[Clinical studies on 6059-S for acute peritonitis. Clinical effect and tissue concentration (author's transl)].
A new antibiotic drug of oxacephem, with marked resistance to beta-lactamase, 6059-S for parenteral use was tested in 10 patients with acute peritonitis. In 4 cases with appendicitis, 6059-S in a dose of 500 mg was given intramuscularly before operation. In 2 cases with perforate MECKEL'S diverticulitis and intestinal obstruction for right femoral hernia, 6059-S in a dose of 1 g was given by intravenous injection or intravenous drip infusion before or during operation. And in a case with peritonitis after gastrectomy for gastric cancer, 6059-S in a dose of 2 g was given by intravenous drip infusion. Tissue specimens of different sites or body fluids were taken during the operation and from the removed organs. The materials or purulent ascites were subsequently taken at intervals. Determination of 6059-S concentration was performed according to plate agar well bioassay method with Escherichia coli 7437 strain. The peak of 6059-S concentration in purulent ascites of patient with peritonitis for perforate MECKEL'S diverticulitis was 30.5 mcg/ml at 50 min. after 1 g intravenous administration. Concentration of 6059-S in drained pus was 8.38 mcg/ml soon after intravenous drip infusion (2 g, for 2 hrs.). In 10 patients with peritonitis, 6 patients were given 6059-S in a dose of 500 mg by intramuscular administration twice a day, and the serious 4 patients were given in a dose of 1 to 2 g by intravenous drip infusion 1 to 2 times a day. Clinical response was excellent in 6 cases, good in 3 cases, fair in 1 case and poor was none. Any clinical adverse effect was not recognized. On the 6059-S concentration in patients with peritonitis, the concentration in purulent ascites, drained pus and infected tissues were observed higher than the MIC of 6059-S against Escherichia coli and Klebsiella pneumoniae. Therefore 6059-S will be a very useful drug when used for chemotherapy of acute or subacute peritonitis.


The debate on ethnicity and dementia: from category fallacy to person-centred care?
The concept of ethnicity remains attractive and meaningful to service developers and professionals, although research suggests that this disguises other facets of identity and difference. An epidemiological perspective on the relationship between ethnicity and dementia supports the idea that ethnicity (defined as particular shared cultural characteristics) is not likely to influence unduly the emergence of dementia in individuals. Cultural factors may protect against dementia, impeding its recognition and influencing its course and these deserve further investigation. Ethnicity is a general concept that subsumes and conceals the impact of migration, education, health beliefs and socio-economic status on health, and therefore is problematic. Empirical research on dementia and ethnicity reveals that intra-ethnic group variation is greater than inter-ethnic group variation; supporting the view that ethnicity as a category may not have great explanatory power and may foster a category fallacy. However, the experiences of people with dementia and their carers show that the important issues for service providers to consider are language, religious belief and observance, cultural practices (including food and personal care practices) and social support and coping mechanisms. In this position paper we argue that these issues are applicable to all individuals with dementia, independent of apparent ethnicity, and that promotion of cultural competence in service provision should not be relegated to an ethnic minority agenda. The task for health and social care providers is therefore to recognise the diversity of users and to increase access to appropriate quality mainstream person-centred services, rather than to develop segregated or specialized services.


New pharmacological approaches in heart failure therapy: developments and possibilities.
There have been few major breakthroughs in heart failure (HF) drug therapies in recent years yet HF morbidity and mortality remain high, and there is a clear need for further research. Several newer agents that appear promising in Phase I and II trials do not progress to show clinical benefit in later trials. Part of the failure to find new therapies may lie in flawed trial design compounded by the need for ever-increasing patient numbers in order to prove outcome benefit. We summarize some of the most recent and promising medical therapies for HF.


Word- and Text-Level Processes Contributing to Fluent Reading of Word Lists and Sentences.
In this study, we investigated how word- and text-level processes contribute to different types of reading fluency measures. We aimed to increase our understanding of the underlying processes necessary for fluent reading. The sample included 73 Dutch Grade 3 children, who were assessed on serial word reading rate (familiar words), word-list reading fluency (increasingly difficult words), and sentence reading fluency. Word-level processes were individual word recognition speed (discrete word reading) and sequential processing efficiency (serial digit naming). Text-level processes were receptive vocabulary and syntactic skills. The results showed that word- and text-level processes combined accounted for a comparable amount of variance in all fluency outcomes. Both word-level processes were moderate predictors of all fluency outcomes. However, vocabulary only moderately predicted sentence reading fluency, and syntactic skills merely contributed to sentence reading fluency indirectly through vocabulary. The findings indicate that sequential processing efficiency has a crucial role in reading fluency across various measures besides individual word recognition speed. Additionally, text-level processes come into play when complexity and context availability of fluency measures increases, but the exact timing requires further study. Findings are discussed in terms of future directions and their possible value for diagnostic assessment and intervention of reading difficulties.


Relationships between patient-related risk factors, processes, structures, and outcomes of cardiac surgical care. Conceptual models.
The processes, Structures, and Outcomes of Care in Cardiac Surgery (PSOCS) study involves data collection on a comprehensive array of patient risk factors, processes, structures, and short-term outcomes of care at 14 participating Veterans Administration medical centers. This article summarizes the PSOCS conceptual models that serve as the theoretical framework for analyzing the hypothesized risk-process-structure-outcome relationships being investigated. The PSOCS data set includes more than 1,100 variables related to each patient and more than 300 variables related to provider-specific and facility-specific characteristics. This massive data set presents a formidable analytic challenge. The conceptual modeling process involved four-steps: 1) establishing a vision of the general conceptual model defining the overall risk-process-structure-outcome relationships, 2) developing specific hypotheses or subhypotheses, 3) visualizing a hierarchical set of dimensions and subdimensions, and 4) uniquely assigning each variable collected in the study to a dimension or subdimension for purposes of testing the study's primary hypotheses. A multidisciplinary team participated in this modeling process. The goal of the conceptual modeling process is to identify clearly the actions (ie, the changes in either processes or structures that are linked to risk-adjusted patient outcomes) that can be taken by clinicians, management, and policymakers to improve the quality of cardiac surgical care.


Effects of cardiotoxin III on NF-kappaB function, proliferation, and apoptosis in human breast MCF-7 cancer cells.
Cardiotoxin III (CTX III), a basic polypeptide with 60 amino acid residues isolated from Naja naja atra venom, has been reported to have anticancer activity. CTX III-induced apoptosis in human breast MCF-7 cancer cells was confirmed by sub-G1 formation, phosphatidylserine (PS) externalization, and poly (ADP-ribose) polymerase (PARP) cleavage with an IC50 of 2 microg/ml at 48 h. Effects of CTX III on proliferation and apoptosis correlated with upregulation of Bax, and downregulation of Bcl-XL, Bcl-2, and XIAP, with no appreciable alteration on the protein levels of Bid, Bim, and survivin. CTX III treatment also caused release of mitochondrial cytochrome c to the cytosol, which led to subsequent activation of capase-9. Moreover, CTX III inhibited the nuclear factor-kappaB (NF-kappaB) activation through inhibition of IkappaB kinase (IkappaK) activity. Overall, our results indicate that CTX III downregulates NF-kappaB in MCF-7 cells, leading to the suppression of proliferation and induction of apoptosis. These findings suggest the molecular basis for CTX III-induced apoptotic death of MCF-7 cells.


Proximal small bowel obstruction in a patient with cystic fibrosis: a case report.
As advancements are made in the management of cystic fibrosis (CF), survival of the CF patient into adulthood has increased, leading to the discovery of previously unknown CF complications. Though gastrointestinal complications of CF, such as distal intestinal obstruction syndrome, are common, this case demonstrates a variant presentation of small bowel obstruction in this population. We describe a 42-year-old male with CF who presented with 2 days of worsening upper abdominal pain, emesis, and loss of bowel function. The patient had no history of any prior abdominal surgeries; however, imaging was concerning for high-grade mechanical small bowel obstruction possibly related to internal hernia. Given leukocytosis and diffusely tender abdomen found on further workup, the decision was made to proceed with diagnostic laparoscopy after a brief period of intravenous fluid resuscitation. Intraoperatively, the transition point was found in the mid-jejunum and was noted to be due to kinking of the bowel causing vascular congestion in the proximal portion. Surgical manipulation of the bowel was required for return of normal perfusion and patency. Though the exact mechanism cannot be definitively delineated, we speculate that the increased viscosity and prolonged intestinal transit time, characteristic of CF, resulted in inspissated fecal content in the proximal small bowel, which then acted as a lead point for obstruction. Thus, though small bowel obstruction in patients with CF is often attributed to distal intestinal obstruction syndrome, a broader differential must be considered. Early surgical intervention may be necessary to prevent bowel ischemia and subsequent small bowel resection in a patient presenting with concerning clinical and image findings, as was seen in this patient.


Chromatographic behaviour predicts the ability of potential nootropics to permeate the blood-brain barrier.
The log BB parameter is the logarithm of the ratio of a compound's equilibrium concentrations in the brain tissue versus the blood plasma. This parameter is a useful descriptor in assessing the ability of a compound to permeate the blood-brain barrier. The aim of this study was to develop a Hansch-type linear regression QSAR model that correlates the parameter log BB and the retention time of drugs and other organic compounds on a reversed-phase HPLC containing an embedded amide moiety. The retention time was expressed by the capacity factor log k'. The second aim was to estimate the brain's absorption of 2-(azacycloalkyl)acetamidophenoxyacetic acids, which are analogues of piracetam, nefiracetam, and meclofenoxate. Notably, these acids may be novel nootropics. Two simple regression models that relate log BB and log k' were developed from an assay performed using a reversed-phase HPLC that contained an embedded amide moiety. Both the quadratic and linear models yielded statistical parameters comparable to previously published models of log BB dependence on various structural characteristics. The models predict that four members of the substituted phenoxyacetic acid series have a strong chance of permeating the barrier and being absorbed in the brain. The results of this study show that a reversed-phase HPLC system containing an embedded amide moiety is a functional in vitro surrogate of the blood-brain barrier. These results suggest that racetam-type nootropic drugs containing a carboxylic moiety could be more poorly absorbed than analogues devoid of the carboxyl group, especially if the compounds penetrate the barrier by a simple diffusion mechanism.


