Mechanistic target of rapamycin is necessary for changes in dendritic spine morphology associated with long-term potentiation.
Alterations in the strength of excitatory synapses in the hippocampus is believed to serve a vital function in the storage and recall of new information in the mammalian brain. These alterations involve the regulation of both functional and morphological features of dendritic spines, the principal sites of excitatory synaptic contact. New protein synthesis has been implicated extensively in the functional changes observed following long-term potentiation (LTP), and changes to spine morphology have similarly been documented extensively following synaptic potentiation. However, mechanistic links between de novo translation and the structural changes of potentiated spines are less clear. Here, we assess explicitly the potential contribution of new protein translation under control of the mechanistic target of rapamycin (mTOR) to LTP-associated changes in spine morphology. Utilizing genetic and pharmacological manipulations of mTORC1 function in combination with confocal microscopy in live dissociated hippocampal cultures, we demonstrate that chemically-induced LTP (cLTP) requires do novo protein synthesis and intact mTORC1 signaling. We observed a striking diversity in response properties across morphological classes, with mushroom spines displaying a particular sensitivity to altered mTORC1 signaling across varied levels of synaptic activity. Notably, while pharmacological inhibition of mTORC1 signaling significantly diminished glycine-induced changes in spine morphology, transient genetic upregulation of mTORC1 signaling was insufficient to produce spine enlargements on its own. In contrast, genetic upregulation of mTORC1 signaling promoted rapid expansion in spine head diameter when combined with otherwise sub-threshold synaptic stimulation. These results suggest that synaptic activity-derived signaling pathways act in combination with mTORC1-dependent translational control mechanisms to ultimately regulate changes in spine morphology. As several monogenic neurodevelopmental disorders with links to Autism and Intellectual Disability share a common feature of dysregulated mTORC1 signaling, further understanding of the role of this signaling pathway in regulating synapse function and morphology will be essential in the development of novel therapeutic interventions.


Intranodal Lymphangiography with Thoracic Duct Embolization for Treatment of Chyle Leak after Thoracic Outlet Decompression Surgery.
From 2015 to 2019, 9 patients underwent ultrasound-guided intranodal lymphangiography for the treatment of a chyle leak following thoracic outlet decompression surgery. Chyle leaks were identified by Lipiodol (Guerbet, Roissy, France) extravasation near the left supraclavicular surgical bed in all patients. The technical success rate of thoracic duct embolization was 67% (6 of 9), including fluoroscopic transabdominal antegrade access (n = 4) and ultrasound-guided retrograde access in the left neck (n = 2). Clinical success was achieved in 89% of patients (8 of 9). The mean interval from lymphangiography to drain removal was 6.6 days (range, 4-18 d). No patients had a chyle leak recurrence during clinical follow-up (mean, 304 d).


Clinical Application of Navigation in the Surgical Treatment of a Pelvic Ring Injury and Acetabular Fracture.
The purpose of this chapter is to review current evidence on indications, techniques, and outcomes of computer-navigated surgical treatment of pelvic ring injuries and acetabular fractures, particularly computer-navigated screw fixation.Iliosacral screw fixation of pelvic ring injury using navigation is attracting attention because the biomechanical stabilization of posterior pelvic ring disruption is of primary importance and is widely indicated because it does not require complete reduction of the fracture site. A cadaver study with a simulated zone II sacral fracture demonstrated a substantial compromise in the space available for iliosacral screws with displacements greater than 10 mm. It is possible to reduce the fracture fragment prior to intraoperative imaging in 2D or 3D fluoroscopic navigation. The use of 3D fluoroscopic navigation reportedly results in lower rates of iliosacral screw malpositioning than the use of the conventional technique or 2D fluoroscopic navigation. Moreover, compared with the conventional technique, it reduces radiation exposure and lowers revision rates. However, the malposition rate associated with 3D fluoroscopic navigation ranges from 0% to 31%, demonstrating that there is still room to improve the navigation performance.Conversely, complete articular surface reduction is required when treating a displaced acetabular fracture to prevent residual hip pain and subsequent osteoarthritic changes. Treating a severely displaced acetabular fracture by screw fixation is very challenging, even with the use of 3D fluoroscopic navigation, because of the difficulty in performing closed anatomical reduction. The indication for percutaneous screw fixation is limited to cases with a small articular displacement. Using 3D fluoroscopic navigation for open surgeries reportedly improves the quality of radiographic fracture reduction, limits the need for an extended approach, and lowers the complication rate.In conclusion, percutaneous screw fixation for pelvic ring injuries is widely indicated, and navigation makes these procedures safe and reliable. The indication for percutaneous screw fixation of acetabular fractures is limited to cases with a small articular displacement. Using 3D fluoroscopic navigation when performing open surgeries is reported to be useful in evaluating fracture reduction and screw position.


Could inguinal hernia be treated medically?
Inguinal hernia is the most common congenital anomaly requiring surgical correction. The cause of the hernia is, most commonly, persistence of the processus vaginalis. Study of testicular descent in rodents has revealed a role for the genitofemoral nerve and calcitonin gene-related peptide (CGRP). Since the testis cannot descend without the processus vaginalis, we wondered whether both descent and hernia closure might be regulated by the same mechanism. Therefore, we tested the idea that CGRP might be active in closure of the inguinal hernia. Using hernial sacs removed at herniotomy operation, fusion of the hernial surfaces was induced by CGRP, but not by CGRP 8-37, CGRP 27-37 or dihydrotestosterone. Hepatocyte growth factor also caused peritoneal obliteration in vitro. We propose that obliteration of the processus vaginalis is under the control of molecules released from the genitofemoral nerve, and that a chemical treatment of inguinal hernia is at least theoretically possible.


Efficacy of postural techniques assessed by videofluoroscopy for myasthenia gravis with dysphagia as the presenting symptom: a case report.
Oropharyngeal weakness leading to dysphagia is rarely the presenting symptom of myasthenia gravis, but it can be a significant source of morbidity and mortality. The earliest possible diagnosis of myasthenia gravis should be made for better management of this cause of treatable dysphagia. A detailed evaluation of swallowing by videofluoroscopy can assist in making an accurate diagnosis and in individualizing appropriate diet compensatory techniques. We present the case of a 57-year-old Taiwanese man with dysphagia as the presenting symptom of myasthenia gravis, and evaluate the pathological findings of swallowing and effectiveness of compensatory postural techniques for dysphagia using videofluoroscopy. Videofluoroscopy is a valuable technique for evaluating myasthenia gravis dysphagia, because it allows swallowing interventions to be precisely individualized in accordance with the results obtained.


A Nanofiltration Decision Tool for Potable Reuse: A New Rejection Model for Recalcitrant CECs.
Effluent samples from three water resource recovery facilities (WRRFs) were individually characterized for presence and concentration of 94 different chemicals of emerging concern (CECs), using analytical methods with reporting limits in the low-parts-per-trillion. Following CEC analysis, each sample was subjected to dead-end, pressurized membrane filtration with either a nanofiltration (NF) or reverse osmosis (RO) membrane. The majority of the measured CECs were rejected by both membranes by 1-log removal (90%) or greater. However, nine of the 94 CECs had average rejection rates by the NF membrane less than 90%. A multilevel, multivariable model was developed to predict the probable rejection coefficients of CECs with the studied NF membrane. The resulting Quantitative Molecular Properties Model (QMPM) predicted the NF rejection of CECs based on size, ionic charge, and hydrophobicity. The model parameters that successfully predicted NF rejection in bench testing were log (Kow/Kaw) and the polar surface area of the CEC molecule.


The effectiveness of topical lidocaine in relieving pain related to intranasal midazolam sedation: a randomized, placebo-controlled clinical trial.
Intranasal midazolam (INM) is an increasingly popular agent for sedation in the emergency department and outside the hospital in physician, imaging, and dental offices, to facilitate diagnostic and minor surgical procedures and avoid the need for an operating room and general anesthesia. The use of INM has been commonly associated with a burning sensation of the nasal mucosa. Despite its significance, this subject has received little adequate research focus. The objective of the current study was to evaluate the effectiveness of topical lidocaine in relieving pain related to INM administration. This was a blinded, randomized placebo-controlled trial. Sixty-three uncooperative children undergoing dental treatment, aged 4 to 11 years, were randomly assigned to one of three groups to receive the drug nasally via a precalibrated spray as per the following assignments: group A received 0.5 mg/kg midazolam, group B received lidocaine 2% prior to 0.5 mg/kg midazolam, and group C received saline 0.9% (placebo), 0.5 mg/kg. Children were asked to record the degree of pain using the Wong-Baker faces scale. Parental acceptance was also rated. Topical lidocaine prior to INM administration reduced the burning sensation in the nasal mucosa and improved the drug acceptance. The median score of pain was 8, 1, and 4 in groups A, B, and C, respectively. The differences among the three groups were statistically significant (P > .05). The children's acceptance and parents' future acceptance regarding the intranasal drug administration was significantly higher in group B. INM administration results in burning sensation in the nasal mucosa with high levels of pain. Using topical lidocaine 2% counteracted the burning sensation and achieved a higher acceptance rate and lower pain scores.


Aluminium-based galvanic anode impacts the photosynthesis of microphytobenthos and supports the bioaccumulation of metals released.
Very few studies have looked at the potential biological effects of degradation products of galvanic anodes particularly on primary producers which are central to food webs in marine ecosystems. The galvanic anode cathodic protection system (GACP) is widely used to protect submerged metallic structures from corrosion. Aluminium (Al) and zinc (Zn) are the main constituents of galvanic anodes and are therefore released in the marine environment by oxidation process to form ions or oxy-hydroxides. The main objective of our study was to evaluate the effects of the metals released from an aluminium-based galvanic anode on microphytobenthos performance in term of biofilm growing through the analysis of photosynthetic parameters, the determination of chlorophyll and extracellular polymeric substances (EPS). The bioaccumulation of Al and Zn were measured in the microphytobenthic compartment collected at the surface of polyvinyl chloride (PVC) plates exposed during 13 days to seawaters enriched in different concentrations of metals released from dissolution of one anode. Determination of bioconcentration factors confirmed that the microphytobenthos has incorporated Al. A significative effect was observed on the Chl a concentration for the higher tested concentration ([Al] = 210.1 ± 60.2 µg L - 1; [Zn] = 20.2 ± 1.4 µg L - 1). The seawater exposed to the anode affected the MPB productivity (ETRIImax) with consequences on acclimatation light (Ek), absorption cross section of PSII (σPII), Fv/Fm and NPQ. Regarding the EPS production, the anode degradation presented an impact on high and low molecular weight of both carbohydrates and protein fractions of microphytobenthos suggesting that EPS play an essential role in sequestering metal contaminants to maintain the integrity of the biological membranes and the functionality of the cellular organelles. The accumulation of Al released by GACP in microphytobenthos cells could lead to physiologic problems in photosynthetic organisms.


