation kit. Cell cycle and apoptosis were investigated with flow cytometry and fluorescence microscopy, respectively. Moreover, the effects of drugs on Akt (S473), c-Kit (Y823) and ERK (pTpY185/187) phosphorylation were studied with ELISA. Finally, quantitative PCR analysis was performed to assess whether sorafenib and gemcitabine modulated the expression of genes related to drug activity. Gemcitabine and sorafenib synergistically interacted on the inhibition of cell proliferation, and assessment of apoptosis demonstrated that drug associations increased the apoptotic index. Sorafenib reduced c-Kit and ERK activation and gemcitabine inhibited Akt phosphorylation. Moreover quantitative PCR showed that sorafenib modulated the expression of targets related to gemcitabine activity, while gemcitabine induced the expression of RKIP. These data demonstrate that sorafenib and gemcitabine synergistically interact against NSCLC cells, through suppression of Akt, c-Kit and ERK phosphorylation, induction of apoptosis and modulation of dCK, RRM1, RRM2 and RKIP gene expression. The association between traditional cytotoxic agents with new target-specific agents, such as sorafenib, is a challenge for both clinical and preclinical future investigations in lung cancer treatments.


Does coping predict CO2-induced panic in patients with panic disorder?
Patients with panic disorder (PD) show maladaptive coping but the role of coping in the pathogenesis of panic is unclear. This study examined general coping and panic-specific coping as predictors of fear responding to CO2 inhalation. Subjective and physiological responses including panic attacks were assessed in 45 patients with PD and 45 matched nonclinical controls. Measures of coping were the primary predictors used in the analyses. Consistent with other reports, patients with PD reported increased emotion-focused coping and there was an association between emotion-focused coping and subjective reactivity. However, only panic-specific coping predicted panic attacks in response to the CO2 challenge.


Influences of base excision repair defects on the lethality and mutagenicity induced by Me-lex, a sequence-selective N3-adenine methylating agent.
Due to its minor groove selectivity, Me-lex preferentially generates N3-methyladenine (3-MeA) adducts in double-stranded DNA. We undertook a genetic approach in yeast to establish the influence of base excision repair (BER) defects on the processing of Me-lex lesions on plasmid DNA that harbors the p53 cDNA as target. We constructed a panel of isogenic strains containing a reporter gene to test p53 function and the following gene deletions: deltamag1, deltaapn1apn2, and deltaapn1apn2mag1. When compared with the wild-type strain, a decrease in survival was observed in deltamag1, deltaapn1apn2, and deltaapn1apn2mag1. The Me-lex-induced mutation frequency increased in the following order: wild type < deltamag1< deltaapn1apn2 = deltaapn1apn2mag1. A total of 77 mutants (23 in wild type, 31 in deltamag1, and 23 in deltaapn1apn2) were sequenced. Eighty-one independent mutations (24 in wild type, 34 in deltamag1, and 23 in deltaapn1apn2) were detected. The majority of base pair substitutions were AT-targeted in all strains (14/23, 61% in wild type; 20/34, 59%, in deltamag1; and 14/23, 61%, in deltaapn1apn2). The Mag1 deletion was associated with a significant decrease of GC > AT transitions when compared with both the wild-type and the AP endonuclease mutants. This is the first time that the impact of Mag1 and/or AP endonuclease defects on the mutational spectra caused by 3-MeA has been determined. The results suggest that 3-MeA is critical for Me-lex cytotoxicity and that its mutagenicity is slightly elevated in the absence of Mag1 glycosylase activity but significantly higher in the absence of AP endonuclease activity.


The fine structure of the "germinal cytoplasm" in the egg ofXenopus laevis.
1. The fine structure of the "germinal cytoplasm" of the dividing egg ofXenopus laevis has been studied. Mitochondria which occur in great numbers and electron-dense bodies associated with them are the two characteristic components of the so-called "germinal cytoplasm". 2. The electron-dense bodies are composed of granular and fibrillar elements and often contain an internal light area. Long fibrillar elements have been found within the light area. The organization of the electron-dense bodies is strongly reminiscent of that of the polar granules inDrosophila.


Long-term results of reconstructive surgery for aorto-iliac arterial occlusive lesions.
We report a review of 215 reconstructions for aorto-iliac arterial occlusive lesions, involving 156 patients. At 13 years, the cumulative patency rate of 158 aorto-femoral or aorto-iliac dacron synthetic bypass prostheses was 71.6 per cent as compared to 52.7 per cent at 5 years for 22 blunt endarterectomies and 47.4 per cent at 6 years for 35 axillo-femoral bypass prostheses. Of the 158 synthetic bypass prostheses, the cumulative patency rate at 13 years was 85.1 per cent in cases with no occlusive involvement of the peripheral arteries, significantly higher (p less than 0.03) than the 39.3 per cent patency rate at 7 years in cases in which associated femoro-popliteal occlusive lesions were not treated. At 12 years, the patency rate was 53.2 per cent in cases in which associated femoro-popliteal occlusive lesions were treated during the same reconstructive intervention, i.e. markedly higher (p less than 0.08) than in patients in whom the degree of outflow in the distal vessels was poor. Our findings indicated that, in order to achieve a satisfactory long-term patency rate, it is important to treat associated occulusive lesions in the femoro-popliteal arteries.


Restriction endonuclease cleavage maps of rat and mouse mitochondrial DNAs.
Mitochondrial DNA from an Old World mouse, Mus musculus, and from an Old World rat, Rattus norvegicus, contain 19 and 22 distinct sites, respectively, for the 8 restriction endonucleases, BamHI, EcoRI, HaeII, HhaI, HincII, HindIII, HpaI and PstI. The relative positions of the sites have been mapped by the study of partial and double enzyme digests. Some sites may been conserverd between the mouse and rat mitochondrial genomes.


