The influence of substrate quality and stream size on wood decomposition dynamics.
Woody materials decayed more rapidly in a first order stream than in larger streams in eastern Quebec, Canada. The rate of annual mass loss (k) was highest (k=1.20) for alder wood chips in a first order stream and lowest (k=0.04) for black spruce wood chips in a ninth order stream. Decay rates for woody materials in a first order stream were inversely related to their initial lignin to nitrogen ratios. In larger streams, decay rates of woody materials were inversely related to their initial lignin concentrations. A number of quantifiable relationships were found to exist between the initial lignin and nitrogen contents of woody materials and the nitrogen dynamics of decaying wood.


Laser Interstitial Thermal Therapy for First-Line Treatment of Surgically Accessible Recurrent Glioblastoma: Outcomes Compared With a Surgical Cohort.
Laser interstitial thermal therapy (LITT) for glioblastoma (GBM) has been reserved for poor surgical candidates and deep "inoperable" lesions. We present the first reported series of LITT for surgically accessible recurrent GBM (rGBM) that would otherwise be treated with surgical resection. To evaluate the use of LITT for unifocal, lobar, first-time rGBM compared with a similar surgical cohort. A retrospective institutional database was used to identify patients with unifocal, lobar, first-time rGBM who underwent LITT or resection between 2013 and 2020. Clinical and volumetric lesional characteristics were compared between cohorts. Subgroup analysis of patients with lesions ≤20 cm 3 was also completed. Primary outcomes were overall survival and progression-free survival. Of the 744 patients with rGBM treated from 2013 to 2020, a LITT cohort of 17 patients were compared with 23 similar surgical patients. There were no differences in baseline characteristics, although lesions were larger in the surgical cohort (7.54 vs 4.37 cm 3 , P = .017). Despite differences in lesion size, both cohorts had similar extents of ablation/resection (90.7% vs 95.1%, P = .739). Overall survival (14.1 vs 13.8 months, P = .578) and progression-free survival (3.7 vs 3.3 months, P = 0. 495) were similar. LITT patients had significantly shorter hospital stays (2.2 vs 3.0 days, P = .004). Subgroup analysis of patients with lesions ≤20 cm 3 showed similar outcomes, with LITT allowing for significantly shorter hospital stays. We found no difference in survival outcomes or morbidity between LITT and repeat surgery for surgically accessible rGBM while LITT resulted in shorter hospital stays and more efficient postoperative care.


Logic of the Temporal Compartmentalization of the Hepatic Metabolic Cycle.
The mammalian liver must cope with various metabolic and physiological changes that normally recur every day and result primarily from rest-activity and fasting-feeding cycles. In this article, I present evidence supporting a temporal compartmentalization of rhythmic hepatic metabolic processes into four main clusters: regulation of energy homeostasis, maintenance of information integrity, immune response, and genetic information flow. I further review literatures and discuss how both the circadian and the newly discovered 12-h ultradian clock work together to regulate these four temporally separated processes in mouse liver, which, interestingly, is largely uncoupled from the liver zonation regulation.


Increased renal sensitivity to aldosterone in the rat: induction by a high potassium diet.
1. The renal response to aldosterone, measured by urinary sodium and potassium excretion, was determined in adrenalectomized rats that had been previously fed either a high potassium diet or a control diet. High K+ rats showed an enhanced response to aldosterone at all doses tested. 2. The induction of this enhanced response to aldosterone could be suppressed by a high sodium intake. It may also require the presence of the adrenal glands during the induction period, although interpretation of adrenalectomy experiments in the present study was made difficult by the effect of maintenance DOC therapy on the renal response to aldosterone. 3. The enhanced response could not be induced by a low sodium diet alone or by the administration of high doses of exogenous aldosterone. 4. No difference between high K+ and control rats could be detected in rat kidney mineralocorticoid receptors, assessed by both in vivo and in vitro binding of tritiated aldosterone. 5. The method of the induction, and the mechanism of the enhanced response remains to be defined.


Silane-based modified papers and their extractive phase roles in a microfluidic platform.
Herein, some (modified) paper-based substrates were prepared and utilized as extractive phases in a microfluidic device and their extraction performances examined for analytes with different polarities. Reagents including hexadecyltrimethoxysilane (HDTMS), phenyltrimethoxysilane (PTES), (3-aminopropyl) triethoxysilane (APTES) and 3-(2,3-epoxypropoxy) propyltrimethoxysilane (EPPTMOS) were implemented for the modification process. Due to the induction of different silane functional groups, it was anticipated to have various interactions for the tested analytes. Eventually, the prepared paper sheets were used as extractive phases for solid-phase extraction within a microfluidic system. The microfluidic setup not only improves the mechanical stability of the paper-based phases but also facilitated the mass transfer process and decreases the energy consumption. The selected analytes contained antidepressant drugs, organophosphates and triazine toxins, having different structures and polarities. Afterward, the existing interactions between the paper-based sorbents and the selected analytes were investigated by Principal Component Analysis (PCA) and Hierarchical Clustering Analysis (HCA) for data analysis. According to the obtained data, the PTES modified surface paper was selected for quantitative investigation and optimization. The major parameters associated with the extraction performance were studied. A linear range was obtained for amitriptyline and trimipramine, 0.05-200 μg L-1, and the calibration graph for clomipramine was linear in the range of 0.02-200 μg L-1. The employment of microfluidic device in conjunction with gas chromatography-mass spectrometry led to the limits of detections of 0.005-0.01 μgL-1 for the antidepressant drugs. The relative recoveries for the tested drugs in urine samples were in the range of 95-103%.


Reactive metabolites of acetaminophen activate and sensitize the capsaicin receptor TRPV1.
The irritant receptor TRPA1 was suggested to mediate analgesic, antipyretic but also pro-inflammatory effects of the non-opioid analgesic acetaminophen, presumably due to channel activation by the reactive metabolites parabenzoquinone (pBQ) and N-acetyl-parabenzoquinonimine (NAPQI). Here we explored the effects of these metabolites on the capsaicin receptor TRPV1, another redox-sensitive ion channel expressed in sensory neurons. Both pBQ and NAPQI, but not acetaminophen irreversibly activated and sensitized recombinant human and rodent TRPV1 channels expressed in HEK 293 cells. The reducing agents dithiothreitol and N-acetylcysteine abolished these effects when co-applied with the metabolites, and both pBQ and NAPQI failed to gate TRPV1 following substitution of the intracellular cysteines 158, 391 and 767. NAPQI evoked a TRPV1-dependent increase in intracellular calcium and a potentiation of heat-evoked currents in mouse spinal sensory neurons. Although TRPV1 is expressed in mouse hepatocytes, inhibition of TRPV1 did not alleviate acetaminophen-induced hepatotoxicity. Finally, intracutaneously applied NAPQI evoked burning pain and neurogenic inflammation in human volunteers. Our data demonstrate that pBQ and NAQPI activate and sensitize TRPV1 by interacting with intracellular cysteines. While TRPV1 does not seem to mediate acetaminophen-induced hepatotoxicity, our data identify TRPV1 as a target of acetaminophen with a potential relevance for acetaminophen-induced analgesia, antipyresia and inflammation.


Protective effects of thrombomodulin on microvascular permeability after subarachnoid hemorrhage in mouse model.
The enhanced vascular permeability is a major early brain injury following subarachnoid hemorrhage (SAH). However, its mechanism is not clear yet. In this work, we explored its potential mechanism and investigated the roles of thrombomodulin (TM) in maintaining microvascular integrity after SAH. SAH models were established in adult male ICR mice (28-32 g) by endovascular perforation. TM was immediately administered by femoral vein injection following SAH. The brain water content, Evans Blue content and neurological functions were evaluated. Brain edema was also detected by magnetic resonance imaging (MRI) (T2 map). The siRNA technique, enzyme-linked immunosorbent assay (ELISA), immunofluorescence staining and western blotting were performed to explore the potential mechanism of TM treatment. The number of microthrombi in the hippocampus microvessels was also recorded. TM significantly decreased brain water content and Evans Blue content, alleviated brain edema and neurological deficits after SAH. The plasma concentration of activated protein C was increased after TM treatment. In addition, the levels of phospho-p38MAPK, phospho-p53, cleaved caspase-3, phospho-NF-κB (p65) were markedly decreased. Additionally, the loss of VE-cadherin and Occludin (markers of vascular integrity) and the number of microthrombi in the hippocampus were also reduced. Our results indicated that TM has protective effects on preserving microvascular integrity following SAH partly through preserving endothelial junction proteins and quenching apoptosis/inflammation in endothelial cells via blocking p38MAPK-p53/NF-κB (p65) pathway.


Internodal Schwann cell fingers in the ventral spinal roots in mice: incidence and relationship to the diameter of myelinated fibers.
Internodal Schwann cell fingers were present in the lumbar, cervical, and thoracic spinal roots of adult mice at the age of 3 months, but they were not recognized in five mice examined at the age of 3 weeks. In the L4 ventral roots of ICR mice aged 3 months, the incidence of internodal Schwann cell fingers was 0.79% at the central-peripheral transitional zone and 2.43% at the distal regions, respectively. The ratio of axon diameter to total fiber diameter of myelinated fibers with internodal Schwann cell fingers was lower than that of fibers without them. Therefore, we conclude that internodal Schwann cell fingers are probably related to the developmental increase in the thickness of the myelin sheaths in the ventral spinal roots at all levels of the spinal cord.


Impact of prolonged sitting on vascular function in young girls.
What is the central question of this study? Children are spending more than 60% of their waking day sedentary. The consequences of excessive sedentary behaviour are not well understood in the child, but there is growing evidence that with increasing sedentary time, cardiovascular risk in childhood also increases. What is the main finding and its importance? Our findings show that a 3 h period of uninterrupted sitting causes a profound (33%) reduction in vascular function in young girls. Importantly, we also demonstrate that breaking up sitting with regular exercise breaks can prevent this. Excessive sedentary behaviour has serious clinical and public health implications; however, the physiological changes that accompany prolonged sitting in the child are not completely understood. Herein, we examined the acute effect a prolonged period of sitting has upon superficial femoral artery function in 7- to 10-year-old girls and the impact of interrupting prolonged sitting with exercise breaks. Superficial femoral artery endothelium-dependent flow-mediated dilatation, total shear rate, anterograde and retrograde shear rates and oscillatory shear index were assessed before and after two experimental conditions: a 3 h uninterrupted period of sitting (SIT) and a 3 h period of sitting interrupted each hour with 10 min of moderate-intensity exercise (EX). A mixed-model analysis of variance was used to compare between-condition and within-condition main effects, controlling for the within-subject nature of the experiment by including random effects for participant. Superficial femoral artery endothelium-dependent flow-mediated dilatation decreased significantly from pre- to post-SIT (mean difference 2.2% flow-mediated dilatation; 95% confidence interval = 0.60-2.94%, P < 0.001). This relative decline of 33% was abolished in the EX intervention. Shear rates were not significantly different within conditions. Our data demonstrate the effectiveness of short but regular exercise breaks in offsetting the detrimental effects of uninterrupted sitting in young girls.