Effects of aerobic cycling training on mobility and functionality of acute stroke subjects: A randomized clinical trial.
Studies demonstrate the benefits of aerobic cycling training in subacute and chronic stroke subjects, but there is a lack in the literature about its effects on the acute phase. Verify the effects of aerobic cycling training on lower limbs muscle strength, gait speed, balance, mobility and functionality of acute stroke subjects. Control group (CG) performed conventional physiotherapy twice a day and the intervention group (IG) performed a conventional physiotherapy and a cycle ergometer session, for five consecutive days. Subjects were assessed for muscle strength by a digital dynamometer, gait speed by the 10-meter-walk-test, balance by the Berg Balance Scale, mobility by the ICU-Mobility-Scale and functionality by the Perme Score. Twenty subjects were enrolled in the study, 10 in the CG and 10 in the IG. Lower limbs muscle strength, the main endpoint, was better in the IG compared to the CG. The same was found in the secondary endpoints. The intragroup analysis was also positive for the CG in the mobility and functionality. Conventional physiotherapy combined with cycling exercise showed better results in the improvement of muscle strength of lower limbs, mobility and functionality of subjects who suffered from acute stroke.


Cultural relevance in medication adherence interventions with underrepresented adults: systematic review and meta-analysis of outcomes.
This meta-analysis systematically compiles intervention research designed to increase medication adherence among underrepresented adults. Comprehensive searching located published and unpublished studies with medication adherence behavior outcomes. Studies were included if samples were adults living in North America who had any of the following backgrounds or identities: African American, Native American, Latino, Latino American, Asian, Asian American, Pacific Islander, Native Alaskan, or Native Hawaiian. Random-effect analyses synthesized data to calculate effect sizes as a standardized mean difference and variability measures. Exploratory moderator analyses examined the association between specific efforts to increase the cultural relevance of medication adherence studies and behavior outcomes. Data were synthesized across 5559 subjects in 55 eligible samples. Interventions significantly improved medication adherence behavior of treatment subjects compared to control subjects (standardized mean difference=0.211). Primary studies infrequently reported strategies to enhance cultural relevance. Exploratory moderator analyses found no evidence that associated cultural relevance strategies with better medication adherence outcomes. The modest magnitude of improvements in medication adherence behavior documents the need for further research with clear testing of cultural relevance features.


Captopril effect on prostaglandin E2, thromboxane B2 and proteinuria in lupus nephritis patients.
High urinary Prostaglandin E2 (PGE2) and thromboxane B2 (TxB2) levels have been reported in lupus nephritis (LN). Captopril diminishes proteinuria and improves glomerular filtration rate (GFR), and may have effect on immune function. We evaluate captopril effect on urinary PGE2, and TxB2. Eighteen LN patients were randomly assigned to two groups. Group 1 received only prednisone plus cyclophosphamide. Group 2 received also captopril. Serum creatinine, GFR, RPF, urinary proteins, PGE2 and TxB2, were assessed. There were no differences between the initial and final assessments in Group 1. Group 2 showed a significant decrement in proteinuria (p=0.003) and serum creatinine (p=0.01) at the end of the study. PGE2 decreased significantly when compared with the initial value (p=0.02). Captopril plus usual treatment, improved serum creatinine and decreased proteinuria in parallel with prostaglandin E2 reduction. This effect is not related to changes in GFR or RPF. Captopril may have an immunomodulatory effect on local inflammatory processes in lupus nephritis.


Advances in Editing Silkworms (Bombyx mori) Genome by Using the CRISPR-Cas System.
CRISPR (clustered regularly interspaced short palindromic repeats)-Cas (CRISPR-associated) represents a powerful genome editing technology that revolutionized in a short period of time numerous natural sciences branches. Therefore, extraordinary progress was made in various fields, such as entomology or biotechnology. Bombyx mori is one of the most important insects, not only for the sericulture industry, but for numerous scientific areas. The silkworms play a key role as a model organism, but also as a bioreactor for the recombinant protein production. Nowadays, the CRISPR-Cas genome editing system is frequently used in order to perform gene analyses, to increase the resistance against certain pathogens or as an imaging tool in B. mori. Here, we provide an overview of various studies that made use of CRISPR-Cas for B. mori genome editing, with a focus on emphasizing the high applicability of this system in entomology and biological sciences.


The ultrastructure of chronic radiation damage in rat skin.
Chronic radiation skin ulcers were produced in rats with the administration of 5,000 or 8,000 rads. Electron microscopy revealed two phases of damage, the first from seven to 14 weeks and the second from 14 to 54 weeks. In the first phase, significant nuclear and cytoplasmic degeneration was prominent. During the second phase, lysosomes were common along with unusual cytoplasmic inclusions. Myofibroblasts were observed in the second phase only, suggesting that delayed would contraction in radiation ulcers was the result of the delayed onset of myofibroblast development.


In vitro induction of tumour-specific immunity. I. Development of optimal conditions for induction and assay of cytotoxic lymphocytes.
A microculture system for in vitro induction of tumour-specific immunity with syngeneic spleen cells and plasma-cell tumours is described. The system generates cytoxic lymphocytes assessed by their ability to lyse 51Cr-labelled target cells in a microcytotoxicity assay. Both the inductive and effector phases are subject to many variables in material and methodology and the optimal conditions are defined in this study. Of particular importance are the responder- to stimulator-cell ratios, the presence of 2-mercaptoethanol, the day of harvest, the method of target-cell 51Cr labelling, and preincubation of the cytotoxic lymphocytes prior to assay.


A functional lignin for heavy metal ions adsorption and wound care dressing.
Recently, the application of lignin activation by demethylation to improve reactivity and enrich multiple functions has intensively attracted attention. However, it is still challenge up to now due to the low reactivity and complexity of lignin structure. Here, an effective demethylation way was explored by microwave-assisted method for substantially enhancing the hydroxyl (-OH) content and retaining the structure of lignin. Then, the optimum demethylated lignin was used to removal heavy metal ions and promote wound healing, respectively. In detail, for microwave-assisted demethylated poplar lignin (M-DPOL), the contents of phenolic (Ar-OH) and total hydroxyl (Tot-OH) groups reached the maximum for 60 min at 90 °C in DMF with 7.38 and 9.13 mmol/g, respectively. After demethylation, with this M-DPOL as lignin-based adsorbent, the maximum adsorption capacity (Qmax) for Pb2+ ions reached 104.16 mg/g. Based on the isotherm, kinetic and thermodynamic models analyses, the chemisorption occurred in monolayer on the surface of M-DPOL, and all adsorption processes were endothermic and spontaneous. Meanwhile, M-DPOL as a wound dressing had excellent antioxidant property, outstanding bactericidal activity and remarkable biocompatibility, suggesting that it did not interfere with cell proliferation. Besides, the wounded rats treated with M-DPOL significantly promoted its formation of re-epithelialization and wound healing of full-thickness skin defects. Overall, microwave-assisted method of demethylated lignin can offer great advantages for heavy metal ions removal and wound care dressing, which facilitates high value application of lignin.


Prelude to the special issue on novel neurocircuit, cellular and molecular targets for developing functional rehabilitation therapies of neurotrauma.
The poor endogenous recovery capacity and other impediments to reinstating sensorimotor or autonomic function after adult neurotrauma have perplexed modern neuroscientists, bioengineers, and physicians for over a century. However, despite limited improvement in options to mitigate acute pathophysiological sequalae, the past 20 years have witnessed marked progresses in developing efficacious rehabilitation strategies for chronic spinal cord and brain injuries. The achievement is mainly attributable to research advancements in elucidating neuroplastic mechanisms for the potential to enhance clinical prognosis. Innovative cross-disciplinary studies have established novel therapeutic targets, theoretical frameworks, and regiments to attain treatment efficacy. This Special Issue contained eight papers that described experimental and human data along with literature reviews regarding the essential roles of the conventionally undervalued factors in neural repair: systemic inflammation, neural-respiratory inflammasome axis, modulation of glutamatergic and monoaminergic neurotransmission, neurogenesis, nerve transfer, recovery neurobiology components, and the spinal cord learning, respiration and central pattern generator neurocircuits. The focus of this work was on how to induce functional recovery from manipulating these underpinnings through their interactions with secondary injury events, peripheral and supraspinal inputs, neuromusculoskeletal network, and interventions (i.e., activity training, pharmacological adjuncts, electrical stimulation, and multimodal neuromechanical, brain-computer interface [BCI] and robotic assistance [RA] devices). The evidence suggested that if key neurocircuits are therapeutically reactivated, rebuilt, and/or modulated under proper sensory feedback, neurological function (e.g., cognition, respiration, limb movement, locomotion, etc.) will likely be reanimated after neurotrauma. The efficacy can be optimized by individualizing multimodal rehabilitation treatments via BCI/RA-integrated drug administration and neuromechanical protheses.


A matched pair analysis of oncological outcomes in human papillomavirus-negative oropharyngeal squamous cell carcinoma: Transoral surgery versus radiotherapy or concurrent chemoradiation.
With the termination of RTOG 1221, there remains a lacuna regarding the optimal treatment for human papillomavirus (HPV)-negative oropharyngeal squamous cell carcinoma (OPSCC). Matched pair analysis with propensity score matching (PSM) between Arm I (transoral surgery [TOS] + risk-stratified adjuvant treatment) and Arm II (nonsurgical treatment - radiation/chemoradiation) in HPV(-) OPSCC. Unmatched comparison of Arm I (n = 57) and Arm II (n = 89) indicated significantly better overall survival (OS) and disease-free survival (DFS) for Arm I. PSM by matched pairs (n = 48, 24 each arm) indicated 5-year OS at 80% and 72.1%, respectively, for Arm I and II (p > 0.05) and corresponding DFS at 65.3% and 33.4% (p > 0.05). Subgroup analysis did not demonstrate statistical difference in outcomes in stage II and III, but stage IV tumors had significantly better outcomes in Arm I than Arm II (4-year OS: 100% vs. 21%, p = 0.04; DFS: 75% vs. 14.3%, p = 0.04). TOS +/- adjuvant was found to have oncological outcomes at par with nonsurgical modalities in stage I-III OPSCC, whereas a distinct survival advantage was noted in case of stage IV tumors.


