Skill acquisition and retention in automated external defibrillator (AED) use and CPR by lay responders: a prospective study.
This prospective study evaluated the acquisition and retention of skills in cardio-pulmonary resuscitation (CPR) and the use of the automated external defibrillator (AED) by lay volunteers involved in the Department of Health, England National Defibrillator Programme. One hundred and twelve trainees were tested immediately before and after and initial 4-h class; 76 were similarly reassessed at refresher training 6 months later. A standardised test scenario that required assessment of the casualty, CPR and the use of on AED was evaluated using recording manikin data and video recordings. Before training only 44% of subjects delivered a shock. Afterwards, all did so and the average delay to first shock was reduced by 57 s. All trainees placed the defibrillator electrodes in an "acceptable" position after training, but very few did so in the recommended "ideal" position. After refresher training 80% of subjects used the correct sequence for CPR and shock delivery, yet a third failed to perform adequate safety checks before all shocks. The trainees self-assessed AED competence score was 86 (scale 0-100) after the initial class and their confidence that they would act in a real emergency was rated at a similar level. Initial training improved performance of all CPR skills, although all except compression rate had deteriorated after 6 months. The proportion of subjects able to correctly perform most CPR skill was higher following refresher training that after the initial class. Although this course was judged to be effective in teaching delivery of counter-shocks, the need was identified for more emphasis on positioning of electrodes, pre-shock safety checks, airway opening, ventilation volume, checking for signs of a circulation, hand positioning, and depth and rate of chest compressions.


Human and rat hepatocyte toxicity and protein phosphatase 1 and 2A inhibitory activity of naturally occurring desmethyl-microcystins and nodularins.
Contamination of water, foods and food supplements by various genera of cyanobacteria is a serious health problem worldwide for humans and animals, largely due to the toxic effects of microcystins (MCs) and nodularin (NOD), a group of hepatotoxic cyclic peptides. The toxins occur in variable structures resulting in more than 90 different MCs and 8 different NODs, many of them not having been investigated for their toxic potency. Potent MCs such as MC-LR have been shown to elicit their hepatotoxic potency via inhibition of hepatic protein phosphatases (PP) 1 and 2A leading to over-phosphorylation of vital cellular proteins. This mechanism of action is also thought to be responsible for the long term tumor promoting action of certain MCs and NOD in the liver. Here, we report on the isolation of certain MCs and NOD as well as a number of their desmethylated derivatives from algae bloom. Subsequently, we determined the cytotoxicity of these compounds in isolated primary human and rat hepatocytes in culture. In parallel experiments, we analyzed the inhibitory potency of these congeners on PP1 and 2A using commercially available enzymes. We found in primary rat hepatocytes that MC-LR, -YR and NOD were cytotoxic, namely in the 10 to >50 nM range, while MC-RR was not. The desmethylated congeners of MC-LR, -YR, and NOD were equally or more-toxic as/than their fully methylated counterparts. In primary human hepatocytes we could show that MC-LR, NOD and the desmethylated variants [³Asp]MC-LR, [⁷Dha]MC-LR and [¹Asp]NOD were cytotoxic in the 20 to >600 nM range. Inhibition data with human, bovine and rabbit protein phosphatases 1 and 2A were roughly in accordance with the cytotoxicity findings in human and rat hepatocytes, i.e. desmethylation had no pronounced effects on the inhibitory potencies. Thus, a variety of naturally occurring desmethylated MC and NOD congeners have to be considered as being at least as toxic as the corresponding fully methylated derivatives.


Treatment Costs of Basal Insulin Regimens for Type 2 Diabetes Mellitus in France.
Our objectives were to describe the basal insulin treatment regimens most widely used in a real-world setting in France and to estimate the associated treatment costs in people with type 2 diabetes mellitus (T2DM). A cross-sectional observational study was conducted (November 2017-February 2018) among adult patients with T2DM requiring basal insulin therapy for their own use in a representative sample of pharmacies. Costs were compared between patients treated with three recently marketed insulins (glargine 300 U/ml [Gla-300], biosimilar glargine 100 U/ml [Gla-100] and a fixed-ratio combination of insulin degludec and liraglutide) and those treated with three established basal or intermediate insulins: branded glargine 100 U/ml, insulin detemir and neutral protamine Hagedorn insulin [NPH]). Overall, 1933 patients were analysed. Gla-300 accounted for 59.9% of novel basal insulin prescriptions, and branded Gla-100 accounted for 67.9% of established insulin prescriptions. Recent insulins were more frequently associated with glucagon-like peptide-1 (GLP-1) analogues. Results confirmed a lower rate of severe hypoglycaemia with Gla-300 than with Gla-100. On average, weekly total costs of treatment with all basal insulins were not significantly different, except with detemir, where they were higher. New basal insulins are expected to be integrated into clinical practice. This analysis shows that their use does not impact upon the management cost of insulin therapy in people with T2DM.


Simple cyst of the rete testis.
We report a case of a simple cyst in the upper pole and connected to the mediastinum testis at the rete testis. The cyst appeared to arise from a dilated rete duct, and it was spherical, smooth-walled and filled with clear fluid. The epithelium was lined with a single layer of cuboidal or flattened cells, with no evidence of squamous differentiation.


An ELISA using recombinant TmHSP70 for the diagnosis of Taenia multiceps infections in goats.
Infections with the tapeworm Taenia multiceps are problematic for ruminant farming worldwide. Here we develop a novel and rapid method for serodiagnosis of T. multiceps infections via an indirect ELISA (iELISA) that uses a heat shock protein, namely, TmHSP70. We extracted the total RNA of T. multiceps from the protoscoleces of cysts dissected from the brains of infected goats. Subsequently, we successfully amplified, cloned and expressed the TmHSP70 gene in Escherichia coli BL21 (DE3). Western blot analysis showed that the recombinant protein (∼34 kDa molecular weight) was recognized by the coenurosis positive serum. Given these initial, robust immunogenic properties for recombinant TmHSP protein, we assessed the ELISA-based serodiagnostic potential of this gene. The indirect ELISA was then optimized to 2.70 μg/well dilution for antigen and 1:80 dilution for serum,while the cut-off value is 0.446. We report that our novel TmHSP ELISA detected T. multiceps sera with a sensitivity of 1:10240 and a specificity of 83.3% (5/6). In a preliminary application, this assay correctly confirmed T. multiceps infection in 30 infected goats, consistent with the clinical examination. This study has revealed that our novel iELISA, which uses the rTmHSP protein, provides a rapid test for diagnosing coenurosis.


Gestational diabetes screening in a private, midwestern American population.
This prospective investigation was undertaken to compare the value of routine versus selective diabetes screening in a group of predominantly middle-class, healthy, Caucasian pregnant women. Two thousand consecutively chosen persons were divided into two groups: those to undergo routine screening between 24 and 28 weeks' gestation and those to be tested selectively in the presence of standard risk factors. The two groups of patients were otherwise similar. The method of screening involved a 50 gm oral glucose challenge, followed by a 3-hour glucose test if necessary. The incidence of gestational onset diabetes in the selectively screened group (19/453, 4.2%) was twice that in the routinely screened group (21/1000, 2.1%). Evidence of glucose intolerance without a risk factor was found in only one case (1/1000, 0.1%) in the routinely screened group. This assessment of our clinical practice has allowed us to safely eliminate the need for diabetes screening in more than half of our private patients, which will reduce office time, patient inconvenience, and expense.


Functional Outcome and Quality of Life after Patient-Specific Instrumentation in Total Knee Arthroplasty.
Patient-specific instrumentation (PSI) surgery may represent the next advancement in total knee arthroplasty (TKA). In 2011, 60 patients were prospectively recruited and divided into two groups based on the patient's choice: (1) PSI surgery; and (2) conventional TKA. At two years after surgery, the Knee Society Function Score, Oxford Knee Score and SF-36 scores were comparable between the two groups. Although the Knee Society Knee Score (KSKS) was 9 ± 3 points better in the PSI group (P=0.008), the two years improvement in KSKS was comparable between the two groups. None of the patients required revision surgery. These findings cannot justify the additional costs and waiting time incurred by the patients with PSI surgery in the practice of a high volume surgeon.


Improved survival in adult acute lymphoblastic leukemia. Need for more effective CNS prophylaxis.
Using a multimodality approach to adult acute lymphoblastic leukemia, 93% of patients achieved a complete remission; among patients achieving a complete remission, 43% are predicted to remain disease-free for 5 years. Despite use of cranial irradiation (2400 rad) and intrathecal methotrexate (12 mg X 5), CNS relapse occurred in 5/14 patients (36%). With improved systemic therapy of adult ALL, survival is increased and "standard" CNS prophylaxis is not as effective as it appeared to be when systemic remissions were of shorter duration. More effective approaches to CNS prophylaxis need to be devised.


Cystatin C- and Creatinine-Based Glomerular Filtration Rate Estimation Differences and Muscle Quantity and Functional Status in Older Adults: The Health, Aging, and Body Composition Study.
The difference in the estimated glomerular filtration rate based on cystatin C and that based on creatinine (eGFRDiff) is known to be associated with frailty and mortality. Creatinine is influenced by muscle mass, more so than cystatin C; we aimed to determine whether eGFRDiff is associated with muscle quantity and to what extent muscle quantity explains the relationship between eGFRDiff and poor functional status. A cohort analysis of the health, aging, and body composition study (HABC). Overall, 2,970 HABC participants had their baseline serum creatinine level, cystatin C level, and body composition measured using imaging. Estimated glomerular filtration rates (eGFRs) were calculated using Chronic Kidney Disease Epidemiology Collaboration equations (estimated glomerular filtration rate based on cystatin C [eGFRCys] and estimated glomerular filtration rate based on creatinine [eGFRCr]), and eGFRDiff was calculated as eGFRCys - eGFRCr. The total thigh muscle area was evaluated using computed tomography. The health, aging, and body composition study physical performance battery was scored on a continuous scale (standing and walking tasks); poor functional status was characterized by the lowest quartile. We used linear regression to model the cross-sectional association of eGFRDiff and muscle measures. We used logistic regression to evaluate the association of eGFRDiff with poor functional status. The mean age was 74 ± 3 years; the eGFRCys, eGFRCr, and eGFRDiff was 72 ± 18, 68 ± 15, and 4 ± 14 mL/min/1.73 m2, respectively. Compared with participants in the reference group (-10 < eGFRDiff ≤ 10 mL/min/1.73 m2), those in the negative eGFRDiff group (≤-10 mL/min/1.73 m2) were more likely to have comorbidities, a slower gait, and worse functional status. They had an approximately 14-cm2 smaller thigh muscle area in a fully adjusted model. Compared with the reference group, those in the negative group had 1.89-fold higher odds of poor functional status (unadjusted). This relationship was minimally attenuated after adjustment for thigh muscle, thigh fat area, appendicular lean mass, and limb fat mass, both individually and in combination. The functional status outcome was specific to HABC. The muscle measures did not capture dynamic turnover. The difference of eGFRCys - eGFRCr provides information on older adults' functional status, which is only partially explained by muscle quantity and quality.


