The potencies of synthetic analogues of saxitoxin and the absolute stereoselectivity of decarbamoyl saxitoxin.
The potencies of synthetic saxitoxin (+/- STX) and six of its synthetic analogues, including the enantioselectively synthesized unnatural (-)enantiomer of decarbamoyl saxitoxin (dcSTX), were measured and compared to those of natural saxitoxin [(+)STX]. The analogues, all of which were racemic (+/-) mixtures except for dcSTX, varied in the substituents at the C6 position, the carbamoyl 'moeity', and the C12 position, the hydrated ketone. The ability of the toxins to inhibit the compound action potential (AP) and to displace radiolabeled natural saxitoxin (3H-STX) from nerve membranes at equilibrium were both used as potency assays. Biological activity of both (+)- and (-)dcSTX was analyzed by the kinetics of block of single Na+ channels reconstituted in planar lipid bilayer membranes, where it was demonstrated that only (+)dcSTX had biological activity. The potency of STX analogues fell markedly as the substituent at the C6 position became smaller; Ki values from the binding competition assay (at 4 degrees C) are: (+/-)6-methanolic-STX, 5 x 10(-10) M; (+/-)6-methyl-STX, 1 x 10(-6) M; (+/-)6-dihydro-STX, 3.5 x 10(-5) M. Replacement of the ketone at the C12 position by a methylene group was accomplished in two derivatives, although both also had substituents at the C6 position. The compound (+/-)6-methyl-12-deoxy-STX was about 0.03 as potent as (+/-)6-methyl-STX and only 10(-5) as potent as racemic (+/-)STX. In synthetic compounds where the benzyloxymethyl (-CH2OCH2C6H5) substituent occurred at the C6 position, the C12-methylene derivative still displayed some binding activity (Ki = 6 x 10(-4) M). However, when the same C6 derivatized compounds also contained a 6-membered heterocyclic group (-C3H8S2-) conjugated to carbon 12, the measured binding affinity was even further decreased (Ki = 2 x 10(-3) M). The findings show that substitutions on the carbon 6 position of STX have stronger effects on STX potency than previously believed, and that the toxin may form a hydrogen bond with the sodium channel at this site. Furthermore, the total removal of oxygen from the C12 position does not completely abolish the binding activity of the molecule.


miR-8-3p regulates mitoferrin in the testes of Bactrocera dorsalis to ensure normal spermatogenesis.
Genetics-enhanced sterile insect techniques (SIT) are promising novel approaches to control Bactrocera dorsalis, the most destructive horticultural pest in East Asia and the Pacific region. To identify novel genetic agents to alter male fertility of B. dorsalis, previous studies investigated miRNA expression in testes of B. dorsalis. One miRNA, miR-8-3p was predicted to bind the 3'UTR of putative B. dorsalis mitoferrin (bmfrn). The ortholog of bmfrn in D. melanogaster is essential for male fertility. Here we show that bmfrn has all conserved amino acid residues of known mitoferrins and is most abundantly expressed in B. dorsalis testes, making miR-8-3p and mitoferrin candidates for genetics-enhanced SIT. Furthermore, using a dual-luciferase reporter system, we show in HeLa cells that miR-8-3p interacts with the 3'UTR of bmfrn. Dietary treatments of adult male flies with miR-8-3p mimic, antagomiR, or bmfrn dsRNA, altered mitoferrin expression in the testes and resulted in reduced male reproductive capacity due to reduced numbers and viability of spermatozoa. We show for the first time that a mitoferrin is regulated by a miRNA and we demonstrate miR-8-3p as well as bmfrn dsRNA to be promising novel agents that could be used for genetics-enhanced SIT.


