Brain activation patterns during visuomotor adaptation in motor experts and novices: An FDG PET study with unrestricted movements.
Speed of performance improvements and the strength of memory consolidation in humans vary with movement expertise. Underlying neural mechanisms of behavioural differences between levels of movement expertise are so far unknown. In this study, PET with [18F]fluorodeoxyglucose (FDG) was proposed as a powerful novel methodology to assess learning-related brain activity patterns during large non-restricted movements (ball throwing with a right hand). 24 male handball players ('Experts') and 24 male participants without handball experience ('Novices') performed visuomotor adaptations to prismatic glasses with or without strategic manoeuvres (i.e., explicit or implicit adaptation). Regional changes in FDG uptake as a marker of neuronal activity, relative to a control condition, were assessed. Prismatic adaptation, in general, was associated with decreased occipital neuronal activity as a possible response to misleading visual information. In 'Experts', the adaptation was associated with altered neuronal activity in a network comprising the right parietal cortex and the left cerebellum. In 'Novices', implicit adaptation resulted in an activation of the middle frontal and inferior temporal gyrus. This study demonstrates the versatility of FDG PET for studying brain activations patterns in experimental settings with unrestricted movements that are not accessible by other techniques (e.g., fMRI or EEG). Observed results are consistent with the involvement of different functional networks related to strategic manoeuvres and expertise levels. This strengthens the assumption of different mechanisms underlying behavioural changes associated with movement expertise. Furthermore, the present study underscores the value of FDG PET for studying brain activation patterns during unrestricted movements.


Transcriptome reprogramming of resistant and susceptible peach genotypes during Xanthomonas arboricola pv. pruni early leaf infection.
Bacterial spot caused by Xanthomonas arboricola pv. pruni (Xap) is a major threat to Prunus species worldwide. The molecular mechanisms of peach resistance to Xap during early leaf infection were investigated by RNA-Seq analysis of two Prunus persica cultivars, 'Redkist' (resistant), and 'JH Hale' (susceptible) at 30 minutes, 1 and 3 hours-post-infection (hpi). Both cultivars exhibited extensive modulation of gene expression at 30 mpi, which reduced significantly at 1 hpi, increasing again at 3 hpi. Overall, 714 differentially expressed genes (DEGs) were detected in 'Redkist' (12% at 30 mpi and 1 hpi and 88% at 3 hpi). In 'JH Hale', 821 DEGs were identified (47% at 30 mpi and 1 hpi and 53% at 3 hpi). Highly up-regulated genes (fold change > 100) at 3 hpi exhibited higher fold change values in 'Redkist' than in 'JH Hale'. RNA-Seq bioinformatics analyses were validated by RT-qPCR. In both cultivars, DEGs included genes with putative roles in perception, signal transduction, secondary metabolism, and transcription regulation, and there were defense responses in both cultivars, with enrichment for the gene ontology terms, 'immune system process', 'defense response', and 'cell death'. There were particular differences between the cultivars in the intensity and kinetics of modulation of expression of genes with putative roles in transcriptional activity, secondary metabolism, photosynthesis, and receptor and signaling processes. Analysis of differential exon usage (DEU) revealed that both cultivars initiated remodeling their transcriptomes at 30 mpi; however, 'Redkist' exhibited alternative exon usage for a greater number of genes at every time point compared with 'JH Hale'. Candidate resistance genes (WRKY-like, CRK-like, Copper amine oxidase-like, and TIR-NBS-LRR-like) are of interest for further functional characterization with the aim of elucidating their role in Prunus spp. resistance to Xap.


Differentiating invasive thymic epithelial tumors from mediastinal lung cancer using spectral CT parameters.
The purpose of the study was to explore the importance of quantitative characteristics of spectral CT between invasive thymic epithelial tumors (TETs) and mediastinal lung cancer. We analyzed 54 patients (28 with invasive TETs and 26 with mediastinal lung cancer) who underwent spectral CT. During the arterial and venous phase, we measured the CT70keV, effective atomic number (Zeff), iodine concentration (IC), and water concentration (WC) and calculated the slope of the spectral curve (K100keV). We compared the clinical findings and spectral CT parameters of both groups and performed receiver operating characteristic analysis to evaluate the diagnostic efficacy and the optimal cutoff values of the spectral CT parameters. During the AP and VP, the CT70keV, Zeff, IC, and K100keV were significantly higher in patients with invasive TETs than those in patients with mediastinal lung cancer (p < 0.05). WC was not statistically significantly different between the two groups (p > 0.05). ROC curve analysis revealed that all quantitative parameters combined in the AP and VP provided the best diagnostic performance in identifying invasive TETs from mediastinal lung cancer (AUC = 0.88, p = 0.002, sensitivity = 0.89 and specificity = 0.77). The cutoff values in the AP for CT70keV, IC, Zeff, and K100keV to differentiate invasive TETs from mediastinal lung cancer were 75.55, 15.86, 8.45, and 1.71, respectively. The cutoff values in the VP for CT70keV, IC, Zeff, and K100keV to differentiate them were 67.06, 15.74, 8.50, and 1.81, respectively. Spectral CT imaging has potential value in the differential diagnosis of invasive TETs and mediastinal lung cancer.


Management of spontaneous pneumothorax.
Management of patients with a spontaneous pneumothorax continues to challenge clinicians. Recent guidelines help provide care pathways for these patients and highlight the many areas in need of additional study. Management options for spontaneous pneumothoraces should be selected based primarily upon a patient's clinical status. Observation or pleural air drainage, in selected patients, plays a significant role in patients with primary spontaneous pneumothorax. By contrast, pleural air drainage plays the central role in patients with a secondary spontaneous pneumothorax. Surgically directed recurrence prevention and air leak management are preferred for both primary and secondary spontaneous pneumothorax patients.


Association between ABCB1-T1236C polymorphism and drug-resistant epilepsy in Iranian female patients.
One third of epileptic patients are resistant to several anti-epileptic drugs (AED). P-glycoprotein (P-gp) is an efflux transporter encoded by ATP-binding cassette subfamily B member 1 (ABCB1) gene that excludes drugs from the cells and plays a significant role in AEDs resistance. Over-expression of P-gp could be a result of polymorphisms in ABCB1 gene. We studied the association of T129C and T1236C single-nucleotide polymorphisms (SNP) of ABCB1 gene with drug-resistant epilepsy in Iranian epileptics. DNA samples were obtained from 200 healthy controls and 332 epileptic patients, of whom 200 were drug responsive and 132 drug resistant. The frequencies of the genotypes of the two SNP were determined by polymerase chain reaction followed by restriction fragment length polymorphism. No significant association was found between T129C and T1236C genotypes and drug-resistant epilepsy neither in adults nor in children. However, the risk of drug resistance was higher in female patients with 1236CC (P = 0.02) or CT (P = 0.008) genotype than in those with TT genotype. The risk of drug resistance was also higher in patients with symptomatic epilepsies with 1236CC (P = 0.02) or CT (P = 0.004) genotype than in those with TT genotype. The risk of drug resistance was lower in patients with idiopathic epilepsies with 129TT genotype (P = 0.001) than in those with CT genotype. Our results indicate that T1236C polymorphism is associated with drug resistance in Iranian female epileptic patients. Replication studies with large sample sizes are needed to confirm our results.


Gallstone ileus at 17 years after living donor liver transplantation: A case report.
Gallstone ileus (GI) occurs in <0.1% of all cases of mechanical bowel obstruction. There have been a few reports of GI occurring after Kasai procedures or Roux-en-Y anastomosis for bariatric surgery. We herein report a case of GI that occurred over 17 years after liver transplantation (LT). A 33-year-old woman who had undergone living donor LT for biliary atresia at 16 years old and had been regularly followed on an outpatient basis in our hospital presented with the sudden onset of increased abdominal distension, pain, and nausea. Enhanced abdominal computed tomography showed dilatation of the intrahepatic bile duct and the whole intestinal tract of the Roux limb as well as ischemic changes near the jejuno-jejunal anastomosis. On laparotomy, a movable and hard foreign body was palpated in the intestinal tract close to the jejuno-jejunal anastomosis site. Enterotomy was performed, and a 4-cm gallstone was removed. The patient had a good postoperative course and was discharged on postoperative day 12. Although GI after LT is a rare complication, it may need to be differentiated as a cause of ileus. An accurate differential diagnosis and early reliable intervention for stone removal will help prevent serious bowel complication, which may lead to graft dysfunction.


What happens in stapled transanal rectum resection?
Stapled transanal rectum resection is becoming increasingly popular as a surgical option for the treatment of obstructive defecation syndrome. However, details about the anatomical changes produced by stapled transanal rectum resection and its correlation with success or failure is poorly understood. The aim of this study was to correlate the defecographical and clinical patterns in patients treated with stapled transanal rectum resection. Based on a multi-institutional stapled transanal rectum resection registry composed of a total of 182 patients, correlation analysis of clinical and radiological parameters was prospectively obtained from 51 patients with a completed 12-month follow-up. Postoperative defecography shows significant changes in the following parameters: intussusception (89%-19%; P < .0001), enterocele (38%-18%; P = .038), rectocele (mean ± SD: 27.1 ± 7.4 mm to 16.5 ± 9.7 mm; P < .0001), rectal lumen (mean ± SD: 46 ± 11.4 mm to 35 ± 9.9 mm; P < .0001), anorectal angle (mean ± SD: 146.4 ± 10.6° to 132.4 ± 11.1°; P = .002), pelvic floor descent (mean ± SD: 59 ± 18 mm to 47 ± 1.3 mm; P = .0001), and, as a dynamic parameter, dynamic pelvic floor descent (mean ± SD: 30 ± 0.8 mm to 17 ± 0.4 mm; P < .0001). Of these parameters, reduction of intussusception (r = 0.433, 95% CI 0.15-0.61; P = .003), rectocele (r = 0.507, 95% CI 0.26-0.67; P = .001), and dynamic pelvic floor descent (r = 0.427, 95% CI 0.31-0.64; P = .001) correlated with a significant improvement in constipation. Reduction of intussusception positively affected postoperative continence (r = 0.524, 95% CI 0.29-0.70; P = .001), whereas reduced rectal lumen size correlated with incontinence and fecal urgency (r = -0.557, 95% CI -0.69 to -0.28; P = .001). Improved constipation after stapled transanal rectum resection is associated with improvement of intussusception, rectocele, and dynamic pelvic floor descent. Postoperative continence is determined by 2 parameters, reduction of intussusception and rectal lumen size, which have opposing effects. Reduction of rectal lumen size may be responsible for new-onset fecal urgency, which is occasionally seen after stapled transanal rectum resection.