Trend in breech delivery in Saudi Arabia.
An analysis of 2,168 consecutive singleton breech deliveries showed significant improvement in neonatal mortality and morbidity rates for babies delivered by Caesarean section (CS) compared with vaginal delivery (p less than 0.001). The CS rate was 19%. The uncorrected perinatal mortality (PNM) rate was 90.4/1,000 which was 2.5 times higher than the overall hospital PNM rate. In the vaginal delivery group the neonatal death (NND) rate of 206/1,000 among low birth-weight infants (less than 2,500 g) was significantly higher than that of 18/1,000 among babies of greater than 2,500 g (p greater than 0.001). There was no significant difference in the NND rate between these 2 birth-weight groups delivered by CS (p greater than 0.3). Social conservatism, large family size and limited neonatal care facilities were deterrents to an increase in the Caesarean section rate.


Age-related shift in brain region activity during successful memory performance.
Coregistered positron emission tomography (PET)/magnetic resonance imaging (MRI) was used to characterize brain function in 70 volunteers, aged 20-87 years, during a verbal memory task. Frontal activity showed an age-related decline that remained significant after statistical control for sulcal atrophy. Analyses of young and old subgroups matched for memory scores revealed that young good performers activated frontal regions, whereas old good performers relied on occipital regions. Although activating different cortical regions, good performers of all ages used the same cognitive strategy semantic clustering. Age-related functional change may reflect dynamic re-allocation in a network of brain areas, not merely anatomically fixed neuronal loss or diminished capacity to perform.


Combined use of transversus abdominis plane block and laryngeal mask airway during implementing ERAS programs for patients with primary liver cancer: a randomized controlled trial.
The incidence and mortality of primary liver cancer are very high and resection of tumor is the most crucial treatment for it. We aimed to assess the efficacy and safety of combined use of transversus abdominis plane (TAP) block and laryngeal mask airway (LMA) during implementing Enhanced Recovery After Surgery (ERAS) programs for patients with primary liver cancer. This was a prospective, evaluator-blinded, randomized, controlled parallel-arm trial. A total of 96 patients were enrolled (48 in each group). Patients in the control group received general anesthesia with endotracheal intubation, while patients in the TAP + LMA group received general anesthesia with LMA and an ultrasound-guided subcostal TAP block. The primary end-point was postoperative time of readiness for discharge. The secondary end-points were postoperative pain intensity, time to first flatus, quality of recovery (QoR), complications and overall medical cost. Postoperative time of readiness for discharge in the TAP + LMA group [7 (5-11) days] was shorter than that of the control group [8 (5-13) days, P = 0.004]. The postoperative apioid requirement and time to first flatus was lower in the TAP + LMA group [(102.8 ± 12.4) µg, (32.7 ± 5.8) h, respectively] than the control group [(135.7 ± 20.1) µg, P = 0.000; (47.2 ± 7.6) h, P = 0.000; respectively]. The QoR scores were significantly higher in the TAP + LMA group than the control group. The total cost for treatment in the TAP + LMA group [(66,608.4 ± 6,268.4) CNY] was lower than that of the control group [(84,434.0 ± 9,436.2) CNY, P = 0.000]. There was no difference in complications between these two groups. The combined usage of a TAP block and LMA is a simple, safe anesthesia method during implementing ERAS programs for patients with primary liver cancer. It can alleviate surgical stress, accelerate recovery and reduce medical cost.


Bone healing in rabbits after compression osteosynthesis: a comparative study between the radiological and histological findings.
The relationship between the radiological and histological findings was studied in a series of rabbit osteotomies and fractures stabilized with plates with and without longitudinal compression. When compression was employed, the gap varied between 10 and 200 micrometers and no radiologically visible callus was seen. After 4 weeks the smallest gaps of 10--30 micrometers were filled histologically with structureless material, while the larger gaps contained 'cortical' bone derived from periosteal and endosteal proliferation. The degree of union could not be assessed from X-ray examination, as there was no correlation between the histological and radiological appearances. When no compression was employed, the gap varied between 200--1200 micrometers; radiologically visible periosteal callus and filling of the gap indicated that consolidation had appeared in four weeks. Gaps of 200--500 micrometers were filled with bone derived from the periosteum and endosteum of lamellar structure which had invaded the original cortical bone ('plugging'). When the gaps were more than 500 micrometers, islands of cartilage and connective tissue were found. In all cases studied, many 'anchoring osteons' passed from the endosteal and periosteal callus into the original cortical bone. It is concluded that a 'compression internal fixation' of cortical bone will not necessarily secure union, as histologically confirmed, even when the formation of radiologically visible callus is suppressed. The lack of periosteal callus appears to be the result of a small gap and rigid fixation, rather than related to strains induced in the bone.


Quantitative evaluation of the effects of interscalene block on physiological responses to the balance between nociception and anti-nociception among inpatients undergoing total shoulder arthroplasty under general anesthesia.
Although the suppression of physiological responses to the balance between nociception caused by surgical trauma and anti-nociception due to anesthesia during total shoulder arthroplasty (TSA) is relevant for better perioperative managements, quantitative evaluations of the effects of ultrasound-guided interscalene brachial plexus block (ISB) on physiological responses have not been performed. Physiological responses were assessed using the nociceptive response (NR) index. In this multi-institutional observational study, associations between ISB and NR values were examined among inpatients undergoing TSA under general anesthesia between March 2019 and January 2021. The effects of ISB on acute postoperative pain and major complications within 30 days after surgery were also examined. NR values after skin incision clearly showed significant suppressions of physiological responses in patients undergoing TSA with ISB (n = 60), compared to those without ISB (n = 24). Acute postoperative pain on the day of surgery was also significantly less in patients with ISB than in those without ISB. Postoperative complications, classified by Clavien-Dindo grades, showed no significant differences between patients with and without ISB. A propensity score-matched sensitivity analysis confirmed the same results in patients with (n = 21) and without ISB (n = 21). In conclusion, suppression of physiological responses to the balance between nociception and anti-nociception by ISB can be quantitatively evaluated by NR index during TSA.


Application of advanced machine learning methods on resting-state fMRI network for identification of mild cognitive impairment and Alzheimer's disease.
The study of brain networks by resting-state functional magnetic resonance imaging (rs-fMRI) is a promising method for identifying patients with dementia from healthy controls (HC). Using graph theory, different aspects of the brain network can be efficiently characterized by calculating measures of integration and segregation. In this study, we combined a graph theoretical approach with advanced machine learning methods to study the brain network in 89 patients with mild cognitive impairment (MCI), 34 patients with Alzheimer's disease (AD), and 45 age-matched HC. The rs-fMRI connectivity matrix was constructed using a brain parcellation based on a 264 putative functional areas. Using the optimal features extracted from the graph measures, we were able to accurately classify three groups (i.e., HC, MCI, and AD) with accuracy of 88.4 %. We also investigated performance of our proposed method for a binary classification of a group (e.g., MCI) from two other groups (e.g., HC and AD). The classification accuracies for identifying HC from AD and MCI, AD from HC and MCI, and MCI from HC and AD, were 87.3, 97.5, and 72.0 %, respectively. In addition, results based on the parcellation of 264 regions were compared to that of the automated anatomical labeling atlas (AAL), consisted of 90 regions. The accuracy of classification of three groups using AAL was degraded to 83.2 %. Our results show that combining the graph measures with the machine learning approach, on the basis of the rs-fMRI connectivity analysis, may assist in diagnosis of AD and MCI.


Algae-induced photodegradation of antibiotics: A review.
Antibiotics are a typical group of pharmaceutical and personal care products (PPCPs) with emerging pollutant effects. The presence of residual antibiotics in the environment is a prominent issue owing to their potential hazards, toxic effects, and persistence. Several treatments have been carried out in aquatic environments in order to eliminate antibiotic residues. Among these, photodegradation is regarded as an environmentally-friendly and efficient option. Indirect photodegradation is the main pathway for the degradation of residual antibiotics in natural water, as opposed to direct photodegradation. Algae, working as photosensitizers, play an important role in the indirect photolysis of residual antibiotics in natural water bodies. They promote this reaction by secreting extracellular organic matters (EOMs) and inducing the generation of active species. In order to provide a thorough understanding of the effects of algae on residual antibiotic degradation in the environment, this paper comprehensively reviews the latest research regarding algae-induced antibiotic photodegradation. The summary of the different pathways and photosensitive mechanisms involved in this process show that EOMs are indispensable to antibiotic photodegradation. The influencing factors of algae-induced photodegradation are also discussed here: these include algae species, antibiotic types, and environmental variables such as light source, ferric ion presence, temperature, and ultrasound treatment. Based on the review of existing literature, this paper also considers several pathways for the future study of algae-induced antibiotic photodegradation.


Mitotic segregation of cytoplasmic determinants for chloramphenicol resistance in mammalian cells II: Fusions with human cell lines.
Cytoplasmically inherited chloramphenicol (CAP) resistance in human cells has been used to study the interaction between sensitive and resistant mitochondria. Cybrids between two HeLa cells were stable for resistance, grew rapidly and cloned well in CAP, and were O2 tolerant. HeLa-HeLa hybrids were also stable up to 70 doublings in the absence of CAP. Cybrids between HeLa and WI-L2 cells were unstable for resistance for up to 40 doublings, grew slowly and cloned poorly in CAP, and were O2 sensitive (S phase). The growth rate then increased and the cells became stable for resistance, cloned well, and were not O2 sensitive (F phase). Doubling time for S but not F phase cells was proportional to CAP concentration, indicating that both kinds of mitochondria were present and functioning. The instability of CAP resistance in many interstrain but not in intrastrain mouse and human cybrids and hybrids is interpreted in relation to lower eukaryotes.


Ligand effects on the dimensionality of oxamato-bridged mixed-metal open-framework magnets.
Increasing dimensionality [from 2D (1) to 3D (2)] and T(C) [from 10 (1) to 20 K (2)] in two new oxamato-bridged heterobimetallic Mn(II)(2)Cu(II)(3) open-frameworks result from the steric hindrance provided by the different alkyl substituents of the N-phenyloxamate bridging ligands.


