Kinetochore kinesin CENP-E is a processive bi-directional tracker of dynamic microtubule tips.
During vertebrate mitosis, the centromere-associated kinesin CENP-E (centromere protein E) transports misaligned chromosomes to the plus ends of spindle microtubules. Subsequently, the kinetochores that form at the centromeres establish stable associations with microtubule ends, which assemble and disassemble dynamically. Here we provide evidence that after chromosomes have congressed and bi-oriented, the CENP-E motor continues to play an active role at kinetochores, enhancing their links with dynamic microtubule ends. Using a combination of single-molecule approaches and laser trapping in vitro, we demonstrate that once reaching microtubule ends, CENP-E converts from a lateral transporter into a microtubule tip-tracker that maintains association with both assembling and disassembling microtubule tips. Computational modelling of this behaviour supports our proposal that CENP-E tip-tracks bi-directionally through a tethered motor mechanism, which relies on both the motor and tail domains of CENP-E. Our results provide a molecular framework for the contribution of CENP-E to the stability of attachments between kinetochores and dynamic microtubule ends.


Amyloid-like aggregation and fibril core determination of TDP-43 C-terminal domain.
Cytoplasmic inclusion of TAR DNA-binding protein 43 (TDP-43) is a hallmark of most ALS (amyotrophic lateral sclerosis) and FTLD (Frontotemporal dementia), yet the aggregation of TDP-43 remains unclear. In this study, we proved the existence of amyloid-like structures of C-terminal domain of TDP-43 (TDP-C) in bacterial inclusion bodies (IBs), and obtained a homogenous fibril sample by seeding from the components of aggregated TDP-C in Escherichiacoli IBs. The results from solid-state NMR spectroscopy suggest that the homogenous fibrils were seeded from a tiny amount of aggregated TDP-C compositions in IBs; the structure characteristics of the rigid fibril core are identified of β-rich structures, and show subtle relativity with the hydrophobicity of residues. Our study here provides a further understanding of TDP-43 protein aggregation and fibrillation.


Gliquidone improves retinal injury to relieve diabetic retinopathy via regulation of SIRT1/Notch1 pathway.
Diabetic retinopathy (DR) is a common and potentially devastating microvascular complication of diabetes mellitus (DM). The main features of DR are inflammation and oxidative damage. Gliquidone (GLI) is confirmed to be a hypoglycemic drug by oral administration. The current study is aimed to investigate the role and mechanism of GLI on the pathogenesis of DR. High glucose (HG)-induced human retinal endothelial cells (HRECs) were used to explore the anti-inflammatory and anti-oxidant effects of GLI on DR in vitro. Streptozotocin (STZ)-induced DM rats were used to investigate the effects of GLI on retinal structures, inflammation, and oxidative stress. The levels of SIRT1/Notch1 pathway-related proteins were determined by western blotting. GLI treatment promoted the viability and inhibited the apoptosis of HG-induced HRECs. Meanwhile, the levels of interleukin (IL)-6, IL-1β, tumour necrosis factor alpha and reactive oxygen species were suppressed, while both catalase and superoxide dismutase were elevated after GLI treatment in HG-induced HRECs. Furthermore, we found that Silencing information regulator 2 related enzyme 1 (SIRT1) silencing reversed the inhibiting effects of GLI on the levels of protein Notch1 and effector genes Hes1 and Hey2. Similar anti-inflammatory and anti-oxidant effects of GLI in STZ-induced DM rats were observed. Additionally, GLI administration also repressed vascular hyperpermeability in vivo. GLI may be an effective agent to improve DR through repression of inflammation and oxidative stress via SIRT1/Notch1 pathway.


Functional group substitutions influence the binding of benzophenone-type UV filters with DNA.
As a class of possible carcinogens, benzophenone-type UV filters (BPs) widely exist in natural environments and organisms. The crucial step of the carcinogenic process induced by cancerous toxins is binding with DNA to form adducts. Here, the binding of 10 typical BPs, i.e., benzophenone (BP1), 2-hydroxyl benzophenone (BP2), 4-hydroxyl benzophenone (BP3), 2,2'-dihydroxyl benzophenone (BP4), 2,4-dihydroxyl benzophenone (BP5), 4,4'-dihydroxyl benzophenone (BP6), 2,4,4'-trihydroxyl benzophenone (BP7), 2,2',4,4'-tetrahydroxyl benzophenone (BP8), 2-hydroxyl-4-methoxyl benzophenone (BP9), and 2,2'-dihydroxyl-4-methoxyl benzophenone (BP10), with DNA was tested via fluorescence quenching experiments. Only hydroxyl group-substituted BPs could bind to DNA by groove binding mode, and the quenching constants were 0.93 × 103-5.89 × 103 L/mol. Substituted BPs were preferentially bound to thymine. Circular dichroism analysis confirmed that BPs could affect DNA base stacking but could not transform its B-form. Based on molecular electrostatic surface potential analyses, molecular dynamics simulations, and energy decomposition calculations, it could be found that the site and number of hydroxyl substitution changed the molecular polarity of BPs, thereby affecting the number and strength of hydrogen bonds between BPs and DNA. The hydroxyl substitution at site 2 was more conducive to binding than at site 4. This study is beneficial in comprehending the carcinogenic mechanisms of BPs.


The classification of osteonecrosis in patients with cancer: validation of a new radiological classification system.
To validate a new, non-joint-specific radiological classification system that is suitable regardless of the site of the osteonecrosis (ON) in patients with cancer. Critical deficiencies in the existing ON classification systems were identified and a new, non-joint-specific radiological classification system was developed. Seventy-two magnetic resonance imaging (MRI) images of patients with cancer and ON lesions were graded, and the validation of the new system was performed by assessing inter- and intra-observer reliability. Intra-observer reliability of ON grading was good or very good, with kappa values of 0.79-0.86. Interobserver agreement was lower but still good, with kappa values of 0.62-0.77. Ninety-eight percent of all intra- or interobserver differences were within one grade. Interobserver reliability of assessing the location of ON was very good, with kappa values of 0.93-0.98. All the available radiological ON classification systems are joint specific. This limitation has spurred the development of multiple systems, which has led to the insufficient use of classifications in ON studies among patients with cancer. The introduced radiological classification system overcomes the problem of joint-specificity, was found to be reliable, and can be used to classify all ON lesions regardless of the affected site.


A complete culture system for the chick embryo.
The embryonic lifespan of the chick is 22 days. Development in the first day takes place in the oviduct, and in the remaining 21 days in the shelled egg. There have been few attempts to culture oviductal embryos, though methods covering the first few days of development in ovo are well established and a method for the final 18 days of development through hatching has recently been devised. I have now succeeded in culturing the fertilized ovum of the chick (Gallus domesticus) for the total embryonic period by growing it in a series of separate culture systems. This is the first report of a complete in vitro method for a homoiothermic animal. The technique opens the way to the investigation of developmental events in birds that require access to the embryo at the single-cell stage, and in particular to the genetic manipulation of the fertilized ovum.


Myofibroblasts: A New Factor Affecting the Hyperlipidemia-Induced Elastic Abnormality of Corpus Cavernosum in Rabbits Detected by 2-D Shear Wave Elastography.
Two-dimensional shear wave elastography (2-D SWE) has been proven to detect hyperlipidemia-induced elastic abnormality in the corpus cavernosum. This study investigated cytological factors affecting the elasticity of the corpus cavernosum in rabbits with hyperlipidemia using single-cell RNA sequencing (scRNA-seq). Male New Zealand white rabbits were randomly divided into a hyperlipidemia group (high-cholesterol diet) and a control group (standard diet). Penile 2-D SWE was performed to detect the elastic abnormality in the corpus cavernosum. ScRNA-seq was performed to observe cellular changes in the corpus cavernosum of rabbits with hyperlipidemia. Immunohistochemistry, immunofluorescence and histological examinations were conducted to verify the results of scRNA-seq. Two-dimensional SWE revealed that the Young's modulus of the corpus cavernosum was significantly greater in the hyperlipidemia group than that in the control group (p < 0.001). Histological findings revealed extracellular matrix accumulation within the corpus cavernosum, with stronger staining of collagen types I and Ⅲ. ScRNA-seq revealed that fibroblasts, smooth muscle cells, and endothelial cells were the major cell types in the corpus cavernosum. A novel subtype of fibroblasts (myofibroblast) was discovered in the hyperlipidemia group, which was verified by immunofluorescence staining and gene ontology analysis. Fibroblasts, smooth muscle cells and endothelial cells were three cellular sources for myofibroblasts. Myofibroblasts are activated and proliferate and secrete large amounts of collagen fibers in the corpus cavernosum during hyperlipidemia, leading to abnormal Young's modulus detected by 2-D SWE and their recognition as a new factor affecting the hyperlipidemia-induced elastic abnormality of the corpus cavernosum.


Evaluation of a progressive algorithmic approach for the treatment of unresectable colon polyps using colon conservation techniques.
The majority of endoscopically unresectable colon polyps (EUCP) are treated by segmental colectomy. However, up to 90% of EUCP do not harbor malignancy, making colectomy an unnecessary procedure. To minimize unnecessary segmental colectomy, we established a progressive treatment algorithm utilizing colon conservation techniques (CCT). In our progressive CCT algorithm, patients with EUCP first underwent endoscopic submucosal dissection (ESD). If unsuccessful, they progressed to combined endo-laparoscopic surgery (CELS) and ultimately to segmental colectomy, if necessary. We performed a retrospective analysis of all patients treated by our progressive CCT algorithm from August 2015 to April 2019. Demographic information, polyp characteristics, and clinical outcomes were analyzed. We also compared the outcomes of our CCT algorithm group to 156 patients undergoing segmental colectomy for EUCP at related institutions from August 2015 to August 2018. A total of 102 EUCP in 97 patients were treated with our progressive CCT algorithm. Of these, 76 of 102 (75.5%) EUCP were removed without requiring segmental colectomy, with 42 EUCP removed via ESD and 34 via CELS. Interval surveillance colonoscopy confirmed that 72 of 97 (74.2%) patients with EUCP treated by CCT completely avoided segmental colectomy. Polyps > 5 cm in size was a significant predictor of CCT failure (OR 3.83, P = 0.03). When compared to an external cohort of patients undergoing segmental colectomy for EUCP, the CCT algorithm was associated with longer operative time, but shorter length of stay, with no difference in postoperative complications. The estimated total healthcare cost of the CCT algorithm was lower than segmental colectomy ($10,956.77 versus $16,692.94), with more dramatic cost savings seen in ESD ($4,492.70) and CELS ($8,507.06). An established progressive CCT algorithm can result in high colon conservation rate and decrease associated health care costs compared to segmental colectomy. It is a reasonable treatment strategy for patients with EUCP.