Gut microbiota and atherosclerosis: role of B cell for atherosclerosis focusing on the gut-immune-B2 cell axis.
Atherosclerosis is the leading cause of cardiovascular mortality and morbidity worldwide and is described as a complex disease involving several different cell types and their molecular products. Recent studies have revealed that atherosclerosis arises from a systemic inflammatory process, including the accumulation and activities of various immune cells. However, the immune system is a complicated network made up of many cell types, hundreds of bioactive cytokines, and millions of different antigens, making it challenging to readily define the associated mechanism of atherosclerosis. Nevertheless, we previously reported a potential persistent inflammatory process underlying atherosclerosis development, centered on a pathological humoral immune response between commensal microbes and activated subpopulations of substantial B cells in the vicinity of the arterial adventitia. Accumulating evidence has indicated the importance of gut microbiota in atherosclerosis development. Commensal microbiota are considered important regulators of immunity and metabolism and also to be possible antigenic sources for atherosclerosis development. However, the interplay between gut microbiota and metabolism with regard to the modulation of atherosclerosis-associated immune responses remains poorly understood. Here, we review the mechanisms by which the gut microbiota may influence atherogenesis, with particular focus on humoral immunity and B cells, especially the gut-immune-B2 cell axis. Graphical abstract Under high-fat and high-calorie conditions, signals driven by the intestinal microbiota via the TLR signaling pathway cause B2 cells in the spleen to become functionally active and activated B2 cells then modify responses such as antibody production (generation of active antibodies IgG and IgG3), thereby contributing to the development of atherosclerosis. On the other hand, intestinal microbiota also resulted in recruitment and ectopic activation of B2 cells via the TLR signaling pathway in perivascular adipose tissue (PVAT), and, subsequently, an increase in circulating IgG and IgG3 led to the enhanced disease development. This is a potential link between microbiota alterations and B cells in the context of atherosclerosis.


Top-down learning of low-level vision tasks.
Perceptual tasks such as edge detection, image segmentation, lightness computation and estimation of three-dimensional structure are considered to be low-level or mid-level vision problems and are traditionally approached in a bottom-up, generic and hard-wired way. An alternative to this would be to take a top-down, object-class-specific and example-based approach. In this paper, we present a simple computational model implementing the latter approach. The results generated by our model when tested on edge-detection and view-prediction tasks for three-dimensional objects are consistent with human perceptual expectations. The model's performance is highly tolerant to the problems of sensor noise and incomplete input image information. Results obtained with conventional bottom-up strategies show much less immunity to these problems. We interpret the encouraging performance of our computational model as evidence in support of the hypothesis that the human visual system may learn to perform supposedly low-level perceptual tasks in a top-down fashion.


Effects of tilorone hydrochloride on cellular immunity (leukocyte inhibiting factor production from human lymphocyte stimulated by E. coli lipopolysaccharide).
Tilorone hydrochloride, a drug able selectively to affect T-lymphocyte fuction, when incorporated (at three different concentrations 0.1, 0.04, 0.02 microgram/ml) in lymphocyte culture, stimulated by 50 microgram/ml of E. coli LPS (026:B6 W), is able to abolish LIF production, due to endotoxin stimulation. Such effect is, may be, due to an impairment of T-cell activity, since tilorone at the same concentration decreases the number of ARFC and TRFC, which are specific markers for T-cells.


Electrochemical disinfection using boron-doped diamond electrode--the synergetic effects of in situ ozone and free chlorine generation.
This work investigated the capability of using a boron-doped diamond (BDD) electrode for bacterial disinfection in different water matrices containing varying amounts of chloride. The feed water containing Pseudomonas aeruginosa was electrochemically treated while applying different electrode conditions. Depending on the applied current density and the exposure time, inactivation between 4- and 8-log of the targeted microorganisms could be achieved. The disinfection efficiency was driven by the generation of free chlorine as a function of chloride concentration in the water. A synergetic effect of generating both free chlorine and ozone in situ during the disinfection process resulted in an effective bactericidal impact. The formation of the undesired by-products chlorate and perchlorate depended on the water matrix, the applied current density and the desired target disinfection level. In case of synthetic water with a low chloride concentration (20 mg L(-1)) and an applied current density of 167 mA cm(-2), a 6-log inactivation of Pseudomonas aeruginosa could be achieved after 5 min of exposure. The overall energy consumption ranged between 0.3 and 0.6 kW h m(-3) depending on the applied current density and water chemistry. Electrochemical water disinfection represents a suitable and efficient process for producing pathogen-free water without the use of any chemicals.


Treatment outcome of doxorubicin versus idarubicin in adult acute myeloid leukemia.
The present study aimed to compare treatment outcome of idarubicin versus doxorubicin in combination with Ara-C as induction therapy for untreated AML patients. This retrospective study included 143 patients with de novo AML. All patients received full dose of standard induction therapy (3 + 7) using anthracyclines (doxorubicin or idarubicin) and cytarabine. The studied groups had comparable CR. No significant differences were noted between the studied groups regarding DFS and OS. The DXR group had significantly lower cost in comparison to IDA group. Idarubicin doesn't have a clear advantage over doxorubicin in treatment of AML.


Creutzfeldt-Jakob disease: A case report and differential diagnoses.
Although sporadic Creutzfeldt-Jakob disease is a rare neurodegenerative disease and often difficult to diagnose at the earliest onset, meticulous clinical examination, electroencephalography, and neuroimaging findings will help in diagnosis.


Diminished exercise capacity and chronotropic incompetence in pediatric patients with congenital complete heart block and chronic right ventricular pacing.
Chronic right ventricular (RV) pacing has been associated with decreased exercise capacity and left ventricular (LV) function in adults with congenital complete atrioventricular block (CCAVB), but not in children. The purpose of this study was to evaluate the exercise capacity and LV function in pediatric patients with CCAVB receiving chronic RV pacing. We prospectively evaluated pediatric patients with isolated CCAVB receiving atrial synchronous RV pacing for at least 5 years. Supine bicycle ergometry was performed, and LV ejection fraction (EF) was evaluated by echocardiography. Ten CCAVB subjects and 31 controls were matched for age, gender, and body surface area. CCAVB subjects had normal resting EF (63.1% ± 4.0%) and had been paced for 7.9 ± 1.4 years. Exercise testing demonstrated reduced functional capacity in CCAVB patients compared to controls with a lower VO₂peak (26.0 ± 6.6 mL/kg/min vs 39.9 ± 7.0 mL/kg/min, P <.001), anaerobic threshold (15.6 ± 3.9 mL/kg/min vs 18.8 ± 2.7 mL/kg/min, P = .007), and oxygen uptake efficiency slope (1210 ± 406 vs 1841 ± 452, P <.001). Maximum heart rate (165 ± 8 bpm vs 185 ± 9 bpm, P <.001) and systolic blood pressure (159 ± 17 mm Hg vs 185 ± 12 mm Hg, P <.019) also were reduced in CCAVB patients despite maximal effort (respiratory exchange ratio 1.2 ± 0.1). EF was augmented with exercise in controls but not in CCAVB patients (13.2% ± 9.3% vs 0.2% ± 4.8% increase, P <.001). Clinically asymptomatic children with chronic RV pacing due to CCAVB have significant reductions in functional capacity accompanied by chronotropic incompetence and inability to augment EF with exercise.


Respiratory dysfunction in patients with chronic neck pain: systematic review and meta-analysis.
To determine the differences in respiratory muscle strength and pulmonary function between patients with chronic neck pain (CNP) and asymptomatic individuals. Databases were MEDLINE, CINAHL, Scopus, Web of Science and EMBASE up to the end of September 2021. Studies with cross-sectional and longitudinal design were selected, with adult patients with CNP and asymptomatic individuals with reports respiratory function. 11 studies met the inclusion criteria and 10 were included in the meta-analysis showing a statistically significant reduction in inspiratory/expiratory muscle strength (MIP/MEP) in the patients with CNP compared with the asymptomatic individuals (mean difference (MD) for MIP, -11.67 [-14.57 to -8.77]; MD for MEP, -11.80 [-14.99 to -8.60]) and pulmonary function: vital capacity (standardized mean difference (SMD), -0.31 [-0.56 to -0.06]); maximum voluntary ventilation (SMD, -0.36 [-0.59 to -0.14]); forced vital capacity (SMD, -0.53 [-0.99 to -0.06]); peak expiratory flow (SMD, -0.58 [-1.03 to -0.12]); and forced expiratory volume in the first second (SMD, -0.28 [-0.51 to -0.05]). Patients with CNP have reduced respiratory muscle strength and pulmonary function compared with asymptomatic individuals, and this difference could be clinically meaningful. However, more studies of high methodological quality and longitudinal studies are needed to strengthen the results of this meta-analysis. IMPLICATIONS FOR REHABILITATIONRespiratory dysfunction has been observed in patients with chronic neck pain.Patients with chronic neck pain present a decrease in respiratory muscle strength and pulmonary function compared with asymptomatic individuals.Respiratory pattern disorders should be considered in the clinical context of chronic neck pain.Interventions focused on respiratory muscle training could be helpful for this population.


A simple model for hand trauma training.
This paper introduces the use of fresh, uncooked chickens as a simple, easily accessible and inexpensive teaching model to simulate the conditions met in cases of human hand injury.


Improved methods for the halogenation of the [HCB(11)H(11)](-) anion.
Expedient and economical methods for the synthesis of undecahalogenated carborane anions have been developed.


Pharmacological studies of jumper ant (Myrmecia pilosula) venom: evidence for the presence of histamine, and haemolytic and eicosanoid-releasing factors.
Jumper ant venom was prepared by extraction of venom sacs in distilled water and centrifugation to remove insoluble material. Jumper ant venom (2 micrograms/ml) produced a biphasic response on isolated guinea-pig ileum, i.e. an initial rapid contraction followed by a slower prolonged contraction. The histamine antagonist mepyramine (0.1 microM) inhibited the first phase of this response by greater than 90%. In the isolated rat stomach fundus strip (which is insensitive to histamine), jumper ant venom (6 micrograms/ml) produced only a single contraction. No tachyphylaxis was observed to repeated doses of jumper ant venom in guinea-pig ileum or rat fundus strip. Responses to jumper ant venom of the egg-albumin-sensitised guinea-pig ileum were not significantly different before and after an in vitro anaphylactic response induced by egg albumin (0.5 mg/ml). Fluorometric assay revealed a mean value of 0.9 +/- 0.2% of the dry weight as histamine in jumper ant venom. Both the lipoxygenase/cyclo-oxygenase inhibitor BW755C and the cyclooxygenase inhibitor indomethacin significantly inhibited the second phase response to jumper ant venom of the guinea-pig ileum, and the response of the rat fundus strip. The muscarinic receptor antagonist atropine (0.1 microM), the bradykinin antagonist [Thi5,8,D-Phe7]-bradykinin (10 microM) and the angiotensin converting enzyme inhibitor captopril (20 microM) did not affect either phase of the venom response in guinea-pig ileum. Jumper ant venom caused haemolysis of guinea-pig blood. The degree of haemolysis was significantly reduced when boiled venom was used. These results suggest that jumper ant venom contains histamine and may cause the release of cyclo-oxygenase products. It also contains a heat-sensitive haemolytic factor.


