Evaluation of lumbar stiffness after long-level fusion for degenerative lumbar scoliosis via a Chinese version of the lumbar stiffness disability index.
Long-level spinal fusion for degenerative lumbar scoliosis (DLS)seeks to eliminate spinal motion in an attempt to alleviate pain, improve deformity, and reduce disability. However, this surgery considerably impairs the performance of activities of daily living (ADL) due to the resulting stiffness. The lumbar stiffness disability index (LSDI) is a validated measure of the effect of lumbar stiffness on functional activity, but this index might not be fully applicable to the elderly Chinese population given several specific lifestyle characteristics. To evaluate lumbar stiffness in patients with DLS after long-level fusion by Chinese-LSDI (C-LSDI). A retrospective study. A total of 129 DLS patients who underwent long-level (≧4 levels) fusion surgery with at least one-year follow-up from June 2009 to September 2017 were retrospectively included. The C-LSDI was designed by modifying LSDI and Korean-LSDI (K-LSDI) based on elderly Chinese lifestyles and the internal consistency and retest repeatability of the patient-reported outcome questionnaire in the measurement of the impact of lumbar stiffness on functional abilities was assessed. The radiographic parameters including Cobb angle, apical vertebral translation (AVT), coronal vertical axis (CVA), sagittal vertical axis (SVA), thoracic kyphosis (TK), thoracolumbar kyphosis (TLK), pelvic tilt (PT), pelvic incidence (PI), sacral slope (SS), lumbar lordosis (LL), and PI-LL, and clinical symptoms including visual analogue scale (VAS) for back and low extremity pain; Oswestry disability index (ODI), Japanese Orthopedic Association-29 (JOA-29), Scoliosis Research Society⁃22 (SRS-22), 36⁃Item short form survey (SF-36), physical component scores (PCS) and mental component scores (MCS) were measured preoperatively and at the last follow-up. Compared with LSDI and K-LSDI, the C-LSDI demonstrated higher internal consistency (Cronbach's alpha=0.902) and retest reliability (Internal consistency coefficients, ICC=0.904) in the elderly Chinese population. All patients showed increased lumbar stiffness and significant improvement in pain and deformity postoperatively. Regarding items, such as performing personal hygiene after toileting and getting out of a car, people reported more inconvenience with increasingly fixed levels. This study demonstrated that the C-LSDI questionnaire was a reliable and valid instrument for assessing functional limitations due to lumbar stiffness among elderly Chinese patients with DLS after long-level fusion. Although the effects of stiffness did trend toward greater impacts among patients who underwent longer fusions, most patients were satisfied with trade-offs of function and pain relief in exchange for perceived increases in lumbar stiffness.


The Hospitalizations for Cardiovascular and Respiratory Conditions, Emergency Department Presentations and Economic Burden of Bushfires in Australia Between 2021 and 2030: A Modelling Study.
The health and environmental impacts of bushfires results in substantial economic costs to society. The present analysis sought to estimate the burden of bushfires in Australia over 10 years from 2021 to 2030 inclusive. A dynamic model with yearly cycles was constructed to simulate follow-up of the entire Australian population from 2021 to 2030, capturing deaths and years of life lived. Estimated numbers of bushfire-related-deaths, costs of related-hospitalizations, and broader economic costs were derived from published sources. A 5% annual discount rate was applied to all costs incurred and life years lived from 2022 onwards. Over the 10 years from 2021 to 2030, the modelled analysis predicted that 2418 [95% confidence interval (CI) 2412 - 2422] lives would be lost to bushfires, as well as 8590 [95% CI 8573 - 8606] years of life lost (discounted). Healthcare costs arising from deaths for smoke-related conditions, hospitalizations amounted to AUD $110 million [95% CI 91-129 million] (discounted). The impact on gross domestic product (GDP) totaled AUD $17.2 billion. A hypothetical intervention that reduces the impact of bushfires by 10% would save $11 million in healthcare costs and $1.9 billion in GDP. The health and economic burden of bushfires in Australia looms large during 2021 and 2030. This underscores the importance of actions to mitigate bushfire risk. The findings are useful for the future design and delivery and help policy makers to make informed decisions about investment in strategies to reduce the incidence and severity of future bushfires.


Laboratory investigation on the retention performance of a soil-bentonite mixture used as an engineered barrier: insight into the effects of ionic strength and associated heavy metal ions.
Soil-bentonite (S-B) materials are promising backfill materials for use as engineered barriers in heavy metal-contaminated sites. The effects of contaminant exposure on the retention performance of the S-B barrier remain unrevealed. In this study, based on the pollution status of an abandoned ferroalloy factory located in southern China, the retention performance of the S-B mixture toward Cr(VI) and Zn(II) was studied through adsorption and diffusion experiments sequentially; the separate effect of ionic strength (binary solution) and the combined effect of ionic strength and associated heavy metal ion (ternary solution) were discussed. In NaCl-Cr(VI)/Zn(II) binary solutions, the adsorption of Zn(II) onto the S-B mixture is larger than that of Cr(VI). Kd, Qmax, and ɛacc (accessible porosity) of Cr(VI) increase through increasing ionic strength, while Zn(II) shows the opposite trend; De (effective diffusion coefficient) values for both Cr(VI) and Zn(II) increased with increasing ionic strength and follow a sequence of Cr(VI) > Zn(II), indicating a better retention performance of the S-B mixture to Zn(II). For a given ionic strength, the adsorption of Zn(II) was larger than that of Cr(VI), which can be attributed to the retention specificity of the S-B mixture to anion and cation. In Cr(VI)-Zn(II)-NaCl ternary solutions, the adsorptions of Cr(VI) and Zn(II) are enhanced in varying degrees when compared with their binary solution, which probably could be attributed to the ion bridge role of Cr(VI)/Zn(II) to connect each other that relatively increased the adsorption capacity of S-B material. This work will contribute to an in-depth understanding of the retention performance of the S-B mixture in complicated chemical environments and facilitate the selection of future remediation strategies.


Back to the origin of HCV 2c subtype and spreading to the Calabria region (Southern Italy) over the last two centuries: a phylogenetic study.
Circulation of HCV genotype 2 has been described in European Countries where numerous subtypes and unclassified HCV 2 lineages have been reported. In Italy, subtype 1b is the most prevalent, followed by genotype 2. In the present study, phylogeny of HCV 2c was investigated. The phylogeny of HCV 2c isolated from 54 Italian patients in the Calabria region (Southern Italy) was investigated by analyzing a fragment of the NS5B gene. Patients came from 5 metropolitan areas and a small village (Sersale). These areas were geographically dispersed throughout the entire region. A Bayesian coalescent-based framework was used to estimate origin and spreading of HCV 2c in this region. Phylogenetic analysis showed that 28 Italian sequences were intermixed with foreign HCV 2c reference sequences and grouped into 3 major clades: A, B, and C. Nineteen inter-clade sequences were associated uniquely with surgery as risk factor for HCV acquisition. By contrast, a sub-cluster within clade B was associated with blood transfusion. Moreover, sequences from Sersale village grouped in the Italian sub-cluster and were intermixed with 10 sequences from metropolitan areas. The three isolates with the longest branch came from Sersale and belonged to patients who had glass syringes as risk factor. HCV 2c isolates from the Calabria region shared a common ancestor whose origin was traced back to 1889. Our results suggest that, after its introduction - possibly as a result of population movements between Italy and African Countries during Italian colonialism - HCV 2c spread through multiple risk factors, not including intravenous drug use. So, transmission chains followed a pathway different from other European Countries. Although HCV incidence is decreasing, these ways are still ongoing, possibly justifying stability in the relative prevalence of HCV 2c.


Spontaneous Isolated Thrombosed True Popliteal Aneurysm in an Eight-Year-Old Child: A Rare Case Report With Literature Review.
Spontaneous aneurysms are rare in the pediatric age group. Aneurysms of peripheral arteries are even rarer. The diagnosis should not be missed to prevent distal limb ischemia and life-threatening complications. Hence, timely surgery to save the affected limb is advised. There is an increasing number of reported cases of such aneurysms in the English scientific literature. We present a rare case of pediatric idiopathic popliteal artery aneurysm (PAA), with no known risk factors. This scientific writing is unique in its way of reporting an idiopathic aneurysm with spontaneous onset. However, we have successfully investigated and managed the patient considering the established guidelines on aneurysmal surgery.


Essential roles of an intercalated disc protein, mXinbeta, in postnatal heart growth and survival.
The Xin repeat-containing proteins mXinalpha and mXinbeta localize to the intercalated disc of mouse heart and are implicated in cardiac development and function. The mXinalpha directly interacts with beta-catenin, p120-catenin, and actin filaments. Ablation of mXinalpha results in adult late-onset cardiomyopathy with conduction defects. An upregulation of the mXinbeta in mXinalpha-deficient hearts suggests a partial compensation. The essential roles of mXinbeta in cardiac development and intercalated disc maturation were investigated. Ablation of mXinbeta led to abnormal heart shape, ventricular septal defects, severe growth retardation, and postnatal lethality with no upregulation of the mXinalpha. Postnatal upregulation of mXinbeta in wild-type hearts, as well as altered apoptosis and proliferation in mXinbeta-null hearts, suggests that mXinbeta is required for postnatal heart remodeling. The mXinbeta-null hearts exhibited a misorganized myocardium as detected by histological and electron microscopic studies and an impaired diastolic function, as suggested by echocardiography and a delay in switching off the slow skeletal troponin I. Loss of mXinbeta resulted in the failure of forming mature intercalated discs and the mislocalization of mXinalpha and N-cadherin. The mXinbeta-null hearts showed upregulation of active Stat3 (signal transducer and activator of transcription 3) and downregulation of the activities of Rac1, insulin-like growth factor 1 receptor, protein kinase B, and extracellular signal-regulated kinases 1 and 2. These findings identify not only an essential role of mXinbeta in the intercalated disc maturation but also mechanisms of mXinbeta modulating N-cadherin-mediated adhesion signaling and its crosstalk signaling for postnatal heart growth and animal survival.