Choroid plexus and ependymal cells in CSF cytology.
Choroid plexus and ependymal cells were only demonstrated in 10 of a series of 2620 CSF cytograms. Choroid plexus cells sometimes stained positive for acid phosphatase while in ependymal cells this enzyme activity was not observed. Choroid plexus and ependymal cells in CSF were found to be associated with various neurological disorders involving mainly the brain stem and spinal cord. This is probably due to the higher chance of sedimentation of viable cells in the lumbar sac in these conditions. Loss of these cells might explain the incidental observation of granular ependymitis in post-mortem brains.


Rising disparities in severe adverse birth outcomes among Haitians in Québec, Canada, 1981-2006.
Perinatal health data for Haitians are scant. We evaluated adverse birth outcomes for Haitians in Québec, Canada. We analyzed 2,124,909 live births from 1981 to 2006. Haitian ethnicity was assessed using maternal birth country (Haiti, other Caribbean country, other foreign country, Canada) and home language (Creole, French/English but Creole mother tongue, French/English, other). Associations between ethnicity and preterm birth (PTB), low birth weight (LBW), and small-for-gestational-age (SGA) birth were calculated. Adverse birth outcomes were more common among mothers with Haitian ethnicity. Relative to Canadian-born mothers, odds for Haitian-born mothers were 4 times greater for extreme PTB (≤27 weeks), twice greater for very PTB (28-31 weeks), and 25% higher for moderate PTB (32-36 weeks). Patterns were similar for SGA birth and severe cases of LBW. Despite overall decreases LBW and SGA birth, relative and absolute inequalities increased over time. Perinatal health inequalities are increasing for Haitian-born mothers.


Use of total dietary fiber across four lemur species (Propithecus verreauxi coquereli, Hapalemur griseus griseus, Varecia variegata, and Eulemur fulvus): does fiber type affect digestive efficiency?
In vivo digestibility and transit of two experimental diets were compared across four lemur species for which gastrointestinal morphology and preliminary data on physiology differ:Varecia variegata (VV), Eulemur fulvus (EF), Propithecus verreauxi (PV), and Hapalemur griseus (HG). Since free-ranging groups consume varied amounts of slowly fermentable insoluble fiber (IF) and rapidly fermentable soluble fiber (SF), differences in digestibility may be related to variation in the fiber types consumed. To investigate this, two diets were designed to provide 28% of dry matter (DM) as total dietary fiber (TDF). The ratio of IF/SF (g/g) differed across the diets (12.15:1 for the IF diet, and 3.76:1 for the IF/SF diet). The DM digestibility (DMD) of both diets differed across species: DMD was lower for EF and VV (approximately 56-58%), and higher for PV (72%) and HG (76%). The fiber digestibility results were as follows: TDF digestibility was similar for VV and EF (23% and 28%), higher for PV (56%), and highest for HG (66%). IF digestibility was lower for VV and EF (20% and 28%), and higher for PV and HG (53% and 62%). The transit times (TTs) of the two markers Cr and Co were similar (approximately 3.5 hr for VV and EF, 25 hr for PV, and 30 hr for HG). The mean retention times (MRTs) showed the same trend. The results from these captive groups suggest there are large differences in digestive efficiency that are likely related to the varied fiber composition of the free-ranging diet, and the amount of time the digesta are retained in the gut.


Insight into the reaction mechanism of cis,cis-muconate lactonizing enzymes: a DFT QM/MM study.
MLEs derived from mycobacterium smegmatis and seudomonas fluorescens share ∼76% identity and have a very similar arrangement of catalytic residues in their active site configuration. However, while they catalyze the conversion of cis,cis-muconate to the same achiral product, muconolactone, studies in deuterated solvent surprisingly show that the cyclo-isomerization proceeds with the formation of a chiral product. In this paper we discuss the application of DFT QM/MM calculations on both MLEs, to our knowledge the first reported in the literature on this protein. We investigate the proposal that the base involved in the catalytic reaction is the lysine residue found at the end of the 2(nd) strand given: (a) that the lysine residue at the end of the 6(th) strand is in an apparently equally effective position to catalyze reaction and (b) that the structural related epimerase in-fact achieve their stereo-specific outcomes by relying on either the base from the 2(nd) or 6(th) strand.


Repeatability and Reproducibility of Photoreceptor Density Measurement in the Macula Using the Spectralis High Magnification Module.
To evaluate the repeatability and reproducibility of photoreceptor density assessment with manual cell counting in healthy participants imaged with the Heidelberg Spectralis High Magnification Module (HMM). Precision study, evaluation of diagnostic test or technology. Eleven eyes of 8 participants. Images were acquired using the Spectralis HMM by a single operator during 2 separate imaging sessions. The 3 highest-quality images of each eye from each session were selected for analysis and coregistered. For a subset of participants, a second operator acquired images in 1 session, and images with the best quality were selected for analysis. Photoreceptor densities were obtained by manual counts in squares of 0.0625 mm2 located in the parafovea. Repeatability (intragrader and intrasession) and reproducibility (interoperator, intergrader, and intersession) were assessed by calculating the intraclass correlation coefficient (ICC) from linear mixed effects models. Bland-Altman plots, coefficients of repeatability, and Pearson correlation results were reported. Intragrader, intrasession, intersession, interoperator, and intergrader ICC estimates and their 95% confidence intervals for photoreceptor density measurements in the parafovea. Twenty-four eyes of 13 healthy participants were imaged initially. Of these, 11 eyes (45.83%) of 8 participants that had at least 3 acceptable images in each session were included in this study. Mean parafoveal photoreceptor density was 14 988 cells/mm2 (standard deviation, 1403.15 cells/mm2). Intragrader ICC was 0.84 (95% confidence interval, 0.57-0.95), intrasession ICC was 0.69 (95% confidence interval, 0.17-0.86), intersession ICC was 0.88 (95% confidence interval, 0.53-0.96), interoperator ICC was 0.70 (95% confidence interval, 0-0.95), and intergrader ICC was 0.22 (95% confidence interval, 0-0.71). Images obtained with the HMM allow for photoreceptor mosaic visualization in the macular area, mainly in the parafovea. Although densities obtained are in accordance with other reported methods in the literature, variability within and between images of the apparent cell mosaic were observed, and this study did not demonstrate high repeatability or reproducibility for quantitative assessments using the manual counting method.