Proposed limits for ordinal echocardiographic estimates of left atrial enlargement in dogs.
To propose echocardiographic left-atrial-to-aortic ratio (LA:Ao) limits for defining ordinal categories of left atrial (LA) enlargement in dogs. Right parasternal short-axis echocardiographic images from 33 dogs with various degrees of LA enlargement. Right parasternal short-axis and long-axis echocardiographic measurements from 238 healthy dogs. Images were duplicated and randomized. Duplicate images contained a LA:Ao estimate. Participants categorized the LA in each image into one of four categories: normal, mildly, moderately or severely enlarged. Distributions of categorization were compared between cardiologists and non-cardiologists. Intra-observer intra-study and inter-study agreement were examined. Effect of measurement was evaluated on agreement between participants. A parametric estimate of LA enlargement was calculated for both short-axis and long-axis views. Cardiologists and non-cardiologists provided similar distributions of LA size estimates, and showed similarly high intra-observer agreement (kappa = 0.84). Having a measurement provided with the image increased agreement for categorizing LA as normal or mildly enlarged (P<0.001). Parametric and consensus-based approaches provided similar limits for categorizing left atrial size in the right parasternal short-axis view - normal = LA:Ao < 1.6, mildly enlarged = 1.6 < LA:Ao < 1.9, moderately enlarged = 1.9 < LA:Ao < 2.3, severely enlarged = LA:Ao ≥ 2.3. A parametric approach for the right parasternal long-axis view provided the following: normal = LA:Ao < 2.1, mildly enlarged = 2.1 < LA:Ao < 2.5, moderately enlarged = 2.5 < LA:Ao < 2.7, severely enlarged = LA:Ao ≥ 2.7. Participants mostly classified LA sizes into four ordinal categories that corresponded to the aforementioned limits. Clinicians estimating LA size in early diastole can use these limits to increase inter-observer agreement when identifying LA enlargement.


Breastfeeding and Inborn Errors of Amino Acid and Protein Metabolism: A Spreadsheet to Calculate Optimal Intake of Human Milk and Disease-Specific Formulas.
Human milk (HM) offers important nutritional benefits. However, except for phenylketonuria (PKU), there are little data on optimal levels of consumption of HM and a special formula free of disease-related amino acids (SF-AA) in infants with inborn errors of metabolism of amino acids and proteins (IEM-AA-P). We designed a spreadsheet to calculate the amounts of SF-AA and HM required to cover amino acid, protein, and energy needs in patients with the nine main IEM-AA-P in infants aged under 6 months. Upon entering the infant's weight and the essential amino acid or intact protein requirements for the specific IEM, the spreadsheet calculates the corresponding required volume of HM based on the amino acid concentration in HM. Next, the theoretical daily fluid intake (typical range, 120-200 mL/kg/day) is entered, and the estimated daily fluid intake is calculated. The required daily volume of SF-AA is calculated as the difference between the total fluid intake value and the calculated volume of HM. The spreadsheet allows for the introduction of a range of requirements based on the patient's metabolic status, and includes the option to calculate the required volume of expressed HM, which may be necessary in certain conditions such as MMA/PA and UCD. In cases in which breastfeeding on demand is feasible, the spreadsheet determines the daily amount of SF-AA divided over 6-8 feeds, assuming that SF-AA is administered first, followed by HM as needed. Intake data calculated by the spreadsheet should be evaluated in conjunction with data from clinical and nutritional analyses, which provide a comprehensive understanding of the patient's nutritional status and help guide individualized dietary management for the specific IEM.


An innovative approach in osteoporosis opportunistic screening by the dental practitioner: the use of cervical vertebrae and cone beam computed tomography with its viewer program.
To investigate the use of cone beam computed tomography (CBCT) for predicting osteoporosis based on the cervical vertebrae CBCT-derived radiographic density (RD) using the CBCT-viewer program. CBCT scans (WhiteFox, de Gotzen S.r.l device, distributed by Satelec-Acteon Group, Italy) and dual-energy X-ray absorptiometry examinations of 38 women who participated in an earlier investigation were examined. A coronal slice, subjectively determined from the cervical vertebrae, was selected and the RD as gray values for the first and second vertebrae, and the dens was calculated by using CBCT-viewer software (WhiteFox imaging). The CBCT-derived RD values of the dens and the left part of the first cervical vertebra showed the strongest correlation coefficients (r=0.7, 0.6; P<.001) and the highest sensitivity (76.9%, 70%), specificity (92%, 92.9%), and accuracy (90.8%, 86.4%) in predicting osteoporosis in the lumbar vertebrae and the femoral neck, respectively. CBCT-derived RD of cervical vertebrae can predict osteoporosis status using a CBCT-viewer program. This finding should be confirmed on other CBCT devices.


Vogesella urethralis-induced aspiration pneumonia and bacteremia in an elderly man: a first case report and literature review.
Vogesella species are common aquatic Gram-negative rods that were first reported in 1997. Vogesella urethralis bacterium was first isolated from human urine in 2020. Only two cases of disease caused by Vogesella species have been reported with no case of Vogesella urethralis-caused disease being reported as yet. Herein, we report a case of aspiration pneumonia and bacteremia caused by Vogesella urethralis. An 82-year-old male patient was admitted with dyspnea, increased sputum production, and hypoxia. Gram-negative rods were isolated from the blood and sputum cultures of the patient. He was diagnosed with aspiration pneumonia and bacteremia. Initially, Vogesella urethralis was wrongly identified as Comamonas testosteroni based on fully automated susceptibility testing; however, additional 16S rRNA gene sequencing identified the causative as Vogesella urethralis. The patient was treated with piperacillin and tazobactam. Unfortunately, he developed aspiration pneumonia again and died during hospitalization. Since no database exists for rare bacteria in traditional clinical microbiology laboratories, 16S rRNA gene sequence analysis is useful. We report the first case of Vogesella urethralis-induced aspiration pneumonia and bacteremia.


β-Hydroxybutyrate attenuates NMDA-induced spasms in rats with evidence of neuronal stabilization on MR spectroscopy.
Infantile spasms (IS) is a devastating epileptic encephalopathy. The ketogenic diet (KD) has been successfully used as a treatment for IS. This study was designed to test whether beta-hydroxybutyrate (BHB), a major metabolite of the KD, is effective in an animal model of IS. Pregnant rats received betamethasone on gestational day 15. The offspring received either single [30min prior to NMDA-triggered spasms on postnatal day (P) 15] or prolonged (three per day from P12 to P15) i.p. BHB. An additional experiment used repeated bouts of spasms on P12, P13, and P15 with randomized prolonged BHB treatment initiated after the first spasms. We determined the latency to onset of spasms and the number of spasms after the NMDA injection on P15. The rats that received randomized BHB treatment were also monitored with open field, sociability, and fear-conditioning tests and underwent in vivo (1)H MR imaging on a 9.4T MR system after NMDA-induced spasms. The acquired (1)H MR spectra were quantified using LC model. Single-dose BHB pretreatment had no effect on spasms. In contrast, prolonged pretreatment with BHB significantly delayed the onset and decreased the frequency of spasms. In addition, randomized prolonged BHB treatment resulted in a significant reduction in number of spasms at P15. BHB treatment had no significant effect on motor activities, but significantly decreased the interactions with strangers and increased the contextual memory. On MR spectroscopic analysis of randomized prolonged BHB-treated rats at 24h after the cluster of spasms, the elevation of GABA, glutamine, glutamate, total creatine, macromolecule-plus lipids, and N-acetylaspartate levels after spasms were significantly attenuated by randomized BHB treatment (p<0.05). Prolonged administration of BHB directly suppresses development of spasms in a rat model of IS with acute stabilization of brain metabolites. Additionally, BHB appears to decrease the interests to other rats and improve memory responses.


Application of "membrane-engineering" to bioelectric recognition cell sensors for the ultra-sensitive detection of superoxide radical: a novel biosensor principle.
A new, hybrid type of ultra-sensitive electrophysiological superoxide anion (O2*-) sensor is described, which is based on "membrane-engineered" mammalian cells immobilized in an alginate matrix. The membrane-engineering process involved the electroinsertion of superoxide dismutase (SOD) molecules in the membranes of Vero fibroblast cells, which acted as catalytic units able to convert O2*- to H2O2. Superoxide dismutation triggered changes to the cell membrane potential that were measured by appropriate microelectrodes, according to the principle of the bioelectric recognition assay (BERA). The sensor instantly responded to O2*- with a detection limit (S/N=3) of 100 pM. Combined with a 4-month storage capacity at room temperature, the novel biosensor principle offers new perspectives for monitoring ultra-low concentrations of free radical species and oxidative agents in biological systems.


Migration of fluoride ions from the permanent teeth into saliva in children with glass ionomer cement restorations: an in vitro study.
Glass ionomer cements (GIC) belong to the group of polycarboxyl cements, and one of the principal characteristics of these materials is their anticariogenic potential of fluorine release into saliva and enamel-dentin substance. The aim of this study was to examine the content of released fluorine from GIC restorations (Fuji IX, GC, Japan) of young permanent teeth in the medium of artificial saliva and similar releases in the same medium by the restorations of these teeth treated with a low concentration fluoride solution. We examined 12 premolars extracted from orthodontic reasons. The GIC restored teeth were divided into the group treated daily with low concentration fluoride solution (334 ppm) and the control, not treated group. The samples of artificial saliva were analyzed for fluorine ion content using an ion selective electrode. Our comparative analysis of the mean values using the Student's t-test demonstrated a statistically significant difference in fluorine ion concentration in artificial saliva of fluoridated and non-fluoridated teeth with GIC fillings after 14 and 21 days (p < 0.05), while the difference detected after 7 days was with no statistical significance. The results of this in vitro study indicated that low-concentration fluoride solutions could serve to refluoridate GIC fillings and contribute to an increased fluorine content in saliva. The process of refluoridation of GIC fillings should be advised 2-3 weeks after the restoration, since the release of fluorine from GIC fillings diminishes in time.