Oestrogenic, anti-oestrogenic and fertility effects of some triphenylethanes and triphenylethylenes related to ethamoxytriphetol (MER 25).
Five triphenylethylenes, a triphenylethane and a triphenylethanol, carrying methyl substituents ortho to one or both of the ring oxygen functions, have been examined for oestrogenic, and antioestrogenic activity in mice, and three of the compounds, alpha-[4-(beta-diethylaminoethoxy)-3, 5-xylyl]-alpha-phenyl-beta-4-methoxyphenyl-ethanol (IV), alpha'-[4-(beta-diethylaminoethoxy)-3, 5-xylyl]-4-methoxy-bibenzyl (V) and alpha'-[4-(beta-diethylaminoethoxy)-3, 5-xylyl]-4-methoxy-stilbene (VI), were tested for their effects on fertility in mice. 2 Orthomethylation reduces oestrogenic and/or anti-oestrogenic activity compared with the reported activities of non-methylated analogues. 3 The anti-oestrogenic ethamoxytriphetol (MER 25) reduced fertility in mice whereas its inactive dimethylated analogue (IV) was ineffective. The weakly active anti-oestrogens, V and VI, did not affect fertility in mice.


Non-interferometric technique to realize vector beams embedded with polarization singularities: publisher's note.
This publisher's note corrects the contents of references in J. Opt. Soc. Am. A37, 1043 (2020)JOAOD60740-323210.1364/JOSAA.393027.


Regional block techniques for pain management after video-assisted thoracoscopic surgery: a covariate-adjusted Bayesian network meta-analysis.
Nerve block is widely used for pain management after video-assisted thoracoscopic surgery (VATS). Thoracic paravertebral block (TPVB), erector spinae plane block (ESPB), serratus anterior plane block (SAPB), and intercostal nerve block (ICNB) are alternative treatments. Network meta-analysis based on Bayesian analyses was performed to obtain results for direct comparison, indirect comparison, and network comparison, and to make rankings based on probabilities. Covariates were adjusted to determine the effect of the covariates on results of this study. The study identified 61 randomized controlled trials (RCTs) (4468 patients). There were results of probability ranking for the first ("best" treatment): 24 h morphine consumption, TPVB > ESPB > ICNB > SAPB. Covariate adjustment allowed the four treatments to change somewhat in the likelihood of the best choice. TPVB ranks best in our analysis. ESPB is a viable alternative. SAPB and ICNB seem to play a limited role in postoperative pain management.


Sequence of the coat protein gene of Bermuda grass etched-line virus, and of the adjacent 'marafibox' motif.
The complete nucleotide sequence of the coat protein (CP) gene of Bermuda grass etched-line virus (BELV), including 376 nucleotides (nt) of the region to its 5' side, was determined and compared with sequences of the other viruses associated with the genus Marafivirus, substantiating the assignment of BELV to this group. The CP gene coding sequence was 585 nt in length. Inferred amino acid sequences showed homologies among marafiviral CP gene products ranging from 41% to 59%. A non-coding sequence motif characteristic of the marafiviruses lies in the region adjacent to the CP gene to the 5' side. In contrast to various homology levels in the coding regions of the CP genes, the interspecific sequence homology in this 18 nt motif was almost perfect.


Editorial: Polygenic Risk Scores in Child Psychiatry, Research Promise, and Potential Clinical Pitfalls.
Polygenic risk scores (PRSs) for mental disorders have become a major player in child psychiatry research. PRSs quantify a child's risk for childhood psychiatric disorders by summing the effects of a multitude of common risk genetic variants across the entire genome. Each genetic variant in isolation contributes a minuscule amount to the disorder, but their combined effect can be substantial. The study by Pat et al.1 illustrates how PRSs can be used as a starting point to examine the mechanisms that might link common genetic variant risk with symptoms. In their exploration of how genes, cognition, and psychopathology may be tied together, the authors apply meticulous analytic techniques to a rich, open dataset (the Adolescent Brain Cognitive Development [ABCD] cohort) and report fascinating results.


Variations in Processes of Care and Outcomes for Hospitalized General Medicine Patients Treated by Female vs Male Physicians.
Hospitalized medical patients cared for by female physicians may have decreased mortality rates compared with patients of male physicians. However, this association has yet to be assessed outside of the US, and little is known about factors that may explain this difference. To determine whether mortality, other hospital outcomes, and processes of care differed between the patients cared for by female and male physicians. This retrospective cross-sectional study included patients admitted to general medical wards at 7 hospitals in Ontario, Canada, between April 1, 2010, and October 31, 2017. The association of physician gender with patient outcomes was examined while adjusting for hospital fixed effects, patient characteristics, physician characteristics, and processes of care. All patients were admitted to a general internal medicine service through the emergency department and were cared for by a general internist or family physician-hospitalist. Patients were excluded if length of stay was greater than 30 days or if the attending physician cared for less than 100 hospitalized general medicine patients over the study period. Statistical analyses were performed from October 15, 2020, to May 8, 2021. In-hospital mortality, length of stay, intensive care unit admission, 30-day readmissions, and process-of-care measures (blood tests, medications, imaging, endoscopy, and interventional radiology services). A total of 171 625 hospitalized patients with a median age of 73 years (interquartile range, 56-84 years) were included (84 221 men [49.1%], 87 402 women [50.9%], and 2 patients with unspecified sex). Patients were cared for by 172 attending physicians (54 female physicians [31.4%] and 118 male physicians [68.6%]). In fully adjusted models, female physicians ordered more imaging tests, including computed tomography (adjusted difference, -1.70%; 95% CI, -2.78% to -0.61%; P = .002), magnetic resonance imaging (-0.88%; 95% CI, -1.37% to -0.38%; P = .001), and ultrasonography (-1.90%; 95% CI, -3.21% to -0.59%; P = .005). Patients treated by female physicians had lower in-hospital mortality (2256 of 46 772 patients [4.8%] vs 6452 of 124 853 patients [5.2%]). This difference persisted after adjustment for patient characteristics but was no longer statistically different after adjustment for other physician characteristics (adjusted difference, 0.29%; 95% CI, -0.08% to 0.65%; P = .12). The difference was similar after further adjustment for processes of care. In this cross-sectional study of patients admitted to general medical units in Canada, patients cared for by female physicians had lower mortality rates than those treated by male physicians, adjusting for patient characteristics. This finding was nonsignificant after adjustment for other physician characteristics.


Machine learning in NQR TNT express detection system.
Nuclear quadruple resonance (NQR) has excellent potential for the remote detection of nitrogen-containing substances, such as trinitrotoluene (TNT). However, using NQR techniques in security systems have some problems. For example, unknown temperature of the detecting explosives and low signal-to-noise ratio (SNR) leads to a priori uncertainty of the parameters of the NQR signal. In the article, we use machine learning methods for detecting the NQR signal. It allows us to increase speed and accuracy of TNT NQR signal detection. We have shown that proposed method of NQR signal detecting is more accurate and 100 times faster than alternative methods if temperature uncertainty is above 10 degrees. We achieve probability of NQR signal detection about 95% for SNR -15 dB.


Prognostic significance of supradiaphragmatic lymph nodes at initial presentation in patients with stage III high-grade serous ovarian cancer.
To identify the optimal size threshold and to assess the prognostic significance of supradiaphragmatic lymph nodes at initial presentation of patients with high-grade serous ovarian cancer (HGSC). This IRB-approved, HIPAA-compliant retrospective study included baseline pretreatment staging abdominal CTs of 88 women (mean age 62 years, SD 10.4, range 29-85) with FIGO stage III HGSC. Patients with stage IV disease were excluded due to worse prognosis and management guided by distant metastases. Two fellowship-trained radiologists independently reviewed abdominal CTs to record the presence of supradiaphragmatic nodes, abdominal lymphadenopathy, peritoneal carcinomatosis, and ovarian mass. Progression-free survival (PFS) and overall survival (OS) were recorded after median 79 months follow-up (IQR 58-115, range 13-144). The optimal short-axis size threshold for supradiaphragmatic lymphadenopathy was determined by correlating 3, 4, 5, 6, 7, and 10 mm thresholds with PFS and OS using Log-rank test. Prognostic significance of supradiaphragmatic lymphadenopathy was assessed using Cox proportional hazards models. There was good interobserver agreement for presence (κ = 0.65, 95%CI 0.51-0.79) and size (ICC = 0.77, 95%CI 0.66-0.86) of supradiaphragmatic nodes. 5 mm short-axis size threshold was associated with significantly shorter PFS (median 14 months, IQR 11-17 vs. 23 months, IQR 12-59; p = 0.02) and OS (median 44 months, IQR 27-69 vs. 65 months, IQR 45-96; p = 0.03). Total 38/88 (43%) patients had supradiaphragmatic lymphadenopathy. On Cox proportion hazards analysis, supradiaphragmatic lymphadenopathy was significantly associated with shorter PFS (p = 0.02; HR 1.81, 95%CI 1.11-2.96) and OS (p = 0.008; HR 2.11, 95%CI 1.21-3.65). In patients with stage III HGSC, supradiaphragmatic lymphadenopathy is associated with shorter PFS and OS. Further studies would help determine its implications on staging, decision regarding neoadjuvant therapy, and surgical technique.