Activation of nanoscale allosteric protein domain motion revealed by neutron spin echo spectroscopy.
NHERF1 is a multidomain scaffolding protein that assembles signaling complexes, and regulates the cell surface expression and endocytic recycling of a variety of membrane proteins. The ability of the two PDZ domains in NHERF1 to assemble protein complexes is allosterically modulated by the membrane-cytoskeleton linker protein ezrin, whose binding site is located as far as 110 Ångstroms away from the PDZ domains. Here, using neutron spin echo (NSE) spectroscopy, selective deuterium labeling, and theoretical analyses, we reveal the activation of interdomain motion in NHERF1 on nanometer length-scales and on submicrosecond timescales upon forming a complex with ezrin. We show that a much-simplified coarse-grained model suffices to describe interdomain motion of a multidomain protein or protein complex. We expect that future NSE experiments will benefit by exploiting our approach of selective deuteration to resolve the specific domain motions of interest from a plethora of global translational and rotational motions. Our results demonstrate that the dynamic propagation of allosteric signals to distal sites involves changes in long-range coupled domain motions on submicrosecond timescales, and that these coupled motions can be distinguished and characterized by NSE.


Efficacy of ACC-9653 (a phenytoin prodrug) in experimental status epilepticus in the rat.
Status epilepticus was induced by injection of homocysteine thiolactone to rats with epileptogenic cortical cobalt lesions. Either standard phenytoin or ACC-9653 (a phenytoin prodrug) was injected after the second generalized tonic-clonic seizure. Rats treated with ACC-9653 had significantly poorer treatment outcomes than rats treated with standard phenytoin, although no differences were found in the concentration of phenytoin in plasma or brain 65 min after injection.


Standard diffusion-weighted, diffusion kurtosis and intravoxel incoherent motion in differentiating invasive placentas.
To investigate the diagnostic value of monoexponential, biexponential, and diffusion kurtosis MR imaging (MRI) in distinguishing invasive placentas. A total of 53 patients with invasive placentas and 47 patients with noninvasive placentas undergoing conventional diffusion-weighted imaging (DWI), intravoxel incoherent motion (IVIM), and diffusion kurtosis imaging (DKI) were retrospectively enrolled. The mean, minimum, and maximum parameters including the apparent diffusion coefficient (ADC) and exponential ADC (eADC) from standard DWI, diffusion kurtosis (MK), and diffusion coefficient (MD) from DKI and pure diffusion coefficient (D), pseudo-diffusion coefficient (D*), and perfusion fraction (f) from IVIM were measured and compared from the volumetric analysis. Receiver operating characteristics (ROC) curve and logistic regression analyses were conducted to evaluate the diagnostic efficiency of different diffusion parameters for distinguishing invasive placentas. Comparisons between accreta lesions in patients with invasive placentas (AL) and lower 1/3 part of the placenta in patients with noninvasive placentas (LP) demonstrated that MD mean, D mean, and D* mean were significantly lower while ADC max and D max were significantly higher in invasive placentas (all p < 0.05). Multivariate analysis demonstrated that D mean, D max and D* mean differed significantly among all the studied parameters for invasive placentas. A combined use of these three parameters yielded an AUC of 0.86 with sensitivity, specificity, and accuracy of 84.91%, 76.60%, and 80%, respectively. The combined use of different IVIM parameters is helpful in distinguishing invasive placentas.


Asymmetric synthesis of the epimeric (3S)-3-((E)-hex-1-enyl)-2-methylcyclohexanones.
The asymmetric rhodium-catalysed 1,4-addition of alkenylzirconium reagents to 2-cyclohexenone can be useful in the synthesis of 3-alkenyl-2-methylcyclohexanones, provided that formaldehyde is used in trapping the intermediate zirconium enolates. In this manner a four-step sequence leading to the two epimeric 3-hexenyl-2-methylcyclohexanones in enantiomeric form was developed.


The promising shadow of microbubble over medical sciences: from fighting wide scope of prevalence disease to cancer eradication.
Microbubbles are typically 0.5-10 μm in size. Their size tends to make it easier for medication delivery mechanisms to navigate the body by allowing them to be swallowed more easily. The gas included in the microbubble is surrounded by a membrane that may consist of biocompatible biopolymers, polymers, surfactants, proteins, lipids, or a combination thereof. One of the most effective implementation techniques for tiny bubbles is to apply them as a drug carrier that has the potential to activate ultrasound (US); this allows the drug to be released by US. Microbubbles are often designed to preserve and secure medicines or substances before they have reached a certain area of concern and, finally, US is used to disintegrate microbubbles, triggering site-specific leakage/release of biologically active drugs. They have excellent therapeutic potential in a wide range of common diseases. In this article, we discussed microbubbles and their advantageous medicinal uses in the treatment of certain prevalent disorders, including Parkinson's disease, Alzheimer's disease, cardiovascular disease, diabetic condition, renal defects, and finally, their use in the treatment of various forms of cancer as well as their incorporation with nanoparticles. Using microbubble technology as a novel carrier, the ability to prevent and eradicate prevalent diseases has strengthened the promise of effective care to improve patient well-being and life expectancy.