Diabetic retinopathy - An update.
Management of diabetes should involve both systemic and ocular aspects. Control of hyperglycemia, hypertension and dyslipidemia are of major role in the management of diabetic retinopathy. In the ocular part; laser treatment remains the cornerstone of treatment of diabetic macular edema (focal/grid), severe non-proliferative and proliferative diabetic retinopathy (panretinal photocoagulation). There is a strong support to combination therapy. Using one or two intravitreal injections such as anti-VEGF and or steroid to reduce central macular thickness followed by focal or grid laser to give a sustained response may offer an alternative to treatment in diabetic macular edema. Anti-VEGF were found to be effective as an adjunct therapy in proliferative diabetic retinopathy patient who is going to have vitrectomy for vitreous hemorrhage with neovascularization, panretinal photocoagulation, and other ocular surgery such as cases with neovascular glaucoma and cataract with refractory macular edema.


An exploration of the role of exercise in modulating breast cancer progression in vitro: a systematic review and meta-analysis.
Breast cancer is the most prevalent cancer in women worldwide. In the United Kingdom, approximately 5% of all breast cancers are already metastatic at the time of diagnosis. An abundance of literature shows that exercise can have beneficial effects on the outcome and prognosis of breast cancer patients, yet the molecular mechanisms remain poorly understood. There are several in vitro models that aim to recapitulate the response of breast cancer to exercise in vivo; this systematic review and meta-analysis summarizes the existing literature. The following search terms were used to conduct a systematic literature search using a collection of databases (last search performed May 2020): "in vitro," "exercise," and "breast cancer." Only studies that investigated the effects of exercise on breast cancer in vitro were included. Standardized mean differences (SMD) were calculated to determine pooled effect sizes. This meta-analysis has successfully demonstrated that various identified exercise interventions on breast cancer cells in vitro significantly reduced breast cancer cell viability, proliferation, and tumorigenic potential (SMD = -1.76, P = 0.004, SMD = -2.85, P = 0.003, and SMD = -3.15, P = 0.0008, respectively). A clear direction of effect was found with exercise on breast cancer cell migration in vitro, however this effect was not significant (SMD = -0.62, P = 0.317). To our knowledge, this is the first meta-analysis and systematic review investigating and summarizing literature on exercise and breast cancer in vitro, highlighting models used and priority areas for future research focus.


A ferroptosis-inducing biomimetic nanocomposite for the treatment of drug-resistant prostate cancer.
Second-generation androgen receptor (AR) inhibitors such as enzalutamide are the first-line treatments for castration-resistant prostate cancer (CRPC). Resistance to enzalutamide will greatly increase the difficulty of prostate cancer treatment and reduce the survival time of patients. However, drug-resistant cancer cells seem to be more sensitive to ferroptosis. Therefore, we constructed a biomimetic tumor-targeting magnetic lipid nanoparticle (t-ML) to codeliver dihomo-γ-linolenic acid (DGLA) and 2,4-dienoyl-CoA reductase 1 (DECR1) siRNA (t-ML@DGLA/siDECR1). DGLA is a dietary polyunsaturated fatty acid (PUFA), while DECR1 is overexpressed in prostate cancer and can inhibit the generation of PUFAs. The combination of DGLA and siDECR1 can efficiently induce ferroptosis by peroxidation of PUFAs, which has been verified both in vitro and in vivo. With the assistance of an external magnet, t-ML showed good tumor targeting ability and biocompatibility, and t-ML@DGLA/siDECR1 exhibited significant ferroptosis induction and tumor suppression capabilities. Moreover, in a nude mouse model of prostate cancer fed on a high-fat diet (HFD), there was no distant organ metastasis when the tumor-bearing mice were treated with t-ML@DGLA/siDECR1 and an external magnet, with upregulated PUFAs and downregulated monounsaturated fatty acids (MUFAs). Hence, this study has broadened the way of treating drug-resistant prostate cancer based on ferroptosis induction.


The role of the lay midwife in childbirth in rural Portugal.
The following article was written shortly after the fieldwork was completed in 1979. The research was conducted just after Portugal's 1974 revolution, prior to which a repressive political regime allowed virtually no social research. Since that time, some significant works have been published, but no other ethnographies focus on the role of the lay midwife. The kind of information obtained in this study required then, and would now require, heavy reliance on ethnographic fieldwork. This publication may serve as a baseline for comparative research. An epilogue provides some updating of statistical information about infant mortality rates; however, little can be determined about rural-urban differences. The limited information available suggests that very little may have changed in the last 15 years for the lay midwives in the rural villages studied.


The white coat phenomenon is benign in referred treated patients: a 14-year ambulatory blood pressure mortality study.
Previous reports on the prognosis of white coat hypertension are ambiguous. We aimed to determine the prognostic implications of the white coat phenomenon in treated patients. Our 14-year hospital-based ambulatory blood pressure (BP) monitoring prospective database was analyzed for all-cause mortality. The relationships of the white coat and masking effects with mortality were assessed both categorically (controlled awake versus clinic BP) and in a continuous mode (clinic-awake BP difference). During the follow-up period, 2285 treated patients (aged 61 +/- 13 years, 57% women) were monitored (17621 patient-years, 286 deaths). Mean BMI was 27.8 +/- 4.5 kg/m2 and 13% were treated for diabetes. Controlled hypertension (normal clinic and awake BP) was found in 15.8%, high clinic BP (with controlled awake BP; namely, white coat uncontrolled hypertension) in 12.1%, awake hypertension (with controlled clinic BP; namely, masked uncontrolled hypertension) in 11.8%, and sustained hypertension (both clinic and awake) in 60.3%. Compared with white coat uncontrolled hypertension, age-adjusted Cox-proportional all-cause mortality hazard ratios were 1.42 (0.81-2.51) for controlled hypertension, 1.88 (1.08-3.27) for masked uncontrolled hypertension, and 2.02 (1.30-3.13) for sustained hypertension. Hazards ratios per 1% increase in the clinic-awake BP difference were 0.992 (0.983-1.002) for systolic BP and 0.981 (0.971-0.991) for diastolic BP, adjusted for age, sex, diabetes, and either systolic or diastolic awake BP, respectively. In treated hypertensive patients referred for ambulatory BP monitoring, the white coat effect is benign compared with the reverse (masking) phenomenon, which has a poorer prognosis.


[Significance of predialysis preparation and patient information in choosing the dialysis method].
Every patient has the right for objective information on all therapeutic options for his disease. Hemodialysis and peritoneal dialysis are equally effective in the treatment of end-stage renal disease. Patients without contraindications who are suitable for both options should receive a balanced education to enable them to select their treatment modality. Any information needs to be unbiased, clearly structured and should be provided by a multidisciplinary team. Extensive information increases the proportion of patients who will opt for peritoneal dialysis. In the future, predialysis education and management should be offered to all patients with advanced chronic kidney disease.


Studies on populations of Folsomia candida (Insecta: Collembola) : The productivity of populations in relation to food and exploitation.
Experiments are described that were designed to investigate the effects of food availability and rate of exploitation on the growth and production of populations of Folsomia candida (Willem). In an initial experiment in which there was excess food it was found that increasing the rate of exploitation resulted in increases in both the numerical and biomass productivity of the populations. In a second experiment it was shown that, when there is severe competition for food, the rate of exploitation does not affect either the biomass or the numerical production. It is concluded that the effect of overcrowding, in the form of competition for space, does contribute to the growth in numbers of populations, but that the supply of food plays a more important role in regulating the population. Anomalous results, showing that exploitation has a lesser effect when there is severe competition for food, are discussed.


Maternal Stress in Gestation: Birth Outcomes and Stress-Related Hormone Response of the Neonates.
Relatively few studies have been made on neurobehavioral outcomes of prenatal maternal stress during the newborn period, and little research has focused on umbilical cord stress hormones including cortisol, adrenocorticotropic hormone (ACTH), norepinephrine, and epinephrine. Our objective was to investigate the effects of prenatal maternal life stressors on neonatal birth outcomes, neurobehavioral development, and stress-related hormones levels. Participants were 142 mothers and their infants; 71 were selected as the prenatal life stressor exposed group and 71 as the control group matched on maternal age, gestational week, delivery type, socioeconomic and education status, and newborns' sex. Maternal life stressors during pregnancy were determined using the Life Events Scale for Pregnant Women. Neonatal neurobehavioral development was assessed with the Neonatal Behavioral Neurological Assessment. Umbilical cord plasma stress-related hormones, including ACTH, cortisol, norepinephrine, and epinephrine were measured using an enzyme-linked immunosorbent assay. In the prenatal life stressors exposed group, newborns had significantly lower birth weight, smaller head circumference (p < 0.01, p < 0.01, respectively). Scores of Neonatal Behavioral Neurological Assessment were significantly reduced (p < 0.001). Cord plasma ACTH, norepinephrine, and epinephrine levels were significantly increased (p < 0.001), but cortisol levels were reduced (p < 0.001). Prenatal maternal stress may negatively affect fetal birth outcomes, neurobehavioral development and affect neonates' cord plasma ACTH, cortisol, norepinephrine, and epinephrine.


The use of cooled saline during bone drilling to reduce the incidence of upper-limb palsy after cervical laminoplasty: clinical article.
No previous hypothesis has attempted to fully account for the occurrence of upper-limb palsy (ULP) after cervical laminoplasty. The authors propose that friction-generated heat from a high-speed drill may cause thermal injury to the nerve roots close to the drilled bone, which may then lead to ULP. The authors investigated the effect of cooling the saline used for irrigation during the drilling on the incidence of upper-limb (C-5) palsy following cervical laminoplasty. The irrigation saline for drilling was used at room temperature (RT, average temperature of 25.6°C) in operations of 79 patients (the RT group) and cooled to an average of 12.1°C in operations of 80 patients (the low-temperature [LT] group). The authors used a hand-held dynamometer to precisely assess muscle strength presurgery and 2 weeks postsurgery. There was a 7.6% and 1.9% decrease in the strength of the deltoid muscle, a 10.1% and 4.4% decrease in the strength of the biceps brachii, a 1.3% and 0.6% decrease in the strength of the triceps brachii, and a 7.6% and 3.1% decrease in grip strength in the RT and LT groups, respectively. Multivariate analysis revealed that a significant predictor for decreased deltoid muscle strength was the use of irrigation saline at RT. Using cooled irrigation saline during bone drilling significantly decreased the incidence of ULP and can thus be recommended as a simple method for the prevention of ULP.