Urovaginal fistulas: 20 years of experience with 45 cases.
We treated 45 patients with urovaginal fistulas owing to operative gynecological procedures and radiotherapy: 36 had vesicovaginal and urethrovaginal, 6 had ureterovaginal and 3 had rectovesicovaginal fistulas. Reconstruction was performed in 40 patients, mainly via a transvesical approach. There was good success in patients not given radiotherapy: 24 of 26 patients experienced primary healing and no failures were noted. Of the 14 patients treated by irradiation 9 had primary healing and 3 failed therapy. Patients with a urovaginal fistula should be referred to centers with special interest in this type of repair. An alternative surgical technique with the carbon dioxide laser deserves consideration in patients with scarred and irradiated tissue.


[Effect of supine body position on the oscillatory airway resistance R(OS)].
Respiratory resistance measurement by forced oscillation method increased in supine body position in consequence of enlargement of pulmonary blood volume and airway resistance.


On the organization of olfactory and vomeronasal cortices.
Classically, the olfactory and vomeronasal pathways are thought to run in parallel non-overlapping axes in the forebrain subserving different functions. The olfactory and vomeronasal epithelia project to the main and accessory olfactory bulbs (primary projections), which in turn project to different areas of the telencephalon in a non-topographic fashion (secondary projections) and so on (tertiary projections). New data indicate that projections arising from the main and accessory olfactory bulbs converge widely in the rostral basal telencephalon. In contrast, in the vomeronasal system, cloning two classes of vomeronasal receptors (V1R and V2R) has led to the distinction of two anatomically and functionally independent pathways that reach some common, but also some different, targets in the amygdala. Tertiary projections from the olfactory and vomeronasal amygdalae are directed to the ventral striatum, which thus becomes a site for processing and potential convergence of chemosensory stimuli. Functional data indicate that the olfactory and vomeronasal systems are able to detect and process volatiles (presumptive olfactory cues) as well as pheromones in both epithelia and bulbs. Collectively, these data indicate that the anatomical and functional distinction between the olfactory and vomeronasal systems should be re-evaluated. Specifically, the recipient cortex should be reorganized to include olfactory, vomeronasal (convergent and V1R and V2R specific areas) and mixed (olfactory and vomeronasal) chemosensory cortices. This new perspective could help to unravel olfactory and vomeronasal interactions in behavioral paradigms.


Acute Thrombosis of an Infrarenal Abdominal Aortic Aneurysm Presenting as Bilateral Critical Lower Limb Ischemia.
Intraluminal thrombosis in the aneurysm sac is commonly seen in abdominal aortic aneurysm (AAA). Complete acute thrombosis of an AAA is a rare and catastrophic event. We report a patient with acute AAA thrombosis presenting as bilateral lower limbs critical ischemia. A79-year-old male with a past history of AAA presented with acute onset of bilateral leg pain, coolness, weakness and numbness. His lower extremity pulses including femorals were absent bilaterally on physical examination. Urgent computed tomography angiography showed an infrarenal AAA measuring 45 mm in diameter. The aneurysm sac and bilateral common iliac arteries were completely occluded. Emergency open repair of AAA and bilateral iliac thrombectomy were successfully performed under general anesthesia. Bilateral femoral pulses were present and the neurological deficits were completely resolved after operation. Patient recovered well and was asymptomatic at 3-month follow-up. Acute thrombosis of aortic aneurysm could be an unusual cause of lower limb ischemia, prompt diagnosis followed by surgical revascularization is essential to avoid prolonged ischemia.


Upright static pelvic posture as rotations and translations in 3-dimensional from three 2-dimensional digital images: validation of a computerized analysis.
The aim of this study was to determine the accuracy in measuring the pelvic orientations of a phantom model using the PosturePrint method. In the Université du Québec à Trois-Rivières biomechanics laboratory, Trois-Rivières, Quebec, Canada, a mannequin was fixed on a rotating platform. For a set of 3 photographs (left lateral, anterior to posterior, right lateral) of each position, the mannequin pelvis was placed in 68 different postures on a stand, 61 cm from a wall, in front of a digital camera. The camera was at 83.8 cm in height and at 3.35 m from a calibrated wall grid. Mannequin postures were in 5 degrees of freedom: lateral translation (Tx), lateral flexion (Rz), axial rotation (Ry), flexion-extension (Rx), and anterior-posterior translation (Tz). Average errors were the differences of the positioned postures to the PosturePrint computed values. Mean and SD of computational errors for rotation displacements were Rx = 0.5 degrees +/- 0.8 degrees , Ry = 1.3 degrees +/- 0.8 degrees , and Rz = 0.5 degrees +/- 0.3 degrees , and for translation, Tz = 1.2 +/- 0.6 mm and Tx = 0.9 +/- 0.5 mm. The PosturePrint system allowed for accurate postural measurement of rotations and translations of a mannequin pelvis. The next step in evaluation of this product would be a reliability study on human subjects.


Transcatheter retrieval of device entrapment: management of a rare complication of percutaneous coronary intervention: case report and literature review.
With the continued advancement in PCI equipment and techniques, complications arising from intracoronary manipulation are encountered. Such complications are associated with major adverse outcome including death; myocardial infarction (MI) and the need for urgent coronary artery bypass surgery (CABG), and they require prompt recognition and mediation by the interventional cardiologist. We report a case of a broken stent shaft system in the setting of acute coronary syndrome and its successful retrieval using a non-compliant balloon to trap the proximal portion of the shaft within the guide ("trapping" a procedure used in coronary Chronic Total Occlusions (CTO) interventions) followed by slow withdrawal of the whole system. This was followed by successful PCI of the culprit lesion using a drug eluting stent without any residual complications.


A Cross-Sequential Study of the Effect of the Coronavirus Disease 2019 Pandemic on the Risk of Anxiety and Depression of Royal Flying Doctors Staff, an Australian Air Medical Organization.
This cross-sequential study examines whether the coronavirus disease 2019 pandemic affected the mental health of staff working at an Australian air medical service, the Royal Flying Doctors Service South Eastern (RFDSSE) Section. The risk of anxiety and depression was measured using a prospective anonymized online survey using the Hospital Anxiety and Depression Scale, which was answered by 119 employees. This cross-sequential study was completed in December 2021 with reference to 2 time points: now and the beginning of the pandemic. A high risk of anxiety was defined using a Hospital Anxiety and Depression Scale score of 11 to 21 (low risk: 0-10). Chi-square testing was used to compare subgroups at single time points. McNemar testing was used to compare the risk of anxiety and depression between the beginning of the pandemic and December 2021. Employees recalled a higher risk of anxiety at the beginning of the pandemic (29%) compared with December 2021 (16%) (P = .012). At the beginning of the pandemic, nonoperational staff members were more anxious than operational staff (P = .019). One third (31%) of operational staff members were concerned about dying at the beginning of the pandemic. Our findings demonstrate that RFDSSE employees recalled higher levels of anxiety at the beginning of the pandemic compared with their risk in December 2021. Operational and nonoperational staff have different mental health needs; anxiety experienced by nonoperational staff during a pandemic should not be underestimated. The overall prevalence of anxiety and depression is high, suggesting health care staff in an air medical service may require extra psychological support. Other air medical organizations may reflect on our study findings and plan how to better support their own staff as a result.


Bioindication of trace metals in Brachythecium rutabulum around a copper smelter in Legnica (Southwest Poland): Use of a new form of data presentation in the form of a self-organizing feature map.
Concentrations of the elements Al, Be, Cd, Co, Cr, Cu, Fe, Mn, Ni, Pb, V, and Zn were measured in the terrestrial moss Brachythecium rutabulum and the soil on which it grew. Soil and moss plants were sampled at sites situated 1.5, 3, 6, 9 and 15 km to the north, south, east and west of the Legnica copper smelter (SW Poland). The self-organizing feature map (SOFM) or Kohonen network was used to classify the soil and moss samples according to the concentrations of the elements. The self-organizing map yielded distinct groups of B. rutabulum and soil samples, depending on the distance from and direction to the source of pollution. When the map-identified groups of sites with similar soil metal concentrations were combined with the map-identified groups of sites with similar metal concentrations in B. rutabulum, these maps were found to correspond closely. The SOFMs accurately represented the least polluted, moderately polluted and severely polluted sites, reflecting the distribution of metals that is typical of the smelter area, caused by the prevailing westerly and northerly winds.


Targeted Locus Amplification and Haplotyping.
Targeted locus amplification (TLA) allows for the detection of all genetic variation (including structural variation) in a genomic region of interest. As TLA is based on proximity ligation, variants can be linked to each other, thereby enabling allelic phasing and the generation of haplotypes. This allows for the study of genetic variants in an allele-specific manner. Here, we provide a step-by-step protocol for TLA sample preparation and a complete bioinformatics pipeline for the allelic phasing of TLA data. Additionally, to illustrate the protocol, we show the ability of TLA to re-sequence and haplotype the complete cystic fibrosis transmembrane (CFTR) gene (> 200 kb in size) from patient-derived intestinal organoids.


C-C bond formation at C-2 of a quinoline ring: synthesis of 2-(1H-indol-3-yl)quinoline-3-carbonitrile derivatives as a new class of PDE4 inhibitors.
A number of 2-(1H-indol-3-yl)quinoline-3-carbonitrile derivatives were synthesized via AlCl(3)-mediated C-C bond forming reaction between 2-chloroquinoline-3-carbonitrile and various indoles. The methodology does not require any N-protection of the indoles employed and provided the corresponding products in good yields. The molecular structure of a representative compound was established unambiguously by single crystal X-ray diffraction and structural elaboration of a compound synthesized has been demonstrated. Many of these compounds synthesized showed PDE4 inhibitory properties in vitro. A brief structure-activity relationship studies within the series along with docking results of a representative compound (EC(50) ∼0.89 μM) is presented.


Correction to: miR-3928v is induced by HBx via NF-κB/EGR1 and contributes to hepatocellular carcinoma malignancy by down-regulating VDAC3.
An amendment to this paper has been published and can be accessed via the original article.


[ROC analysis of detection of interval changes in interstitial lung diseases on digital chest radiographs using the temporal subtraction technique].
To demonstrate the clinical usefulness of a temporal subtraction technique for the detection of interval changes in various interstitial lung diseases on digital chest radiographs. One hundred pairs of chest radiographs in 34 patients (63 with and 37 without interval changes) with various interstitial lung diseases were selected. All cases were confirmed by serial chest computed tomography (CT) and ascertained by radiologists. All chest radiographs were obtained with a computed radiography (CR) system, and temporal subtraction images were produced with an iterative image-warping technique. Four radiologists and two thoracic physicians provided confidence levels for interval changes in interstitial lung diseases with and without temporal subtraction. Their performances with and without temporal subtraction were evaluated by means of receiver operating characteristic (ROC) analysis using a sequential test. The area under the ROC curve (Az) values of six observers obtained with and without temporal subtraction were 0.90 and 0.78, respectively. Results showed that the detection of interval changes in interstitial lung diseases was significantly improved by the use of temporal subtraction images compared with CR images alone(P = 0.002). Furthermore, the high detection rate was achieved with temporal subtraction images regardless of the subtlety and location of interval changes. Temporal subtraction improved the diagnostic accuracy of radiologists in detecting interval changes in interstitial lung diseases on chest radiographs. It was also useful for cases of multiple interval changes.