Hospital length of stay, do not resuscitate orders, and survival for post-cardiac arrest patients in Michigan: A study for the CARES Surveillance Group.
Current guidelines recommend deferring prognostic decisions for at least 72 h following admission after Out of Hospital cardiac arrest (OHCA). Most non-survivors experience withdrawal of life sustaining therapy (WLST), and early WLST may adversely impact survival. We sought to characterize the hospital length of stay (LOS) and timing of Do Not Resuscitate (DNR) orders (as surrogates for WLST), to assess their relationship to survival following cardiac arrest. We performed a retrospective cohort study of probabilistically linked cardiac arrest registries (Cardiac Arrest Registry to Enhance Survival (CARES) and Michigan Inpatient Database (MIDB) from 2014 to 2017. Adult (≥18 years) patients admitted following OHCA were included. We considered LOS ≤ 3 days (short LOS) and written DNR order with LOS ≤ 3 days (Early DNR) as indicators of early WLST. Our primary outcome was survival to hospital discharge. We utilized multilevel logistic regression clustered by hospital to examine associations of these variables, patient characteristics and survival to hospital discharge. We included 3644 patients from 38 hospitals with >30 patients. Patients mean age was 62.4 years and were predominately male (59.3%). LOS ≤ 3 days (ORadj = 0.11) and early DNR (ORadj = 0.02) were inversely associated with survival to discharge. There was a non-significant inverse association between hospital rates of LOS ≤ 3 days and survival (p = 0.11), and Early DNR and survival (p = 0.83). In the multilevel model, using median odd ratios to assess variation in LOS ≤ 3 days and survival, patient characteristics contributed more to variability in surviival than between-hospital variation. However, between-hospital variation contributed more to variability than patient characteristics in the provision of early DNR orders. We observed that LOS ≤ 3 days for post-arrest patients was negatively-associated with survival, with both patient characteristics and between-hospital variation associated with outcomes. However, between-hospital variation appears to be more highly-associated with provision of early DNR orders than patient characteristics. Further work is needed to assess variation in early DNR orders and their impact on patient survival.


Physics Considerations for Evaluation of Dose for Dose-Response Models of Pediatric Late Effects From Radiation Therapy.
We describe the methods used to estimate the accuracy of dosimetric data found in literature sources used to construct the Pediatric Normal Tissue Effects in the Clinic (PENTEC) dose-response models, summarize these findings of each organ-specific task force, describe some of the dosimetric challenges and the extent to which these efforts affected the final modeling results, and provide guidance on the interpretation of the dose-response results given the various dosimetric uncertainties. Each of the PENTEC task force medical physicists reviewed all the journal articles used for dose-response modeling to identify, categorize, and quantify dosimetric uncertainties. These uncertainties fell into 6 broad categories. A uniform nomenclature was developed for describing the "dosimetric quality" of the articles used in the PENTEC reviews. Among the multidisciplinary experts in the PENTEC effort, the medical physicists were charged with the dosimetric evaluation, as they are most expert in this subject. The percentage dosimetric uncertainty was estimated for each late effect endpoint for all PENTEC organ reports. Twelve specific sources of dose uncertainty were identified related to the 6 broad categories. The most common reason for organ dose uncertainty was that prescribed dose rather than organ dose was reported. Percentage dose uncertainties ranged from 5% to 200%. Systematic uncertainties were used to correct the dose component of the models. Random uncertainties were also described in each report and in some cases used to modify dose axis error bars. In addition, the potential effects of dose binning were described. PENTEC reports are designed to provide guidance to radiation oncologists and treatment planners for organ dose constraints. It is critical that these dose constraint recommendations are as accurate as possible, acknowledging the large error bars for many. Achieving this accuracy is important as it enables clinicians to better balance target dose coverage with risk of late effects. Evidence-based dose constraints for pediatric patients have been lacking and, in this regard, PENTEC fills an important unmet need. One must be aware of the limitations of our recommendations, and that for some organ systems, large uncertainties exist in the dose-response model because of clinical endpoint uncertainty, dosimetric uncertainty, or both.


Nanotechnology-assisted production of value-added biopotent energy-yielding products from lignocellulosic biomass refinery - A review.
The need to develop sustainable alternatives for pretreatment and hydrolysis of lignocellulosic biomass (LCB) is a massive concern in the industrial sector today. Breaking down of LCB yields sugars and fuel in the bulk scale. If explored under nanotechnology, LCB can be refined to yield high-performance fuel sources. The toxicity and cost of conventional methods can be reduced by applying nanoparticles (NPs) in refining LCB. Immobilization of enzymes onto NPs or used in conjugation with nanomaterials would instill specific and eco-friendly options for hydrolyzing LCB. Nanomaterials increase the proficiency, reusability, and stability of enzymes. Notably, magnetic NPs have bagged their place in the downstream processing of LCB effluents due to their efficient separation and cost-effectiveness. The current review highlights the role of nanotechnology and its particles in refining LCB into various commercial precursors and value-added products. The relationship between nanotechnology and LCB refinery is portrayed effectively in the present study.


A fast track influenza virus vaccine produced in insect cells.
The viral surface protein hemagglutinin (HA) has been recognized as a key antigen in the host response to influenza virus in both natural infection and vaccination because neutralizing antibodies directed against HA can mitigate or prevent infection. The baculovirus-insect cell system can be used for the production of recombinant HA molecules and is suitable for influenza vaccine production where annual adjustment of the vaccine is required. This expression system is generally considered safe with minimal potential for growth of human pathogens. Extensive characterization of this novel cell substrate has been performed, none of which has revealed the presence of adventitious agents. Multiple clinical studies have demonstrated that the vaccine is safe, well-tolerated and immunogenic. The baculovirus-insect cell system could, therefore, be used for the expedited production of a safe and efficacious influenza vaccine. As a result, this technology should provide a fast track worldwide solution for newly emerging influenza strains or pandemic preparedness within a few years.


Major and minor blood group phenotyping and database generation for recruits : A pilot study.
Alloimmunization to minor blood group antigens is a problem that has for long befuddled the blood bankers, requiring blood group phenotyping of target populations worldwide. However, the same exercise had been lacking in our Armed Forces population necessitating this pilot study. A total of 2000 recruits of a regimental center in northern India were phenotyped for major and minor blood group antigens including ABO, Rhesus (D, C, c, E, and e antigens), Kell (K), MNSs (S and s antigens), Kidd (Jka and Jkb), and Duffy (Fya and Fyb) using commercially prepared polyclonal antisera on a fully automated system based on electromagnetic technology. Typing for M and N antigens (MNSs system) was performed using the tube method using company provided specific polyclonal antisera. The results were also compared with that of Indian and other populations of the world. Blood group antigen frequencies observed in our study population were mostly in sync with the prevalence rates of major and minor blood group antigens reported in other studies; however, in certain cases, they were also at variance. In our study, Rh D-negative antigen, JKa-Jkb- phenotype frequency were comparatively much higher than those reported in other Indian studies. To conclude, ours was a pilot study to establish the database of major and minor antigens of Armed Forces combatants. However, it is recommended that if the same effort can be replicated at the other transfusion centers and major hospitals of Armed Forces, it will vastly benefit their alloimmunized patient clientele needing lifesaving transfusions.


A highly selective fluorescent sensor for chlortetracycline based on histidine-templated copper nanoclusters.
In this study, histidine-protected copper nanoclusters (Cu NCs@His) were established by using a one-pot method, which histidine and ascorbic acid were applied as the template and reducing agent, respectively. The as-developed Cu NCs@His endued green emission wavelength at 494 nm with the excitation of 378 nm. The Cu NCs@His exhibited green fluorescence under UV light (365 nm). Using Cu NCs@His as a pattern nanosensor, the fluorescent "turn off" mechanism was fabricated for the determination of chlortetracycline in the light of the linear decrease of fluorescence intensities around 494 nm. The chlortetracycline conducted as a quencher, leading to reveal an excellent linear relationship between ln(F0/F) of Cu NCs@His and chlortetracycline concentrations with the range of 0.5-200 μM, and the detection limit was 0.876 μM. The fluorescence quenching of Cu NCs@His revealed excellent selectivity for chlortetracycline over other potential interfering substances in the human body. This strategy was exhibited to be a convenient sensing platform for the detection of chlortetracycline in real medical samples, which could unfold a brand new and direct system for the sensing of chlortetracycline in real samples.


Generation of strength in a drying film: How fracture toughness depends on dispersion properties.
The fracture toughness of colloidal films is measured by characterizing cracks which form during directional drying. Images from a confocal microscope are processed to measure the crack width as a function of distance from the crack tip. Applying theory for thin elastic films the fracture toughness is extracted. It is found that the fracture toughness scales with the particle size to the -0.8 power and that the critical energy release rate scales with the particle size to the -1.3 power. In addition, the fracture toughness is found to increase at lower evaporation rates, but the film thickness does not have a significant effect.


MiR-146a suppresses the expression of CXCR4 and alters survival, proliferation and migration rate in colorectal cancer cells.
CXCR4 plays an important role in colorectal cancer (CRC) development and metastasis. Some previous studies have indicated CXCR4 as a therapeutic target in cancer. CXCR4 is known as a direct target of miR-146a. The present study aimed to investigate how exogenous induction of miR-146a affects CXCR4 gene and protein expression and also proliferation, apoptosis and migration of CRC cells. Transfection of Caco-2 and SW480 cells by a synthetic miR-146a mimic led to downregulation of CXCR4 expression at both gene and protein levels. It also downregulated expression of several miR-146a targets, including GSK3B, IRAK1, TRAF6, AKT2, SMAD4, EGFR and NFKB1, mostly in SW480 cells. Overexpression of miR-146a resulted in a partial cell cycle arrest in the both cell lines, while the apoptotic rate was also decreased. In regards to epithelial-mesenchymal transition factors, VIM was downregulated in the both cell lines, but SNAI1 was upregulated in Caco-2 cells. The wound closure assay showed a reduction in cell migration in SW480 cells, but an opposite effect was detected in Caco-2 cells following transfection with miR-146a mimic. Therefore, our results are indicating that overexpression of miR-146a, despite downregulation of oncogenic CXCR4, may not lead to a universal tumor suppressive effect in all CRC cells, and this is possibly due to differences in miR-146a effects on signaling pathways in each cell type. Selection of miR-146a for tumor suppression requires enough details regarding the signaling profile of cancer cells otherwise it may produce unexpected outcome.


Improved outcomes in patients with severely depressed LVEF undergoing percutaneous coronary intervention with contemporary practices.
Contemporary practices for hemodynamically supported high-risk percutaneous coronary intervention have evolved over the last decade. This study sought to compare outcomes of the prospective, multicenter, PROTECT III study to historic patients treated with Impella in the PROTECT II randomized controlled trial. Of 1,134 patients enrolled in PROTECT III from March 2017 to March 2020, 504 were "PROTECT II-like" (met eligibility for PROTECT II randomized controlled trial) and are referred to as PROTECT III for comparative analysis. Major adverse cardiac and cerebrovascular events (MACCE), comprising all-cause mortality, stroke/transient ischemic attack, myocardial infarction, and repeat revascularization, were compared at hospital discharge and 90 days. Compared with PROTECT II (N = 216), PROTECT III patients were less often Caucasian (77.1% vs 83.8%, P = .045), with less prior CABG (13.7% vs 39.4%; P < .001) and prior myocardial infarction (40.7% vs 69.3%; P < .001). More PROTECT III patients underwent rotational atherectomy (37.1% vs 14.8%, P < .001) and duration of support was longer (median 1.6 vs 1.3 hours; p<0.001), with greater improvement achieved in myocardial ischemia jeopardy scores (7.0±2.4 vs 4.4±2.9; P < .001) and SYNTAX scores (21.4±10.8 vs 15.7±9.5; P < .001). In-hospital bleeding requiring transfusion was significantly lower in PROTECT III (1.8% vs 9.3%; P < .001), as was procedural hypotension (2.2% vs 10.1%; P < .001) and cardiopulmonary resuscitation or ventricular arrhythmia (1.6% vs 6.9%; P < .001). At 90 days, MACCE was 15.1% and 21.9% in PROTECT III and PROTECT II, respectively (p=0.037). Following propensity score matching, Kaplan-Meier analysis showed improved 90-day MACCE rates in PROTECT III (10.4% vs 16.9%, P = .048). The PROTECT III study demonstrates improved completeness of revascularization, less bleeding, and improved 90-day clinical outcomes compared to PROTECT II for Impella-supported high-risk percutaneous coronary intervention among patients with severely depressed LVEF.