Osseous valgus alignment and posteromedial ligament complex deficiency lead to increased ACL graft forces.
To biomechanically investigate the influence of osseous valgus alignment, with and without deficiency of the posteromedial ligament complex (PMC), on ACL-graft forces under axial load. ACL reconstruction was performed on ten cadaveric knee joints. A lateral distal femur osteotomy was then done to adjust for three different alignment conditions according to the position, where the axial weight bearing line (WBL) dissected the tibial plateau (% from medial to lateral): 50%, 85% and 115%. Each alignment was tested with the PMC intact, deficient and reconstructed. Axial loads of 400 N were applied in 15° of knee flexion and changes of ACL-graft forces and dynamic valgus angle (DVA) were recorded. In the PMC intact state, lateralization of the WBL to 85% and to 115% led to significantly increased ACL graft forces (85%: p = 0.010; 115%: p < 0.001) and DVAs (85%: p = 0.027; 115%: p = 0.027). Dissection of the PMC led to a significant increase of ACL graft forces and DVAs at 85% and 115% valgus alignment (p < 0.001) only. In comparison to valgus aligned knees with additional PMC deficiency, ligament reconstruction alone was able to significantly decrease ACL graft forces (p < 0.001) and DVAs (p < 0.001). However, alignment correction alone was significantly more effective in reducing ACL graft forces (p < 0.001) and DVAs (p = 0.010). Osseous valgus alignment led to significantly increased forces on ACL grafts under axial joint compression, which was even further enhanced, when the PMC was deficient. In the valgus aligned and PMC deficient knee, correction to a straight leg axis was significantly more effective in decreasing forces on the ACL graft than reconstruction of the PMC. In patients with valgus alignment and combined injuries of the ACL and PMC, a correction osteotomy to a straight leg axis as well as reconstruction of the PMC should be considered to protect the reconstructed ACL.


5α-reductase inhibitors impact prognosis of urothelial carcinoma.
5α-reductase inhibitors (5-ARIs) inhibit the pathway of converting the testosterone to dihydrotestosterone and are widely used in benign prostatic hyperplasia patients. Since androgen receptor activation may play a role in urothelial tumorigenesis, we conducted this retrospective cohort study to determine whether 5α-reductase inhibitors (5-ARIs) administration is associated with bladder cancer mortality, bladder cancer recurrence and upper tract urothelial carcinoma mortality, using the Taiwan National Health Insurance database. The data of this retrospective cohort study were sourced from the Longitudinal Health Insurance Database of Taiwan, compiled by the Taiwan National Health Insurance database from 1996 to 2010. It consists of 18,530 men with bladder cancer, of whom 474 were 5-ARIs recipients and 4384 men with upper tract urothelial carcinoma, of whom 109 were 5-ARIs recipients. Propensity Score Matching on the age and geographic data was done at the ratio of 1:10. We analyzed the odds ratios (OR) and 95% confidence interval (CI) of the risk of bladder cancer death, bladder cancer recurrence rate and upper tract urothelial carcinoma related death by the 5-ARIs administration. Those who received 5-ARIs showed a lower risk of bladder cancer related death compared to nonusers in multivariable adjusted analysis (OR 0.835, 95% CI 0.71-0.98). However, there was no significant difference in the bladder cancer recurrence rate (OR 0.956, 95% CI 0.82-1.11) and upper tract urothelial carcinoma related mortality in multivariable adjusted analysis (OR 0.814, 95% CI 0.6-1.1). Patients who receive 5-ARIs have lower bladder cancer related mortality compared to those who don't. 5-ARIs may prove to be a viable strategy to improve bladder cancer outcomes.


Peroxisome proliferator-activated receptor alpha-retinoid X receptor agonists induce beta-cell protection against palmitate toxicity.
Fatty acids can stimulate the secretory activity of insulin-producing beta-cells. At elevated concentrations, they can also be toxic to isolated beta-cells. This toxicity varies inversely with the cellular ability to accumulate neutral lipids in the cytoplasm. To further examine whether cytoprotection can be achieved by decreasing cytoplasmic levels of free acyl moieties, we investigated whether palmitate toxicity is also lowered by stimulating its beta-oxidation. Lower rates of palmitate-induced beta-cell death were measured in the presence of L-carnitine as well as after addition of peroxisome proliferator-activated receptor alpha (PPARalpha) agonists, conditions leading to increased palmitate oxidation. In contrast, inhibition of mitochondrial beta-oxidation by etomoxir increased palmitate toxicity. A combination of PPARalpha and retinoid X receptor (RXR) agonists acted synergistically and led to complete protection; this was associated with enhanced expression levels of genes involved in mitochondrial and peroxisomal beta-oxidation, lipid metabolism, and peroxisome proliferation. PPARalpha-RXR protection was abolished by the carnitine palmitoyl transferase 1 inhibitor etomoxir. These observations indicate that PPARalpha and RXR regulate beta-cell susceptibility to long-chain fatty acid toxicity by increasing the rates of beta-oxidation and by involving peroxisomes in fatty acid metabolism.


Effects of Dapagliflozin Compared with Sitagliptin and Metformin in Drug-Naïve Japanese Patients with Type 2 Diabetes: A 12-Week, Open-Label, Randomized, Active-Controlled Trial.
To compare the efficacy and tolerability of dapagliflozin with those of sitagliptin and metformin in patients with type 2 diabetes who have never received glucose-lowering agents. In this randomized, 12-week, open-label, active-controlled trial, 32 patients were randomly assigned to receive dapagliflozin 5 mg, sitagliptin 50 mg, or metformin 1000 mg per day for 12 weeks. At baseline and at week 12, the patients underwent a meal tolerance test (MTT). After 12 weeks of treatment, the changes in fasting and postprandial plasma glucose and plasma glucose area under the curve (AUC)0-120 min levels during the MTT from baseline were significantly improved in the three study groups, and there were no significant differences among the three study groups (P < 0.05). The mean changes in glycated hemoglobin (HbA1c) from baseline to week 12 were - 0.96%, - 1.24%, and - 1.40% in the dapagliflozin, sitagliptin, and metformin groups, respectively. Although there was no significant difference among the three study groups, the lowering effect of HbA1c tended to be greater in the metformin group than in the dapagliflozin group. In contrast, the insulin AUC0-120 min levels at week 12 significantly decreased only in the dapagliflozin group (P = 0.049). Similarly, body weight was significantly reduced only in the dapagliflozin group (- 2.1 kg [- 2.7%], P = 0.047). Moreover, dapagliflozin significantly improved serum adiponectin levels (P = 0.003). However, there were no significant differences in the changes in these glycemic and metabolic parameters among the three study groups. No serious adverse events were documented in any group. Dapagliflozin exerted beneficial effects similar to sitagliptin and metformin on glycemic parameters. In addition, dapagliflozin significantly reduced body weight and insulin AUC levels and improved serum adiponectin levels. Therefore, we suggest that these three hypoglycemic agents could be viable first-line medications for drug-naïve Japanese patients with type 2 diabetes. University Hospital Medical Information Network (UMIN000024427).


Time course changes in corticospinal excitability during repetitive peripheral magnetic stimulation combined with motor imagery.
Repetitive peripheral magnetic stimulation (rPMS) induces proprioceptive afferents and facilitates corticospinal excitability. Short-term sessions of rPMS combined with motor imagery (MI) enhance corticospinal excitability more than rPMS alone. However, it is not clear how long the intervention of rPMS combined with MI would be needed to facilitate corticospinal excitability. Therefore, we investigated the time course change in corticospinal excitability during the combination of rPMS and MI. Thirteen healthy volunteers participated in a 20-min intervention under the following three experimental conditions on different days: rPMS, MI, and rPMS combined with MI (rPMS + MI). In the rPMS and rPMS + MI, the participants were delivered rPMS, which was 25 Hz, 2 s/train at 1.5 × of the train intensity induced muscle contractions, through the wrist extensor muscles. In the MI and rPMS + MI, the participants repeatedly imagined wrist movements for 2 s. Motor evoked potentials (MEPs) were recorded from the extensor carpi radialis (ECR) and flexor carpi radialis (FCR) muscles every 5 min for each condition. The MEP amplitudes of the ECR after > 10 min of intermittent rPMS combined with MI were greater than baseline. The MEP amplitude of the ECR in rPMS + MI was greater than that in rPMS condition after 20 min of intervention. The present results suggest that over 10 min of intermittent rPMS combined with MI facilitates corticospinal excitability, and that the effect of rPMS combined with MI on corticospinal excitability might be greater than that of rPMS alone.


Differentiation of subgroups of monosymptomatic enuresis according to prepulse inhibition of the startle reflex.
Monosymptomatic enuresis (ME) is a common disorder in children with serious social and psychological consequences. Treatment is usually initiated with desamino-arginine vasopressin (dDAVP) and/or alarm therapy as first-line treatment and imipramine as second-line. All treatments have proven efficacy, but are not successful with all patients. Therefore, a differentiation into subgroups according to treatment efficacy would be beneficial. A group of patients resistant to first-line treatment was treated with imipramine and compared with matched controls successfully treated with dDAVP and/or alarm therapy. Prepulse inhibition (PPI) to acoustic startle reflexes was measured in all patients. In a group of 23 nonresponders, the median PPI was 72% (range 43-94%) compared with the matched dDAVP/alarm - responders with a median PPI of 26% (range 0-61%) (p < 0.0001). The response rate to imipramine was 87%. The presented data provide evidence that PPI allows to identify two subgroups of ME. The results offer further insight into (at least) two different pathomechanisms involved in ME: (i) a maturational delay of reflex inhibition with reduced PPI and (ii) a normal PPI, possibly with abnormal sleep patterns, that can be influenced by imipramine.


