N-terminal Pro-B-type natriuretic peptide and its correlation to haemodialysis-induced myocardial stunning.
Haemodialysis (HD) is able to induce recurrent myocardial ischemia and segmental left-ventricular dysfunction (myocardial stunning). The association of N-terminal Pro-B-type natriuretic peptide (NTpro-BNP) with HD-induced myocardial stunning is unclear. In 70 prevalent HD patients, HD-induced myocardial stunning was assessed echocardiographically at baseline and after 12 months. The extent to which pre-dialysis NTpro-BNP was associated with the occurrence of HD-induced myocardial stunning was assessed as the primary endpoint. The median Ntpro-BNP concentration in this cohort was 2,154 pg/ml (IQR 1,224-3,014). Patients experiencing HD-induced myocardial stunning at either time point displayed elevated NTpro-BNP values (2,418 pg/ml, IQR, 1,583-3,474 vs. 1,751 pg/ml, IQR (536-2,029), p = 0.02). NTpro-BNP levels did not differ between patients showing HD-induced stunning at baseline and those developing stunning during the observational period (p = 0.8). NTpro-BNP levels drawn at the beginning of the dialysis session achieved a poor diagnostic accuracy for the detection of myocardial stunning (area under the ROC curve 0.61, 95% CI 0.45-0.77), but provided an accurate rule out for myocardial stunning during the subsequent year (AUC 0.85, 95% CI 0.70-0.99). The calculated cut-off of 1,570 pg/ml achieved a sensitivity of 66% and a specificity of 78% for the exclusion of myocardial stunning at any time point. In logistic regression analysis, only low NTpro-BNP levels (OR 0.92 for every additional 100 pg/ml, 95% CI 0.85-0.99, p = 0.03) were significantly associated with absence of myocardial stunning at any time point. Predialytic NTpro-BNP levels fail to adequately diagnose current dialysis-induced myocardial stunning, but help to identify patients with a propensity to develop dialysis-induced myocardial stunning at any time during the next 12 months.


Temperature and Embryonic Development in Relation to Spawning and Field Occurrence of Larvae of Three Antarctic Echinoderms.
The effects of temperature on development and viability were measured at 14 levels between -2{deg}C and +3{deg}C on embryos of two asteroids (Odontaster validus and Odontaster meridionalis) and an echinoid (Sterechinus neumayeri) from Signy Island, Antarctica. Development rates were 2 to 10 times slower than those for temperate or tropical echinoderms, with times to hatching up to 240 h. Development rates for the two asteroids differed by 1.15 x, and rates for both species approximately doubled over the experimental temperature range. In O. validus, embryo viability was independent of temperature, but in O. meridionalis viability declined with increasing temperature. Development rates for S. neumayeri were little affected by temperature above +0.2{deg}C, but declined rapidly at lower temperatures. Conversely, the number of nonviable eggs was low and constant below +1.7{deg}C, but rose rapidly at higher temperatures. A window of optimal temperature, between +0.2{deg}C and +1.7{deg}C, has therefore been proposed for development time and embryo viability in this population of S. neumayeri. Spawning trials and field observations of larvae indicated that the time of gamete release and periods of larval development in S. neumayeri coincided with austral summer sea temperatures in the same window. Embryos of O. meridionalis and O. validus are released in winter, when temperatures are constantly below -1.6{deg}C. Comparison of the different strategies suggests that larval food supply and predation during planktonic phases are not the dominant ecological factors for these species.


Diabetes Knowledge Among Adults with Serious Mental Illness and Comorbid Diabetes Mellitus.
This study examined the association between psychiatric symptoms and diabetes knowledge (DK) among 90 adults with serious mental illness (SMI) and type 2 diabetes. The relationship between DK and glucose control (i.e., A1C) was also examined. In a hierarchical linear regression, greater negative symptom severity and lower cognitive functioning both predicted lower DK, though cognitive functioning superseded negative symptom severity when analyzed simultaneously. A Pearson correlation showed no significant relationship between DK and A1C. Although symptom severity and cognitive functioning are both related to DK among this population, cognitive functioning maybe particularly important.


Competition for zinc binding in the host-pathogen interaction.
Due to its favorable chemical properties, zinc is used as a structural or catalytic cofactor in a very large number of proteins. Despite the apparent abundance of this metal in all cell types, the intracellular pool of loosely bound zinc ions available for biological exchanges is in the picomolar range and nearly all zinc is tightly bound to proteins. In addition, to limit bacterial growth, some zinc-sequestering proteins are produced by eukaryotic hosts in response to infections. Therefore, to grow and multiply in the infected host, bacterial pathogens must produce high affinity zinc importers, such as the ZnuABC transporter which is present in most Gram-negative bacteria. Studies carried in different bacterial species have established that disruption of ZnuABC is usually associated with a remarkable loss of pathogenicity. The critical involvement of zinc in a plethora of metabolic and virulence pathways and the presence of very low number of zinc importers in most bacterial species mark zinc homeostasis as a very promising target for the development of novel antimicrobial strategies.


Confinement and Exciton Binding Energy Effects on Hot Carrier Cooling in Lead Halide Perovskite Nanomaterials.
The relaxation of the above-gap ("hot") carriers in lead halide perovskites (LHPs) is important for applications in photovoltaics and offers insights into carrier-carrier and carrier-phonon interactions. However, the role of quantum confinement in the hot carrier dynamics of nanosystems is still disputed. Here, we devise a single approach, ultrafast pump-push-probe spectroscopy, to study carrier cooling in six different size-controlled LHP nanomaterials. In cuboidal nanocrystals, we observe only a weak size effect on the cooling dynamics. In contrast, two-dimensional systems show suppression of the hot phonon bottleneck effect common in bulk perovskites. The proposed kinetic model describes the intrinsic and density-dependent cooling times accurately in all studied perovskite systems using only carrier-carrier, carrier-phonon, and excitonic coupling constants. This highlights the impact of exciton formation on carrier cooling and promotes dimensional confinement as a tool for engineering carrier-phonon and carrier-carrier interactions in LHP optoelectronic materials.


Traumatic Enthesophyte From a Chronic Pectoralis Major Tendon Rupture: A Case Report.
A 24-year-old active duty soldier with a chronic pectoralis major tendon rupture presented a year later with a bony lesion consistent with an enthesophyte at the humeral insertion. The patient continued to have pain that was affecting his activities of daily living and underwent surgical intervention. Operative management with enthesophyte excision and pectoralis major tendon repair provided relief to the patient's symptoms and return to preinjury levels of function as evaluated with Tegner, single assessment numeric evaluation, and visual analog scale scores at the 2-year follow-up.


Highly enantioselective conjugate addition of diethylzinc to acyclic enones with fine-tunable phosphite-pyridine ligands.
A new series of fine-tunable phosphite-pyridine (P,N) ligands derived from (S)-2-amino-2'-hydroxy-6,6'-dimethyl-1,1'-biphenyl and (S)-2-amino-2'-hydroxy-4,4',6,6'-tetramethyl-1,1'-biphenyl was employed in Cu(I)-catalyzed conjugate addition of diethylzinc to acyclic enones. Excellent enantioselectivities (up to 98% ee) and highly catalytic activities were achieved for a variety of acyclic enones.


Strength and Electrical Properties of Cementitious Composite with Integrated Carbon Nanotubes.
The main objective of this work was to study the effects of carbon nanotubes (CNTs) on the strength and electrical properties of cement mortar. Molecular dynamic simulations (MDSs) were carried out to determine the mechanical and electrical properties of a cementitious composite and its associated mechanisms. To model the atomic structure of a calcium silicate hydrate (C-S-H) gel, tobermorite 11Å was chosen. Single-walled carbon nanotubes (SWCNTs) embedded in a tobermorite structure were tested numerically. In particular, it was concluded that a piezoelectric effect can be effectively simulated by varying the concentration levels of carbon nanotubes. The deformation characteristics were analyzed by subjecting a sample to an electrical field of 250 MV/m in the z-direction in a simulation box. The results indicated a progressively stronger converse piezoelectric response with an increasing proportion of carbon nanotubes. Additionally, it was observed that the piezoelectric constant in the z-direction, denoted by d33, also increased correspondingly, thereby validating the potential for generating an electrical current during sample deformation. An innovative experiment was developed for the electrical characterization of a cementitious composite of carbon nanotubes. The results showed that the electrostatic current measurements exhibited a higher electric sensitivity for samples with a higher concentration of CNTs.


Genetic differences affecting the potency of stereoisomers of halothane.
The mechanism of action of volatile anesthetics is the subject of some debate. Much of the controversy has centered on whether the site of such actions is purely lipid in nature or may contain a protein target. This report studies the interaction of stereoisomers of halothane on the wild type and on a variety of genetic mutants of Caenorhabditis elegans. The mutants studied have previously been shown to have altered sensitivities to volatile anesthetics. In one mutant, fc34, (R)-halothane [the (+) isomer] was 3 times more potent than its S (-) isomer. Other mutants and wild-type animals displayed more modest differences in sensitivity to the enantiomers. The results indicate that a genetic pathway exists in C. elegans controlling sensitivity to halothane and that both lipid and protein targets may mediate halothane's effects.


Induced Fetal Human Muscle Stem Cells with High Therapeutic Potential in a Mouse Muscular Dystrophy Model.
Duchenne muscular dystrophy (DMD) is a progressive and fatal muscle-wasting disease caused by DYSTROPHIN deficiency. Cell therapy using muscle stem cells (MuSCs) is a potential cure. Here, we report a differentiation method to generate fetal MuSCs from human induced pluripotent stem cells (iPSCs) by monitoring MYF5 expression. Gene expression profiling indicated that MYF5-positive cells in the late stage of differentiation have fetal MuSC characteristics, while MYF5-positive cells in the early stage of differentiation have early myogenic progenitor characteristics. Moreover, late-stage MYF5-positive cells demonstrated good muscle regeneration potential and produced DYSTROPHIN in vivo after transplantation into DMD model mice, resulting in muscle function recovery. The engrafted cells also generated PAX7-positive MuSC-like cells under the basal lamina of DYSTROPHIN-positive fibers. These findings suggest that MYF5-positive fetal MuSCs induced in the late stage of iPSC differentiation have cell therapy potential for DMD.


3D echocardiography in congenital heart disease: a valuable tool for the surgeon.
Real-time 3D echocardiography has been used increasingly in the assessment of patients with congenital heart disease. A number of studies have confirmed that this modality can be used as a complementary method to delineate morphology and spatial relationships of simple and more complex congenital heart lesions during surgical planning. Communication between the echocardiographer and surgeon can be simplified as simulation of surgical views can be achieved, thus minimizing the potential for error related to mental reconstruction. This review summarizes the available evidence for the role of real-time 3D echocardiography in congenital heart disease as an imaging modality to assist surgeons.