Anticipatory and reactive responses to underfoot perturbations during gait in healthy adults and individuals with a recent mild traumatic brain injury.
Following mild traumatic brain injury, individuals often exhibit quantifiable gait deficits over flat surfaces, but little is known about how they control gait over complex surfaces. Such complex surfaces require precise neuromotor control to anticipate and react to small disturbances in walking surfaces, and mild traumatic brain injury-related balance deficits may adversely affect these gait adjustments. This study investigates anticipatory and reactive gait adjustments for expected and unexpected underfoot perturbations in healthy adults (n = 5) and individuals with mild traumatic brain injury (n = 5). Participants completed walking trials with random unexpected or expected underfoot perturbations from a mechanized shoe and inertial measurement units collected kinematic data from the feet and sternum. Linear mixed-effects models assessed the effects of segment, group, and their interaction on standardized difference of accelerations between perturbation and non-perturbation trials. Both groups demonstrated similar gait strategies when perturbations were unexpected. During late swing phase before expected perturbations, persons with mild traumatic brain injury exhibited greater lateral acceleration of their perturbed foot and less lateral movement of their trunk compared with unperturbed gait. Control participants exhibited less lateral foot acceleration and no difference in mediolateral trunk acceleration compared with unperturbed gait during the same period. A significant group*segment interaction (p < 0.001) during this part of the gait cycle suggests the groups adopted different anticipatory strategies for the perturbation. Individuals with mild traumatic brain injury may be adopting cautious strategies for expected perturbations due to persistent neuromechanical deficits stemming from their injury.


Molecular surveillance of tuberculosis-causing mycobacteria in wastewater.
The surveillance of tuberculosis infections has largely depended on clinical diagnostics and hospitalization data. The advancement in molecular methods creates an opportunity for the adoption of alternative surveillance systems, such as wastewater-based epidemiology. This study presents the use of conventional and advanced polymerase chain reaction techniques (droplet digital PCR) to determine the occurrence and concentration of total mycobacteria and members of the Mycobacterium tuberculosis complex (MTBC) in treated and untreated wastewater. Wastewater samples were taken from three wastewater treatment plants (WWTPs) in the city of Durban, South Africa, known for a high burden of TB/MDR-TB due to HIV infections. All untreated wastewater samples contained total mycobacteria and MTBC at varying percentages per WWTP studied. Other members of the MTBC related to tuberculosis infection in animals, M. bovis and M. caprae were also detected. The highest median concentration detected in untreated wastewater was up to 4.9 (±0.2) Log10 copies/ml for total mycobacteria, 4.0 (±0.85) Log10 copies/ml for MTBC, 3.9 (±0.54) Log10 copies/ml for M. tuberculosis, 2.7 (±0.42) Log10 copies/ml for M. africanum, 4.0 (±0.29) Log10 copies/ml for M. bovis and 4.5 (±0.52) Log10 copies/ml for M. caprae. Lower concentrations were detected in the treated wastewater, with a statistically significant difference (P-value ≤ 0.05) in concentrations observed. The log reduction achieved for these bacteria in the respective WWTPs was not statistically different, indicating that the treatment configuration did not have an impact on their removal. The detection of M. africanum in wastewater from South Africa shows that it is possible that some of the TB infections in the community could be caused by this mycobacterium. This study, therefore, highlights the potential of wastewater-based epidemiology for monitoring tuberculosis infections.


Rare Variants in Triglycerides-Related Genes Increase Pancreatitis Risk in Multifactorial Chylomicronemia Syndrome.
Severe hypertriglyceridemia (fasting triglycerides [TG] concentration ≥10 mmol/L) can be caused by multifactorial chylomicronemia syndrome (MCS) or familial chylomicronemia syndrome (FCS). Both conditions are associated with an increased risk of acute pancreatitis. The clinical differences between MCS patients with or without a rare variant in TG-related genes have never been studied. To compare the clinical and biochemical characteristics of FCS, positive-MCS patients, and negative-MCS patients, as well as to investigate the predictors of acute pancreatitis in MCS patients. All patients referred at the clinic for severe hypertriglyceridemia underwent genetic testing for the 5 canonical genes involved in TG metabolism (LPL, APOC2, GPIHBP1, APOA5, and LMF1) using next-generation sequencing. A total of 53 variant negative-MCS, 22 variant positive-MCS and 28 FCS subjects were included in this retrospective cross-sectional study. A significant difference was observed in the prevalence of pancreatitis (9%, 41%, and 61%) and multiple pancreatitis (6%, 23%, and 46%) in the negative-MCS, the positive-MCS, and the FCS groups, respectively (P < 0.0001). Predictors of pancreatitis among MCS subjects included the presence of a rare variant, lower apolipoprotein B, as well as higher gamma-glutamyl transferase, maximal TG value, and fructose consumption. We observed that the MCS individuals who carried a rare variant have an intermediate phenotype between FCS and negative-MCS subjects. Since novel molecules such as the antisense oligonucleotide against APOC3 mRNA showed high efficacy in reducing TG levels in patients with multifactorial chylomicronemia, identification of higher-risk MCS patients who would benefit from additional treatment is essential.


Elephantine but not elephantiasis: Subcutaneous zygomycosis.
Subcutaneous zygomycosis is an unusual disorder caused by a rare fungus, Basidiobolus ranarum. We report this entity in a 4- yr- old boy. Biopsy showed the Splendore Hoeppli phenomenon and the culture yielded Basidiobolus ranarum. The child responded to saturated solution of potassium iodide within 1 month of starting treatment.


Total Adverse Childhood Experiences and Preterm Birth: A Systematic Review.
Total adverse childhood experiences (ACEs) are gaining prominence as a risk factor for preterm birth (PTB). The emerging literature examining this relationship reports inconsistent findings. The purpose of this systematic review was to summarize the available evidence exploring whether total ACEs predict PTB. A total of 386 studies were returned from searches on PubMed, PsycINFO, and Cumulative Index to Nursing and Allied Health Literature (CINAHL). Nine studies were selected for final analysis and synthesis based on reporting of total ACEs and preterm birth gestational weeks or standard definition of birth before 37 weeks' gestational age. A systematic review rather than meta-analysis was selected to present the findings given the clinical and methodological (e.g., sample studied, measurement tools) heterogeneity of the retrieved studies and pregnancy outcomes measured. The nine studies report on birth outcomes for 6,087 women from a range of sociodemographic and ethnic backgrounds. Despite a wide range of study designs, measurement tools, and timings of ACEs exposure across studies, seven of the nine included studies showed significant relationships between ACEs and PTB. Systematic review of the literature suggests that total ACEs are associated with PTB and provides an overview on the known associations. However, to date only nine studies have assessed this link, and more studies are needed, to explore the associations between ACEs and PTB using appropriate and valid instruments and doing so among more diverse populations. Future research should also explore possible biological mechanisms (allostatic load), and moderating and mediating variables.


In vitro effects and ex vivo binding of an EGFR-specific immunotoxin on rhabdomyosarcoma cells.
Rhabdomyosarcoma (RMS) is a rare and aggressive soft tissue sarcoma with limited treatment options and a high failure rate during standard therapy. New therapeutic strategies based on targeted immunotherapy are therefore much in demand. The epidermal growth factor receptor (EGFR) has all the characteristics of an ideal target. It is overexpressed in up to 80 % of embryonal RMS and up to 50 % of alveolar RMS tumors. We therefore tested the activity of the EGFR-specific recombinant immunotoxin (IT) 425(scFv)-ETA' against EGFR(+) RMS cells in vitro and ex vivo. We tested the specific binding and internalization behavior of 425(scFv)-ETA' in RMS cell lines in vitro by flow cytometry, compared to the corresponding imaging probe 425(scFv)-SNAP monitored by live cell imaging. The cytotoxic activity of 425(scFv)-ETA' was tested using cell viability and apoptosis assays. Specific binding of the IT was confirmed on formalin-fixed paraffin-embedded tissue samples from two RMS patients. We confirmed the specific binding of 425(scFv)-ETA' to RMS cells in vitro and ex vivo. Both the IT and the corresponding imaging probe were rapidly internalized. The IT killed EGFR(+) RMS cells in a dose-dependent manner, while showing no effect against control cells. It showed specific apoptotic activity against one selected RMS cell line. This is the first study showing the promising therapeutic potential of a recombinant, EGFR-targeting, ETA'-based IT on RMS cells. We confirmed the selective killing with IC50 values of up to 50 pM, and immunohistochemical staining confirmed the specific ex vivo binding to primary RMS material.


Critical review of laboratory investigations in clinical practice guidelines: proposals for the description of investigation.
Correct information provided by guidelines may reduce laboratory test related errors during the pre-analytical, analytical and post-analytical phase and increase the quality of laboratory results. Twelve clinical practice guidelines were reviewed regarding inclusion of important laboratory investigations. Based on the results and the authors' experience, two checklists were developed: one comprehensive list including topics that authors of guidelines may consider and one consisting of minimal standards that should be covered for all laboratory tests recommended in clinical practice guidelines. The number of topics addressed by the guidelines was related to involvement of laboratory medicine specialists in the guideline development process. The comprehensive list suggests 33 pre- analytical, 37 analytical and 10 post-analytical items. The mean percentage of topics dealt with by the guidelines was 33% (median 30%, range 17%-55%) and inclusion of a laboratory medicine specialist in the guideline committee significantly increased the number of topics addressed. Information about patient status, biological and analytical interferences and sample handling were scarce in most guidelines even if the inclusion of a laboratory medicine specialist in the development process seemingly led to increased focus on, e.g., sample type, sample handling and analytical variation. Examples underlining the importance of including laboratory items are given. Inclusion of laboratory medicine specialist in the guideline development process may increase the focus on important laboratory related items even if this information is usually limited. Two checklists are suggested to help guideline developers to cover all important topics related to laboratory testing.


A proinflammatory factor in lymphocytes. Its role in the development of acute, non-immunological inflammatory reactions.
Drug-induced leucopenia renders rats hyporeactive to various inflammatory stimuli. Administration to leucopenic rats of suspensions of lymphocytes, sufficient to apparently correct the induced lymphocytopenia, led to a partial but marked reversal of the inhibited responses. Similar results were observed when lysates of lymphocytes or filtrates of the disintegrated cells were injected. Suspensions of polymorphonuclear granulocytes, on the contrary, were ineffective in producing a reversal of inhibited inflammatory reactions in leucopenic rats. The presence of a proinflammatory factor (LpIF) in lymphocytes, which might be involved in the modulation of acute inflammatory responses is suggested.


Metal organic framework-assisted in-situ synthesis of β-NiMnOOH nanosheets with abundant NiOOH active sites for efficient electro-oxidation of urea.
NiOOH has been considered as the active center for urea oxidation reaction (UOR), but it remains challenging to synthesize high-performance NiOOH-based catalysts. Herein, we realize the synthesis of a high-performance NiOOH-based catalyst through in-situ transformation from the NiMn-based metal-organic framework to NiMnOOH. X-ray photoelectron spectroscopy characterization shows that the Ni3+/Ni2+ ratio in the NiMnOOH is 3.9 times as big as that in the Ni(OH)2, and in-situ Raman characterization further consolidates the presence of the NiOOH species in the NiMnOOH and as well unveils the faciliated Ni2+/Ni3+ redox reaction. The abundant NiOOH species, the markedly facilitated Ni2+/Ni3+ redox reaction and the Ni-Mn synergy contribute to the high intrinsic activity of the NiMnOOH towards UOR. The NiMnOOH exhibits an impressively low onset potential of 1.305 V vs reversible hydrogen electrode (RHE) and requires only a small potential of 1.34 V vs RHE to deliver a current density of 100 mA cm-2 in 1.0 M KOH + 0.33 M urea. In addition, the NiMnOOH catalyst possesses good long-term working stability.