[Phosphorylation and nuclear translocation of serine 722 and serine 910 of focal adhesion kinase in hypertrophic cardiac myocytes of left ventricle of spontaneously hypertensive rats].
To investigate the role of focal adhesion kinase (FAK) in cardiac hypertrophy induced by hypertension. Using immunofluorescent labeling, confocal microscopy and Western blot, the expression and subcellular location of FAK-pSer722 and FAK-pSer910 were determined in cardiac myocytes of the left ventricles from 2, 6, 12, and 18 month-old spontaneously hypertensive heart failure (SHHF) rats and age-matched Wistar-Kyoto (WKY) control rats, respectively. There was no obvious difference in FAK-pSer722 and FAK-pSer910 expression between 2 month-old SHHF and WKY rats. In contrast with the control groups, the expression of FAK-pSer722 and FAK-pSer910 significantly increased in cardiac myocytes of the left ventricle, from 6, 12 and 18 month-old SHHF rats. Both FAK-pSer722 and FAK-pSer910 were translocated and acummulated in nuclei of cardiac myocytes from 6, 12, and 18 month-old SHHF rats. Phosphorylation and translocation of serine 722 and serine 910 of phosphorylated FAK play an important role in the de-compensatory cardiac hypertrophy.


Recurrent chorioamnionitis and second-trimester abortion because of an enterouterine fistula.
Chorioamnionitis, a common cause of second-trimester abortion, is usually secondary to an ascending infection. Recurrent chorioamnionitis with second-trimester abortion secondary to an occult enterouterine fistula has not been reported previously. A 26-year-old Indian woman, para 0-0-2-0, presented with two spontaneous second-trimester losses. Her third pregnancy carried to 24 weeks, but she delivered after the development of pneumonia, bacteremia, preterm labor, and chorioamnionitis. The patient passed melena containing blood clots after the delivery. After the last pregnancy, laparoscopy and laparotomy revealed an ileal-uterine fistula and a foreign body (necrotic cartilage). The blind loop of bowel was resected and the fistulous tract excised. Our patient's recurrent pregnancy wastage was caused by chorioamnionitis secondary to an enterouterine fistula resulting from foreign body ingestion. A complete reversal of this problem is anticipated.


A diabetic milieu increases ACE2 expression and cellular susceptibility to SARS-CoV-2 infections in human kidney organoids and patient cells.
It is not well understood why diabetic individuals are more prone to develop severe COVID-19. To this, we here established a human kidney organoid model promoting early hallmarks of diabetic kidney disease development. Upon SARS-CoV-2 infection, diabetic-like kidney organoids exhibited higher viral loads compared with their control counterparts. Genetic deletion of the angiotensin-converting enzyme 2 (ACE2) in kidney organoids under control or diabetic-like conditions prevented viral detection. Moreover, cells isolated from kidney biopsies from diabetic patients exhibited altered mitochondrial respiration and enhanced glycolysis, resulting in higher SARS-CoV-2 infections compared with non-diabetic cells. Conversely, the exposure of patient cells to dichloroacetate (DCA), an inhibitor of aerobic glycolysis, resulted in reduced SARS-CoV-2 infections. Our results provide insights into the identification of diabetic-induced metabolic programming in the kidney as a critical event increasing SARS-CoV-2 infection susceptibility, opening the door to the identification of new interventions in COVID-19 pathogenesis targeting energy metabolism.


Ring chromosome 20 mosaicism in a girl with complex partial seizures.
The authors report an 11-year-old girl with epilepsy, poor school-performance and minor behavioural disorders. The epilepsy is characterized by complex partial seizures, sometimes progressing secondarily into generalized tonic-clonic seizures, and is poorly controlled by medical treatment. Chromosomal analysis revealed a ring chromosome 20 mosaicism. The affected patient shows signs of ring chromosome 20 syndrome, characterized in the present case by poor school-performance, behavioural disorders and epilepsy.


The global world--a domain for development in adolescence?
Two cases studies are presented for the purpose of providing material for theoretical discussion on the development of adolescents in the nuclear age. The two cases originate from a study of 15 girls who were followed from the age of 15-16 to 17-18. Both cases showed an initial concern about nuclear war in earlier adolescence, but their subsequent development proceeded in opposite directions. The first case demonstrates how privatization and turning away from global issues might develop in one's mind and way of life. The second case demonstrates widening interests and activities in the global domain. The cases are analysed using the Vygotskian concepts of internalization and the zone of proximal development. It is suggested that the development of mass media has created a new zone of proximal development in adolescence, the global domain. It is suggested further that an integrated world view is a developmental potential inherent in the global domain.


A new educational tool for neuropsychological test raters in the dementia field: A Delphi study.
Neuropsychological testing is the primary endpoint of clinical research in the field of dementia, making it essential for the rater to accurately calculate test data for an extensive assessment. However, many raters lack adequate skill to complete neuropsychological tests with sufficient confidence. Therefore, we developed and examined the utility of a checklist and a manual as tools for educating raters on their basic behaviours when conducting comprehensive neuropsychological evaluations in the field of dementia. We conducted a seven-step comprehensive study to develop rater training tools and examine their usefulness between April 2019 and February 2021 involving: 1. Development of a draft checklist, 2. Delphi review rounds, 3. Design of the final checklist, 4. Item weighting, 5. Examination of reliability, 6. Creating the manual, and 7. Examination of the usefulness of learning through rater educational tools (checklist and manual). The Delphi review round led to a highly reliable and valid checklist and manual. The total checklist score improved significantly (t = 2.37, P = 0.029) before and after manual learning. We found that the appropriate basic behaviours required by the rater to conduct neuropsychological testing skilfully within the dementia field could be acquired with this tool. Using a robust development process, we integrated expert knowledge and experience, and developed a checklist and a manual for learning the basic behaviours of neuropsychological test raters in the field of dementia. Establishing standards of basic behaviour for neuropsychological raters will help promote dementia research and advances in medicine.


Effects of a chronic exposure to different water temperatures and/or to an environmental cadmium concentration on the reproduction of the threespine stickleback (Gasterosteus aculeatus).
Knowledge about combined effects of chemicals and temperature on reproductive capacity of fish are rare in literature, especially when it comes to the effects of chronic low-dose chemical exposure combined to the thermal stress. The aim of the study was to evaluate the single and combined effects of temperature (16, 18, 21 °C) and an environmentally relevant concentration of waterborne cadmium (1 µg L-1, nominal concentration) on the reproductive outputs of threespine stickleback (Gasterosteus aculeatus), and their consequences on offspring survival parameters. The high temperature (21 °C) was the only factor that affected parental parameters (gonadosomatic index "GSI", and vitellogenin "VTG" particularly). On females, 21 °C had a stimulating effect on gonadal development evaluated by an early increase, followed by a sharp decrease of GSI, probably indicating gonadal atresia. Promoting effect of temperature was corroborated by an early production of VTG. In vitro fertilization assays showed interesting results, particularly cadmium effects. As it was supposed, high temperature had a negative impact on offspring parameters (significant decrease in survival and an increase of unhatched embryos). Parental exposure to the very low concentration of cadmium had also negative consequences on mortality rate (significant increase) and hatching rate (significant decrease). Our results indicate that in a global warming context, high temperature and its combination with contaminant may impact reproductive capacity of G. aculeatus, by decreasing parental investment (low eggs and/or sperm quality).


Obstetrical brachial plexus palsy.
Obstetrical brachial plexus palsy is considered to be the result of a trauma during the delivery, even if there remains some controversy surrounding the causes. Although most babies recover spontaneously in the first 3 months of life, a small number remains with poor recovery which requires surgical brachial plexus exploration. Surgical indications depend on the type of lesion (producing total or partial palsy) and particularly the nonrecovery of biceps function by the age of 3 months. In a global palsy, microsurgery will be mandatory and the strategy for restoration will focus first on hand reinnervation and secondarily on providing elbow flexion and shoulder stability. Further procedures may be necessary during growth in order to avoid fixed contractured deformities or to give or increase strength of important muscle functions like elbow flexion or wrist extension. The author reviews the history of obstetrical brachial plexus injury, epidemiology, and the specifics of descriptive and functional anatomy in babies and children. Clinical manifestations at birth are directly correlated with the anatomical lesion. Finally, operative procedures are considered, including strategies of reconstruction with nerve grafting in infants and secondary surgery to increase functional capacity at later ages. However, normal function is usually not recovered, particularly in total brachial plexus palsy.


Establishing a Centralized Virtual Visit Support Team: Early Insights.
With the removal of many barriers to direct-to-consumer telehealth during the COVID-19 pandemic, which resulted in a historic surge in the adoption of telehealth into ongoing practice, health systems must now identify the most efficient and effective way to sustain these visits. The Medical University of South Carolina Center for Telehealth developed a Telehealth Centralized Support team as part of a strategy to mature the support infrastructure for the continued large-scale use of outpatient virtual care. The team was deployed as the Center for Telehealth rolled out a new ambulatory telehealth software platform to monitor clinical activity, support patient registration and virtual rooming, and ensure successful visit completion. A multi-method, program-evaluation approach was used to describe the development and composition of the Telehealth Centralized Support Team in its first 18 months utilizing the Reach, Effectiveness, Adoption, Implementation, Maintenance framework. In the first 18 months of the Telehealth Centralized Support team, over 75,000 visits were scheduled, with over 1500 providers serving over 46,000 unique patients. The team was successfully deployed over a large part of the clinical enterprise and has been well received across the health system. It has proven to be a scalable model to support enterprise-level virtual health care delivery. While further research is needed to evaluate the long-term program outcomes, the results of its early implementation suggest great promise for improved telehealth patient and provider satisfaction, the more equitable delivery of virtual services, and more cost-effective means for supporting virtual care.


Analgesic Effects of Preincision Ketamine on Postspinal Caesarean Delivery in Uganda's Tertiary Hospital: A Randomized Clinical Trial.
Background. Good postoperative analgesic management improves maternal satisfaction and care of the neonate. Postoperative pain management is a challenge in Mulago Hospital, yet ketamine is accessible and has proven benefit. We determined ketamine's postoperative analgesic effects. Materials and Methods. We did an RCT among consenting parturients that were randomized to receive either intravenous ketamine (0.25 mg/kg) or placebo after spinal anesthetic. Pain was assessed every 30 mins up to 24 hours postoperatively using the numerical rating scale. The first complaint of pain requiring treatment was noted as "time to first breakthrough pain." Results. We screened 100 patients and recruited 88 that were randomized into two arms of 44 patients that received either ketamine or placebo. Ketamine group had 30-minute longer time to first breakthrough pain and lower 24-hour pain scores. Postoperative diclofenac consumption was lesser in the ketamine group compared to placebo and Kaplan-Meier graphs showed a higher probability of experiencing breakthrough pain earlier in the placebo group. Conclusion. Preincision intravenous ketamine (0.25 mg/kg) offered 30-minute prolongation to postoperative analgesia requirement with reduced 24-hour pain scores. We recommend larger studies to explore this benefit. This trial is registered with Pan African Clinical Trial Registry number PACTR201404000807178.