RNA extraction-free workflow integrated with a single-tube CRISPR-Cas-based colorimetric assay for rapid SARS-CoV-2 detection in different environmental matrices.
On-site environmental surveillance of viruses is increasingly important for infection prevention and pandemic control. Herein, we report a facile single-tube colorimetric assay for detecting severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) from environmental compartments. Using glycerol as the phase separation additive, reverse transcription recombinase polymerase amplification (RT-RPA), CRISPR-Cas system activation, G-quadruplex (G4) cleavage, and G4-based colorimetric reaction were performed in a single tube. To further simplify the test, viral RNA genomes used for the one-tube assay were obtained via acid/base treatment without further purification. The whole assay from sampling to visual readout was completed within 30 min at a constant temperature without the need for sophisticated instruments. Coupling the RT-RPA to CRISPR-Cas improved the reliability by avoiding false positive results. Non-labeled cost-effective G4-based colorimetric systems are highly sensitive to CRISPR-Cas cleavage events, and the proposed assay reached the limit of detection of 0.84 copies/µL. Moreover, environmental samples from contaminated surfaces and wastewater were analyzed using this facile colorimetric assay. Given its simplicity, sensitivity, specificity, and cost-effectiveness, our proposed colorimetric assay is highly promising for applications in on-site environmental surveillance of viruses.


Development of microencapsulated anthocyanin-rich powder using soy protein isolate, jackfruit seed starch and an emulsifier (NBRE-15) as encapsulating materials.
A trend of present encapsulation research indicates an increased interest in the search for natural encapsulants for bioactive phytochemicals. The present study in pursuit of the same studies the use of jackfruit seed starch (JSS), an underutilized natural polysaccharide in conjugation with soy protein isolate (SPI) as an encapsulating material and NBRE-15 as an emulsifier. Three independent variables viz., total soluble solids (TSS, 20, 25 and 30° Brix), SPI: JSS (1:1, 1:3 and 1:5) and NBRE-15 (0.1, 0.2 and 0.3%) were optimized for achieving the most efficient encapsulation of anthocyanin using a three level, three parameter, Box-Behnken design (BBD) of the Design of Experiments (DOE). The responses considered for the optimization were monomeric anthocyanin content, antioxidant activity and encapsulation efficiency. A combination of 27.0% TSS, 1:5 SPI: JSS ratio and 0.3% NBRE-15 was found to be optimum for the encapsulation of anthocyanin with the desirability of 92.6%. Microcapsules obtained using the optimized combination of independent variables was found to contain 3215.59 mg/100 g monomeric anthocyanin. The antioxidant activity and encapsulation efficiency of the encapsulated material obtained using optimized combinations of independent variable were found to be 365.26 µmol Trolox/g and 89.71%, respectively. The microcapsules were also additionally analyzed for the particle size distribution and morphological characterization. Particle size analysis indicated that the microcapsules obtained had a mean particle size of 60.97 µm. Scanning electron microscopy for morphological characterization indicated that the microcapsules so obtained were oval to round in shape and had a smooth surface. Storage studies to estimate the half-life of anthocyanin in the microcapsule at room temperature (37 °C) clearly indicated greater stability i.e. 63 days when stored under amber-colored vial compared to only 35 days when stored under clear transparent vial.


Pythiosis presenting with chronic swelling and painful subcutaneous lesion at right deltoid.
Pythiosis is a fatal disease which has high incidence in tropical regions. In contrast with vascular pythiosis, cutaneous and subcutaneous pythiosis are both uncommon. Here, we report a case of subcutaneous pythiosis in a pregnant farmer manifested with a progressively larger and more painful mass at right deltoid. The tissue culture and molecular test were negative for fungi. The diagnosis was supported by the positivity of serum immunochromatographic test (ICT) for pythiosis. Patients responded well to the combination therapy of itraconazole, terbinafine and azithromycin.


Transforming growth factor beta contributes to lung leak in rats given interleukin-1 intratracheally.
Interleukin-1 (IL-1) is increased in lung lavages obtained from patients with acute lung injury (ALI) and administering recombinant human IL-1alpha (rhIL-1alpha) (50 ng) intratracheally causes an acute, neutrophil-dependent, oxidative lung leak in rats that closely resembles human ALI. In the present work, the authors tested the hypothesis that transforming growth factor beta (TGFbeta) contributes to the lung inflammation and injury that develops in rats given IL-1 intratracheally. They found that intravenous administration of a monoclonal antibody to TGFbeta (1.D.11.16, 0.5 mg/kg) attenuated lung injury responses, specifically lung leak index, lung lavage protein concentrations, and blood oxygenation abnormalities, that are observed 5 hours after intratracheal instillation of IL-1 in rats, but did not decrease indices of lung inflammation, specifically myeloperoxidase (MPO) activity in lung tissue, neutrophil counts in lung lavage, and cytokine-induced neutrophil chemoattractant (CINC) levels in lung lavage, in rats given IL-1 intratracheally. The results suggest that TGFbeta contributes to lung leak, but not lung inflammation, following intratracheal administration of IL-1 in rats.


Versatility of temporal muscle and fascial flaps.
The muscle and superficial fascia of the temporal area differ in their physical characteristics, vascular supply and clinical applications. Both can be employed independently or simultaneously as regional flaps in the reconstruction of a variety of complex craniofacial defects. The present paper reviews the anatomy, surgical technique and utilisation of temporal flaps.


Volumetric-modulated Arc Therapy Lung Stereotactic Body Radiation Therapy Dosimetric Quality Assurance: A Comparison between Radiochromic Film and Chamber Array.
The aim of this work is to verify the use of radiochromic film in the quality assurance (QA) of volumetric-modulated arc therapy (VMAT) lung stereotactic body radiation therapy (SBRT) plans and compare the results with those obtained using an ion chamber array. QA was performed for 14 plans using a two-dimensional-array seven29 and EBT3 film. Dose values per session ranged between 7.5 Gy and 18 Gy. The multichannel method was used to obtain a dose map for film. The results obtained were compared with treatment planning system calculated profiles through gamma analysis. Passing criteria were 3%/3 mm, 2%/2 mm and 3%/1.5 mm with maximum and local dose (LD) normalization. Mean gamma passing rate (GPR) (percentage of points presenting a gamma function value of <1) was obtained and compared. Calibration curves were obtained for each color channel within the dose range 0-16 Gy. Mean GPR values for film were >98.9% for all criteria when normalizing per maximum dose. When using LD, normalization was >92.7%. GPR values for the array were lower for all criteria; this difference being statistically significant when normalizing at LD, reaching 12% for the 3%/1.5 mm criterion. Both detectors provide satisfactory results for the QA of plans for VMAT lung SBRT. The film provided greater mean GPR values, afforded greater spatial resolution and was more efficient overall.


Ruptured benign cystic teratomas mimicking gynecologic malignancy.
Ruptured benign cystic teratomas of the ovary mimicking gynecologic malignancy are uncommon, but frequently misdiagnosed. Two cases are reported that, preoperatively, were believed to represent ovarian carcinoma, but were found to have diffuse granulomatous peritonitis, secondary to perforation of the teratomas. Intra-abdominal adhesions and/or masses are frequent sequelae. A diagnosis of malignancy must be confirmed prior to performing radical surgery. A review of the literature is presented.


Operant conditioning of brain steady potential shifts in man.
Steady potential shifts (SPS) recorded from the scalp were conditioned operantly by visual and acoustical feedback. Three groups of seven subjects were each tested with a different response-reinforcement contingency: positive reinforcement for a positive SPS after a cue stimulus, positive reinforcement for a negative SPS after a cue stimulus, and noncontingent reinforcement. The steady potential shifts learned under these three conditions differed significantly. Negative shifts were associated with subjective feelings of activation, positive shifts with inactivation. Cortical genesis and possible artifacts are discussed.


Soil cadmium stress reduced host plant odor selection and oviposition preference of leaf herbivores through the changes in leaf volatile emissions.
The Elemental defense hypothesis suggested that metal accumulation in plant tissues could serve as direct defense to reduce herbivore feeding preference as metals are toxic to phytophagous insects. However, the indirectly defensive role of heavy metals on host plant odor selection and oviposition preference of leaf herbivores through the changes in leaf volatile organic compounds (VOCs) is still unknown. In this study, we used a local woody plant species, Populus yunnanensis, to investigate whether soil cadmium (Cd) stress could affect plant VOC production and whether Cd-mediated changes in leaf VOC emissions will further influence the host plant odor and oviposition preferences of female adults of a specialist and a generalist herbivore species. The results clearly showed that the soil Cd stress could prominently induce leaf total VOC emissions of P. yunnanensis and such induction was positively correlated with leaf Cd accumulation. Herbivore olfactometer bioassays further demonstrated that the VOCs released by P. yunnanensis under Cd exposure are far less attractive to both of the specialist and generalist female adults compared to control plants, leading to significant reduction in oviposition on Cd-treated plants. Moreover, the host plant odor selection and oviposition preference of the two herbivore species were all negatively correlated with leaf total VOC emissions, which confirmed the defensive role of Cd-induced VOCs for deterring the female insects. The result will extend the existing knowledge of the Elemental defense hypothesis and provide new insight into predicting the herbivore damage level of poplar species that naturally occurred in metal-polluted habitats.


Second-trimester acute fatty liver disease of pregnancy: A brief review of the literature and a case report.
Acute fatty liver disease of pregnancy (AFLP) is a rare life-threatening medical emergency unique to pregnancy. It is characterized by progressive microvesicular fatty infiltration of maternal hepatocytes, but the exact etiology has yet to be elucidated. AFLP typically manifests in late third trimester or immediately postpartum and seldom during second trimester. Prompt delivery, irrespective of gestational age or severity, is crucial for arresting the insult and permitting recovery. We hereby report a 21-year-old Lebanese second-gravid woman at 20 weeks' gestation diagnosed with AFLP depending on clinical features and compatible laboratory studies (score of 8 on Swansea criteria), in spite of early occurrence. A review and analysis of early AFLP (second trimester) compared to late (third trimester) was also presented. AFLP appearing during second trimester is as serious as the disease manifesting in late third trimester, with similar diagnostic difficulties, less association with hypertension, but with greater hesitation of obstetricians to affect prompt delivery and higher adverse perinatal outcome due to added effect of premature delivery in second trimester.


Oxygen sensing decoded: a Nobel concept in biology.
Oxygen is essential to most organisms as it is a necessity for aerobic metabolism and energy production. Too much or too little oxygen can be deadly, such that mechanisms for fast and titrated response to changing oxygen levels are crucial. These mechanisms have evolved from the studies of Gregg L. Semenza, William G. Kaelin and Peter J. Ratcliffe. It is through the work of their three laboratories, performed in the 1990s, that the cellular oxygen sensing mechanisms have been decoded. Their discoveries have had major impact for innovation in medicine, especially in the field of angiogenesis research, where oxygen sensing and its consequences have led to enhanced insight in vascular development and strategies for combating angiogenic diseases. On October 7, the Nobel Assembly in Stockholm announced at the Karolinska Institute that the Nobel Prize for Medicine 2019 is jointly awarded to these three scientists for their seminal discoveries on how cells sense and respond to oxygen.