Early development of the human embryonic testis.
Human gonadal development culminating in testicular differentiation is described through analysis of histologic sections derived from 33-day to 20-week human embryos/fetuses, focusing on early development (4-8 weeks of gestation). Our study updates the comprehensive studies of Felix (1912), van Wagenen and Simpson (1965), and Juric-Lekic et al. (2013), which were published in books and thus are unsearchable via PubMed. Human gonads develop from the germinal ridge, a thickening of coelomic epithelium on the medial side of the urogenital ridge. The bilateral urogenital ridges contain elements of the mesonephric kidney, namely the mesonephric duct, mesonephric tubules, and mesonephric glomeruli. The germinal ridge, into which primordial germ cells migrate, is initially recognized as a thickening of coelomic epithelium on the urogenital ridge late in the 4th week of gestation. Subsequently, in the 5th week of gestation, a dense mesenchyme develops sub-adjacent to the epithelium of the germinal ridge, and together these elements bulge into the coelomic cavity forming bilateral longitudinal ridges attached to the urogenital ridges. During development, primordial cells migrate into the germinal ridge and subsequently into testicular cords that form within the featureless dense mesenchyme of the germinal ridge at 6-8 weeks of gestation. The initial low density of testicular cords seen at 8 weeks remodels into a dense array of testicular cords surrounded by α-actin-positive myoid cells during the second trimester. Human testicular development shares many features with that of mice being derived from 4 elements: coelomic epithelium, sub-adjacent mesenchyme, primordial germ cells, and the mesonephros.


First-order liquid-liquid phase transition in compressed nitrogen.
We report results of first-principles molecular dynamics simulations, which predict a first-order phase transition from molecular to polymeric liquid nitrogen. The liquid-liquid phase boundary is near 88 GPa along the 2000 K isotherm and has a critical point between 4000 and 5000 K and 50 to 75 GPa. At higher temperatures, molecular nitrogen undergoes temperature-driven dissociation to an atomic liquid. The nature of the liquid-liquid transition and the structure of the new polymeric phase are characterized, and ways to experimentally confirm our findings are proposed.


Seasonal characteristics of temperature variability impacts on childhood asthma hospitalization in Hefei, China: Does PM2.5 modify the association?
Evidence of childhood asthma hospitalizations associated with temperature variability (TV) and the attributable risk are limited in China. We aim to use a comprehensive index that reflected both intra- and inter-day TV to assess the TV-childhood asthma relationship and disease burden, further to identify seasonality vulnerable populations, and to explore the effect modification of PM2.5. A quasi-distributed lagged nonlinear model (DLNM) combined with a linear threshold function was applied to estimate the association between TV and childhood asthma hospitalizations during 2013-2016 in Hefei, China. Subgroup analysis was conducted by age and sex. Disease burden is reflected by the attributable fraction and attributable number. Besides, modifications of PM2.5 were tested by introducing the cross-basis of TV and binary PM2.5 as an interaction term. The risk estimates peaked at TV0-3 and TV0-4 in the cool and the warm season separately, with RR of 1.051 (95%CI: 1.021-1.081) and 1.072 (95%CI: 1.008-1.125), and the effects lasted longer in the cool season. The school-age children in the warm season and all subgroups except pre-school children in the cool season were vulnerable to TV. It is estimated that the disease burden related to TV account for 6.2% (95% CI: 2.7%-9.4%) and 4% (95% CI: 0.6%-7.1%) during the cool and warm seasons in TV0-3. In addition, the risks of TV were higher under the high PM2.5 level compared with the low PM2.5 level in the cool season, although no significant differences between them. TV exposure significantly increases the risk and disease burden of childhood asthma hospitalizations, especially in the cool season. More medical resources should be allocated to school-age children. Giving priority to pay attention to TV in the cool season in practice could obtain the greatest public health benefits and those days with high TV and high PM2.5 need more attention.


[Dynamic observation of the biomechanic properties of sciatic nerve at the suture site in rats following repairing].
To observe the biomechanic properties of sciatic nerve at the suture site in rats following repairing. The right sciatic nerves of 40 white Sprague-Dawley 300-350 gm rats were exposed, cut and then repaired with 10-0 nylon sutures, laced in the epineurium. 0, 1, 3, 6 weeks after operation, the tensile strength of the sciatic nerves were measured, the data analyzed statistically. The load-elongation curves for both the normal unoperated and operated nerves had the similar shape. The tensile strength of the 0 week was significant difference to 1, 3 and 6 weeks (P < 0.01). No significant difference was found among 1, 3 and 6 weeks. The tensile strength of the injured nerves are recovered in the first week and resistant in 6 weeks after repairing.


Identification of monodentate oxazoline as a ligand for copper-promoted ortho-C-H hydroxylation and amination.
The use of a weakly coordinating monodentate directing group for copper mediated ortho-hydroxylation and amination reactions allows for the identification of an external oxazoline ligand as a promoter.


Post-mortem finding of a non-fatal left heart ventricle perforation by a pleural drain. A case report.
A 76-year-old male with a previous history of heart arrhythmia and decompensation was treated for a complicated thoraco-abdominal trauma. Accidentally, a pleural drain was inserted in his heart through the ventricular septum, perforating the left ventricle, the drain tip being buried in its posterior wall. This injury was not recognized until autopsy. The patient died 7 days after insertion of the drain of lung emboli, which were related to his primary trauma and not to the heart perforation.


Distinct functions and temporal regulation of methylated histone H3 during early embryogenesis.
During the first hours of embryogenesis, formation of higher-order heterochromatin coincides with the loss of developmental potential. Here, we examine the relationship between these two events, and we probe the processes that contribute to the timing of their onset. Mutations that disrupt histone H3 lysine 9 (H3K9) methyltransferases reveal that the methyltransferase MET-2 helps terminate developmental plasticity, through mono- and di-methylation of H3K9 (me1/me2), and promotes heterochromatin formation, through H3K9me3. Although loss of H3K9me3 perturbs formation of higher-order heterochromatin, embryos are still able to terminate plasticity, indicating that the two processes can be uncoupled. Methylated H3K9 appears gradually in developing C. elegans embryos and depends on nuclear localization of MET-2. We find that the timing of H3K9me2 and nuclear MET-2 is sensitive to rapid cell cycles, but not to zygotic genome activation or cell counting. These data reveal distinct roles for different H3K9 methylation states in the generation of heterochromatin and loss of developmental plasticity by MET-2, and identify the cell cycle as a crucial parameter of MET-2 regulation.


Tenosynovitis caused by Mycobacterium marseillense, initially identified as Mycobacterium avium complex using AccuProbe and COBAS TaqMan.
Mycobacterium marseillense is a new species of the Mycobacterium avium complex. There has been only a few human infections caused by M. marseillense worldwide. We report a case of tenosynovitis caused by M. marseillense in an immunocompetent adult in Japan. The isolate was initially identified as M. intracellulare using commercial real time polymerase chain reaction assays and later identified as M. marseillense with sequencing of the the rpoB and hsp65 regions, and matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS). This is the first case reporting on M. marseillense generating a positive result with commercial real time PCR assays targeting MAC. Human infections associated by M. marseillense might be underreported due to similarities with Mycobacterium intracellulare. To accurately identify M. marseillese, MALDI-TOF MS might provide a rapid and reliable method.


Generation mechanism of singlet oxygen from the interaction of peroxymonosulfate and chloride in aqueous systems.
Peroxymonosulfate (PMS, HSO5-) is a widely-used disinfectant and oxidant in environmental remediation. It was deemed that PMS reacted with chloride (Cl-) to form free chlorine during water purification. Here, we demonstrated that singlet oxygen (1O2) was efficiently generated from PMS and Cl- interaction. Mechanism of 1O2 formation was uniquely verified by the reaction of HSO5- and chlorine molecule (Cl2) and the oxygen atoms in 1O2 deriving from the peroxide group of HSO5- were revealed. Density functional theory calculations determined that the reaction of HSO5- and Cl2 was thermodynamically favorable and exergonic at 37.8 kcal/mol. Quite intriguingly, 1O2 was generated at a higher yield (1.5 × 105 M - 1 s - 1) than in the well-known reaction of H2O2 with Cl2 (35 M - 1 s - 1). Besides chlorine, 1O2 formed in PMS-Cl- interaction dominated the degradation of micropollutants, also it substantially enhanced the damage of deoxynucleoside in DNA, which were beneficial to micropollutant oxidation and pathogen disinfection. The contribution of 1O2 for carbamazepine degradation was enhanced at higher Cl- level and lower pH, and reached 96.3% at pH 4.1 and 5 min. Natural organic matter (NOM) was a sink for chlorine, thereby impeding 1O2 formation to retard carbamazepine degradation. 1O2 also played important roles (48.3 - 63.5%) on the abatement of deoxyguanosine and deoxythymidine at pH 4.1 and 10 min in PMS/Cl-. On the other hand, this discovery also alerted the harm of 1O2 for human health as it can be formed during the interaction of residual PMS in drinking water/swimming pools and the high-level Cl- in human bodies.


Aluminum Plasmonics Enriched Ultraviolet GaN Photodetector with Ultrahigh Responsivity, Detectivity, and Broad Bandwidth.
Plasmonics have been well investigated on photodetectors, particularly in IR and visible regimes. However, for a wide range of ultraviolet (UV) applications, plasmonics remain unavailable mainly because of the constrained optical properties of applicable plasmonic materials in the UV regime. Therefore, an epitaxial single-crystalline aluminum (Al) film, an abundant metal with high plasma frequency and low intrinsic loss is fabricated, on a wide bandgap semiconductive gallium nitride (GaN) to form a UV photodetector. By deliberately designing a periodic nanohole array in this Al film, localized surface plasmon resonance and extraordinary transmission are enabled; hence, the maximum responsivity (670 A W-1) and highest detectivity (1.48 × 1015 cm Hz1/2 W-1) is obtained at the resonance wavelength of 355 nm. In addition, owing to coupling among nanoholes, the bandwidth expands substantially, encompassing the entire UV range. Finally, a Schottky contact is formed between the single-crystalline Al nanohole array and the GaN substrate, resulting in a fast temporal response with a rise time of 51 ms and a fall time of 197 ms. To the best knowledge, the presented detectivity is the highest compared with those of other reported GaN photodetectors.