Pollen proteases compromise the airway epithelial barrier through degradation of transmembrane adhesion proteins and lung bioactive peptides.
Allergic disorders, such as seasonal rhinitis and asthma, are increasing causes of morbidity worldwide and often result from exposure to airborne pollen. Pollen allergy has a remarkable clinical impact all over Europe. In fact, epidemiological longitudinal studies confirm that pollen species usually considered with low allergenic potential became more recently responsible for intense allergic reactions. In this study, we aimed to characterize major pollen proteolytic activity and evaluate its contribution to the immunologic and inflammatory response to airborne allergens. Proteolytic activity in four pollen diffusates with distinct allergenicity, Olea europaea, Dactylis glomerata, Cupressus sempervirens and Pinus sylvestris, was evaluated through several enzymatic assays. The action of pollen proteases on the paracellular integrity of Calu-3, grown at the air-liquid interphase, was evaluated through a transepithelial permeability assay. Immunoblot and immunofluorescence experiments were performed to analyse the disruption of intercellular complexes. Degradation of bioactive peptides by pollen crude extracts was assessed by mass spectrometry. All pollen diffusates were shown to have high molecular weight proteases with serine and/or aminopeptidase activity. These proteases increased Calu-3 transepithelial permeability through disruption of transmembrane adhesion proteins: occludin, claudin-1 and E-cadherin. Moreover, they were able to degrade airway bioactive peptides and were not blocked by endogenous protease inhibitors. Pollen grains with distinct allergenic abilities release proteases that might be involved in the sensitization to a range of airborne allergens by facilitating allergen delivery across the epithelium and also contribute directly to the inflammation characteristic of allergic diseases.


Integrated environmental characterization and assessment of an exposed historic manure repository.
Historic manure stockpiled (active from 1935 through 2018) in a repository mound approximately 15 m high with a 31,415.93 m2 footprint was sampled from various depths at six locations in an environmental assessment framework. The manure samples were analyzed for nutrient content to investigate potential application as a soil amendment to local fields in combination with biowaste disposal regulations. Results indicate that manure can be used as a soil amendment; however, different crops and land conditions require specific nutrients, and application must be determined accordingly. Likewise, the manure analysis did not indicate any negative issues that would disallow land application as a disposal option. In addition to limiting environmental soil boring into the manure repository, two-dimensional geophysical electrical resistivity imaging was performed to characterize and quantify the deposited manure. Based on those efforts, the material volume within the site's manure repository was calculated to be 611,942.354 cubic meters (m3). Finally, based on the geophysical results and the historical information about the manure's deposited volume in the study area, an estimation of the released landfill gases and its expected produced energy is presented.


High Performance Bi-2212 Round Wires Made with Recent Powders.
Multifilamentary Bi2Sr2CaCu2Ox (Bi-2212) wire made by the powder-in-tube technique is the only high temperature superconductor made in the round shape preferred by magnet builders. The critical current density (J C ) of Bi-2212 round wire was improved significantly by the development of overpressure heat treatment in the past few years. Bi-2212 wire is commercially available in multiple architectures and kilometer-long pieces and a very promising conductor for very high field NMR and accelerator magnets. We studied the effects of precursor powder and heat treatment conditions on the superconducting properties and microstructure of recent Bi-2212 wires. Short samples of recent wire with optimized overpressure processing showed J C (4.2 K, 15 T) = 6640 A/mm2 and J C (4.2 K, 30 T) = 4670 A/mm2, which correspond to engineering critical current densities J E (4.2 K, 15 T) = 1320 A/mm2 and J E (4.2 K, 30 T) = 930 A/mm2.


Synthesis of beta-bisabolol by ring-closing olefin metathesis reaction.
A ring-closing olefin metathesis is the key step in the synthesis of the beta-bisabolols.


Radiation Drives the Evolution of Orthotopic Xenografts Initiated from Glioblastoma Stem-like Cells.
A consequence of the intratumor heterogeneity (ITH) of glioblastoma (GBM) is the susceptibility to treatment-driven evolution. To determine the potential of radiotherapy to influence GBM evolution, we used orthotopic xenografts initiated from CD133+ GBM stem-like cells (GSC). Toward this end, orthotopic xenografts grown in nude mice were exposed to a fractionated radiation protocol, which resulted in a significant increase in animal survival. Brain tumors from control and irradiated mice were then collected at morbidity and compared in terms of growth pattern, clonal diversity, and genomic architecture. In mice that received fractionated radiation, tumors were less invasive, with more clearly demarcated borders and tumor core hypercellularity as compared with controls, suggesting a fundamental change in tumor biology. Viral integration site analysis indicated a reduction in clonal diversity in the irradiated tumors, implying a decrease in ITH. Changes in clonal diversity were not detected after irradiation of GSCs in vitro, suggesting that the radiation-induced reduction in ITH was dependent on the brain microenvironment. Whole-exome sequencing revealed differences in mutation patterns between control and irradiated tumors, which included modifications in the presence and clonality of driver mutations associated with GBM. Moreover, changes in the distribution of mutations as a function of subpopulation size between control and irradiated tumors were consistent with subclone expansion and contraction, that is, subpopulation evolution. Taken together, these results indicate that radiation drives the evolution of the GSC-initiated orthotopic xenografts and suggest that radiation-driven evolution may have therapeutic implications for recurrent GBM. SIGNIFICANCE: Radiation drives the evolution of glioblastoma orthotopic xenografts; when translated to the clinic, this may have therapeutic implications for recurrent tumors.