The fragile site at 16q22, distamycin A, and the normal pachytene structure of chromosome 16: some possible interrelationships.
It is possible to interpret the fragile site at 16q22 as an exaggerated expression of normal structure observed at pachytene, and to interpret the potential for such expression as a heritable trait. Exposure of cells from affected individuals to distamycin A in vitro may function to facilitate realization of this potential where the trait is not expressed spontaneously.


Intracellular Aβ-oligomers and early inflammation in a model of Alzheimer's disease.
Lifelong use of nonsteroidal anti-inflammatory drugs (NSAIDs) has been shown to diminish the incidence of Alzheimer's disease (AD), suggesting a key role of inflammation in early stages of the pathology. While amyloid plaque-associated inflammation has been extensively studied in human and animal models, little is known about the inflammatory process prior to plaque deposition, i.e., in preclinical stages of AD. In this study we investigated microglial and neuronal inflammatory markers in preplaque transgenic McGill-Thy1-APP mice. We found evidence that prior to plaque deposition classical markers of microglial activation such as major histocompatibility complex class II (MHC-II), inducible nitric oxide synthase (i-NOS), and CD40 are already upregulated in the hippocampus of transgenic mice. Microglial cells from transgenic mice in the preplaque stage displayed intermediately activated morphology and appeared to be recruited toward intracellular amyloid-β peptide (Aβ)-oligomer burdened neurons. The inducible, neuron-specific cyclooxygenase 2 (COX-2) enzyme was found to be upregulated and specifically expressed by neurons in close relationship with Aβ-bearing cells, at this early stage of the AD-like pathology. Our study suggests that neuroinflammation might be one of the earliest pathological responses to intracellular accumulation of Aβ-oligomers.


Dipole-quadrupole and dipole-octopole polarizability of OsO4 from depolarized collision-induced light scattering experiments, ab initio and density functional theory calculations.
The dipole-quadrupole and dipole-octopole polarizability of osmium tetroxide (OsO(4)) has been determined from collision-induced light-scattering experiments. Our final estimates for these properties are |A|=(84+/-5)e(2)a(3)(0)E(-1)(h) and |E|=(214+/-25)e(2)a(4)(0)E(-1)(h). We have also analyzed previous experimental data of the relative permittivity and refractivity of OsO(4) to propose the electronic part of the static dipole polarizability of alpha=51.0e(2)a(2)(0)E(-1)(h). To support our findings we have performed high-level ab initio and density functional theory calculations to obtain theoretical static estimates alpha=(50.2+/-1.6)e(2)a(2)(0)E(-1)(h), A=(84+/-10)e(2)a(3)(0)E(-1)(h), and E=(-252+/-32)e(2)a(4)(0)E(-1)(h), in essential agreement with the proposed experimental values.


DNA sequence and coding properties of mutD(dnaQ) a dominant Escherichia coli mutator gene.
The mutD(dnaQ) gene in Escherichia coli codes for the epsilon subunit of the DNA polymerase pol III holoenzyme. Previous work has shown that this gene lies adjacent to the gene coding for RNase H (rnh). The two products are translated from diverging promoters. Here we report on the 1.6 kb (1 kb = 10(3) bases or base-pairs) sequence of the region coding for both genes, and the transcripts encoded by them. mutD codes for two transcripts, one of whose origins lies within the rnh structural gene. Both transcripts overlap and are complementary to a region of the rnh transcript. Thus, they can potentially form double-stranded helices with rnh. Of the two possible double-stranded structures, the shorter does not interfere with a likely rnh ribosome binding site, while the longer one does. We suggest that this unique organization may regulate rnh translation rates.


Environmental selection and epistasis in an empirical phenotype-environment-fitness landscape.
Fitness landscapes, mappings of genotype/phenotype to their effects on fitness, are invaluable concepts in evolutionary biochemistry. Although widely discussed, measurements of phenotype-fitness landscapes in proteins remain scarce. Here, we quantify all single mutational effects on fitness and phenotype (EC50) of VIM-2 β-lactamase across a 64-fold range of ampicillin concentrations. We then construct a phenotype-fitness landscape that takes variations in environmental selection pressure into account. We found that a simple, empirical landscape accurately models the ~39,000 mutational data points, suggesting that the evolution of VIM-2 can be predicted on the basis of the selection environment. Our landscape provides new quantitative knowledge on the evolution of the β-lactamases and proteins in general, particularly their evolutionary dynamics under subinhibitory antibiotic concentrations, as well as the mechanisms and environmental dependence of non-specific epistasis.


Metal-Catalyzed Hydride Transfer from Alcohols to Photoexcited Dipyridophenazine.
Dipyridophenazine (dppz) is known to react with alcohols upon photoexcitation into an n-π* transition at 378 nm to yield dihydrodipyridophenazine (dppzH2 ). This process occurs via H-atom abstraction from alcohols and subsequent disproportionation of the dppzH• radical species, to the final product. This reaction shows a primary kinetic isotope effect (KIE = 4.9) in methanol/perdeuteromethanol solvents, consistent with H-atom transfer processes. Addition of excess Zn(II) ions to the dppz solution not only accelerates the rate of photoreduction, but also lowers the KIE to 1.7, indicating a change in reaction mechanism. We postulate that the coordination of the alcoholic solvent to Zn(II) activates the alcohol α C-H bonds toward hydride transfer processes which would be consistent with the lowered KIE and faster overall reduction of the aromatic ligand. Interestingly, this appears to be an intramolecular process in which the Zn(II) is coordinated to both the dppz ligand and the reactive alcohol, as a sharp inflection in the overall rate increase is observed at a Zn:dppz ratio of 2:1. At this ratio, the dominant dppz species involves a Zn(II) bound to one dppz and several solvent molecules (methanol and water).


The contribution of health anxiety to retrospectively-recalled emergency department visits within a sample of patients in residential substance abuse treatment.
With the burden of emergency department (ED) use increasing, research examining the factors associated with ED visits among individuals who use the ED most frequently is needed. Given that substance use is strongly linked to ED visits, this study sought to examine the factors associated with greater ED visits among patients with substance use disorders (SUD). More precisely, we examined whether health anxiety incrementally contributes to the prediction of ED visits for medical care among adult patients (N = 118) in a residential substance abuse disorder treatment facility. As predicted, health anxiety was significantly positively correlated with ED visits during the past year. Furthermore, health anxiety remained a significant predictor of ED visits after accounting for sociodemographic variables, frequency of substance use, and physical health status. These results suggest that health anxiety may contribute to increased ED visits for medical care among individuals with SUD.


The CBFs: three arabidopsis transcription factors to cold acclimate.
Low temperature is one of the adverse environmental factors that most affects plant growth and development. Temperate plants have evolved the capacity to acquire chilling and freezing tolerance after being exposed to low-nonfreezing temperatures. This adaptive response, named cold acclimation, involves many physiological and biochemical changes that mainly rely on reprogramming gene expression. Currently, the best documented genetic pathway leading to gene induction under low temperature conditions is the one mediated by the Arabidopsis C-repeat/dehydration-responsive element binding factors (CBFs), a small family of three transcriptional activators (CBF1-3) that bind to the C-repeat/dehydration-responsive element, which is present in the promoters of many cold-responsive genes, and induce transcription. The CBF genes are themselves induced by cold. Different evidences indicate that the CBF transcriptional network plays a critical role in cold acclimation in Arabidopsis. In this review, recent advances on the regulation and function of CBF factors are provided and discussed.


Civic communicators' view of and approach to health promotion for newly arrived migrants in Sweden.
For newly arrived migrants, integration is important in promoting health and decreasing health inequities. In a Swedish context, civic orientation is a program to promote integration and increase the chance of employment for newly arrived migrants. The aim of this project was to explore how civic communicators view and approach health promotion in their work with newly arrived migrants in the civic orientation program in Sweden. Data were collected through interviews with eight civic communicators working with newly arrived migrants in civic orientation in the north of Sweden. The interviews followed a semi-structured interview guide and were transcribed verbatim and analyzed using thematic analysis. The analysis resulted in the main theme "To dress the participants for a (healthy) life in Sweden," with two sub-themes "Knowledge-a key to health" and "Being a guide for participants in a new context." In their work with civic orientation for newly arrived migrants, civic communicators are involved in health promotion by preparing their participants for a life in Sweden. They work to empower their participants to be able to make informed decisions and live healthy lives by both providing information to enhance knowledge and skills. They also work to guide them through the complexity of being in a new situation and country.


Repurposing beta-3 adrenergic receptor agonists for Alzheimer's disease: beneficial effects in a mouse model.
Old age, the most important risk factor for Alzheimer's disease (AD), is associated with thermoregulatory deficits. Brown adipose tissue (BAT) is the main thermogenic driver in mammals and its stimulation, through β3 adrenergic receptor (β3AR) agonists or cold acclimation, counteracts metabolic deficits in rodents and humans. Studies in animal models show that AD neuropathology leads to thermoregulatory deficits, and cold-induced tau hyperphosphorylation is prevented by BAT stimulation through cold acclimation. Since metabolic disorders and AD share strong pathogenic links, we hypothesized that BAT stimulation through a β3AR agonist could exert benefits in AD as well. CL-316,243, a specific β3AR agonist, was administered to the triple transgenic mouse model of AD (3xTg-AD) and non-transgenic controls from 15 to 16 months of age at a dose of 1 mg/kg/day i.p. Here, we show that β3AR agonist administration decreased body weight and improved peripheral glucose metabolism and BAT thermogenesis in both non-transgenic and 3xTg-AD mice. One-month treatment with a β3AR agonist increased recognition index by 19% in 16-month-old 3xTg-AD mice compared to pre-treatment (14-month-old). Locomotion, anxiety, and tau pathology were not modified. Finally, insoluble Aβ42/Aβ40 ratio was decreased by 27% in the hippocampus of CL-316,243-injected 3xTg-AD mice. Overall, our results indicate that β3AR stimulation reverses memory deficits and shifts downward the insoluble Aβ42/Aβ40 ratio in 16-month-old 3xTg-AD mice. As β3AR agonists are being clinically developed for metabolic disorders, repurposing them in AD could be a valuable therapeutic strategy.