Variation of growth and transcriptome responses to arbuscular mycorrhizal symbiosis in different foxtail millet lines.
Arbuscular mycorrhizal fungi (AMF) have been applied to promote the growth of different crop species, but knowledge about the impacts of symbiosis on foxtail millet at the physiological and molecular levels have remained limited. In this study, we compared the mycorrhization phenotypes of one cultivar and three different landraces and performed a comprehensive transcriptomic analysis to assess the effects of genetic variation on the responses to symbiosis. Our results showed that colonization by AMF did not enhance biomass accumulation but significantly increased grain production only in three lines. More than 2,000 genes were affected by AMF colonization in all lines. Most AM symbiosis-conserved genes were induced, but the induction levels varied between lines. Gene Ontology (GO) analysis showed that Biological Function terms related to nitrogen transport and assimilation were only enriched in TT8. Similarly, two of phosphate starvation-induced phosphate transporters were only simultaneously downregulated in TT8. In the other two lines, the enrichment of GO terms associated with cell wall reorganization and lignification was observed, though the effects were different. This study reveals the impacts of genetic variation of millet lines on the responses to AM symbiosis and provides information regarding AMF application for millet production.


Deciphering the map of METTL14-mediated lncRNA m6A modification at the transcriptome-wide level in breast cancer.
Emerging studies have demonstrated the critical role of RNA m6A methylation in tumor progression, whereas lncRNA m6A modification profiles in breast cancer remain largely unknown. Our previous study has shown that METTL14 accelerates breast cancer migration and invasion in an m6A-dependent manner, making it critical to analyze METTL14-mediated m6A modification at a transcriptome-wide scale in breast cancer. Here, we performed MeRIP-seq analysis in METTL14 overexpressed and control MDA-MB-231 cells. Conjoint analysis of MeRIP-seq and RNA-seq data was used to select lncRNAs with m6A methylation and differential expression. Finally, the screened lncRNA was verified by MeRIP-PCR and its function was studied via transwell assay. Our results determined that high expression of METLL14 results in 3996 hypermethylation peaks from 3107 transcripts, and 4100 hypomethylation peaks from 2918 transcripts. Furthermore, conjoint analysis of MeRIP-seq and RNA-seq data identified 25 lncRNAs with discrepant methylation and simultaneously discrepant expression, among which the top 10 differentially expressed LncRNAs were AC026401.3, CYTOR, LINC01943, AC084125.2, FLJ20021, LINC00472, and NORAD, MALAT1, AL161431.1, and LINC01764. Moreover, over-expressed METTL14 stimulated the m6A modification of AC084125.2, while decreasing its expression. Compared to adjacent tissues, AC084125.2 was lowly expressed in tumors and could be used as a biomarker in the diagnosis of breast cancer. Meanwhile, AC084125.2 inhibited the migration and invasion of cancer cells. In conclusion, METTL14-mediated m6A modification of lncRNAs, which might provide reference for future intervention in tumor progression.


7,12-Dimethylbenz[a]anthracene exposure induces the DNA repair response in neonatal rat ovaries.
7,12-Dimethylbenz[a]anthracene (DMBA) destroys ovarian follicles at all stages of development. This study investigated DMBA-induced DNA double strand break (DSB) formation with subsequent activation of the ovarian DNA repair response in models of pre-antral or pre-ovulatory follicle loss. Postnatal day (PND) 4 Fisher 344 (F344) rat ovaries were cultured for 4 days followed by single exposures of vehicle control (1% DMSO) or DMBA (12.5 nM or 75 nM) and maintained in culture for 4 or 8 days. Alternately, PND4 F344 rat ovaries were exposed to 1 μM DMBA at the start of culture for 2 days. Total RNA or protein was isolated, followed by qPCR or Western blotting to quantify mRNA or protein level, respectively. γH2AX and phosphorylated ATM were localized and quantified using immunofluorescence staining. DMBA exposure increased caspase 3 and γH2AX protein. Additionally, DMBA (12.5 nM and 1 μM) increased levels of mRNA encoding Atm, Xrcc6, Brca1 and Rad51. In contrast, Parp1 mRNA was decreased on d4 and increased on d8 of DMBA exposure, while PARP1 protein increased after 8 days of DMBA exposure. Total ATM increased in a concentration-dependent temporal pattern (75 nM d4; 12.5 nM d8), while pATM was localized in large primary and secondary follicles and increased after 8 days of 75 nM DMBA exposure compared to both control and 12.5 nM DMBA. These findings support that, despite some concentration effects, DMBA induces ovarian DNA damage and that DNA repair mechanisms are induced as a potential mechanism to prevent follicle loss.


Covalent attachment of polymeric monolith to polyether ether ketone (PEEK) tubing.
A new method of reproducible preparation of vinylic polymeric monolithic columns with a key step of covalently anchoring the monolith to PEEK surface is described. In order to chemically attach the polymer monolith to the tube wall, methacrylate functional groups were introduced onto PEEK surface by a three-step procedure, including surface etching, surface reduction and surface methacryloylation. The chemical state of the modified tubing surface was characterized by attenuated total reflectance infrared (ATR-IR) spectroscopy. It was found that the etching step is the key to successfully modifying the PEEK tubing surface. Poly(styrene-co-divinylbenzene) monoliths were in situ synthesized by thermally initiated free radical copolymerization within the confines of surface-vinylized PEEK tubings of dimensions close to ones conventionally used in HPLC and UHPLC (1.6 mm internal diameter, 10.0-12.5 cm length). Adhesion test was done by measuring the operating pressure drop, which the prepared stationary phases can withstand. Good pressure resistance, up to 140 bar/10 cm (flow rate 0.5 mL min(-1), acetonitrile as a mobile phase), indicates strong bonding of monolith to the tubing wall. The monolithic material was proven to have a permeability of 1.7 × 10 (-14) m(2), applying acetonitrile-water 70:30 (v/v) as a mobile phase. The column performance was reproducible from column to column and was evaluated via the isocratic separation of a series of alkylbenzenes in the reversed-phase mode (acetonitrile-water 70:30, v/v). The numbers of plates per meter at optimal flow rate were found to be between 26 000 and 32 000 for the different analytes.


DNA ploidy of primary and recurrent irradiated laryngeal tumors.
Radiosensitivity of diploid laryngeal cancers, as compared with that of aneuploid ones, appears to be increased. However, no conclusive data exist. If a causal relationship exists, then recurrent laryngeal cancer after irradiation should predominantly be characterized by aneuploidy. To test this hypothesis we compared ploidy of 24 primarily irradiated laryngeal cancers and their subsequent recurrences. T and N stages were assessed in accordance with the TNM classification system of the UICC. With flow cytometry DNA ploidy was assessed. 1. Ploidy of 16 locally recurrent tumors did not differ from those of primary tumors, i.e. ten and six recurrences of diploid and aneuploid primary tumors, respectively, remained unchanged, 2. recurrences of four aneuploid primary tumors showed diploidy, 3. recurrences of four diploid primary tumors showed aneuploidy. The results of our study do not support the hypothesis that recurrent laryngeal cancer after irradiation of the primary tumor is characterized by aneuploidy.


A bridging [4Fe-4S] cluster and nucleotide binding are essential for function of the Cfd1-Nbp35 complex as a scaffold in iron-sulfur protein maturation.
The essential P-loop NTPases Cfd1 and Nbp35 of the cytosolic iron-sulfur (Fe-S) protein assembly machinery perform a scaffold function for Fe-S cluster synthesis. Both proteins contain a nucleotide binding motif of unknown function and a C-terminal motif with four conserved cysteine residues. The latter motif defines the Mrp/Nbp35 subclass of P-loop NTPases and is suspected to be involved in transient Fe-S cluster binding. To elucidate the function of these two motifs, we first created cysteine mutant proteins of Cfd1 and Nbp35 and investigated the consequences of these mutations by genetic, cell biological, biochemical, and spectroscopic approaches. The two central cysteine residues (CPXC) of the C-terminal motif were found to be crucial for cell viability, protein function, coordination of a labile [4Fe-4S] cluster, and Cfd1-Nbp35 hetero-tetramer formation. Surprisingly, the two proximal cysteine residues were dispensable for all these functions, despite their strict evolutionary conservation. Several lines of evidence suggest that the C-terminal CPXC motifs of Cfd1-Nbp35 coordinate a bridging [4Fe-4S] cluster. Upon mutation of the nucleotide binding motifs Fe-S clusters could no longer be assembled on these proteins unless wild-type copies of Cfd1 and Nbp35 were present in trans. This result indicated that Fe-S cluster loading on these scaffold proteins is a nucleotide-dependent step. We propose that the bridging coordination of the C-terminal Fe-S cluster may be ideal for its facile assembly, labile binding, and efficient transfer to target Fe-S apoproteins, a step facilitated by the cytosolic iron-sulfur (Fe-S) protein assembly proteins Nar1 and Cia1 in vivo.


Studies on the oral absorption of cyclic peptides from Pseudostellaria heterophylla and interacting with membrane receptors.
Pseudostellaria heterophylla (Miq.) Pax. (Taizishen, TZS) contains a variety of natural active cyclic-peptide compounds (CP). In this article, four kinds of CP monomers were isolated by HPLC and the structures were identified by mass spectrometry. The in vivo absorption of CP was detected by UPLC-MS/MS. The interaction between CP and membrane receptor was analyzed by SPR. As a result, the relative absorption rate of CP was Pesudostellarin B > Heterophyllin B > Pesudostellarin C > Pesudostellarin E. The difference in absorption rate of CP in vivo was related to its interaction with membrane receptors. The absorption mechanism of CP might be different. This is the first report that in vivo absorption study of different CP from TZS and explore its absorption mechanism, laying a theoretical foundation for the research and development of its oral drugs, and providing new ideas for the study of the absorption mechanism of CP from traditional Chinese medicine.


Platyhelminthes in tongue--a rare case and review.
Humans are the only known definitive host of the tapeworm Taenia solium and become a carrier by eating undercooked pork contaminated with "Cysticercus cellulosae" (cysticerci). Pigs act as an intermediate host and acquire cysticercosis by ingestion of eggs or proglottids from human feces, which develop into cysticerci within tissue, mostly without causing clinical symptoms in the host. Cysticercosis occurs in humans in a context of "fecal peril" by ingestion of egg-contaminated soil, water, vegetation, or auto-infestation. It has been reported in the published data that the separation of swine from humans, healthy cooking, and hygienic practices would lead to the eradication of the disease. However, cysticercosis is still a major public health problem in endemic regions, with more than 50 million infected people and is now a re-emerging disease in industrialized countries owing to human migration. It is the second most common cause of seizures in tropical countries. We report a case of oral cysticercosis in a 28-year-old woman who presented with a painless swelling in the ventral portion of the tongue. An excisional biopsy was performed, and histopathologic examination revealed a cystic cavity containing the tapeworm.