Surgical safety and efficacy of a multi-stent system, the comet stent, in Baerveldt glaucoma implant surgery: a prospective pilot study.
This study aimed to introduce a new technique for lowering intraocular pressure (IOP) using a multi-stent system after the implantation of a Baerveldt glaucoma implant (BGI) and evaluate its clinical effectiveness. Prospective case series. Six patients with uncontrolled refractory glaucoma were enrolled between December 2021 and May 2022. Six 6-0 nylon sutures were preoperatively inserted into the tube of a BGI. These sutures were named "comet stents" (CSs). BGI implantation was performed, and the CSs were removed one-by-one whenever the IOP rose during the follow-up period. IOP was measured 30-60 min after the removal of each CS, and the reduction in IOP was recorded to assess the effect of CS removal. IOP reduction and the effect of CS removal on IOP reduction were evaluated for 6 months. The cut and trimmed stented tubes were examined with scanning electron microscopy, and the ratio of the patent cross-sectional area to the total luminal area (PCSA, %) and the luminal area occupation rate per stent (%) were calculated. The mean (±standard deviation) IOP decreased from 31.5 ± 2.8 mmHg at the baseline to 14.8 ± 8.3 mmHg at 1 month, 8.8 ± 4.7 mmHg at 3 months, and 9.2 ± 3.4 mmHg at 6 months. The IOP reduction induced by CS removal ranged from 0 to 19 mmHg. The mean PCSA was 52.7 ± 1.7%, and the mean luminal area occupation rate per stent was 7.9 ± 0.3%. The use of CSs is an effective technique for controlling IOP in a step-by-step manner after BGI surgery.


The role of tertiary neurosurgical intervention in non-missile penetrating injuries of the spine.
The objective of the study was to determine whether all patients with spinal non-missile penetrating injuries (NMPIs) need to be managed at a tertiary neurosurgical centre. A retrospective analysis of clinical, demographic, and imaging records was performed on all NMPI patients referred to the Department of Neurosurgery at Tygerberg Academic Hospital in Cape Town, South Africa, between 1 January 2016 and 31 December 2019. Ninety-six patients were identified (94 males and 2 females) with 35 cervical, 60 thoracic, and 1 lumbar spinal stab. Eighty-six had an incomplete spinal cord injury. Six patients presented with cerebrospinal fluid (CSF) leak, all of which resolved spontaneously. MRI was performed in nine patients. Six patients had retained blades, of which 5 were removed in the emergency room (ER). Surgery was performed in two patients (cervical intramedullary abscess and a retained blade). Two patients developed meningitis, and one an intramedullary abscess. Twenty-two patients had associated injuries (pneumothorax, bowel injury). The average length of stay was 17 days, with 81% being unchanged neurologically. The average time from discharge to leaving the hospital was 11 days. Early management of NMPI should include prophylactic antibiotics and wound debridement and X-ray imaging to exclude retained blades. Bowel and lung injury must be managed accordingly. Tertiary neurosurgical referral is not routinely necessary and is only warranted for deteriorating neurology, retained blades not removable in the ER, and respiratory failure secondary to spinal cord injury. Complications include meningitis and persistent CSF leak, which should be referred timeously.


Characteristic of c-Kit+ progenitor cells in explanted human hearts.
According to literature data, self-renewing, multipotent, and clonogenic cardiac c-Kit(+) progenitor cells occur within human myocardium. The aim of this study was to isolate and characterize c-Kit(+) progenitor cells from explanted human hearts. Experimental material was obtained from 19 adult and 7 pediatric patients. Successful isolation and culture was achieved for 95 samples (84.1%) derived from five different regions of the heart: right and left ventricles, atrium, intraventricular septum, and apex. The average percentage of c-Kit(+) cells, as assessed by FACS, ranged between 0.7 and 0.9%. In contrast to published data we do not observed statistically significant differences in the number of c-Kit(+) cells between disease-specific groups, parts of the heart or sexes. Nevertheless, c-Kit(+) cells were present in significant numbers (11-24%) in samples derived from three explanted pediatric hearts. c-Kit(+) cells were also positive for CD105 and a majority of them was positive for CD31 and CD34 (83.7 ± 8.6 and 75.7 ± 11.4%, respectively). Immunohistochemical analysis of the heart tissue revealed that most cells possessing the c-Kit antigen were also positive for tryptase, a specific mast cell marker. However, flow cytometry analysis has shown cultured c-Kit(+) cells to be negative for hematopoietic marker CD45 and mast cell marker CD33. Isolated c-Kit(+) cells display mesenchymal stem cell features and are thought to differentiate into endothelial cells.


Episodic weakness and axonal sensorimotor neuropathy caused by a mitochondrial MT-ATP6 mutation.
Episodic weakness is typically associated with a group of disorders so called periodic paralyses. Their major causes are mutation of ion channels, and have rarely been linked to mitochondrial disorders. We report a 20-year-old man with episodic weakness and axonal sensorimotor neuropathy since the age of 10 years. Analysis of the next generation sequencing data of the entire mitochondrial genome extracted from the blood revealed a homoplasmic m.9185T > C variant in MT-ATP6. Acetazolamide may be responsive for episodic weakness, and supplements with l-carnitine with coenzyme-Q10 seem to be beneficial as well. To the best of our knowledge, this is the first report in Taiwan which reveals episodic weakness and sensorimotor polyneuropathy as a unique phenotype of MT-ATP6 mutations.


Role of lipid-lowering pharmacotherapy in children.
For patients with coronary artery disease and healthy middle-aged or older individuals with elevated cholesterol levels, treatment with cholesterol-lowering drugs reduces morbidity and sometimes mortality. Treatment reverses established atherosclerotic lesions within a relatively short period of time, suggesting that starting cholesterol-lowering drugs in adulthood is adequate for most people at risk. Children with genetic lipid disorders, including familial hypercholesterolaemia and familial combined hyperlipidaemia, may be candidates for earlier therapy. A complete assessment of risk factors should be undertaken to determine which children are at highest risk. Treatment should start with diet, because diet is an important independent protective factor for disease. The bile acid sequestrants (resins) are the only drugs approved for children and may reduce low density lipoprotein (LDL)-cholesterol levels by 15 to 20% at best. Long term tolerability is good, but many children will not take the resins because they find them unpalatable. Tablet formulations have higher acceptability. Some children require supplementation with fat soluble vitamins or folate. Although hydroxymethylglutaryl coenzyme A (HMG-CoA) reductase inhibitors have not been tested in long term studies in children, safety records are excellent in adults. Short term studies show that HMG-CoA reductase inhibitors reduce LDL-cholesterol levels similarly in children and in adults. Thus, the drugs may be used in low dosages to treat some adolescents with exceptional risk of disease.


Myonectin protects against skeletal muscle dysfunction in male mice through activation of AMPK/PGC1α pathway.
To maintain and restore skeletal muscle mass and function is essential for healthy aging. We have found that myonectin acts as a cardioprotective myokine. Here, we investigate the effect of myonectin on skeletal muscle atrophy in various male mouse models of muscle dysfunction. Disruption of myonectin exacerbates skeletal muscle atrophy in age-associated, sciatic denervation-induced or dexamethasone (DEX)-induced muscle atrophy models. Myonectin deficiency also contributes to exacerbated mitochondrial dysfunction and reduces expression of mitochondrial biogenesis-associated genes including PGC1α in denervated muscle. Myonectin supplementation attenuates denervation-induced muscle atrophy via activation of AMPK. Myonectin also reverses DEX-induced atrophy of cultured myotubes through the AMPK/PGC1α signaling. Furthermore, myonectin treatment suppresses muscle atrophy in senescence-accelerated mouse prone (SAMP) 8 mouse model of accelerated aging or mdx mouse model of Duchenne muscular dystrophy. These data indicate that myonectin can ameliorate skeletal muscle dysfunction through AMPK/PGC1α-dependent mechanisms, suggesting that myonectin could represent a therapeutic target of muscle atrophy.


Global workspace theory of consciousness: toward a cognitive neuroscience of human experience.
Global workspace (GW) theory emerged from the cognitive architecture tradition in cognitive science. Newell and co-workers were the first to show the utility of a GW or "blackboard" architecture in a distributed set of knowledge sources, which could cooperatively solve problems that no single constituent could solve alone. The empirical connection with conscious cognition was made by Baars (1988, 2002). GW theory generates explicit predictions for conscious aspects of perception, emotion, motivation, learning, working memory, voluntary control, and self systems in the brain. It has similarities to biological theories such as Neural Darwinism and dynamical theories of brain functioning. Functional brain imaging now shows that conscious cognition is distinctively associated with wide spread of cortical activity, notably toward frontoparietal and medial temporal regions. Unconscious comparison conditions tend to activate only local regions, such as visual projection areas. Frontoparietal hypometabolism is also implicated in unconscious states, including deep sleep, coma, vegetative states, epileptic loss of consciousness, and general anesthesia. These findings are consistent with the GW hypothesis, which is now favored by a number of scientists and philosophers.


Expression and DNA methylation profiles of EZH2-target genes in plasma exosomes and matched primary tumor tissues of the patients with diffuse large B-cell lymphoma.
Diffuse large B-cell lymphoma (DLBCL) is the most common type of aggressive lymphoma. This study was designed to compare epigenetic alterations observed in Enhancer of Zeste Homolog 2 (EZH2)-target genes between plasma-derived exosomes and primary tumors in DLBCL patients. Exosomes were isolated from plasma of 21 DLBCL patients and 21 controls. We analyzed the methylation status of the target genes using methylation-specific PCR. We also examined whether the exosomes and the tumor samples contained transcripts of the target genes. We found that CDKN2A and CDKN2B were methylated in both plasma exosomes and primary tumor tissue samples. None of the transcripts were found in the exosomes except CDKN1B which was expressed in 8 (38%) of the exosome samples. This study showed that plasma exosomes might preferably package certain target molecules from primary tumors and the exosomes containing dual methylated DNAs of CDKN2A and CDKN2B, or CDKN1B transcript may contribute to DLBCL pathogenesis.