[Side effects of novel cancer immunotherapies].
Systemic treatment with immune checkpoint inhibitors (ICI) has revolutionized the treatment of hematological and oncological diseases in recent years. The mechanism of action hinges on enhancing the natural ability of the immune system to eliminate malignant cells. The most important substances in this arena include inhibitors of PD‑1, PD-L1 and CTLA‑4. As a consequence, the spectrum of treatment-associated adverse reactions is shifting away from classical cytotoxic effects (e.g. pancytopenia and polyneuropathy) towards novel entities of immune-mediated complex diseases. These so-called immune-related adverse events (irAEs) can involve any organ system and mimic known classical autoimmune conditions. Timely recognition of irAEs is the key for rapid initiation of a suitable treatment and is especially challenging in the clinical routine as it requires an intensive interdisciplinary management. Nephrologists are particularly confronted with this kind of problem due to the highly interdisciplinary nature of their work. This article summarizes the broad spectrum of currently known renal and more frequently occuring non-renal forms of irAEs and aims to prime the reader on diagnostic and therapeutic options.


A tunnelling model to explain the reduction of ferricytochrome c by H and OH radicals.
The kinetics of the reaction of OH radicals with ferricytochrome c was studied in the time range 1 microsecond to 1 s by means of pulse radiolysis. The OH radicals reduce ferricytochrome c by 40% +/- 10%. The time course of the reduction is explained by a mechanism whereby a radical formed after hydrogen has been abstracted from the outer surface of the protein reduces the iron by electron tunnelling. We have calculated that the reducing electron in the radical is bound with an energy of at least 1.75 eV and that the frequency factor of the tunnelling process is v=10(11.5)s-1. This model accounts for the observed absorbance change in time range 5 . 10(-6)--10(-1)s. The time course of the reduction of ferricytochrome c by H radicals (Lichtin, N.N., Shafferman A. and Stein, G. (1974) Biochim. Biophys. Acta 357, 386--398) is explained by the same model.


Coexpression and estrogen-mediated regulation of TRPV6 and PMCA1 in the human endometrium during the menstrual cycle.
Maintenance of calcium balance in the uterus is essential for many of its functions, including embryo implantation. The plasma membrane Ca(2+) -pumping ATPase proteins are encoded by four genes designated PMCA1-4, and PMCA1 is expressed in the uterus of rats during the estrous cycle. Although transient receptor potential cation channel subfamily V, member 6 (TRPV6), has been detected in the human placenta, pancreas and the prostate gland, expression patterns of uterine TRPV6 and PMCA1 and their potential roles in the human endometrium remain to be elucidated. In the present study, the expression patterns of TRPV6 and PMCA1 were examined to predict their potential roles in the human endometrium during the menstrual cycle. Human classified endometrial tissues (total n = 40) were separated into three groups according to menstrual cycle phase: menstrual, proliferative (early-, mid-, late), and secretory phase (early-, mid-, late). The expression of TRPV6 and PMCA1 mRNA and protein in the uterine endometrium during the menstrual cycle increased by 1.5- to 1.8-fold at the proliferative phase (early-, mid-, and late-) in comparison to the other phases. Estrogen treatment caused a significant increase in TRPV6 and PMCA1 mRNA expression. Immunohistochemical analysis of the distribution of TRPV6 and PMCA1 in the uterus revealed that both proteins are abundantly expressed in the cytoplasm of endometrial and glandular epithelial cells during menstrual phases. Taken together, these results suggest that uterine expression of TRPV6 and PMCA1 may be involved in human reproductive function.


Computational framework of cobalt ferrite and silver-based hybrid nanofluid over a rotating disk and cone: a comparative study.
The dominant characteristics of hybrid nanofluids, including rapid heat transfer rates, superior electrical and thermal conductivity, and low cost, have effectively piqued the interest of global researchers. The current study will look at the impacts of a silver and cobalt ferrite-based hybrid nanofluid with MHD between a revolving disk and cone. The collection of partial differentiable equations is converted into a set of ODEs via similarity transformations. We used the Homotopy analysis approach from the BVPh 2.0 package to solve the ordinary differential equations. The volume proportion of nanoparticles increases and the temperature distribution profile also increased. It is more efficient for metallurgical, medicinal, and electrical applications. Furthermore, the antibacterial capabilities of silver nanoparticles might be used to restrict the growth of bacteria. A circulating disc with a stationary cone has been identified to provide the optimal cooling of the cone disc device while maintaining the outer edge temperature constant. This study's findings might be useful in materials science and engineering. The usage of hybrid nanofluid in heat transfer and heat pumps, coolants in manufacturing and production, producing cooling, refrigerators, solar thermal collectors, and heating, air conditioning, and climate control applications are only a few examples.


A binge high sucrose diet provokes systemic and cerebral inflammation in rats without inducing obesity.
While the dire cardiometabolic consequences of the hypercaloric modern 'Western' diet are well known, there is not much information on the health impact of a high sucrose diet not inducing weight gain. Here, we tested the hypothesis that rats reared with intermittent binge access to sucrose in addition to normal chow would develop an inflammatory response in brain. To test this hypothesis, we undertook serial PET/MRI scans with the TSPO ligand [18F]DPA714 in a group of (n=9) rats at baseline and again after voluntarily consuming 5% sucrose solution three days a week for three months. Compared to a control group fed with normal chow (n=9), the sucrose rats indeed showed widespread increases in the availability of cerebral binding sites for the microglial marker, despite normal weight gain compared to the control diet group. Subsequent immunofluorescence staining of the brains confirmed the PET findings, showing a widespread 20% increase in the abundance of IBA-1-positive microglia with characteristic 'semi-activated' morphology in the binge sucrose rats, which had 23% lower density of microglial endpoints and 25% lower mean process length compared to microglia in the control rats with ordinary feeding. GFAP immunofluorescence showed no difference in astroglial coverage in the sucrose rats, except for a slight reduction in hypothalamus. The binge sucrose diet-induced neuroinflammation was associated with a significant elevation of white blood cell counts. Taking these results together, we find that long-term intake of sucrose in a binge paradigm, similar in sucrose content to the contemporary Western diet, triggered a low-grade systemic and central inflammation in non-obese rats. The molecular mechanism of this phenomenon remains to be established.


Computer Informatics for Infection Control.
Computer informatics have the potential to improve infection control outcomes in surveillance, prevention, and public health. Surveillance activities include surveillance of infections, device use, and facility/ward outbreak detection and investigation. Prevention activities include awareness of multidrug-resistant organism carriage on admission, identification of high-risk individuals or populations, reducing device use, and antimicrobial stewardship. Enhanced communication with public health and other health care facilities across networks includes automated electronic communicable disease reporting, syndromic surveillance, and regional outbreak detection. Computerized public health networks may represent the next major evolution in infection control. This article reviews the use of informatics for infection control.


Gene Therapy.
Gene therapy refers to a rapidly growing field of medicine in which genes are introduced into the body to treat or prevent diseases. Although a variety of methods can be used to deliver the genetic materials into the target cells and tissues, modified viral vectors represent one of the more common delivery routes because of its transduction efficiency for therapeutic genes. Since the introduction of gene therapy concept in the 1970s, the field has advanced considerably with notable clinical successes being demonstrated in many clinical indications in which no standard treatment options are currently available. It is anticipated that the clinical success the field observed in recent years can drive requirements for more scalable, robust, cost effective, and regulatory-compliant manufacturing processes. This review provides a brief overview of the current manufacturing technologies for viral vectors production, drawing attention to the common upstream and downstream production process platform that is applicable across various classes of viral vectors and their unique manufacturing challenges as compared to other biologics. In addition, a case study of an industry-scale cGMP production of an AAV-based gene therapy product performed at 2,000 L-scale is presented. The experience and lessons learned from this largest viral gene therapy vector production run conducted to date as discussed and highlighted in this review should contribute to future development of commercial viable scalable processes for vial gene therapies.


Effect of IFN-γ and IL-4 levels on the expression of Fas and Bcl-2 in peripheral blood lymphocytes in hemodialysis patients.
To study the correlation between the levels of IFN-γ and IL-4 and the expression of Fas and Bcl-2 in peripheral blood lymphocytes (PBL) in hemodialysis patients, the indirect immune fluorescein labeling method of flow cytometry and solid sandwich enzyme-linked immunosorbent assay were performed for detecting the expression of Fas and Bcl-2 in PBL and the levels of IFN-γ and IL-4 in the serum of 30 hemodialysis patients, respectively. It was found that the expression of Fas in PBL and the level of IL-4 in the serum of hemodialysis patients were significantly higher (P < 0.01), whereas Bcl-2 in PBL and IFN-γ in the serum were significantly lower (P < 0.01) than those of the normal controls. According to statistical analysis, the expression of Fas in PBL had a negative correlation with the level of IFN-γ, but a positive correlation with IL-4 in the serum of hemodialysis patients. Contrarily, the expression of Bcl-2 had a positive correlation with IFN-γ, but a negative correlation with IL-4 in the serum of hemodialysis patients. These results suggest that hemodialysis patients have a suppressed secretion of Th1-associated cytokine IFN-γ, but an increased secretion of Th2-associated cytokines IL-4, and these two aspects may play an important role in the abnormal apoptosis of PBL and its accompanying immune deficiency.


rRNA-based monitoring of the microbiota involved in Fontina PDO cheese production in relation to different stages of cow lactation.
Fontina Protected Denomination of Origin (PDO) cheese is a full-fat semi-cooked cheese traditionally made in Northwest Italy (Aosta Valley) and manufactured from raw cow's milk. The management of cattle farms in Aosta Valley calls for seasonal migration to high pastures during the summer and the concentration of calving during the autumn and the beginning of the winter. Based on cattle physiology and given to calving seasonality, three cow lactation phases i.e. post-partum, oestrus and early gestation, can be identified and an effect could be hypothesized on average milk composition and on cheese quality. The aim of the present paper was to investigate the bacterial dynamics during Fontina PDO cheese manufacturing and ripening, in relation to the different lactation stages, in order to evaluate a possible correlation between microbiota and phase of lactation. For this purpose, microbial RNA analysis was carried out by RT-PCR coupled with DGGE and high-throughput sequencing. A good performance of the starter cultures was highlighted throughout Fontina PDO manufacturing and ripening; in fact, the starter prevailed against the autochthonous microbiota. Thus, the microbial activity, which was supposed to affect the final quality of Fontina PDO cheese, appeared to be strictly associated to the presence of the starter, which did not show any difference in its performance according to the different stages of cow lactation. Therefore, the results of this research highlighted a negligible correlation between the microbiota of raw milk and the organoleptic quality and typicity of Fontina cheese in relation to lactation seasonality.