MhURI:A Supervised Segmentation Approach to Leverage Salient Brain Tissues in Magnetic Resonance Images.
Accurate segmentation of critical tissues from a brain MRI is pivotal for characterization and quantitative pattern analysis of the human brain and thereby, identifies the earliest signs of various neurodegenerative diseases. To date, in most cases, it is done manually by the radiologists. The overwhelming workload in some of the thickly populated nations may cause exhaustion leading to interruption for the doctors, which may pose a continuing threat to patient safety. A novel fusion method called U-Net inception based on 3D convolutions and transition layers is proposed to address this issue. A 3D deep learning method called Multi headed U-Net with Residual Inception (MhURI) accompanied by Morphological Gradient channel for brain tissue segmentation is proposed, which incorporates Residual Inception 2-Residual (RI2R) module as the basic building block. The model exploits the benefits of morphological pre-processing for structural enhancement of MR images. A multi-path data encoding pipeline is introduced on top of the U-Net backbone, which encapsulates initial global features and captures the information from each MRI modality. The proposed model has accomplished encouraging outcomes, which appreciates the adequacy in terms of some of the established quality metrices when compared with some of the state-of-the-art methods while evaluating with respect to two popular publicly available data sets. The model is entirely automatic and able to segment gray matter (GM), white matter (WM), and cerebrospinal fluid (CSF) from brain MRI effectively with sufficient accuracy. Hence, it may be considered to be a potential computer-aided diagnostic (CAD) tool for radiologists and other medical practitioners in their clinical diagnosis workflow.


Enzyme replacement therapy attenuates disease progression in two Japanese siblings with mucopolysaccharidosis type VI: 10-Year follow up.
Early initiation of enzyme replacement therapy (ERT) has demonstrated clinical benefit in patients with mucopolysaccharidosis type VI (MPS VI), a progressive, multisystem autosomal recessive lysosomal disorder caused by N-acetylgalactosamine-4-sulphatase (ASB) deficiency and the consequent accumulation of glycosaminoglycan. A previous case report highlighted that 3 years of ERT with recombinant human ASB (galsulfase) was well tolerated and effective in two Japanese siblings with MPS VI who initiated ERT at 5.6 years and 6 weeks of age, respectively. This report describes 10-year follow-up data from these two siblings who continued ERT with weekly infusions of galsulfase 1 mg/kg. Ten years of ERT was well tolerated, and the older sibling reached puberty. He had typical MPS VI phenotypic features, but exhibited significant improvement in shoulder range of motion and had largely unchanged hearing and cardiac function. His skeletal deformity remained unchanged. In contrast, in the younger sibling, typical symptoms of MPS VI, including progressive dysmorphic facial features, hepatosplenomegaly, and hearing impairment were largely absent. Her joint mobility was preserved, although skeletal deformity, including claw-hand deformity, was observed. Both siblings had progressive corneal clouding. The observations in these two patients suggest that early ERT initiated in newborns can be well tolerated and effective in preventing or slowing MPS VI disease progression, but is limited in terms of its effects on bone symptoms. For this, new approaches or bone-targeting treatments would be necessary.


Are temporomandibular disorder symptoms and diagnoses associated with pubertal development in adolescents? An epidemiological study.
In addition to low back pain, temporomandibular disorders (TMDs) are the most prevalent pain- and disability-related musculoskeletal conditions. However, the influence of pubertal development on TMD diagnoses remains unknown. To assess whether the prevalence of TMD diagnoses, in addition to self-reported symptoms (pain, restricted mandibular mobility, clicking), change according to pubertal stage. A random sample of 1,011 children and adolescents was chosen from the general population of 24,129 children and adolescents aged 10-17 years living in the urban area of Halle, Germany. Study participants were examined for TMD symptoms and diagnoses according to the Research Diagnostic Criteria for TMDs (RDC/TMD). Status of pubertal development was assessed using the Pubertal Development Scale (PDS). The χ(2) tests and multivariate logistic regression models were used, and odds ratios (ORs) and 95% confidence intervals calculated. The observed increase in TMD symptoms during adolescence was mainly due to the higher frequency of self-reports of these symptoms by girls than boys (ORs for girls vs. boys: 1.42-1.53; p ≤ 0.05), whereas clinical TMD diagnoses (any RDC/TMD diagnosis, or RDC/TMD group IIa diagnosis) in adolescence increased mainly due to pubertal development itself (ORs for subjects beyond vs. before puberty: 1.58-2.00; p < 0.05; no significant sex-related effect was found). Pubertal development increases the probability of self-reported TMD symptoms among girls, while the probability thereof decreases among boys. Independent of sex, pubertal growth increases the prevalence of RDC/TMD-related diagnoses-mainly disk displacement-in both sexes.


[MR morphometry in epileptology: progress and perspectives].
Morphometric MRI analysis improves neuroimaging of structural changes in epilepsy. To investigate diagnostic potential of MR brain morphometry in neurosurgical epileptology. An interdisciplinary working group reviewed the studies devoted to MR morphometry in epileptology as a part of state assignment No. 056-00119-22-00. Study subject was trials of MR-morphometry in epilepsy. Searching for literature data was conducted in international and national databases between 2017 and 2022 using certain keywords. Final analysis included 36 publications. Currently, MR brain morphometry allows measurement of cortical volume and thickness, surface area and depth of furrows, as well as analysis of cortical tortuosity and fractal changes. In neurosurgical epileptology, MR-morphometry has the greatest diagnostic value in MR-negative epilepsy. This method simplifies preoperative diagnosis and reduces costs. Morphometry in neurosurgical epileptology is an additional method for verifying the epileptogenic zone. Automated programs simplify application of this method.


Prevalence of Needle Stick and Sharps Injury and Hepatitis B Vaccination among Healthcare Workers in a South-East Nigerian Tertiary Hospital.
Daily, HCWs are exposed to needle stick and sharps injury (NSSI) and associated risk of life-threatening infections. A cross-sectional study was conducted to determine the prevalence of NSSI and HBV vaccination among 341 HCWs at NAUTH, Nnewi. Data was collected using a self-administered. questionnaire and interview of key staff. The mean age of participants was 33.4±11.9 years while male: female ratio was 1:1.7. Prevalence of NSSI in the preceding 12 months was 25.5% with doctors (43.0% [34/79]), laboratory scientists (27.5%[14/51]) and nurses (21.8%[17/78]) leading (p=0.014). Noncompliance with standard precaution (SP) and non-display of relevant SP SOPs in prominent places were significantly associated with NSSI (p=0.001). Among those exposed to NSSI, only 33.7% (28/83) consulted a doctor, while 16.9%(14/83) took post-exposure prophylaxis. Two-third (68.8% [190/276]) of respondents correctly cited HBV/HCV as vaccine-preventable blood-borne healthcare-associated infection (HAI) while half (50.9% [161/316]) had received HBV vaccination. Profession (p=0.018), display of SOPs in prominent places (p=0.015), ability to cite HBV/HCV as vaccine-preventable blood-borne HAI (p=0.001), and compliance with SP (p<0.001) were significantly associated with HBV vaccination. Unit heads' responses implied lack of written policy on HBV vaccination, adequate training on NSSI prevention, and HBV vaccination support. Among HCWs, NSSI is high but under-reported while HBV vaccination rate is unimpressive. Profession, display of relevant SOPs, and compliance with SP positively affected both NSSI occurrence and HBV vaccination while knowledge about vaccine-preventable blood-borne HAI also influence HBV vaccination status. Written policies on HBV vaccination and NSSI prevention/ management, their communication and enforcement among HCWs, adequate training/retraining, display of SOPs in prominent places, and free HBV vaccination are recommended.


Determination of engraftment potential of human cord blood stem-progenitor cells as a function of donor cell dosage and gestational age in the NOD/SCID mouse model.
The purpose of this study was to determine cell dosage parameters for successful engraftment of human cord blood hematopoietic stem cells (HSC) using an in vivo assay system, and to determine if there are differences with donor gestational age. HSCs were transplanted into nonobese diabetic-severe combined immunodeficient (NOD/SCID) mice. Donor cell dosage and gestational age ranges were 1 to 40 x 10(6) CD34+ cells per mouse, and 23 to 40 weeks, respectively. Recipient bone marrow was assessed for engraftment capacity of the HSCs. There was increasing engraftment levels with increasing dosages of transplanted HSCs. When controlled for donor HSC dosage, engraftment levels using donor cord blood from earlier gestational ages were not different from that seen using later gestational ages. Similar dose responses are seen using HSCs derived from the late second trimester until term in engraftment potential in the NOD/SCID mouse model. Results from this study may be applicable to human postnatal and in utero transplantation studies.


Chronic diarrhea as the presenting feature of primary systemic AL amyloidosis: serendipity or delayed diagnosis?
Chronic diarrhea in adults is a common symptom with a wide range of underlying etiologies. Although various strategies have been proposed for evaluation, there are still cases with undetermined origins even after extensive workup. Amyloidosis with gastrointestinal (GI) involvement is one of the causes that should be considered in adult patients with chronic diarrhea. We report a case of primary systemic amyloid light-chain (AL) amyloidosis, presenting initially as chronic diarrhea and weight loss. A 43-year-old man with chronic diarrhea and weight loss was referred to our hospital. Prior to his presentation, extensive evaluation including an exploratory laparotomy was carried out and did not yield any valuable findings. An echocardiography performed after repeated episodes of orthostatic hypotension revealed infiltrative cardiomyopathy. Moreover, biopsies of the terminal ileum revealed amyloid deposition confirmed by Congo Red staining. Finally, a diagnosis of systemic AL amyloidosis was made after hematological workup. Anti-plasma cell therapy did ameliorate his GI symptoms. Although amyloidosis with GI involvement is a rare cause of chronic diarrhea, it should be considered especially in patients with intestinal malabsorption and extra-GI manifestations, such as orthostatic hypotension. The delayed diagnosis in the present case highlights the importance of recognizing clinical "red flags" not seemingly related to one another, and underscores the need to get intestinal biopsies even with normal endoscopic appearance of the mucosa.