Human papillomavirus prevalence in paired urine and cervical samples in women invited for cervical cancer screening.
With the introduction of Human papillomavirus (HPV) vaccination in young girls in 2007, it is important to monitor HPV infections and epidemiological changes in this target population. The present study has evaluated the detection of human papillomavirus DNA in paired cervical and urine samples to understand if HPV testing in urine could be used as non-invasive method to monitor HPV status in young women. The study enrolled 216 twenty five-year-old women, resident in Florence and invited for the first time to the cervical cancer Screening Program within a project evaluating the impact of HPV vaccination. HPV genotyping was performed on 216 paired urine and cervical samples. The overall concordance between cervix and urine samples, investigated by HPV genotyping (INNO-LiPA HPV Genotyping Extra), was: 85.6% (184/215), 84.6% (182/215), 80% (172/215) when the same HPV, at least the same HR HPV and all HR HPV, respectively, were detected. HPV type specific concordance in paired urine and cervical samples was observed in 85.8% (175/204) of women with normal cytology and in seven out of nine women with abnormal cytology. Urine seems to be a suitable and reliable biological material for HPV DNA detection as evidenced by the high concordance with HPV detected in cervical samples. These results suggest that urine could be a good noninvasive tool to monitor HPV infection in vaccinated women.


Methylglyoxal, a glycolysis metabolite, triggers metastasis through MEK/ERK/SMAD1 pathway activation in breast cancer.
Elevated aerobic glycolysis rate is a biochemical alteration associated with malignant transformation and cancer progression. This metabolic shift unavoidably generates methylglyoxal (MG), a potent inducer of dicarbonyl stress through the formation of advanced glycation end products (AGEs). We have previously shown that the silencing of glyoxalase 1 (GLO1), the main MG detoxifying enzyme, generates endogenous dicarbonyl stress resulting in enhanced growth and metastasis in vivo. However, the molecular mechanisms through which MG stress promotes metastasis development remain to be unveiled. In this study, we used RNA sequencing analysis to investigate gene-expression profiling of GLO1-depleted breast cancer cells and we validated the regulated expression of selected genes of interest by RT-qPCR. Using in vitro and in vivo assays, we demonstrated the acquisition of a pro-metastatic phenotype related to dicarbonyl stress in MDA-MB-231, MDA-MB-468 and MCF7 breast cancer cellular models. Hyperactivation of MEK/ERK/SMAD1 pathway was evidenced using western blotting upon endogenous MG stress and exogenous MG treatment conditions. MEK and SMAD1 regulation of MG pro-metastatic signature genes in breast cancer cells was demonstrated by RT-qPCR. High-throughput transcriptome profiling of GLO1-depleted breast cancer cells highlighted a pro-metastatic signature that establishes novel connections between MG dicarbonyl stress, extracellular matrix (ECM) remodeling by neoplastic cells and enhanced cell migration. Mechanistically, we showed that these metastasis-related processes are functionally linked to MEK/ERK/SMAD1 cascade activation in breast cancer cells. We showed that sustained MEK/ERK activation in GLO1-depleted cells notably occurred through the down-regulation of the expression of dual specificity phosphatases in MG-stressed breast cancer cells. The use of carnosine and aminoguanidine, two potent MG scavengers, reversed MG stress effects in in vitro and in vivo experimental settings. These results uncover for the first time the key role of MG dicarbonyl stress in the induction of ECM remodeling and the activation of migratory signaling pathways, both in favor of enhanced metastatic dissemination of breast cancer cells. Importantly, the efficient inhibition of mitogen-activated protein kinase (MAPK) signaling using MG scavengers further emphasizes the need to investigate their therapeutic potential across different malignancies.


Tumor promoting effect of goitrogens on the rat thyroid.
To evaluate the mechanism of the promoting effect of goitrogens on thyroid tumorigenesis, well-known goitrogens having different pharmacologic action, i.e., thiourea, phenobarbital sodium (PB), potassium thiocyanate (KSCN), and 3,4,5,6-tetrachloro-2',4',5',7'-tetraiodo-fluorescein sodium salt (Rose Bengal B, FD&C Red No. 105) (FR105) were administered to the DHPN-initiated and non-initiated F344 male rats in the drinking water for 25 weeks. Remington's iodine deficient diet (I-def) was fed as a positive control. These goitrogens showed significant tumor promoting effect or promoting tendency on the rat thyroids. According to the changes in thyroid morphology and thyroid-related hormone titers observed in the present study, we proposed to classify goitrogens at least into 2 groups, i.e., iodine deficiency-type promoters and the iodine excess-type promoters. The former contains goitrogens inducing TSH-stimulated diffuse goiter composed of uniform follicles with activated tall follicular epithelial cells, such as thiourea, KSCN and PB, and the latter contains goitrogens inducing colloid goiter composed of a mixture of colloid-rich follicles with flat follicular cells and normal-looking follicles with cuboidal follicular cells, such as FR105. This classification may be useful for the risk assessment of goitrogens.


Colorectal cancer-related mutant KRAS alleles function as positive regulators of autophagy.
The recent interest to modulate autophagy in cancer therapy has been hampered by the dual roles of this conserved catabolic process in cancer, highlighting the need for tailored approaches. Since RAS isoforms have been implicated in autophagy regulation and mutation of the KRAS oncogene is highly frequent in colorectal cancer (CRC), we questioned whether/how mutant KRAS alleles regulate autophagy in CRC and its implications. We established two original models, KRAS-humanized yeast and KRAS-non-cancer colon cells and showed that expression of mutated KRAS up-regulates starvation-induced autophagy in both. Accordingly, KRAS down-regulation inhibited autophagy in CRC-derived cells harboring KRAS mutations. We further show that KRAS-induced autophagy proceeds via up-regulation of the MEK/ERK pathway in both colon models and that KRAS and autophagy contribute to CRC cell survival during starvation. Since KRAS inhibitors have proven difficult to develop, our results suggest using autophagy inhibitors as a combined/alternative therapeutic approach in CRCs with mutant KRAS.


New protein deposition tracers in the pipeline.
Traditional nuclear medicine ligands were designed to target cellular receptors or transporters with a binding pocket and a defined structure-activity relationship. More recently, tracers have been developed to target pathological protein aggregations, which have less well-defined structure-activity relationships. Aggregations of proteins such as tau, α-synuclein, and β-amyloid (Aβ) have been identified in neurodegenerative diseases, including Alzheimer's disease (AD) and other dementias, and Parkinson's disease (PD). Indeed, Aβ deposition is a hallmark of AD, and detection methods have evolved from coloured dyes to modern 18F-labelled positron emission tomography (PET) tracers. Such tracers are becoming increasingly established in routine clinical practice for evaluation of Aβ neuritic plaque density in the brains of adults who are being evaluated for AD and other causes of cognitive impairment. While similar in structure, there are key differences between the available compounds in terms of dosing/dosimetry, pharmacokinetics, and interpretation of visual reads. In the future, quantification of Aβ-PET may further improve its utility. Tracers are now being developed for evaluation of tau protein, which is associated with decreased cognitive function and neurodegenerative changes in AD, and is implicated in the pathogenesis of other neurodegenerative diseases. While no compound has yet been approved for tau imaging in clinical use, it is a very active area of research. Development of tau tracers comprises in-depth characterisation of existing radiotracers, clinical validation, a better understanding of uptake patterns, test-retest/dosimetry data, and neuropathological correlations with PET. Tau imaging may allow early, more accurate diagnosis, and monitoring of disease progression, in a range of conditions. Another marker for which imaging modalities are needed is α-synuclein, which has potential for conditions including PD and dementia with Lewy bodies. Efforts to develop a suitable tracer are ongoing, but are still in their infancy. In conclusion, several PET tracers for detection of pathological protein depositions are now available for clinical use, particularly PET tracers that bind to Aβ plaques. Tau-PET tracers are currently in clinical development, and α-synuclein protein deposition tracers are at early stage of research. These tracers will continue to change our understanding of complex disease processes.


Correlation of healing capacity with vascular response in the anterior cruciate and medial collateral ligaments of the rabbit.
In clinical terms, functional recovery after anterior cruciate ligament (ACL) injury is generally poorer than after medial collateral ligament (MCL) injury. In experimental studies of injury, the early phases of ligament healing require an augmented blood supply. We hypothesized that the differences in healing properties of the ACL and MCL would be reflected in the magnitude of their vascular responses to partial injury. This study is the first to quantify and define the time course of changes in blood flow and vascular volume following hemisection of the rabbit ACL and MCL. Adult female rabbits were assigned to control, sham operation, ACL hemisection or MCL hemisection groups. Standardized ACL or MCL injuries were surgically induced. About 2, 6 or 16 weeks later, blood flow and vascular volume of the ACL and MCL were measured. The MCL of the rabbit responded to hemisection with a large significant increase in blood flow and a substantial angiogenic response associated with inflammation and scar formation. During subsequent matrix remodelling, blood flow and vascular volume returned towards control values. In contrast, the ACL showed only a 2-fold increase in vascular volume, no increase in blood flow and atrophied after hemisection. The superior capacity of the MCL to increase its blood supply through angiogenesis and increased flow is essential for ligament healing to occur, and may be the major difference in healing potential between the ACL and MCL.


What drives bacteria to produce a biofilm?
Nearly 40 years ago, Dr. R.J. Gibbons made the first reports of the clinical relevance of what we now know as bacterial biofilms when he published his observations of the role of polysaccharide glycocalyx formation on teeth by Streptococcus mutans [Sci. Am. 238 (1978) 86]. As the clinical relevance of bacterial biofilm formation became increasingly apparent, interest in the phenomenon exploded. Studies are rapidly shedding light on the biomolecular pathways leading to this sessile mode of growth but many fundamental questions remain. The intent of this review is to consider the reasons why bacteria switch from a free-floating to a biofilm mode of growth. The currently available wealth of data pertaining to the molecular genetics of biofilm formation in commonly studied, clinically relevant, single-species biofilms will be discussed in an effort to decipher the motivation behind the transition from planktonic to sessile growth in the human body. Four potential incentives behind the formation of biofilms by bacteria during infection are considered: (1) protection from harmful conditions in the host (defense), (2) sequestration to a nutrient-rich area (colonization), (3) utilization of cooperative benefits (community), (4) biofilms normally grow as biofilms and planktonic cultures are an in vitro artifact (biofilms as the default mode of growth).