Glial activity during axonal regrowth following cryogenic injury of rat spinal cord.
The cryogenic model of spinal cord injury is associated with regrowth of axons through a zone of injury which is composed of a complex matrix of intact blood vessels, cells and extracellular materials. We have used this, therefore, as a means for studying the relationship between these cellular components, particularly the astrocytes, and the regrowing axons. For the time period of 60 days following injury we have found that, from an undifferentiated group of cells which appears early, there develops a population of astrocytes which is associated with the restoration of neural structure, including the return of axons, to the damaged area. We interpret these associations to be supportive through direct axonal interactions and indirect environmental contributions.


Assessing the reliability of Curriculum-Based Measurement: an application of Latent Growth Modeling.
The purpose of this study was to demonstrate the use of Latent Growth Modeling (LGM) as a method for estimating reliability of Curriculum-Based Measurement (CBM) progress-monitoring data. The LGM approach permits the error associated with each measure to differ at each time point, thus providing an alternative method for examining of the reliability of CBM reading aloud data over repeated measurements. The analysis revealed that the reliability of CBM data was not a fixed property of the measure, but it changed with time. The study demonstrates the need to consider reliability in new ways with respect to the use of CBM data as repeated measures.


3D-poly (lactic acid) scaffolds coated with gelatin and mucic acid for bone tissue engineering.
Three-dimensional (3D) printing is a promising technology to fabricate the intricate biomimetic structure. The primary focus of this study was to develop the bioactive 3D-scaffolds to enhance bone regeneration. The 3D-poly (lactic acid) (PLA) scaffolds were extruded based on a computer-aided design (CAD) model and coated with gelatin (Gel) containing different concentrations of mucic acid (MA) and were investigated for their osteogenic potential. Coating the PLA scaffolds with Gel/MA improved their physicochemical properties, and the addition of MA did not alter these properties. The viability of mouse mesenchymal stem cells (mMSCs, C3H10T1/2) seeded onto the PLA/Gel/MA scaffolds remained unaffected both at metabolic and cell membrane integrity levels. Alkaline phosphatase and von Kossa staining indicated the promotion of osteoblast differentiation of mMSCs by MA in the PLA/Gel scaffolds. Inclusion of MA in PLA/Gel scaffolds also increased the expression of the master bone transcription factor, Runx2, and other osteoblastic differentiation marker genes in mMSCs. Thus, our results suggested that the 3D-printed PLA scaffolds coated with Gel/MA favor osteoblast differentiation and have potential applications in bone tissue engineering.


Dysregulated microRNAs in neural system: Implication in pathogenesis and biomarker development in Parkinson's disease.
Parkinson's disease is a debilitating neurodegenerative movement disorder, characterized by the progressive and selective loss of dopaminergic neurons located in the substantia nigra, leading to clinical motor symptoms. The factors involved in PD are rather multifaceted. There are many cellular pathways contributing to its neuro-pathogenesis, which include abnormal protein aggregation, impaired ubiquitin proteasome system, autophagy, and neuroinflammation. However, despite years of investigation, still little is known about early events in the molecular pathogenesis. MicroRNAs are small non-coding RNAs that can regulate post-transcriptional expression of mRNAs. Since they somewhat modulate many mRNA targets simultaneously, many cellular pathways may be affected by one individual miRNA. Moreover, miRNAs can stably circulate in cerebrospinal fluid and blood, and their expression pattern can reflect the molecular pathophysiology, thus making them promising biomarkers in PD diagnosis and prognosis. In this review, we will review the recent progress on miRNA's mechanism in PD pathogenesis and discuss the possibilities of miRNAs as PD molecular biomarkers.