Comparison of [68Ga]Ga-FAPI and [18F]FDG uptake in patients with gastric signet-ring-cell carcinoma: a multicenter retrospective study.
In this study, we investigated the role of [68Ga]Ga-FAPI PET imaging in the detection of primary and metastatic gastric signet-ring-cell carcinoma (GSRCC) and compared with [18F]FDG PET. This retrospective multicenter analysis included 34 patients with histologically confirmed GSRCCs from four medical centers. The maximum standard uptake value (SUVmax), tumor-to-background ratio (TBR), and diagnostic accuracy were compared between the two modalities. [18F]FDG and [68Ga]Ga-FAPI uptakes were compared by using the Wilcoxon signed-rank test. McNemar's test was used to compare the diagnostic accuracy between the two techniques. Data were analyzed from 27 paired PET/CT and 7 paired PET/MRI scans for 34 GSRCC patients (16 men and 18 women) who had a median age of 51 years (range: 25-85 years). [68Ga]Ga-FAPI PET showed higher SUVmax and TBR values than did [18F]FDG PET in the primary tumors (SUVmax: 5.2 vs. 2.2, p = 0.001; TBR: 7.6 vs. 1.3, p < 0.001), involved lymph nodes (SUVmax: 6.8 vs. 2.5, p < 0.001; TBR: 5.8 vs. 1.3, p < 0.001), and bone and visceral metastases (SUVmax: 6.5 vs. 2.4, p < 0.001; TBR: 6.3 vs. 1.3, p < 0.001). In diagnostic performance, [68Ga]Ga-FAPI PET exhibited higher sensitivity than [18F]FDG PET for detecting primary tumors (73% [16/22] vs. 18% [4/22], p < 0.001), local recurrences (100% [7/7] vs. 29% [2/7], p = 0.071), lymph node metastases (77% [59/77] vs. 23% [18/77], p < 0.001), and distant metastases (93% [207/222] vs. 39% [86/222], p < 0.001). The results from this multicenter retrospective analysis justify the clinical use of [68Ga]Ga-FAPI tracers for GSRCC diagnosis and staging. • [68Ga]Ga-FAPI PET/CT is a promising imaging modality for the detection of primary and metastatic disease and has implications for TNM staging in GSRCC. • In this multicenter study of 34 patients with GSRCC, [68Ga]Ga-FAPI PET exhibited greater radiotracer uptake, tumor-to-background ratios, and diagnostic accuracy than [18F]FDG PET for detecting primary/recurrent tumors and metastatic lesions.


Synergistic effect of adsorptive photocatalytic oxidation and degradation mechanism of cyanides and Cu/Zn complexes over TiO2/ZSM-5 in real wastewater.
The treatment of cyanide wastewater from the gold industry is essential. Photocatalytic oxidation is an effective method for the elimination of cyanides and metal cyanide complexes. TiO2/ZSM-5 composite photocatalysts with different SiO2/Al2O3 ratios were prepared using the solid-state dispersion (SSD) method. The composite catalysts were characterized by X-ray diffraction (XRD), scanning electron microscopy (SEM), N2 adsorption-desorption, and ultraviolet-visible diffuse reflectance spectroscopy (UV-Vis DRS). The catalytic efficiency of different SiO2/Al2O3 ratios and the synergistic effect of adsorptive photocatalytic oxidation for the degradation of cyanide wastewater was investigated under different adsorption and illumination times. With the extension of the photocatalytic time (>2.0 h), the composite catalyst with a high SiO2/Al2O3 ratio had better photocatalytic performance. A 93.97% degradation efficiency of total cyanides was observed after adsorption for 3.0 h and illumination for 4.0 h under room temperature with air as the oxidant. The removal efficiencies of the copper and zinc ions were 81.67% and 100%, respectively. The degradation of cyanide followed pseudo-first-order kinetics. Energy dispersive spectroscopy (EDS) results showed that the generally irregular surface of the catalyst with a high SiO2/Al2O3 ratio contains more nano-TiO2. The adsorption capacities of copper and zinc were relatively high. X-ray photoelectron spectroscopy (XPS) suggested that cyanide was eventually degraded to CO2 and NO3-. Copper and zinc were removed in the form of Cu(II) and Zn(II).


A National Survey of Health and Safety Knowledge and Beliefs Among Technical Vocational Faculty in Autobody Collision Repair Technology.
Career technical education (CTE) programs prepare new generations of technicians in a variety of trades. Even though occupational safety and health (OSH) ought to be included as an essential part of CTE curricula it is frequently absent or inadequately taught. OSH knowledge and beliefs were assessed in a national sample of 125 secondary and post-secondary faculty in autobody collision repair technology. Over 50% of faculty thought at least 75% of OSH knowledge was learned at school, and 9% felt that safety was primarily learned on the job. Knowledge scores ranged from 22% to 78%. Overall knowledge scores were significantly lower high school than post-secondary instructors (42% vs 50%, P ≤ 0.001) and in two categories: hazard recognition (44% vs 54%, P ≤ 0.05) and hazard control and shop equipment (30% vs 37%, P ≤ 0.05). There are substantial gaps in OSH knowledge among secondary and post-secondary CTE instructors. CTE programs should address these gaps by providing trade-specific safety and health education to their instructors upon hiring.


Health care professionals' conceptions of respiratory symptoms and physical activity in patients with acute pulmonary embolism. A phenomenographic interview study.
Acute pulmonary embolism (PE) often presents with respiratory symptoms, such as dyspnea and respiratory pain, and patients are affected both physically and mentally by the consequences of PE for a long time after the event. This study aimed to explore health care professionals (HCPs) conceptions of respiratory symptoms, physical activity, and information given to patients during in-hospital care. Qualitative individual interviews were conducted with twenty-one HCPs (physicians, nurses, physiotherapist) working with patients with PE, and analyzed with a phenomenographic approach. The findings resulted in an overall theme: "Health care professionals' knowledge of PE, and an individualized patient approach, are cornerstones for adequate management of respiratory symptoms in PE". Three major categories described conceptions of a heterogenous patient group physically and mentally affected by their respiratory symptoms, of accurate information given at right time being crucial, and of giving appropriate information about respiratory symptoms and physical activity being complex due to many prerequisites needing to be fulfilled. This study provides new knowledge about the complexity of management of patients with PE and respiratory symptoms. The patient group was conceived as heterogenous with different needs for information given at the appropriate time. Structural prerequisites, such as time and staff rotation in the hospital setting, and personal issues, for example levels of knowledge of PE among HCPs affected the ability of HCPs to give correct information. Further research is needed to ensure optimal design of in-hospital care for patients with PE.