Sec13 promotes oligodendrocyte differentiation and myelin repair through autocrine pleiotrophin signaling.
Dysfunction of protein trafficking has been intensively associated with neurological diseases, including neurodegeneration, but whether and how protein transport contributes to oligodendrocyte (OL) maturation and myelin repair in white matter injury remains unclear. ER-to-Golgi trafficking of newly synthesized proteins is mediated by coat protein complex II (COPII). Here, we demonstrate that the COPII component Sec13 was essential for OL differentiation and postnatal myelination. Ablation of Sec13 in the OL lineage prevented OPC differentiation and inhibited myelination and remyelination after demyelinating injury in the central nervous system (CNS), while improving protein trafficking by tauroursodeoxycholic acid (TUDCA) or ectopic expression of COPII components accelerated myelination. COPII components were upregulated in OL lineage cells after demyelinating injury. Loss of Sec13 altered the secretome of OLs and inhibited the secretion of pleiotrophin (PTN), which was found to function as an autocrine factor to promote OL differentiation and myelin repair. These data suggest that Sec13-dependent protein transport is essential for OL differentiation and that Sec13-mediated PTN autocrine signaling is required for proper myelination and remyelination.


The First Case of Eosinophilic Granulomatosis with Polyangiitis Simultaneously Demonstrating Various Clinical Manifestations with Retroperitoneal Fibrosis and Membranous Nephropathy.
The first case of eosinophilic granulomatosis with polyangiitis (EGPA) simultaneously demonstrating various clinical manifestations, including retroperitoneal fibrosis (RPF) causing hydronephrosis and membranous nephropathy (MN) leading to nephrotic syndrome, is presented. There have been no previous case reports demonstrating the simultaneous onset of these three disease categories with significant complex pathologies. This case was successfully managed by providing adequate combination therapies according to each disease category, leading to complete remission (CR) of all three diseases. In conclusion, we believe this case is extremely rare and clinically suggestive, and that these findings can be applied to a future phenotype-tailored treatment strategy for EGPA.


Training Loads, Wellness and Performance Before and During Tapering for a Water-Polo Tournament.
We investigated the effectiveness of a short-duration training period including an overloaded (weeks 1 and 2) and a reduced training load period (weeks 3 and 4) on wellness, swimming performance and a perceived internal training load in eight high-level water-polo players preparing for play-offs. The internal training load was estimated daily using the rating of perceived exertion (RPE) and session duration (session-RPE). Perceived ratings of wellness (fatigue, muscle soreness, sleep quality, stress level and mood) were assessed daily. Swimming performance was evaluated through 400-m and 20-m tests performed before (baseline) and after the end of weeks 2 and 4. In weeks 3 and 4, the internal training load was reduced by 19.0 ± 3.8 and 36.0 ± 4.7%, respectively, compared to week 1 (p = 0.00). Wellness was improved in week 4 (20.4 ± 2.8 AU) compared to week 1 and week 2 by 16.0 ± 2.2 and 17.3 ± 2.9 AU, respectively (p =0.001). At the end of week 4, swimming performance at 400-m and 20-m tests (299.0 ± 10.2 and 10.2 ± 0.3 s) was improved compared to baseline values (301.4 ± 10.9 and 10.4 ± 0.4 s, p < 0.05) and the overloading training period (week 2; 302.9 ± 9.0 and 10.4 ± 0.4 s, p < 0.05). High correlations were observed between the percentage reduction of the internal training load from week 4 to week 1 (-25.3 ± 5.5%) and the respective changes in 20-m time (-2.1 ± 2.2%, r = 0.88, p < 0.01), fatigue perception (39.6 ± 27.1%), muscle soreness (32.5 ± 26.6%), stress levels (25.6 ± 15.1%) and the overall wellness scores (28.6 ± 21.9%, r = 0.74-0.79, p < 0.05). The reduction of the internal training load improved the overall perceived wellness and swimming performance of players. The aforementioned periodization approach may be an effective training strategy in the lead-up to play-off tournaments.


Model-driven CDA Clinical Document Development Framework.
The Health Level 7 (HL7) Clinical Document Architecture, Release 2 (CDA R2) standardizes the structure and semantics of clinical documents in order to permit interchange. We have applied this standard to generate a platform independent CDA model and write a toolset that permits model specialization, generation of XML implementation artifacts, and provides an interface for clinical data managers. The resulting work was tested using US Department of Veterans Affairs Operative Note templates.


The role of protein kinase C in diabetic microvascular complications.
Protein kinase C (PKC) is a family of serine/threonine protein kinases, the activation of which plays an important role in the development of diabetic microvascular complications. The activation of PKC under high-glucose conditions stimulates redox reactions and leads to an accumulation of redox stress. As a result, various types of cells in the microvasculature are influenced, leading to changes in blood flow, microvascular permeability, extracellular matrix accumulation, basement thickening and angiogenesis. Structural and functional disorders further exacerbate diabetic microvascular complications. Here, we review the roles of PKC in the development of diabetic microvascular complications, presenting evidence from experiments and clinical trials.


Protocol for black student well-being study: a multi-site qualitative study on the mental health and well-being experiences of black UK university students.
There is an increasing concern about the mental health and mental well-being of university students in the UK. Black university students who report a mental health condition are less likely to complete their course, achieve a first-class or upper second-class degree and progress to further education. This study will document black university students' accounts of their mental health experiences and perceptions of key turning points of biographical changes to their mental health as they move through the university life cycle. This is a qualitative study. Data will be collected through a biographical narrative interpretive method. Interviews will enable the researcher to study systematically how participants make sense of themselves and account for the complexities of their life experiences, from their own perspectives and language. An interpretative phenomenological approach will be used to offer insights into what black students studying at UK universities report affects their mental health and well-being. Data collection for this study commenced in October 2020. Data collection and analyses will be completed by January 2022. Full ethical approval for the current study was obtained from King's College London Psychiatry, Nursing and Midwifery Research Ethics Subcommittee (Rec Ref: 20489, Project Ref: HR-19/20-20489, 2 October 2020). From the study findings, we aim to contribute to the evidence base, make recommendations for interventions and encourage further study into black student mental health.


Effectiveness of a mobile phone text messaging intervention on dietary behaviour in patients with type 2 diabetes: a post-hoc analysis of a randomised controlled trial.
Evidence suggests that mobile phone health (mHealth) programs may improve healthy behaviours and clinical outcomes in patients with type 2 diabetes mellitus (T2DM). However, data on mHealth dietary behaviour is scarce in low-and-middle-income countries. This study aims to determine the effectiveness of a text messaging program on dietary habits in patients with T2DM. We performed a post-hoc analysis of a randomised controlled trial of text messaging intervention in 236 patients with T2DM recruited from a tertiary hospital. Data were collected on socio-demographics, mobile phone use, family and medical history, self-reported diseases, medication use, health-seeking behaviour, diet and physical activity. Dietary behaviour was assessed using a modified version of WHO STEPS and the Indian Migration Study Food Frequency Questionnaire. Intervention participants received one message/day over six months focusing on lifestyle modification. Dietary intake of fruits, vegetables, sugar beverages and teaspoons of sugar in tea/coffee were determined in serves-per-week and were analysed using Chi-square tests. Poisson regression models, adjusted for age, sex and baseline values following an intention-to-treat approach were performed and expressed as an estimate of effect size. At 6 months, the adjusted difference in vegetable consumption was -0.02 serves/week [95% confidence interval (CI): -0.11-0.06, P>0.05] and fruit intake was 0.02 serves/week (95% CI: -0.15-0.21, P>0.05). Consumption of sugar beverages reduced in both groups at 6 months with an adjusted difference of -0.34 serves/week (95% CI: -1.10-0.42, P>0.05). Teaspoons of sugar in tea reduced to 0.1±0.3 teaspoons/week in the control group, however, remained the same at 0.2±0.6 teaspoons/week in the intervention group with an adjusted difference of 0.94 teaspoons/week (95% CI: 0.04-1.84, P<0.05). Our results suggest that a text messaging program did not significantly improve dietary behaviour in patients with T2DM. Further studies are warranted to explore the effectiveness of text messaging on dietary behaviour in adults with T2DM. German Clinical Trials Register DRKS00005188, http://www.drks.de.


Transient depression of LWa antigen with coincident production of anti-LWa repeated in relapses of malignant lymphoma.
Three years ago, a 71-year-old female was admitted because of general lymphadenopathy. She had been on medication for hypothroidism, but had no history of pregnancy or blood transfusion. T-cell lymphoma was found. Since then, she has been treated with intermittent chemotherapy. The patient's LWa antigen was depressed during two relapses of the lymphoma and anti-LWa was detected simultaneously on both occasions. When she entered remission after therapy, her LW phenotype converted from LW(a-) to LW(a+), and this was accompanied by the disappearance of anti-LWa. This suggests that LW(a-) was a transient phenotype. In the first relapse, a total of 8 units of D- LW(a+) packed red cells and 20 units of platelets were transfused during 1 month without any haemolytic reaction. In these relapses, nonhaemolytic anaemia, hyper-gamma-globulinaemia and remarkable bone-marrow infiltration with lymphoplasma cells were recognized. She also possessed antithyroglobulin and antimicrosomal antibodies; however, these autoantibodies did not change with the relapses. These results suggests that the recurrent depressions of LWa may be closely related to the underlying disease.


Optimal sparsity allows reliable system-aware restoration of fluorescence microscopy images.
Fluorescence microscopy is one of the most indispensable and informative driving forces for biological research, but the extent of observable biological phenomena is essentially determined by the content and quality of the acquired images. To address the different noise sources that can degrade these images, we introduce an algorithm for multiscale image restoration through optimally sparse representation (MIRO). MIRO is a deterministic framework that models the acquisition process and uses pixelwise noise correction to improve image quality. Our study demonstrates that this approach yields a remarkable restoration of the fluorescence signal for a wide range of microscopy systems, regardless of the detector used (e.g., electron-multiplying charge-coupled device, scientific complementary metal-oxide semiconductor, or photomultiplier tube). MIRO improves current imaging capabilities, enabling fast, low-light optical microscopy, accurate image analysis, and robust machine intelligence when integrated with deep neural networks. This expands the range of biological knowledge that can be obtained from fluorescence microscopy.