Fabrication and biomedical applications of Arabinoxylan, Pectin, Chitosan, soy protein, and silk fibroin hydrogels via laccase - Ferulic acid redox chemistry.
The unique physiochemical properties and the porous network architecture of hydrogel seek the attention to be explored in broad range of fields. In the last decade, numerous studies on the development of enzymatically cross-linked hydrogels have been elucidated. Implementing enzyme based cross-linking for fabrication of biomaterials over other cross-linking methods harbor various advantages, especially hydrogels designed using laccase exhibits mild reaction environment, high cross-linking efficiency and less toxicity. To our knowledge this is the first report reviewing the formulation of laccase mediated cross-linking for hydrogel preparation. Here, laccase catalyzed synthesis of hydrogel using polysaccharide viz. arabinoxylan, sugar beet pectin, galactomannan, chitosan etc. and proteins namely soy protein, gelatin, silk fibroin were discussed on highlighting their mechanical properties and its possible field of application. We have summarized the role of phenolic acids in laccase mediated cross-linking particularly ferulic acid which is a component of lignocellulose, serving cell rigidity via cross-linkage. The review also discusses on various biomedical applications such as controlled protein release, tissue engineering, and wound healing. It is anticipated that this review will give a detailed information on different laccase mediated reaction strategies that can be applied for the synthesis of various new biomaterials with tailor made properties.


Inhibition of FGF receptor signalling in Xenopus oocytes: differential effect of Grb7, Grb10 and Grb14.
The role of Grb7 adapters, Grb7, Grb10, and Grb14, was investigated in Xenopus oocytes expressing fibroblast growth factor receptors (FGFR). FGF-induced maturation of FGFR-expressing oocytes was blocked by previous injection of Grb7 or Grb14, but not Grb10. This effect correlated with Grb7/14 binding to the receptor, and inhibition of the Ras-dependent pathway. Interestingly, the phosphorylated insulin receptor interacting region (PIR) and Src 2 homology domains (SH2) of Grb7 and Grb14 were differently implicated in the inhibition of FGFR signalling. This study provided further evidence for specificity of the biological action of the Grb7 adapters on receptor tyrosine kinase signalling.


Protein expression patterns of ezrin are predictors of progression in T1G3 bladder tumours treated with nonmaintenance bacillus Calmette-Guérin.
Bacillus Calmette-Guérin (BCG) is a standard treatment for reducing tumour recurrence and delaying progression of high-risk, non-muscle-invasive bladder tumours. However, it is not clear yet which patients are more likely to be responders to BCG. To evaluate the role of ezrin expression in bladder cancer (BCa) progression in T1G3 bladder tumours treated with BCG. Ezrin protein expression patterns were analysed on tumour specimens belonging to 92 patients with T1G3 non-muscle-invasive BCa undergoing nonmaintenance BCG treatment. Re-resection was not performed. The median follow-up was 90.5 mo (range: 3.0-173.0). A specific tissue array was created containing three representative cores of each of the tumour specimens belonging to these patients. Ezrin protein expression patterns were assessed by immunohistochemistry on this tissue array. Proliferation rates were assessed by means of Ki67 staining. Recurrence, progression into muscle-invasive tumours, and disease-specific overall survival (OS) rates were analysed using univariate and multivariate tests. Among the 92 patients analysed, 40 recurred (43.5%), 17 progressed (18.5%), and 14 died of the disease (15.2%). Log-rank survival analyses revealed that an ezrin membrane expression <20% was significantly associated with increased progression (p=0.009) and shorter disease-specific OS (p=0.006). Multivariate analyses showed that ezrin was an independent prognostic marker of progression (p=0.031) and disease-specific survival (p=0.035). Interestingly, the low ezrin membrane expression correlated with high proliferation rates (p=0.033). Immunohistochemistry analyses revealed that the membrane expression of ezrin is associated with the clinical outcome of patients with T1G3 tumours undergoing BCG treatment. Protein expression patterns of ezrin were associated with tumour progression in T1G3 disease. The differential expression of ezrin distinguished patients responding to BCG from those who may require a more aggressive therapeutic approach.


Structure and developmental regulation of Golli-mbp, a 105-kilobase gene that encompasses the myelin basic protein gene and is expressed in cells in the oligodendrocyte lineage in the brain.
We have identified a novel transcription unit of 105 kilobases (called the Golli-mbp gene) that encompasses the mouse myelin basic protein (MBP) gene. Three unique exons within this gene are alternatively spliced into MBP exons and introns to produce a family of MBP gene-related mRNAs that are under individual developmental regulation. These mRNAs are temporally expressed within cells of the oligodendrocyte lineage at progressive stages of differentiation. Thus, the MBP gene is a part of a more complex gene structure, the products of which may play a role in oligodendrocyte differentiation prior to myelination. One Golli-mbp mRNA that encodes a protein antigenically related to MBP is also expressed in the spleen and other non-neural tissues.


The fluctuation of serum myoglobin levels in Duchenne muscular dystrophy and the carrier.
The diurnal changes of serum myoglobin level and CK activity were investigated in 20 cases of Duchenne dystrophy and 6 normal males under ordinary circumstances in their daily lives. Changes of myoglobin levels were also checked in 25 cases of Duchenne carrier and 11 control females with muscular exercise by ergometer of 70 W for 3 min. In Duchenne dystrophy, the myoglobin level was rather low before waking up, then it abruptly increased thereafter and remained high until retiring. The fluctuation range of myoglobin was greater than that of CK. The myoglobin level of control males was extremely low compared with that in Duchenne dystrophy. In Duchenne carriers, although CK activity did not significantly change after the exercise, 5 of 11 known carriers showed an increased myoglobin level.


Acquired childhood aphasia as a consequence of COVID-19 and its differential diagnosis from speech-language pathologist perspective: A case study.
It is essential to be more vigilant in understanding impact of COVID-19 on children's speech and language skills. As studies in these lines are very sparse, it is imperative to profile these children and derive accurate diagnosis. Accurate diagnosis aids Speech-Language Pathologists (SLPs) to render speech and Language therapy systematically.


Duration and accuracy of automated stroke CT workflow with AI-supported intracranial large vessel occlusion detection.
The Automation Platform (AP) is a software platform to support the workflow of radiologists and includes a stroke CT package with integrated artificial intelligence (AI) based tools. The aim of this study was to evaluate the diagnostic performance of the AP for the detection of intracranial large vessel occlusions (LVO) on conventional CT angiography (CTA), and the duration of CT processing in a cohort of acute stroke patients. The diagnostic performance for intracranial LVO detection on CTA by the AP was evaluated in a retrospective cohort of 100 acute stroke patients and compared to the diagnostic performance of five radiologists with different levels of experience. The reference standard was set by an independent neuroradiologist, with access to the readings of the different radiologists, clinical data, and follow-up. The data processing time of the AP for ICH detection on non-contrast CT, LVO detection on CTA, and the processing of CTP maps was assessed in a subset 60 patients of the retrospective cohort. This was compared to 13 radiologists, who were prospectively timed for the processing and reading of 21 stroke CTs. The AP showed shorter processing time of CTA (mean 60 versus 395 s) and CTP (mean 196 versus 243-349 s) as compared to radiologists, but showed lower sensitivity for LVO detection (sensitivity 77% of the AP vs mean sensitivity 87% of radiologists). If the AP would have been used as a stand-alone system, 1 ICA occlusion, 2 M1 occlusions and 8 M2 occlusions would have been missed, which would be eligible for mechanical thrombectomy. In conclusion, the AP showed shorter processing time of CTA and CTP as compared with radiologists, which illustrates the potential of the AP to speed-up the diagnostic work-up. However, its performance for LVO detection was lower as compared with radiologists, especially for M2 vessel occlusions.


Comparative analysis of (239)Pu, (137)Cs, (210)Pb and (40)K spatial distributions in the top soil layer at the Baltic coast.
This paper presents the results of an investigation into the spatial distribution of radionuclides of artificial ((239,240)Pu, (137)Cs) and natural ((210)Pb, (40)K) origins in the upper (0-5 cm) soil layers on the Baltic coastline of Lithuania ( approximately 5 km(2) area). The samples were analysed by gamma ray spectrometry and combined radiochemical procedures. The highest (210)Pb, (239,240)Pu and (137)Cs activity concentrations were determined in the forest samples, whereas (40)K activity was rather homogeneous across the study area. Relatively high (239,240)Pu and (40)K activity concentrations were determined along the surf zone. The (210)Pb and (137)Cs activity concentrations showed a gradual increase from the surf zone to the forest. The average activity concentrations of (239,240)Pu, (137)Cs, (210)Pb and (40)K in the beach and forest samples, respectively, were as follows: 0.32+/-0.08 and 0.74+/-0.14; 50+/-4 and 1190+/-50; 4.7+/-2.0 and 48+/-6; 186+/-15 and 216+/-17 Bq/kg.


Primary pulmonary artery sarcoma: A rare and overlooked differential diagnosis of pulmonary embolism. Clues to diagnosis.
Primary pulmonary artery sarcoma (PPAS) is a very rare tumor that mimics pulmonary embolism (PE) in clinical presentation and on imaging studies, therefore leading to diagnostic delay and increased patient mortality. We discuss the case of 37-year-old man with a rapidly progressing PPAS, which was initially managed as PE. Imaging studies, particularly computed tomography and magnetic resonance imaging, were helpful in reaching the correct diagnosis. Because of the dismal prognosis of such cases, which improves by definite surgery, the patient underwent extensive surgical resection which got complicated by pulmonary reperfusion injury and intrapulmonary hemorrhage, and thus died. Owing to the rarity of the tumor, PPAS is often initially mistakenly diagnosed as PE, leading to a diagnostic delay and increased mortality. Having a high index of suspicion in "atypical PE" cases and a knowledge of the characteristic radiological and clinical features of PPAS may expedite the diagnosis and improve survival. Pulmonary artery distension by the mass on imaging studies and compression of neighboring structures are in favor of a tumor rather than PE. Additionally, tissue characterization on magnetic resonance imaging is particularly useful in differentiating tumor from PE. PPAS has a very poor prognosis which improves by early definitive surgery. Perioperative and late mortality however, remain high. Physicians should be alert of this tumor despite its rarity because diagnostic delay increases mortality. In this report, we summarize the features that differentiate PPAS from PE and the importance of imaging in diagnosing the tumor.