Life-threatening Skin Disorders Treated in the Burn Center: Impact of Health care-associated Infections on Length of Stay, Survival, and Hospital Charges.
This article reviews a single burn center experience with life-threatening skin disorders, over a 10-year period. It explores the incidence of health care-associated infections and the impact on length of stay, hospital charges, and mortality.


Ferromagnetic ordering in Mn-doped ZnO nanoparticles.
Zn1 - x Mn x O nanoparticles have been synthesized by hydrothermal technique. The doping concentration of Mn can reach up to 9 at% without precipitation or secondary phase, confirmed by electron spin resonance (ESR) and synchrotron X-ray diffraction (XRD). Room-temperature ferromagnetism is observed in the as-prepared nanoparticles. However, the room-temperature ferromagnetism disappears after post-annealing in either argon or air atmosphere, indicating the importance of post-treatment for nanostructured magnetic semiconductors.


Sequential acid/reduction response of triblock copolymeric nanomicelles to release camptothecin and toll-like receptor 7/8 agonist for orchestrated chemoimmunotherapy.
Immunosuppressive tumor immune microenvironment (TIME) lowers immunotherapy effectiveness. Additionally, low penetration efficiency and unpredictable drug release in tumor areas restrict tumor therapy. A triblock copolymeric micelle (NanoPCPT+PIMDQ) was developed to carry the chemotherapeutic drug camptothecin (CPT) and the TLR7/8 agonist 1-(4-(aminomethyl)benzyl)-2-butyl-1H-imidazo[4,5-c] quinoline-4-amine (IMDQ) to achieve deep tumor penetration and on-demand drug release by responding to acid and reduction stimuli sequentially. The synergistic antitumour efficacy of NanoPCPT+PIMDQ was assessed both in vitro and in vivo. NanoPCPT+PIMDQ is composed of a hydrophilic PEG(polyethylene glycol) outer layer, an acid-sensitive EPEMA middle layer, and a drug inner core. Upon intratumoral injection, (i) NanoPCPT+PIMDQ first responds to the acidic tumor microenvironment and disintegrates to PIMDQ and PCPT, penetrating deep regions of the tumor; (ii) tumor cells are killed by the released CPT; (iii) DCs are activated by PIMDQ to increase the infiltration of cytotoxic T lymphocyte (CTL); and (iv) both downregulated Foxp3+ Tregs by CPT and repolarized M2 macrophages by PIMDQ can relieve the TIME. This pH/GSH-responsive triblock polymer-drug conjugate reduces immunosuppression and enhances the infiltration of CTLs by codelivering CPT and IMDQ in a controllable manner, providing a promising platform for synergistic tumor chemoimmunotherapy.


Diffusion Tensor Imaging in Preclinical Huntington's Disease.
Diffusion tensor imaging was used to study brain related changes in white matter that may be associated with Huntington's Disease progression. Thirty-one preclinical gene-mutation carriers were imaged cross-sectionally using diffusion tensor and anatomical brain imaging. Subjects were individuals who had a known gene mutation for HD but did not manifest motor diagnostic criteria for HD. Fractional anisotropy scalar maps showed a positive correlation with five year probability of diagnosis (based upon gene repeat length and current age) in the putamen and a negative correlation in the external capsule. This study shows that scalar maps generated from diffusion tensor imaging may be directly related to the earliest stages of disease progression within HD, even before a diagnosis is given. Findings suggest that DTI measures, therefore, may have the ability to act as a biomarker for disease progression in clinical trials of pre-manifest subjects.


Myeloid cell neuropilin 1 ameliorates high-fat diet-induced insulin resistance via suppression of Nlrp3 inflammasome.
The history of neuropilin 1 (Nrp1) research is checkered with many unexpected and exciting findings. Nrp1 functions as a co-receptor for class 3 semaphorins, and several canonical growth factors, including vascular endothelial growth factor (VEGF) and hepatocyte growth factor (HGF). It has been implicated in the development of central nervous system, angiogenesis, and migration. Accumulating evidence demonstrates that Nrp1 is also highly expressed in immune cells, including macrophages and dendritic cells. Until now, the functions of Nrp1 within these cells remained poorly studied and elusive. Here, we provide exciting insights on a novel role for myeloid cell Nrp1 in the mitigation of dietary insulin resistance through inhibiting Nlrp3 inflammasome.


Induced changes in bioactive compounds of broccoli juices after fermented by animal- and plant-derived Pediococcus pentosaceus.
To investigate the metabolism of bioactive compounds in broccoli juice fermented by animal- and plant-derived Pediococcus pentosaceus, levels of glucosinolates (GS), sulforaphane, and sulforaphane-nitrile; activity of myrosinase; and profiles of organic acids, vitamins, and amino acids were determined. Three aliphatic GS and four indolyl GS were identified. After fermentation by plant- and animal-derived P. pentosaceus, myrosinase activity, contents of total GS and sulforaphane nitrile, and levels of malic acid, acetic acid, ascorbic acid, and thiamine significantly decreased in pasteurized broccoli juice, whereas levels of sulforaphane, lactic acid, and citric acid significantly increased. Fermentation by plant-derived P. pentosaceus decreased levels of riboflavin and β-carotene and increased total levels of free amino acids, in contrast to the trends observed in broccoli juice after fermentation by animal-derived P. pentosaceus. This study indicates that P. pentosaceus may potentially be used in starter cultures to improve the nutritional and functional properties of fermented foods.


A Scoping Review of the Experiences of Adolescents and Young Adults in the ICU, Their Family Members, and Their Health Care Team.
Adolescents and young adults (AYAs) may be cared for in a pediatric or adult ICU. Specific needs of AYAs differ from those of populations typically found in either ICU. This review identifies research focused on experiences of AYAs in ICUs, their family members, and the health care professionals who care for them, revealing limited research about AYAs in ICUs: 10 articles met inclusion criteria and findings revealed that AYAs want to be treated as individuals and need health care professionals to partner with them. Further research is needed to inform developmentally appropriate care and improve serious illness communication.