Tetanic stimulation and cyclic adenosine monophosphate regulate segregation of presynaptic inputs on a common postsynaptic target neuron in vitro.
Previous studies indicated that Aplysia sensory neurons (SNs) compete when reestablishing synapses with a motor cell target (L7) in vitro. The competition is characterized by a cell number-dependent decrease in the efficacy of each connection, an increase in the elimination of SN varicosities, a reduction in the formation of new SN varicosities, and the segregation of varicosities of each SN to restricted portions of the target axons. The changes do not require spike activity, since both the SNs and L7 do not fire spontaneously. Here, we examined whether adding activity to SNs during the early stages of synapse formation with stimuli known to evoke facilitatory responses in stable SN-L7 connections--tetanic stimulation or increase in intracellular cyclic adenosine monophosphate (cAMP)--would modulate the intrinsic segregatory process. Tetanic stimulation to one SN increased synapse efficacy and the number of varicosities of the stimulated SNs while reducing the functional changes by the nonstimulated SNs in the same cultures. An increase in the stability of preexisting varicosities contributed to the overall increase in varicosities evoked by tetanus. The functional changes evoked by tetanus were not expressed when the same tetanic stimulation was also given to the other SN, or when L7 was hyperpolarized during the tetanus to the SN. Raising cAMP levels in one SN increased synapse efficacy and the rate of new varicosity formation by the injected SNs without affecting the development of the connections formed by the noninjected SNs. These results suggest that different forms of presynaptic and postsynaptic activities in neurons can regulate specific aspects of the competitive process associated with the fine-tuning of connections formed by converging presynaptic inputs.


The B cell helper side of neutrophils.
Neutrophils use opsonizing antibodies to enhance the clearance of intruding microbes. Recent studies indicate that splenic neutrophils also induce antibody production by providing helper signals to B cells lodged in the MZ of the spleen. Here, we discuss the B cell helper function of neutrophils in the context of growing evidence indicating that neutrophils function as sophisticated regulators of innate and adaptive immune responses.


[Aspects of primary tuberculosis infection in children: 27 cases observed at Children's Hospital, Antananarivo].
A retrospective study on tubercular primary infection in children was carried-out for 18 months (January 1994--June 1995) at the Child Hospital of Tsaralalana in Antananarivo-City. 27 cases were reported. The sex-ratio was of 1,01/1. The most clinical forms were pulmonary tuberculosis. An associated factor was malnutrition. Contact has been traced back to close family. Short course treatment regimen was the standard applied.


A study on the weights and ratios of hepatic segments in 438 adult Japanese autopsies.
This study presents relationships of the actual weights and their weight ratios of each hepatic segment. A total of 438 adult Japanese autopsies performed at the Tokyo Metropolitan Medical Examiner's Office were used. Examined cases consisted of 258 normal livers and 182 pathological livers. Weights of the whole liver, the right and left surgical hepatic lobes, and each hepatic segment, and the results of their statistical analyses, are reported by age and sex. The normal 256 liver weights were significantly different according to age (P < 0.001) and sex (P = 0.001). An approximate liver weight per kilogram of body weight is roughly about 25 g in all ages and both sexes. The weight ratios of the lateral, medial, anterior, and posterior segments were approximated to be 20:20:35:25, respectively, not only in normal and pathological livers in which the liver retained an ordinary shape but also in adult age groups and both sexes.


A Langmuir monolayer study of the interaction of E1(145-162) hepatitis G virus peptide with phospholipid membranes.
E1(145-162), a peptide corresponding to the structural protein E1 of the GB virus C, has been shown earlier to bind at pH 7.4 to vesicles containing 1,2-dimyiristoyl-sn-glycero-3-phospho-rac-(1-glycerol)] (DMPG) and 1,2-dimyiristoyl-sn-glycero-3-phosphocholine (DMPC) phospholipids. To deepen the understanding of the interaction of E1(145-162) with the lipid membrane, in this paper, we report a detailed study of the surface properties of peptide, miscibility properties, and behavior of mixed monomolecular films of it and three phospholipids DMPG, DMPC, and 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPG). These studies were performed using the Langmuir balance by means of surface adsorption studies, surface pressure-mean molecular area compression isotherms, and penetration kinetics. The Brewster angle microscopy (BAM) was used to study the morphological properties of pure peptide and the mixed monolayers. The results show us that the peptide showed surface activity concentration dependent when injected beneath a buffered solution (HEPES/NaCl, pH 7.4). This tendency to accumulate into the air/water interface confirms its potential capacity to interact with membranes; the higher penetration of peptide into phospholipids is attained when the monolayers are in the liquid expanded state and the lipids are charged negatively maybe due to its negative electric charge that interacts with the positive global charge of the peptide sequence. The area per molecule values obtained suggested that the main arrangement structure for E1(145-162) peptide is the alpha-helical at the air-water interface that agreed with computational prediction calculations. Miscibility studies indicated that mixtures become thermodynamically favored at low peptide molar fraction.


Do iconic gestures pave the way for children's early verbs?
Children produce a deictic gesture for a particular object (point at dog) approximately three months before they produce the verbal label for that object ("dog") (Iverson & Goldin-Meadow, 2005). Gesture thus paves the way for children's early nouns. We ask here whether the same pattern-gesture preceding and predicting speech-holds for iconic gestures-that is, do gestures that depict actions precede and predict early verbs? We observed spontaneous speech and gestures produced by 40 children (22 girls, 18 boys) from age 14 to 34 months. Children produced their first iconic gestures 6 months later than they produced their first verbs. Thus, unlike the onset of deictic gestures, the onset of iconic gestures conveying action meanings followed, rather than preceded, children's first verbs. However, iconic gestures increased in frequency at the same time as verbs did and, at that time, began to convey meanings not yet expressed in speech. Our findings suggest that children can use gesture to expand their repertoire of action meanings, but only after they have begun to acquire the verb system underlying their language.


Randomized controlled trial on the effectiveness of web-based Genomics Nursing Education Intervention for undergraduate nursing students: a study protocol.
To describe a randomized controlled trial protocol that will evaluate the effectiveness of two web-based genomic nursing education interventions. Preparing future nurses to be competent in genetic and genomic concepts is fundamental to ensure appropriate clinical application. However, genetics-genomics concepts are still new in the field of nursing. Little is known about what type and kind of web-based nursing education is effective in improving the knowledge of nursing students. To address these knowledge gaps, a web-based 'Genomic Nursing Education Intervention' will be developed and compared with an existing online education programme. A randomized controlled trial of two groups with pre-test and repeated posttesting. The Genomic Nursing Concept Inventory, a validated tool, will be used to assess the genetics-genomics knowledge of nursing students. Participants will be randomly allocated to either a control or an intervention group. The control group will receive the standard web-based nursing education, while the intervention group will receive a newly developed web-based education intervention. Outcome measures include the students' knowledge level of nursing genetics-genomics concepts. Participants will be retested at 3 and 6 months. Current evidence shows that ensuring nurses have adequate education in genetic-genomic concepts is challenging. This study will demonstrate which of two web-based nursing education methods is more effective in teaching genetic-genomic concepts. This research project will better prepare the nursing profession in their careers for the emerging advance technologies in genetics-genomics and personalized health care. Current evidence shows major challenges in ensuring that nurses have adequate education in genetics-genomics concepts. Less is known about what approaches to web-based education are effective to improve the knowledge gaps of nursing students in genetics-genomics concepts. This study will determine which type of web-based nursing education is effective in improving the genetics-genomics knowledge of nursing students. This research project will help better prepare nurses in dealing with advances in genetics-genomics in their careers. This study is registered in ClinicalTrials.gov (ID number NCT03963687) https://clinicaltrials.gov/show/NCT03963687.


Microalbuminuria in Patients with Hypertension Visiting Tertiary Care Centre, Western Nepal.
Renal complications of hypertension are associated with high morbidity and mortality. Prediction of such complications at the earliest is of utmost importance. We aimed to assess the prevalence of microalbuminuria in hypertensive patients. A total of 130 clinically diagnosed hypertensive patients were enrolled in the study. Biochemical parameters that included serum creatinine, urinary albumin, and urinary creatinine were measured using standard methods. Albumin Creatinine ratio and estimated glomerular filtration rate were calculated. Albumin Creatinine ratio values between 30-300 mg/g were considered as microalbuminuria. Statistical analysis was performed on 120 samples after excluding frank proteinuria. The prevalence of microalbuminuria in hypertensive patients was 19.16%. Mean ranks of systolic blood pressure, pulse pressure, and serum creatinine levels were significantly higher in hypertensive patients with microalbuminuria. Mean estimated glomerular filtration rate was significantly low in hypertensive patients with microalbuminuria. Older age and increased duration as well as severity of hypertension were not associated with a higher prevalence of microalbuminuria. The prevalence of microalbuminuria was high in hypertensive patients. Serum creatinine and estimated glomerular filtration rate were significantly altered in patients with microalbuminuria. Early screening of microalbuminuria in such patients might help prevent renal complications.


Theoretical investigations of broadband mid-infrared optical parametric amplification based on a La3Ga5.5Nb0.5O14 crystal.
Recent progress in strong-field physics has stimulated the quest for intense mid-infrared ultrashort light sources. Optical parametric amplification (OPA) is one promising method to build up such sources, however, its development significantly relies on the availability of suitable nonlinear crystals. Here, we introduce a positive uniaxial crystal La3Ga5.5Nb0.5O14 (LGN), which exhibits a favorable set of optical properties for the application in a mid-IR OPA. We theoretically evaluate the performance of LGN as the nonlinear crystal of a mid-infrared OPA, with an emphasis on the bandwidth characteristic. We find that this crystal can support broadband amplifications across its entire mid-infrared transparent region up to 6 μm, outperforming other commonly-used mid-infrared crystals in terms of gain bandwidth. Few-cycle mid-infrared pulses at various wavelengths can be generated from the LGN-based optical parametric chirped-pulse amplifiers.


Emotion speeds up conflict resolution: a new role for the ventral anterior cingulate cortex?
It has been hypothesized that processing of conflict is facilitated by emotion. Emotional stimuli signal significance in a situation. Thus, when an emotional stimulus is task relevant, more resources may be devoted to conflict processing to reduce the time that an organism is unable to act. In the present electroencephalography and functional magnetic resonance imaging (fMRI) studies, we employed a conflict task and manipulated the emotional content and prosody of auditory target stimuli. In line with our hypothesis, reaction times revealed faster conflict resolution for emotional stimuli. Early stages of event-related potential conflict processing were modulated by emotion as indexed in an enhanced frontocentral negativity at 420 ms. FMRI yielded conflict activation in the dorsal anterior cingulate cortex (dACC), a crucial part of the executive control network. The right ventral ACC (vACC) was activated for conflict processing in emotional stimuli, suggesting that it is additionally activated for conflict processing in emotional stimuli. The amygdala was also activated by emotion. Furthermore, emotion increased functional connectivity between the vACC and activity in the amygdala and the dACC. The results support the hypothesis that emotion speeds up conflict processing and suggest a new role for the vACC in processing conflict in particularly significant situations signaled by emotion.