Improving transitions and outcomes of sepsis survivors (I-TRANSFER): a type 1 hybrid protocol.
This protocol is based on home health care (HHC) best practice evidence showing the value of coupling timely post-acute care visits by registered nurses and early outpatient provider follow-up for sepsis survivors. We found that 30-day rehospitalization rates were 7 percentage points lower (a 41% relative reduction) when sepsis survivors received a HHC nursing visit within 2 days of hospital discharge, at least 1 more nursing visit the first week, and an outpatient provider follow-up visit within 7 days compared to those without timely follow-up. However, nationwide, only 28% of sepsis survivors who transitioned to HHC received this timely visit protocol. The opportunity exists for many more sepsis survivors to benefit from timely home care and outpatient services. This protocol aims to achieve this goal. METHODS: Guided by the Consolidated Framework for Implementation Research, this Type 1 hybrid pragmatic study will test the effectiveness of the Improving Transitions and Outcomes of Sepsis Survivors (I-TRANSFER) intervention compared to usual care on 30-day rehospitalization and emergency department use among sepsis survivors receiving HHC. The study design includes a baseline period with no intervention, a six-month start-up period followed by a one-year intervention period in partnership with five dyads of acute and HHC sites. In addition to the usual care/control periods from the dyad sites, additional survivors from national data will serve as control observations for comparison, weighted to produce covariate balance. The hypotheses will be tested using generalized mixed models with covariates guided by the Andersen Behavioral Model of Health Services. We will produce insights and generalizable knowledge regarding the context, processes, strategies, and determinants of I-TRANSFER implementation. As the largest HHC study of its kind and the first to transform this novel evidence through implementation science, this study has the potential to produce new knowledge about the impact of timely attention in HHC to alleviate symptoms and support sepsis survivor's recovery at home. If effective, the impact of this intervention could be widespread, improving the quality of life and health outcomes for a growing, vulnerable population of sepsis survivors. A national advisory group will assist with widespread results dissemination.


CeO2@NC nanozyme with robust dephosphorylation ability of phosphotriester: A simple colorimetric assay for rapid and selective detection of paraoxon.
Enzyme-mediated dephosphorylation reaction is the important approach to realize the inactivation and detection of hazardous phosphate chemicals. To date, many phosphatases-like nanozymes (e.g., CeO2) have demonstrated the catalytic hydrolysis ability of the phosphomonoesters, rather than phosphotriester, and the CeO2 nanozyme only work under relatively harsh conditions of high temperature, and large dosage. Thus, exploration of efficient nanozymes for the rapid dephosphorylation of phosphotriester under mild conditions remains a challenge. Here, a novel CeO2@NC nanozyme is developed with excellent phosphatases-like activity based on substrate synergistic effect, in which, CeO2 nanoparticles embedded in N-doped carbon (NC) material. Taking paraoxon as the model substrate, such CeO2@NC nanozyme can drive rapid dephosphorylation of phosphotriester over a broad temperature range, which not only significantly outperforms natural phosphatases and neat CeO2, but also can preserve >80% of the optimal activity after exposure of harsh conditions, such as strong acidic/basic medium, high temperature of up to 80 °C. The excellent catalytic performance could be due to that Ce(IV)/Ce(III) species act as the active sites to realize the polarization and hydrolysis of P-O bond while NC template works as the synergistic group to adsorb the substrate. Furthermore, a simple colorimetric assay is developed for the rapid and selective detection of paraoxon. Overall, this work not only develops a highly efficient phosphatases-like nanozyme via substrate synergetic strategy, but also opens an interesting avenue for the rapid detection of organophosphorus pesticides.


[A reinforcement of acupuncture on the cardiac effect of dobatamine: exhibition of acupoint's functional specificity].
To investigate the functional specificity of acupoint by means of acupoint injection of Dobutamine Hydrochloride (DH). Male SD rats were randomized into normal control (NC), EA-Neiguan (PC6) + acupoint injection (AI, EA-PC 6 + AI), EA-Zusanli (ST 36) + AI (EA-ST 36 + AI), and EA-intramuscular injection site (IMIS) + intramuscular injection (EA-IMIS+ IMI) groups,with 8 rats being in each group. EA (2 Hz/15 Hz, 3 mA) was applied to bilateral "Neiguan" (PC 6), "Zusanli "(ST 36) and muscular-injection site for 10 min. DH (a beta1-adrenoceptor agonist) solution (100 microg/kg) was injected intramuscularly into the gluteus maximus after termination of EA intervention. The left ventricular systolic pressure (LVSP), heart rate (HR) and + dp/dt max were recorded before and 2, 5, 15 and 30 min after injection of DH. The values of LVSP, HR and + dp/dt max in EA-PC 6 + AI group were significantly higher than those in NC, EA-ST 36 + AI, and EA-IMIS + IMI groups (P < 0.01) 2 and 5 minutes after EA plus acupoint injection of DH. No significant differences were found between EA-ST 36 + AI and EA-IMIS+ IMI groups in LVSP, HR and +dp/dt max (P > 0.05). After injection of DH for 30 minutes, the values of LVSP, HR and + dp/dt max in EA-PC 6 + AI group were still significantly higher than those in NC group (P < 0.01). EA-PC 6+ AI DH is significantly superior to EA-ST 36 + AI DH and EA-IMIS+ IMI DH in producing a stronger cardiac excitatory effect and a longer post-effect, showing a relative specificity of the acupoint in upregulating cardiac functional activities.


[Rapid identification and quantitation of barbiturates in plasma using solid-phase extraction combined with GC-FID and GC-MS method].
A rapid screening method for the quantitation and identification of 7 barbiturates in plasma is presented. The method employs solid-phase extraction at pH 3 using X-5 resin as absorbent. Identification of each barbiturate is achieved by retention time and GC-MS. Detection threshold (0.3-0.5 micrograms.ml-1 in a 0.5 ml plasma sample and 1 microliter injection volume), precision (RSD 3.46-6.41%), and linearity (r > 0.99) were satisfactory for blood level monitoring and clinical toxicological applications.


Quantification and significance of fluid shear stress field in biaxial cell stretching device.
A widely used commercially available system for the investigation of mechanosensitivity applies a biaxial strain field to cells cultured on a compliant silicone substrate membrane stretched over a central post. As well as intended substrate strain, this device also provides a fluid flow environment for the cultured cells. In order to interpret the relevance of experiments using this device to the in vivo and clinical situation, it is essential to characterise both substrate and fluid environments. While previous work has detailed the substrate strain, the fluid shear stresses, to which bone cells are known to be sensitive, are unknown. Therefore, a fluid structure interaction computational fluid dynamics model was constructed, incorporating a finite element technique capable of capturing the contact between the post and the silicone substrate membrane, to the underside of which the pump control pressure was applied. Flow verification experiments using 10-μm-diameter fluorescent microspheres were carried out. Fluid shear stress increased approximately linearly with radius along the on-post substrate membrane, with peak values located close to the post edge. Changes in stimulation frequency and culture medium viscosity effected proportional changes in the magnitude of the fluid shear stress (peak fluid shear stresses varied in the range 0.09-3.5 Pa), with minor effects on temporal and spatial distribution. Good agreement was obtained between predicted and measured radial flow patterns. These results suggest a reinterpretation of previous data obtained using this device to include the potential for a strong role of fluid shear stress in mechanosensitivity.


Assessment of daily profiles of ADHD and ODD symptoms, and symptomatology related to ADHD medication, by parent and teacher ratings.
DAYAS is a new two-part rating scale that assesses: (1) ADHD and ODD symptoms (externalising symptom ratings) and (2) symptomatology potentially related to ADHD medication (potentially medication-related symptoms) in real-world settings at different time periods throughout a normal school day. Data from a proof-of-concept study and two observational trials (Medikinet(®) retard [methylphenidate] and the Equasym XL(®) [methylphenidate] OBSEER study) evaluated: (1) validity of weekly externalising symptom ratings using DAYAS, in place of daily ratings; (2) reliability and internal consistency of DAYAS ratings for externalising symptoms and potentially medication-related symptoms; and (3) convergent and divergent validity of the externalising symptom ratings with existing validated scales. From the proof-of-concept study, daily scores by period of day and during the whole day correlated strongly with equivalent weekly scores (r = 0.83-0.92). Internal consistency of externalising symptom rating scales calculated from pooled data were acceptable or good by period of day (Cronbach's alpha = 0.68-0.90) and very high for whole day scores (Cronbach's alpha = 0.88-0.95). Internal consistency of the rating scale for potentially medication-related symptoms was also good for both teacher and parent ratings. From OBSEER data, correlations between FBB-ADHD total symptom scores and ratings on both parent and teacher versions of DAYAS were high (r = 0.73 and r = 0.84, respectively). Correlations between DAYAS and SDQ were highest for the SDQ subscales hyperactivity and conduct problems and substantially lower for pro-social behaviour, peers and emotional problems. The DAYAS rating scale had good internal consistency, and DAYAS scores correlated well with existing validated scales and the SDQ subscales hyperactivity and conduct problems. Weekly DAYAS scores (whole day and by period of day) could be considered a suitable replacement for daily assessment scores.


In vivo evaluation of the reliability and validity of three digital occlusion analysis methods.
The reliability and validity of three digital occlusion analysis methods was evaluated in vivo. The three method evalueated were:scanning of articulating paper marks (SA), dental prescale occlusal analysis system (DP) and a virtual occlusion constructed method (VO). A conventional silicone transmission method (ST) was used as the standard for comparison. Each of the 20 enroled human subjects was tested with the four methods. Retest of each method was performed at 2-week intervals. Occlusal contact area (OCA) and occlusal contact numbers (OCN) were calculated for analyses. For reliability evaluation, intraclass correlation coefficients (ICC) of the OCA and OCN values obtained from each method were compared. For validity evaluation, Pearson correlations coefficients, paired t-tests, regression analysis and Bland-Altman analysis were examined. The ICC values of OCA and OCN were in the order: ST>SA>DP>VO. The highest OCA and OCN values were found ST while the lowest values were obtained from DP. Paired t-test identified a significant difference when OCA values obtained from the three digital methods were compared with ST, and between the OCN values of DP and ST. Pearson correlation showed high coefficients between ST and three digital methods (0.583-0.885 for OCA; 0.779-0.836 for OCN). A significant linear correlation was found between the results from ST and those from SA or VO. Bland-Altman analysis showed good agreement between OCN values of SA and ST, and between those of VO and ST. The three digital occlusal analysis methods showed good reliability and validity for in vivo clinical application. The three digital occlusion analysis systems examined demonstrate good potential in in vivo quantitative analysis, with good reliability and validity. The use of these analytical methods should facilitate digital workflow in clinical practice.