Cardiometabolic index is associated with urinary albumin excretion and renal function in aged person over 60: Data from NHANES 2011-2018.
Cardiometabolic index (CMI) is recently considered to have certain significance in the screening of diabetes, atherosclerosis, and renal dysfunction. Therefore, this study intends to explore the relationship between CMI and the risk of albuminuria. This is a cross-sectional study involving 2732 elderly people (age ≥ 60). The research data are from the National Health and Nutrition Examination Survey (NHANES) from 2011 to 2018. Calculate CMI index: Triglyceride (TG) (mmol/L)/ High density lipid-cholesterol (HDLC) (mmol/L) × WHtR. The CMI level in microalbuminuria group was significantly higher than that in normal albuminuria group (P < 0.05 or P < 0.01), whether in the general population or in diabetes and hypertensive population respectively. The proportion of abnormal microalbuminuria increased gradually with the increase of CMI tertile interval (P < 0.01). Correlation analysis showed that CMI was positively correlated with urinary albumin-creatinine ratio (UACR), blood urea nitrogen (BUN), and serum creatinine (Scr), and negatively correlated with estimated glomerular filtration rate (eGFR). With the occurrence of albuminuria as the dependent variable, weighted logistic regression analysis showed that CMI was an independent risk factor for microalbuminuria. Weighted smooth curve fitting showed that CMI index was linearly related to the risk of microalbuminuria. Subgroup analysis and interaction test showed that they participated in this positive correlation. Obviously, CMI is independently associated with microalbuminuria, suggesting that CMI, a simple indicator, can be used for risk assessment of microalbuminuria, especially in diabetes patients.


Effect of probenecid on the excretion of ampicillin in human bile.
1. Ampicillin concentrations were determined in serum and bile after intravenous injection into patients with T-tube bile drainage of 1 gram ampicillin before and during probenecid medication. The concentrations were followed up to fifteen hours after injection.2. Probenecid increased the half-life of ampicillin in serum from 74 minutes to 137 minutes.3. Ampicillin concentrations in bile were higher following probenecid medication and a concentration over 5 mug/ml was obtained for 3 h longer than before probenecid.4. The ampicillin concentrations in bile were approximately the same as those in serum both before and during probenecid medication suggesting passive transport of ampicillin from blood to bile.5. A combined treatment of ampicillin and probenecid might be of clinical value in the therapy of cholangitis and typhoid carriers.


Determinants of persistent Salmonella infections.
Persistent bacterial infections constitute an enormous challenge for public health. Amongst infections with other bacteria, infections with typhoidal and nontyphoidal Salmonella enterica serovars can result in long-term infections of the human and animal host. Persistent infections that are asymptomatic are difficult to identify and thus can serve as a silent reservoir for transmission. Symptomatic persistent infections are often difficult to treat as they harbor a combination of antibiotic-tolerant and antibiotic-resistant bacteria and boost the spread of genetic antibiotic resistance. In the last couple of years, the field has made some major progress in understanding the role of persisters, their reservoirs as well as their interplay with host factors in persistent Salmonella infections.


Long non-coding RNA 00152 slicing represses the growth and aggressiveness of hemangioma cell by modulating miR-139-5p.
Long non-coding RNA (lncRNA) linc00152 has been recognized as an oncogenic lncRNA in various cancers. This study attempts to investigate the roles of linc00152 in the metastasis-related traits of infantile hemangioma (IH). Linc00152 was overexpressed in the proliferating-phase hemangioma tissues when compared with that in involuting-phase. Downregulation of linc00152 strikingly suppressed the cell viability, migration and invasion of hemangioma cells. Furthermore, silence of linc00152 repressed the growth and lung metastasis of hemangioma cell in vivo. Subsequent analysis revealed that linc00152 bound with miR-139-5p and linc00152 expression was inversely correlated with the level of miR-139-5p in IH. Same effects of miR-139-5p transfection on HemECs cells were observed as downregulation of linc00152. Moreover, tumor protein D52 (TPD52) was confirmed to be the target of miR-139-5p. Besides, the anti-tumor effect of linc00152 silence on hemangioma cell was reversed by rexpression of TPD52. This study demonstrates that downregulatuon of linc00152 restrains the aggressiveness of hemangioma cell in vitro and in vivo via interacting with miR-139-5p and further modulates the level of TPD52.


Electron microscopical studies on the resorption of vitreous hemorrhages.
An electron microscopical study of vitreous structure in 14 eyes suffering from different types and durations of vitreous hemorrhages submitted to vitrectomy showed the typical stages of disintegration of erythrocytes. Neither the type (retrovitreal, intravitreal or combined retro- and intravitreal) nor the duration of the vitreous hemorrhages influenced the histological picture significantly. In cases of shrinkage of the vitreous body the collagen fibrillar meshwork showed normal periodicity of 640 A, partly split and irregular.


Application of micellar liquid chromatography to model ecotoxicity of pesticides. Comparison with immobilized artificial membrane chromatography and n-octanol-water partitioning.
The potential of Micellar Liquid Chromatography (MLC) to model ecotoxicological endpoints for a series of pesticides was investigated. To exploit the flexibility in MLC conditions, different surfactants were employed and retention mechanism was tracked and compared to Immobilized Artificial Membrane (IAM) chromatographic retention and n-octanol- water partitioning, logP. Neutral polyoxyethylene (23) lauryl ether (Brij-35), anionic sodium dodecyl sulfate (SDS) and cationic cetyltrimethylammonium bromide (CTAB) were used in presence of PBS at pH=7.40 and acetonitrile as organic modifier when necessary. Similarities/ dissimilarities between MLC retention and IAM or logP were investigated by Principal Component Analysis (PCA) and Liner Solvation Energy Relationships (LSER). LSER revealed that hydrogen bonding acidity is the most important factor for differentiation between MLC and IAM or logP. The impact of hydrogen bonding is exemplified in the relationships of MLC retention factors with IAM or logP, which necessitate the inclusion of a relevant descriptor. PCA further revealed that MLC retention factors are clustered together with IAM indices and logP within a broader ellipse formed by ecotoxicological endpoints, involving LC50/ EC50 values of six aquatic organisms namely Rainbow Trout, Fathead Minnow, Bluegill Sunfish, Sheepshead Minnow, Eastern Oyster and Water Flea as well as LD50 values of Honey Bee, thus justifying their use to construct relevant models. Satisfactory specific models for individual organisms, as well as general fish models, were obtained, in most cases, upon combination of MLC retention factors with Molecular Weight (MW) or/ and hydrogen bond parameters. All models were evaluated and compared to previously reported IAM and logP based models using an external validation data set. Predictions with Brij-35 and SDS based models were comparable, although slightly inferior than those obtained with IAM, while they were in all cases better than those obtained with logP. CTAB led to a satisfactory prediction model for Honey Bee, but it was found less suitable for aquatic organisms.


[Validation into Spanish of the revised Patients' Attitudes Towards Deprescribing (rPATD) questionnaire to assess patients' attitudes towards deprescribing. Research protocol].
Polypharmacy has become a priority public health problem in developed countries. In response to its approach, deprescription stands out. Its success will depend largely on the attitudes and beliefs of patients towards the number of drugs they are taking and their willingness to initiate a process of deprescription. To explore these factors, researchers have developed the revised Patients' Attitudes Towards Deprescribing (rPATD) questionnaire, originally in English. The objective of this study is the validation into Spanish of rPATD questionnaire, both older adults and caregivers versions. A first qualitative validation phase and a second phase of analysis of its psychometric characteristics will be carried out through an observational descriptive study of validation of a measurement instrument. One hundred and twenty subjects (polymedicated older adults and caregivers) from three health centers will be selected by consecutive sampling. The questionnaire will be provided and clinical and sociodemographic data will be collected. Feasibility, reliability (through internal consistency and intraobserver reliability) and validity (apparent, construct and criterion) of the questionnaire will be evaluated. It is expected to obtain a questionnaire that will serve as a tool for the clinician to identify patients with a favorable predisposition to deprescription and that will allow to contribute the patient's perspective to this process. The use of the rPATD questionnaire, alone or integrated into other more complex interventions, may lead to an improvement in the quality of care for the polymedicated patients.


Calcium-dependent expression of transient receptor potential canonical type 3 channels in patients with chronic kidney disease.
It is unknown whether extracellular calcium may regulate the expression of transient receptor potential canonical type 3 (TRPC3) channels in patients with chronic kidney disease. Using quantitative in-cell Western assay we compared the expression of TRPC3 channel protein in monocytes from 20 patients with chronic kidney disease and 19 age- and sex-matched healthy control subjects. TRPC3 channels were identified by immunoblotting using specific antibodies and TRPC3 protein was further confirmed by mass spectrometry. We observed a significant increase of TRPC3 channel protein expression in patients with chronic kidney disease compared to healthy control subjects (normalized expression, 0.42±0.06 vs. 0.19±0.03; p<0.01). Expression of TRPC3 was significantly inversely correlated with estimated glomerular filtration rates (Spearman r=-0.41) or serum calcium concentration (Spearman r=-0.34). During a hemodialysis session serum calcium concentrations significantly increased, whereas the expression of TRPC3 channels and calcium influx significantly decreased. In vitro studies confirmed that higher calcium concentrations but not magnesium, barium nor sodium concentrations significantly decreased TRPC3 expression in human monocytes. This study indicates that reduced extracellular calcium concentrations up-regulate TRPC3 channel protein expression in patients with chronic kidney disease.


Pneumothorax as a rare presentation of bronchial schwannoma.
Tracheobronchial schwannomas are rare diseases. Common signs and symptoms of this tumor include cough, wheezing, and dyspnea. In contrast, pneumothorax is an exceptional presentation. This study reports the first case of bronchial schwannoma presenting with pneumothorax. A 79-year-old woman was diagnosed with pneumothorax by chest radiography. Chest computed tomography unexpectedly revealed a tumor occluding the right main bronchus. Following the pathological diagnosis of bronchial schwannoma, the patient underwent thoracoscopic tumor enucleation. The airway lumens are consequently secured postoperatively. We reviewed the literature and discussed the mechanisms and treatment options for bronchial benign tumor-associated pneumothorax. Pneumothorax should be aware of a rare presentation of non-malignant tracheobronchial tumors.


Guanosine 3',5'-monophosphate and the action of alkylating agents.
The intracellular level of guanosine 3',5'-monophosphate (cGMP) has been measured in Walker carcinoma cells in tissue culture after treatment with various alkylating agents. At concentrations which caused a rise in the level of adenosine 3',5'-monophosphate (cAMP) chlorambucil and 5-(1-aziridinyl)-2,4-dinitrobenzamide (CB 1954) produced only a small (35%) elevation of cGMP, while merophan had no such effect. This suggests that any effect of cAMP will not be outweighed by an equivalent rise in cGMP. Sepcific cytosolic binding of cGMP decreased with increasing resistance of Walker cells to alkylating agents, while the dissociation constant, KD, for binding increased. This was also observed with cAMP binding which suggests that the same protein in responsible for binding both nucleotides.