Comparative study and multiple linear regression analysis for assessment of chromatographic behavior of structurally related β-blockers on different stationary phases.
A quantitative structure-retention relationship study was performed by thin layer chromatography on a number of β-blockers using 315 molecular descriptors of which nine were selected to be having the most important physicochemical properties. These descriptors provide good correlations with chromatographic behavior of the studied structurally related drugs. This research was completed on three pretreated silica gel plates via impregnation in urea, sodium dodecyl sulfate, and dimethylformamide, hence it possesses varying interplay mechanisms and polarities. The retention parameters were obtained by utilizing four solvent systems of two additives of variable ratios, consequently specific polarities in addition to imparted different pH values using either glacial acetic acid or liquid ammonia. Calculated theoretical approaches prove good correlations between investigated descriptors and retention factors. Some correlations show excellent predicting models, which might be critical for toning better know-how relationships between chemical structures and retention of β-blockers.


The correlation between osteoarthritis stage and the effect of the lateral wedge insole for 3 months on medial meniscus extrusion in the knee joint.
Medial meniscus extrusion (MME) leads to symptomatic knee osteoarthritis (OA) due to increased mechanical stress. MME increases with weight-bearing, and the difference in MME between non-weight-bearing and weight-bearing status (ΔMME) is a factor that causes greater MME. The lateral wedge insole (LWI) is an ideal approach for decreasing the amount of ΔMME associated with the reduction of medial loading stress in the early stage of knee OA. However, the effect of the LWI for 3 months on the ΔMME and its response to OA stage have not been elucidated. To investigate the effects of the LWI for 3 months on MME and the ΔMME in each stage of OA. Participants were divided into three groups: no intervention with the LWI (control group; n = 9) and intervention with the LWI in early OA (early OA group: Kellgren-Lawrence (K/L) stage = 2, n = 17) and late OA (late OA group: K/L stage > 2, n = 13). MME was evaluated using ultrasound, and the ΔMME was obtained as the difference in MME from non-weight-bearing and weight-bearing conditions. These measurements were performed at two time points: the initial office visit as a baseline and post-3 months. The weight-bearing MME and ΔMME values post-3 months were significantly decreased compared with those at baseline in the early OA group but not in the control or late OA groups. The use of the LWI for 3 months decreased weight-bearing MME and ΔMME values, and its effectiveness was more pronounced in the early stage of knee OA.


Cloning of the canine RNA polymerase I promoter and establishment of reverse genetics for influenza A and B in MDCK cells.
Recent incidents where highly pathogenic influenza A H5N1 viruses have spread from avian species into humans have prompted the development of cell-based production of influenza vaccines as an alternative to or replacement of current egg-based production. Madin-Darby canine kidney (MDCK) cells are the primary cell-substrate candidate for influenza virus production but an efficient system for the direct rescue of influenza virus from cloned influenza cDNAs in MDCK cells did not exist. The objective of this study was to develop a highly efficient method for direct rescue of influenza virus in MDCK cells. The eight-plasmid DNA transfection system for the rescue of influenza virus from cloned influenza cDNAs was adapted such that virus can be generated directly from MDCK cells. This was accomplished by cloning the canine RNA polymerase I (pol I) promoter from MDCK cells and exchanging it for the human RNA pol I promoter in the eight plasmid rescue system. The adapted system retains bi-directional transcription of the viral cDNA template into both RNA pol I transcribed negative-sense viral RNA and RNA pol II transcribed positive-sense viral mRNA. The utility of this system was demonstrated by rescue in MDCK cells of 6:2 genetic reassortants composed of the six internal gene segments (PB1, PB2, PA, NP, M and NS) from either the cold-adapted (ca) influenza A vaccine strain (ca A/Ann Arbor/1/60) or the ca influenza B vaccine strain (ca B/Ann Arbor/1/66) and HA and NA gene segments from wild type influenza A and B strains. Representative 6:2 reassortants were generated for influenza A (H1N1, H3N2, H5N1, H6N1, H7N3 and H9N2) and for both the Victoria and Yamagata lineages of influenza B. The yield of infectious virus in the supernatant of transfected MDCK cells was 106 to 107 plaque forming units per ml by 5 to 7 days post-transfection. This rescue system will enable efficient production of both influenza A and influenza B vaccines exclusively in MDCK cells and therefore provides a tool for influenza pandemic preparedness.


Three-dimensional sonography in the prenatal diagnosis of aortic arch abnormalities.
To assess the added value of 3-dimensional (3D) echocardiography with spatiotemporal image correlation (STIC) in the diagnosis of aortic arch abnormalities in fetuses with isolated abnormal upper thoracic 3-vessel view (3VV). A total of 3,420 women underwent a targeted anatomic survey at 18-22 weeks' gestation in a 1-year period. An isolated abnormal upper thoracic 3VV detected on 2-dimensional (2D) imaging was followed up by conventional 2D echocardiography and 3D fetal echocardiography with STIC. Offline reconstruction by a second operator blinded to the suspected diagnosis was performed. Neonatal echocardiography and MRI with 3D reconstruction were performed to verify the prenatal diagnosis. Of the 3,420 patients referred, 4 had an isolated abnormal 3VV (0.09%). A right-sided aortic arch (RAA, n = 3) and double aortic arch (DAA, n = 1) were suspected. In all aortic arch abnormalities, 3D fetal echocardiography and STIC correctly identified RAA with aberrant left subclavian artery in 3 cases and DAA in 1 case with a degree of definition that was equal to the confirmatory postnatal echocardiography and 3D MRI. Although the 2D upper 3VV is a powerful screening tool for isolated aortic arch abnormalities, 3D fetal echocardiography with STIC allows an accurate prenatal characterization of the abnormality to a degree that is typically attainable only by post partum imaging.


Rebamipide ameliorates indomethacin-induced small intestinal injury in rats via the inhibition of matrix metalloproteinases activity.
The pathogenesis of non-steroidal anti-inflammatory drugs (NSAIDs)-induced small intestinal lesions remains unclear, although it is considered to be quite different from that of upper gastrointestinal tract ulcers due to the absence of acid and the presence of bacteria and bile in the small intestine. The aim of this study was to characterize specific gene expression profiles of intestinal mucosa in indomethacin-induced small intestinal injury, and to investigate the effects of rebamipide on the expression of these genes. Intestinal injury was induced in male Wistar rats by subcutaneous administration of indomethacin. Total RNA of the intestinal mucosa was extracted 24 h after indomethacin administration, gene expression was investigated using microarray analysis, and the identified genes were confirmed by real-time polymerase chain reaction (PCR). In addition, we investigated whether the treatment with rebamipide altered the expression of these identified genes. The administration of indomethacin induced small intestine injuries, and these lesions were significantly inhibited by the treatment with rebamipide. Microarray analysis showed that the genes for several matrix metalloproteinases (MMPs) and several chemokine-related genes were significantly upregulated, and metallothionein 1a (MT1a) was downregulated in the intestinal mucosa after administration of indomethacin. The expressions of these genes were reversed by the treatment with rebamipide. These data suggest that MMPs, chemokines, and MT1a may play an important role in the intestinal mucosal injury induced by indomethacin. In particular, the inhibition of MMP genes and chemokine-related genes by rebamipide may be important for the therapeutic effect against NSAIDs-induced small intestinal injury.


[WT inhibit human hepatocellular carcinoma BEL-7402 cells growth by modulating Akt and ERK1/2 phosphorylation].
To investigate effects of Akt and ERK1/2 signaling pathways on waltonitone (WT) induced cell growth inhibition in human hepatocellular carcinoma BEL-7402 cells. Cell viability of BEL-7402 cells was examined using MTT assay. Phosphorylation of E Akt and RK1/2 were detected by Western blot analysis, while cell cycle distribution of BEL7402 cells was analyzed by flow cytometry. WT could inhibit the BEL-7402 cells growth, induce the S-phase cell cycle arrest, activate Akt and ERK1/2 phosporylation. Moreover, the cell growth inhibition and S-phase cell cycle arrest induction of WT on BEL-7402 cells could be blocked by Akt and ERK1/2 inhibitors. WT induce the cell cycle arrest and inhibit the cell growth on BEL-7402 cells by modulating Akt and ERK1/2 phosphorylation.


Application of a continuously stirred tank bioreactor (CSTR) for bioremediation of hydrocarbon-rich industrial wastewater effluents.
A continuously stirred tank bioreactor (CSTR) was used to optimize feasible and reliable bioprocess system in order to treat hydrocarbon-rich industrial wastewaters. A successful bioremediation was developed by an efficient acclimatized microbial consortium. After an experimental period of 225 days, the process was shown to be highly efficient in decontaminating the wastewater. The performance of the bioaugmented reactor was demonstrated by the reduction of COD rates up to 95%. The residual total petroleum hydrocarbon (TPH) decreased from 320 mg TPH l(-1) to 8 mg TPH l(-1). Analysis using gas chromatography-mass spectrometry (GC-MS) identified 26 hydrocarbons. The use of the mixed cultures demonstrated high degradation performance for hydrocarbons range n-alkanes (C10-C35). Six microbial isolates from the CSTR were characterized and species identification was confirmed by sequencing the 16S rRNA genes. The partial 16S rRNA gene sequences demonstrated that 5 strains were closely related to Aeromonas punctata (Aeromonas caviae), Bacillus cereus, Ochrobactrum intermedium, Stenotrophomonas maltophilia and Rhodococcus sp. The 6th isolate was affiliated to genera Achromobacter. Besides, the treated wastewater could be considered as non toxic according to the phytotoxicity test since the germination index of Lepidium sativum ranged between 57 and 95%. The treatment provided satisfactory results and presents a feasible technology for the treatment of hydrocarbon-rich wastewater from petrochemical industries and petroleum refineries.


Role of cyclic GMP in the modulation by endothelium of the adrenolytic action of prazosin in the rat isolated aorta.
The effect of endothelium on the adrenolytic action of prazosin was studied in the rat isolated aorta. Prazosin showed a non-competitive type of antagonism in preparations with intact endothelium while in preparations where endothelium had been removed, prazosin at concentrations between 0.3 nM-10 nM acted as a competitive antagonist. Methylene blue, used to decrease tissue levels of guanosine 3':5'-cyclic monophosphate (cyclic GMP), converted prazosin from a non-competitive antagonist into an apparently competitive antagonist in the presence of endothelium. Increasing tissue levels of cyclic GMP by incubation with 8-bromo-cyclic GMP converted prazosin from an apparently competitive antagonist into a non-competitive antagonist in the absence of endothelium. Analysis of concentration-response curves for noradrenaline in the presence and absence of endothelium showed that the affinity for noradrenaline was the same but the efficacy, measured by estimating the receptor reserve, was not; it was lower in the presence than in the absence of endothelium. It was concluded that the change in the mode of antagonism of prazosin after endothelium removal could be related to an alteration in the efficacy of the agonist, brought about by a change in the tissue levels of cyclic GMP.