Fine-needle aspiration cytology of sarcomatoid carcinoma of the breast: a cytologically overlooked neoplasm.
Sarcomatoid carcinoma of the breast is a very uncommon neoplasm. Fine-needle aspiration findings have been rarely reported. We report a case of sarcomatoid carcinoma of the breast that was diagnosed as a typical ductal carcinoma cytologically. The patient was a 45-year-old female who had a right breast mass for a short duration. Fine-needle aspiration (FNA) showed smears predominantly composed of single cells exhibiting plasmacytoid features with moderate degree of pleomorphism. A granular bluish background was noted on the Papanicolaou-stained smears. This background was thought to represent tumor diathesis, and the diagnosis of grade II ductal carcinoma of the breast was rendered. The patient underwent a subsequent lumpectomy with axillary node dissection. Histological examination of the lumpectomy revealed a neoplasm predominantly composed of a grade II chondrosarcoma with increased cellularity. A small (10%) component showed grade II invasive ductal carcinoma of the breast. No in situ component was seen. The sarcomatoid component was positive for S-100 protein and vimentin and negative for keratin, whereas the carcinomatous component was positive for vimentin, epithelial membrane antigen, and low molecular weight keratin. Ultrastructurally, the tumor showed features of a poorly differentiated epithelial neoplasm without evidence of chondrosarcoma. Metastases were seen in seven of ten axillary lymph nodes with exclusive epithelial component. Retrospective evaluation of the FNA smears revealed an extensive metachromatic stroma of the DIFF QUIK-stained smears. Our findings and review of the literature suggest that sarcomatoid carcinoma of the breast will be very frequently overlooked or misdiagnosed either because of the subtlety of the stroma or the predominance of the mesenchymal component. Our findings also provide supportive evidence that the use of the DIFF QUIK stain can be very helpful in the identification of the stroma in this neoplasm. The predominance of epithelium in the metastases in our case is further proof that tumors with dual differentiation such as sarcomatoid carcinomas and mixed muellerian tumors are truly carcinomas with metaplastic features.


Social anxiety and the effects of negative self-imagery on emotion, cognition, and post-event processing.
Numerous studies have shown that social phobia patients experience negative self-impressions or images during social situations. Clark and Wells (1995) posited that such negative self-images are involved in the maintenance of social phobia. Thus, the present study investigated the effects of negative self-imagery on cognition and emotion during and following a brief social situation. Specifically, high and low socially anxious participants (N = 77) were instructed to hold either a negative or control self-image as they engaged in a brief speech. Participants then rated their anxiety, performance, cognitions, and focus of attention. Twenty-four hours later, they returned to the laboratory and completed questionnaires assessing the amount of post-event processing (PEP) they engaged in. The results showed that, irrespective of the level of social anxiety or depressive symptoms, participants that held the negative self-image experienced higher levels of anxiety, were more self-focused, experienced more negative thoughts, rated their anxiety as more visible, appraised their performance more negatively, and engaged in more negative and less positive PEP than participants that held the control self-image. Collectively the results indicate that negative imagery is causally involved in the maintenance of social phobia, as well as in the generation of social anxiety among non-anxious individuals.


[A.G. Krieger. To the 70th anniversary of his birth].
October 30, 2021 will be the 70th birthday of Prof. Andrey Germanovich Krieger!


Post-Traumatic Amputations Epidemiology and Outcomes Within The National Trauma Data Bank: Improved Survival Over Time Results in Increased Population in Need of Rehabilitation Support.
Acute trauma care has significantly reduced mortality over the last two decades. The last study to examine the epidemiology of traumatic amputees predates these gains. The majority of those who sustain traumatic amputation are male; therefore, limited data exist on female amputees. This study aimed to (1) provide a current epidemiological analysis of traumatic amputees, and (2) compare male and female amputees. All patients sustaining a major limb amputation in the National Trauma Data Bank (NTDB) from 2013 to 2017 were identified. First, descriptive analyses of patient demographics and injury characteristics were performed and compared with a prior 2000-2004 NTDB study. Second, female and male traumatic amputees were compared in this study. From 2013 to 2017 we identified 7,016 patients who underwent major limb amputation. Compared to prior years, the current amputees were older and more severely injured. Mortality was 6.3% in the current years compared to 13.4% in the prior years (odds ratio [OR] 0.44, 95% CI = 0.37 to 0.51, p < 0.001). After multivariable analysis, mortality remained significantly decreased, with no difference in hospital length of stay. Contemporary NTDB analysis demonstrated that patients with traumatic amputations, regardless of sex, often survive until hospital discharge, despite more severe injuries.


Quantitative ultrasound imaging of intrinsic hand muscles after traumatic cervical spinal cord injury.
This is a cross-sectional descriptive study. To quantify differences in hand muscle morphology between persons with cervical spinal cord injury (SCI) and uninjured adults. The study was performed at the Guangdong Work Injury Rehabilitation Hospital. We quantified hand muscle cross-sectional area (CSA), thickness, and echo intensity (EI) in 18 persons with subacute to chronic SCI and 23 controls using ultrasound imaging. Mean SCI abductor pollicis brevis (APB), abductor digiti minimi (ADM), and first dorsal interosseous (FDI) CSA were ~26%, 43%, and 37% smaller than the control means, the deficit in the APB being less than the ADM (P < 0.05). Muscle thickness was also smaller after SCI, but deficits in ADM (31%) and FDI (20%) thickness were less than the CSA deficits (P < 0.05). In five SCI persons, APB CSA and/or opponens pollicis (OP) thickness were normal despite complete motor paralysis. Mean longitudinal image EI was 40% higher in the OP and 15% higher in the flexor pollicis brevis (FPB) after SCI (P < 0.05), suggesting denervation-induced infiltration of fat and fibrous tissues. OP EI was related to OP thickness (r = -0.6, P = 0.007, n = 18). Mean axial image EI was 10% higher in the APB and ADM after SCI (P < 0.05). There were no significant correlations between muscle morphological properties and clinical features in the SCI participants. Our results indicate significant SCI atrophy and elevated EI that are muscle dependent.


Piperlongumine: the amazing amide alkaloid from Piper in the treatment of breast cancer.
Piperlongumine (PL), an alkaloid found primarily in the fruits and roots of the plant Piper longum L. (Piperaceae), is a natural compound that exhibits potent activity against various cancer cell proliferation. The most frequently caused malignancy in women globally, breast cancer (BC), has been demonstrated to be significantly inhibited by PL. Apoptosis, cell cycle arrest, increased ROS generation, and changes in the signalling protein's expression are all caused by the numerous signalling pathways that PL impacts. Since BC cells resist conventional chemotherapeutic drugs (doxorubicin, docetaxel etc.), researchers have shown that the drugs in combination with PL can exhibit a synergistic effect, greater than the effects of the drug or PL alone. Recently, techniques for drug packaging based on nanotechnology have been employed to improve PL release. The review has presented an outline of the chemistry of PL, its molecular basis in BC, its bioavailability, toxicity, and nanotechnological applications. An attempt to understand the future prospects and direction of research about the compound has also been discussed.


Stabilization, not polymerization, of microtubules inhibits the nuclear translocation of STATs in adipocytes.
Signal transducers and activators of transcriptions (STATs) are a family of latent transcription factors which are activated by a variety of growth factors and cytokines in many cell types. However, the mechanism by which these transcription factors translocate to the nucleus is poorly understood. The goal of this study was to determine the requirement of microfilaments and microtubules for cytokine induced STAT activation in cultured adipocytes. We used seven different actin-specific and microtubule-specific agents that are well-established effectors of these cytoskeletal networks. Our results clearly demonstrate that inhibition of microfilaments or the prevention of microtubule polymerization has no effect on the ability of STATs to be tyrosine phosphorylated or to translocate to the nucleus. However, we observed that paclitaxel, a microtubule stabilizer, resulted in a significant decrease in the nuclear translocation of STATs without affecting the cytosolic tyrosine phosphorylation of these transcription factors. In summary, our results demonstrate that the dynamic instability, but not the polymerization, of microtubules contributes to nuclear translocation of STAT proteins in adipocytes.


Demographic, clinical, and anthropometric profiles and postoperative outcomes in patients with chronic limb threatening ischemia: A prospective descriptive study.
Chronic limb-threatening ischemia (CLTI) is a complex disease caused by peripheral artery disease. It is associated with ischemic foot pain (rest pain) and tissue loss in the form of chronic nonhealing foot ulcers or gangrene. CLTI has a high short-term risk of limb amputations, postoperative sepsis, and cardiovascular-related events. The present study was conducted to assess the demographic and anthropometric profile of patients with CLTI and their postoperative outcomes after 2-year follow-up at Groote Schuur Hospital, Cape Town, South Africa. This prospective descriptive pilot study, nested in a prospective cohort study, included adult patients with CLTI admitted to Groote Schuur Hospital from 1st January 2015 to 31st December 2016. Demographic data, anthropometric markers of CLTI, and the postoperative outcomes were documented using piloted and pretested vascular questionnaire. Descriptive statistics were used for baseline data, and postoperative outcomes were presented using actuarial life-table method (Kaplan-Meier analysis). Odds ratio, 95% confidence interval, and P value < 0.05 were used to test the hypothesis. Thirty-seven (50.6%) patients had a BMI >25.0. The mean waist: hip ratio was 0.96. Prevalence of smoking was 86%. Limb salvage and ambulation at 1 year were 79% and 67%, respectively. Majority of the patients who were ambulant preoperatively remained ambulant postoperatively. Most patients had truncal obesity with a high prevalence of smoking. High postoperative ambulatory recovery among ambulant preoperative patients was a significant outcome observed in our study.


Impact of synthetic silver nanoparticles on the biofilm microbial communities and wastewater treatment efficiency in experimental hybrid filter system treating municipal wastewater.
Silver nanoparticles (AgNPs) threaten human and ecosystem health, and are among the most widely used engineered nanomaterials that reach wastewater during production, usage, and disposal phases. This study evaluated the effect of a 100-fold increase in collargol (protein-coated AgNP) and Ag+ ions concentrations in municipal wastewater on the microbial community composition of the filter material biofilms (FMB) and the purification efficiency of the hybrid treatment system consisting of vertical (VF) and horizontal (HF) subsurface flow filters. We found that increased amounts of collargol and AgNO3 in wastewater had a modest effect on the prokaryotic community composition in FMB and did not significantly affect the performance of the studied system. Regardless of how Ag was introduced, 99.9% of it was removed by the system. AgNPs and AgNO3 concentrations did not significantly affect the purification efficiency of the system. AgNO3 induced a higher increase in the genetic potential of certain Ag resistance mechanisms in VFs than collargol; however, the increase in Ag resistance potential was similar for both substances in HF. Hence, the microbial community composition in biofilms of vertical and horizontal flow filters is largely resistant, resilient, or functionally redundant in response to AgNPs addition in the form of collargol.