Relapsing polychondritis with p-ANCA associated vasculitis: Which triggers the other?
Relapsing polychondritis (RP) is a rare autoimmune disease with chronic inflammatory/destructive lesions of the cartilaginous tissues. In one third of the cases it is associated with other autoimmune disorders, mostly with anti-neutrophil cytoplasmic antibody (ANCA) associated vasculitis (AAV). We report three cases of RP with p-ANCA positive AAV. In the first patient RP developed 1.5 years after the onset of AAV. In the others the signs of RP were present before the onset of severe crescent glomerulonephritis. Patients responded well on steroid and cyclophosphamide. In dialysis dependent cases plasmapheresis was also used successfully. During the 2 and 1.5 years of follow up, they were symptom-free, and had stable glomerular filtration rate. The first patient died after four years of follow-up due to the complications of sudden unset pancytopenia, which raises the possibility of associated hemophagocytic syndrome. In the setting of RP or AAV physicians should always be aware of the possibility of sudden or insidious appearance of the other disease.


A particularly complex case of matricide by means of plastic bag suffocation: Case report.
A rare case of homicide with plastic bag suffocation is presented in which forensic genetic investigations were carried out on the inner surface of a plastic bag placed over the head of an elderly woman, bedridden after a stroke. The results obtained suggested that she had been murdered and hinted at the perpetrator of the crime. In fact, it emerged that biological traces left by the victim matched those of her principal caregiver, her psychotic daughter, who later confessed to the crime. The old woman also had a son affected by a serious illness, whose genetic profile was found on the same bag. In a later interview, he stated that his sister had tried to kill him too, thus confirming the genetic findings and allowing the investigators to hypothesise that the daughter had used the same means to try to kill him. Based on these results, the usefulness of forensic genetic testing when investigating complex plastic bag suffocation deaths is highlighted. This peculiar case deserves interest, since no murder of this kind has ever been reported in the Italian forensic literature.


Metabolic Abnormalities, Inflammatory Markers and Endothelial Dysfunction in Hyperprolactinemia due to Prolactinoma before and after Normalization of Serum Prolactin: A Prospective Case Control Study.
Hyperprolactinemia is associated with obesity, dyslipidemia, insulin resistance, and low-grade inflammation which may promote endothelial dysfunction (EnD). Limited work has been done on EnD in prolactinomas and we, therefore, studied serum markers of inflammation and EnD in patients with prolactinomas before and after treatment with dopamine agonists. Fifty-six treatment naïve patients with prolactinomas and fifty-three (apparently healthy age and sex-matched) controls were enrolled in the study and subjected to clinical assessment and laboratory investigations including blood glucose, total cholesterol, triglycerides, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, urea, creatinine, uric acid, erythrocyte sedimentation rate (ESR), highly sensitive C-reactive protein (hsCRP) and markers of EnD i.e., intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1 (VCAM-1). Patients were treated with a dopamine agonist (cabergoline) and parameters (like ESR, hsCRP, ICAM-1, and VCAM-1) were measured at 12 weeks. The majority of the patients (84%) were female, more than half (52%) had metabolic syndrome and over a third (36%) were obese. Blood glucose fasting, HbA1c, lipid fractions, ESR, hsCRP, ICAM-1, and VCAM-1 were significantly higher in patients than in controls. Median ICAM-1 was 1331.95 ng/ml (IQR 803.43-1825.99) in patients vs 753.04 ng/ml (IQR 402.04-871.55) in controls, P < 0.001 and median VCAM-1in patients was 971.35 ng/ml (IQR 695.03-1285.23) as against 634.56 ng/ml (IQR 177.49-946.50) in controls, p0.001. Serum ICAM-1 and VCAM-1 correlated positively with hsCRP. On multivariate regression analysis, serum hsCRP was the only significant predictor of change in ICAM-1 and VCAM-1. Normalization of serum PRL with CAB resulted in a significant decrease in metabolic parameters, ESR, hsCRP, ICAM-1, and VCAM-1. Hyperprolactinemia because of prolactinoma is associated with EnD secondary to systemic inflammation and metabolic abnormalities which improve after treatment with DA.


[Hygienic assessment of a recirculatory combined air-conditioning extract-and-input system in office building].
The high concentrations of lead were reveled in the air and dust of some premises and on the filters of a combined air-conditioning extract-and-input system in the high-rise office buildings located in the ecologically lead favorable environment. The dust content of lead in some premises on the first floors dust was as high as 200 mg/kg, which was more than 6 times higher than that in the soil at the highway near the office buildings. The use of new technologies and devices for cleaning and optimizing the air in the premises requires analytical studies to assess the quality of the environment, by taking into account the optimal conditions of their operation.


Injury Characteristics of Low-Energy Lisfranc Injuries Compared With High-Energy Injuries.
Lisfranc injuries result from high- and low-energy mechanisms though the literature has been more focused on high-energy mechanisms. A comparison of high-energy (HE) and low-energy (LE) injury patterns is lacking. The objective of this study was to report injury patterns in LE Lisfranc joint injuries and compare them to HE injury patterns. Operative Lisfranc injuries were identified over a 5-year period. Patient demographics, mechanism of injury, injury pattern, associated injuries, missed diagnoses, clinical course, and imaging studies were reviewed and compared. HE mechanism was defined as motor vehicle crash, motorcycle crash, direct crush, and fall from greater than 4 feet and LE mechanism as athletic activity, ground level twisting, or fall from less than 4 feet. Thirty-two HE and 48 LE cases were identified with 19.3 months of average follow-up. There were no differences in demographics or missed diagnosis frequency (21% HE vs 18% LE). Time to seek care was not significantly different. HE injuries were more likely to have concomitant nonfoot fractures (37% vs 6%), concomitant foot fractures (78% vs 4%), cuboid fractures (31% vs 6%), metatarsal base fractures (84% vs 29%), displaced intra-articular fractures (59% vs 4%), and involvement of all 5 rays (23% vs 6%). LE injuries were more commonly ligamentous (68% vs 16%), with fewer rays involved (2.7 vs 4.1). LE mechanisms were a more common cause of Lisfranc joint injury in this cohort. These mechanisms generally resulted in an isolated, primarily ligamentous injury sparing the lateral column. Both types had high rates of missed injury that could result in delayed treatment. Differences in injury patterns could help direct future research to optimize treatment algorithms. Level III, comparative series.


A flotation/sieving method to detect Echinococcus multilocularis and Toxocara spp. eggs in soil by real-time PCR.
Soil can be a source of human infection by many zoonotic helminth species including Echinococcus multilocularis and Toxocara spp. The prevention of alveolar echinococcosis could be greatly improved through the identification of at-risk areas. Yet very few data are available about the detection of E. multilocularis in soil, while more studies have been reported for Toxocara spp. Identification of soil contamination by E. multilocularis eggs requires the use of specific methods. This study describes the development of a method for the detection of E. multilocularis in soil samples with the concentration of eggs using a flotation/sieving method and detection by duplex real-time polymerase chain reaction (PCR). Toxocara spp. egg detection was also undertaken due to the widespread presence of this parasite in soil, despite it being considered less pathogenic. Method sensitivity of 100% was reached for the detection of 10 E. multilocularis eggs spiked in 10 g of soil. Concerning Toxocara spp., method sensitivity was lower but assumed to be due to the reduced effectiveness of the DNA extraction protocol. The parasitological status for E. multilocularis and Toxocara spp. of 63 carnivore fecal samples collected in highly endemic rural areas of France and of soil samples collected under and near these fecal samples was compared. The contamination of soil samples collected under positive fecal samples for E. multilocularis (n = 3) or Toxocara spp. (n = 19) confirmed the transfer of eggs from the definitive host to the environment.


Glycemic control and coronary heart disease risk in persons with and without diabetes: the atherosclerosis risk in communities study.
Chronic hyperglycemia has been hypothesized to contribute to coronary heart disease (CHD), but the extent to which hemoglobin A(1c) (HbA(1c)) level, a marker of long-term glycemic control, is independently related to CHD risk is uncertain. We conducted a prospective case-cohort study of 1321 adults without diabetes and a cohort study of 1626 adults with diabetes from the Atherosclerosis Risk in Communities Study. Using proportional hazards models, we assessed the relation between HbA(1c) level and incident CHD during 8 to 10 years of follow-up. In adults with diabetes, the relative risk (RR) of CHD was 2.37 (95% confidence interval [CI], 1.50-3.72) for the highest quintile of HbA(1c) level compared with the lowest after adjustment for CHD risk factors. In persons without diabetes, the adjusted RR of CHD in the highest quintile of HbA(1c) level was 1.41 (95% CI, 0.90-2.30); however, there was evidence of a nonlinear relationship in this group. In nondiabetic adults, HbA(1c) level was not related to CHD risk below a level of 4.6% but was significantly related to risk above that level (P<.001). In diabetic adults, the risk of CHD increased throughout the range of HbA(1c) levels. In the adjusted model, the RR of CHD for a 1-percentage point increase in HbA(1c) level was 2.36 (95% CI, 1.43-3.90) in persons without diabetes but with an HbA(1c) level greater than 4.6%. In diabetic adults, the RR was 1.14 (95% CI, 1.07-1.21) per 1-percentage point increase in HbA(1c) across the full range of HbA(1c) values. Elevated HbA(1c) level is an independent risk factor for CHD in persons with and without diabetes.


p600/UBR4 in the central nervous system.
A decade ago, the large 600 kDa mammalian protein p600 (also known as UBR4) was discovered as a multifunctional protein with roles in anoikis, viral transformation and protein degradation. Recently, p600 has emerged as a critical protein in the mammalian brain with roles in neurogenesis, neuronal migration, neuronal signaling and survival. How p600 integrates these apparently unrelated functions to maintain tissue homeostasis and murine survival remains unclear. The common molecular basis underlying many of the actions of p600 suggests, however, certain conservation and transposition of these functions across systems. In this review, we summarize the central nervous system functions of p600 and propose new perspectives on its biological complexity in neuronal physiology and neurological diseases.