Nitrate and nitrite as mixed source of nitrogen for Chlorella vulgaris: Growth, nitrogen uptake and pigment contents.
Chlorella vulgaris was grown using mixed sources of nitrogen (nitrate and nitrite). Starting from B3N as basal medium, nitrate was substituted by nitrite keeping total nitrogen constant over 7 conditions: 0, 20, 40, 50, 60, 80 and 100% NO2-. Growth rate, nitrogen uptake, photosynthetic apparatus status and pigment contents were monitored. Nitrite addition triggered a growth rate inhibition from early introduction (20% NO2-, 81 mgNO2-/l). Nitrate uptake rate increased with nitrate content in the culture medium (maximum at 5.87 mg/l/Nd, 100% NO3-), while nitrite uptake remained constant around 2.93 mgN/l/d. Photosynthetic apparatus was not impacted by the nitrogen source substitution. Pigments profiles (chlorophyll a, b and total carotenoids) were not statistically different for all the tested conditions. From a biotechnological perspective, this finding rules out the use of nitrite substitution as a pigment manipulating stress strategy.


Parental Life Span and Polygenic Risk Score of Longevity Are Associated With White Matter Hyperintensities.
Human longevity is moderately heritable and is hence influenced by both genetic and environmental factors. However, there remains considerable uncertainty regarding its relationship with brain aging. Here, we used a discovery sample (N = 19 136, aged 45-81 years) from the UK Biobank and a replication sample (N = 809, aged 66-93 years) from the Sydney Memory and Ageing Study and the Older Australian Twins Study to investigate the associations between both parental life span (parental age at death) and polygenic risk score (PRS) for longevity (longevity-PRS) and structural magnetic resonance imaging brain metrics, which are considered to reflect the brain aging process, namely white matter hyperintensities (WMHs), total gray matter, and cortical volumes. We found lower volumes of WMHs to be significantly associated with longer parental life span in the discovery (whole WMH, β = -0.0323, padj = .0002) and replication samples (whole WMH, β = -0.0871, padj = .0208) and higher longevity-PRS in the discovery sample (whole WMH, β = -0.0331, padj = .0015) and a similar trend in the replication sample (significant before multiple comparison adjustment). The association of longevity-PRS with WMH remained significant after removing the influence of the apolipoprotein E locus (whole WMH, β = -0.0297, padj = .0048). While total gray matter and cortical volumes were related to parental life span in the discovery sample, they were not significantly associated with longevity-PRS. Additionally, the effects of longevity-PRS on the association were more prominent in males. Our findings suggest that enrichment of longevity-related alleles may provide some protection against WMH burden and highlight the important aspect of genetic relationship between longevity and WMH.


TESC gene-regulating genetic variant (rs7294919) affects hippocampal subfield volumes and parahippocampal cingulum white matter integrity in major depressive disorder.
Two recent genome-wide association studies have suggested that rs7294919 is associated with changes in hippocampal volume. rs7294919 regulates the transcriptional products of the TESC gene, which is involved in neuronal proliferation and differentiation. We investigated the interactive effect of rs7294919 and major depressive disorder (MDD) on the volume of the hippocampal subfields and the integrity of the parahippocampal cingulum (PHC). We also investigated the correlation of these structural changes with the DNA methylation status of rs7294919. A total of 105 patients with MDD and 85 healthy control subjects underwent T1-weighted structural magnetic resonance imaging and diffusion tensor imaging. The rs7294919 was genotyped and its DNA methylation status was assessed in all the participants. We analyzed the hippocampal subfield volumes and PHC integrity using FreeSurfer and the Tracts Constrained by Underlying Anatomy (TRACULA) respectively. Significant interactive effects of rs7294919 and MDD were observed in the volumes of the dentate gyrus and CA4. The patients with MDD had increased methylation in two of the three CpG loci of rs7294919, and the methylation of CpG3 was significantly correlated with right PHC integrity in the MDD group. Our results provide neurobiological evidence for the association of rs7294919 with brain structural changes in MDD.


Ketamine and xylazine effects in murine model of acute pancreatitis.
Ketamine and xylazine (Ket/Xyl) are anesthetic agents that target neural pathways and are commonly used in combination in mouse studies. Since neural pathways can modulate acute pancreatitis severity, we asked if Ket/Xyl affect disease severity. C57BL/6 mice were treated with six hourly injections of cerulein to induce mild acute pancreatitis. Mice were also treated with and without ketamine, xylazine, and Ket/Xyl before pancreatitis induction in vivo and in vitro. Ket/Xyl pretreatment in vivo increased selected parameters of pancreatitis severity such as trypsin activity and edema; these effects were predominantly mediated by xylazine. Ket/Xyl also changed markers of autophagy. These in vivo effects of Ket/Xyl were not attenuated by atropine. The drugs had no little to no effect on pancreatitis responses in isolated pancreatic cells or lobules. These findings suggest that Ket/Xyl administration can have substantial effect on acute pancreatitis outcomes through nonmuscarinic neural pathways. Given widespread use of this anesthetic combination in experimental animal models, future studies of inflammation and injury using Ket/Xyl should be interpreted with caution.NEW & NOTEWORTHY Ketamine and xylazine anesthetic agent administration before acute pancreatitis induction in mice lead to changes in pancreatitis responses independent of acute pancreatitis induction. Future studies should consider the potential effects of anesthesia administration when studying disease processes associated with inflammation and injury.


Epidemiological and clinical characteristics of road traffic crashes related thoracic traumas: analysis of 5095 hospitalized chest injury patients.
Road traffic crashes related (RTCR) chest traumas remain important global public health challenge. The impact of boosting market of automobile vehicles in China during last decade on thoracic injury needs to be defined. This study aimed to review and analyze the demographic and clinical characteristics of RTCR thoracic injuries in China. Clinical records of patients with thoracic trauma admitted to thoracic surgery department between January 2003 and June 2020 were retrospectively retrieved and reviewed. Patients' profiles and clinical characteristics were comparatively analyzed between road traffic crashes caused injury and other injury mechanisms, and in RTCR chest trauma patients before January 2011 (2003 group), and after January 2011 (2011 group), when is considered as the beginning year of Chinese household vehicle era. The study included 5095 thoracic trauma patients with mean age of 50.2 years, of whom 79.4% were male. Most of the patients (70.3%, n = 3583) had rib fractures. Associated injuries were present in 52.0% of the patients, of them 78.5% (n = 2080) were extremity fractures. Road traffic crashes accounted for 41.4% (n = 2108) of the injuries, most of them (98.0%) were related to motor vehicles. In comparison with other chest trauma mechanisms, RTCR chest injuries affected females and older males more frequently, with a higher incidence of rib fractures and sternum fractures, and higher injury severity scores (ISS) (all p < 0.05). Surgeries were required in 1495 (70.9%) patients of the RRTCR chest traumas, while the majority of non-RTCR thoracic injuries were managed conservatively or with tube thoracostomy (30.2%, n = 901). RTCR chest traumas caused longer hospital stay (13.0 ± 9.6 days vs. 11.8 ± 7.4 days, p = 0.001), higher ICU usage (30.7% vs. 19.6%, p = 0.001), higher rate of ventilator support (12.9% vs. 7.5%, p = 0.001), and higher mortalities (3.8% vs. 1.6%, p = 0.005) than that of non-RTRA chest injuries. For RTCR patients, when compared with 2003 group, 2011 group had similar patterns in terms of accident category, associated injury and treatment. However, 2011 group had more females (38.5% vs. 18.0%, p = 0.001) and older males (50.6 ± 9.7 vs. 47.9 ± 17.2, p = 0.001), with a higher ISS (18.3 ± 10.2 vs. 17.1 ± 8.9, p = 0.004), and fewer were managed with chest tubes (25.0% vs. 29.2%, p = 0.031). Clinical outcomes were not significantly different between the groups in terms of hospital length of stay, intensive care unit (ICU) usage, ICU length of stay, duration of ventilator hours and mortality. However, the 2011 group had more patients requiring ventilator support (14.4% vs. 10.6%, p = 0.011). Road traffic crashes remain to be the major etiology of thoracic injuries in China, which usually affects middle-aged males, causing rib fractures with concomitant injuries frequently occurring to other organ systems. Treatments mainly include tube thoracotomy and surgical procedures. Although the clinical characteristics and outcomes of traffic accident related chest traumas are largely unchanged in spite of the rapid increasing numbers of motor vehicles, variations in the pattern of injuries by gender, age, injury severity and ventilator usage may still provide important information for targeted management.


The tumor suppressor gene rap1GAP is silenced by miR-101-mediated EZH2 overexpression in invasive squamous cell carcinoma.
Rap1GAP is a critical tumor suppressor gene that is downregulated in multiple aggressive cancers, such as head and neck squamous cell carcinoma, melanoma and pancreatic cancer. However, the mechanistic basis of rap1GAP downregulation in cancers is poorly understood. By employing an integrative approach, we demonstrate polycomb-mediated repression of rap1GAP that involves Enhancer of Zeste Homolog 2 (EZH2), a histone methyltransferase in head and neck cancers. We further demonstrate that the loss of miR-101 expression correlates with EZH2 upregulation, and the concomitant downregulation of rap1GAP in head and neck cancers. EZH2 represses rap1GAP by facilitating the trimethylation of histone 3 at lysine 27, a mark of gene repression, and also hypermethylation of rap1GAP promoter. These results provide a conceptual framework involving a microRNA-oncogene-tumor suppressor axis to understand head and neck cancer progression.


Health technology prioritization: which criteria for prioritizing new technologies and what are their relative weights?
To review the criteria and 'other' considerations used internationally for prioritizing new health technologies, and to demonstrate a conjoint-analysis methodology (also known as discrete choice experiments) for deriving relative weights for the criteria. We searched the literature for criteria and other considerations for prioritizing new technologies. A convenience sample of 74 respondents completed a conjoint-analysis survey involving criteria related to technologies' 'benefits'. Encompassing 11 countries and the US state of Oregon, we were able to distinguish three main groups of criteria: (a) Need, appropriateness and clinical benefits; (b) Efficiency (including cost-effectiveness); and (c) Equality, solidarity and other ethical or social values. For several countries, the quality of the clinical and economic evidence and factors related to strategic issues and procedural justice respectively are also considered. The criteria and their weights from the conjoint-analysis survey are: 'Lives saved'=0.343, 'Life-prolongation benefits'=0.243, 'Quality-of-life gains'=0.217, a criterion representing the availability of alternative treatments=0.107, and 'Other important social/ethical benefits'=0.087. The criteria represent a pluralistic combination of needs-based, maximizing and egalitarian principles, and we demonstrated a methodology for deriving the weights for criteria related to technologies' 'benefits'.