Limited versus Whole-Brain Perfusion for the Indication of Thrombolysis in the Extended Time Window of Acute Cerebral Ischemia.
Perfusion computed tomography (PCT) has emerged as alternative to magnetic resonance imaging (MRI) for assessment of patients clinically qualifying for off-label thrombolysis within 4.5 to 9 hours after onset of ischemic stroke. However, disadvantage of PCT is its often limited anatomic coverage with only 2 or 3 slices when using a 4- to 64-section scanner. Our purpose was therefore to evaluate the value of 2- and 3-slice perfusion compared to whole-brain perfusion. One hundred twenty-five patients undergoing MRI beyond 4.5 hours after symptom onset with supratentorial perfusion deficit were selected retrospectively. Accordingly to PCT slice positioning, 2 or 3 slices of the whole-brain perfusion weighted imaging data set were depicted. Volumes of infarct (using cerebral blood volume) and penumbra (using time-to-peak and cerebral blood volume) were calculated, and results were compared with 2- and 3-slice-derived volumes, respectively. Whole-brain imaging revealed a mismatch of more than 20% in 68.8% of patients (defined as 100%). Two-slice imaging detected a perfusion deficit in 72% and a mismatch in 48.8% (sensitivity = 70.9%). Three-slice imaging detected a perfusion deficit in 76% and a mismatch in 50.4% (sensitivity = 73.3%). Although there was no significant difference between 2- and 3-slice imaging (P > .23), both techniques revealed significantly less patients with mismatch compared to whole-brain coverage (P < .01). Two- and 3-slice imaging like obtained with PCT on most installed CT systems to assess perfusion deficits with subsequent mismatch calculation in acute stroke outside the 4.5-hour time window is significantly inferior to whole-brain coverage and, hence, has to be considered as a less-than-ideal solution.


Human pluripotent stem cell (hPSC) and organoid models of autism: opportunities and limitations.
Autism spectrum disorder (ASD) is a complex neurodevelopmental disorder caused by genetic or environmental perturbations during early development. Diagnoses are dependent on the identification of behavioral abnormalities that likely emerge well after the disorder is established, leaving critical developmental windows uncharacterized. This is further complicated by the incredible clinical and genetic heterogeneity of the disorder that is not captured in most mammalian models. In recent years, advancements in stem cell technology have created the opportunity to model ASD in a human context through the use of pluripotent stem cells (hPSCs), which can be used to generate 2D cellular models as well as 3D unguided- and region-specific neural organoids. These models produce profoundly intricate systems, capable of modeling the developing brain spatiotemporally to reproduce key developmental milestones throughout early development. When complemented with multi-omics, genome editing, and electrophysiology analysis, they can be used as a powerful tool to profile the neurobiological mechanisms underlying this complex disorder. In this review, we will explore the recent advancements in hPSC-based modeling, discuss present and future applications of the model to ASD research, and finally consider the limitations and future directions within the field to make this system more robust and broadly applicable.


Quality-assurance monitoring in thrombolytic therapy.
Use of thrombolytic agents for patients within the first 6 hours of AMI has become a standard approach to care. With this standard approach the nurse is charged with the task of not only skillfully administering this therapy, but also with monitoring its safe, effective, and appropriate use. The presence of well-established standards for thrombolytic therapy serve a twofold purpose: that of promoting continuity and consistency of care. The QA process evolves out of these set standards. It seeks to determine compliance to standards and to identify existing problems. One of the most effective approaches to this process is a unit-based approach. This type of approach enhances clinical competence and increases professional accountability. Finally, the QA process is a systematic means by which identified problems are addressed and reevaluated. In so doing, quality in the use of thrombolytic therapy may be maintained.


Association of the bradykinin receptors genes variants with hypertension: a case-control study and meta-analysis.
The present study was to investigate the role of bradykinin receptors genes polymorphisms on hypertension risk in Northern Han Chinese population. We also carried out a meta-analysis on Chinese to derive a more full assessment of this association. A total of 976 subjects from Northern Han Chinese and 7 studies with 1599 cases and 1425 controls were included in this case-control study and in the current meta-analysis, respectively. For the case-control study, we identified the genotypes of -58T/C and 1098A/G polymorphism in BDKRB2 and BDKRB1 genes, respectively, by TaqMan PCR method. Overall, we found significant association between the -58T/C polymorphism and the increased risk of hypertension in the allele comparison (p = 0.01, OR = 1.386, 95% CI [1.138-1.688]). Subgroup analysis by gender suggested that this obvious association could still be found in males, but not in females. For the 1098A/G polymorphism, no significant association was revealed in overall and subgroup analysis. For the meta-analysis involving the -58T/C polymorphism, a significant association between this polymorphism and hypertension was observed in the whole group. In Chinese Han subgroup, we found significant association with hypertension in allele comparison(C vs. T: p = 0.03, OR = 1.28, 95% CI 1.03-1.59, pheterogeneity = 0.05). Our case-control study indicated that -58T/C might be significantly associated with the increased risk of hypertension in Northern Han Chinese population, which was partially confirmed by our meta-analysis.