High-Efficiency and High-Quality Extraction of Hemicellulose of Bamboo by Freeze-Thaw Assisted Two-Step Alkali Treatment.
Hemicellulose is a major component of the complex biomass recalcitrance structure of fiber cell walls. Even though biomass recalcitrance protects plants, it affects the effective utilization of lignocellulosic biomass resources. Therefore, the separation and extraction of hemicellulose is very important. In this study, an improved two-step alkali pretreatment method was proposed to separate hemicellulose efficiently. Firstly, 16.61% hemicellulose was extracted from bamboo by the weak alkali treatment. Then, the physical freezing and the alkali treatment were carried out by freezing at -20 °C for 12.0 h and thawing at room temperature, heating to 80 °C, and treating with 5.0% sodium hydroxide for 90 min; the extraction yield of hemicellulose reached 73.93%. The total extraction yield of the two steps was 90.54%, and the molecular weight and purity reached 44,865 g·mol-1 and 89.60%, respectively. It provides a new method for breaking the biomass recalcitrance of wood fiber resources and effectively extracting hemicellulose.


Energy from Waste--clean, efficient, renewable: transitions in combustion efficiency and NOx control.
Traditionally EfW (Energy from Waste) plants apply a reciprocating grate to combust waste fuel. An integrated steam generator recovers the heat of combustion and converts it to steam for use in a steam turbine/generator set. This is followed by an array of flue gas cleaning technologies to meet regulatory limitations. Modern combustion applies a two-step method using primary air to fuel the combustion process on the grate. This generates a complex mixture of pyrolysis gases, combustion gases and unused combustion air. The post-combustion step in the first pass of the boiler above the grate is intended to "clean up" this mixture by oxidizing unburned gases with secondary air. This paper describes modifications to the combustion process to minimize exhaust gas volumes and the generation of noxious gases and thus improving the overall thermal efficiency of the EfW plant. The resulting process can be coupled with an innovative SNCR (Selective Non-Catalytic Reduction) technology to form a clean and efficient solid waste combustion system. Measurements immediately above the grate show that gas compositions along the grate vary from 10% CO, 5% H(2) and 0% O(2) to essentially unused "pure" air, in good agreement with results from a mathematical model. Introducing these diverse gas compositions to the post combustion process will overwhelm its ability to process all these gas fractions in an optimal manner. Inserting an intermediate step aimed at homogenizing the mixture above the grate has shown to significantly improve the quality of combustion, allowing for optimized process parameters. These measures also resulted in reduced formation of NO(x) (nitrogenous oxides) due to a lower oxygen level at which the combustion process was run (2.6 vol% O(2,)(wet) instead of 6.0 vol% O(2,)(wet)). This reduction establishes optimal conditions for the DyNOR™ (Dynamic NO(x) Reduction) NO(x) reduction process. This innovative SNCR technology is adapted to situations typically encountered in solid fuel combustion. DyNOR™ measures temperature in small furnace segments and delivers the reducing reagent to the exact location where it is most effective. The DyNOR™ distributor reacts precisely and dynamically to rapid changes in combustion conditions, resulting in very low NO(x) emissions from the stack.


Cranial nerve palsy in childhood acute lymphoblastic leukemia and non-Hodgkin's lymphoma.
Forty-five children with acute lymphoblastic leukemia or non-Hodgkin's lymphoma had cranial nerve palsy (CNP) as a complication of their disease. Twenty-two of these children had CNP initially and 23, at relapse, with or without previous hematologic relapse. Only one of the 23 patients with CNP at relapse was a long-term survivor. In contrast, 11 of the 22 children who had CNP initially survived in remission for 3+ months to 13+ years. Two factors are associated with an improved outcome for patients with CNP at diagnosis: treatment after 1979 (P less than 0.004) and male gender (P less than 0.01). Patients who received radiation therapy fared better than those for whom radiation was not given (disease-free survival at 2 years 53% versus 29%). The authors conclude that CNP signifies an aggressive or advanced disease requiring intensive systemic chemotherapy and that the role of irradiation should be examined for this group of patients.


Consideration of slice profiles in inversion recovery Look-Locker relaxation parameter mapping.
To include the flip angle distribution caused by the slice profile into the model used for describing the relaxation curves observed in inversion recovery Look-Locker FLASH T1 mapping for a more accurate determination of the relaxation parameters. For each inversion time, the flip angle dependent signal of the mono-exponential relaxation model is integrated across the slice profile. The resulting Consideration of Slice Profiles (CSP) relaxation curves are compared to the mono-exponential signal model in numerical simulations as well as in phantom and in-vivo experiments. All measured relaxation curves showed systematic deviations from a mono-exponential curve increasing with flip angle and T1 but decreasing with repetition time. Additionally, the accuracy of T1 was found to be largely dependent on the temporal coverage of the relaxation curve. All these systematic errors were largely reduced by the CSP model. The proposed CSP model represents a useful extension of the conventionally used mono-exponential relaxation model. Despite inherent model inaccuracies, the mono-exponential model was found to be sufficient for many T1 mapping situations. However, if only a poor temporal coverage of the relaxation process is achievable or a very precise modeling of the relaxation course is needed as in model-based techniques, the mono-exponential model leads to systematic errors and the CSP model should be used instead.


Effect of stimulation of the nucleus reticularis gigantocellularis on the membrane potential of cat lumbar motoneurons during sleep and wakefulness.
The present study was performed in order to determine the effect of electrical stimulation of the medullary nucleus reticularis gigantocellularis (NRGc) on the membrane potential of spinal cord motoneurons during sleep and wakefulness. Accordingly, intracellular recordings were obtained from lumbar motoneurons in unanesthetized normally respiring cats during naturally occurring states of wakefulness, quiet sleep and active sleep. Electrical stimuli applied to the NRGc evoked synaptic potentials which occurred at short latency (less than 10 ms) and did not exhibit consistent changes in their waveforms during any states of sleep or wakefulness. During wakefulness and quiet sleep, longer latency (greater than 20 ms) low-amplitude hyperpolarizing potentials occasionally followed NRGc stimulation. However, during active sleep, NRGc stimulation produced, in all motoneurons, relatively large hyperpolarizing potentials that were characterized by a mean amplitude of 3.5 +/- 0.4 mV (mean +/- S.E.M.), a mean latency-to-peak of 43.0 +/- 0.8 ms, and an average duration of 34.4 +/- 1.7 ms. These potentials were capable of blocking the generation of orthodromic spikes elicited by sciatic nerve stimulation. When anodal current or chloride was passed through the recording electrode, the hyperpolarizing potentials decreased in amplitude, and in some cases their polarity was reversed. These results indicate that the active sleep-specific hyperpolarizing potentials were inhibitory postsynaptic potentials. Thus, the NRGc possesses the capability of providing a postsynaptic inhibitory drive that is directed toward lumbar motoneurons which is dependent on the occurrence of the behavioral state of active sleep.(ABSTRACT TRUNCATED AT 250 WORDS)


Transperineal percutaneous I-125 implant of prostate.
Although Iodine-125 seeds for interstitial radiation of prostatic cancer via the retropubic route is an established method of treatment, the retropubic implant technique has disadvantages: inadequate space for proper placement of the needles, possible bleeding from the prostatic venous plexus by the insertion of needles through these veins, and possible wound infection due to inadvertent puncturing of the bladder and/or rectum by the needles. A technique is described whereby Iodine-125 seeds for interstitial radiation are placed into the prostate through the perineum allowing more accurate placement of the seeds, assuring homogenous dose distribution, and decreasing the risk of bleeding and of bacterial contamination.


Ascending aortic dissection in weight lifters with cystic medial degeneration.
We report 4 cases of ascending aortic dissection in patients with long histories of weight lifting. In 2 of the patients, the initial symptoms of dissection developed while they were lifting weights. Two patients had a history of hypertension and 2 had previously used anabolic steroids. All 4 were successfully treated surgically. Histopathology showed aortic medial changes in all 4. We believe that the hemodynamic stresses of weight lifting, namely, a rapid increase in systemic arterial blood pressure without a decrease in total peripheral vascular resistance, in combination with aortic medial degeneration may have contributed to the development of the aortic dissection.


Optimal performance comparison of the simulated moving bed process variants based on the modulation of the length of zones and the feed concentration.
The VariCol and ModiCon processes are two variants of the simulated moving bed (SMB) process, characterized by the modulation of the length of zones of the chromatographic column train and the feed concentration. These features give more flexibility than the conventional operation, leading to essential improvements in the separation and purification of mixtures. The optimal performance comparison of these two variants, the hybrid formed by their combination, and the conventional SMB process are scarce in the literature. This comparison helps discover new characteristics of each single and combined operation mode and creates guidelines to select the appropriate operation mode for possible real applications. In this work, the performance comparison of the ModiCon, VariCol, ModiCon+VariCol, and SMB processes is carried out in terms of maximal throughput for specific product purity values. Particular emphasis is placed on both the ModiCon and the hybrid ModiCon+VariCol processes characteristics. A strategy for combining and optimizing the ModiCon and the VariCol processes was determined. As a case study, the enantioseparation of guaifenesin was considered. In the ModiCon process, more than two modulation subintervals did not improve the performance in the separation. The optimal pattern, based on two subintervals, has zero feed concentration in the first subinterval and the maximal concentration in the second one. The best result for the hybrid operation (ModiCon+VariCol) was reached when the feed port moves simultaneously as the SMB process switching period. The optimal throughput of the ModiCon and the ModiCon+VariCol processes was almost doubled than that of the SMB process. These performances were based on larger zones I and II and not in zones II and III as occur with the SMB and VariCol process. The throughput in the hybrid operation increases more significantly than the ModiCon process when 5 columns were considered instead of 6. The hybrid operation could be more attractive for a system with a few numbers of columns.