Micro-tensile bond strength of three luting resins to human regional dentin.
To evaluate the micro-tensile bonding strength (muTBS) of three luting resins to human regional dentin. Dentin disks from non-carious third molars were prepared from different regions (s, superficial dentin; d, deep dentin; c, cervical dentin), and divided into groups based on anatomical locations and luting resins (Super-Bond C&B: SB; Panavia F 2.0: PF; RelyX Unicem: RU): SB-s, SB-d, SB-c; PF-s, PF-d, PF-c; RU-s, RU-d, RU-c. Luting resins were used according to the manufacturers' instructions, to bond 1-mm-diameter PMMA or composite rods to the exposed dentin specimens under a load of 7.5 N, in the self-curing mode. After storage for 1 or 3 days, muTBS was tested at a cross-head speed of 1mm/min. Data were analyzed with ANOVA and Fisher's PLSD test. The bonding interface and fractography analyses were performed with SEM and TEM. ANOVA results showed that muTBS to superficial dentin was significantly higher than to deep or cervical dentin for all three luting resins. SB-s and PF-s, with the highest muTBS, failed primarily cohesively in luting resin. muTBS of SB-d and SB-c were significantly higher than those of PF and RU. RU, with the lowest regional muTBS, failed mostly within demineralized dentin. SEM and TEM showed that adhesive failures in SB and PF occurred at the top of the hybrid layer (HL), but no obvious HL was observed in RU. Luting resins with different chemical formulations and applications yield significantly different bond strengths to different regions in human dentin.


A particularly labile Asp-Pro bond in the green mamba muscarinic toxin MTX2. Effect of protein conformation on the rate of cleavage.
The single Asp53-Pro54 bond of the MTX2 toxin from the mamba snake Dendroaspis angusticeps is rapidly and efficiently cleaved in acidic solution (pH 1.5-2.5) at 45 degrees C. Unfolding of the toxin slows down the cleavage reaction by several times. Modelling studies indicate that the native toxin conformation can catalyse the Asp53-Pro54 bond cleavage. The implications of this study are: (i) cleavage of Asp-Pro bond for sequence determination may occur better in absence than in presence of denaturant, (ii) mild acid conditions, commonly used in NMR structure determinations, may irreversibly affect the structural integrity of Asp-Pro containing peptides and proteins.


Radio-gas chromatography on wide-bore capillary columns equipped with a synchronized accumulating radioisotope detector.
A gas chromatographic system with wide-bore capillary columns and synchronized accumulating radioisotope detector (SARD) was developed. A direct injection method and constant-flow regulation were applied. The performance of wide-bore capillary columns was good and the correspondence of the resolution obtained with SARD and that with mass detection was excellent. It was proved that the apparatus could detect of the order of 1 pg of 3H-labelled substances (3.7 TBq/mmol) and compete in terms of sensitivity with gas chromatography-mass spectrometry.


The effect of intravenous salbutamol upon plasma and urinary potassium during premature labour.
Plasma potassium and urinary potassium excretion were measured in eight patients in premature labour treated with salbutamol, and in ten patients at full term in spontaneous labour. There was a significant fall in plasma potassium concentration following salbutamol infusion, but no change during labour in the control groups. Urinary potassium excretion was similar in both groups.


Mechanisms of injury, patterns of extravasation and management of extraperitoneal bladder rupture due to blunt trauma.
During the last 7 years we have managed more than 100 cases of bladder rupture, the majority owing to blunt trauma. Of these ruptures 62 were extraperitoneal, including 59 (95 per cent) with associated pelvic fractures. Twelve patients had an associated urethral injury and 5 had a concomitant intraperitoneal bladder rupture. Complex injuries with extravasation outside the confines of the perivesical space were noted in 42 per cent of the patients. Extravasation extended into the scrotum, thigh, anterior abdominal wall and penis, and through the obturator foramen. The 41 patients who were treated with catheter drainage alone did well.


Insight into the Wetting Property of a Nanofiber Membrane by the Geometrical Potential.
There are many patents on design of a material surface with special wetting property, however, theoretical methods are lacked. The wetting property of a nanofiber member has attracted much attention. A material with different sizes or with different structures possesses different wetting properties. No theory can explain the phenomenon. The contact angle, fiber fineness, pore size and layer of the nanofiber membrane were tested. The contact angles were measured for membranes with different thicknesses. The geometrical potential is used to explain the experimental phenomenon. The wetting property of a nanofiber membrane mainly depends on fiber diameter and thickness. Wetting property of a PVA nanofiber membrane depends upon not only the hydrophilic groups, but also the geometrical structure of its surface, the latter prevails when the porous size of the membrane tends to a nanoscale, and the wetting property can be inverted from hydrophilicity to hydrophobicity.


Effect of neuraminidase treatment on serum reactivity to autologous leukemic blast cells.
The sera of 35 patients with acute lymphoblastic leukemia (ALL) and acute non-lymphoblastic leukemia (ANLL) were tested for reactivity against cell surface antigens of autologous leukemic blast cells by protein A assay (PA), immune adherence assay (IA), and anti-C3 mixed hemadsorption assay (C3-MHA). Autologous serum reactivity was detectable by PA in four cases and by IA and C3-MHA in about half the patients. Autologous serum reactivity occurred more often in ALL than in ANLL. Absorption studies revealed that in one patient only the autologous reactivity was directed against a restricted antigen, which could be detected only on the individual T-ALL blast cells. All other autologous antibodies detected unspecific antigens. Neuraminidase treatment had two effects: first, it increased antibody attachment to antigens which are also present on untreated cells; secondly, after neuraminidase treatment an antigen was detectable on the cell surface which could also be demonstrated on neuraminidase-treated non-leukemic cells (e.g., erythrocytes). Neither of these two effects of neuraminidase treatment seems to be tumor-specific. Possible therapeutic effects of neuraminidase are probably caused by unspecific adjuvant effects of the enzyme.


Iodine Nutrition During Pregnancy: Past, Present, and Future.
Iodine is a trace element that is important for the synthesis of thyroid hormones. During pregnancy, iodine requirements are increased by approximately 50% because of physiological changes. Adequate iodine status in pregnancy is crucial for maternal health and fetal growth. The World Health Organization (WHO) recommends a daily intake of 250 μg iodine for pregnant women to maintain adequate iodine status. Severe iodine deficiency during pregnancy can result in a series of detrimental effects on maternal and fetal health including hypothyroidism, goiter, stillbirth, abortion, increased neonatal mortality, neurological damage, and intellectual impairment. Correction of severe iodine deficiency can reduce the risk of adverse impacts. However, the influences of mild-to-moderate maternal iodine deficiency on fetal neural development and cognitive function are less clear. The safety and efficacy of iodine supplementation in mildly-to-moderately iodine-deficient women also remain uncertain. In addition, excess iodine during pregnancy carries a risk of adverse effects, and the recommended safe upper limits of iodine intake are controversial. Effective iodine supplementation should be implemented, and routine monitoring is necessary to guarantee adequate iodine status.


Uncaging Alcohols Using UV or Visible Light Photoinduced Electron Transfer to 9-Phenyl-9-tritylone Ethers.
The clean and efficient photorelease of primary and secondary alcohols is reported from the deprotection of a new photoremovable protecting group, the 9-phenyltritylone (PTO) group. Deprotection is initiated by 350 nm excitation of the PTO chromophore in the presence of triethylamine or using 447 nm light in the presence of a visible light absorbing photocatalyst and triethylamine. Laser flash photolysis results are reported in support of a proposed deprotection mechanism for the release of alcohols on a ca. 20 μs time scale.


Asymmetric functionalization of gold nanoparticles with oligonucleotides.
Gold nanoparticles (AuNPs) were anisotropically functionalized with two different oligonucleotide sequences using magnetic microparticles as geometric restriction templates for site-selective enzymatic extension of particle-bound oligonucleotides. The divalent linking capability of the resulting AuNPs allowed for the design and programmable assembly of discrete nanoparticle heterostructures.


Automated cell-type classification combining dilated convolutional neural networks with label-free acoustic sensing.
This study aimed to automatically classify live cells based on their cell type by analyzing the patterns of backscattered signals of cells with minimal effect on normal cell physiology and activity. Our previous studies have demonstrated that label-free acoustic sensing using high-frequency ultrasound at a high pulse repetition frequency (PRF) can capture and analyze a single object from a heterogeneous sample. However, eliminating possible errors in the manual setting and time-consuming processes when postprocessing integrated backscattering (IB) coefficients of backscattered signals is crucial. In this study, an automated cell-type classification system that combines a label-free acoustic sensing technique with deep learning-empowered artificial intelligence models is proposed. We applied an one-dimensional (1D) convolutional autoencoder to denoise the signals and conducted data augmentation based on Gaussian noise injection to enhance the robustness of the proposed classification system to noise. Subsequently, denoised backscattered signals were classified into specific cell types using convolutional neural network (CNN) models for three types of signal data representations, including 1D CNN models for waveform and frequency spectrum analysis and two-dimensional (2D) CNN models for spectrogram analysis. We evaluated the proposed system by classifying two types of cells (e.g., RBC and PNT1A) and two types of polystyrene microspheres by analyzing their backscattered signal patterns. We attempted to discover cell physical properties reflected on backscattered signals by controlling experimental variables, such as diameter and structure material. We further evaluated the effectiveness of the neural network models and efficacy of data representations by comparing their accuracy with that of baseline methods. Therefore, the proposed system can be used to classify reliably and precisely several cell types with different intrinsic physical properties for personalized cancer medicine development.


HIV and neoplasms: What do we know so far?
The human immunodeficiency virus (HIV) pandemic remains an important issue. In 2020, approximately 37.7 million people were living with the disease and there were more than 680 thousand deaths due to complications linked to the disease. Despite these exorbitant numbers, the introduction of highly active antiretroviral therapy has marked a new era, changing the epidemiological profile of the infection and related pathologies, including neoplasms. We performed a literature review to assess the role of neoplasms in patients with HIV after the introduction of antiretroviral therapy. A literature review was conducted based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) method, searching the MEDLINE, LILACS, and COCHRANE databases for articles published from 2010 onwards. Using specific key terms, 1,341 articles were identified; two were duplicates, 107 were selected for full-text evaluation, and 20 were included in the meta-analysis. The selected studies included 2,605,869 patients. Fifteen of the 20 articles indicated a reduction in the global incidence of AIDS-defining neoplasms and 12 indicated an overall increase in non-AIDS-defining cancers after the introduction of antiretrovirals. This growth trend could be explained by a range of factors including the aging population with HIV, risky behaviors, and coinfection with oncogenic viruses. There was a decreasing trend in the incidence of AIDS-defining neoplasms and increasing trend in non-AIDS-defining neoplasms. However, the carcinogenic effect of antiretrovirals could not be confirmed. In addition, studies focusing on the oncogenic role of HIV and screening for neoplasms in individuals with HIV are required.