Pterisolic acids A-F, new ent-kaurane diterpenoids from the fern Pteris semipinnata.
Six new ent-15-oxokauran-19-oic acid derivatives, named pterisolic acids A-F (1-6), were isolated from the ethanol extract of the fern Pteris semipinnata (Pteridaceae), and the structures of these new ent-kauranoids were elucidated on the basis of extensive spectroscopic studies and single crystal X-ray diffraction analysis.


What Factors Predict Patient Dissatisfaction After Contemporary Medial Opening-Wedge High Tibial Osteotomy?
Although current advances in surgical techniques have improved outcomes of the medial opening-wedge high tibial osteotomy (MOWHTO), the factors associated with patient dissatisfaction remain unclear. Thus, the purpose of this study is to identify risk factors for patient dissatisfaction following contemporary MOWHTO. We retrospectively reviewed prospectively collected data on 140 consecutive MOWHTO patients using an anatomical locking plate with a minimum follow-up of 2 years. Patient demographics, pain Visual Analogue Scale, Western Ontario and McMaster Universities Osteoarthritis Index, Kellgren-Lawrence (K-L) grade, activity level, articular cartilage and meniscal status, hip-knee-ankle angle, change in alignment, and postoperative weight-bearing line ratio were recorded. Patients were categorized using the New Knee Society Score into satisfied (satisfaction score ≥20) or dissatisfied (satisfaction score <20) groups. Patient and surgical factors were compared between the groups by the identified predictors. Multiple logistic regression analysis was used to analyze risk factors, including K-L grade IV medial osteoarthritis (OA), preoperative pain Visual Analogue Scale, total Western Ontario and McMaster Universities Osteoarthritis Index score, postoperative hip-knee-ankle angle, change in alignment, and partial meniscectomy. Of the 140 patients, 24 (17.1%) were dissatisfied with their results. Multiple logistic regression analysis showed that only K-L grade IV medial OA was statistically associated with patient dissatisfaction following MOWHTO (odds ratio 4.911, 95% confidence interval 1.820-13.256, P < .01). Severe medial OA was an independent risk factor for dissatisfaction following contemporary MOWHTO using a rigid locking plate. Surgeons should take this into consideration when counseling and choosing surgical options in MOWHTO candidates with severe medial OA. Level III.


Perception and awareness towards malaria vaccine policy implementation in Nigeria by health policy actors.
This study aimed to assess the perception and awareness of malaria vaccine policy implementation among health policy actors in Nigeria. A descriptive study was conducted to assess the opinions and perceptions of policy actors on the implementation of a vaccination programme against malaria in Nigeria. Descriptive statistics were carried out to study the characteristics of the population and the univariate analysis of the responses to questions presented to the participants. Multinomial logistic regression was conducted to evaluate the association between demographic characteristics and the responses. The study revealed that malaria vaccine awareness was poor, with only 48.9% of the policy actors having previous knowledge of the malaria vaccine. The majority of participants (67.8%) declared that they were aware of the importance of vaccine policy in efforts to manage disease transmission. As the number of years of work experience of the participants increased, the odds of being more likely to be aware of the malaria vaccine increased [OR 2.491 (1.183-5.250), p value < 0.05]. It is recommended that policy-makers develop methods of educating populations, increase awareness of the acceptability of the vaccine and ensure that an affordable malaria vaccine programme is implemented in the population.


Specific tissue engineering for temporomandibular joint disc perforation.
The temporomandibular joint (TMJ) disc is a critical fibrocartilaginous structure with limited regenerative capacity in the oral system. Perforation of the TMJ disc can lead to osteoarthritis and ankylosis of the TMJ because of the lack of disc protection. Clinical treatments for TMJ disc perforation, such as discectomy, hyaluronic acid injection, endoscopic surgery and high position arthroplasty of TMJ, are questionable with regard to long-term outcomes, and only three fourths of TMJ disc perforations are repairable by surgery, even in the short-term. Tissue engineering offers the potential for cure of repairable TMJ disc perforations and regeneration of unrepairable ones. This review discusses the classification of TMJ disc perforation and defines typical TMJ disc perforation. Advancements in the engineering-based repair of TMJ disc perforation by stem cell therapy, construction of a disc-like scaffold and functionalization by offering bioactive stimuli are also summarized in the review, and the barriers developing engineering technologies need to overcome to be popularized are discussed.


Impact of MASP2 gene polymorphism and gene-tea drinking interaction on susceptibility to tuberculosis.
Mannan-binding lectin-associated serine protease-2 (MASP-2) has been reported to play an important role as a key enzyme in the lectin pathway of the complement system. The objectives of our study were to determine whether the single-nucleotide polymorphism (SNPs) of MASP2 and the gene-tea drinking interaction were associated with the susceptibility to TB. In total, 503 patients and 494 healthy controls were contained. Three SNPs (rs12142107, rs12711521, and rs7548659) were genotyped. The association between the SNPs and susceptibility to TB were investigated by conducting multivariate unconditional logistic regression analysis. The gene-tea drinking interactions were analyzed by the additive model of marginal structural linear odds models. Both genotype AC + AA at rs12711521 of MASP2 genes and genotype GT + GG at rs7548659 of MASP2 genes were more prevalent in the TB patient group than the healthy control group (OR: 1.423 and 1.439, respectively, P < 0.05). In addition, The relative excess risk of interaction (RERI) between tea drinking and rs12142107, rs12711521, and rs7548659 of MASP2 genes was found to suggest negative interactions, which reached - 0.2311 (95% confidence interval (CI): - 0.4736, - 0.0113), - 0.7080 (95% CI - 1.3998, - 0.0163), and - 0.5140 (95% CI - 0.8988, - 0.1291), respectively (P < 0.05). Our finding indicated that the SNPs (rs12711521 and rs7548659) of MASP2 were associated with the susceptibility to TB. Furthermore, there were negative interactions between tea drinking and rs12142107, rs12711521, and rs75548659 of MASP2 gene, respectively. Our research provides a basis for studying the pathogenesis and prevention of tuberculosis.