Procedural, clinical, and health status outcomes in chronic total coronary occlusion revascularization: Results from the PERSPECTIVE study.
Limited research has detailed the outcomes of chronic total occlusion (CTO) percutaneous coronary intervention (PCI) with independent core laboratory and event adjudication. This study examined procedural, clinical, and patient-reported health status outcomes among patients undergoing CTO PCI with specific focus on outcomes for those treated with zotarolimus-eluting stents (ZES). Among 500 consecutive patients undergoing attempted CTO PCI, procedural and in-hospital clinical outcomes were examined in addition to the 1-year composite endpoint of death, myocardial infarction, and target lesion revascularization (major adverse cardiac events, MACE). In a pre-specified cohort of 250 patients, health status measures were ascertained at baseline and 1 year. A powered secondary endpoint was 1-year MACE among patients treated with ZES compared with a performance goal. Demographic, lesion, and procedural characteristics for the overall population included prior bypass surgery, 29.8%; diabetes, 35.2%; occlusion length >20 mm, 71.3%; J-CTO score, 2.5 ± 1.1; and primary retrograde strategy, 30.8%. Overall guidewire crossing was 90.9%; clinical success following guidewire crossing, 94.3%; and 1-year MACE rate, 12.1%. One-year health status significantly improved from baseline with successful CTO-PCI (angina frequency, 72.7 ± 26.5 at baseline to 96.0 ± 10.8, p < .0001). Compared with a performance goal derived from prior CTO DES trials (1-year hierarchal MACE, 25.2%), treatment with ZES was associated with significantly lower MACE (18.2%, one-sided upper CI, 23.6%, p = .017). Favorable procedural success, health status improvements and late-term clinical outcomes inform the relative risks and benefits of CTO PCI when performed in a clinically indicated, complex patient population representative of those treated in clinical practice.


Cohen syndrome and early-onset epileptic encephalopathy in male triplets: two disease-causing mutations in VPS13B and NAPB.
Cohen syndrome (CS) is a rare multisystem autosomal recessive disorder associated with mutations in VPS13B (vacuolar protein sorting homolog 13B). The NAPB-related neurodevelopmental disorder is characterized mainly by early-onset epileptic encephalopathy (EOEE) and is associated with mutations in NAPB that encodes for SNAP-beta (soluble NSF attachment protein beta). Here we describe male triplets, clinically presenting with the phenotype of subtle but distinctive facial features, intellectual disability, increased body weight, neonatal EOEE, and prominently variable abnormal behaviors of autism and sexual arousal. The EEG showed multifocal epilepsy, while the brain MRI showed no abnormalities. Diagnostic exome sequencing (ES), the applied next-generation sequencing approach, revealed the interesting finding of two novel homozygous variants in two genes: VPS13B missense variant (c.8516G > A) and NAPB splice-site loss (c.354 + 2 T > G). Sanger sequencing verified the segregation of the two recessive gene variants with the phenotype in family members. The prediction algorithms support the pathogenicity of these variants. Homozygosity mapping of ES data of this consanguineous family revealed multiple chromosomal regions of homozygosity stretches with the residing of VPS13B (chr8: 100830758G > A) and NAPB (Chr20: 23,375,774 A > C) variants within the largest homozygous blocks further supporting the disease-genes causal role. Interestingly, the functions of the two proteins; VPS13B, a transmembrane protein involved in intracellular protein transport, and SNAP-beta involved in neurotransmitters release at the neuronal synaptic complexes, have been associated with Golgi-mediated vesicular trafficking. Our ES findings provide new insights into the pathologic mechanism underlying the expansion of the neurodevelopmental spectrum in CS and further highlight the importance of Golgi and Golgi-membrane-related proteins in the development of neurodevelopmental syndromes associated with early-onset non-channelopathy epilepsy. To our knowledge, this is the first report documenting multifocal EOEE in CS patients with the association of a pathogenic NAPB variant.


Energy supply and cell yield in aerobically growth microorganisms.
Cell yields of Pseudomonas fluorescens, Aerobacter cloacae UW-C83, Escherichia coli K-12, Candida utilis UW-3, and Saccharomyces carlsbergensis UW-110 grown aerobically on several carbon sources are reported. The Y(atp) concept is discussed in relation to the yields on oxygen and to assumed P to O ratios for bacteria and reported P to O ratios for yeast.


Endoscopic repair of posterior ankle impingement syndrome due to os trigonum in soccer players.
An os trigonum may cause posterior ankle impingement syndrome (PAIS), which may lead to poor sports performance, especially in soccer players. The aim of the present study was to analyze the outcomes of endoscopic repaired posterior ankle impingement (PAI) secondary to os trigonum syndrome within a group of soccer players as well as their return to play time. A retrospective review of 20 soccer players with Tegner activity level 9 was performed. All players were diagnosed of PAIS due to os trigonum. Chief complaint was pain produced with forced plantarflexion when kicking the ball. Conservative treatment was first performed during a 6-week rehabilitation program. When conservative treatment failed, arthroscopic surgical resection of the os trigonum was proposed. Visual analogue scale (VAS) was used to measure pain before and after surgery as well as time until their return to previous sports level. VAS showed a mean preoperative pain score of 7.5 (SD = 0.9), whereas postoperative VAS at 1 month after surgery decreased to 0.8 (SD = 1.36). Mean symptomatic period was 8.5 months (SD = 4.3), from the beginning of symptoms up to the surgery day. Once patients had undergone surgery, mean time until their return to previous level of sports was 46.9 days (SD = 25.96), reaching the same pre-lesion Tegner level. Endoscopic treatment of posterior ankle impingement syndrome due to os trigonum showed excellent results. Hindfoot endoscopy with a posterior approach was an effective treatment and allowed for a prompt return to play in soccer players with a high activity level. Level IV, therapeutic study.


The incidence and prevalence of patients with paroxysmal nocturnal haemoglobinuria and aplastic anaemia PNH syndrome: A retrospective analysis of the UK's population-based haematological malignancy research network 2004-2018.
A retrospective population-based study to determine the incidence and prevalence of patients with the rare blood disease paroxysmal nocturnal haemoglobinuria (PNH). All patients were identified by flow cytometric detection of blood cells deficient in glycosylphosphatidylinositol (GPI) linked proteins at a single diagnostic reference laboratory that serves the Yorkshire based, Haematological Malignancy Research Network (HMRN) with a population of 3.8 million. One hundred and ninety-seven patients with detectable PNH clones at a level of >0.01% in at least two lineages of cells (neutrophils, monocytes and/or red cells) were identified over a 15-year period (2004-2018). Of these, 88% had aplastic anaemia (AA), 8% classical PNH and 3% myelodysplastic syndrome. The overall incidence rate was estimated at 0.35 cases per 100 000 people per year. This equates to 220 cases newly diagnosed in the United Kingdom each year. The overall prevalence rate was 3.81 per 100 000, this equates to an estimated 2400 prevalent cases in the UK. The overall and relative 5-year survival rates were 72% and 82.7%, respectively. This study showed that classical haemolytic PNH is a rare disease and represents only a small proportion overall of patients with detectable PNH cells, the majority of which have aplastic anaemia.


Optogenetically-induced long term depression in the rat orbitofrontal cortex ameliorates stress-induced reversal learning impairment.
Cognitive flexibility is a higher-order executive function that requires plasticity in neuronal circuits of the prefrontal cortex. Deficits in cognitive flexibility are prominent in a variety of psychiatric disorders, such as major depression, obsessive-compulsive disorder, and posttraumatic stress disorder. Chronic stress induces deficits in cognitive flexibility, perhaps through effects on plasticity, but the mechanism is not well understood. Previous work has demonstrated that stress reduces activity and dendritic elaboration in the medial prefrontal cortex (mPFC). In contrast, stress appears to increase dendritic elaboration in the orbitofrontal cortex (OFC). This suggests that there may be a differential effect of stress on plasticity in different prefrontal cortical areas. To test this hypothesis, we examined the effects of inducing plasticity optogenetically in the OFC on reversal learning, an OFC-mediated form of cognitive flexibility, in stressed and non-stressed rats. Inducing opto-LTD in the projection from mediodorsal thalamus to OFC ameliorated reversal learning deficits in rats exposed to chronic intermittent cold (CIC) stress. Additionally, we found that inducing opto-LTP in non-stressed rats produced deficits in reversal learning similar to those seen in rats after CIC stress. Finally, CIC stress produced complex subregion-specific changes in dendritic material and spine subtype composition in the OFC. These results indicate that the effects of stress on plasticity in the OFC are distinct from those in the mPFC, and that the PFC should therefore not be treated as a homogenous region in studying either stress effects or potential treatments for stress-related psychiatric disorders.


Synthesis, structure, and olefin polymerization with nickel(II) N-heterocyclic carbene enolates.
Two novel N-heterocylic carbene enolate nickel complexes have been prepared and shown to be active for ethylene and propylene polymerization to yield linear polymers.


Gender-associated diverse mitochondrial DNA molecules of the mussel Mytilus californianus.
The Pacific-rim, dioecious bivalve Mytilus californianus contains two distinct sequence types of mitochondrial (mt) DNA that are gender-limited in their occurrence. One type (F) is found in both females and males, but the second type (M) is strictly limited to males. Although F- and M-type mtDNAs occur in approximately equal proportion in testes, there is a preponderance of M-type in sperm. Segments of the COI and ND5 genes of F-type and M-type mtDNAs differ in nucleotide sequence by 21.1% and 31.6%, and in predicted amino-acid sequence by 7.9% and 27.1%, respectively. These latter observations raise hitherto unconsidered questions regarding the number of different variants of cytochrome c oxidase and NADH dehydrogenase that may occur in Mytilus non-gametic male cells.


Viral fibrotic scoring and drug screen based on MAPK activity uncovers EGFR as a key regulator of COVID-19 fibrosis.
Understanding the molecular basis of fibrosis, the lethal complication of COVID-19, is urgent. By the analysis of RNA-sequencing data of SARS-CoV-2-infected cells combined with data mining we identified genes involved in COVID-19 progression. To characterize their implication in the fibrosis development we established a correlation matrix based on the transcriptomic data of patients with idiopathic pulmonary fibrosis. With this method, we have identified a cluster of genes responsible for SARS-CoV-2-fibrosis including its entry receptor ACE2 and epidermal growth factor EGF. Then, we developed Vi-Fi scoring-a novel drug repurposing approach and simultaneously quantified antiviral and antifibrotic activities of the drugs based on their transcriptomic signatures. We revealed the strong dual antifibrotic and antiviral activity of EGFR/ErbB inhibitors. Before the in vitro validation, we have clustered 277 cell lines and revealed distinct COVID-19 transcriptomic signatures of the cells with similar phenotypes that defines their suitability for COVID-19 research. By ERK activity monitoring in living lung cells, we show that the drugs with predicted antifibrotic activity downregulate ERK in the host lung cells. Overall, our study provides novel insights on SARS-CoV-2 dependence on EGFR/ERK signaling and demonstrates the utility of EGFR/ErbB inhibitors for COVID-19 treatment.