Is One Anastomosis Gastric Bypass with a Biliopancreatic Limb of 150 cm Effective in the Treatment of People with Severe Obesity with BMI > 50?
The treatment of people with severe obesity and BMI > 50 kg/m2 is challenging. The present study aims to evaluate the short and mid-term outcomes of one anastomosis gastric bypass (OAGB) with a biliopancreatic limb of 150 cm as a primary bariatric procedure to treat those people in a referral center for bariatric surgery. Data of patients who underwent OAGB for severe obesity with BMI > 50 kg/m2 between 2010 and 2017 were collected prospectively and analyzed retrospectively. Follow-up comprised clinical and biochemical assessment at 1, 3, 6, 12, 18, and 24 months postoperatively, and once a year thereafter. Overall, 245 patients underwent OAGB. Postoperative mortality was null, and early morbidity was observed in 14 (5.7%) patients. At 24 months, the percentage total weight loss (%TWL) was 43.2 ± 9, and percentage excess weight loss (%EWL) was 80 ± 15.7 (184 patients). At 60 months, %TWL was 41.9 ± 10.2, and %EWL was 78.1 ± 18.3 (79 patients). Conversion to Roux-en-Y gastric bypass was needed in three (1.2%) patients for reflux resistant to medical treatment. Six patients (2.4%) had reoperation for an internal hernia during follow-up. Anastomotic ulcers occurred in three (1.2%) patients. Only two patients (0.8%) underwent a second bariatric surgery for insufficient weight loss. OAGB with a biliopancreatic limb of 150 cm is feasible and associated with sustained weight loss in the treatment of severe obesity with BMI > 50 kg/m2. Further randomized studies are needed to compare OAGB with other bariatric procedures in this setting.


Perceived friend support buffers against symptoms of depression in peer victimized adolescents: Evidence from a population-based cohort in South Korea.
Peer victimization is associated with an increased risk for depression, but there is less evidence on how certain factors such as friend support can buffer this association. This study investigated the associations between friend support and depressive symptoms among victimized and non-victimized adolescent girls and boys from South Korea. Participants includes 2258 students from the Korean Children and Youth Panel Survey, a nationally representative sample of middle school students in South Korea. Self-reported perceived friend support, depressive symptoms and peer victimization were measured using validated scales during middle school year 3 (mean age= 15.7 years). The association between peer victimization and depressive symptoms varied by sex (p for sex by peer victimization interaction<0.05). Peer victimization was more strongly associated with same year depressive symptoms in girls (β=0.55) than boys (β=0.24). After controlling for key confounders, including prior year mental health symptoms, higher levels of friend support were found to attenuate the association between peer victimization and depressive symptoms (p for friend support by peer victimization interaction <0.05). Peer victimization was associated with more depressive symptoms for adolescents with low and moderate friend support, but not those with high friend support. Peer victimization, depressive symptoms, and friend support, were self-reported and measured the same year. Friend support protects victimized South Korean adolescents from the negative effect of peer victimization on depressive symptoms, hence contributes to closing the gap in depression between victimized and non-victimized adolescents.


Recent advances in sample preparation techniques and methods of sulfonamides detection - A review.
Sulfonamides (SAs) have been the most widely used antimicrobial drugs for more than 70 years, and their residues in foodstuffs and environmental samples pose serious health hazards. For this reason, sensitive and specific methods for the quantification of these compounds in numerous matrices have been developed. This review intends to provide an updated overview of the recent trends over the past five years in sample preparation techniques and methods for detecting SAs. Examples of the sample preparation techniques, including liquid-liquid and solid-phase extraction, dispersive liquid-liquid microextraction and QuEChERS, are given. Different methods of detecting the SAs present in food and feed and in environmental, pharmaceutical and biological samples are discussed.


Primary melanoma of submandibular gland: case report and literature review of a very rare entity.
Cutaneous melanomas account for more than 95% of all cases of primary melanoma, making non-cutaneous primary melanomas truly rare. Cases of primary mucosal melanomas of the oral cavity have been widely described; however, instances of primary melanomas arising from salivary glands have been rarely described. To date, this is only the second case of primary melanoma of the submandibular gland. This is a report of a case of a 36-year-old healthy male patient, who was referred to us with the chief complaint of a growing swelling on the left side of his lower jaw. Evaluations revealed an evident facial asymmetry in the frontal view with a firm, non-tender swelling. Initial orthopantomogram did not reveal any alterations in the trabeculation or morphology of the jaws and the surrounding structures. A soft tissue ultrasonography of the left submandibular gland and anterior region of mandible revealed a hypoechoic cystic mass with numerous micro-echoes. Further para-clinical examinations yielded the definitive diagnosis of primary melanoma of the submandibular gland. Moreover, no evidence of distant osteometastasis was observed in whole-body scans. Subsequent surgical management with the approach of excising the submandibular salivary gland and concurrent selective neck dissection was implemented. This report emphasizes the importance of thorough examination and prompt referral to designated specialists in cases with suspicious behaviors which are unresponsive to treatments. It can be further concluded that melanoma can mimic a range of benign pathologies; therefore, putting it in the list differential diagnosis of similar lesions seems plausible.


Outcome of lower extremity revascularization for peripheral artery occlusive disease: is there a difference between men and women?
The incidence of peripheral arterial occlusive disease (PAD) increases with age. Women represent a growing percentage of the elderly population who present with PAD. While speculation exists that gender affects outcome after revascularization procedures, the literature is confusing and often conflicting. This review compares outcomes by gender after open surgical and endovascular lower extremity revascularization (LER) procedures including: demographic differences, patency rates, limb salvage rates, long-term survival, perioperative complications and 30-day mortality. This review summarizes the existing data and discusses current influences on outcome after LER.


Solvent-induced shape evolution of PVP protected spherical silver nanoparticles into triangular nanoplates and nanorods.
The reaction between silver nitrate and poly(N-vinyl-2-pyrrolidone) (PVP) in pyridine at ambient conditions could lead to the formation of spherical nanoparticles or quadrilateral and triangular silver nanoplates, depending on the silver-to-PVP ratio used. It is proposed that the spherical Ag nanoparticles, which were formed early in the reaction, were transformed into nanoplates through an Ostwald ripening process driven by the bridging flocculation of small spherical Ag nanoparticles. This unique and hitherto unreported shape evolution process was carefully followed by a combination of techniques, viz., UV-visible spectroscopy, TEM, and powder X-ray diffraction.


Validation of a two-dimensional liquid chromatography method for quality control testing of pharmaceutical materials.
Despite the advantages of 2D-LC, there is currently little to no work in demonstrating the suitability of these 2D-LC methods for use in a quality control (QC) environment for good manufacturing practice (GMP) tests. This lack of information becomes more critical as the availability of commercial 2D-LC instrumentation has significantly increased, and more testing facilities begin to acquire these 2D-LC capabilities. It is increasingly important that the transferability of developed 2D-LC methods be assessed in terms of reproducibility, robustness and performance across different laboratories worldwide. The work presented here focuses on the evaluation of a heart-cutting 2D-LC method used for the analysis of a pharmaceutical material, where a key, co-eluting impurity in the first dimension (1D) is resolved from the main peak and analyzed in the second dimension (2D). A design-of-experiments (DOE) approach was taken in the collection of the data, and the results were then modeled in order to evaluate method robustness using statistical modeling software. This quality by design (QBD) approach gives a deeper understanding of the impact of these 2D-LC critical method attributes (CMAs) and how they affect overall method performance. Although there are multiple parameters that may be critical from method development point of view, a special focus of this work is devoted towards evaluation of unique 2D-LC critical method attributes from method validation perspective that transcend conventional method development and validation. The 2D-LC method attributes are evaluated for their recovery, peak shape, and resolution of the two co-eluting compounds in question on the 2D. In the method, linearity, accuracy, precision, repeatability, and sensitivity are assessed along with day-to-day, analyst-to-analyst, and lab-to-lab (instrument-to-instrument) assessments. The results of this validation study demonstrate that the 2D-LC method is accurate, sensitive, and robust and is ultimately suitable for QC testing with good method transferability.


Sensitive approach to smoking ban.
Following the recent ban on smoking in enclosed public spaces, it is in hospitals where the sick, bereaved or emotionally unstable are most likely to find it difficult to abstain, according to the company that provides security services at many NHS hospitals.


Formation of diacetyl and acetoin by Lactococcus lactis via aspartate catabolism.
To verify whether diacetyl can be produced by Lactococcus lactis via amino acid catabolism, and to investigate the impact of the pH on the conversion. Resting cells of L. lactis were incubated in reaction media at different pH values, containing L-aspartic acid or L-alanine as a substrate. After incubation, the amino acid and metabolites were analysed by HPLC and GC/MS. At pH 5 about 75% of aspartic acid and only 40% of alanine was degraded to pyruvate via a transamination step that requires the presence of alpha-ketoglutarate in the medium, but diacetyl was only produced from aspartic acid. Three per cent of pyruvate was transformed to acetolactate of which 50% was converted into diacetyl. At pH 5 x 5 and above the pyruvate conversion into acetolactate was less efficient than at pH 5, and acetolactate was mainly decarboxylated to acetoin. Acetoin and diacetyl can be formed as a result of aspartate or alanine catabolism by L. lactis in the presence of alpha-ketoglutarate in the medium. Lactic acid bacteria exhibiting both glutamate dehydrogenase activity and high aspartate aminotransferase activity are expected to be good diacetyl producers during cheese ripening at pH close to 5.