Differential influences of angiotensin converting-enzyme inhibitors on the coronary circulation.
The effects of captopril and zofenoprilate (the active form of the prodrug zofenopril and also a sulfhydryl-containing angiotension converting-enzyme inhibitor) on coronary flow in the isolated rat heart were compared with the effects of a nonsulfhydryl converting-enzyme inhibitor, ramiprilate (the active form of the prodrug ramipril) and of sulfhydryl-containing compounds with no converting-enzyme inhibiting properties such as glutathione, cysteine, and the (R,S)-isomer of captopril. Drug concentrations of the angiotensin converting-enzyme inhibitors were equipotent in their effect on angiotensin I pressor response. Concentrations of the other compounds were equimolar with respect to the sulfhydryl group. Hearts treated with captopril, its isomer, zofenoprilate, cysteine, and glutathione showed significant increases in coronary flow by 5 min of perfusion. In contrast, ramiprilate treatment resulted in a slower increase in coronary flow that was only significant after 20 min of perfusion. The effect of ramiprilate was associated with a significant increase in 6-keto-prostaglandin (PG) F1 alpha overflow in the coronary effluent compared with that in saline-treated hearts, whereas captopril and glutathione had no significant effect on overflow of the measured cyclooxygenase products 6-keto-PGF1 alpha, thromboxane B2, and PGE2. The effects of captopril, zofenoprilate, and glutathione on coronary flow were dose dependent. These results corroborate the view that ramiprilate enhances coronary flow by affecting prostacyclin synthesis, mediated by an increase of endogenous bradykinin.(ABSTRACT TRUNCATED AT 250 WORDS)


Testis and brown adipose tissue xenografts from yellowish myotis (Myotis levis).
Yellowish myotis present a seasonal reproduction, influenced by rainfall distribution, in which the testis mass, germ cell composition, and brown adipose tissue mass change along the reproductive stages. In the present study, tissue xenografts were performed in immunodeficient mice to investigate spermatogenesis development in a stable endocrine milieu and the possible androgenic role of brown adipose tissue. Forty-one adult male bats were captured in the Santuário do Caraça, Minas Gerais, Brazil. The gonads and brown adipose tissue were collected, weighed, and grafted under the mice's back skin. Mice biometric and hormonal data were evaluated after grafting, and the testis grafts and mice gonads were fixed for histological and immunohistochemical analyses. As a result, testis grafts from adult bats presented a continuous germ cell development in all reproductive phases, showing round spermatids in all testis tissues. Furthermore, testis fragments in the Rest stage presented elongating spermatids as the most advanced germ cell type in the seminiferous epithelium after seven months of grafting. These data indicated that yellowish myotis spermatogenesis could be continued (presenting a constant spermatogonial differentiation) in a stable endocrine milieu, as found in mice. In addition, the best spermatogenic development was achieved when testis fragments were transplanted at their lowest activity (Rest stage). Regarding the brown adipose tissue grafts, the adipose tissue consumption by mice increased seminal vesicle mass and testosterone serum levels. This data proved that the brown adipose tissue is related to testosterone synthesis, which may be critical in stimulating the differentiation of spermatogonia in yellowish myotis.


Patient Blood Management in Vascular Surgery.
Patient blood management (PBM) is an evidence-based, multidisciplinary approach aimed at appropriately allocating blood products to patients requiring transfusion while simultaneously minimizing inappropriate transfusions. The 3 pillars of patient blood management are optimizing erythropoiesis, minimizing blood loss, and optimizing physiological reserve of anemia. Benefits seen from PBM include limiting hospital costs and mitigating harm from numerous risks of transfusion.


Microvascular reconstruction of the mouth, jaws, and face: experience of an Australian oral and maxillofacial surgery unit.
Microvascular reconstruction of oncologic surgical and traumatic defects has been globally practiced by plastic and orthopedic surgical disciplines since the early 1970s. During the past 20 years, reconstructive techniques have been progressively incorporated into the purview of oral and maxillofacial and otolaryngology-head and neck surgeons, particularly those practicing in Europe, the United Kingdom, and China. There has also been a steady increase in the adoption of these techniques in North America, South America, and Japan. We reviewed our experience (during a 5-year period) with microvascular reconstruction of postablative defects in the oral and maxillofacial region. To our knowledge, resection and neck dissection (or neck exploration in benign free tissue transfer); undertaken by an oral and maxillofacial surgeon), and free tissue transfer reconstruction (undertaken by otolaryngology head and neck and oral and maxillofacial surgeons) of ablative defects of the mouth, jaws, and face (managed within an Australian head and neck cancer multidisciplinary care team) have not been previously reported. The study cohort comprised 107 patients who underwent 109 microvascularly anastomosed free tissue transfers. Of the 107 patients, 79 were males and 38 were females. The median age was 62 years (range 15 to 87). The clinicodemographic analyses and the range of complications observed in this patient cohort are reported. The overall flap success rate in our study was 97%. The surgical outcomes of our study compare favorably with those previously reported.


Industrial arsenic contamination causes catastrophic changes in freshwater ecosystems.
Heavy metal pollution is now widely recognized to pose severe health and environmental threats, yet much of what is known concerning its adverse impacts on ecosystem health is derived from short-term ecotoxicological studies. Due to the frequent absence of long-term monitoring data, little is known of the long-tem ecological consequences of pollutants such as arsenic. Here, our dated sediment records from two contaminated lakes in China faithfully document a 13.9 and 21.4-fold increase of total arsenic relative to pre-1950 background levels. Concurrently, coherent responses in keystone biota signal pronounced ecosystem changes, with a >10-fold loss in crustacean zooplankton (important herbivores in the food webs of these lake systems) and a >5-fold increase in a highly metal-tolerant alga. Such fundamental ecological changes will cascade through the ecosystem, causing potentially catastrophic consequences for ecosystem services in contaminated regions.


Solubilization of inclusion body proteins using n-propanol and its refolding into bioactive form.
Inclusion bodies of recombinant human growth hormone (r-hGH) were isolated from Escherichia coli, enriched and solubilized in 100mM Tris buffer containing 6M n-propanol and 2M urea. Around 4 mg/ml of r-hGH from inclusion bodies were solubilized in 6M n-propanol-based buffer containing 2M urea. Existence of native-like secondary structure of r-hGH in 6M n-propanol solution was confirmed by CD and fluorescence spectra. Solubilized r-hGH was subsequently refolded by pulsatile dilution, purified to homogeneity and found to be functionally active. Tris buffer containing 6M n-propanol and 2M urea also effectively solubilized a number of proteins expressed as inclusion bodies in E. coli. Mild solubilization of inclusion body proteins, chaotropic effect of n-propanol at high concentration and kosmotropic effect at lower concentration helped in improved refolding of the solubilized protein. Around 40% of the r-hGH in the form of inclusion body aggregates was refolded into bioactive form while using n-propanol as solubilization agent. Solubilization with 6M n-propanol solution thus can be a viable alternative for achieving high throughput recovery of bioactive protein from inclusion bodies of E. coli.


Organization of mammalian chromosomal DNA: supercoiled and folded circular DNA subunits from interphase cell nuclei.
Chinese hamster cells (line V79/4) in the G2 phase of the mitotic cycle were lysed onto neutral sucrose gradients and the released chromosomal DNA was characterized according to its size and shape by sedimentation velocity studies. Using the intercalating agent, ethidium bromide, in the gradients and the induction of DNA single- and double-strand breaks by irradiation, the DNA was proved to be released into the gradient in supercoiled circular subunits whose homogenous size corresponds to 2.8 . 10(9) Dalton. Supercoiling of these DNA subunits was found to be confined to smaller regions sized on the average about 9 . 10(7) Dalton and maintained by folding the DNA into loops. The average superhelix density was determined to be--0.09 turns per 10 base pairs of DNA. The functional aspects of the experimental findings are discussed in terms of replicative and transcriptional units.


Anatomy and Physiology of the Breast during Pregnancy and Lactation.
The mature breast is located within the anterior thoracic wall, lying atop the pectoralis major muscle. Pubertal changes lead to incomplete development of the breast , a process which is only completed during pregnancy . The incomplete breast consists mostly of adipose tissue but also lactiferous units called lobes. These eventually drain into the lactiferous ducts and then into the lactiferous sinus and then to the nipple-areolar complex. During pregnancy , the breast undergoes both anatomic and physiologic changes to prepare for lactation. During the first trimester, the ductal system expands and branches out into the adipose tissue in response to the increase of estrogen. Elevated levels of estrogen also cause a decrease in adipose tissue and ductal proliferation and elongation. Estrogen also stimulates the pituitary gland which leads to elevated levels of prolactin. By the twentieth week of gestation, mammary glands are sufficiently developed to produce components of milk due to prolactin stimulation. Milk production is inhibited by high estrogen and progesterone levels and colostrum is produced during this time. In the third trimester and then rapidly after birth, these levels decrease, allowing for milk production and eventual let-down to allow for breastfeeding. Most pregnancies cause the areola to darken, the breast to increase in size, and the Montgomery glands to become more prominent. Post-lactational involution occurs at the cessation of milk production caused by a decline in prolactin.


Shared Genetics and Comorbid Genes of Amyotrophic Lateral Sclerosis and Parkinson's Disease.
Comorbidity exists between amyotrophic lateral sclerosis (ALS) and Parkinson's disease (PD), but the role of genetic factors is unclear. We aim to investigate genetic correlation, causal relationship, and comorbid genes between ALS and PD. Leveraging the largest genome-wide association study data (ALS: 27,205 cases, 110,881 controls; PDG: 33,674 cases, 449,056 controls), we used linkage disequilibrium score regression and Mendelian randomization analysis for genetic correlation and causal inference. We performed genome-wide cross-trait analysis via Multi-Trait Analysis of Genome-Wide Association Studies and Cross-Phenotype Association to identify specific single-nucleotide polymorphisms, followed by functional mapping and annotation. Integrating expression quantitative trait loci data from 13 brain regions, we conducted a transcriptome-wide association study via functional summary-based imputation and joint-tissue imputation to explore comorbid genes, followed by pathway enrichment analysis. We found that PD positively correlates with ALS (rg = 0.144, P = 0.026) and confers a causal effect (odds ratio = 1.09, 95% confidence interval: 1.03-1.15, P = 3.00 × 10-3 ). We identified nine single-nucleotide polymorphisms (eight new), associating with three risk loci (chromosomes 4, 10, and 17) and seven genes (TMEM175, MAPT, NSF, LRRC37A2, ARHGAP27, GAK, and FGFRL1). In transcriptome-wide association study analysis, we showed six previously unreported pleiotropic genes (KANSL1, ARL17B, EFNA1, WNT3, ERCC8, and ADAM15), and we found these candidate genes are mainly enriched in negative regulation of neuron projection development (GO:0010977). Our work demonstrates shared genetic architecture between ALS and PD, reports new pleiotropic genes, and sheds light on the comorbid mechanism. © 2023 International Parkinson and Movement Disorder Society.