The regressive effect of an angiotensin II receptor blocker on formed fatty streaks in monkeys fed a high-cholesterol diet.
To clarify the regressive effect of an angiotensin II type 1 receptor blocker (ARB) on already formed fatty streaks, we investigated the effect of the administration of an ARB, olmesartan, on formed fatty streaks in monkeys fed a high-cholesterol diet. After the monkeys were fed a high-cholesterol diet for 6 months, intimal hyperplasia was clearly observed on intravascular ultrasound. For the next 6 months, the high-cholesterol diet was continued, and olmesartan (3 mg/kg per day) or placebo was administered. A control group was fed a normal diet for 12 months. Olmesartan did not significantly affect blood pressure or plasma cholesterol levels throughout the experiment. After 6 months of treatment with olmesartan, intimal hyperplasia was significantly lower than before treatment. Acetylcholine-induced relaxation in isolated carotid arteries was significantly less in the high-cholesterol diet placebo-treated group compared to the normal diet group, whereas its response was improved by olmesartan. Serum levels of monocyte chemoattractant protein were significantly increased with a high cholesterol load, but they were significantly suppressed by olmesartan. We have demonstrated for the first time that an ARB, olmesartan, was found to have a regressive effect on formed fatty streaks in monkeys.


Systemic injection of AAV9-GDNF provides modest functional improvements in the SOD1G93A ALS rat but has adverse side effects.
Injecting proteins into the central nervous system that stimulate neuronal growth can lead to beneficial effects in animal models of disease. In particular, glial cell line-derived neurotrophic factor (GDNF) has shown promise in animal and cell models of Parkinson's disease, Huntington's disease and amyotrophic lateral sclerosis (ALS). Here, systemic AAV9-GDNF was delivered via tail vein injections to young rats to determine whether this could be a safe and functional strategy to treat the SOD1G93A rat model of ALS and, therefore, translated to a therapy for ALS patients. We found that GDNF administration in this manner resulted in modest functional improvement, whereby grip strength was maintained for longer and the onset of forelimb paralysis was delayed compared to non-treated rats. This did not, however, translate into an extension in survival. In addition, ALS rats receiving GDNF exhibited slower weight gain, reduced activity levels and decreased working memory. Collectively, these results confirm that caution should be applied when applying growth factors such as GDNF systemically to multiple tissues.


Atorvastatin inhibits osteoclast differentiation by suppressing NF-κB and MAPK signaling during IL-1β-induced osteoclastogenesis.
To define the effect of statins on interleukin 1β (IL-1β)-induced osteoclastogenesis and elucidate the underlying mechanisms. Bone marrow cells were obtained from 5-week-old male ICR (Institute for Cancer Research) mice, and they were cultured to differentiate them into osteoclasts with macrophage colony-stimulating factor and the receptor activator of nuclear factor (NF)-κB ligand in the presence or absence of IL-1β or atorvastatin. The formation of osteoclasts was evaluated by tartrate-resistant acid phosphatase (TRAP) staining and resorption pit assay with dentine slice. The molecular mechanisms of the effects of atorvastatin on osteoclastogenesis were investigated using reverse transcription polymerase chain reaction and immunoblotting for osteoclast specific molecules. Atorvastatin significantly reduced the number of TRAP-positive multinucleated cells as well as the bone resorption area. Atorvastatin also downregulated the expression of the NF of activated T-cell c1 messenger RNA and inhibited the expression of osteoclast-specific genes. A possible underlying mechanism may be that atorvastatin suppresses the degradation of the inhibitors of NF-κB and blocks the activation of the c-Jun N-terminal kinase, extracellular signal-regulated kinase, and p38; thus, implicating the NF-κB and mitogen-activated protein kinases pathway in this process. Atorvastatin is a strong inhibitor of inflammation-induced osteoclastogenesis in inflammatory joint diseases.


[Preface to special issue: "Molecular mechanism of the adaptation of terrestrial plants to gravity environment on Earth"].
Organisms borne in the primitive sea about 30 million years ago had evolved in water without a large influence of gravity on earth. About 4 million years ago, the first terrestrial organisms, plants appeared on the land from the sea. The terrestrial plants have adapted to and evolved on the land environment so that they can extend their roots downward in soil and their shoots upward against 1 g gravity. At least two functions that were acquired during the process of evolution helped the terrestrial plants to adapt to gravity environment on earth. One is gravitropism. The other is the reinforcement of the cell wall, particularly the secondary cell wall. In the present feature articles, the molecular mechanism of the adaptation of terrestrial plants to gravity environment on earth will be reviewed, paying special attention to the mechanism of the genetic control of the signaling of gravity stimulus in gravitropism, automorphogenesis, genes involved in auxin transport, gravity effect on cell wall properties and gravimorphogenesis in terrestrial plants.


Use of transcutaneous electrical nerve stimulation for postoperative pain.
This study examined the effects of transcutaneous electrical nerve stimulation (TENS) on incisional pain caused by the procedure of cleaning and packing an abdominal surgical wound. Seventy-five subjects (mean age 56.9 years) were randomly assigned to one of three intervention groups: TENS, placebo-TENS, or no-treatment control. The appropriate experimental treatment was administered during the routine dressing change which took place two mornings after surgery. Using an 11-point, visual analogue pain scale, subjects described pain experienced during the dressing change. Subjects who received TENS reported a significantly lower level of pain after dressing change than did those subjects who received either placebo-TENS or no-treatment. Drug administration variables did not contribute significantly to level of reported pain.


Designing modulators of monoamine transporters using virtual screening techniques.
The plasma-membrane monoamine transporters (MATs), including the serotonin (SERT), norepinephrine (NET) and dopamine (DAT) transporters, serve a pivotal role in limiting monoamine-mediated neurotransmission through the reuptake of their respective monoamine neurotransmitters. The transporters are the main target of clinically used psychostimulants and antidepressants. Despite the availability of several potent and selective MAT substrates and inhibitors the continuing need for therapeutic drugs to treat brain disorders involving aberrant monoamine signaling provides a compelling reason to identify novel ways of targeting and modulating the MATs. Designing novel modulators of MAT function have been limited by the lack of three dimensional structure information of the individual MATs. However, crystal structures of LeuT, a bacterial homolog of MATs, in a substrate-bound occluded, substrate-free outward-open, and an apo inward-open state and also with competitive and non-competitive inhibitors have been determined. In addition, several structures of the Drosophila DAT have also been resolved. Together with computational modeling and experimental data gathered over the past decade, these structures have dramatically advanced our understanding of several aspects of SERT, NET, and DAT transporter function, including some of the molecular determinants of ligand interaction at orthosteric substrate and inhibitor binding pockets. In addition progress has been made in the understanding of how allosteric modulation of MAT function can be achieved. Here we will review all the efforts up to date that has been made through computational approaches employing structural models of MATs to design small molecule modulators to the orthosteric and allosteric sites using virtual screening techniques.


Third delay in traumatic brain injury: time to management as a predictor of mortality.
Traumatic brain injury (TBI) is a global epidemic with an increasing incidence in low- and middle-income countries (LMICs). The time from arrival at the hospital to receiving appropriate treatment ("third delay") can vary widely in LMICs, although its association with mortality in TBI remains unknown. A retrospective cohort analysis with multivariable logistic regression was conducted using the Toward Improved Trauma Care Outcomes in India database, which contains data from 4 urban trauma centers in India from 2013-2015. There were 6278 TBIs included in the cohort. The patients' median age was 39 years (interquartile range 27-52 years) and 80% of patients were male. The most frequent mechanisms of injury were road traffic accidents (52%) and falls (34%). A majority of cases were transfers from other facilities (79%). In-hospital 30-day mortality was 27%; of patients who died, 21% died within 24 hours of arrival. The median third delay was 10 minutes (interquartile range 0-60 minutes); 34% of cases had moderate third delay (10-60 minutes) and 22% had extended third delay (≥ 61 minutes). Overall 30-day mortality was associated with moderate third delay (OR 1.3, p = 0.001) and extended third delay (OR 1.3, p = 0.001) after adjustment by pertinent covariates. This effect was pronounced for 24-hour mortality: moderate and extended third delays were independently associated with ORs of 3.4 and 3.8, respectively, for 24-hour mortality (both p < 0.001). Third delay is associated with early mortality in patients with TBI, and represents a target for process improvement in urban trauma centers.


A new chest compression depth feedback algorithm for high-quality CPR based on smartphone.
Although many smartphone application (app) programs provide education and guidance for basic life support, they do not commonly provide feedback on the chest compression depth (CCD) and rate. The validation of its accuracy has not been reported to date. This study was a feasibility assessment of use of the smartphone as a CCD feedback device. In this study, we proposed the concept of a new real-time CCD estimation algorithm using a smartphone and evaluated the accuracy of the algorithm. Using the double integration of the acceleration signal, which was obtained from the accelerometer in the smartphone, we estimated the CCD in real time. Based on its periodicity, we removed the bias error from the accelerometer. To evaluate this instrument's accuracy, we used a potentiometer as the reference depth measurement. The evaluation experiments included three levels of CCD (insufficient, adequate, and excessive) and four types of grasping orientations with various compression directions. We used the difference between the reference measurement and the estimated depth as the error. The error was calculated for each compression. When chest compressions were performed with adequate depth for the patient who was lying on a flat floor, the mean (standard deviation) of the errors was 1.43 (1.00) mm. When the patient was lying on an oblique floor, the mean (standard deviation) of the errors was 3.13 (1.88) mm. The error of the CCD estimation was tolerable for the algorithm to be used in the smartphone-based CCD feedback app to compress more than 51 mm, which is the 2010 American Heart Association guideline.


Intrasac fibrin glue injection after platinum coils placement: the efficacy of a simple intraoperative procedure in preventing type II endoleak after endovascular aneurysm repair.
To verify in our experience if fibrin glue injection into the aneurysm sac, made at the end of endovascular aneurysm repair (EVAR), can reduce type II endoleak rates. Between January 2005 and February 2008, 38 patients underwent EVAR for an unruptured abdominal aortic aneurysm. The first 20 consecutive patients (Group A) had standard EVAR while the last 18 patients (Group B) had EVAR with fibrin glue injection into the sac, regardless of type II endoleak's presence. There was no statistically significant difference between the two groups concerning the surgical time and the time of X-ray exposure (P=0.30 and 0.54, respectively). Type II endoleak rate was significantly higher in Group A compared to Group B (6 cases, 30% vs. 1 case, 5.5%, respectively, P=0.05). Primary short-term clinical success was 95% and 100%, respectively. At 12 months, selective lumbar embolization was performed in two patients in Group A and in one patient in Group B. Patients in Group A had less computed tomography (CT) studies than patients in Group B (2.0 vs. 1.2, respectively, P=0.024). Fibrin glue injection is a safe procedure and seems to reduce type II endoleak rates. Patients who received this procedure had fewer CT examinations, with reduced health-care costs.