Drug toxicity in the proximal tubule: new models, methods and mechanisms.
The proximal tubule (PT) reabsorbs most of the glomerular filtrate and plays an important role in the uptake, metabolism and excretion of xenobiotics. Some therapeutic drugs are harmful to the PT, and resulting nephrotoxicity is thought to be responsible for approximately 1 in 6 of cases of children hospitalized with acute kidney injury (AKI). Clinically, PT dysfunction leads to urinary wasting of important solutes normally reabsorbed by this nephron segment, leading to systemic complications such as bone demineralization and a clinical scenario known as the renal Fanconi syndrome (RFS). While PT defects can be diagnosed using a combination of blood and urine markers, including urinary excretion of low molecular weight proteins (LMWP), standardized definitions of what constitutes clinically significant toxicity are lacking, and identifying which patients will go on to develop progressive loss of kidney function remains a major challenge. In addition, much of our understanding of cellular mechanisms of drug toxicity is still limited, partly due to the constraints of available cell and animal models. However, advances in new and more sophisticated in vitro models of the PT, along with the application of high-content analytical methods that can provide readouts more relevant to the clinical manifestations of nephrotoxicity, are beginning to extend our knowledge. Such technical progress should help in discovering new biomarkers that can better detect nephrotoxicity earlier and predict its long-term consequences, and herald a new era of more personalized medicine.


Signaling switch of the axon guidance receptor Robo3 during vertebrate evolution.
Development of neuronal circuits is controlled by evolutionarily conserved axon guidance molecules, including Slits, the repulsive ligands for roundabout (Robo) receptors, and Netrin-1, which mediates attraction through the DCC receptor. We discovered that the Robo3 receptor fundamentally changed its mechanism of action during mammalian evolution. Unlike other Robo receptors, mammalian Robo3 is not a high-affinity receptor for Slits because of specific substitutions in the first immunoglobulin domain. Instead, Netrin-1 selectively triggers phosphorylation of mammalian Robo3 via Src kinases. Robo3 does not bind Netrin-1 directly but interacts with DCC. Netrin-1 fails to attract pontine neurons lacking Robo3, and attraction can be restored in Robo3(-/-) mice by expression of mammalian, but not nonmammalian, Robo3. We propose that Robo3 evolution was key to sculpting the mammalian brain by converting a receptor for Slit repulsion into one that both silences Slit repulsion and potentiates Netrin attraction.


ABA-mediated inhibition of seed germination is associated with ribosomal DNA chromatin condensation, decreased transcription, and ribosomal RNA gene hypoacetylation.
Seed germination is a highly organized biological process accompanied by many cellular and metabolic changes. The ribosomal RNA (rRNA) gene, which forms the nucleolus at interphase and is transcribed for ribosome production and protein synthesis, has an important role during seed germination. In this study, we report that there is a decondensation of ribosomal DNA (rDNA) chromatin during seed germination accompanied with increased rRNA gene expression and overall genomic hyperacetylation. Analysis of the rRNA gene promoter region by using chromatin immunoprecipitation (ChIP) shows that there is an increase in acetylation levels at the rRNA gene promoter region. Application of seed germination inhibitor abscisic acid (ABA) suppresses rDNA chromatin decondensation, the expression of rRNA genes and global genomic acetylation. The further ChIP experiments show that ABA treatment hinders the elevation of acetylation levels in the promoter region of the rRNA gene. The data together indicate that ABA treatment inhibits seed germination, which is associated with rDNA chromatin condensation, decreased transcription and rRNA gene hypoacetylation.


An analysis of the concept dignity.
Dignity is a highly abstract, vague concept that is difficult to measure within the context of general nursing. Despite this, it is a central phenomenon to nursing and so it is crucial that health care workers have a clear depiction of dignity. This concept analysis uses the framework established by Walker and Avant [Walker, L.O., Avant, K.C., 1995. Strategies for Theory Construction in Nursing, third ed., Appleton and Lange, Connecticut] in order to heighten knowledge and awareness of the concept dignity. This approach also ensures that the concept is not being used erroneously. Respect, autonomy, empowerment and communication have been identified within the literature as being the defining attributes of dignity. Within these, further attributes are defined, which explain the complex, ambiguous concept that it is. This concept analysis is important for areas where the maintenance of dignity may be unintentionally overlooked. This can be related to many Emergency Departments in various parts of the world, where patients are awaiting beds. This is prevalent and has been slowly worsening for more than a decade [Derlet, R.W., Richards, J.R., 2000. Overcrowding in the Nation's emergency departments: complex causes and disturbing effects. Annals of Emergency Medicine 35 (1), 63-68; Schneider, S., Zwemer, F., Doniger, A., Dick, R., Czapranski, T., Davis, E., 2001. Rochester, New York: A decade of emergency department overcrowding. Academic Emergency Medicine 8, 1044-1050; Nairn, S., 2003. The politics of beds. Accident and Emergency Nursing 11, 68-74]. Commonly patients are nursed in a corridor, which does not lend itself to upholding the dignity, privacy and confidentiality of those patients [Ball, J., Dixon, M., Dolan, B., Holt, L., Wilkinson, R., 2000. Why are we waiting? Emergency Nurse 8 (1), 173-180]. However, patients' dignity should be maintained at all times and health care workers need to recognise that they themselves need dignity in order to promote dignity in others.


Impact of arteriovenous fistula on flow states in the evaluation of aortic stenosis among ESKD patients on dialysis.
An arteriovenous fistula (AVF) in patients with end-stage kidney disease (ESKD) can influence flow states. We sought to evaluate if assessment of aortic stenosis (AS) by transthoracic echocardiographic (TTE) differs in the presence of AVF compared to other dialysis accesses in patients on dialysis. We identified consecutive ESKD patients on dialysis and concomitant AS from a single center between January 2000 and March 2021. We analyzed TTE parameters of AS severity (velocities, gradients, aortic valve area [AVA]) and hemodynamics (cardiac output [CO], valvuloarterial impedance [Zva]) and compared AS parameters in patients with AVF versus other dialysis access. The cohort included 94 patients with co-prevalent ESKD and AS; mean age 66 years, 71% male; 43% Black, 24% severe AS. Dialysis access: 53% AVF, 47% others. In the overall cohort, no significant differences were noted between AVF versus non-AVF in AVA/CO/Zva, but with notable subgroup differences. In mild AS, CO was significantly higher in AVF versus non-AVF (6.3 vs. 5.2 L/min; p = .04). In severe AS, Zva was higher in the AVF versus non-AVF (4.6 vs. 3.6 mm Hg/mL/m2 ). With increasing AS severity in the AVF group, CO decreased, coupled with increase in Zva, likely counterbalancing the net hemodynamic impact of the AVF. Among ESKD patients with AS, TTE parameters of flow states and AS severity differed in those with AVF versus other dialysis accesses and varied with progression in severity of AS. Future longitudinal assessment of hemodynamic parameters in a larger cohort of co-prevalent ESRD and AS would be valuable.


Gender difference in determinant factors of being overweight among the 40-70-year-old population of Kharameh cohort study, Iran.
Iranians face being overweight as one of the most common health problems, which is more prevalent among women. This study aimed to identify gender differences in determinants of being overweight in 40- to 70-year-old participants from Kharameh, Iran. This cross-sectional study was conducted during 2015-2016. The total 10,663 inhabitants of Kharameh, Iran, aged 40-70 years old, were target population. Those with a body mass index (BMI) < 18.5 or > 29.9 were excluded. A checklist composed of socio-demographic, lifestyle, and BMI items was used; a p-value < 0.05 was considered significant. Overall, 53.4% of 8222 participants were overweight. The prevalence of overweight women (62.7%) was significantly higher (p < 0.001) than men (43.6%). The logistic regression model for men showed that being overweight was more likely among men with cigarette smoking history (OR = 1.49) and those with a moderate physical activity level (OR = 1.35), but less likely among those with a higher socio-economic status (SES) (OR = 0.74). Among women, being overweight was associated with high SES (OR = 1.61), an education level below high school diploma (OR = 1.57) and primary school education (OR = 1.50), being married (OR = 2.39), widowed (OR = 2.11) and having a greater calorie intake (OR = 1.01). Being overweight was less likely among employed women (OR = 0.85), those with cigarette smoking history (OR = 0.65), and those with high (OR = 0.72) and intensive physical activity (OR = 0.73). This study revealed the gender differences in determining factors affecting being overweight. As being overweight was more prevalent among women, the priority of health policies to control this issue should also be focused on women.


An attempt to improve the identification of alcohol-dependent patients in a teaching general hospital.
The information on drinking habits contained in medical records with that obtained through the CAGE alcoholism screening test was compared for 124 inpatients of a teaching general hospital. This survey was followed by testing the possibility of introducing the CAGE test into the routine clinical interview. A second analysis of 110 medical records performed 2 months later indicated the failure of this attempt, as the general pattern of information on drinking habits remained unaltered and characterized by either no information at all or information that was too ambiguous to be of clinical value. Among the different hypotheses that could account for the negative results is the possibility that physicians are not sufficiently informed on the wide spectrum of clinical disorders associated to alcohol abuse. Another important factor is the lack of motivation shown by attending physicians to detect less obvious cases of alcohol dependence as they feel pessimistic about dealing with this condition.


Growth reduction and alteration of nonstructural carbohydrate (NSC) allocation in a sympodial bamboo (Indocalamus decorus) under atmospheric O3 enrichment.
Regional increases in atmospheric O3, mainly produced photochemically from anthropogenic precursor gases, have phytotoxicity due to its strong oxidizing properties. To determine the response of bamboo physiology to elevated O3 levels, three-year-old dwarf bamboo (Indocalamus decorus) clones were exposed to three O3 concentrations (Ambient-AA, 21.3 to 80.9 ppb in the daytime; -AA+70, 70 ppb O3 above ambient; -AA+140, 140 ppb O3 above ambient) in open-top chambers for one growing season in Beijing, China. Gas exchange, biomass, growth, soluble sugar, and starch contents were examined at the end of the experiment. Our findings indicated that: (1) elevated O3 treatments decreased the photosynthesis rate, total biomass, and bud numbers but increased individual bud biomass and rhizome bud to rhizome biomass ratio. The most severe reduction was observed in new rhizome biomass (35.9% reduction in AA+70 and 57.2% reduction in AA+140), whereas individual bud biomass increased by 50% and 75% in the AA+70 and AA+140 groups compared with AA, respectively; (2) the starch contents in the rhizome decreased by 28.4%, whereas soluble sugar increased by 38.1% in the AA+140 rhizome buds compared to AA; (3) only the culm numbers of pachymorph rhizomes (clumped) decreased, whereas no changes in leptomorph rhizomes were observed. However, the mean distance between two ramets was lengthened by 49.4% and 86.5% in AA+70 and AA+140, respectively. In conclusion, Indocalamus decorus allocated more nonstructural carbohydrates (NSCs) from the rhizome to the buds to form stronger buds and ensure the survival of newer generations as a high priority in response to O3 exposure. Indocalamus decorus may be conducive to escaping from disadvantaged habitats and decreasing resource competition by lengthening the distance between two ramets.