New surgical adjuncts in the treatment of rhinophyma: the microdebrider and FloSeal.
Rhinophyma is considered to be the final stage of rosacea and has an unknown aetiology. We present two new surgical adjuncts for the treatment of this condition. The microdebrider is easy to use and allows precise contouring of the nose. It shares the same underlying principle as free-hand scalpel shaving but outperforms this method in key areas. We also describe a novel use for FloSeal((R)), a gelatin-thrombin co-mixture, utilizing its haemostatic properties to address bleeding from the re-shaped denuded nose.


Unmet needs following hospitalization with heart failure: implications for clinical assessment and program planning.
Measuring health status is increasingly important in both clinical practice and research. The Heart Failure Needs Assessment Questionnaire (HFNAQ) is a self-administered, disease-specific, 30-item questionnaire that measures an individual's perception of his/her needs in the physical, psychological, social, and spiritual domains. To assess the prevalence of needs in patients with heart failure (HF) recently discharged from hospital. The HFNAQ was administered to participants (n = 132; mean [SD] age, 72.3 [9.69] years; 63% male) consenting to attend an HF-specific cardiac rehabilitation program. The total mean HFNAQ score was 67.3 (95% confidence interval, 65.03-69.75), indicating an average level of need around the midrange of the scale. In this vulnerable postdischarge phase, there was evidence of predominance of psychological and social concerns over physical needs. None of the variables that were examined for associations with the measures of needs reached statistical significance, highlighting the strongly individualized perception of need. Higher levels of unmet needs in the psychological and social domains, compared with physical needs, identify psychosocial care as an important consideration for nursing interventions for people with HF. This study further demonstrates the importance of assessing the needs from the perspective of the individual to ascertain each person's unique perspective of the HF illness experience. Study findings further underscore the importance of individualized care planning for patients with HF after discharge from hospital to address their unique needs and circumstances.


Studies on antithrombotic effects of recombinant hirudin.
Recombinant desulfato hirudin (rH) was studied with regard to its effects on various models of thrombosis, its pharmacokinetic behaviour as well as its influence on primary haemostasis in rats. The pharmacological behaviour of rH proved to be similar to that of native hirudin. Depending on the different models of experimental thrombosis different dosages of rH were required to prevent thrombus formation. This corresponds to rH plasma concentrations of 0.5-1.5 micrograms/ml. Primary haemostasis is influenced only after excess dosages and plasma concentrations of 4 micrograms/ml and above.


The shape of the epiglottis reflects improvement in upper airway obstruction after weight loss.
Obstructive sleep apnea (OSA) is a sleep disorder characterized by recurrent episodes of closure of the upper airway during sleep, and is highly prevalent among overweight individuals. A significant percentage of patients with OSA remain undiagnosed. This condition creates chronic nighttime hypoxemia that can result in significant complications including systemic and pulmonary hypertension, cor pulmonale, and stroke. Polysomnography is still the most widely used method for diagnosing OSA. Studies have shown that in the majority of patients with OSA the airway obstruction involves the retroglossal region. Upon performing esophagogastroduodenoscopy on patients with a wide range of body mass indices (from 21 to 63), we noticed a gradual increase in the concavity of the posterior epiglottal surface as the BMI increases. Upon following some of the patients who underwent laparoscopic gastric banding and lost significant weight, we noticed a dramatic change in the shape of the epiglottis. This reflects a relief in the pressure on the epiglottis created by the collapsing airways in periods of apnea. Thus, the deformity in the shape of the epiglottis reflects the chronic airway collapse in obese patients, and improvement in this deformity after weight loss indicates a relief of the chronic upper airway obstruction.