Structural basis for Ca2+-regulated muscle relaxation at interaction sites of troponin with actin and tropomyosin.
Troponin and tropomyosin on actin filaments constitute a Ca2+-sensitive switch that regulates the contraction of vertebrate striated muscle through a series of conformational changes within the actin-based thin filament. Troponin consists of three subunits: an inhibitory subunit (TnI), a Ca2+-binding subunit (TnC), and a tropomyosin-binding subunit (TnT). Ca2+-binding to TnC is believed to weaken interactions between troponin and actin, and triggers a large conformational change of the troponin complex. However, the atomic details of the actin-binding sites of troponin have not been determined. Ternary troponin complexes have been reconstituted from recombinant chicken skeletal TnI, TnC, and TnT2 (the C-terminal region of TnT), among which only TnI was uniformly labelled with 15N and/or 13C. By applying NMR spectroscopy, the solution structures of a "mobile" actin-binding domain (approximately 6.1 kDa) in the troponin ternary complex (approximately 52 kDa) were determined. The mobile domain appears to tumble independently of the core domain of troponin. Ca2+-induced changes in the chemical shift and line shape suggested that its tumbling was more restricted at high Ca2+ concentrations. The atomic details of interactions between actin and the mobile domain of troponin were defined by docking the mobile domain into the cryo-electron microscopy (cryo-EM) density map of thin filament at low [Ca2+]. This allowed the determination of the 3D position of residue 133 of TnI, which has been an important landmark to incorporate the available information. This enabled unique docking of the entire globular head region of troponin into the thin filament cryo-EM map at a low Ca2+ concentration. The resultant atomic model suggests that troponin interacted electrostatically with actin and caused the shift of tropomyosin to achieve muscle relaxation. An important feature is that the coiled-coil region of troponin pushed tropomyosin at a low Ca2+ concentration. Moreover, the relationship between myosin and the mobile domain on actin filaments suggests that the latter works as a fail-safe latch.


Primary neurocytoma of the spinal cord: a case report and review of literature.
Most central neurocytomas (CN) and spinal neurocytomas (SN) have a bland well-differentiated histologic picture and uneventful clinical course. However, rare examples showing histologic atypia, recurrence and even CSF dissemination have been reported. Herein we report a case of recurrent spinal neurocytoma in a 24-year-old male who presented with a 2-month history of weakness and numbness of the left upper and lower limbs, and was previously operated at the same site 10 months ago. MRI revealed a contrast enhancing intramedullary mass involving C5-T1 region. Radiologic and operative impression at both surgeries was that of a glioma, possibly anaplastic. Histologic and immunohistochemical features in both resections were those of an atypical neurocytoma. The tumor showed rare mitoses, focal mild vascular proliferation in both specimens, and necrosis in the initial specimen. MIB1 labeling indices were 9 and 10%, respectively. Based on the analysis of this case and limited data from the literature, it is hypothesized that SN shows a histopathologic picture, immunoprofile and biologic behavior very similar to CN. However, the presence of histologic atypia and increased MIB1 index in SN appear to more closely correlate with tumor recurrence and a worse overall outcome, in part due to their location in the critical region of cervical spinal cord. Therefore, we hypothesize that SN with atypia requires a close clinical follow up. As in CN, radiation therapy is perhaps best reserved for atypical, progressive and recurrent SN.


Procalcitonin levels in acute exacerbation of COPD admitted in ICU: a prospective cohort study.
Antibiotics are recommended for severe acute exacerbation of chronic obstructive pulmonary disease (AECOPD) admitted to intensive care units (ICU). Serum procalcitonin (PCT) could be a useful tool for selecting patients with a lower probability of developing bacterial infection, but its measurement has not been investigated in this population. We conducted a single center prospective cohort study in consecutive COPD patients admitted to the ICU for AECOPD between September 2005 and September 2006. Sputum samples or tracheal aspirates were tested for the presence of bacteria and viruses. PCT levels were measured at the time of admittance, six hours, and 24 hours using a sensitive immunoassay. Thirty nine AECOPD patients were included, 31 of which (79%) required a ventilator support at admission. The median [25%-75% interquartile range] PCT level, assessed in 35/39 patients, was: 0.096 microg/L [IQR, 0.065 to 0.178] at the time of admission, 0.113 microg/L [IQR, 0.074 to 0.548] at six hours, and 0.137 microg/L [IQR, 0.088 to 0.252] at 24 hours. The highest PCT (PCTmax) levels were less than 0.1 microg/L in 14/35 (40%) patients and more than 0.25 microg/L in 10/35 (29%) patients, suggesting low and high probability of bacterial infection, respectively. Five species of bacteria and nine species of viruses were detected in 12/39 (31%) patients. Among the four patients positive for Pseudomonas aeruginosa, one had a PCTmax less than 0.25 microg/L and three had a PCTmax less than 0.1 microg/L. The one patient positive for Haemophilus influenzae had a PCTmax more than 0.25 microg/L. The presence or absence of viruses did not influence PCT at time of admission (0.068 vs 0.098 microg/L respectively, P = 0.80). The likelihood of bacterial infection is low among COPD patients admitted to ICU for AECOPD (40% with PCT < 0.1 microg/L) suggesting a possible inappropriate use of antibiotics. Further studies are necessary to assess the impact of a procalcitonin-based therapeutic strategy in critically ill COPD patients.


Impact of patient age on the outcome of primary breast carcinoma.
The poorer outcome amongst younger breast cancer patients continues to be an issue of debate. In order to clarify the prognostic value of patient age, we retrospectively analyzed the data of 1098 breast cancer patients. Patients were divided into two groups based on the age 35 (Group I, women aged 35 or younger, and Group II, women aged over 35). Clinico-pathological parameters, 10-year loco-regional recurrence-free (10LRRFS), distant relapse-free (10DRFS), and overall (10OS) survival estimates were determined. Among the 1098 patients, approximately 16.7% (183) were allocated to Group I and the other 83.3% (915) to Group II. There were no significant differences between the two groups in terms of histopathologic features or mean follow-up. Group I had a poorer 10LRRFS of 86.8% (P = 0.036), 10DRFS of 57.7% (P < 0.0001), and 10OS of 68.3% (P = 0.0001), compared with 93.9, 76.2, and 81.4% for Group II, respectively. Group I also showed a poorer 10DRFS when matched for stage and lymph node status as well. With lymph node status and tumor size, a patient age of younger than 35 was determined to be an independent prognostic factor by multivariate analysis. These results indicate that patient age (younger than 35) shows an independent prognostic value and that survival differences by age may reflect differences in the tumor biology.


Are the 1/3-Octave Band 63- and 125-Hz Noise Levels Predictive of Vessel Activity? The Case in the Cres-Lošinj Archipelago (Northern Adriatic Sea, Croatia).
A 3-years sea ambient-noise (SAN) monitoring was carried out in the Cres-Lošinj Archipelago (Croatia), where a bottlenose dolphin population is threatened by unregulated nautical tourism. A total of 540 5-min SAN samples were collected and analyzed in an Indicator 11.2.1 (Marine Strategy Framework Directive) perspective. The 1/3-octave band center frequencies of 63 and 125 Hz (re 1 μPa.rms) proved to be predictive of local predominant ship type over time. However, the noisiest band level was centered on 200 Hz. We therefore suggest measuring a wider frequency band than those requested in Indicator 11.2.1.


Laparoscopic CBD Exploration.
Laparoscopic CBD exploration (LCBDE) is a cost effective, efficient and minimally invasive method of treating choledocholithiasis. Laparoscopic Surgery for common bile duct stones (CBDS) was first described in 1991, Petelin (Surg Endosc 17:1705-1715, 2003). The surgical technique has evolved since then and several studies have concluded that Laparoscopic common bile duct exploration(LCBDE) procedures are superior to sequential endolaparoscopic treatment in terms of both clinical and economical outcomes, Cuschieri et al. (Surg Endosc 13:952-957, 1999), Rhodes et al. (Lancet 351:159-161, 1998). We started doing LCBDE in 1998.Our experience with LCBDE from 1998 to 2004 has been published, Gupta and Bhartia (Indian J Surg 67:94-99, 2005). Here we present our series from January 2005 to March 2009. In a retrospective study from January 2005 to March 2009, we performed 3060 laparoscopic cholecystectomies, out of which 342 patients underwent intraoperative cholangiogram and 158 patients eventually had CBD exploration. 6 patients were converted to open due to presence of multiple stones and 2 patients were converted because of difficulty in defining Calots triangle; 42 patients underwent transcystic clearance, 106 patients had choledochotomy, 20 patients had primary closure of CBD whereas in 86 patients CBD was closed over T-tube; 2 patients had incomplete stone clearance and underwent postoperative ERCP. Choledochoduodenosotomy was done in 2 patients. Patients were followed regularly at six monthly intervals with a range of six months to three years of follow-up. There were no major complications like bile leak or pancreatitis. 8 patients had port-site minor infection which settled with conservative treatment. There were no cases of retained stones or intraabdominal infection. The mean length of hospital stay was 3 days (range 2-8 days). LCBDE remains an efficient, safe, cost-effective method of treating CBDS. Primary closure of choledochotomy in select patients is a viable & safe option with shorter operative time and length of stay. LCBDE can be performed successfully with minimal morbidity & mortality.


"I miss the normalness": Mother and child perspectives of well-being and effective remote support from primary schools during Covid-19 school closures.
Covid-19 related school closures radically disrupted children's access to social and educational opportunities and changed daily life for millions of families across the world. Emerging evidence indicates that, overall, closures were associated with a decline in children's mental health and well-being, although individual experiences varied widely. The extent to which primary schools adapted remote well-being support is likely to have contributed to child and family adjustment, although this has not yet been fully explored in Covid related research. This longitudinal qualitative study examines variability in remote well-being provision in primary schools during the pandemic, and following school reopening, from the perspective of mothers and children using a whole school approaches framework. Twenty-one primary school aged children and their mothers took part in a semi-structured interview at two time points: time one during the first UK national lockdown and time two approximately seven months later after most children had returned to school. A hybrid inductive-deductive thematic analysis approach identified key themes relating to trajectories of well-being and remote school approaches over this period. School closures were associated with a decline in well-being for most children. Disrupted contact with friends and teachers, and limited opportunities for enriched, meaningful activity were identified as key risk factors. Protective factors included family and child characteristics that mitigated against the loss of wider systems of support, including family socioeconomic status, parental availability, child temperament, and structured daily routines. Four key dimensions of effective remote well-being provision were identified (the 4Cs). The 4Cs - contact, content, creativity and community - provide an accessible framework for schools to foster children's social relationships and sense of belonging during periods of closure. Analysis of pupil reintegration outcomes suggest that post-Covid support priorities should include extending social and play-based universal interventions in schools. Remote well-being support for children during Covid-related school closures varied in quality with implications for children's mental health and well-being. Findings from this study highlight the importance of ongoing social contact and enriched daily activities to protect children's well-being and development and present a framework of effective remote wellbeing support for primary schools in the event of future closures or prolonged pupil absence.


Data analytics in a clinical setting: Applications to understanding breathing patterns and their relevance to neonatal disease.
In this review, we focus on the use of contemporary linear and non-linear data analytics as well as machine learning/artificial intelligence algorithms to inform treatment of pediatric patients. We specifically focus on methods used to quantify changes in breathing that can lead to increased risk for apnea of prematurity, retinopathy of prematurity (ROP), necrotizing enterocolitis (NEC) and provide a list of potentially useful algorithms that comprise a suite of software tools to enhance prediction of outcome. Next, we provide a brief overview of machine learning/artificial intelligence methods and applications within the sphere of perinatal care. Finally, we provide an overview of the infrastructure needed to use these tools in a clinical setting for real-time data acquisition, data synchrony, data storage and access, and bedside data visualization to assist in clinical decision making and support the medical informatics mission. Our goal is to provide an overview and inspire other investigators to adopt these tools for their own research and optimization of perinatal patient care.