Quinones as Strecker degradation reagents in wine oxidation processes.
The Strecker aldehydes formed during the reaction between α-amino acids (phenylalanine or methionine) and either gallic acid, caffeic acid or (+)-catechin ortho-quinones were evaluated in wine-model systems. It was demonstrated that phenylacetaldehyde was formed by quinone intermediates at wine pH. The highest amounts of phenylacetaldehyde during the 10days of experiment (69±5µg/L/day; 7x>Control) were obtained from (+) catechin, followed by gallic acid (61±4µg/L/day; 6x>Control) and caffeic acid (41±4µg/L/day; 4x>Control). The intermediate structures delivered from the reaction of ortho-quinones with α-amino acids were demonstrated by MSn.


Reduction of catheter-associated bloodstream infections in pediatric patients: experimentation and reality.
Few data exist on successes at reducing pediatric catheter-associated bloodstream infections (CA-BSI). The objective was to eradicate CA-BSI with a multifaceted pediatric-relevant intervention proven effective in adult patients. Prospective cohort of pediatric intensive care (PICU) patients with historical controls. Multidisciplinary PICU. PICU patients with intervention targeting PICU providers. Multifaceted intervention involving preintervention staff surveys, provider educational program, creation of central catheter procedure cart, guideline-supported central catheter insertion checklist, nursing staff empowerment to stop procedures that breached guidelines, and real-time data feedback to PICU leadership. We measured rate of CA-BSI per 1000 catheter days from August 2001 through September 2006. Reliable use of evidence-based best practices for insertion of central catheters in our PICU was associated with a statistically and clinically significant decrease in our CA-BSI rate for 24 months postintervention (p < .05). During a portion of this postintervention period, we experienced a dramatic increase in our CA-BSI rate that was ultimately found to be due to the introduction of a new positive displacement mechanical valve intravenous port in April 2004. After removal of this positive displacement mechanical valve, our CA-BSI rate dropped from 5.2 +/- 4.5 CA-BSI per 1000 central catheter days to a rate of 3.0 +/- 1.9 CA-BSI per 1000 central catheter days. Chart review of postintervention CA-BSI cases revealed that these patients acquired CA-BSI weeks after both PICU admission and after insertion of the most recent central catheter. Our data show that improving practices for insertion of central catheters leads to a reduction of CA-BSI among pediatric patients but not elimination of CA-BSI. More research is needed to identify best practices for maintenance of central catheters for children. In addition, our experience shows that even despite good interventions to control CA-BSI, institutions must remain vigilant to factors such as new technology with apparent advantages but short track records of use.


Characteristics of The Cancer Genome Atlas cases relative to U.S. general population cancer cases.
Despite anecdotal reports of differences in clinical and demographic characteristics of The Cancer Genome Atlas (TCGA) relative to general population cancer cases, differences have not been systematically evaluated. Data from 11,160 cases with 33 cancer types were ascertained from TCGA data portal. Corresponding data from the Surveillance, Epidemiology, and End Results (SEER) 18 and North American Association of Central Cancer Registries databases were obtained. Differences in characteristics were compared using Student's t, Chi-square, and Fisher's exact tests. Differences in mean survival months were assessed using restricted mean survival time analysis and generalised linear model. TCGA cases were 3.9 years (95% CI 1.7-6.2) younger on average than SEER cases, with a significantly younger mean age for 20/33 cancer types. Although most cancer types had a similar sex distribution, race and stage at diagnosis distributions were disproportional for 13/18 and 25/26 assessed cancer types, respectively. Using 12 months as an end point, the observed mean survival months were longer for 27 of 33 TCGA cancer types. Differences exist in the characteristics of TCGA vs. general population cancer cases. Our study highlights population subgroups where increased sample collection is warranted to increase the applicability of cancer genomic research results to all individuals.


Epitopes of bovine leukemia virus glycoprotein gp51 recognized by sera of infected cattle and sheep.
Sera of BLV-infected cattle and sheep are tested for their reactivity with different gp51 subregions by competition with radiolabeled monoclonal antibodies directed against 8 different gp51 epitopes. Sheep antisera are found to be very polyvalent, since they are able to displace the fixation of any of the mouse monoclonal antibodies to gp51. Bovine antisera do not display significant competition with monoclonal antibodies direct against 5 out of 8 gp51 epitopes. The bovine antibody response to gp51 is focused to a limited subregion of this molecule, bearing 3 epitopes (F, G and H) recognized by antibodies with virus-neutralizing activity. The differential reactivity of cattle and sheep antisera to BLV gp51 is discussed in relation to the pathology of BLV infection in these two species.


An unusual ring contraction in the formation of N-nitrosohexamethyleneimine and N-nitrosopiperidine from tolazamide.
The previously reported reaction of tolazamide with nitrite, under physiological conditions, to form N-nitrosohexamethyleneimine and surprisingly, N-nitrosopiperidine was confirmed. By using the six-membered ring analogue of tolazamide, 1-(piperidyl)-3-(p-tolylsulfonyl)urea, which yields the corresponding N-nitrosopiperidine and N-nitrosopyrrolidine, the present study shows that an unusual ring contraction occurs, excising the carbon alpha to the nitrogen.


Polymyxin-based fluorescent probes to combat Gram-negative antimicrobial resistance.
Reliable diagnostic approaches especially those targeting critical Gram-negative bacteria are urgently needed for the prevention of antimicrobial resistance. Polymyxin B (PMB) which specifically targets the outer membrane of Gram-negative bacteria is the last-line antibiotic against life-threatening multidrug-resistant Gram-negative bacteria. However, increasing number of studies have reported the spread of PMB-resistant strains. With the aim to specifically detect Gram-negative bacteria and potentially reduce the irrational use of antibiotics, we herein rationally designed two Gram-negative bacteria specific fluorescent probes based on our previous activity-toxicity optimization of PMB. The in vitro probe PMS-Dns showed fast and selective labeling of Gram-negative pathogens in complex biological cultures. Subsequently, we constructed the caged in vivo fluorescent probe PMS-Cy-NO2 by conjugating bacterial nitroreductase (NTR)-activatable positive charged hydrophobic near-infrared (NIR) fluorophore with polymyxin scaffold. Significantly, PMS-Cy-NO2 exhibited excellent Gram-negative bacterial detection capability with the differentiation between Gram-positive and Gram-negative in a mouse skin infection model.


A description of Apocarchesium rosettum n. gen., n. sp. and a redescription of Ophrydium eichornii Ehrenberg, 1838, two freshwater peritrichous ciliates from Japan.
This paper includes the proposal of a new genus for a new species of peritrichous ciliate, Apocarchesium rosettum n. gen., n. sp., as well as the first description by modern techniques of another peritrich, Ophrydium eichornii Ehrenberg, 1838. The genus Apocarchesium is separated from the related genus Carchesium by the appearance of the stalk and the arrangement of zooids, and diagnosed as follows: colonial vorticellid, with all zooids attached in rosette fashion to the tip of their common stalk, which is unbranched and contracts spirally; pellicle with parallel silverlines. The morphology, infraciliature, and silverline system of both species were investigated by observation in vivo and silver-staining methods.


Scaling of quantum interference from single molecules to molecular cages and their monolayers.
The discovery of quantum interference (QI) is widely considered as an important advance in molecular electronics since it provides unique opportunities for achieving single-molecule devices with unprecedented performance. Although some pioneering studies suggested the presence of spin qubit coherence and QI in collective systems such as thin films, it remains unclear whether the QI can be transferred step-by-step from single molecules to different length scales, which hinders the application of QI in fabricating active molecular devices. Here, we found that QI can be transferred from a single molecule to their assemblies. We synthesized and investigated the charge transport through the molecular cages using 1,3-dipyridylbenzene (DPB) as a ligand block with a destructive quantum interference (DQI) effect and 2,5-dipyridylfuran (DPF) as a control building block with a constructive quantum interference (CQI) effect using both single-molecule break junction and large area junction techniques. Combined experiments and calculations revealed that both DQI and CQI had been transferred from the ligand blocks to the molecular cages and the monolayer thin film of the cages. Our work introduced QI effects from a ligand to the molecular cage comprising 732 atoms and even their monolayers, suggesting that the quantum interference could be scaled up within the phase-coherent distance.


Brønsted Acid Catalysis in Visible-Light-Induced [2+2] Photocycloaddition Reactions of Enone Dithianes.
1,3-Dithiane-protected enones (enone dithianes) were found to undergo an intramolecular [2+2] photocycloaddition under visible-light irradiation (λ=405 nm) in the presence of a Brønsted acid (7.5-10 mol %). Key to the success of the reaction is presumably the formation of colored thionium ions, which are intermediates of the catalytic cycle. Cyclobutanes were thus obtained in very good yields (78-90 %). It is also shown that the dithiane moiety can be reductively or oxidatively removed without affecting the photochemically constructed ring skeleton.


Dural venous sinus stenting for idiopathic intracranial hypertension: An updated review.
Dural venous sinus stenting (DVSS) is an accepted treatment option in selected patients with medically refractory idiopathic intracranial hypertension and obstructive venous outflow physiology prior to cerebrospinal flow diversion (CSFD) surgery. There are no randomized controlled studies focusing on outcomes and complication rates for dural venous sinus stenting. We present the largest comprehensive meta-analysis on DVSS for idiopathic intracranial hypertension (IIH) focusing on success rates, complications, and re-stenting rates to date. We also present a simplified approach to direct retrograde internal jugular vein (IJ) access for DVSS that allows for expedited procedures. We performed a retrospective electronic PubMed query of all peer-reviewed articles in the last 15 years between 2003 to 2018. We included all patients who underwent dural venous sinus stenting for a medically refractive IIH and excluded articles without sufficient data on outcomes, complication rates and re-stenting rates. We also evaluated and compared outcomes in patients undergoing direct retrograde IJ access DVSS to traditional transfemoral vein access. A total of 29 papers and 410 patients who underwent DVSS met criteria for inclusion. DVSS was associated with high technical success [99.5%], low rates of repeated procedure [10%], and low major complication rates [1.5%]. Our retrospective comprehensive review of DVSS for medically refractory IIH suggests that stenting in appropriately chosen patients is associated with low complication rates, high technical success, and low repeat procedure rates.