Bivariate empirical mode decomposition for ECG-based biometric identification with emotional data.
Emotions modulate ECG signals such that they might affect ECG-based biometric identification in real life application. It motivated in finding good feature extraction methods where the emotional state of the subjects has minimum impacts. This paper evaluates feature extraction based on bivariate empirical mode decomposition (BEMD) for biometric identification when emotion is considered. Using the ECG signal from the Mahnob-HCI database for affect recognition, the features were statistical distributions of dominant frequency after applying BEMD analysis to ECG signals. The achieved accuracy was 99.5% with high consistency using kNN classifier in 10-fold cross validation to identify 26 subjects when the emotional states of the subjects were ignored. When the emotional states of the subject were considered, the proposed method also delivered high accuracy, around 99.4%. We concluded that the proposed method offers emotion-independent features for ECG-based biometric identification. The proposed method needs more evaluation related to testing with other classifier and variation in ECG signals, e.g. normal ECG vs. ECG with arrhythmias, ECG from various ages, and ECG from other affective databases.


Influence of N-rich material in valorization of industrial eggshell by co-composting.
Industrial eggshell (ES) is an animal by-product (ABP) involving some risk if not properly managed. Composting is a possible treatment approved for its safe use. This study aims to assess the influence of using N-rich material (grass clippings (GC)) to improve co-composting of ES mixtures for reaching sanitizing temperatures imposed by the ABP regulation from the European Union. Two sets of mixtures (M1 and M2) were investigated, each containing industrial potato peel waste, GC and rice husks at 3:1.9:1 and 3:0:1 ratios by wet weight. In each set, ES composition ranged from 0% to 30% (w/w). Co-composting trials were performed in self-heating reactors for 25 days, followed by maturation in piles. Results showed that only M1 trials attained temperatures higher than 70°C for nine consecutive hours, but N-losses by stripping on average were four- to five-fold higher than M2. In the absence of N-rich material, biodegradability of mixtures was 'low' to 'moderate' and organic matter conversion was impaired. Physical, chemical and phytotoxic properties of finished composts were suitable for soil improvement, but M1 took 54 more days to achieve maturity. In conclusion, co-composting ES with N-rich materials is important to assure the fulfilment of sanitizing requirements, avoiding any additional thermal treatment.


Prevalence of mucosal lesions in the stomach and duodenum due to chronic use of NSAID in patients with rheumatoid arthritis or osteoarthritis, and interim report on prevention by misoprostol of diclofenac associated lesions.
We review preliminary findings of the screening and prophylaxis phases of a study of misoprostol in patients with arthritis receiving nonsteroidal antiinflammatory drugs (NSAID). Endoscopic evaluation of over 1,800 patients with rheumatoid arthritis or osteoarthritis, more than 95% of whom qualified for screening on the basis of continuous NSAID use over the prior 6 months, has revealed clinically significant gastroduodenal lesions in 37% and ulceration in 24%. In the prophylaxis phase, patients without significant lesions were randomized to receive misoprostol or placebo and NSAID therapy with diclofenac for 52 weeks. Product-limit and crude incidence analyses of data from patients thus far enrolled indicate that misoprostol is associated with significant protection against the development of gastroduodenal lesions compared with placebo after 12 or 24 weeks of study. No adverse effect of misoprostol administration on underlying arthritis activity has been observed thus far. Definitive conclusions await completion of the study.


Spatiotemporal transcription of the P element and the 412 retrotransposon during embryogenesis of Drosophila melanogaster and D. willistoni.
Transposable elements (TEs) are mobile nucleotide sequences which, through changing position in host genomes, partake in important evolutionary processes. The expression patterns of two TEs, P element transposon and 412 retrotransposon, were investigated during Drosophila melanogaster and D. willistoni embryogenesis, by means of embryo hybridization using riboprobes. Spatiotemporal transcription patterns for both TEs were similar to those of developmental genes. Although the two species shared the same P element transcription pattern, this was not so with 412 retrotransposon. These findings suggest that the regulatory sequences involved in the initial development of Drosophila spp are located in the transposable element sequences, and differences, such as in this case of the 412 retrotransposon, lead to losses or changes in their transcription patterns.


PEG adsorption of autoantibodies causes loss of concomitant alloantibody.
Use of polyethylene glycol (PEG) to promote adsorption of autoantibodies is reported to give good recovery of concomitant alloantibodies. In initial experiments, PEG and ZZAP (Ficin and DTT) adsorption procedures were compared for removal of autoantibody and recovery of alloantibody. Postadsorption studies (n = 11) were performed and hemagglutination scores compared. In subsequent studies, equal volumes of alloantibody containing sera, PEG, and antigen-negative red blood cells (RBCs) were used in twofold adsorption experiments. Saline was substituted for PEG for control purposes. Postadsorption titers and immunoglobulin levels were determined. Autoantibodies were completely removed by both methods (n = 5); better by PEG (n = 3); better by ZZAP (n = 1); and not adsorbed (n = 1), and partially adsorbed by both (n = 1). Alloantibody recovery was comparable in three cases (E, K, Jka) but weaker by at least one reaction grade in four (K,E, Jka, and antibody to low-frequency antigen). The latter anti-Jka reacted 1+ with Jk(a+b+) RBCs after ZZAP adsorption but was nonreactive with the same RBCs following PEG adsorption. Titers of six alloantibodies adsorbed with antigen-negative RBCs in PEG were markedly weaker (range 2 to 8) compared to saline controls (range 4 to 32). IgG levels for PEG adsorbed (range 128 to 243 mg/dL) were 50% lower than controls (range 265 to 505 mg/dL). Although PEG adsorption is effective in removing autoantibody, the precipitation of immunoglobulin by PEG may result in failure to detect underlying alloantibody.


Beyond the List: Bioagent-Agnostic Signatures Could Enable a More Flexible and Resilient Biodefense Posture Than an Approach Based on Priority Agent Lists Alone.
As of 2021, the biothreat policy and research communities organize their efforts around lists of priority agents, which elides consideration of novel pathogens and biotoxins. For example, the Select Agents and Toxins list is composed of agents that historic biological warfare programs had weaponized or that have previously caused great harm during natural outbreaks. Similarly, lists of priority agents promulgated by the World Health Organization and the National Institute of Allergy and Infectious Diseases are composed of previously known pathogens and biotoxins. To fill this gap, we argue that the research/scientific and biodefense/biosecurity communities should categorize agents based on how they impact their hosts to augment current list-based paradigms. Specifically, we propose integrating the results of multi-omics studies to identify bioagent-agnostic signatures (BASs) of disease-namely, patterns of biomarkers that accurately and reproducibly predict the impacts of infection or intoxication without prior knowledge of the causative agent. Here, we highlight three pathways that investigators might exploit as sources of signals to construct BASs and their applicability to this framework. The research community will need to forge robust interdisciplinary teams to surmount substantial experimental, technical, and data analytic challenges that stand in the way of our long-term vision. However, if successful, our functionality-based BAS model could present a means to more effectively surveil for and treat known and novel agents alike.


Fine mapping of the human endothelin-converting enzyme gene by fluorescent in situ hybridization and radiation hybrids.
Based on the sequence of the human endothelin-1-converting enzyme (hECE-1) cDNA, we cloned a 1982 bp cDNA fragment and we amplified by PCR a 3' fragment located on the last exon (exon 19). Human metaphase chromosomes were studied by Fluorescent in Situ Hybridization (FISH) using the 1982 digoxigenated hECE-1 fragment as a probe and chromosome 1-specific probes. Twin spot signals on each of the two homologous chromosomes 1 were found by FISH on band p36. The results of monochromosomal hybrids confirmed that hECE-1 is on chromosome 1. Radiation hybrid mapping localized the hECE-1 gene 3.15 cR far from D1S2436 (WI-3177), at about 25 cM from the telomere of the short arm, possibly at the border between 1p36.3 and 1p36.2.


In utero exposure to diethylstilboestrol or 4-n-nonylphenol in rats: number of sertoli cells, diameter and length of seminiferous tubules estimated by stereological methods.
The effects on testis weight and histopathology were studied in 11-day-old male Wistar rats after prenatal exposure to peanut oil (control), diethylstilboestrol 30 microg/kg b.wt./day, or 4-n-nonylphenol 75 mg/kg b.wt./day from gestational day 11 to 18. Additionally, the diameter and length of seminiferous tubules, and the number of Sertoli cells were investigated with stereological methods. Such unbiased methods have not previously been applied on testis diameter and length or on Sertoli cell number of 11-day-old rats. In the control group, the mean length of the seminiferous tubule was 3.0 m+/-0.6, the mean diameter of the seminiferous tubule was 83 microm+/-6, and the mean number of Sertoli cells was 26.1x10(6)+/-4.6. No differences in testis weight, histopathology, or length or diameter of the seminiferous tubules were observed in the diethylstilboestrol and nonylphenol exposed groups when compared to the control group. In the diethylstilboestrol-treated group, a statistically significant decrease in the number of Sertoli cells was observed (P<0.01) when compared to the control group, whereas nonylphenol had no effect. The result suggests that diethylstilboestrol decreases Sertoli cell proliferation in the foetal testis and furthermore indicate that oestrogens may pose a risk to the reproductive capacity in sensitive species, including man.


Appearance and Disappearance of Cyanide-Resistant Respiration in Vigna mungo Cotyledons during and following Germination of the Axis.
Mitochondrial preparations isolated from black gram (Vigna mungo L.) cotyledons exhibited cyanide-resistant respiration which was of mitochondrial origin. The appearance and the disappearance of this alternative respiration took place during and following imbibition. During the first 6 hours of imbibition, the respiration was completely inhibited by cyanide, but after this time the alternative respiration markedly developed, reaching a maximal cyanide-resistance 12 to 16 hours after the start of imbibition. Subsequently, the alternative respiration gradually disappeared. The actions of cycloheximide and chloramphenicol indicated that the appearance was dependent on cytoplasmic protein synthesis and that the disappearance depended on both cytoplasmic and mitochondrial protein synthesis. The alternative pathway contributed to state 4 respiration, but not to state 3 respiration, in mitochondria from 1-day-old cotyledons. On day 3, it contributed to neither state 3 nor state 4.


Genetic relationship between Trichophyton mentagrophytes var. interdigitale and Arthroderma vanbreuseghemii.
Thirty-nine Arthroderma vanbreuseghemii isolates identified by mating behavior were assayed to determine their ribosomal RNA gene internal transcribed spacer (ITS) region genotypes. Twenty-two isolates of mating type (+) and 4 of (-) showed the genotype of Trichophyton mentagrophytes var. interdigitale, 9 isolates of mating type (+) and 4 of (-) showed the genotype of A. vanbreuseghemii. Nine of 14 isolates with granular or asteroid colony morphology showed the genotype of T. mentagrophytes var. interdigitale. There was no relation between ITS genotype and morphology or mating type of the isolates. Isolates of T. mentagrophytes var. interdigitale genotype were shown to include non-sexually degenerate zoophilic strains with granular colony morphology as well as sexually and morphologically degenerate anthropophilic strains and may be just one genotype of a heterogeneous species, A. vanbreuseghemii.