The prevalence of cirrhotic cardiomyopathy according to different diagnostic criteria.
Recently published criteria by 2019 Cirrhotic Cardiomyopathy Consortium set a lower threshold for reduced ejection fraction to diagnose systolic dysfunction in cirrhotic patients, and stress testing was replaced by echocardiography strain imaging. The criteria to diagnose diastolic dysfunction are in general concordant with the 2016 ASE/EACVI guidelines and differ considerably from the 2005 Montreal recommendations. We aimed to assess the prevalence of cirrhotic cardiomyopathy according to different diagnostic criteria. Cirrhotic patients without another structural heart disease, arterial hypertension, portal vein thrombosis, HCC outside Milan criteria and presence of TIPS were enrolled. Speckle-tracking echocardiography was performed by EACVI certified investigators. A total of 122 patients with cirrhosis fulfilled the inclusion criteria. Overall prevalence of cirrhotic cardiomyopathy was similar for 2005 Montreal and 2019 CCC: 67.2% vs 55.7% (P = .09); and significantly higher compared to 2009 ASE/EACVI criteria: 67.2% vs 35.2% (P < .0001) and 55.7% vs 35.2% (P = .002) respectively. Significantly more patients had diastolic dysfunction according to the 2005 Montreal compared to the 2009 ASE/EACVI and 2019 CCC criteria: 64.8% vs 32.8% (P < .0001) and 64.8% vs 7.4% (P < .0001). Systolic dysfunction was more frequently diagnosed according to 2019 CCC criteria compared to 2005 Montreal (53.3% vs 16.4%,P < .0001) or ASE/EACVI criteria (53.3% vs 4.9%,P < .0001). Cirrhotic cardiomyopathy was present in around 60% of cirrhotic patients when applying the hepatological criteria. A considerably higher prevalence of systolic dysfunction according to the 2019 CCC criteria was observed. Long-term follow-up studies are needed to establish the validity of these criteria to predict clinically relevant outcomes.


PML2-mediated thread-like nuclear bodies mark late senescence in Hutchinson-Gilford progeria syndrome.
Progerin accumulation disrupts nuclear lamina integrity and causes nuclear structure abnormalities, leading to premature aging, that is, Hutchinson-Gilford progeria syndrome (HGPS). The roles of nuclear subcompartments, such as PML nuclear bodies (PML NBs), in HGPS pathogenesis, are unclear. Here, we show that classical dot-like PML NBs are reorganized into thread-like structures in HGPS patient fibroblasts and their presence is associated with late stage of senescence. By co-immunoprecipitation analysis, we show that farnesylated Progerin interacts with human PML2, which accounts for the formation of thread-like PML NBs. Specifically, human PML2 but not PML1 overexpression in HGPS cells promotes PML thread development and accelerates senescence. Further immunofluorescence microscopy, immuno-TRAP, and deep sequencing data suggest that these irregular PML NBs might promote senescence by perturbing NB-associated DNA repair and gene expression in HGPS cells. These data identify irregular structures of PML NBs in senescent HGPS cells and support that the thread-like PML NBs might be a novel, morphological, and functional biomarker of late senescence.


How successful are we in relieving terminal dyspnea in cancer patients? A real-world multicenter prospective observational study.
Parenteral morphine is widely used for dyspnea of imminently dying cancer patients, but the outcomes to expect over time remain largely unknown. We examined outcomes after the administration of parenteral morphine infusion over 48 h in cancer patients with a poor performance status. This was a multicenter prospective observational study. Inclusion criteria were metastatic/locally advanced cancer, ECOG performance status = 3-4, a dyspnea intensity ≥ 2 on a Support Team Assessment Schedule, Japanese version (STAS-J), and receiving specialized palliative care. After initiating parenteral morphine infusion, we measured dyspnea STAS-J as well as Memorial Delirium Assessment Scale (MDAS), item 9, and Communication Capacity Scale (CCS), item 4, every 6 h over 48 h. We enrolled 167 patients (median survival = 4 days). The mean age was 70 years, 80 patients (48%) had lung cancer, and 109 (65%) had lung metastases. The mean STAS-J scores decreased from 3.1 (95% confidence interval (CI) = 3.0-3.2) at the baseline to 2.1 (95%CI = 1.9-2.2) at 6 h, and remained 1.6-1.8 over 12-48 h. The proportion of patients with dyspnea relief (STAS-J ≤ 1) increased to 39% at 6 h, and ranged between 49 and 61% over 12-48 h. In contrast, up to 6.6 and 20% of patients showed hyperactive delirium (MDAS item 9 ≥ 2) and an inability to communicate (CCS item 4 = 3), respectively, over 48 h. Overall, terminal dyspnea was relatively well controlled with parenteral morphine, though a significant number of patients continued to suffer from dyspnea. Future efforts are needed to improve outcomes following standardized dyspnea treatment using patient-reported outcomes for imminently dying patients.


Blood donor candidates and blood donations performed between 2005 and 2019 in Minas Gerais, Brazil: A time series analysis.
Time series studies related to blood donor candidates and blood donations are rare in Brazil. Population aging suggests a better understanding of the context related to blood donor candidates and blood donations performed. The monthly series of candidates eligible to donate blood and actual donations between 2005 and 2019 at the Hemominas Foundation, Minas Gerais, Brazil, were described and analyzed. Ten time series were constructed of blood donor candidates and blood donations. Each series covered the period from January 2005 to December 2019. The stationarity of the series was verified by the unit root test; the data distribution, by the Shapiro-Wilk test; the trend, by the Cox-Stuart test, and; the seasonality, by the Fisher's test (significance levels of 10% for the first test and 5% for the last three). All series were identified as non-stationary and presented trend and seasonality components. The rate of blood donor candidates and the rate of blood donations performed evidenced a positive upward trend until the last two-year analysis, when a drop occurred, from 1.75% and 1.42% in 2017 to 1.64% and 1.35% in 2019, respectively. The rate of blood donations trended downward, from 0.054% in 2005 to 0.046% in 2019. The proportion of unsuitable or unretained candidates reduced. The study emphasized the need to stimulate blood donation by specific groups and increase ways to reduce the demand for blood components through the implementation of programs that expand alternatives to blood transfusions.


N-Glycosyl-thiophene-2-carboxamides: synthesis, structure and effects on the growth of diverse cell types.
A range of N-glycosyl-thiophene-2-carboxamides, including a 6H-thieno[2,3-c]pyridin-7-one and a bivalent compound, have been synthesised and assayed for their effects on DNA synthesis in bovine aortic endothelial cells or on the growth of synoviocytes. Per-O-acetylated analogues of the glycoconjugates were significantly more effective inhibitors when compared to their corresponding non-acetylated analogues, indicating that the lower potency observed for hydroxylated derivatives is due to less efficient transport of these compounds across the cell membrane. Thiophene-2-carboxamide was inactive as an inhibitor of bFGF induced proliferation, confirming the requirement of the carbohydrate residue for the observed biological properties. Glucose, mannose, galactose and 2-amino-2-deoxy-glucose analogues were active as were a variety of substituted thiophene derivatives; the 6H-thieno[2,3-c]pyridin-7-one conjugate was inactive. Conformational analysis of the title compounds was investigated. X-ray crystal structural analysis of four N-glucosyl-thiophene-2-carboxamides showed that the pyranose rings adopted the expected 4C1 conformations and that Z-anti structures were predominant (H1-C1-N-H anomeric torsion angle varied from -168.2 degrees to -175.0 degrees ) and that the carbonyl oxygen and sulfur of the thiophene adopted an s-cis conformation in three of the isomers. In a crystal structure of a 3-alkynyl derivative, the hydrogen atom of the NH group was directed toward the acetylene group. The distance between the hydrogen atom and acetylene carbons and angles between nitrogen, hydrogen and carbon atoms were consistent with hydrogen bonding and this was supported by IR and NMR spectroscopic studies. The geometries of thiophene-2-carboxamides were explored by density functional theory (DFT) and Møller-Plesset (MP2) calculations and the s-cis conformer of thiophene-2-carboxamide was found to be more stable than its s-trans isomer by 0.83 kcal mol(-1). The s-cis conformer of 3-ethynyl-thiophene-2-carboxamide was 5.32 kcal mol(-1) more stable than the s-trans isomer. The larger stabilisation for the s-cis conformer in the 3-alkynyl derivatives is explained to be due to a moderate hydrogen bonding interaction between the alkyne and NH group.


Local recurrence in sigmoid cancer is a hidden problem, could CT prognostic factors be of value in their prevention? A multi-centre study of 414 patients.
The incidence and patterns of local recurrence of colon cancer are not well reported. The aim of this study was to investigate the contemporary rates and patterns of local recurrence after sigmoid cancer resection, comparing pre and post-operative biomarkers in predicting local disease recurrence. A multi-centre, retrospective analysis of 414 patients undergoing resectional surgery for sigmoid colon cancer was conducted. Multivariable Cox Proportional Hazard models were created to identify variables associated with local disease recurrence. Patterns of recurrence and prognostic significance of pre and post-operative variables were identified. In 414 patients, the local recurrence rate was 12.6%. The R1/R2 rate was 2.4%. Local recurrence occurred most commonly within the peri-anastomotic region (50%), followed by the peritoneum (33%). On multivariate analysis, local recurrence was predicted by pathological T stage (HR 1.15) and R1 resection (HR 2.95), but also computerised tomography (CT) identified tumour deposits (HR 2.40) and local peritoneal infiltration (2.70). Contemporary local recurrence rates for sigmoid cancer are high at 12.6%. Outcomes may be improved if local recurrence is reduced at the most common sites such as the peri-anastomotic area or peritoneum. Extra-nodal CT-imaging biomarkers of local peritoneal infiltration and tumour deposits were prognostically significant on multivariate analysis in addition to pathology staging variables.