Thoracic spine fracture associated with an extradural lipoma: Case report and systematic review of the literature.
Isolated extradural lipoma (IEL), not associated to spinal dysraphisms, is a rare condition. Frequently IEL was confused with much more frequent diffuse lipomatosis. The lesion can be completely asymptomatic and occasionally diagnosed with magnetic resonance (MR) imaging. This paper describes a case of a patient with an axial compression fracture of the thoracic spine associated with an extradural lipoma. We also performed a systematic review of the pertinent literature in order to retrieve the key information regarding: the diagnosis, the clinical features and the treatment.


Current status of bariatric surgery in Japan and effectiveness in obesity and diabetes.
The rate of obesity in Japan, defined as having a body mass index (BMI) of 25 kg/m(2) or greater, is reportedly at 24 %, a lower level of severe obesity than in the EU and US. However, the incidence of obesity-related health problems is reportedly higher among Asians. Laparoscopic sleeve gastrectomy (LSG) is the most frequently performed bariatric surgery in Japan and accounted for 54 % of such surgeries in 2011; procedures such as laparoscopic adjustable gastric banding and laparoscopic Roux-en-Y gastric bypass (LRYGB), practiced frequently worldwide, were uncommon. Possible reasons include concern over delayed postoperative discovery of gastric cancer in LRYGB, and rapid adoption of the comparatively simple LSG procedure. In type 2 diabetes mellitus (T2DM) patients, where continued pursuit of medical treatment is difficult and a potential exists for future deterioration of diabetes-complicated diseases, the criterion for surgical indication in the EU and US is a BMI of 30-35 kg/m(2), with priority given to BMI >35 kg/m(2). For Asian patients, the recommendation is to lower this indication criterion by 2.5 kg/m(2). Efficacy of metabolic surgery is anticipated particularly among T2DM patients with obesity complication, a short history of insulin treatment, and intact insulin secreting ability, and in these cases bariatric surgery should be contemplated.


Evaluation of a urinary test as a diagnostic tool of a nonprogressive pregnancy.
To evaluate the performance of a one-step test detecting intact hCG and free β-hCG isoforms in the urine of pregnant women to diagnose an abnormal pregnancy. Prospective study. Emergency gynecology departments in teaching hospitals. Five hundred twenty-six patients were enrolled, 272 who were not pregnant and 254 who were pregnant. Semiquantitative determination of intact urinary hCG of supposedly not pregnant and pregnant women with vaginal bleeding and/or vaginal pain between 5 and 8 weeks of amenorrhea. The sensitivity and specificity of the urine test for diagnosing nonpregnancy were, respectively, 100% (252/252) and 100% (272/272). The sensitivity and specificity of the urine test for diagnosing ectopic pregnancy (EP) were, respectively, 97% (32/33) and 83% (142/171). The negative predictive value is 99.3% (142/143). The sensitivity and specificity or the urine test for diagnosing miscarriage were, respectively, 89.6% (43/48) and 83% (142/171). The negative predictive value is 96.6% (142/147). Abnormal pregnancy, such as an EP or a miscarriage, can be rapidly detected with the one-step test for intact hCG and free β-hCG isoforms. If ultrasound cannot confirm the localization and/or evolution of a pregnancy, using this test reduces medical supervision and repeated quantification of hCG.


In silico screening of potential β-secretase (BACE1) inhibitors from VIETHERB database.
For the purpose of discovering potential inhibitors of β-amyloid (BACE1), which is a crucial element in Alzheimer's disease (AD) pathogenesis, an in silico study of naturally occurring compounds was performed using precise computational approaches. Autodock4 package was preliminary used to predict the binding affinities to BACE1 of more than four thousand compounds presented in the Vietnamese plants (VIETHERB) database. Based on docking results, twenty top-lead compounds having the largest docking energy to BACE1 were rigorously examined using steered molecular dynamics (SMD) simulations. Interestingly, SMD results found that the binding affinity values of three compounds, including myricetin 3-O-(3''-galloylrhamnopyranoside), quercetin 3-O-neohesperidoside, and hydroxysafflor yellow A, are remarkably higher than that of the well-known BACE1 inhibitor, 23I, and these compounds can thus be considered the promising candidates for inhibitors of BACE1.


Method to Create Multiple Primary Malignant Neoplasms with Stimulation of Tumor Growth under Conditions of Primary Immunodeficiency in Experiment.
The experimental model of synchronous multiple primary malignant tumors (MPMT) was created. B16/F10 melanoma (0.5 ml of suspension diluted 1:20 in saline) and sarcoma 45 (0.5 million tumor cells in 0.5 ml saline) were simultaneously subcutaneously inoculated to male BALB/c nude mice. In the model of synchronous MPMT, the tumors appeared faster by 2.4 times and had greater volumes: melanoma by 2.2 times and sarcoma by 3.2 times; melanoma metastasized into sarcoma in 71.4% cases; the survival of mice with MPMT was lower. The altered dynamics of malignant growth in the MPMT model is based on the mutual influence of tumors, which results in the exchange of "structural information".


[Effect of lipopolysaccharide on the stromal cell-derived factor-1 expression in human stem cells from apical papilla].
To investigate the expression of stromal cell-derived factor-1 (SDF-1) in human stem cells from apical papilla (SCAP), and to evaluate the effect of lipopolysaccharide (LPS) on SDF-1 expression by SCAP. SCAP were isolated from dental papilla of human immature third molars. The expression of SDF-1 was evaluated by reverse transcription-PCR (RT-PCR). After SCAP being exposed to different concentrations (0.1, 1.0, 10 mg/L) of LPS for 24 and 48 h, the effect of LPS on cell proliferation and gene expression of SDF-1 was investigated by cell counting kit-8 and real-time PCR respectively, while cells without LPS stimulation were considered as negative control. LPS had no significant effect on SCAP proliferation until day 7. RT-PCR assays demonstrated that SCAP expressed SDF-1 mRNA. Different concentrations of LPS significantly promoted the SDF-1 expression in SCAP after 24 h (F = 12.102, P = 0.002) and 48 h (F = 39.054, P < 0.001) exposure, with relative gene expression ratio (experimental/control) increased to 1.4 ± 0.1, 2.2 ± 0.4, 2.3 ± 0.5 in 24 h group and 2.1 ± 0.4, 3.4 ± 0.3, 3.8 ± 0.5 in 48 h group. Isolated SCAP in cultures have the expression of SDF-1 mRNA. LPS can significantly promote the expression of SDF-1 in SCAP.


Stereotactic Body radiotherapy and pedicLE screw fixatioN During one hospital visit for patients with symptomatic unstable spinal metastases: a randomized trial (BLEND RCT) using the Trials within Cohorts (TwiCs) design.
Spinal metastases can lead to unremitting pain and neurological deficits, which substantially impair daily functioning and quality of life. Patients with unstable spinal metastases receive surgical stabilization followed by palliative radiotherapy as soon as wound healing allows. The time between surgery and radiotherapy delays improvement of mobility, radiotherapy-induced pain relief, local tumor control, and restart of systemic oncological therapy. Stereotactic body radiotherapy (SBRT) enables delivery of preoperative high-dose radiotherapy while dose-sparing the surgical field, allowing stabilizing surgery within only hours. Patients may experience earlier recovery of mobility, regression of pain, and return to systemic oncological therapy. The BLEND RCT evaluates the effectiveness of SBRT followed by surgery within 24 h for the treatment of symptomatic, unstable spinal metastases. This phase III randomized controlled trial is embedded within the PRospective Evaluation of interventional StudiEs on boNe meTastases (PRESENT) cohort. Patients with symptomatic, unstable spinal metastases requiring stabilizing surgery and radiotherapy will be randomized (1:1). The intervention group (n = 50) will be offered same-day SBRT and surgery, which they can accept or refuse. According to the Trial within Cohorts (TwiCs) design, the control group (n = 50) will not be informed and receive standard treatment (surgery followed by conventional radiotherapy after 1-2 weeks when wound healing allows). Baseline characteristics and outcome measures will be captured within PRESENT. The primary outcome is physical functioning (EORTC-QLQ-C15-PAL) 4 weeks after start of treatment. Secondary endpoints include pain response, time until return to systemic oncological therapy, quality of life, local tumor control, and adverse events up to 3 months post-treatment. The BLEND RCT evaluates the effect of same-day SBRT and stabilizing surgery for the treatment of symptomatic, unstable spinal metastases compared with standard of care. We expect better functional outcomes, faster pain relief, and continuation of systemic oncological therapy. The TwiCs design enables efficient recruitment within an ongoing cohort, as well as prevention of disappointment bias and drop-out as control patients will not be informed about the trial. ClinicalTrials.gov NCT05575323. Registered on October 11, 2022.


Familial communicating syringomyelia.
Calssical cervical syringomyelia was found in 3 members of one family. All 3 underwent air myelogram, and a Chiari malformation type I and postural collapse of the spinal cord was found in each case. An affected 7-year-old boy was discovered after a clinical and radiological survey of 8 first-degree relatives on the basis of mild scoliosis, pyramidal tract signs in the lower limbs and enlarged sagittal diameter of the cervical canal. One other member had basilar impression of the skull but no neurological abnormalities. No positive correlation was found between either the size of the cystic cord enlargement or descent of the ectopic tonsils with the duration or severity of the neurological findings. Suboccipital decompressive craniotomy and upper cervical laminectomy in one case was followed by improvement in strength and sensation 1 year later. Progression in familial syringomyelia appears to occur through a mechanism identical to that in the sporadic form and surgery is therefore also indicated. In affected families, routine survey of close relatives for abnormal neurological signs, and radiological evidence of scoliotic deformity of the spine, enlarged cervical canal and bone abnormalities at the craniovertebral junction may prove valuable for early detection. A dominantly inherited, genetically determined malformation seems to be the probable mechanism of inheritance in this family.


Using a spatial point process framework to characterize lung computed tomography scans.
Pulmonary emphysema is a destructive disease of the lungs that is currently diagnosed via visual assessment of lung Computed Tomography (CT) scans by a radiologist. Visual assessment can have poor inter-rater reliability, is time consuming, and requires access to trained assessors. Quantitative methods that reliably summarize the biologically relevant characteristics of an image are needed to improve the way lung diseases are characterized. The goal of this work was to show how spatial point process models can be used to create a set of radiologically derived quantitative lung biomarkers of emphysema. We formalized a general framework for applying spatial point processes to lung CT scans, and developed a Shot Noise Cox Process to quantify how radiologically based emphysematous tissue clusters into larger structures. Bayesian estimation of model parameters was done using spatial Birth-Death MCMC (BD-MCMC). In simulations, we showed the BD-MCMC estimation algorithm is able to accurately recover model parameters. In an application to real lung CT scans from the COPDGene cohort, we showed variability in the clustering characteristics of emphysematous tissue across disease subtypes that were based on visual assessments of the CT scans.