Parietal seeding of unsuspected gallbladder carcinoma after laparoscopic cholecystectomy.
Laparoscopic cholecystectomy (VALC) represents the treatment of choice for the symptomatic gallstones. However the occurrence of an adenocarcinoma of the gallbladder results a controindication for this surgical technique. We present a case of a 52 years old woman who underwent a VALC; histology revealed a gallbladder adenocarcinoma. For this reason the patient underwent a second operation that is right hepatic trisegmentectomy. Six months later the patient presented with a parietal recurrence at the extraction site of the gallbladder. We discuss the possible mechanism responsible for carcinomatous dissemination during laparoscopic surgery and we raccommend the use of some procedures in order to limit the risk and eventually to treat a neoplastic parietal seeding. These complications suggest the problem about the utility and the future played by video assisted laparoscopic surgery in the diagnosis and treatment of intraabdominal malignancies.


[Application of bionics in spinal surgery].
Spinal bionic therapy is the application of bionics concept, by imitating the natural anatomical structure and physiological function of the spine, to treat spinal diseases using various modern technology, materials and equipment .How to repair or preserve the anatomical structure and function of spine to the maximum extent while treating spinal diseases is an important content of spinal bionic therapy.Firstly, the use of movable spinal implants not only preserves the spinal mobility function to a certain extent, reduces the degeneration of adjacent segments, but also reduces the incidence of internal fixation fracture and improves the long-term efficacy.Secondly, with the help of the development of three dimensional printing technology, personalized artificial prostheses can be made to fill the spinal structure with complex defects, and biological scaffolds and functional prostheses with anti-tumor drugs can not only realize the biomimetic and functional spine anatomy, but also become a multiplier of the efficacy of anti-tumor drugs.Thirdly, in the design and manufacture of spinal orthopaedic braces, computer aided design and manufacturing technology can make spinal orthopaedic braces more comfortable with better orthopaedic effect and ergonomic characteristics.How to apply bionics concepts and relate technologies to spinal surgery have not been determined yet, and no relevant diagnosis and treatment guidelines have been formulated.It is foreseeable that with the continuous development of medical technology, the content of spinal bionic therapy will be gradually enriched and improved, and become a powerful measure to overcome difficulties in the diagnosis and treatment of spinal surgery diseases.


Moderate aging does not exacerbate cisplatin-induced kidney injury or fibrosis despite altered inflammatory cytokine expression and immune cell infiltration.
Aging is a risk factor for certain forms of kidney injury due to normal physiological changes, but the role of aging in cisplatin-induced kidney injury is not well defined in humans or animal models of the disease. To improve on current knowledge in this field, we treated 8- and 40-wk-old FVB/n mice with one high dose of cisplatin as a model of acute kidney injury or with repeated low doses of cisplatin (7 mg/kg cisplatin once a week for 4 wk) as a clinically relevant model of chronic kidney disease to determine if aging exacerbates cisplatin-induced kidney injury. Levels of acute kidney injury were comparable in 8- and 40-wk-old mice. In 40-wk-old mice, fibrotic markers were elevated basally, but treatment with cisplatin did not exacerbate fibrosis. We concluded that this may be the result of a decreased inflammatory response in 40-wk-old cisplatin-treated mice compared with 8-wk-old mice. Despite a decreased inflammatory response, the level of immune cell infiltration was greater in 40-wk-old cisplatin-treated mice than 8-wk-old mice. Our data highlight the importance of examining age as a risk factor for cisplatin-induced kidney injury.


Structural Comparison of Diverse HIV-1 Subtypes using Molecular Modelling and Docking Analyses of Integrase Inhibitors.
The process of viral integration into the host genome is an essential step of the HIV-1 life cycle. The viral integrase (IN) enzyme catalyzes integration. IN is an ideal therapeutic enzyme targeted by several drugs; raltegravir (RAL), elvitegravir (EVG), dolutegravir (DTG), and bictegravir (BIC) having been approved by the USA Food and Drug Administration (FDA). Due to high HIV-1 diversity, it is not well understood how specific naturally occurring polymorphisms (NOPs) in IN may affect the structure/function and binding affinity of integrase strand transfer inhibitors (INSTIs). We applied computational methods of molecular modelling and docking to analyze the effect of NOPs on the full-length IN structure and INSTI binding. We identified 13 NOPs within the Cameroonian-derived CRF02_AG IN sequences and further identified 17 NOPs within HIV-1C South African sequences. The NOPs in the IN structures did not show any differences in INSTI binding affinity. However, linear regression analysis revealed a positive correlation between the Ki and EC50 values for DTG and BIC as strong inhibitors of HIV-1 IN subtypes. All INSTIs are clinically effective against diverse HIV-1 strains from INSTI treatment-naïve populations. This study supports the use of second-generation INSTIs such as DTG and BIC as part of first-line combination antiretroviral therapy (cART) regimens, due to a stronger genetic barrier to the emergence of drug resistance.


Urethral pressure measurement--problems and clinical value.
Urethral pressure measurements are in use to assess urethral closure and voiding function. The lack of general agreement on an explicit definition of urethral pressure and standardisation of the methodology for measurement has limited the clinical utility of urethral pressure measurements.


SECUREment bundles to prevent peripheral intravenous catheter failure-the SECURE-PIVC trial: study protocol for a pilot randomized controlled trial.
Peripheral intravenous catheters (PIVCs) are widely used, but failure is unacceptably common with up to 69% failing before treatment is complete. PIVC securement reduces failure, but the optimal way to achieve this is unclear. Tapes and supplementary securement products are widely used, however rigorous testing of these to reduce PIVC failure remains unexplored. In adult medical-surgical wards at a tertiary hospital, this pilot randomized controlled trial tests standard care (bordered polyurethane dressing plus nonsterile tape over the extension tubing) against two securement interventions (intervention one: standard care plus two sterile tape strips over the PIVC hub; intervention two: intervention one plus a tubular bandage). Patients >18 years of age requiring a PIVC for >24 hours are eligible. Patients with laboratory-confirmed positive blood cultures within 24 hours of screening, known allergy to study products, current or high-risk of skin tear, or non-English speaking without interpreter are excluded. Sample size is 35 per trial arm, and central randomization is computer-generated with allocation concealed until entry. Patients and clinical staff cannot be blinded to treatment allocation. However, infection outcomes are assessed by a blinded investigator. Primary outcome is study feasibility. Secondary outcomes (PIVC failure, dwell time, skin adverse events, PIVC colonization, and cost) are compared between groups. Feasibility outcomes are reported descriptively. Ethical approvals were received from Royal Brisbane and Women's Hospital (HREC/18/QRBW/44571) and Griffith University (2018/1000). Trial commencement was May 2019. Trial registration: ACTRN12619000026123.


Acute Effects of Hemodiafiltration Versus Conventional Hemodialysis on Endothelial Function and Inflammation: A Randomized Crossover Study.
Endothelial dysfunction and chronic inflammatory process are prevalent in patients with end-stage renal disease (ESRD) on maintenance hemodialysis (HD). The aim of this study was to evaluate the acute and short-term effects of online hemodiafiltration (OL-HDF) versus conventional HD on endothelial function and inflammation. A prospective, randomized, crossover trial. Twenty stable ESRD patients undergoing chronic HD treatments were randomly assigned with a 1:1 ratio to conventional HD and to OL-HDF both for 2 weeks (either HD followed by OL-HDF or OL-HDF followed by HD). Markers of endothelial dysfunction such as flow-mediated dilatation (FMD) of the brachial artery, soluble endothelial protein C receptor (sEPCR), and soluble thrombomodulin (sTM) were measured at baseline, after the first dialysis session and after 2 weeks. Meanwhile, serum interleukin 6 (IL-6) and high-sensitivity C-reactive protein (hs-CRP) levels were measured as well. Both a single OL-HDF session and 2-week OL-HDF significantly improved brachial FMD% (18.7 ± 6.9% at baseline; 21.5 ± 5.4% after the first dialysis; 21.5 ± 5.7% after 2 weeks; P < 0.05 vs baseline), decreased the levels of sEPCR (from 394.4 [297.9-457.0] ng/ml at baseline to 234.7 [174.1-345.5] ng/ml after the first dialysis, and to 191.5 [138.2-255.0] ng/ml after 2 weeks; P < 0.01 vs baseline) and sTM. In contrast, HD did not change FMD%, even increased the levels of sEPCR and sTM. A reduction in IL-6 level was observed in OL-HDF patients after 2-week dialysis, while IL-6 did not change in HD patients. There was no significant difference in change of hs-CRP level between the OL-HDF and HD treatments. OL-HDF has both acute and short-term beneficial effects on endothelial dysfunction compared to conventional HD.


Sensitivity of the hippocampus to objective but not subjective episodic memory judgments.
We assessed whether neural activity in the hippocampus dissociates according to whether memory test items elicit a subjective sense of recollection or accurate retrieval of contextual information. We reanalyzed a previously acquired dataset from a study in which participants made both objective (source memory for spatial context) and subjective (Remember-Know) judgments for each test item. Results indicated that the hippocampus was exclusively sensitive to the amount of contextual information retrieved, such that accurate source memory judgments were associated with greater activity than inaccurate judgments, regardless of Remember/Know status. The findings add to the evidence that the hippocampus is insensitive to the subjective experience of recollection, but supports retrieval of contextual information.


Stable isotope fingerprinting: a novel method for identifying plant, fungal, or bacterial origins of amino acids.
Amino acids play an important role in ecology as essential nutrients for animals and as currencies in symbiotic associations. Here we present a new approach to tracing the origins of amino acids by identifying unique patterns of carbon isotope signatures generated by amino acid synthesis in plants, fungi, and bacteria ("13C fingerprints"). We measured amino acid delta 13C from 10 C3 plants, 13 fungi, and 10 bacteria collected and isolated from a boreal forest in interior Alaska, USA, using gas chromatography-combustion-isotope ratio mass spectrometry (GC-C-IRMS). Microorganisms were cultured under amino-acid-free conditions and identified based on DNA sequences. Bacteria, fungi, and plants generated consistent, unique 13C fingerprints based on the more complex amino acids (five or more biosynthetic steps) that are classified as essential for animals. Linear discriminant analysis classified all samples correctly with >99% certainty and correctly classified nearly all insect samples from a previous study by diet. Our results suggest that 13C fingerprints of amino acids could provide a powerful in situ assay of the biosynthetic sources of amino acids and a potential new tool for understanding nutritional linkages in food webs.