Immuno-spin trapping of heme-induced protein radicals: Implications for heme oxygenase-1 induction and heme degradation.
Heme, in the presence of hydrogen peroxide, can act as a peroxidase. Intravascular hemolysis results in a massive release of heme into the plasma in several pathophysiological conditions such as hemolytic anemia, malaria, and sickle cell disease. Heme is known to induce heme oxygenase-1(HO-1) expression, and the extent of induction depends on the ratio of albumin to heme in plasma. HO-1 degrades heme and ultimately generates the antioxidant bilirubin. Heme also causes oxidative stress in cells, but whether it causes protein-radical formation has not yet been studied. In the literature, two purposes for the degradation of heme by HO-1 are discussed. One is the production of the antioxidant bilirubin and the other is the prevention of heme-dependent adverse effects. Here we have investigated heme-induced protein-radical formation, which might have pathophysiological consequences, and have used immuno-spin trapping to establish the formation of heme-induced protein radicals in two systems: human serum albumin (HSA)/H2O2 and human plasma/H2O2.We found that excess heme catalyzed the formation of HSA radicals in the presence of hydrogen peroxide. When heme and hydrogen peroxide were added to human plasma, heme was found to oxidize proteins, primarily and predominantly HSA; however, when HSA-depleted plasma was used, heme triggered the oxidation of several other proteins, including transferrin. Thus, HSA in plasma protected other proteins from heme/H2O2-induced oxidation. The antioxidants ascorbate and uric acid significantly attenuated protein-radical formation induced by heme/H2O2; however, bilirubin did not confer significant protection. Based on these findings, we conclude that heme is degraded by HO-1 because it is a catalyst of protein-radical formation and not merely to produce the relatively inefficient antioxidant bilirubin.


An Investigation of Undergraduate Nursing Students' Therapeutic Communication with Patients.
Therapeutic Communication (TC) is the process of purposeful and understandable communication between patients and caregivers, which helps facilitate optimized care. Here, we assessed nursing students' interaction with patients and its related factors. In this descriptive-analytical study, a convenience sample of 240 undergraduate nursing students from Tehran University of Medical Sciences, Tehran, Iran, completed consent forms, a demographic information questionnaire, and a TC questionnaire in 2018. Data were analyzed using descriptive and inferential statistics. TC score of most students was moderate and good, with the mean (SD) of 143.07 (12.86). Factors, including gender (Χ2 = 8.02, p ≤ 0.01), semester (Χ2 = 4.01, p ≤ 0.05), employment (r = 0.49, p ≤ 0.01), and workshop attendance (r = 0.80, p ≤ 0.01), influenced the students' TC knowledge and skills. Future nurses' TC can be improved by part-time employment and practical training. Conducting more research with a larger sample size from all nursing faculties is suggested.


Comparison of in-hospital and one-year outcomes after multiple coronary arterial stenting in patients > or =80 years old versus those <80 years old.
The present study evaluated in-hospital and 1-year outcomes after multivessel stenting in patients aged > or =80 (75 patients, 241 lesions) and <80 years (894 patients, 2,678 lesions). Despite a high technical success rate of multivessel stenting, octogenarians had higher in-hospital cardiac and noncardiac complication rates and a higher mortality rate at 1-year clinical follow-up compared with their younger counterparts.


Plant-rich diets: Healthier for people and the planet.
There are strong links between the rise in unhealthy diets and non-communicable diseases, which are a major cause of morbidity and mortality in the community and have a strong impact on the health system. The current food system encourages poor food choices and fails to help many people follow the principles set out in the Australian Dietary Guidelines. There is also good evidence that healthier diets are likely to be more environmentally sustainable than the typical Australian diet. New diets are constantly appearing, and it can be a confusing area for doctors and patients to make sense of their benefit. This paper aims to provide evidence that GPs can use to support healthier diets for their patients. General practitioners can provide education and motivation for patients to change their dietary patterns. This will involve choosing more healthy plant foods, with fewer highly processed products and less red meat, as currently recommended in the Australian Dietary Guidelines. Such dietary choices provide proven co-benefits for health and the environment.


Preoperative interpleural administration of sufentanil or bupivacaine reduces intraoperative intravenous sufentanil requirements during thoracotomy.
The efficacy of interpleural administration of sufentanil, 50 micrograms, was compared with that of 150 mg of bupivacaine, 0.5%, with epinephrine, 5 micrograms/mL, or saline, in 30 patients (N = 10 in each group) undergoing lateral thoracotomy. Sufentanil, bupivacaine, or saline was administered interpleurally after induction of anesthesia with sufentanil, 1 microgram/kg intravenously, and thiopental, 2 to 5 mg/kg. Anesthesia was maintained with nitrous oxide, 66%, and halothane, 0.3% inspired concentration. Supplementary intravenous sufentanil, 25 micrograms, was given whenever the systolic arterial blood pressure increased more than 15 mmHg above the preoperative value, heart rate exceeded 90 beats/min in the absence of hypovolemia, or when other autonomic or somatic signs of inadequate anesthesia occurred. The additional intravenous sufentanil requirement and the incidence of hypotension were compared between the groups. All patients in the placebo group needed supplementary sufentanil. Significantly fewer patients in the interpleural sufentanil (N = 1, P < 0.0002) and bupivacaine (N = 1, P < 0.0002) groups required supplementary sufentanil compared to the placebo group (N = 10). The time from interpleural administration of the study drug to the first administration of postoperative analgesic was significantly longer (P < 0.001) in the sufentanil group (228 +/- 72 min) and bupivacaine group (242 +/- 76 min) compared to the placebo group (141 +/- 50 min). It was concluded that interpleural administration of either sufentanil or bupivacaine contributes to intraoperative analgesia during thoracotomy.


Improving Identification and Treatment Outcomes of Treatment-Resistant Depression Through Measurement-Based Care.
Measurement-based care (MBC) is the systematic screening and ongoing assessment of symptoms, side effects, and adherence to adjust treatments as needed based on these factors. Studies show MBC leads to improved outcomes for depression and treatment-resistant depression (TRD). In fact, MBC may reduce the chances of developing TRD, as it leads to optimized treatment strategies based on symptom changes and compliance. There are many rating scales available for monitoring depressive symptoms, side effects, and adherence. These rating scales can be used in a variety of clinical settings to help guide treatment decisions, including depression treatment decisions.


A highly sensitive method for the analysis of nitrite ions by capillary zone electrophoresis using water-soluble aminophenylporphyrin derivative as chromogenic reagent.
The water soluble 5-p-aminophenyl)-10,15,20-tris(p-sulfonatophenyl) porphyrin, 4, acts as an extremely efficient chromogenic reagent for the detection of very low amounts of nitrites. The amino group of porphyrin 4 reacts smoothly with nitrite in acidic conditions 0.2 M HCl) producing the corresponding diazo-porphyrin derivative which is stable and does not show any appreciable hydrolysis to phenol within 6 h. The reaction is carried out in the presence of 25 mM heptakis-(2,6-di-O-methyl)-beta-cyclodextrin that prevents precipitation of the protonated form of porphyrins 4 or 5 due to the formation of strong inclusion complexes. The capillary zone electrophoresis of the diazoporphyrin and amino-porphyrin mixture shows severe peak tailing. However, symmetrical peaks can be obtained by adding 5 mM beta-cyclodextrin to the background electrolyte (20 mM phosphate buffer, pH 7.0). Calibration curve for nitrite analysis is linear up to 0.25 mM nitrite and the detection limit (at a signal-to-noise ratio of 3) has been estimated to be a 1 microM (50 ppb) of nitrite concentration in aqueous solutions.


Medical student reporting of factors affecting pre-clerkship changes in empathy: a qualitative study.
To isolate factors that medical students identify as possibly affecting empathy in pre-clerkship years of medical school. 12 students in their second year of medical school at Queen's University were randomly selected and asked to participate in semi-structured interviews conducted from an ethnographic perspective. Students reported both negative and positive changes in empathy. Negative changes included desensitization and focusing on the disease process, decreased ability to see things from patients' perspectives, and routine responses in emotional situations. These changes occur due to time constraints, objective lessons in empathy, and a changing identity. Positive changes included an increased awareness of the impact of illness, and increased ability to read feelings. These changes result from increased exposure to patients, discussions surrounding the psychosocial impact of illness, and positive role models. Students should be made aware of the limitations of objective lessons in empathy, and non-evaluated, implicit lessons should be emphasized when possible. Students should be encouraged to maintain relationships outside of medicine. Aspects of medical school that currently promote empathy should be reinforced, including exposure to patients, opportunities to work closely with positive role models, and practical discussions surrounding the psychosocial impact of illness.


Surgical Tips to Improve Completeness of Transsubxiphoid Robotic Extended Thymectomy.
Removal of adipose tissues located behind the left innominate vein and at the aortocaval groove is technically complex for minimally invasive extended thymectomy. The study describes the technical tips of the subxiphoid robotic procedure to remove these adipose tissues. Extended thymectomy by the presented procedure was performed in 39 patients, and 6 patients were diagnosed with ectopic thymic tissues behind the left innominate vein. Satisfactory short-term surgical outcomes demonstrated that dissection of adipose tissues located between mediastinal major vessels is technically feasible and safe by this novel procedure.


The influence of social norms on anticipated snacking: An experimental study comparing different types of social norms.
Previous studies have found that social norms affect eating behavior for different types of social norm measures and manipulations as well as different types of eating behavior. The current study investigated the effects of descriptive, injunctive, and liking norms on intentions to consume healthy snacks and anticipated snack choice, compared to a no-norm control condition. Moreover, we distinguished between descriptive norms that stress the frequency versus the quantity of food consumption. An experiment was conducted among 189 young adults. It was hypothesized that participants who received a descriptive quantity or frequency norm would intend to consume, and make an anticipated selection of, more low-calorie snacks than participants who received a no-norm control message. Due to inconsistency or lacking evidence regarding the effects of the other types of norms on eating behavior, no hypotheses were formulated for the injunctive and liking norm conditions. The hypothesis was partly confirmed. Descriptive quantity and frequency norms did not result in a stronger intention to consume healthy snacks in the upcoming week, but they did result in lower-calorie snack choices when people were asked to select three snacks that they planned to eat on the following day. No other differences between the conditions were found. These findings show that emphasizing both how much and how often most other people consume healthy foods affects anticipated healthy food choices. This can provide health professionals more options to mobilize the power of descriptive social norms for affecting health behavior change.