Synthesis of Simple Strigolactone Mimics.
Strigolactones (SLs) are natural compounds occurring in plants which have a numerous functions in plant development; therefore, they are plant hormones. Unfortunately, their natural abundance is very low and because of their structure complexity it is difficult to prepare them in big quantities; alternatives with simpler structures and similar biological activity was developed. SLs mimics are compounds with simple synthesis. Methods for preparation of basic SLs mimics are described here.


Intention to Exclusively Breastfeed Is Associated with Lower Rates of Cesarean Section for Nonmedical Reasons in a Cohort of Mothers in Vietnam.
Breastfeeding brings benefits to both mothers and children in the short term and long term. Unnecessary cesarean sections can bring risks to both parties. This study was undertaken to examine the relationship between exclusive breastfeeding intention and cesarean delivery. We analyzed data collected from 554 single mothers who delivered in Dong Anh General District Hospital or Hanoi Obstetrics and Gynecology Hospital, Vietnam, in 2020-2021. The relationship between exclusive breastfeeding intention and cesarean delivery for nonmedical reasons was adjusted for maternal education, maternal age, parity, history of fetal loss, having at least eight antenatal contacts, hospital of delivery, child sex, and birth weight. Antenatally, 34.8% (184/529) of mothers intended to breastfeed exclusively until 6 months and 30.8% (84/274) underwent cesarean section for a nonmedical reason. After adjusting for other factors, mothers who intended to breastfeed exclusively until 6 months were less likely to undergo cesarean delivery for nonmedical reasons (OR = 0.55, 95% CI: 0.31-0.96, p = 0.034). This study adds to the growing evidence related to unnecessary cesarean sections and routine over-medicalization of normal birth in the urban areas of Vietnam. The association between breastfeeding intentions and a lower rate of cesarean section suggests that education on breastfeeding could be a useful intervention for reducing the rate of cesarean sections and improving maternal and child health.


Transcription of the pain-related TRPV1 gene requires Runx1 and C/EBPβ factors.
Transient Receptor Potential Vanilloid type 1 channel (TRPV1) is an important endogenous transducer of noxious heat and chemical stimuli and is required during development of inflammatory hypersensitivity. The transcription factor Runx1 is known to play a relevant role in sensory neuron differentiation as it controls the expression of several sensory nociceptive receptors, including TRPV1. Here, we show that Runx1 up-regulates TRPV1 transcription activity by interacting directly with the proximal TRPV1 gene promoter sequence. Importantly, C/EBPβ a well-established heterodimer partner of Runx1 also binds to the TRPV1 promoter and cooperates with Runx1 to further stimulate TRPV1 transcription. Our results support a mechanism where Runx1-C/EBPβ-containing transcription regulatory complexes are recruited to the TRPV1 gene promoter to modulate TRPV1 expression in dorsal root ganglia neurons.


BAC-probes applied for characterization of fragile sites (FS).
Genomic instability tends to occur at specific genomic regions known as common fragile sites (FS). FS are evolutionarily conserved and generally involve late replicating regions with AT-rich sequences. The possible correlation between some FS and cancer-related breakpoints emphasizes on the importance of understanding the mechanisms of chromosomal instability at these sites. Although about 230 FS have already been mapped cytogenetically, only a few of them have been characterized on a molecular level. In this chapter, we provide a protocol for mapping of common FS using bacterial artificial chromosome (BAC) probes in fluorescence in situ hybridization (FISH) and suggest the usage of lymphocytes from Fanconi anemia patients as a model system. In the latter, rare FS are expressed much more frequently than in, for example, aphidicolin-induced blood lymphocyte preparations. Knowing the exact location of FS enables the molecular comparison of their location and breakpoints that appear during evolution, cancer development and inherited disorders.


Expression Levels of Glutathione S-Transferase and Cytochrome P450 Isoenzymes in Nasal Polyp Tissue.
Nasal polyps are benign sinonasal masses composed of eosinophils and extracellular edema. Pathogenesis of the polyp formation is unclear but several studies strongly suggest a correlation with infection, inflammation and allergy conditions. Our aim is to investigate the potential link between allergy and nasal polyp in tissue level. Nasal polyp group included 60 patients whose diagnosis was confirmed with biopsy and the control group included 38 healthy patients. Tissue sample of the control group was taken from inferior turbinate mucosa under local anesthesia and nasal polyp tissue was collected from functional endoscopic sinus surgery. The glutathione S-transferase (GST) and cytochrome P450 (CYP) isoenzyme expressions of the tissue samples were investigated under light microscopy and graded by a senior pathologist. GSTP1 protein expression was significantly higher in tissue samples from nasal polyp group compared to that of control group (p < 0.05). However, CYP1A1, GSTM1 and GSTA1 isoenzymes were not different between the two groups (p > 0.05). We have found that GSTP1 isoenzyme was elevated in nasal polyp tissue compared to the control. The increase in protein expression of GSTP1 might have occured as a tissue response to the increased oxidative stress thus suggesting a role of GSTP1 in polyp formation.


[Critical mass, explosive participation at the Max-Planck Institute about research of the living conditions of the scientific-technical world in Starnberg].
Reviewers of the Max-Planck-Institut zur Erforschung der Lebensbedingungen der wissenschaftlich-technischen Welt (MPIL) did focus upon an abundance of vague reports of evaluative commissions, of benchmarking, of scientific modes. Thus it remained rather neglected, what staff actually had researched. An example: Progression and end of project AKR (Work-Consumption-Assessment) does display all kinds of related emotions at MPIL, and the sensitive guidance by Carl Friedrich von Weizsäcker.