Downbeat nystagmus due to anticonvulsant toxicity.
Isolated downbeat nystagmus was observed in 2 patients on multiple anticonvulsant regimens. The nystagmus disappeared when phenytoin dosage was reduced. Electrooculographic analysis revealed impaired downward tracking, supporting the concept of "pursuit" nystagmus.


Identification of EPZ004777 and FG2216 as inhibitors of TGF-β1 induced Treg cells by screening a library of epigenetic compounds.
Regulatory T cells play an essential role in immune tolerance and homeostasis. Their long-term stability depends on epigenetic modifications and identification of small molecule modulators of Treg differentiation therefore has many applications. In this study, we performed a novel functional screen of an epigenetic compound library to identify compounds that can modulate generation of TGF-β1 induced T regulatory cells. A screening strategy based on IFN-γ ELISA was designed to screen epigenetic compound library. Effect of hit compounds on Treg phenotype and function was assessed by RT-PCR, flow cytometry and suppression assays. TGF-β signalling proteins were assayed by western blotting. Chromatin Immunoprecipitation (ChIP) assay was used to assess epigenetic modifications at Foxp3 gene locus. We screened 160 compounds to identify hits capable of reversing TGF-β induced inhibition of IFN-γ production in activated spleen cells and CD4+ T cells. Two compounds EPZ004777 and FG-2216 consistently reversed TGF-β1 iTregs in terms of (a) differentiation of naïve T cells into CD4+CD25+Foxp3+Treg cells, (b) Foxp3 target gene expression and (c) Treg suppressive function without affecting TGF-β downstream signalling. ChIP assay revealed that the compounds were able to reverse - TGF- β mediated decrease in epigenetic marks H3K27me3 and 5-mC and an increase in epigenetic marks H3K4me3 and H3K27Ac in the promoter and conserved non coding sequence (CNS1) regions of the Foxp3 gene. EPZ004777 and FG-2216 have been identified as potent epigenetic modulators that can reverse TGF-β1 induced T regulatory cells and may be used to treat diverse immune disorders.


Management of type 2 diabetes in older people.
The prevalence of diabetes is increasing due to aging of the population and increasing obesity. In the developed world, there is an epidemiologic shift from diabetes being a disease of middle age to being a disease of older people due to increased life expectancy. In old age, diabetes is associated with high comorbidity burden and increased prevalence of geriatric syndromes in addition to the traditional vascular complications. Therefore, comprehensive geriatric assessment should be performed on initial diagnosis of diabetes. Due to the heterogeneous nature of older people with diabetes and variations in their functional status, comorbidities, and life expectancy, therapeutic interventions, and glycemic targets should be individualized taking into consideration patients' preferences and putting quality of life at the heart of their care plans.


Validation of a neurovascular comorbidity index for risk adjustment of comorbid conditions among ischemic stroke patients receiving reperfusion treatment.
To validate a comorbidity index specific to neurovascular patients and determine its performance relative to the Charlson Comorbidity Index (CCI) and Elixhauser Comorbidity Index (ECI) among ischemic stroke patients receiving reperfusion treatments. Patients with ischemic stroke were identified in the National Inpatient Sample from Quarter 4 2015 to Quarter 4 2017. Ischemic stroke patients receiving reperfusion treatment, either with intravenous thrombolysis (IVT) only or mechanical thrombectomy (MT), were studied. The accuracy of the neurovascular comorbidities index (NCI) was compared to both the CCI and ECI in predicting in-hospital death and poor outcome (defined as death prior to discharge or discharge to a short-term hospital, a skilled nursing facility, an intermediate care facility, another long-term facility, or home health care). There were 25,147 ischemic stroke patients who received reperfusion therapy with either IVT only or MT (with or without IVT). Approximately 6.9% of patients died during their hospitalization, and 65.4% of patients were classified as having a poor outcome based on their discharge disposition. The NCI outperformed both the CCI and ECI in predicting in-hospital death (IVT only, p<0.0001; MT, p<0.0001) and poor outcomes (IVT only, p<0.0001; MT, p<0.0001). The NCI is a more powerful predictor of in-hospital death and poor outcomes when compared to the CCI or ECI among ischemic stroke patients receiving reperfusion therapies. Further validation studies are needed to confirm the accuracy of the NCI among other neurovascular patient populations.


Statherin-derived peptide protects against intrinsic erosion.
In the present study, we used an in vitro initial intrinsic erosion model to evaluate: (experiment 1) the influence of the degree of serine (Ser) phosphorylation of peptides containing the 15 N-terminal residues of statherin and (experiment 2) the effect of different concentrations of the peptide with the best performance in experiment 1 on initial enamel erosion. Bovine enamel specimens were divided into 6 groups (n = 15/group) for each experiment. In experiment 1, the peptides evaluated (at 1.88 × 10-5 M) were: not phosphorylated (StatSS), phosphorylated in Ser2 (StatpSS), phosphorylated in Ser3 (StatSpS) phosphorylated in Ser2 and Ser3 (StatpSpS). Phosphate buffer and human recombinant statherin were used as negative and positive controls, respectively. In experiment 2, StatpSpS was evaluated at different concentrations: 0.94, 1.88, 3.76 and 7.52 × 10-5 M. Phosphate buffer and 0.1 mg/mL CaneCPI-5 were employed as negative and positive controls, respectively. In each experiment, the specimens were incubated with the solutions for 2 h, then the AEP was allowed to form (under human pooled saliva) for 2 h. The specimens were then challenged with 0.01 M HCl for 10 s. Demineralization was evaluated by percentage of surface hardness change (%SHC). Data were analyzed by ANOVA and Tukey's test (p < 0.05). In experiment 1, only StatpSpS significantly reduced the % SHC in comparison with control. In experiment 2, 1.88 × 10-5 M StatpSpS significantly reduced the %SHC in comparison with control. This is the first study showing that statherin-derived peptide might protect against intrinsic erosion.


6-Gingerol via overexpression of miR-322-5p impede lipopolysaccharide-caused inflammatory response in RAW264.7 cells.
Acute lung injury (ALI) and sepsis are complicated syndromes that are often left untreated in critically ill patients. 6-Gingerol is a phenolic phytochemical compound that is found in fresh ginger, has pharmacological effects against inflammation. This study explored the roles of 6-gingerol in a mouse model of acute lung injury caused by lipopolysaccharide (LPS) and RAW-264.7 cells inflammation. The LPS-induced animal model underwent histopathological examinations, and RAW-264.7 cells viability was determined by Cell counting Kit-8 (CCk-8) assay. Additionally, qRT-PCR, Immunofluorescence, Western blot, and ELISA were used in vivo and in vitro to identify inflammatory factors and proteins associated with NF-κB and MAPK signaling pathways. In a histological examination 6-gingerol exhibited protective effects. Moreover, 6-gingerol elevated cell viability and downregulated inflammatory factors Interlukin-1β (IL-1β), Interlukin-6 (IL-6) and Tumor necrosis factor-α (TNF-α) in LPS-treated RAW-264.7 cells. Furthermore, 6-gingerol decreased phosphorylation of P65, P38 and the level of JNK in NF-κB and MAPK pathways. Importantly, 6-gingerol increased transcript abundance of miR-322-5p which suppressed by LPS and miR-322-5p downregulation negated the protective functions of 6-gingerol. The protective activity of 6-gingerol was mediated by miR-322-5p up-regulation.


Inhibition of amiloride-sensitive Na(+) absorption by activation of CFTR in mouse endometrial epithelium.
Previous studies have demonstrated amiloride-sensitive Na(+) absorption under basal conditions and cystic fibrosis transmembrane conductance regulator (CFTR)-mediated Cl(-) secretion following neurohormonal stimulation in the mouse endometrial epithelium. The present study investigated the inhibition of amiloride-sensitive Na(+) absorption accompanying activation of CFTR in the mouse endometrium using the short-circuit current ( I(sc)) technique. RT-PCR demonstrated the co-expression of CFTR and epithelial Na(+) channels (ENaC) in primary cultured mouse endometrial epithelia and cultured endometrial monolayers exhibited a basal amiloride-sensitive I(sc) of 5.4 +/- 0.6 microA/cm(2). The amiloride-sensitive current fell to 3.1 +/- 0.5 microA/cm(2) after stimulation with forskolin. When the possible contribution of Na(+) absorption to the I(sc) was eliminated by amiloride (1 microM) or Na(+) replacement, the forskolin-induced I(sc) was not reduced, but rather increased significantly compared with that in the absence of amiloride or in Na(+)-containing solutions ( P < 0.02), indicating that the forskolin-induced I(sc) was mediated by Cl(-) secretion, portion of which may be masked by concurrent inhibition of basal Na(+) absorption if the contribution of Na(+) is not eliminated. When the contribution of Cl(-) to the I(sc) was eliminated by diphenylamine 2,2'-dicarboxylic acid (DPC, 2 mM) or Cl(-) replacement, forskolin now decreased, rather than increased the I(sc), demonstrating the inhibition of Na(+) absorption upon stimulation. Our data suggest an interaction between CFTR and ENaC, which may be the underlying mechanism for balancing Na(+) absorption and Cl(-) secretion across the mouse endometrial epithelium.


The effect of body temperature on leukocyte kinetics during cardiopulmonary bypass.
Leukocyte kinetics were investigated in 22 patients undergoing cardiopulmonary bypass to determine the nature of the changes in the white blood cell count associated with this procedure. Both polymorphonuclear leukocytes and lymphocytes were taken up by the lung as pulmonary blood flow was lowered, but only polymorphonuclear leukocytes were taken up as blood flow was restored. The complement 3a level was increased approximately twice the control value within 2 minutes of going on bypass and remained elevated throughout the procedure. The peripheral white blood cell count doubled during the bypass procedure owing to a release of polymorphonuclear leukocytes and their precursors from the bone marrow. The increase in polymorphonuclear leukocytes was prevented by hyperthermia but reappeared quickly when the body temperature was restored to 36 degrees to 37 degrees C.