Clinical Outcomes of Surgical Management of Primary Brachial Plexus Tumors.
Introduction This study evaluates the clinical presentation, tumor characteristics, and clinical outcomes of surgically treated benign and malignant brachial plexus tumors (BPTs). Methods A prospective study of patients with BPTs from June 2015 to August 2020 was conducted. All patients underwent surgical resection with microneurolysis and intraoperative electrical stimulation to preserve the functioning nerve fascicles. Results Fourteen patients with 15 BPTs underwent surgical resection. Mean age was 37.8 ± 12.3 years; with male to female ratio 4:10. The clinical presentations were swelling (100%), pain (84.6%), and paresthesia (76.9%). The lesions involved roots (5/15), trunk (5/15), division (1/15), and cords (4/15). Thirteen patients had benign pathology (8 schwannomas, 3 neurofibromas, 2 lipomas) and two had malignant neurofibrosarcoma. Gross total resection was achieved in all cases except a dumbbell tumor. The mean follow-up period was 24 ± 5 months. Postoperatively, all patients reported improvement in pain and paresthesia with no new sensory deficit. All patients had developed initial motor weakness (Grades 2-4); however, full power (Grade 5) was recovered by 3 to 5 months. Conclusion Total resection can be achieved by appropriate microneural dissection and electrophysiologic monitoring and is potentially curative with preserving function.


Differential regulation of RNA polymerases I, II, and III by the TBP-binding repressor Dr1.
RNA polymerases I, II, and III each use the TATA-binding protein (TBP). Regulators that target this shared factor may therefore provide a means to coordinate the activities of the three nuclear RNA polymerases. The repressor Dr1 binds to TBP and blocks the interaction of TBP with polymerase II- and polymerase III-specific factors. This enables Dr1 to coordinately regulate transcription by RNA polymerases II and III. Under the same conditions, Dr1 does not inhibit polymerase I transcription. By selectively repressing polymerases II and III, Dr1 may shift the physiological balance of transcriptional output in favor of polymerase I.


HLA-G in melanoma: A new strategy to escape from immunosurveillance?
The non-classical HLA class-I molecule HLA-G, primarily expressed on fetal cells of the human placenta, has been shown to play a crucial role in maintaining an immuno-privileged environment at the materno-fetal interface. Fetal trophoblast cells are protected from attack by CD8+ cytotoxic T lymphocytes due to their lacking expression of classical HLA class-I molecules, again rendering them susceptible to natural killer (NK) cell lysis. HLA-G has been shown to interact with killing inhibitory receptors, hereby rescuing the fetal placenta cells from NK cell attack. Likewise, classical HLA class-I molecules are known to be frequently downregulated or lost during the development of malignancies. This abnormality is often associated with a poor clinical course of disease, despite of the frequent detection of tumor-infiltrating NK cells. This controversy seemed to be resolved with the detection of HLA-G expression on cells of malignant melanoma and other solid tumors. Since interferon(IFN)s are known for their ability of upregulation or induction of HLA-G expression, the potential function of HLA-G as a new strategy of cancer cells to escape from immunosurveillance might be of particular importance in malignant melanoma. The frequent use of IFN-alpha in the immunotherapy of this malignancy might possibly worsen the already impaired antitumoral immune response state of melanoma patients. However, several studies recently failed to detect any HLA-G protein expression in cancer cell lines and tissues of different origin, particularly in malignant melanoma, yet rendering the expression and function of HLA-G in malignancies as a possibly overrated matter of controversial debate.


Expression of the c-myc oncoprotein in human metaplastic epithelial cells of fibrocystic disease.
Sections derived from fibrocystic disease in human breast tissue were examined for the presence of the c-myc oncoprotein by using the c-myc specific monoclonal antibody 9E10 (1). The results obtained revealed that the c-myc gene was not expressed in normal epithelial cells either of ducts or lobules. It was expressed mainly in mucous metaplastic cells and very rarely in apocrine cells. The c-myc protein was observed at a higher level in mucous metaplastic cells of epitheliosis and multiple papillomas. The number and intensity of positive mucous metaplastic cells was significantly increased after pretreating the sections with neuraminidase. We suggest that elevated expression of the c-myc nuclear oncoprotein in human breast metaplastic epithelial cells play a role in the early stages of malignant cell transformation.


Effect of Nintedanib Nanothermoreversible Hydrogel on Neovascularization in an Ocular Alkali Burn Rat Model.
To compare the therapeutic effects of different forms of nintedanib ophthalmic preparations on neovascularization corneal alkali burns in rats. Forty rat models of left eye corneal alkali burns were constructed, and the five groups (N = 8) were treated with normal saline, dexamethasone ointment (dexamethasone), 0.2% nintedanib aqueous solution and nintedanib nano thermoreversible hydrogel (NNTH). A slit lamp microscope was used to observe the area of neovascularization. The levels of the inflammatory factors were detected by ELISA. HE staining was performed on the rat corneas. Vascular endothelial growth factor (VEGFA) was detected by immunohistochemistry, and the expression of corneal VEGFA and CD31 was detected by western blotting. An MTT assay was performed to detect the cytotoxicity of nintedanib on human corneal epithelial cells (HCECs) and human umbilical vein vascular endothelial cells (HUVECs). Cell migration was detected by a cell scratch assay, and the proportion of apoptotic cells was detected by Annexin/PI double staining. Immunofluorescence and western blotting were performed to detect the protein expression of VEGFA and CD31. NNTH had a stronger inhibitory effect on corneal neovascularization (CNV) in alkali-burned rats while reducing the level of inflammatory factors. NNTH had a longer drug duration of release than nanoformulations in vitro. Nintedanib at low concentrations (<8 μM) had no significant cytotoxicity to HCECs but significantly induced apoptosis and inhibited the expression of VEGFA and CD31 and the migration of HUVECs. Nanomorphic thermoreversible hydrogel is superior among the nintedanib ophthalmic preparations, showing better inhibition of CNV in alkali-burned eyeballs and it blocked the migration and proangiogenic ability of HUVECs.


Evaluation of deepfake detection using YOLO with local binary pattern histogram.
Recently, deepfake technology has become a popularly used technique for swapping faces in images or videos that create forged data to mislead society. Detecting the originality of the video is a critical process due to the negative pattern of the image. In the detection of forged images or videos, various image processing techniques were implemented. Existing methods are ineffective in detecting new threats or false images. This article has proposed You Only Look Once-Local Binary Pattern Histogram (YOLO-LBPH) to detect fake videos. YOLO is used to detect the face in an image or a frame of a video. The spatial features are extracted from the face image using a EfficientNet-B5 method. Spatial feature extractions are fed as input in the Local Binary Pattern Histogram to extract temporal features. The proposed YOLO-LBPH is implemented using the large scale deepfake forensics (DF) dataset known as CelebDF-FaceForensics++(c23), which is a combination of FaceForensics++(c23) and Celeb-DF. As a result, the precision score is 86.88% in the CelebDF-FaceForensics++(c23) dataset, 88.9% in the DFFD dataset, 91.35% in the CASIA-WebFace data. Similarly, the recall is 92.45% in the Celeb-DF-Face Forensics ++(c23) dataset, 93.76% in the DFFD dataset, and 94.35% in the CASIA-Web Face dataset.


[Studies on the crystal structure of ivermectin (H2B1a)].
The crystal structure of ivermectin (H2B1a) was determined by X-ray diffraction. Ivermectin was found to be composed of more than 80% H2B1a and less than 20% H2B1b. The crystal of H2B1a belongs to the space group C2 with a = 40.736(6)A, b = 9.295(3)A, c = 14.966(3)A, beta = 106.93(1) degree. After structure refinement using least-squares method, the final R factor of H2B1a is 0.0658. The space configuration of H2B1a is a long chain along the C-axis. The molecular aggregates are extended into pairs of long chains parallel to each other, some distance apart. The distance between chains is the same, but their direction is opposite. This structure of H2B1a is similar to some biomacromolecules.


Effect of several acoustic cues on perceiving Mandarin retroflex affricates and fricatives in continuous speech.
Relatively little attention has been paid to the perception of the three-way contrast between unaspirated affricates, aspirated affricates and fricatives in Mandarin Chinese. This study reports two experiments that explore the acoustic cues relevant to the contrast between the Mandarin retroflex series /tʂ/, /tʂ(h)/ and /ʂ/ in continuous speech. Twenty participants performed two three-alternative forced-choice tasks, in which acoustic cues including closure, frication duration (FD), aspiration, and vocalic contexts (VCs) were systematically manipulated and presented in a carrier phrase. A subsequent classification tree analysis shows that FD distinguishes /tʂ/ from /tʂ(h)/ and /ʂ/, and that closure cues the affricate manner. Interactions between VC and individual cues are also found. The FD threshold for separating /ʂ/ and /tʂ/ is susceptible to the influence of the following vocalic segments, shifting to lower values if frication is followed by the low vowel /a/. On the other hand, while aspiration cues /tʂ(h)/ before /a/ and //, this acoustic cue is obscured by gesture continuation when /tʂ(h)/ precedes its homorganic approximant /ɻ/ in natural speech, which might cause potential confusion between /tʂ(h)/ and /ʂ/.


Dielectric Spectroscopy and Optical Density Measurement for the Online Monitoring and Control of Recombinant Protein Production in Stably Transformed Drosophila melanogaster S2 Cells.
The production of recombinant proteins in bioreactors requires real-time process monitoring and control to increase process efficiency and to meet the requirements for a comprehensive audit trail. The combination of optical near-infrared turbidity sensors and dielectric spectroscopy provides diverse system information because different measurement principles are exploited. We used this combination of techniques to monitor and control the growth and protein production of stably transformed Drosophila melanogaster S2 cells expressing antimicrobial proteins. The in situ monitoring system was suitable in batch, fed-batch and perfusion modes, and was particularly useful for the online determination of cell concentration, specific growth rate (µ) and cell viability. These data were used to pinpoint the optimal timing of the key transitional events (induction and harvest) during batch and fed-batch cultivation, achieving a total protein yield of ~25 mg at the 1-L scale. During cultivation in perfusion mode, the OD880 signal was used to control the bleed line in order to maintain a constant cell concentration of 5 × 10⁷ cells/mL, thus establishing a turbidostat/permittistat culture. With this setup, a five-fold increase in productivity was achieved and 130 mg of protein was recovered after 2 days of induced perfusion. Our results demonstrate that both sensors are suitable for advanced monitoring and integration into online control strategies.