Clinical and phenomenological comparisons of delusional and non-delusional major depression in the Chinese elderly.
Distinct clinical entities, with and without delusions, have been reported for depressed patients. This study explores the clinical and phenomenological aspects of delusional and non-delusional major depression in elderly Chinese patients. A total of 156 depressed patients (105 males and 51 females) admitted to our geriatric psychiatry ward were investigated. Sociodemographic and clinical characteristics were compared between patients divided into two groups-according to presence or absence of delusions. On admission, higher risk of suicide attempt, higher chance of guilt feelings, and greater daily functional impairment were observed for the deluded group. Further, the score of Hamilton Depression Rating Scale was higher and the score of Mini-Mental State Examination was lower for delusional depressives. Our findings were grossly concordant with previous Western reports, and highlight the importance of identifying the delusional subgroup of depressive patients because of the higher risk of suicide attempt.


AET-treated sheep red blood cell and immunobead for combined detection of human peripheral lymphocyte subpopulations.
This paper describes a method for the simultaneous determination of human thymus-dependent lymphocyte (T cell) and thymus-independent lymphocyte (B cell) populations by mixing lymphocytes, sheep red blood cells, and immunobeads. This method also detects lymphocytes possessing both T and B cell markers. T cells are detected by rosette formation with AET-treated sheep red blood cells and B cells are identified by rosette formation with polyacrylamide gel coated with antibody specific to immunoglobulin classes. The major advantages of this technique is that it is simple, convenient, and reproducible. Three different types of rosettes are distinguishable under light microscopic observation. The detection of double marker lymphocytes, using this combined technique, may have further application in clinical investigation.


An integrative review of primary health care nurses' mental health knowledge gaps and learning needs.
The global COVID-19 pandemic has escalated the prevalence of mental illness in the community. While specialist mental health nurses have advanced training and skills in mental health care, supporting mental health is a key role for all nurses. As front-line health care professionals, primary health care (PHC) nurses need to be prepared and confident in managing mental health issues. To critically analyse and synthesise international literature about the knowledge gaps and learning needs of PHC nurses in providing mental health care. An integrative review. The quality of papers was assessed using the Mixed Methods Appraisal Tool. Data were extracted into a summary table and analysed using narrative analysis. CINAHL, Ovid MEDLINE, Web of Science and EBSCO electronic databases were searched between 1999 and 2019. Papers were included if they reported original research which explored mental health education/training of nurses working in PHC. Of the 652 papers identified, 13 met the inclusion criteria. Four themes were identified: preparedness; addressing knowledge gaps, education programs, and facilitators and barriers. Despite increasing integration of physical and mental health management in PHC, there is limited evidence relating to knowledge gaps and skills development of PHC nurses or their preparedness to provide mental health care. Findings from this review, together with the global increase in mental illness in communities arising from COVID-19, highlight the need for PHC nurses to identify their mental health learning needs and engage in education to prepare them to meet rising service demands.


Phase 2 clinical trial of TORC1 inhibition with everolimus in men with metastatic castration-resistant prostate cancer.
Activation of the PI3K-Akt-mTOR signaling pathway is common in advanced castration resistant prostate cancer (CRPC), typically through PTEN loss. Preclinical studies suggest that Akt-driven CaP cells are genetically susceptible to mammalian target of rapamycin (mTOR, or TORC1) inhibition. Everolimus is a Food and Drug Administration-approved inhibitor of TORC1. We performed a phase II study of everolimus in patients with mCRPC, who were refractory to standard of care hormonal and chemotherapeutic agents. Patients received everolimus 10 mg daily until unacceptable adverse events or disease progression. The primary efficacy outcome was confirmed 50% or greater prostate-specific antigen (PSA) response, using a 2 stage design with futility rules. Paired biopsies were utilized to assess for treatment effect on downstream TORC1 targets as well as tumor cell proliferation and apoptosis. Out of 35 men enrolled with heavily pretreated mCRPC, 32 were evaluable for clinical efficacy. No PSA responses were observed, the median progression-free survival time was 3.6 months (95% confidence interval = 2.9-4.8) and the median overall survival time was 10.4 months (95% confidence interval = 5.8-15.8). Several patients had declines in serum PSA upon cessation of everolimus. Thus, the study was closed due to clinical futility. The most common toxicities were mucositis, fatigue, anorexia, hypertriglyceridemia, and thrombocytopenia and were largely low grade. Pathologic evaluation of paired metastatic biopsies demonstrated consistent inhibition of pS6, a downstream mTOR pharmacodynamics biomarker, but the tumor proliferation marker Ki-67 increased with therapy. Everolimus demonstrated predictable toxicity in advanced and heavily pretreated patients with mCRPC. No clinical or clear pathologic effects despite downstream TORC1 target inhibition, suggesting that single agent everolimus has no clinical utility in men with mCRPC.


Dietary attitudes and diseases of comfort.
This article reviews Western dietary attitudes and lifestyle choices by identifying the environmental, social and personal factors that determine said attitudes and choices. Environmental factors exert a major influence on, and complicate, dietary behavior, primarily by facilitating the consumption of meals away from home and by minimizing time dedicated to meal preparation and consumption. Social factors, from mass media to advertising and cultural traditions, also influence food intake, to an extent that is still underestimated. Ignorance of the real influence of environment and society on food choices could well blind consumers to the real significance of such choices. Accordingly, this review discusses differing aspects of emerging dietary trends and/or philosophies, and underlines their potentially harmful influence on health. Western countries are increasingly witnessing a dichotomy between the findings of nutritional science and the choices that dietary trends propose and impose. Coinciding with the obesity epidemic and the spread of other food-related diseases, this dichotomy calls for the development of effective preventive strategies.


Effects of oral butyrate application on insulin signaling in various tissues of chickens.
The influence of butyrate on insulin signaling in chickens was studied because butyrate is produced during microbial fermentation in the large intestine of birds, and butyrate is widely used as a feed additive in animal production. Ross 308 broiler chickens received a daily intraingluvial bolus of sodium butyrate (0.25 g/kg body weight) on days 20-24 of life (n = 10). Plasma butyrate concentration increased after receiving oral butyrate treatment (P < 0.001). Oral butyrate application was associated with decreased protein expression of insulin receptor β subunit (IRβ) in liver (P = 0.008) and both abdominal (P = 0.003) and subcutaneous adipose tissue (P < 0.001), but with elevated IRβ expression in muscle (P = 0.045), assessed by Western blotting. The quantity of hepatic phosphatidyl-inositol-3-kinase was reduced in the butyrate-treated group (P = 0.007); further, mammalian target of rapamycin was downregulated by butyrate in liver (P < 0.001) and subcutaneous adipose tissue (P = 0.038). Oral butyrate application provoked reduced systemic insulin sensitivity in chickens, indicated by elevated fasting blood glucose and subsequently, insulin level. However, responses of insulin signaling cascade to butyrate were tissue specific, suggesting that butyrate could act on glucose shifting among tissues by selectively increasing the glucose uptake of skeletal muscle via IRβ upregulation.


What is the mechanism of this post ablation atrial flutter "recurrence"?
We present the case of a patient with typical atrial flutter treated with radiofrequency ablation of the cavo-tricuspid isthmus, which presented 5 days later with an ECG suggesting an atrial flutter recurrence. However, careful analysis of this ECG demonstrated a potentially different mechanism of the arrhythmia, underlying the importance of a pragmatic approach to ECG interpretation of arrhythmias. A secondary electrophysiological study was performed diagnosing a focal atrial tachycardia with origin at the coronary sinus ostium, in the presence of a blocked cavotricuspid isthmus. RF ablation successfully suppressed the arrhythmia.


Formation of a Large Confined Spherical Space with a Small Aperture Using Flexible Hexasubstituted Sumanene.
Two sumanene-based porous coordination networks were successfully prepared by the complexation of hexapyridylsumanene with Zn(NO3)2·6H2O or Cd(NO3)2·4H2O. X-ray single crystal analysis unambiguously revealed that the curved structure of the central sumanene skeleton of the ligand resulted in the formation of a large confined space with a small aperture size. In the Zn2+ network, the beltlike trimer units were connected to each other to form a 1D channel separated by the counteranion to afford isolated spaces. The Cd2+ network formed spherical tetramer units, which also eventually afforded a 1D channel with open windows smaller than the kinetic diameter of helium. The investigation of the structural parameters of the ligand in both networks revealed the unique feature of hexapyridylsumanene, which flexibly changed its bond length and angles depending on the structural requirements for the network formations.


Two potential fields fused adaptive path planning system for autonomous vehicle under different velocities.
Path planning is a basic function for autonomous vehicle (AV). However, it is difficult to adapt to different velocities and different types of obstacles including dynamic obstacle and static obstacle (such as road boundary) for AV. To solve the problem of path planning under different velocities and different types of obstacles, a two potential fields fused adaptive path planning system (TPFF-APPS) which includes two parts, a potential field fusion controller and an adaptive weight assignment unit, is presented in this work. In the potential field fusion controller, a novel potential velocity field is built by velocity information and fused with a traditional artificial potential field for adapting various velocities. The adaptive weight assignment unit is designed to distribute adaptively the weights of two potential fields for adapting different types of obstacles at the same time, including road boundary and dynamic obstacles. The simulation is carried on the Carsim-Matlab co-simulation platform, and the simulation results indicate that the proposed TPFF-APPS has excellent performance for path planning adapting to different velocities and different types of obstacles.


The effects of variable encoding contexts on item and source recognition.
How repeated encoding affects retention of item details is an unresolved question. The Competitive Trace theory (Yassa & Reagh, Frontiers in Behavioral Neuroscience, 7, 107, 2013) assumes that even slight variations in encoding contexts across item repetitions induce competition among non-overlapping contextual traces, leading to semanticization and decontextualized memory traces. However, empirical support for this assumption is mixed. In extension of previous research, the current study attempted to increase the competition between contextual traces by increasing encoding context variability. In three experiments we tested how repeated encoding in the same context or different contexts affects target recognition, similar lure discrimination, and source memory. Participants viewed images of objects once, three times in the same or three times in different contexts. Context variability was implemented through variations in background color or encoding tasks. Repeated encoding improved memory for item details, independent of context variability. Background color was poorly remembered but answering different encoding questions for repeated items impaired recollection of specific encoding tasks, in comparison to encoding items only once or repeatedly with the same encoding task. Our findings show that repetitions enhance memory for perceptual details but can impair memory for contextual elements, a dissociation that needs to be considered by the Competitive Trace Theory and other consolidation theories.


Prenatal diagnosis: whose right?
The question who is the subject of the right to prenatal diagnosis may be answered in four ways: the parents, the child, society, or no one. This article investigates the philosophical issues involved in each of these answers, which touch upon the conditions of personal identity, the principle of privacy, the scope of social responsibility, and the debate about impersonalism in ethics.