Exploring RNA methylation as a promising biomarker for assessing sublethal effects of fipronil on honeybees (Apis mellifera L.).
Honeybees play a crucial role as pollinators for crops and are regarded as sensitive bioindicators of environmental health. The widespread use of pesticides poses a severe threat to honeybee survival. However, there is limited information available on the specific risks associated with fipronil exposure in honeybees, particularly concerning the impact on RNA methylation throughout their lifespan. This study aimed to evaluate the effects of sublethal concentrations of fipronil on RNA m6A and m5C methylations, along with the associated genes in honeybee larvae and newly emerged adults. LC-MS/MS analysis revealed a notable hypomethylation of m5C in larvae, while hypermethylation of m6A was observed in the adult brain. Significant changes in the expression of genes such as AmWTAP, AmYTHDF, AmALKBH4, AmALKBH6, AmALKBH8, AmNSUN5, AmNOP2, AmTET1, and AmYBX1 were observed in the adult brain, whereas alterations in the expression of AmNSUN2, AmMETTL14, AmALKBH1, AmALKBH4, AmALKBH6 AmALYREF, AmTET1, and AmYBX1 were observed in the larvae. Notably, the expression of AmALKBH1 was not detected in any fipronil-treated larvae, suggesting its potential as an early risk indicator for honeybee larvae in future assessments. This pioneering study provides insights into the effects of fipronil on RNA methylations in honeybees and explores the possibility of employing RNA methylation as a tool for assessing pesticide risks in this important pollinator species. These findings offer new perspectives on honeybee protection and the development of toxicity evaluation systems for pesticides.


Sustainable LiCoO2 by collective glide of CoO6 slabs upon charge/discharge.
SignificanceTraditional views indicate that the well-known layered LiCoO2 cathode delivers a typical solid-solution reaction upon delithiation. The problem is that "solid solution" is a vague concept, and the phase transition remains ambiguous. Here, we reveal a mechanism with the collective and quasi-continuous glide of CoO6 slabs in layered LiCoO2 through combining in situ XRD and ex situ STEM characterizations. Such a delithiation mechanism does not involve the nucleation-and-growth-type delithiation process and represents a completely different manner from the conventional two-phase or solid solution-phase transition processes. The lessons provide a different insight into understanding the working mechanism of layered oxide materials.


Making change pay. Survey: more hospitals tap compensation as a tool of change.
No matter how much you say you want your health care organization's performance levels to change, you've got to put your money where your wish list is. That, in a nutshell, is the bottom-line finding of this year's Hay Hospital Compensation Survey, exclusively in this issue. But while the concept is simple, the execution is not, as the authors point out in their analysis.


Mechanistic insights into recognition of symmetric methylated cytosines in CpG and non-CpG DNA by UHRF1 SRA.
Non-CpG DNA methylation (non-mCpG) is enriched in the genome of brain neurons and germline cells in mammals. Accumulation of non-mCpG during postnatal brain development correlates with gene regulation and inactivation of distal regulatory elements. Recently, UHRF1 has been found to contribute to de novo non-CpG methylation, however, whether UHRF1 could recognize non-mCpG is unknown. Here, we have demonstrated through calorimetric measurements that the UHRF1 SRA can recognize mCpH and fully-mCpHpG, types of non-mCpG. Our ITC binding studies endorse the preferential reading of hemi-mCpG by UHRF1 SRA and also show 6-fold weaker binding for fully-mCpG than hemi-mCpG. Despite presence of symmetrical (5-methyl cytosine) 5mCs, stoichiometry of 1:1 for UHRF1 SRA binding to fully-mCpG indicates that UHRF1 SRA may not form a stable complex with fully-mCpG DNA. Contrarily, UHRF1 SRA recognizes fully-mCpHpG with a stoichiometry of 2:1 protein to DNA duplex with binding affinity higher than fully-mCpG. Our crystal structure of UHRF1 SRA bound to fully-mCpHpG DNA reveals dual flip-out mechanism of 5mC recognition. Metadynamics studies corroborates with ITC data that UHRF1 SRA could not form a stable complex with fully-mCpG DNA. Altogether, this study demonstrates that UHRF1 SRA recognizes non-mCpG DNA and exhibits contrasting mechanisms for hemi-mCpG and fully-mCpHpG DNA recognition.