Brugada phenocopy clinical reproducibility demonstrated by recurrent hypokalemia.
Brugada phenocopies (BrP) are clinical entities that are etiologically distinct from true congenital Brugada syndrome (BrS). BrP are characterized by type 1 or type 2 Brugada electrocardiogram (ECG) patterns in precordial leads V1 -V3 ; however, BrP are elicited by various underlying clinical conditions such as electrolyte disturbances, myocardial ischemia, or poor ECG filters. In this report, we describe the first case of clinically reproducible BrP which is important to the conceptual evolution of BrP.


[Social demography in Quebec: a preliminary account].
"The goal of this paper is to review those explanatory models that dominate social demography in Quebec. The classical organization of demography, which calls upon the three components of demographic reproduction--fertility, migration and mortality--is followed. The concluding part of the paper deals with the concept of 'demographic regime', which aims to bring the three components together into an overall theory of demographic reproduction. The paper shows that if the functionalist and empirical tradition (mostly American) has dominated the field of demography for a very long time, feminist and materialistic approaches have recently appeared for the interpretation of demographic realities." (SUMMARY IN ENG AND SPA)


[Effects of hydrogen-rich saline on Akt/GSK3β signaling pathways and cardiac function during myocardial ischemia-reperfusion in rats].
To explore the effects of hydrogen-rich saline on Akt/GSK3β signaling pathways and cardiac function during myocardial ischemia-reperfusion (I/R) in rats. A total of 150 healthy male Sprague-Dawley rats were selected and divided randomly into 5 groups of normal control (I), sham operation (II), myocardial ischemia-reperfusion (III), hydrogen-rich saline (IV) and normal saline group (V) (n = 30 each). Group I had no treatment at all. In group II, anterior descending branch was merely exposed but not ligated. Myocardial I/R was induced by 30-min occlusion of anterior descending branch of left coronary artery followed by 12/24 h reperfusion of Bimbaum. Hydrogen-rich saline 1 ml/100 g were injected intraperitoneally 5 min before reperfusion in group IV. Normal saline 1 ml/100 g was injected intraperitoneally 5 min before reperfusion in group V. The values of ± dp/dt max, left ventricular diastolic pressure (LVDP) and left ventricular systolic pressure (LVSP) during the procedure were recorded by BL-420 biological function experimental system at pre-ischemia, ischemia 30 min, 60 min and 120 min of reperfusion. The animals were sacrificed at 60 min, 120 min of reperfusion and hearts harvested. The pathological changes of myocardial tissue were detected by hematoxylin and eosin staining. And the expressions of Akt and GSK3β in myocardial tissue were examined by Western blot. Compared with groups I and II, the values of ± dp/dt max, LVDP and LVSP significantly increased. And the expressions of Akt and GSK3β in myocardial tissue significantly increased in groups III, IV and V. Compared with groups III and V, the values of ± dp/dt max, LVDP and LVSP significantly decreased. And the expressions of Akt and GSK3β in myocardial tissue significantly decreased in group IV. Compared with T0, the values of ± dp/dt max, LVDP and LVSP significantly decreased at T(1-3) in groups III, IV and V. Compared with T(1), the values of ± dp/dt max, LVDP and LVSP significantly increased at T(2-3) in group IV. Compared with T(2), the expressions of Akt and GSK3β in myocardial tissue significantly decreased at T(3) in group IV. Hydrogen-rich saline can reduce myocardial reperfusion injury and improve heart function. The mechanism may be due to associated with the down-regulated expressions of Akt and GSK3β in myocardial tissue.


[Assessment of fetal kidney function by determining the microprotein levels (alpha-1 and beta-2 microglobulin) in fetal blood].
Fetal renal function cannot be assessed with clearance methods. Fetal urea and creatinine serum levels correspond to maternal values, the fetus being hemodialyzed by his mother till birth. To predict glomerular filtration independently of maternal renal function, levels of alpha 1-microglobulin (MG) and beta 2MG and creatinine were routinely determined in cord blood of 375 newborns (GA 25.-42 weeks) in cord blood and in 154 cases in corresponding maternal blood samples. alpha 1MG was determined in a radial immunodiffusion method, beta 2MG by radioimmunoassay, creatinine enzymatically. The mean alpha 1MG concentration fell from 3.1 mg/dl in 25-31 weeks prematures to 2.3 mg/dl in 38-42 week group (p less than 0.005), beta 2MG concentration fell from 3.9 mg/l to a mean of 2.6 mg/l (p less than 0.0005), while in maternal blood, levels rose from 4.0 to 4.3 mg/dl (alpha 1MG) and from 1.7 to 1.8 mg/l (beta 2MG) (n.s.). Creatinine levels rose from 0.63 to 0.75 mg/dl in both fetal and maternal blood. Parallel to the rise in GFR, microprotein levels fall during intrauterine development, while maternal serum levels increase. There is no correlation between maternal and cord blood alpha 1MG or beta 2MG concentrations. This is distinct in cases with severe maternal or fetal renal insufficiency (n = 10). Thus microprotein determination in fetal serum can be used to detect severe renal function disturbances and to estimate glomerular filtration rate independently of maternal renal function.


[Beneficial effects of pituitary grafts under the renal capsule on behavior of dwarf mutant mice].
The effects of pituitary grafts under the kidney capsule were studied in "dwarf" mutant mice which because of anterohypophyseal deficiency, exhibit dwarfism, sterility and important behavioral deficits. One month after grafting, the body weight was 120% in the grafted mutants while only 11 and 8% respectively in normal and sham-grafted controls. At the behavioral level, the animals were examined on 2 tasks: spontaneous alteration in a T maze and passive avoidance (step-through). Grafted mutant mice, as well as sham-grafted normal controls, were able to alternate successfully, while the sham-grafted "dwarf" mice persevered. In the step-through task, grafted animals as well as sham-grafted normal mice, avoided, entering the dark compartment, 24 h after the shock trial. On contrast, sham-grafted dwarf mice did not show passive avoidance of the shock. According to the literature, pituitary grafts under the kidney capsule secrete high levels of prolactin and very little, if any, of other pituitary hormones. It is not yet clear how the presence of only prolactin can explain the body weight and the maintenance of the behaviors we investigated.


Nuclear localization signal binding protein from Arabidopsis mediates nuclear import of Agrobacterium VirD2 protein.
T-DNA nuclear import is a central event in genetic transformation of plant cells by Agrobacterium. Presumably, the T-DNA transport intermediate is a single-stranded DNA molecule associated with two bacterial proteins, VirD2 and VirE2, which most likely mediate the transport process. While VirE2 cooperatively coats the transported single-stranded DNA, VirD2 is covalently attached to its 5' end. To better understand the mechanism of VirD2 action, a cellular receptor for VirD2 was identified and its encoding gene cloned from Arabidopsis. The identified protein, designated AtKAPalpha, specifically bound VirD2 in vivo and in vitro. VirD2-AtKAPalpha interaction was absolutely dependent on the carboxyl-terminal bipartite nuclear localization signal sequence of VirD2. The deduced amino acid sequence of AtKAPalpha was homologous to yeast and animal nuclear localization signal-binding proteins belonging to the karyopherin alpha family. Indeed, AtKAPalpha efficiently rescued a yeast mutant defective for nuclear import. Furthermore, AtKAPalpha specifically mediated transport of VirD2 into the nuclei of permeabilized yeast cells.


[High-dose Omega-3 for cardiovascular prevention, a bad idea?]
Hypertriglyceridemia is a cardiovascular risk factor independent of LDL cholesterol. Omega-3 reduce triglycerides levels, but without proven benefit to reduce cardiovascular risk. Recently, two studies on high-dose omega-3 derivatives have shown contradictory results on the risk of cardiovascular events: REDUCE-IT (4 g/day of icosapent ethyl) showed a 25 % reduction; STRENGTH (4 g/day of a mixture of eicosapentaenoic acid and docosahexaenoic acid) showed no effect. An increased risk of atrial fibrillation was observed in both studies. The European 2021 cardiovascular prevention guidelines propose to consider high-dose ethyl icosapent on a case-by-case basis in patients with hypertriglyceridemia.


[Maternal postures and epidural analgesia during labour].
The evolution of birth is of interest for obstetricians and midwives. Postures with asymmetric stretching and balance, kneeling, or sitting have been claimed to be able to help foetal head rotation. Although walking during labour have no influence on the outcome of labour, hip-flexed postures enlarging the pelvic diameter are yet evaluated to improve the obstetric course of labour. In a prospective randomised study including 93 parturients, we compared the supine 30 degrees lateral tilt (control group) to three hip-flexed postures: sitting (S), right hip-flexed left lateral position (L) and left hip-flexed right lateral position (R). Epidural analgesia with 12 ml ropivacaine 0.1% and sufentanil 0.5 microg/ml was administered over a period of six minutes. The total epidural spread was 15+/-0.3 dermatomes and the upper level of thermo-analgesic blockade reached T7-T8 (T5 to T10) in each group. There were no differences between groups for the left and right total spread and upper level of epidural blockade, for the time to maximal block and pain relief. There was no motor block and no maternal or foetal side effects. We conclude that, for the three hip-flexed postures tested, position does not influence local anesthetic spread or symmetry of analgesia after induction of obstetric epidural anaesthesia.


7-Epiclusianone, a Benzophenone Extracted from Garcinia brasiliensis (Clusiaceae), Induces Cell Cycle Arrest in G1/S Transition in A549 Cells.
Lung cancer is the leading cause of cancer deaths in the world. Disease stage is the most relevant factor influencing mortality. Unfortunately, most patients are still diagnosed at an advanced stage and their five-year survival rate is only 4%. Thus, it is relevant to identify novel drugs that can improve the treatment options for lung cancer. Natural products have been an important source for the discovery of new compounds with pharmacological potential including antineoplastic agents. We have previously isolated a prenylated benzophenone (7-epiclusianone) from Garcinia brasiliensis (Clusiaceae) that has several biological properties including antiproliferative activity against cancer cell lines. In continuation with our studies, the present work aimed to investigate the mechanisms involved with antiproliferative activity of 7-epiclusianone in A549 cells. Our data showed that 7-epiclusianone reduced the viability of A549 cells in a concentration-dependent manner (IC50 of 16.13 ± 1.12 μM). Cells were arrested in G1/S transition and apoptosis was induced. In addition, we observed morphological changes with cytoskeleton disorganization in consequence of the treatment. Taken together, the results showed that cell cycle arrest in G1/S transition is the main mechanism involved with antiproliferative activity of 7-epiclusianone. Our results are promising and open up the prospect of using this compound in further anticancer in vivo studies.