Personalized text message and checklist support for initiation of antihypertensive medication: the cluster randomized, controlled check and support trial.
Objective: To assess whether the use of a checklist combined with text message support improves systolic blood pressure (SBP) control.Design and setting: A cluster randomized controlled trial in Finnish primary care.Interventions: Personalized text message support and a checklist for initiation of antihypertensive medication.Patients: 111 newly diagnosed hypertensive patients aged 30-75 years.Main outcome measures: The proportion of patients achieving 1) the office SBP target <140 mmHg or 2) the home SBP target <135 mmHg at 12 months.Results: 28% (n = 16) and 31% (n = 17) of patients in the intervention and control groups met the office SBP target, respectively (p = 0.51). The corresponding proportions were 36% (n = 18) and 42% (n = 21) for the home SBP target (p = 0.21). Office SBP decreased 23 mmHg (95% CI: 29-17) in the intervention group and 21 mmHg (95% CI: 27-15) in the control group (p = 0.61). Medication changes, number of antihypertensives at 12 months and health care utilization were similar in both study groups. Patients considered checklist and text message support useful and important.Conclusion: Only a small proportion of patients in the intervention and control groups reached their treatment target despite multiple health care contacts and medication changes. The study interventions did not improve SBP control. However, this study demonstrates new information about hypertension control, antihypertensive medication and health service utilization during the first treatment year.


Fritillaria thunbergii Miq. (Zhe Beimu): A review on its traditional uses, phytochemical profile and pharmacological properties.
Fritillaria thunbergii Miq. (Zhe beimu) ranked as oldest known homeopathic traditional folk medicine in China. The bulbs are medicinally important curing cough, inflammation, gastric ulcers, hypertension, diarrhea, and bronchitis. The aim of this review is to enlighten the deeper knowledge about F. thunbergii giving a comprehensive overview on its traditional uses, phytochemistry and pharmacology for future investigation of plant-based drugs and therapeutic applications. Total 48 medicinally important species of Fritillaria were described; total 122 compounds have been identified as results only 72 chemical constituents were described with proper chemical and biological details. F. thunbergii and its bulbs mainly constitute alkaloids, essential oils, diterpenoids, carbohydrates, sterols, amino acids, nucleosides, fatty acids, and lignans. The pharmacological studies demonstrate that F. thunbergii and its bulbs displays a wide range of bioactivities e.g., anti-inflammatory, anticancer, antitussive, expectorant, anti-ulcer, antimicrobial, antioxidant, anti-thyroid, regulation of blood rheology, anti-diarrhea, neuroprotection, and analgesic effects. Although promising reports on the various chemical bioactive constituents and biological properties of F. thunbergii have been published, very few reviews are related specifically to the traditional uses, phytochemistry and pharmacological applications. Further, various other studies on these plants should deserve our more attention for future investigation for drug development and its therapeutic applications.


Lung transthoracic ultrasound elastography imaging and guided biopsies of subpleural cancer: a preliminary report.
Despite the usefulness of elastography in assessing the stiffness/elasticity of tissues, and its proven diagnostic accuracy in thyroid, breast, and prostate cancers, among others, it is not yet applied in transthoracic ultrasound (TUS) scans to investigate lung nodules. To investigate the potential clinical utility of TUS elastography in diagnosing lung cancer proven by fine-needle aspiration biopsy (FNAB). TUS elastography was performed in 95 consecutive patients (71 men, 24 women; age, 62.84 ± 7.37 years) with lesions suspected of involving the chest wall or the pleura detected on chest X-ray or computed tomography (CT). Patients with pleural effusions were not enrolled, but were further evaluated by pleural fluid cytology. Patients were excluded from the study if a diagnosis had already been made based on sputum cytology and/or bronchoscopic histology (making TUS biopsy unnecessary) or if their lung lesions could not be visualized under standard US. Under FNAB, 34 consolidations were ascribed to pneumonia and 65 to cancer. Under TUS, tissue stiffness, detected using a convex multifrequency 2-8-mHz probe and a MyLab™Twice - ElaXto, was scored from 1 (greatest elasticity) to 5 (no elasticity). Subpleural solid masses (2-5 cm) were initially detected by TUS and subsequently assessed by FNAB. Histological diagnoses were: small cell lung cancer (4/61), adenocarcinoma (29/61), squamous cell carcinoma (SCC) (12/61), large cell lung carcinoma (12/61), and lymphomas (4/61). Patients' age and mass sizes (3.06 ± 0.88 cm) were not significantly associated with any histological type. A significant lower elasticity of SCC (4.67 ± 0.492) was observed versus other types of lung cancer (P < 0.005), and versus pneumonia (2.35 ± 0.48). Since only squamous cell lung carcinoma displays the feature of significantly reduced elasticity, and since no clear-cut diagnostic key is yet available, the clinical usefulness of TUS elastography is currently limited with a view to characterizing tumors. Nevertheless, it does enable good non-invasive imaging of lung nodules, providing information on their stiffness, and can improve the accuracy and yield of FNAB.


Diagnosis and Therapy of Infectious Encephalitis in Children: A Ten-Years Retrospective Study.
Infectious encephalitis represents a rare but potentially severe clinical condition. However, limited international data are available in pediatric age. We conducted a retrospective study to review (a) the clinical presentation; (b) laboratory, radiology, and neurophysiology findings; (c) the correlations between these exams and outcome; and (d) the therapy performed. Fifty-six patients were enrolled [22 female (39.6%), mean age 4.7 years, IQR 0.7-8.7 years], 19.6% presented neurologic sequelae. HSV was the single most frequently isolated pathogen (19.6%), although in most cases, the etiology remained undefined. 41.1% children presented prodromal before the development of neurologic signs. Fever was the most frequent constitutional symptom (83.9% of cases). Cerebrospinal fluid was normal in 48.5% of cases and electroencephalograpy in 24.5% cases. Brain computed tomography scans was normal in 33 (91.7%) cases, while cerebral magnetic resonance imaging (MRI) showed pathologic findings in 62.5% of cases. MRI was the only parameter associated with neurologic sequalae [P = 0.01; OR, 8.1 (95% CI: 1.52-42.84)]. Pediatric encephalitis is a heterogeneous entity with nonspecific clinical and laboratory findings, with undefined etiologies in most times. MRI can play a primary role, both on a diagnostic and prognostic point-of-view, and its role should be implemented and made more accessible. Further studies are needed to define the exact role and timing of steroids.


A tongue for all seasons: extreme phenotypic flexibility in salamandrid newts.
Many organisms faced with seasonally fluctuating abiotic and biotic conditions respond by altering their phenotype to account for the demands of environmental changes. Here we discovered that newts, which switch seasonally between an aquatic and terrestrial lifestyle, grow a complex adhesive system on their tongue pad consisting of slender lingual papillae and mucus-producing cells to increase the efficiency of prey capture as they move from water onto land. The adhesive system is reduced again as newts switch back to their aquatic stage, where they use suction to capture prey. As suction performance is also enhanced seasonally by reshaping of the mouth due to the growth of labial lobes, our results show that newts are exceptional in exhibiting phenotypic flexibility in two alternating components (i.e. tongue pad and labial lobes) within a single functional system, and suggest that this form of phenotypic flexibility demands complex genetic regulation.


The effect of porcine epidemic diarrhea (PED) on ovarian function and reproductive performance after weaning in Berkshire sows.
The purpose of this study was to investigate the ovarian condition at weaning and subsequent reproductive performance of Berkshire sows following an outbreak of PED. This study was conducted on a farrow-to-finish farm that experienced a PED outbreak beginning on January 6, 2014. Blood samples were collected at weaning from 19 to 20 sows every month from July 2013 until July 2014 to investigate the ovarian condition. The mean progesterone concentration was numerically higher during January 2014 than the other months, but this difference was not significant. The mean estradiol-17β concentration was higher during January 2014 than during July and October 2013 (P < 0.05). In addition, reproductive performance was compared during January, February, and March before (2013) and after (2014) the PED outbreak. Sows that farrowed in January had higher preweaning mortality in 2014 than in 2013 (P < 0.05), but sows that farrowed in February and March had similar preweaning mortality in 2013 and 2014 (P > 0.10). Sows that farrowed between January and March 2014 had 15% lower farrowing rate than those that farrowed during the same months in 2013 (P < 0.05). In conclusion, our results demonstrate poorer reproductive performance of Berkshire sows after a PED outbreak compared with before the outbreak.


Neural network for 3D trajectory tracking control of a CMG-actuated underwater vehicle with input saturation.
This paper considers the trajectory tracking problem of an underactuated underwater vehicle actuated by control moment gyros (CMGs) in three-dimensional (3D) space, with the constraints from input saturation, partial parameter uncertainty and unknown external disturbance. First, utilizing a physical translation of the motion equations, the overall system can be decomposed to an input decoupling system. Then a modified virtual velocity guidance law is derived to transform the tracking error signals into the controllable velocity signals. Subsequently, the Gaussian error function is employed to update the common saturation model. To avoid complex derivations of the virtual control signals, first-order sliding mode differentiator is explored in the dynamic control layer. Then, the adaptive neural network (NN) control method is introduced into the backstepping procedure to account for nonlinear uncertainties and bounded disturbances. Among this, the constrained steering law is used to steer the CMG system to avoid its inherent singularity and fulfill the global tracking control. It is proved that the proposed controller can guarantee all closed-loop signals converge to a small neighborhood of the origin. Finally, two case studies are presented to illustrate the tracking performance of the proposed design.


Isolation and feeder-free primary culture of four cell types from a single human skin sample.
Four types of primary cells-dermal fibroblasts, dermal microvascular endothelial cells, epidermal keratinocytes, and epidermal melanocytes-can be isolated simultaneously from a single human skin sample, without the use of xenogeneic murine feeder cells. This protocol describes the procedures for isolation of these cells from adult full-thickness skin obtained from surgical discard tissue. The cells isolated using this protocol contain stem cell populations and are competent to form functional skin tissue in three-dimensional reconstructed skin models. For complete details on the use and execution of this profile, please refer to Supp et al. (2002), Boyce et al. (2015), Boyce et al. (2017a), Boyce et al. (2017b), and Supp et al. (2019).


Deciphering the quorum-sensing lexicon of the gut microbiota.
The enduring coexistence between the gut microbiota and the host has led to a symbiotic relationship that benefits both parties. In this complex, multispecies environment, bacteria can communicate through chemical molecules to sense and respond to the chemical, physical, and ecological properties of the surrounding environment. One of the best-studied cell-to-cell communication mechanisms is quorum sensing. Chemical signaling through quorum sensing is involved in regulating the bacterial group behaviors, often required for host colonization. However, most microbial-host interactions regulated by quorum sensing are studied in pathogens. Here, we will focus on the latest reports on the emerging studies of quorum sensing in the gut microbiota symbionts and on group behaviors adopted by these bacteria to colonize the mammalian gut. Moreover, we address the challenges and approaches to uncover molecule-mediated communication mechanisms, which will allow us to unravel the processes that drive the establishment of gut microbiota.