Evoked potential topography in major depression. I. Comparisons with nonpatients and schizophrenics.
This study compared evoked potential (EP) topography in major depression (MD), schizophrenia and nonpatient controls. EPs to four kinds of stimuli were recorded from 15 locations. Patients were 69 MDs and 52 schizophrenics, currently unmedicated. EP waveforms of 195 controls were subjected to principal component factor analysis (PCA). The structures of 32 factors so extracted have been shown to encompass the data space of disparate groups; they were used to compute factor scores for all subjects. Age- and gender-matched groups were compared. Factor scores were normalized across leads (Z-transform) to distinguish between topographic and mean level differences. Topographic differences (P < 0.05) between MD and controls were demonstrated for scores of 8 factors, with 2 others at P = 0.053. Unlike those for schizophrenia/control comparisons, these topographic differences did not converge regionally in MD. EP findings were not related to duration of withdrawal from drugs. There were few differences between bipolar and unipolar patients. Topographies of 5 factors differed between MDs and schizophrenics; these involved all modalities and reflected long latency, cognition-related events, such as P300. These topographic differences were antero-posterior (AP); values were greater posteriorly in MDs and anteriorly in schizophrenics. Deviant AP gradients appear specific to MD; gradients were similar in schizophrenics and controls.


Purification, physicochemical characterization, saccharide specificity, and chemical modification of a Gal/GalNAc specific lectin from the seeds of Trichosanthes dioica.
A new galactose-specific lectin has been purified from the extracts of Trichosanthes dioica seeds by affinity chromatography on cross-linked guar gum. The purified lectin (T. dioica seed lectin, TDSL) moved as a single symmetrical peak on gel filtration on Superose-12 in the presence of 0.1 M lactose with an M(r) of 55 kDa. In the absence of ligand, the movement was retarded, indicating a possible interaction of the lectin with the column matrix. In SDS-PAGE, in the presence of beta-mercaptoethanol, two non-identical bands of M(r) 24 and 37 kDa were observed, whereas in the absence of beta-mercaptoethanol, the lectin yielded a single band corresponding to approximately 55,000 Da, indicating that the two subunits of TDSL are connected by one or more disulfide bridges. TDSL is a glycoprotein with about 4.9% covalently bound neutral sugar. Analysis of near-UV CD spectrum by three different methods (CDSSTR, CONTINLL, and SELCON3) shows that TDSL contains 13.3% alpha-helix, 36.7% beta-sheet, 19.4% beta-turns, and 31.6% unordered structure. Among a battery of sugars investigated, TDSL was inhibited strongly by beta-d-galactopyranosides, with 4-methylumbelliferyl-beta-d-galactopyranoside being the best ligand. Chemical modification studies indicate that tyrosine residues are important for the carbohydrate-binding and hemagglutinating activities of the lectin. A partial protection was observed when the tyrosine modification was performed in the presence of 0.2 M lactose. The tryptophan residues of TDSL appear to be buried in the protein interior as they could not be modified under native conditions, whereas upon denaturation with 8 M urea two Trp residues could be selectively modified by N-bromosuccinimide. The subunit composition and size, secondary structure, and sugar specificity of this lectin are similar to those of type-2 ribosome inactivating proteins, suggesting that TDSL may belong to this protein family.


'Cellulomonas timonensis' sp. nov., taxonogenomics description of a new bacterial species isolated from human gut.
'Cellulomonas timonensis' sp. nov. strain sn7T is a new species within the Cellulomonas genus. We present the main phenotypic characteristics and provide a complete annotation of its genome sequence. This facultative anaerobic bacterium, isolated from the stool of 38-year-old obese Frenchman, is Gram-positive, has motile rods and is sporulating. The genome is 4 057 828 bp long with 72.42% G + C content. Of the 3732 predicted genes, 3667 were protein-coding genes and 65 were RNAs.


Targeting the PEDV 3CL protease for identification of small molecule inhibitors: an insight from virtual screening, ADMET prediction, molecular dynamics, free energy landscape, and binding energy calculations.
The porcine epidemic diarrhea virus (PEDV) represents a major health issue for piglets worldwide and does significant damage to the pork industry. Thus, new therapeutic approaches are urgently needed to manage PEDV infections. Due to the current lack of a reliable remedy, this present study aims to identify novel compounds that inhibit the 3CL protease of the virus involved in replication and pathogenesis. To identify potent antiviral compounds against the 3CL protease, a virtual screening of natural compounds (n = 97,999) was conducted. The top 10 compounds were selected based on the lowest binding energy and the protein-ligand interaction analyzed. Further, the top five compounds that demonstrated a strong binding affinity were subjected to drug-likeness analysis using the ADMET prediction, which was followed by molecular dynamics simulations (500 ns), free energy landscape, and binding free energy calculations using the MM-PBSA method. Based on these parameters, four putative lead (ZINC38167083, ZINC09517223, ZINC04339983, and ZINC09517238) compounds were identified that represent potentially effective inhibitors of the 3CL protease. Therefore, these can be utilized for the development of novel antiviral drugs against PEDV. However, this requires further validation through in vitro and in vivo studies.


Physical and psychological functioning of patients with chronic limb ischemia during a 1-year period after endovascular revascularization.
Symptoms of peripheral artery disease (PAD) and patients' physical and psychological status are related in a vicious circle. The aim of this study was to determine the relationships between improvement in parameters of PAD after endovascular procedures and changes in patients' physical and psychological status. We studied 140 consecutive patients with PAD: 50 patients with chronic limb-threatening ischemia (CLTI), 50 patients with intermittent claudication (IC) undergoing an endovascular procedure, and 40 patients with IC who were not qualified for leg revascularization. All participating patients were assessed at the beginning of the study and at 3 and 12 months of follow-up; scores taken included ankle-brachial index, 6-minute walking test distance, Barthel Index, activities of daily living index, instrumental activities of daily living (IADL) index, Mini-Mental State Examination, and Hospital Anxiety and Depression Scale. After 12 months of follow-up, an improvement in PAD-related symptoms following leg revascularization had been maintained in 56% of the patients with CLTI and in 68% of those with IC. Twelve months after endovascular leg revascularization, the scores in respect of activities of daily living, IADL, and Mini-Mental State Examination had increased, and scores for Hospital Anxiety and Depression Scale had decreased in patients with both CLTI and IC. A higher baseline score in the IADL index was associated with a reduction in the 1-year cardiovascular event risk (odds ratio, 95% confidence interval, 0.70; 0.54-0.91; P < .01). In patients with PAD, endovascular procedures not only improved PAD-related symptoms, but also ameliorated patients' physical state, improved cognitive function, and reduced depression.


Upregulation of ASCL1 and inhibition of Notch signaling pathway characterize progressive astrocytoma.
Astrocytoma is the most common type of brain cancer constituting more than half of all brain tumors. With an aim to identify markers describing astrocytoma progression, we have carried out microarray analysis of astrocytoma samples of different grades using cDNA microarray containing 1152 cancer-specific genes. Data analysis identified several differentially regulated genes between normal brain tissue and astrocytoma as well as between grades II/III astrocytoma and glioblastoma multiforme (GBM; grade IV). We found several genes known to be involved in malignancy including Achaete-scute complex-like 1 (Drosophila) (ASCL1; Hash 1). As ASCL has been implicated in neuroendocrine, medullary thyroid and small-cell lung cancers, we chose to examine the role of ASCL1 in the astrocytoma development. Our data revealed that ASCL1 is overexpressed in progressive astrocytoma as evidenced by increased levels of ASCL1 transcripts in 85.71% (6/7) of grade II diffuse astrocytoma (DA), 90% (9/10) of grade III anaplastic astrocytoma (AA) and 87.5% (7/8) of secondary GBMs, while the majority of primary de novo GBMs expressed similar to or less than normal brain levels (66.67%; 8/12). ASCL1 upregulation in progressive astrocytoma is accompanied by inhibition of Notch signaling as seen by uninduced levels of HES1, a transcriptional target of Notch1, increased levels of HES6, a dominant-negative inhibitor of HES1-mediated repression of ASCL1, and increased levels of Notch ligand Delta1, which is capable of inhibiting Notch signaling by forming intracellular Notch ligand autonomous complexes. Our results imply that inhibition of Notch signaling may be an important early event in the development of grade II DA and subsequent progression to grade III AA and secondary GBM. Furthermore, ASCL1 appears to be a putative marker to distinguish primary GBM from secondary GBM.


The association between the health-related physical fitness and inhibitory control in preschool children.
Inhibitory control develops rapidly during the preschool stage, and development of inhibitory control in this period is significant for the healthy growth of the future. However, most studies paid more attention to children and adolescents in recent years, but less focus on preschool children. Therefore, the purpose of this study was to explore the association between the health-related physical fitness and inhibitory control in preschool children. This cross-sectional study was based on a baseline data from randomized controlled trial by cluster sampling(including 128 preschoolers, 70 boys, 58girls).The health-related physical fitness T-score (HPFT) was obtained by adding standard scores of six indicators: body mass index, handgrip strength, standing long jump, one-leg balance, 2 × 10 m shuttle run test, and 20 m shuttle run test. Inhibitory control was assessed using the flanker task and reflected by reaction time and accuracy. A total of 120 preschoolers were included in the final statistical analysis. After adjusting the confounders, HPFT was associated with reaction time (β=-2.49 ms, 95%CI: -4.22, -0.75). Similarly, a negative association was observed between one-leg balance and reaction time (β=-12.04 ms, 95%CI: -18.94, -5.15), and between 20 m shuttle run test and reaction time (β=-23.28 ms, 95%CI: -37.00, -9.56). Compared with the participants in the lowest tertile, HPFT (β=-158.74, 95%CI: -309.63, -7.84), one-leg balance (β=-267.25 ms, 95%CI: -420.71, -113.79) and 20 m shuttle run test (β=-215.58 ms, 95%CI: -374.67, -56.49) were all negatively associated with reaction time of those in the highest tertile. Negative relationships between HPFT and RT of the inhibitory control were observed in preschoolers. To have better inhibitory control, it's suggested that HPFT of preschoolers should be at least 249. These findings are of great significance for the early improvement of HPFT and the development of inhibitory control in preschool children.


A behavioral treatment of compulsive lip-biting.
This case report describes the successful behavioral treatment of compulsive lip-biting and face scarring in a 12 yr-old boy. The condition had been long standing, self-mutilating and intractable. A regime of tracking (self-recording), aversive response substitution, and relaxation effected immediate and long lasting tissue repair and cure.


Degrees of separation as a statistical tool for evaluating candidate genes.
Selection of candidate genes is an important step in the exploration of complex genetic architecture. The number of gene networks available is increasing and these can provide information to help with candidate gene selection. It is currently common to use the degree of connectedness in gene networks as validation in Genome Wide Association (GWA) and Quantitative Trait Locus (QTL) mapping studies. However, it can cause misleading results if not validated properly. Here we present a method and tool for validating the gene pairs from GWA studies given the context of the network they co-occur in. It ensures that proposed interactions and gene associations are not statistical artefacts inherent to the specific gene network architecture. The CandidateBacon package provides an easy and efficient method to calculate the average degree of separation (DoS) between pairs of genes to currently available gene networks. We show how these empirical estimates of average connectedness are used to validate candidate gene pairs. Validation of interacting genes by comparing their connectedness with the average connectedness in the gene network will provide support for said interactions by utilising the growing amount of gene network information available.