Biochemical and immunohistochemical studies on dysmyelination of quaking mutant mice in vivo and in vitro.
Dysmyelination in the central nervous system of the quaking mutant mouse was studied biochemically and immunohistochemically. We found, by measuring CNPase activity, that myelination in the central nervous system of quaking mice was affected to a different degree in different areas. The pallium cerebri was the most severely affected and the medulla and spinal cord were least affected. The density of astroglia observed by GFA staining wash higher in the white matter of quaking mice than in controls, but the total area of the white matter in the cerebellum was smaller in the quaking mice than in the controls. The DNA content in the pallium cerebri and brain stem showed no increase and that of the cerebellum was even lower in quaking mice than in the controls. Hypertrophy of the astroglia was observed in the white matter of the cerebellum of quaking mice, though Bergmann astroglial fibers in the molecular layer did not show any hypertrophy. The cerebella of quaking mice in primary culture showed very poor myelination under the phase-contrast microscope. However, Purkinje cells from the quaking mutants appeared normal with regard to Bodian silver impregnation, hematoxylineosin staining, and Purkinje cell specific P 400 protein. Addition of the conditioned culture medium of qk/qk to the culture of the control cerebellum did not interfere with the myelination. We concluded that the cause of dysmyelination in the quaking mouse could be a genetic defect of the oligodendroglia rather than hypertrophy of the astroglial cells.


Multiplexed detection of tumor markers with multicolor quantum dots based on fluorescence polarization immunoassay.
A multicolor quantum dot (QD)-based nanosensor for multiplex detection of two tumor markers in a homogeneous format based on fluorescence polarization immunoassay was proposed. QDs520 and QDs620 were labeled alpha-fetoprotein(α-AFP) and carcinoembryonic antigen (CEA), respectively. After separated and purified by ultrafiltration, they were used in fluorescence polarization immunoassay for the simultaneous detection of human serum alpha-fetoprotein and carcinoembryonic antigen. Under the optimal conditions, the multi-analyte immunosensor had a wide linear range (from 0.5 ng mL(-1) to 500 ng mL(-1)) for both two tumor markers and good correlation (0.996 for α-AFP and 0.993 for CEA). The detection limits (LOD) were 0.36 ng mL(-1) for CEA and 0.28 ng mL(-1) for α-AFP (S/N=3). The carcinoembryonic antigen and fetoprotein in clinical serum samples were simultaneously detected. The results from 28 serum samples had a good agreement with enzyme-linked immunosorbent assay (ELISA). The relative standard deviation and the recovery suggested that the precision and the accuracy of this analytical method were satisfactory. This strategy with high sensitivity, good specificity, easy procedures and short analysis time shows great promise for clinical diagnoses and basic discovery. The application of QDs with longer fluorescence lifetime and small fluorescence polarization can be used for the determination of high molecular-weight substances which cannot be analyzed using dye fluorescence polarization immunoassay.


Barotrauma: a complication of positive pressure for nasal foreign body removal in a pediatric patient.
Emergency physicians are frequently called on to remove impacted nasal foreign bodies in children. Multiple positive pressure techniques for the removal of nasal foreign bodies have been described. This case report details a previously unreported complication of barotrauma after the use of a published positive pressure technique that uses unmodulated piped hospital oxygen (wall oxygen) in the emergency department setting. We caution against the use of sustained, unmodulated positive pressure to dislodge a retained nasal foreign body.


Using intervention-oriented evaluation to diagnose and correct students' persistent climate change misconceptions: A Singapore case study.
The evaluation of classroom-based educational interventions is fraught with tensions, the most critical of which is choosing between focusing the inquiry on measuring the effects of treatment or in proximately utilizing the data to improve practice. This paper attempted to achieve both goals through the use of intervention-oriented evaluation of a professional development program intended to diagnose and correct students' misconceptions of climate change. Data was gathered, monitored and analyzed in three stages of a time-series design: the baseline, treatment and follow-up stages. The evaluation itself was the 'intervention' such that the data was allowed to 'contaminate' the treatment. This was achieved through giving the teacher unimpeded access to the collected information and to introduce midcourse corrections as she saw fit to her instruction. Results showed a significant development in students' conceptual understanding only after the teacher's decision to use direct and explicit refutation of misconceptions. Due to the accessibility of feedback, it was possible to locate specifically at which point in the process that the intervention was most effective. The efficacy of the intervention was then measured through comparing the scores across the three research stages. The inclusion of a comparison group to the design is recommended for future studies.


[Pulmonary ultrastructural changes in dogs following experimental hemorrhagic shock (author's transl)].
The authors have studied the ultrastructure of the lung in dogs following experimental hemorrhagic shock. They found intra-alveolar edema, red cells in the alveolar sac, disappearance of the substance of the lamellated osmiophilic bodies and cellular degeneration. Correlation among these alterations and increase of capillary permeability as well as consumption of surfactant secretion were established.


In vitro activity of telithromycin and quinupristin/dalfopristin against methicillin-resistant coagulase-negative staphylococci with defined resistance genotypes.
We determined the activities of new antibiotics telithromycin (ketolide) and quinupristin/dalfopristin (streptogramins) against 88 macrolide and/or lincosamide resistant coagulase-negative staphylococci (CoNS) isolates with defined resistance gene status. Telithromycin susceptibility was determined only in erythromycin-sensitive isolates (15) indicating the same mechanisms of resistance. In contrast, all erythromycin-resistant isolates (73) were either constitutively resistant to telithromycin (13 isolates with constitutive erm genes) or demonstrated telithromycin D-shaped zone (60 isolates with inducible msr(A) and/or erm). However, the level of inducible resistance conferred by msr(A) (35 isolates) was borderline even after induction by erythromycin. No quinupristin/dalfopristin resistant isolate was observed if tested by disk-diffusion method (DDM) but 18 isolates were intermediate (MIC = 1-3 mg/L) and two isolates resistant (MIC = 8 mg/L) if tested by E-test. All these isolates were resistant to streptogramin A and harbored vga(A) gene (1 isolate) or vga(A)LC gene (19 isolates). MICs for quinupristin/dalfopristin were higher for isolates with combination of streptogramin A resistance and constitutive MLSB resistance (MIC = 3-8 mg/L in 4 isolates) than for streptogramin A-resistant isolates susceptible to streptogramin B (MIC = 0.5-2 mg/L in 16 isolates). In addition to S. haemolyticus, vga(A)LC was newly identified in S. epidermidis and S. warnerii indicating its widespread occurrence in CoNS. Misidentification of low-level resistant isolates by DDM may contribute to dissemination of streptogramin A resistance.


Targeting the hypoxia-adenosinergic signaling pathway to improve the adoptive immunotherapy of cancer.
The recent approval by the FDA of cancer vaccines and drugs that blockade immunological negative regulators has further enhanced interest in promising approaches of the immunotherapy of cancer. However, the disappointingly short life extension has also underscored the need to better understand the mechanisms that prevent tumor rejection and survival even after the blockade of immunological negative regulators. Here, we describe the implications of the "metabolism-based" immunosuppressive mechanism, where the local tissue hypoxia-driven accumulation of extracellular adenosine triggers suppression via A2 adenosine receptors on the surface of activated immune cells. This molecular pathway is of critical importance in mechanisms of immunosuppression in inflamed and cancerous tissue microenvironments. The protection of tumors by tumor-generated extracellular adenosine and A2 adenosine receptors could be the misguided application of the normal tissue-protecting mechanism that limits excessive collateral damage to vital organs during the anti-pathogen immune response. The overview of the current state of the art regarding the immunosuppressive effects of extracellular adenosine is followed by a historical perspective of studies focused on the elucidation of the physiological negative regulators that protect tissues of vital organs from excessive collateral damage, but, as a trade-off, may also weaken the anti-pathogen effector functions and negate the attempts of anti-tumor immune cells to destroy cancerous cells.


Screens, maps & networks: from genome sequences to personalized medicine.
Genome sequencing of tumors provides a wealth of information on mutations and structural variations, instilling hope that this data can be used to predict individual tumor progression and response to treatment. Yet currently, our ability to predict the functional consequences of these aberrations remains poor. How do cancer-associated mutations give rise to the hallmark phenotypes of cancer? Recently, information about the genetic makeup of cancer cells has been combined with novel functional genomics approaches to identify novel targets, exploit synthetic lethality and explore the rewiring of cellular pathways. Here, we highlight recent developments revealing the hidden landscape of genetic interactions in model organisms and cancer cells, a key step toward personalized cancer diagnostics and therapy.


[Acute-on-chronic liver failure - new Definition of a complex clinical picture].
Acute-on-chronic liver failure (ACLF) is characterized by a sudden onset of decompensation in patients with preexisting liver disease followed by subsequent organ failure and high short-term mortality. ACLF is extremely heterogeneous in terms of predisposing stage of liver disease, precipitating events, and the course of organ failure and has been defined differently by different medical associations in the East and in the West. A recent consensus working definition is the basis for further research in order to understand underlying pathophysiological mechanisms, to establish diagnostic and prognostic biomarkers, and to implement risk-adapted treatment strategies.


Lab-made flexible third-generation fructose biosensors based on 0D-nanostructured transducers.
Herein, we report a scalable benchtop electrode fabrication method to produce highly sensitive and flexible third-generation fructose dehydrogenase amperometric biosensors based on water-dispersed 0D-nanomaterials. The electrochemical platform was fabricated via Stencil-Printing (StPE) and insulated via xurography. Carbon black (CB) and mesoporous carbon (MS) were employed as 0D-nanomaterials promoting an efficient direct electron transfer (DET) between fructose dehydrogenase (FDH) and the transducer. Both nanomaterials were prepared in water-phase via a sonochemical approach. The nano-StPE exhibited enhanced electrocatalytic currents compared to conventional commercial electrodes. The enzymatic sensors were exploited for the determination of D-fructose in model solutions and various food and biological samples. StPE-CB and StPE-MS integrated biosensors showed appreciable sensitivity (∼150 μA cm-2 mM-1) with μmolar limit of detection (0.35 and 0.16 μM, respectively) and extended linear range (2-500 and 1-250 μM, respectively); the selectivity of the biosensors, ensured by the low working overpotential (+0.15 V), has been also demonstrated. Good accuracy (recoveries between 95 and 116%) and reproducibility (RSD ≤8.6%) were achieved for food and urine samples. The proposed approach because of manufacturing versatility and the electro-catalytic features of the water-nanostructured 0D-NMs opens new paths for affordable and customizable FDH-based bioelectronics.