[Interventional endoscopy in hepatico-pancreatico-biliary disease].
Interventional endoscopy in hepatico-pancreatico-biliary disease Abstract. Interventional endoscopy has undergone an exciting evolution in recent years, especially in the treatment of hepatico-pancreatico-biliary disease. However, novel endoscopes have also improved diagnostics through direct visualization of the biliary tract and the pancreatic duct, including targeted biopsy-sampling of suspicious endoluminal lesions. The use of cholangioscopy also allows for lithotripsy of complex gallstones under direct visualization. In patients with malignant biliary obstruction, endosonography(EUS)-guided insertion of novel lumen-apposing metal stents allow for extraanatomical access to intra- or extrahepatic bile ducts, if traditional transpapillary stent insertion fails. Especially in patients with altered anatomy e. g., after surgery, EUS-guided transgastric drainage may be the most sensible approach. Using similar techniques, EUS-guided drainage of the pancreatic duct is also possible. Local tumor therapy may be achieved with novel endoscopic retrograde cholangiography-guided catheter-based radiofrequency ablation and photodynamic therapy. In chronic pancreatitis, similar to biliary disease, methods of endoluminal diagnosis, lithotripsy, and transgastric drainage may also be applied. This article provides an overview of novel endoscopic techniques and methods that are available in hepatico-pancreatico-biliary disease.


Effect of specific versus variable practice upon overhead throwing speed in children.
This study compared the effect of practice throwing with specific weights (specificity principle) or with variable weights (variability of practice) for a short practice period in children. Primary school children (N = 41; M age = 7.7 yr., SD = 0.5) were randomly divided into three homogenous groups. The first two groups used specific overhead throwing practice: throws with a soccer ball or 1 kg balls, while the third group used variable practice with 0.35, 0.45, 0.5, and 1 kg balls. All groups trained twice per week for six weeks. The same workload per session between the three groups varied from 24 throws (1 kg practice group) to 43 throws (soccer ball practice group). Throwing speed and distance with different balls was measured before and after the practice period. Statistically significant increases in performance in all three practice groups were found with no significant differences between groups. The results indicate that both specific and variable practice of throwing in children lead to increases in performance. However, it seems that the increased workload (practice) is a more important factor than the type of practice (specific or variable) in enhancing performance in children.


Oral and intraperitoneal LD50 of thymoquinone, an active principle of Nigella sativa, in mice and rats.
Thymoquinone is the major active principle of Nigella sativa (N. sativa) and constitutes about 30% of its volatile oil or ether extract. N. sativa oil and seed are commonly used as a natural remedy for many ailments. Using modern scientific techniques, a number of pharmacological actions of N. sativa have been investigated including immunostimulant, anti-inflammatory, anticancer, antioxidant, antihistaminic, antiasthmatic, hypoglycemic, antimicrobial and antiparasitic. There are only few reports regarding the toxicity of thymoquinone. The present study was carried out to determine LD50 of thymoquinone both in mice and rats, orally as well as intraperitoneall, by the method of Miller and Tainter. Autopsy and histopathology of liver, kidney, heart and lungs were also determined. The LD50 in mice after intraperitoneal injection was determined to be 104.7 mg/kg (89.7-119.7, 95% confidence interval) and after oral ingestion was 870.9 mg/kg (647.1-1094.8, 95% confidence interval). Whereas, LD50 in rats after intraperitoneal injection was determined to be 57.5 mg/kg (45.6-69.4, 95% confidence intervals) and after oral ingestion was 794.3 mg/kg (469.8-1118.8, 95% confidence intervals). The LD50 values presented here after intraperitoneal injection and oral gavages are 10-15 times and 100-150 times greater than doses of thymoquinone reported for its anti-inflammatory, anti-oxidant and anti-cancer effects. Thymoquinone is a relatively safe compound, particularly when given orally to experimental animals.


Differential regulation of adenine nucleotide translocators by hypertonicity in the brain.
To determine the gene(s) induced by hypertonicity in the brain, we performed a differential display analysis using RNA isolated from isotonic and hypertonic rat astrocytes. One cDNA rapidly up-regulated by hypertonicity was isolated, and the DNA sequence revealed that it was identical to adenine nucleotide translocator (ANT)2. ANT2 protein exchanges intramitochondrial ATP for cytoplasmic ADP. Among three ANT isoforms, only ANT2 mRNA was up-regulated markedly from 1 to 4 h after exposure to hypertonicity. Induction of the mRNA did not require de novo protein synthesis. Furthermore, ADP translocase activity in mitochondria of astrocytes was increased significantly by hypertonicity. To see the localization and regulation of ANT2 mRNA in the brain, we performed in situ hybridization of rat brain after intraperitoneal injection of a high concentration of NaCl. Although there were only weak signals in the control, intense hybridization signals were seen in hypertonic rat whole brain. Microscopic examination showed that ANT2 signals were present in the neurons, as well as glial cells. These results suggest that ANT2 may play a role in brain cells to adapt to the hypertonic environment.


Porcine satellite cells are restricted to a phenotype resembling their muscle origin.
Muscles in most domestic animals differ in function and growth potential based largely on muscle fiber type composition. Though much is known about satellite cells (SC), information is limited regarding how populations of SC differ with muscle fiber type, especially in pigs. Therefore, the objective of this study was to isolate and culture SC from red (RST) and white (WST) portions of the semitendinosus muscle of neonatal and adult pigs and determine their capacity to proliferate, differentiate, and express various myosin heavy chain (MyHC) isoforms in vitro. Porcine satellite cells were isolated from RST and WST muscles of 6-wk-old and adult (>6-mo-old) pigs and cultured under standard conditions. Muscle from neonatal pigs yielded nearly 10 times more (P < 0.001) presumptive satellite cells as those from adult pigs, with fusion percentages close to 60% for the former. The RST yielded more (P < 0.001) SC per gram muscle compared to WST, 8.1 ± 0.2 × 10(4) cells versus 6.7 ± 0.1 × 10(4) cells/gram muscle in young pigs, and 9.7 ± 0.4 × 10(3) cells versus 5.5 ± 0.4 × 10(3) cells/gram muscle in adult pigs, respectively. Likewise, satellite cells from RST proliferated faster (P < 0.001) than those from WST across both ages, as indicated by a shorter cell doubling time, 18.6 ± 0.8 h versus 21.3 ± 0.9 h in young pigs, and 23.2 ± 0.7 h versus 26.7 ± 0.9 h in adult pigs, respectively. As a result of shorter times to confluence, satellite cells from RST also formed myotubes earlier than those SC originating from WST. Once induced, however, SC from WST differentiated and fused faster (P < 0.05) as evidenced by fusion percentage within the first 24 h, 41.6% versus 34.3%, respectively; but reached similar ultimate fusion percentages similar to WST by 48 h. Over 90% of MyHC expressed in maximally fused SC cultures from both RST and WST was restricted to the embryonic isoform. Type IIX MyHC mRNA was not detected in any culture. Myotube cultures from RST expressed more (P < 0.01) Type I MyHC isoform mRNA than those from WST, whereas those cultures from WST expressed more (P < 0.05) Type II (including Types IIA and IIB) MyHC transcripts. These data show SC cultures from porcine fast and slow muscles express MyHC profiles largely reflective of their muscle of origin and suggest satellite cells are partially restricted to a particular muscle phenotype in which they are juxtapositioned. Understanding the molecular nature of these intrinsic control mechanisms may lead to improved strategies for augmenting meat animal growth or muscle regeneration.


Critical requirement of BAX for manifestation of apoptosis induced by multiple stimuli in human epithelial cancer cells.
Studies with mouse embryo fibroblasts deficient for the BCL-2 family multidomain proapoptotic proteins BAX and BAK have revealed that both of these proteins are essential for apoptosis induced by multiple stimuli, suggesting that these proapoptotic proteins are functionally overlapping in these cells [M. C. Wei et al., Science (Wash. DC), 292: 727-730, 2001; W. X. Zong et al., Genes Dev., 15: 1481-1486, 2001]. We have determined the effect of several different apoptotic stimuli in a Bax-deficient human epithelial cancer cell line (HCT116BaxKO). We show that this cell line expresses functional BAK protein and is defective in manifestation of apoptosis induced by the BH3-only proteins BIK and BID as well as extrinsic stimuli that engage the death receptors, tumor necrosis factor receptor, tumor necrosis factor-related apoptosis-inducing ligand receptor, and Fas. In addition, this cell line is deficient for apoptosis induced by cytotoxic agents such as UV, staurosporine, and thapsigargin that induce either mitochondrial or endoplasmic reticulum stress. Our results suggest that BAX plays a critical role in the manifestation of apoptosis paradigms induced by multiple stimuli in human epithelial cancer cells. Our results also suggest that the integrity of BAX may have important consequences in the progression of epithelial tumors and in determining the outcome of chemotherapeutic regimens of such tumors.


[Lifestyle of adolescent students from public and private schools in Recife: ERICA].
This study analyzes the behavior patterns related to the lifestyle of adolescents in Recife, Brazil. A cross-sectional study was conducted with data from the Cardiovascular Risk Study among Adolescents (ERICA) and 2400 students aged 12 to 17 were interviewed. The prevalence of physical activity, eating behavior, smoking and alcohol consumption were analyzed. The Chi-square test and 95% confidence interval (95%CI) were used to evaluate the statistical significance of the measurements. It was observed that 60% of the adolescents presented inadequate eating behaviors regarding the consumption of breakfast, daily water intake and meals eaten in front of the TV. About 40% (95%CI: 39.7-45) did not sit down to meals with their parents or guardians. The prevalence of physical inactivity was 52.4% (95%CI: 50-55). Female adolescents were more inactive (68.7%, 95%CI: 65-72) than males (36.4%, 95%CI: 33-40). Teenagers of economic classes D and E were the most inactive (60.7%, 95%CI: 46-73). Alcohol consumption was 18.7% (95%CI: 2.6-5.6) and smoking was prevalent in 3.8% (95%CI: 2-6) of the individuals. Inadequate eating behaviors and physical inactivity were the main areas responsible for an unhealthy lifestyle, followed by alcohol consumption and smoking.