Mammographic image quality in relation to positioning of the breast: A multicentre international evaluation of the assessment systems currently used, to provide an evidence base for establishing a standardised method of assessment.
Optimum mammography positioning technique is necessary to maximise cancer detection. Current criteria for mammography appraisal lack reliability and validity with a need to develop a more objective system. We aimed to establish current international practice in assessing image quality (IQ), of screening mammograms then develop and validate a reproducible assessment tool. A questionnaire sent to centres in countries undertaking population screening identified practice, participants for an expert panel (EP) of radiologists/radiographers and a testing panel (TP) of radiographers. The EP developed category criteria and descriptors using a modified Delphi process to agree definitions. The EP scored 12 screening mammograms to test agreement then a main set of 178 cases. Weighted scores were derived for each descriptor enabling calculation of numerical parameters for each new category. The TP then scored the main set. Statistical analysis included ANOVA, t-tests and Kendall's coefficient. 11 centres in 8 countries responded forming an EP of 7 members and TP of 44 members. The EP showed moderate agreement when the scoring the mini test set W = 0.50 p < 0.001 and the main set W = 0.55 p < 0.001, 'posterior nipple line' being the most difficult descriptor. The weighted total scores differentiated the 4 new categories Perfect, Good, Adequate and Inadequate (p < 0.001). We have developed an assessment tool by Delphi consensus and weighted consensus criteria. We have successfully tabulated a range of numerical scores for each new category providing the first validated and reproducible mammography IQ scoring system.


Flip Autograft Technique for Anterolateral Femoral Deficiency in Total Knee Arthroplasty.
Anterolateral bone loss of the femur within the trochlear groove presents a unique and rare issue in primary total knee arthroplasty (TKA). Unlike distal and posterior femur bone loss for which most contemporary TKA systems have modular augments, the same does not exist for anterolateral bone loss. We present a technique in which a patient's host bone from the standard distal femoral cuts was used to augment and provide a stable base for cementing of final femoral implants. Currently, the patient has 3-year follow-up with excellent results in terms of pain control with no evidence of component failure on the most recent radiographs. This technique provides a simple solution to a complex problem within primary TKA.


[Becoming requesting couples after their registration in oocyte donation].
Many studies have investigated the causes of discontinuation during intraconjugal medically assisted procreation. However, there are currently very few data justifying the causes of discontinuation during the oocyte donation program. The main objective of this study is to determine the causes of discontinuation in oocyte donation and their respective frequency, excluding live births by oocyte donation in our center. This is an observational, retrospective, single-center study focused on receiving or requesting couples who stopped their oocyte donation program between January 1, 2005 and April 29, 2021. A total of 390 couples were included in the study. Of the 390 couples included, 306 couples or nearly 80%, left our oocyte donation program without obtaining a live birth through this method. The three most frequent reasons for discontinuation were: failure of several oocyte donations (18%), desire of the couples to voluntarily discontinue their care (15%) and separation (14%). Finally, 84 couples obtained at least one live birth by oocyte donation in our center. In addition, 38 women conceived spontaneously and 33 couples benefited from an oocyte donation abroad. The most common reason for discontinuation in oocyte donation program, excluding live births by oocyte donation in our center, is failure after several oocyte donations. However, 40% of the couples in the study obtained at least one live birth.