Third Case of Streptococcus suis Infection in Greece.
Streptococcus suis is a facultative anaerobic, Gram-positive coccus that can cause severe disease to both pigs and humans. Its zoonotic potential was first recognized in 1968 when the first human case of meningitis was reported in Denmark. Since then, over 1600 human cases have been reported worldwide, the vast majority of which originated in Southeast Asia, and, thus, S. suis has been fairly characterized as an emerging pathogen. Infection in humans presents most commonly as bacteremia and/or meningitis while less common clinical manifestations such as endocarditis and septic arthritis can occur. S. suis infection is extremely uncommon in Greece and this is the third human case to be reported. Correct identification is of importance for optimization of antimicrobial treatment and epidemiological monitoring.


Improved electrode material for deep brain stimulation.
Deep brain stimulation (DBS) devices have been implanted for treatment of basic tremor, Parkinson's disease and dystonia. These devices use electrodes in contact with tissue to deliver electrical pulses to targeted cells, to elicit specific therapeutic responses. In general, the neuromodulation industry has been evolving towards smaller, less invasive electrodes. However, current electrode materials do not support small sizes without severely restricting the stimulus output. Hence, an improved electrode material will benefit present and future DBS systems. In this study, five DBS leads were modified using a cost-effective and materials-efficient process for applying an ultra-low impedance platinum-iridium alloy coating. One DBS lead was used for insertion test and four DBS leads were chronically pulsed for 12 weeks. The platinum-iridium alloy significantly improved the electrical properties of the DBS electrodes and was robust to insertion into brain and to 12 weeks of chronic pulsing.


Conservative management of herniated nucleus pulposes: treatment approaches.
Herniated nucleus pulposus (HNP) is a significant cause of physical impairment to the afflicted individual and a major factor in a wide range of socioeconomic issues. This paper examines various disc herniation therapies and compares conservative treatment modes with surgical intervention. Results of a 10-yr study are reviewed and recommendations are made concerning conservative treatment management in the physician's office and at home, return-to-work considerations, preventive care and the importance of cooperation among patient, physician, employer and third-party provider. The authors conclude that conservative treatment is an acceptable, cost-effect alternative to surgery.


Rheologic properties of mixed hemoglobin gels: deoxyhemoglobins S and F.
To obtain new information concerning the behaviors--and in turn, the structures--of gels formed from mixtures of S and F hemoglobins, their rheologic properties have been characterized by stress relaxation. The variables manipulated were (1) initial total hemoglobin concentration; (2) mole fraction of hemoglobin S present in the mixture; (3) hemoglobin F as only intact tetramer or as both tetramers and hybridized hemoglobin; (4) hemoglobin F as predominantly G gamma, A gamma, or a mixture of gamma chain types; (5) annealing time; (6) shear history, (7) temperature; and (8) temperature and time of annealing. Characteristics monitored to gain information about the effect of these variables on gel properties were (1) lag time, (2) polymer mass, (3) polymer fraction, (4) polymer composition, (5) equilibrium total hemoglobin activity, and (6) solidity/total or hemoglobin S polymer mass (or total or hemoglobin S fraction). As expected, mixed hemoglobin S and F gels were less solid than pure hemoglobin S gels of similar initial total hemoglobin concentrations because of lower polymer mass, and gel properties were influenced by annealing time, shear history, temperature, and temperature and time of annealing. However, when solidities were compared on the basis of similar quantities of gel present, mixed hemoglobin S and F gels were found to be more solid than those of pure S as the mole fraction of hemoglobin S decreased in the initial mixture. This is explained by the predominant influence on gel properties of high hemoglobin activity incurred by the volume exclusion effect of the total hemoglobin concentration. Pathophysiologic implications of these findings for various sickle cell disorders are proposed.


Variation in surface texture measurements.
Surface texture influences cellular response to implants, implant wear, and fixation, yet measurement and reporting of surface texture can be confusing and ambiguous. Seven specimens of widely different surface textures were submitted to three internationally renowned laboratories for surface texture characterization. The specimens were from dental implants, orthopedic implants, and femoral heads. Areas to be measured were clearly marked; simplified instructions were supplied but specific measurement parameters were not requested. Techniques used included contact profilometry, two- and three-dimensional laser profilometry, and atomic force microscopy. Four to thirteen parameters were reported, 2D or 3D, including R(a) or S(a); only three were common to all centers. The results varied by as much as +/-300-1000%, depending on technique and surface type. Some surfaces were not measurable by some techniques. One dental implant surface was reported with R(a) of 0.17, 0.85, 1.9, and 4.4 microm. The CoCr femoral head ranged from an R(a) of 0.011 to 0.10 microm; the zirconia head from 0.006 to 0.05 microm. Similar variability was reported for the other parameters. Useful surface texture characterization requires reporting of all measurement parameters. Comparisons between studies may be compromised if differences in technique are not considered.


Periodontal health status in patients treated with the Invisalign(®) system and fixed orthodontic appliances: A 3 months clinical and microbiological evaluation.
The aim of this prospective study was to compare the periodontal health and the microbiological changes via real-time polymerase chain reaction (PCR) in patients treated with fixed orthodontic appliances and Invisalign(®) system (Align Technology, Santa Clara, California). Seventy-seven patients were enrolled in this study and divided into three groups (Invisalign(®) group, fixed orthodontic appliances group and control group). Plaque index, probing depth, bleeding on probing were assessed. Total biofilm mass and periodontal pathogens were analyzed and detected via real-time PCR. All these data were analyzed at the T0 (beginning of the treatment) T1 (1-month) and T2 (3 months); and statistically compared using the Mann-Whitney test for independent groups. After 1-month and after 3 months of treatment there was only one sample with periodontopathic anaerobes found in patient treated using fixed orthodontic appliances. The Invisalign(®) group showed better results in terms of periodontal health and total biofilm mass compared to the fixed orthodontic appliance group. A statistical significant difference (P < 0.05) at the T2 in the total biofilm mass was found between the two groups. Patients undergoing orthodontic treatment with the Invisalign(®) System show a superior periodontal health in the short-term when compared to patients in treatment with fixed orthodontic appliances. Invisalign(®) should be considered as a first treatment option in patients with risk of developing periodontal disease.


Assessment and comparison of rhizosphere communities in cultivated Vaccinium spp. provide a baseline for study of causative agents in decline.
It has long been recognized that the community of organisms associated with plant roots is a critical component of the phytobiome and can directly or indirectly contribute to the overall health of the plant. The rhizosphere microbial community is influenced by a number of factors including the soil type, the species of plants growing in those soils, and in the case of cultivated plants, the management practices associated with crop production. Vaccinium species, such as highbush blueberry and American cranberry, are woody perennials that grow in sandy, acidic soils with low to moderate levels of organic matter and a paucity of nutrients. When properly maintained, fields planted with these crops remain productive for many years. In some cases, however, yields and fruit quality decline over time, and it is suspected that degenerating soil health and/or changes in the rhizosphere microbiome are contributing factors. Determining the assemblage of bacterial and fungal microorganisms typically associated with the rhizosphere of these crops is a critical first step toward addressing the complex issue of soil health. We hypothesized that since blueberry and cranberry are in the same genus and grow in similar soils, that their associated rhizosphere microbial communities would be similar to each other. We analyzed the eukaryotic (primarily fungal) and bacterial communities from the rhizosphere of representative blueberry and cranberry plants growing in commercial fields in New Jersey. The data presented herein show that while the bacterial communities between the crops is very similar, the fungal communities associated with each crop are quite different. These results provide a framework for examining microbial components that might contribute to the health of Vaccinium spp. crops in New Jersey and other parts of the northeastern U.S.


Neurotrophins and nerve regeneration-associated genes are expressed in the cornea after lamellar flap surgery.
To determine the in vivo expression of neurotrophins (NTs) and nerve regeneration-associated genes (RAGs) after surgically creating a hinged lamellar corneal flap in thy1-YFP mice. Lamellar corneal flaps with multiple hinges were created in thy1-YFP mice. Mice were killed at weeks 2, 4, and 8. Quantitative polymerase chain reaction was performed to determine the expression of NTs and RAGs in the corneas after lamellar transection. Nerve growth factor (Ngf), brain-derived neurotrophic factor (Bdnf), glial cell-derived neurotrophic factor (Gdnf), neurotrophin 3, neurotrophin 5, small proline-rich repeat protein 1A (Sprr1a), growth-associated protein 43 (Gap43), and beta III tubulin (Tubb3) gene expressions were analyzed. Whole-mount confocal immunofluorescence and Western analyses were performed for localization and abundance of robustly expressed genes. Sprouts of fine YFP-positive fronds emanating from transected (injured) nerve bundles were seen in the flap area at 2 weeks onward. Bdnf and Sprr1a were robustly and significantly expressed at 2 weeks postoperatively (>2-fold increase in expression; P<0.05). Bdnf localized to thy1-YFP+ cells in operated corneas. Sprr1a localized to corneal epithelial cell membranes. At 8 weeks, none of the NTs and RAGs had increased expression. Bdnf (ρ=0.73, P=0.001) and Sprr1a (ρ=0.76, P=0.001) showed a significant positive correlation with beta III tubulin. The neurotrophin Bdnf and RAG Sprr1a are robustly and significantly expressed during corneal nerve regeneration in vivo.


Effects of microorganisms on effective oxygen diffusion coefficients and solubilities in fermentation media.
Effective oxygen diffusion coefficients and solubilities were measured for submerged cultures of Saccharomyces cerevisiae, Escherichia coli, and Penicillium chrysogenum. Both effective oxygen diffusion coefficients and solubilities were found to decrease with increasing cell concentrations in the fermentation media. Comparison of the experimental results of effective oxygen diffusion coefficients in fermentation media with values theoretically predicted on the assumption of unpenetrable microbial cells indicates that oxygen molecules diffuse through the cells during the diffusion process. Within the cell concentration range of typical submerged fermentations, the effective oxygen diffusion coefficient of the fermentation media can be described as De/Dl = 1 + A, f + A2f2. In this equation, f is the cell volume fraction and both A(1) and A(2) are functions of the shape of the cells and the ratio of effective oxygen diffusion coefficient in microbial cells to that in the medium.


Generation of a stable mammalian cell line for simultaneous expression of multiple genes by using 2A peptide-based lentiviral vector.
Generation of mammalian cells stably expressing multiple exogenous genes is currently difficult. Here we provide a strategy to facilitate this process. First, a helper vector p2A containing three coding sequences for viral 2A peptides was constructed. Three reporter genes coding for red fluorescent protein (DsRed), firefly luciferase (Fluc) and enhanced green fluorescent protein (EGFP) were then inserted into p2A to form a fusion open reading frame that was subsequently subcloned into a lentiviral vector. After transduction, EGFP-positive 293T cells were selected by fluorescence activated cell sorting. The expression of exogenous genes in selected cells was stable for more than 15 passages, and EGFP-positive cells were over 95%. The efficient cleavages of 2A-peptide mediated polyprotein were also observed and all three reporter proteins were functional. Thus, a stable DsRed/Fluc/EGFP-coexpressing cell line was readily established within a short time. The strategy could be useful for basic research and protein production.