Fluorescent Labeling and Confocal Microcopy of Plastids and Stromules.
While chlorophyll has served as an excellent label for plastids in green tissue, the development of fluorescent proteins has allowed their ready visualization in all tissues of the plants, revealing new features of their morphology and motility, including the presence of plastid extensions known as stromules. Gene regulatory sequences in nuclear transgenes that target proteins to plastids, as well as in transgenes introduced into plastid genomes, can be assessed or optimized through the use of fluorescent protein reporters. Fluorescent labeling of plastids simultaneously with other subcellular locations reveals dynamic interactions and mutant phenotypes. Transient expression of fluorescent protein fusions is particularly valuable to determine whether or not a protein of unknown function is targeted to the plastid. Fluorescent biosensors can assay molecules such as ATP, calcium, or reactive oxygen species. Particle bombardment and agroinfiltration methods described here are convenient for imaging fluorescent proteins in plant organelles. With proper selection of fluorophores for labeling the components of the plant cell, confocal microscopy and multiphoton microscopy can produce extremely informative images at high resolution at depths not feasible by standard epifluorescence microscopy.


The structure and formation of the glucose 6-phosphate adduct of hemoglobin A: a 31P-NMR study.
The glucose 6-phosphate adduct of hemoglobin formed on deoxy incubation of the sugar with hemoglobin is primarily present in solution as the unstable aldimine compound; in contrast, the percent ketoamine is higher if the adduct is formed in the presence of carbon monoxide. The adduct has a 31P nuclear magnetic resonance peak with a chemical shift which is 0.7 ppm up-field from the shift of unreacted glucose 6-phosphate at pH 7.0 and is constant between pH 6 and 8, while the unreacted sugar phosphate shows the characteristic change of chemical shift due to ionization of one of the phosphate protons. This suggests that, in the adduct, phosphate is involved in a salt bridge, probably at the 2,3-diphosphoglyceric acid binding site.


Effects of winter and summer conditions on Cd fractionation and bioavailability, bacterial communities and Cd phytoextraction potential of Brachiaria decumbens and Panicum maximum grown in a tropical soil.
The interactions between soil properties, microorganisms, plant species and climate affect cadmium (Cd) availability in tropical soils. In this study, we investigated the effects of simulated summer and winter conditions on Cd fractionation and bacterial communities in Oxisols and on growth of two high biomass production-grasses (Brachiaria decumbens and Panicum maximum) that were evaluated for their Cd phytoextraction potential. We also assessed how these interactions could influence the availability of Cd and its possible phytoextraction by these grasses. The Cd fraction bound to carbonates was higher in the winter conditions, while Cd bound to Fe- and Mn oxides was higher in the summer conditions, which resulted in a higher Cd availability in winter compared to summer conditions. B. decumbens and P. maximum took up more Cd when grown in the winter conditions, but their biomasses were not affected by the higher Cd uptake. The occurrence and relative abundance of bacterial taxa in the bare soil differed from the soils cultivated with grasses, where the Gammaproteobacteria predominated. However, no positive correlations were observed between the rhizosphere bacterial community in the cultivated soils and Cd availability, irrespective of the season conditions.


Mitochondrial DNA analysis by multiplex denaturing high-performance liquid chromatography and selective sequencing in pediatric patients with cardiomyopathy.
Mitochondrial DNA testing is typically performed by targeted mutation analysis only. We applied a more comprehensive approach to study the mitochondrial genome in 24 pediatric patients with idiopathic cardiomyopathy. Patients in the cohort did not show overt multisystemic disease and were previously tested for mutations in a subset of structural genes associated with cardiomyopathy. Mutation screening of the mitochondrial DNA by multiplex denaturing high-performance liquid chromatography was complemented by sequence analysis. We identified 130 individual (unique) sequence changes. Among several potentially pathogenic changes, a novel heteroplasmic mutation in nicotinamide adenine dinucleotide dehydrogenase subunit 4 (10677G>A) was identified in one fraternal twin with worse clinical symptoms than his sibling. Another proband carried homoplasmic mutation 13708G>A (in nicotinamide adenine dinucleotide dehydrogenase subunit 5) that has been associated with Leber's hereditary optic neuropathy. Changes in mitochondrial DNA may represent a relatively rare cause of idiopathic pediatric cardiomyopathies and/or influence their phenotypic expression. Interpretation of variants with uncertain pathogenicity, however, currently impedes clinical diagnostic use of comprehensive mitochondrial DNA testing. Whereas combined use of multiplex denaturing high-performance liquid chromatography and sequencing is more comprehensive than targeted mutation analysis, measurement of additional functional parameters, such as tissue respiratory chain activity, remains important to establishing a definitive diagnosis.


2-[18F]fluoroputrescine: preparation, biodistribution, and mechanism of defluorination.
A new radiolabeled analog of putrescine, 18F labeled 2-fluoroputrescine, has been prepared as a potential in vivo imaging agent for prostate and prostate derived tumors. The radiosynthesis yielded 1.5-4.5 mCi amounts of the 18F labeled putrescine analog (1-3% yields at end-of-synthesis), with specific activities ranging from 0.85-4.3 Ci/mmol, in a synthesis time of 2 h. The in vivo biodistribution in mature male rats showed considerable uptake by the bone, indicating defluorination of the compound. In animals pretreated with aminoguanidine, an inhibitor of diamine oxidase, the enzyme important in the metabolism of putrescine, defluorination was markedly reduced, but uptake by the prostate did not improve. These results suggest the need for development of a 18F labeled analog of putrescine which does not defluorinate in vivo, and which has biological properties similar to putrescine.


Tracking of menstrual cycles and prediction of the fertile window via measurements of basal body temperature and heart rate as well as machine-learning algorithms.
Fertility awareness and menses prediction are important for improving fecundability and health management. Previous studies have used physiological parameters, such as basal body temperature (BBT) and heart rate (HR), to predict the fertile window and menses. However, their accuracy is far from satisfactory. Additionally, few researchers have examined irregular menstruators. Thus, we aimed to develop fertile window and menstruation prediction algorithms for both regular and irregular menstruators. This was a prospective observational cohort study conducted at the International Peace Maternity and Child Health Hospital in Shanghai, China. Participants were recruited from August 2020 to November 2020 and followed up for at least four menstrual cycles. Participants used an ear thermometer to assess BBT and wore the Huawei Band 5 to record HR. Ovarian ultrasound and serum hormone levels were used to determine the ovulation day. Menstruation was self-reported by women. We used linear mixed models to assess changes in physiological parameters and developed probability function estimation models to predict the fertile window and menses with machine learning. We included data from 305 and 77 qualified cycles with confirmed ovulations from 89 regular menstruators and 25 irregular menstruators, respectively. For regular menstruators, BBT and HR were significantly higher during fertile phase than follicular phase and peaked in the luteal phase (all P < 0.001). The physiological parameters of irregular menstruators followed a similar trend. Based on BBT and HR, we developed algorithms that predicted the fertile window with an accuracy of 87.46%, sensitivity of 69.30%, specificity of 92.00%, and AUC of 0.8993 and menses with an accuracy of 89.60%, sensitivity of 70.70%, and specificity of 94.30%, and AUC of 0.7849 among regular menstruators. For irregular menstruators, the accuracy, sensitivity, specificity and AUC were 72.51%, 21.00%, 82.90%, and 0.5808 respectively, for fertile window prediction and 75.90%, 36.30%, 84.40%, and 0.6759 for menses prediction. By combining BBT and HR recorded by the Huawei Band 5, our algorithms achieved relatively ideal performance for predicting the fertile window and menses among regular menstruators. For irregular menstruators, the algorithms showed potential feasibility but still need further investigation. ChiCTR2000036556. Registered 24 August 2020.


Artificial intelligence in adrenal imaging: A critical review of current applications.
In the elective field of adrenal imaging, artificial intelligence (AI) can be used for adrenal lesion detection, characterization, hypersecreting syndrome management and patient follow-up. Although a perfect AI tool that includes all required steps from detection to analysis does not exist yet, multiple AI algorithms have been developed and tested with encouraging results. However, AI in this setting is still at an early stage. In this regard, most published studies about AI in adrenal gland imaging report preliminary results that do not have yet daily applications in clinical practice. In this review, recent developments and current results of AI in the field of adrenal imaging are presented. Limitations and future perspectives of AI are discussed.


Does wearing helmets reduce motorcycle-related death? A global evaluation.
The high risk of injury and death of motorcycle riders is a major global health problem. This study aimed to evaluate the effect of helmet wearing on motorcycle riders' death rates on a global level. Data for motorcycle riders were collected from 70 countries. These data included motorcycle-related death rates per 100,000 population, helmet non-usage percentage, Gross National Income per capita (GNI), number of registered motorized 2-3 wheelers, the effectiveness of law enforcement in each country, and whether there was standards for helmets use or not. Correlations between studied variables were done using Pearson correlation. Multiple linear regression models were used to define factors affecting motorcycle-related death rates. The correlation between motorcycle-related death rate and helmet non-usage, was almost significant (p=0.056, r=0.28). Helmet non-usage percentage was significantly correlated with GNI (p<0.0001, r=-0.61) and effectiveness of the law (p<0.0001, r=-0.73). A multiple linear regression model which was highly significant (adjusted R-squared=0.3, F=6.69, p<0.001) has shown that helmet non-usage percentage (p=0.003), motorcycle per person ratio (p=0.01) and the presence of helmet standards (p=0.05) were positively associated with motorcycle-related death rates. A simple linear regression model between helmet usage and road traffic death rate has shown that for each 10% increase in helmet usage, one life per 1,000,000 inhabitants can be saved per year. Helmet non-usage percentage was the most significant factor affecting motorcyclists' death rate. Wearing a motorcycle helmet reduces the risk of death from a motorcycle crash. Enforcement of motorcycle helmet laws should be effectively supported by motorcycle safety programs.


1-(4-Chloro-phen-yl)-3-(2-meth-oxy-anilino)propan-1-one.
In the title compound, C(16)H(16)ClNO(2), the mol-ecule adopts a bowed conformation, with a dihedral angle of 39.9 (2)° between the aromatic rings. In the crystal, mol-ecules are linked by C-H⋯O hydrogen bonds, generating C(6) chains propagating in [010]. Very weak aromatic π-π stacking is also observed [centroid-centroid distance = 4.040 (2) Å].