Isosorbide dinitrate in acute and chronic heart failure.
The hemodynamic effects of sublingual isosorbide dinitrate (ISD) were studied in 12 patients with congestive heart failure (CHF) of many causes. The duration of CHF in the chronic group varied from 3 to 62 months (mean, 29.5). Hemodynamic parameters were obtained serially before and 10, 20, 30, 45, 60, and 120 min after a 5 to 15 mg dose of ISD sublingually. The hemodynamic effects were pronounced at 45 min and returned to control levels in 120 min. Heart rate did not change. Hemodynamic parameters that changed after ISD were mean arterial pressure (-7%, p less than 0.05), mean pulmonary artery pressure (-17%, p less than 0.05), and mean pulmonary capillary wedge pressure (-29%, p less than 0.005). Mean cardiac index (+3%, p = NS) and mean stroke work index rose (+9.4%, P X NS); mean total systemic resistance fell (-10%, p = NS). Thus the duration of hemodynamic effects of ISD is less than 2 hr and sublingual ISD induces beneficial reduction of pulmonary capillary wedge pressure in patients with acute and chronic CHF without increasing cardiac index and stroke work index.


Quantifying solid waste and recycling employment in Florida, USA: Trends in public and private sectors.
Measuring and tracking the numbers of jobs in solid waste management and recycling industries over time provide basic data to inform decision makers about the important role played by this sector in a state or region's 'green economy'. This study estimates the number of people employed in the solid waste and recycling industry from 1989 through 2011 in the state of Florida (USA), applying a classification scheme based on the Standard Industrial Code (SIC) and utilizing the National Establishment Time Series (NETS) database. The results indicate that solid waste and recycling jobs in the private sector steadily increased from 1989 to 2011, whereas government employment for solid waste management fluctuated over the same period.


Immuno-affinitive supramolecular magnetic nanoparticles incorporating cucurbit[8]uril-mediated ternary host-guest complexation structures for high-efficient small extracellular vesicle enrichment.
Enriching small extracellular vesicles (sEVs) with undamaged structure and function is a pivotal step for further applications in biological and clinical fields. It has prompted researchers to explore a carrier material that can efficiently capture sEVs while also gently release the captured sEVs. Here, 1-adamantylamine (1-ADA) responsive immuno-affinitive supramolecular magnetic nanoparticles (ISM-NPs) incorporating ternary host-guest complexation structures mediated by CB[8] were proposed to achieved the goal. In particular, the ternary host-guest complexation was constructed by the host molecule (cucurbit[8]uril, CB[8]) mediated assembly of two guest molecules (naphthol and bipyridine), and served as a cleavable bridge to connect the magnetic core and peripheral antibody. These constructed ISM-NPs performed well in the applications of capturing sEVs with a high capture efficiency of 85.5%. Further, the CB[8]-mediated ternary host-guest complexation structures can be disassembled with addition of the 1-ADA. Thus, the sEVs recognized by the anti-CD63 were released competitively, with a decent release efficiency more than 82%. The released sEVs kept intact morphology and exhibited appropriate size distribution and concentration. This supramolecular magnetic system, with 1-ADA responsive ternary host-guest complexation structures, may contribute to efficient enrichment of any other biomarkers, likely cells, proteins, peptides, etc.