Gualou Xiebai Decoction ameliorates increased Caco-2 monolayer permeability induced by bile acids via tight junction regulation, oxidative stress suppression and apoptosis reduction.
Gualou Xiebai Decoction (GXD), a classic prescription, is widely used to dealing with inflammatory diseases in China for thousands of years. Abnormal metabolic state of bile acids (BAs) is confirmed to cause intestinal epithelial barrier dysfunction. In preliminary work, we observed that GXD could decrease intestinal permeability in hyperlipidemia mice. The present study aimed to explore the protective effect of GXD on intestinal mucosa in vitro. Caco-2 cell monolayer permeability among different groups was determined by measuring the concentrations of FITC-dextran in the lower compartments and transepithelial electrical resistance (TEER). Meanwhile, mRNA and protein expressions of tight junctions (TJs) were investigated. Generation of intracellular reactive oxygen species (ROS) and the ratio of cell apoptosis induced by BAs were assessed by fluorescence probe and flow cytometry. GXD was shown to keep the cell monolayer in low permeable status, increase TEER and mRNA and protein expressions of occludin (Ocln) and zonula occluden 2 (ZO2) remarkably in cells challenged with cholic acid (CA), deoxycholic acid (DCA) and glycocholic acid (GCA). However, no significant effects were uncovered against the pathological effects of taurocholic acid (TCA). Meanwhile, generation of ROS and increased levels of apoptotic cells caused by CA, DCA and GCA were dramatically decreased by GXD, which were not observed on TCA. GXD could significantly attenuate intestinal barrier dysfunction induced by BAs via TJs regulation, oxidative stress suppression and cell apoptosis decrease, but such effects and behind mechanisms differed among different kinds of BAs.


Physicochemical properties of starches isolated from pumpkin compared with potato and corn starches.
The aim of the study was to characterize the selected physicochemical, thermal and rheological properties of pumpkin starches and compared with the properties of potato and corn starches used as control samples. Pumpkin starches could be used in the food industry as a free gluten starch. Better thermal and rheological properties could contribute to reduce the costs of food production. The syneresis of pumpkin starches was similar to that of potato starch but much lower than that for corn starch. Pasting temperatures of pumpkin starches were lower by 17-21.7°C and their final viscosities were over 1000cP higher than corn paste, but were close to the values obtained for potato starch. The thermodynamic characteristic showed that the transformation temperatures of pumpkin starches were lower than those measured for control starches. A level of retrogradation was much lower in pumpkin starch pastes (32-48%) than was in the case of corn (59%) or potato (77%) starches. The pumpkin starches gels were characterized by a much greater hardness, cohesiveness and chewiness, than potato or corn starches gels.


Construction of an Escherichia coli K-12 ada deletion by gene replacement in a recD strain reveals a second methyltransferase that repairs alkylated DNA.
We constructed an ada deletion by gene replacement in a recD1014 strain of Escherichia coli. Characterization of a delta ada-25 recD+ strain revealed the presence of a second DNA methyltransferase activity in E. coli K-12 which transfers a methyl group from methylated DNA to a protein with a molecular weight of 18,000 to 20,000.


Efficacy of calcium propionate against fungicide-resistant fungal plant pathogens and suppression of botrytis blight of ornamental flowers.
Conventional fungicides are used in IPM programs to manage fungal plant pathogens, but there are concerns about resistance development in target organisms, environmental contamination, and human health risks. This study explored the potential of calcium propionate (CaP), a common food preservative generally recognized as safe (GRAS) to control fungicide-resistant plant pathogens, mainly Botrytis cinerea, and botrytis blight in ornamentals. In-vitro experiments using mycelium growth inhibition indicated a mean EC50 value for CaP (pH 6.0) of 527 mg/L for six isolates of Botrytis cinerea as well as 618, 1354, and 1310 mg/L for six isolates each of Monilinia fructicola, Alternaria alternata, and Colletotrichum acutatum. In vitro efficacy tests indicated CaP equally inhibited mycelium growth of fungal isolates sensitive and resistant to FRAC codes 1, 2, 3, 7, 9, 11, 12, and 17 fungicides. CaP at 0.1% (pH 6.0-6.5) reduced infection cushion (IC) formation in vitro, botrytis blight on petunia flowers, and botrytis blight of cut flower roses with little to no visible phytotoxicity. Although higher concentrations strongly inhibited infection cushion formation, they did not improve efficacy and exhibited phytotoxicity. We hypothesize that high concentrations may create tissue damage that facilitates direct fungal penetration without the need for infection cushion and subsequent appressoria formation. This study indicates the potential usefulness of CaP for blossom blight disease management in ornamentals if applied at concentrations low enough to avoid phytotoxicity.


Complication Avoidance in Neurosurgery with Use of Intraoperative Ultrasonography.
Intraoperative ultrasonography is an extremely valuable tool for avoidance of complications during neurosurgical procedures, including resection of intracranial and spinal cord tumors, removal of spontaneous intracerebral hemorrhages and arteriovenous malformations, and ventricular access for shunt placements. Nevertheless, application of this highly useful technique may be accompanied by some challenges and difficulties, as well as human errors; thus, it requires specific knowledge and continuous training.


Protein surface engineering of endoglucanase Penicillium verruculosum for improvement in thermostability and stability in the presence of 1-butyl-3-methylimidazolium chloride ionic liquid.
Thermostability and stability in ionic liquids are essential properties of cellulases that are applied in industrial processes of bioconversion. Engineering of protein surface of endoglucanase II from Penicillium verruculosum was used to improve the enzyme thermostability and stability in 1-butyl-3-methylimidazolium chloride ([Bmim]Cl). The engineering was based on analysis of the protein surface topography and enhanced by multiple sequence alignment and ΔΔG calculations. In the case of the thermostability, half-life time was improved in 1.3-1.6 times at 70 °C and 1.2-1.4 times at 80 °C. In the case of the stability in [Bmim]Cl, the residual activity after 72 h of incubation in the presence of [Bmim]Cl (50 g/L, 50 °C, pH 4.5) was 1.7-1.9 times greater for the tailored enzyme. The yield of reducing sugars after enzymatic hydrolysis of aspen wood pretreated with [Bmim]Cl was 10-20% higher with the tailored endoglucanase.


Efficacy of Invariant Natural Killer T Cell Infusion Plus Transarterial Embolization vs Transarterial Embolization Alone for Hepatocellular Carcinoma Patients: A Phase 2 Randomized Clinical Trial.
Invariant NKT cells (iNKT) are CD1d-restricted T cells with the capacity of antitumor immunity. The safety of autologous iNKT cell treatment in hepatocellular carcinoma (HCC) has been verified. This study aimed to investigate its efficacy in advanced HCC after transarterial chemoembolization (TACE) failure. This open-label, randomized, controlled, trial enrolled 60 patients with unresectable HCC after TACE failure at three centers. Transarterial embolization (TAE) was used instead of TACE to protect iNKT cell function. Patients were randomly assigned (1:1) to receive TAE therapy with (TAE-iNKT) or without (TAE) biweekly iNKT cell infusion. The primary endpoint was progression-free survival (PFS). Secondary endpoints included overall survival (OS), objective response rate (ORR), disease control rate (DCR), quality of life (QoL), peripheral blood cell count, and safety. Fifty-four patients completed the study. Median PFS was significantly higher in TAE-iNKT patients (5.7 months [95% CI, 4.3-7.0 months]) compared with TAE patients (2.7 months [95% CI, 2.3-3.2 months]; hazard ratio 0.32 [95% CI, 0.16-0.63]; P<0.001). Higher ORR and DCR were observed in TAE-iNKT patients (52% and 85%, respectively) compared with TAE patients (11% and 33%; respectively). Five TAE-iNKT patients and 1 TAE patient achieved completed response. The median time to deterioration in QoL was longer in TAE-iNKT patients (9.2 months [95% CI, 6.0-13.3 months]) compared with TAE patients (3.0 months [95% CI, 2.9-3.0 months]). The mean lymphocytes were higher in the TAE-iNKT group than in the TAE group at 8 (1.48 vs 0.95×109/L, P = 0.007) and 12 (1.49 vs 0.89×109/L, P = 0.001) weeks. Grade 3 adverse events occurred in 1 TAE-iNKT patient (4%) and 5 TAE patients (19%). All the other adverse events were grade 1-2. iNKT cell infusion significantly improved PFS, ORR, DCR, and QoL with manageable toxicity during TAE therapy in patients with HCC. Trial Registration ClinicalTrials.gov Identifier: NCT04011033.


Molecular Cloning, Structural Modeling and the Production of Soluble Triple-Mutated Diphtheria Toxoid (K51E/G52E/E148K) Co-expressed with Molecular Chaperones in Recombinant Escherichia coli.
CRM197 is a diphtheria toxin (DT) mutant (G52E) which has been used as a carrier protein for conjugate vaccines. However, it still possesses cytotoxicity toward mammalian cells. The goal of this project was to produce a non-toxic and soluble CRM197EK through introduction of triple amino acid substitutions (K51E/G52E/E148K) in Escherichia coli. The expression of CRM197EKTrxHis was optimized and co-expressed with different molecular chaperones. The soluble CRM197EKTrxHis was produced at a high concentration (97.33 ± 17.47 μg/ml) under the optimal condition (induction with 0.1 mM IPTG at 20 °C for 24 h). Cells containing pG-Tf2, expressing trigger factor and GroEL-GroES, accumulated the highest amount of soluble CRM197EKTrxHis at 111.24 ± 10.40 μg/ml after induction for 24 h at 20 °C. The soluble CRM197EKTrxHis still possesses nuclease activity and completely digest λDNA at 25 and 37 °C with 8- and 4-h incubation, respectively. Molecular modeling of diphtheria toxin, CRM197 and CRM197EK indicated that substitutions of two amino acids (K51E/E148K) may cause poor NAD binding, consistent with the lack of toxicity. Therefore, CRM197EK might be used as a new potential carrier protein. However, further in vivo study is required to confirm its roles as functional carrier protein in conjugate vaccines.


Interaction between hypothalamic peptides in a superfused pituitary cell system.
Recently two hypothalamic releasing factors have been isolated, sequenced and synthesized: corticotropin-releasing factor (CRF) from sheep and rat hypothalami; and growth hormone-releasing factor (GH-RF) from tumors in human pancreas (hpGH-RF) and from rat hypothalami (rhGH-RF). Their biological potencies were tested by various laboratories in vivo and in vitro using rat pituitary cell cultures and the pituitary quarters method. In the present study, we investigated the dynamics of the release of pituitary hormones and the interaction between CRF and hGH-RF and several brain peptides in a pituitary cell-superfusion system. A dose-related ACTH release was found when the cells were superfused with different doses of synthetic CRF. Synthetic hGH-RF44, hGH-RF40, hGH-RF1-29 and purified porcine hypothalamic GH-RF caused similar dose-related releases of GH. In this system, we demonstrated interactions between CRF and vasopressin, CRF and SP, hGH-RF and vasopressin and hGH-RF and PHI-27. We conclude that the control of pituitary hormone secretion is a complex process; several factors may interact with each releasing or inhibiting factor to modulate their effects.