Possible role of vitamin E, coenzyme Q10 and rutin in protection against cerebral ischemia/reperfusion injury in irradiated rats.
To investigate the possible role of vitamin E, coenzyme Q10 and rutin in ameliorating the biochemical changes in brain and serum induced by cerebral ischemia/reperfusion (I/R) in whole body γ-irradiated rats. Cerebral ischemia was induced in male Wistar rats (either irradiated or non-irradiated) followed by reperfusion. I/R increased brain content of malondialdehyde (MDA) and depleted its glutathione (GSH) content with a compensatory elevation in cytosolic activities of glutathione peroxidase (GPx) and glutathione reductase (GR) enzymes. It also raised brain cytosolic lactate dehydrogenase (LDH) activity and calcium (Ca(2+)) level. Furthermore, I/R provoked an inflammatory response reflected by an increment in serum levels of the proinflammatory cytokines tumour necrosis factor-α (TNF-α) and interlukin-1β (IL-1β). Moreover, induction of I/R in irradiated rats resulted in a further increase in brain oxidative stress and cytosolic LDH activity, disturbed brain Ca(2+) homeostasis and exaggerated the inflammatory reaction. During irradiation, administration of each of vitamin E, coenzyme Q10 (CoQ10) and rutin to irradiated rats before induction of I/R, alleviated the brain oxidative stress. Moreover, these antioxidants caused attenuation of the rise of the cytosolic activities of GPx and GR. A lowering effect of the cytosolic LDH activity and Ca(2+) level were caused by treatment with antioxidants. Each of vitamin E and rutin revealed an anti-inflammatory action of these antioxidants, while CoQ10 had no effect on serum levels of TNF-α and IL-1β. These findings indicate that supplementation with either vitamin E, CoQ10 or rutin ameliorated most of the biochemical changes induced by I/R in irradiated rat brain and serum.


Plasmonic Nanozymes: Engineered Gold Nanoparticles Exhibit Tunable Plasmon-Enhanced Peroxidase-Mimicking Activity.
Enzyme-mimicking inorganic nanoparticles, also known as nanozymes, have emerged as a rapidly expanding family of artificial enzymes that exhibit superior structural robustness and catalytic durability when serving as the surrogates of natural enzymes for widespread applications. However, the performance optimization of inorganic nanozymes has been pursued in a largely empirical fashion due to lack of generic design principles guiding the rational tuning of the nanozyme activities. Here we choose Au surface-roughened nanoparticles as a model plasmonic nanozyme that combines peroxidase-mimicking behaviors with tunable plasmonic characteristics to demonstrate the feasibility of fine-tuning nanozyme activities through plasmonic excitations using visible and near-infrared light sources. Taking full advantage of the unique plasmonic tunability offered by Au surface-roughened nanoparticles, we were able to unravel the detailed relationship between plasmonic excitations and nanozyme activities that underpins the hot electron-mediated working mechanism of peroxidase-mimicking plasmonic nanozymes.


In silico Optimization of Left Atrial Appendage Occluder Implantation Using Interactive and Modeling Tools.
According to clinical studies, around one third of patients with atrial fibrillation (AF) will suffer a stroke during their lifetime. Between 70 and 90% of these strokes are caused by thrombus formed in the left atrial appendage. In patients with contraindications to oral anticoagulants, a left atrial appendage occluder (LAAO) is often implanted to prevent blood flow entering in the LAA. A limited range of LAAO devices is available, with different designs and sizes. Together with the heterogeneity of LAA morphology, these factors make LAAO success dependent on clinician's experience. A sub-optimal LAAO implantation can generate thrombi outside the device, eventually leading to stroke if not treated. The aim of this study was to develop clinician-friendly tools based on biophysical models to optimize LAAO device therapies. A web-based 3D interactive virtual implantation platform, so-called VIDAA, was created to select the most appropriate LAAO configurations (type of device, size, landing zone) for a given patient-specific LAA morphology. An initial LAAO configuration is proposed in VIDAA, automatically computed from LAA shape features (centreline, diameters). The most promising LAAO settings and LAA geometries were exported from VIDAA to build volumetric meshes and run Computational Fluid Dynamics (CFD) simulations to assess blood flow patterns after implantation. Risk of thrombus formation was estimated from the simulated hemodynamics with an index combining information from blood flow velocity and complexity. The combination of the VIDAA platform with in silico indices allowed to identify the LAAO configurations associated to a lower risk of thrombus formation; device positioning was key to the creation of regions with turbulent flows after implantation. Our results demonstrate the potential for optimizing LAAO therapy settings during pre-implant planning based on modeling tools and contribute to reduce the risk of thrombus formation after treatment.


[Effect of clorgyline and of alpha-methyl-p-tyrosine on the plasma levels of corticosterone in the rat].
The effect of a type A MAO inhibitor, clorgyline, injected alone or with alpha-methyl-p-tyrosine (aMpT) on the plasmatic corticosterone levels estimated at 9 a.m. and 5 p.m. has been studied in male Wistar rats. The clorgyline injected alone produced significant decreases in corticosterone values, especially at 5 p.m., determining a variation lack between the morning and the afternoon levels. When alpha-MpT is associated to IMAO, increases at both points of the day considered in this experiment take place. The amount of NA and 5-HT in the brain was also estimated; clorgyline high increases in Na and 5-HT contents, 5-HT; aMpT reduces the effect of clorgyline, especially as regards content. The results are discussed in relation to this highly specific MAO inhibitor and with the role of these amines as modulators of ACTH secretion. In view of the changes introduced by the aMpT injection, the modifications produced by clorgyline alone are related to NA, but to 5-HT, when the NA synthesis has been interrupted by the tyrosine hydroxylase inhibitor.


Far-advanced otosclerosis.
Patients with 'far-advanced' or 'very far-advanced' otosclerosis have a profound bilateral hearing loss, with apparently no cochlear reserve measured by standard clinical audiometers. These patients have no benefit from a powerful hearing aid, have severe feedback problems and the cochlear implant may be the only solution. A total of 12 stapedotomies were performed in 8 patients with far-advanced or very far-advanced otosclerosis, with satisfactory results, improved air conduction thresholds and improved cochlear function and speech discrimination. Stapedotomy is a useful procedure for patients with far-advanced otosclerosis which improves patient's hearing to levels where they can benefit from less powerful hearing aids with fewer feedback problems, compared to no measurable preoperative hearing aid benefit. It also spares those patients being submitted to cochlear implantation.


An antecedent diagnosis of refractory anemia with excess blasts has no prognostic relevance in acute myeloid leukemia of older adult patients.
Conflicting results have been reported about the prognostic relevance of antecedent myelodysplastic syndrome (MDS) in acute myeloid leukemia (AML) of older adults. Data from 87 intensively treated AML patients (median age 69 years) were analyzed, with the aim of comparing therapeutic results and toxicity between de novo and AML secondary to a previous MDS (s-AML). Rate of CD34+ cells mobilization and feasibility of autologous stem cell transplantation (ASCT) were also compared. Complete remission rate, death in induction and primary resistance were not statistically different between the two groups. Median time for neutrophil recovery was similar, while s-AML patients required a longer time for platelet recovery (P = 0.04). There was no difference as to eligibility for consolidation as well as for mobilization and feasibility of ASCT. S-AML had negligible impact on overall survival (OS) and disease-free survival (DFS). In the multivariate analysis the only parameter significantly related to either OS or DFS duration was adverse karyotype (P = 0.02 and 0.04, respectively). A diagnosis of s-AML does not represent a clinically relevant prognostic factor in elderly AML patients treated with aggressive therapy. Furthermore, s-AML patients can be mobilized and autografted with comparable results as opposed to de novo cases.


[Intrahepatic lithiasis (considerations on 20 cases)].
The authors present an analysis of 20 cases with intrahepatic lithiasis, stressing the possibility of the development of lithiasis inside the liver as a result of either metabolic disturbances (one case), or secondary to congenital obstacles (2 cases), or following surgery (3 cases). In the remaining 12 cases intrahepatic lithiasis was secondary to lithiasis in the hepato-choledocus canal through a mechanism of ascending obstruction - identified in 5 cases -,or it was due to ascending migration of calculi (in 7 cases). The diagnosis is made with the aid of good quality intra-surgery cholangiographia. There are various possibilities for surgical solution, but the authors have preferred the bilio-digestive anastomosis that was performed in 15 of the patients. The hepatic duct-jejunal anastomosis on a "Y" loop is considered to be the method that responds most satisfactorily to operatory objectives. Various conditions are discussed, that may render the solution of the condition more difficult from the surgical viewpoint, such as the presence of congenital intrahepatic septa, or the development of intrahepatic lithiasis in a patient with a narrow hepato-choledocus duct. The mortality rate was of 20% (4 patients). Death occurred through acute hepator-renal failure.


Terahertz circular polarization sensing for protein denaturation based on a twisted dual-layer metasurface.
Protein denaturation has very important research value in nutrition, biomedicine, and the food industry, which is caused by the changes in the molecular structure of the protein. Since the collective vibrational and torsional modes of protein molecules are within the terahertz (THz) frequency range, THz spectroscopy can characterize the protein denaturation with several advantages of non-contact, label-free, real-time, and non-destructive. Therefore, we proposed a reflective THz time-domain polarization spectroscopy sensing method, and use a flexible twisted dual-layer metasurface film as a sensor to realize the thermal denaturation sensing, concentration sensing, and types identification of protein aqueous solutions. The experiment tested three proteins (bovine serum albumin, whey protein, and ovalbumin), and the results show that: for the thermal denaturation sensing, its detection sensitivity can reach 6.30 dB/% and the detection accuracy is 0.77%; for the concentration sensing, the detection sensitivity and detection accuracy reach 52.9 dB·mL/g and 3.6·10-5 g/mL, respectively; in addition, different protein types can be distinguished by the difference of the circular polarization spectra.


Thematic review series: patient-oriented research. Free fatty acid metabolism in human obesity.
Adipose tissue lipolysis provides circulating FFAs to meet the body's lipid fuel demands. FFA release is well regulated in normal-weight individuals; however, in upper-body obesity, excess lipolysis is commonly seen. This abnormality is considered a cause for at least some of the metabolic defects (dyslipidemia, insulin resistance) associated with upper-body obesity. "Normal" lipolysis is sex-specific and largely determined by the individual's resting metabolic rate. Women have greater FFA release rates than men without higher FFA concentrations or greater fatty acid oxidation, indicating that they have greater nonoxidative FFA disposal, although the processes and tissues involved in this phenomenon are unknown. Therefore, women have the advantage of having greater FFA availability without exposing their tissues to higher and potentially harmful FFA concentrations. Upper-body fat is more lipolytically active than lower-body fat in both women and men. FFA released by the visceral fat depot contributes only a small percentage of systemic FFA delivery. Upper-body subcutaneous fat is the dominant contributor to circulating FFAs and the source of the excess FFA release in upper-body obesity. We believe that abnormalities in subcutaneous lipolysis could be more important than those in visceral lipolysis as a cause of peripheral insulin resistance. Understanding the regulation of FFA availability will help to discover new approaches to treat FFA-induced abnormalities in obesity.