High-resolution melting curve analysis for infectious bronchitis virus strain differentiation.
Belonging to the Coronaviridae family, avian infectious bronchitis virus (IBV) causes respiratory, reproductive, and renal diseases in poultry. Preventative measures lie mainly in vaccination, while the gold standard for IBV classification and differentiation is based on the sequence analysis of the spike 1 (S1) gene. In this study, we tested a new assay for IBV strain classification that is less expensive and requires reduced time and effort to perform. We carried out a quantitative real-time polymerase chain reaction followed by high-resolution melting (qRT-PCR/HRM) curve analysis. In this study, qRT-PCR was conducted on a partial fragment S1 gene followed by a high resolution melting curve analysis (qRT-PCR/HRM) on 23 IBV-positive samples in Jordan. For this assay, we utilized the most common IBV vaccine strains (Mass and 4/91) as a reference in the HRM assay. To evaluate the discrimination power of the qRT-PCR/HRM, we did the sequencing of the partial S1 gene. It was shown that HRM was able to classify IBV samples into four clusters based on the degree of similarity between their melting points: The first cluster exhibited the highest similarity to the 4/91 strain, while the second was similar to the Mass-related IBV strain. Although the third cluster contained the highest number of samples, it displayed no similarity to any of the reference vaccine strains, and, after comparing them with the sequencing results, we found that the samples in the third cluster were similar to the variant II-like (IS-1494-06) IBV field strain. Finally, the fourth cluster comprised one unique sample that was found to belong to the Q1 IBV strain. Our developed qRT-PCR/HRM curve analysis was able to detect and rapidly identify novel and vaccine-related IBV strains as confirmed by S1 gene nucleotide sequences, making it a rapid and cost-effective tool.


A protein kinase inhibitor, staurosporine, mimics nerve growth factor induction of neurotensin/neuromedin N gene expression.
Nerve growth factor (NGF) cooperates with glucocorticoids, activators of adenylate cyclase, and lithium to induce the expression of teh gene encoding the neuropeptides neurotensin and neuromedin N (NT/N gene) in PC 12 pheochromocytoma cells. High level expression requires simultaneous treatment with three or all four inducers. To examine the mechanism underlying this complex synergism, we have examined the effects of protein kinase inhibitors and other agents which influence intracellular signal transduction on NT/N gene expression. Two structurally similar bacterial alkaloids, staurosporine and K-252a, inhibit several protein kinases in vitro, including protein kinase C and cyclic nucleotide-dependent kinases. K-252a has been reported to specifically inhibit the effects of NGF on PC12 pheochromocytoma cells. Surprisingly, staurosporine in combination with other inducers markedly potentiated NT/N gene expression. In contrast, K-252a had no effect on NT/N gene expression when added simultaneously with other inducers. Expression of the NT/N gene was also potentiated by the phorbol ester 12-O-tetradecanoylphorbol-13-acetate, which directly activates protein kinase C, and by bradykinin, which stimulates phosphatidylinositol turnover in PC12 cells, and these effects were not blocked by staurosporine. Staurosporine was generally more effective in stimulating NT/N gene expression when used in inducer combinations that did not include NGF. These results, taken together with recent evidence that staurosporine is also able to induce neurite outgrowth from PC12 cells, suggest that the effects of staurosporine and NGF may converge, in part, on a common intracellular target.


Intention to Quit Smoking among Intermediate and Secondary School Students in Saudi Arabia.
Smoking is one of the most preventable causes of disease and death, including cancer, and quitting at an early age can reduce smoking-related morbidity and mortality. This study aimed to estimate the prevalence and to identify factors affecting the "intention to quit" among intermediate and secondary school current cigarette smoker students in Al Madinah city, Saudi Arabia. This study cohort included 307 current smoker students in a school-based survey. The intention to quit and its related determinants were assessed using a self-administered questionnaire. More than half of the participants were ≥17 years, and of male gender (54.7%, 77.9% respectively). An intention to quit smoking was reported in 71.7% of participants, and was been significantly associated with: male gender (OR=3.25, 95% CI=1.65-6.41): age at 1st trial of smoking. 10-15 years (OR=2.11, 95% CI=1.03-4.32) along with age of ≥15 years (OR=3.10, 95% CI=1.20-7.88); days of smoking in the past 30 days (days<10 (OR=2.31, 95% CI=1.23-4.35) along with days ranging from 10-19 days (OR= 3.42, 95% CI=1.18-9.91); knowing that smoking is hazardous to health (OR=3.04, 95% CI=1.42-6.47); and finally, supporting smoking bans in public places (OR=1.89, 95% CI=1.11-3.25). A substantial number of participants were willing to quit smoking. Effective interventions focusing on providing information about the hazards of smoking and prohibiting smoking in public places could help initiate the intention to quit among youth smokers.


Evaluation of Chemical Analysis Method and Determination of Polycyclic Aromatic Hydrocarbons Content from Seafood and Dairy Products.
This study was carried out to investigate contents of 8 polycyclic aromatic hydrocarbons (PAHs) from frequently consumed seafood and dairy products and to evaluate their chemical analysis methods. Samples were collected from markets of 9 cities in Korea chosen as the population reference and evaluated. The methodology involved saponification, extraction with n-hexane, clean-up on Sep-Pak silica cartridges and gas chromatograph-mass spectrometry analysis. Validation proceeded on 2 matrices. Recoveries for 8 PAHs ranged from 86.87 to 103.57%. The limit of detection (LOD) 8 PAHs was 0.04~0.20 µg/kg, and limit of quantification (LOQ) of 8 PAHs was 0.12~0.60 µg/kg. The mean concentration of benzo[a]pyrene (BaP) was 0.34 µg/kg from seafood and 0.34 µg/kg from dairy products. The total PAHs concentration was 1.06 µg/kg in seafood and 1.52 µg/kg in dairy products.


Neurophysiological assessment of early hepatic encephalopathy.
The spontaneous EEG, pattern reversal VEPs, and the P300 wave were studied in patients with liver cirrhosis and early stages of hepatic encephalopathy (HE). The sensitivities of the different neurophysiological methods in the early stages of hepatic encephalopathy were compared with each other and with several neuropsychological tests. P300 latency was shown to be the most appropriate neurophysiological method for detection of early HE. The diagnostic sensitivity of the P300 latency resembled that of the number connection test (NCT). These results are discussed with regard to methodological considerations and the clinical use of both methods.


Fluticasone propionate attenuates platelet-activating factor-induced gas exchange defects in mild asthma.
Inhaled glucocorticosteroids may reduce airway mucosal oedema in acute asthma. Inhaled platelet-activating factor (PAF) provokes pulmonary gas exchange disturbances, similar to those shown in severe asthma, which may be due to increased airway plasma leakage. This randomized, double-blind, placebo-controlled, crossover study investigated the effects of high doses of inhaled fluticasone propionate (FP) in 12 patients with mild asthma before and after PAF inhalation. Patients were studied before and 12 h after inhaling FP (6 mg) or placebo (P), and then at 5, 15 and 45 min after PAF challenge. Compared with vehicle, FP inhaled before PAF improved forced expiratory volume in one second and respiratory system resistance (Rrs), increased peripheral blood neutrophils and reduced eosinophil counts. After PAF, FP enhanced transient neutropenia at 5 min and facilitated the recovery of oxygen tension in arterial blood (FP: 93+/-4 mmHg; P: 83+/-4 mmHg) at 45 min, without influencing the increases in Rrs. In conclusion, the improvement of platelet-activated factor-induced oxygen tension in arterial blood disturbances after fluticasone proprionate suggests that inhaled glucocorticosteroids may possess vasoconstrictor properties in the pulmonary circulation.


Endometrial cancer: predictors and oncological safety of tumor tissue manipulation.
The main goal of this study is to assess the impact of tumor manipulation on the presence of lympho-vascular space invasion and its influence on oncological results. We performed a retrospective multi-centric study amongst patients who had received primary surgical treatment for apparently early-stage endometrial cancer. A multivariate statistical analysis model was designed to assess the impact that tumor manipulation (with the use of uterine manipulator or preoperative hysteroscopy) has on lympho-vascular development (LVSI) in the final surgical specimen. A total of 2852 women from 15 centers were included and divided into two groups based on the lympho-vascular status in the final surgical specimen: 2265 (79.4%) had no LVSI and 587 (20.6%) presented LVSI. The use of uterine manipulator was associated with higher chances of lympho-vascular involvement regardless of the type used: Balloon manipulator (HR: 95% CI 4.64 (2.99-7.33); p < 0.001) and No-Balloon manipulator ([HR]: 95% CI 2.54 (1.66-3.96); p < 0.001). There is no evidence of an association between the use of preoperative hysteroscopy and higher chances of lympho-vascular involvement (HR: 95% CI 0.90 (0.68-1.19); p = 0.479). Whilst performing common gynecological procedures, iatrogenic distention and manipulation of the uterine cavity are produced. Our study suggests that the use of uterine manipulator increases the rate of LVSI and, therefore, leads to poorer oncological results. Conversely, preoperative hysteroscopy does not show higher rates of LVSI involvement in the final surgical specimen and can be safely used.


Mussel-Derived Bioadaptive Artificial Tendon Facilitates the Cell Proliferation and Tenogenesis to Promote Tendon Functional Reconstruction.
Tendon injuries range from acute-related trauma to chronic-related injuries are prevalent and bring substantial pain, functional loss, and even disability to the patients. The management of tendon injuries is tricky due to the innate limited regenerative capability of the tendon. Currently, surgical intervention of tendon injuries with artificial tendons remains the standard of care. However, most of artificial tendons are manufactured with synthetic materials, which possess relatively poor biomimetic characteristics and inadequate inherent biodegradability, hence rendering limited cell proliferation and migration for tendon healing. To address these limitations, this work develops a mussel-derived artificial tendon based on double-cross-linked chitosan modification. In this design, decellularized artificial tendon serves as a natural biomimetic scaffold to facilitate the migration and adhesion of tendon repair cells. Additionally, as the cells proliferate, the artificial tendon can be degraded to facilitate tendon regeneration. Moreover, the chitosan cross-linking further enhances the mechanical strength of artificial tendon and offers a controllable degradation. The in vitro and in vivo experimental results demonstrate that mussel-derived artificial tendon not only accelerate the tendon functional reconstruction but also enable harmless clearance at postimplantation. The finding provides a promising alternative to conventional artificial tendons and spurs a new frontier to explore nature-derived artificial tendons.


Coordination chemistry of cis,cis and trans,trans 1,1'-[1,2-phenylenebis(methylene)]bis(2,2,3,4,4-pentamethylphosphetane).
The cis,cis (5) and trans,trans (9) forms of the bidentate ligand 1,1'-[1,2-phenylenebis(methylene)]bis(2,2,3,4,4-pentamethylphosphetane) have been prepared from common precursors using two separate synthetic routes. The cis,cis isomer is attained selectively through the direct reaction of two mol equivalents of 2,2,3,4,4-pentamethylphosphetane with alpha,alpha'-dibromo-o-xylene in acetone. Protection of the 2,2,3,4,4-pentamethylphosphetane with BH(3) and conversion to the lithium phosphido-borane prior to adding the alpha,alpha'-dihalo-o-xylene leads to the isolation of the trans,trans isomer of 1,1'-[1,2-phenylenebis(methylene)]bis(2,2,3,4,4-pentamethylphosphetane). Both isomers have been fully characterised by spectroscopic and, in the case of the all-cis isomer, single-crystal X-ray methods. The two isomers have been coordinated to Mo(0) to give complexes of the type cis-Mo(CO)(4)(L). The solid state structures of cis-Mo(CO)(4)(5), 10, and cis-Mo(CO)(4)(9), 12, have been determined by single-crystal X-ray methods and reveal significant differences between the two forms, most notably in the chelate bite angle which is 100.68(18) degrees in 10 compared to 88.12(2) degrees in 12. Ligand 5 has also been coordinated to Pd(II) and Pd(0) and the structure of the complex Pd(5)Cl(2) (11) determined by single-crystal methods. The solid-state structure of Pd(5)Cl(2) reveals a significant tetrahedral distortion from the normal square planar geometry.


Talaromyces halophytorum sp. nov. Isolated from Roots of Limonium tetragonum in Korea.
Talaromyces halophytorum sp. nov. was isolated from the roots of halophyte Limonium tetragonum collected from Seocheon-gun, Korea in November 2015. It showed a slow growth on yeast extract sucrose agar at 25 °C, no growth at 4 °C or 37 °C and produced smooth-walled and globose to sub-globose conidia. T. halophytorum is phylogenetically distinct from the other reported Talaromyces species of section Trachyspermi based on multi-locus sequence typing results using partial fragments of β-tubulin, calmodulin, ITS, and RNA polymerase II genes.


Taylor dispersion in equilibrium gradient focusing at steady state.
An analytic expression is presented for the effective dispersion coefficient in the case where a solute is focused in a parabolic flow against a linear gradient in a restoring force. This expression was derived by employing a minor variation on the method of moments used by Aris in his development of the dispersion coefficients for a time-dependent, isocratic system. In the present case, dispersion is controlled by two dimensionless groups, a Peclet number which is proportional to the parabolic component of the flow, and a gradient number which is proportional to the slope of the restoring force. These results confirm that the Aris-Taylor expression for the dispersion coefficient should not be applied in cases where a solute is focused to a stationary steady state.


Conservation genomics of an endangered montane amphibian reveals low population structure, low genomic diversity and selection pressure from disease.
Wildlife diseases are a major global threat to biodiversity. Boreal toads (Anaxyrus [Bufo] boreas) are a state-endangered species in the southern Rocky Mountains of Colorado and New Mexico, and a species of concern in Wyoming, largely due to lethal skin infections caused by the amphibian chytrid fungus Batrachochytrium dendrobatidis (Bd). We performed conservation and landscape genomic analyses using single nucleotide polymorphisms from double-digest, restriction site-associated DNA sequencing in combination with the development of the first boreal toad (and first North American toad) reference genome to investigate population structure, genomic diversity, landscape connectivity and adaptive divergence. Genomic diversity (π = 0.00034-0.00040) and effective population sizes (Ne = 8.9-38.4) were low, likely due to post-Pleistocene founder effects and Bd-related population crashes over the last three decades. Population structure was also low, likely due to formerly high connectivity among a higher density of geographically proximate populations. Boreal toad gene flow was facilitated by low precipitation, cold minimum temperatures, less tree canopy, low heat load and less urbanization. We found >8X more putatively adaptive loci related to Bd intensity than to all other environmental factors combined, and evidence for genes under selection related to immune response, heart development and regulation and skin function. These data suggest boreal toads in habitats with Bd have experienced stronger selection pressure from disease than from other, broad-scale environmental variations. These findings can be used by managers to conserve and recover the species through actions including reintroduction and supplementation of populations that have declined due to Bd.


The Reality of Inadequate Patient Care and the Need for a Global Action Framework in Organ Donation and Transplantation.
Transplant therapy is considered the best and often the only available treatment for thousands of patients with organ failure that results from communicable and noncommunicable diseases. The number of annual organ transplants is insufficient for the worldwide need. We elaborate the proceedings of the workshop entitled "The Role of Science in the Development of International Standards of Organ Donation and Transplantation," organized by the Pontifical Academy of Sciences and cosponsored by the World Health Organization in June 2021. We detail the urgency and importance of achieving national self-sufficiency in organ transplantation as a public health priority and an important contributor to reaching relevant targets of the United Nations Agenda for Sustainable Development. It details the elements of a global action framework intended for countries at every level of economic development to facilitate either the establishment or enhancement of transplant activity. It sets forth a proposed plan, by addressing the technical considerations for developing and optimizing organ transplantation from both deceased and living organ donors and the regulatory oversight of practices. This document can be used in governmental and policy circles as a call to action and as a checklist for actions needed to enable organ transplantation as treatment for organ failure.


[The segmental distribution of afferent neurons of liver, and "qi men" point, "tai chong" point in the spinal ganglion].
Experimental animals were 38 cats, 10% HRP 50-60 microliters was injected into "Tai Chong", "Qi Men" points respectively and 10 cats were used for each point. Another 18 cats were injected with 10% HRP 100 microliters into the liver. The segmental distribution of afferent neurons of points and liver was observed under light microscope. We observed the majority of labeled cells in the spinal ganglion. The segmental distribution of afferent neurons of "Tai Chong" point was T12, L1-7 and S1-3. The segmental distribution of afferent neurons of "Qi Men" point was T5-8. The segmental distribution of afferent neurons of liver was T3-12 and L1. The results show that the afferent of "Tai Chong, Qi Men" points and the liver are mutual intersected and overlapped for 2-4 segments. The mutual intersection and overlapping were probably the morphological foundation of treatment of liver disease by needing "Tai Chong", "Qi Men" point, at the same time, the results may elucidate the underlying mechanism of correlation between acupoints and viscera, too.


Bactericidal effect of ceftriaxone versus imipenem plus cilastatin in bronchial secretion.
The bactericidal quotient (BQ) assessed in the site of infection represents an essential parameter for evaluating the real bactericidal potency of an antibiotic in vivo. The assessment and knowledge of BQ values allow us to set up a more accurate and appropriate antibacterial therapy. The two drugs--ceftriaxone (Rocephin) and imipenem plus cilastatin (Tienam)--that have been taken into consideration in this study, having a similar antibacterial spectrum though with different kinetics, may have the same BQ values in bronchial secretion versus Haemophilus influenzae, Klebsiella pneumoniae and Streptococcus pneumoniae, when administered at different dosages, i.e. ceftriaxone 1 g (i.v.) every 24 h, imipenem 0.5 g (i.v.) every 8 h.


[Pharmacotherapeutic aspects of early postoperative period in patients with complicated gastroduodenal ulcer].
There were analyzed the immediate and remote results of treatment of 556 patients with complicated gastroduodenal ulcer, in whom radical operation and ulcer excision with various variants of medicinal correction in early postoperative period were performed. The best immediate result was achieved after performance of radical operation (vagotomy, thrifty gastric resection). But in 5-10 years after vagotomy performance the ulcer recurrency have occurred in 11.3% of observations. Excision of the ulcer morphological substratum in combination with antiulcer medicinal therapy in early postoperative period constitutes an alternative method of treatment of such patients. Important role of Helicobacter pylori in the ulcer complications occurrence was established, demanding application of antibacterial preparations. Of many schemes of antibacterial therapy existing preference should be given to combination of macrolides (clarythromycine) with nitroimidazole (tinidazole) and the proton pump inhibitors (pylobact) as most secure and quite effective one.


Experiences and perceptions of newly prepared Health Care Assistants (Level 3 NVQ).
Increasing demands on the skills of qualified nurses and a recognized shortage of personnel in the NHS emphasize the need to maximize scarce resources and realise the full potential of the nursing contribution. One strategy has been to introduce higher level support roles in line with the recommendations of the DoH (1997) report, often utilizing NVQ qualifications. This study using focused interviews explores the perceptions and experiences of a group of Health Care Assistants who had completed a development programme at level three NVQ. The transcribed interviews were phenomenologically analysed using a framework developed by Hycner in 1985. The emerging themes suggest that they view nursing and its role differently from nursing assistants, but similarly to that of previous State Enrolled Nurses. The development increased their sense of alienation from all other grades of nurse, but afforded improved job satisfaction. Questions are raised in relation to the impact on skill-mix and care delivery from a higher level of support, career progression and the effect on the qualified nurse's role. More research is required to assess the impact of developing higher level support roles and what might constitute the registered nurse's unique professional role, before new supportive or substitutory roles are developed on a larger scale in line with Government directives.


Bioactivity-Guided Screening of Wound-Healing Active Constituents from American Cockroach (Periplaneta americana).
Ethanol extract (EE) from Periplaneta americana (PA) is the main ingredient of Kangfuxin, which is a popular traditional chinese medicine (TCM) and has long been used for the clinical treatment of burns, wounds and ulcers. We compared the wound-healing activities of three extracts of PA using cutaneous wound-healing in mice as the bioactivity model. These three extracts were EE, total polysaccharide and total protein. We also tracked bioactive fractions in the EE by organic reagent extraction, column chromatography and HPLC. Seven compounds were successfully identified from the water elution fraction of the EE of PA using UPLC-MS. Among these compounds, four compounds (P2, P3, P4, P5(1)) were first reported in PA. Some of these compounds have been previously reported to have various pharmacological activities that could contribute to the high wound-healing activity of PA.