Regulating the balance between differentiation and apoptosis: role of CREM in the male germ cells.
Various endocrine and neuronal functions are governed by the cAMP-dependent signaling pathway. In eukaryotes, transcriptional regulation upon stimulation of the adenylyl cyclase signaling pathway is mediated by a family of cAMP-responsive nuclear factors. This family consists of a large number of members which may act as activators or repressors. These factors contain the basic domain/leucine zipper motifs and bind as dimers to cAMP-response elements (CRE). The function of CRE-binding proteins (CREBs) is modulated by phosphorylation by several kinases. Direct activation of gene expression by CREBs requires phosphorylation by the cAMP-dependent protein kinase A to the serine-133 residue. The gene CREM encodes various transcription factors which play key physiological and developmental roles within the hypothalamic-pituitary-gonadal axis. We have previously shown that the transcriptional activator CREMtau is highly expressed in postmeiotic cells. Spermiogenesis is a complex process by which postmeiotic male germ cells differentiate into mature spermatozoa. This process involves remarkable structural and biochemical changes which are under the hormonal control of the hypothalamic-pituitary axis. We have addressed the specific role of CREM in spermiogenesis using CREM-mutant mice generated by homologous recombination. Analysis of the seminiferous epithelium from mutant male mice reveals that spermatogenesis stops at the first step of spermiogenesis. Late spermatids are completely absent while there is a significant increase in apoptotic germ cells. A series of postmeiotic germ cell-specific genes are not expressed. Mutant male mice completely lack spermatozoa. This phenotype is reminiscent of cases of human infertility.


[Diverticular disease - clinical patterns and treatment].
Diverticulosis, diverticular disease and diverticulitis have come into focus again because new aspects concerning diagnosis, risk factors and treatment arose only recently which prompted a new Guideline released by the DGVS and DGAV summarising the current evidence. Along with the guideline's essentials for medical practice a diagnosis of diverticulitis is considered unsatisfactory unless a cross-sectional imaging method (either ultrasonography [US] or computed tomography [CT] ) has proven that the clinical findings and inflammation (CRP considered superior to WBC and temperature) are due to diverticular inflammation. For reasons of practicability and considering relevant legislation for radiation exposure protection, US is the primary - and usually effectual - diagnostic method of choice as it is equipotent to CT. While US offers better resolution and enables precise imaging exactly at the location of pain as well as reiterative application, the latter implies advantages in the case of a deep abscess or diverticulitis in difficult locations (e. g. the small pelvis). Clinical evidence and laboratory and imaging findings allow for distinguishing a large number of differential diagnoses and also form the basis of a new classification (classification of diverticular disease, CDD) which comprises all forms of diverticular disease, from diverticulosis to bleeding and to the different facettes of diverticulitis. This classification -which should be applied in any patient with the diagnosis of diverticular disease- is independent of specific diagnostic preferences and applicable both to conservative and operative treatment options. While the number of recurrent episodes is no longer a significant indicator for surgery in diverticulitis, severity and / or complications determine treatment options along with the patients preferences. According to first data, conservative treatment may waive antibiotics under certain circumstances, however they are indispensible in complicated disease or patients bearing risk factors. Spasmoanalgetics and supportive fluid supply are individually necessary, and avoidance of potentially aggravating medications (e. g. NSAIDS) appears advisable, but many suggestions (nil by mouth, bed rest, laxatives) come along without an adaequate body of evidence. Similarly medical advice concerning prevention and secondary prophylaxis relies mainly on epidemiological plausibility. Because minor perforations (CDD type 2 a) as well as recurrent episodes of uncomplicated diverticulitis and even some abscesses > 1 cm (CDD type 2 b) respond favourably to medical treatment, the timely indication for surgery in these cases requires precise classification along with a close surveillance in trustful cooperation between the gastroenterologist and the surgeon.


Don't lose money with your technology upgrade.
Hospitals nationwide have seen revenue drop after implementing new financial and clinical IT platforms, typically because their adoption teams did not plan for the impact on downstream revenue. Technology is rarely a panacea. Although an upgrade can catch some problems, it can also add a new level of complexity that will make it harder to fix poor processes if they are not addressed up front. Finance departments should be involved in design and testing phases of all IT system changes--even nonfinancial systems--to protect revenues before, during, and after implementation.


The optics of occupational progressive lenses.
Occupational progressive lenses (OPLs) utilize progressive power optics and are designed primarily to meet near and intermediate viewing needs such as working at a computer workstation for presbyopic patients. OPLs are fabricated to have the prescribed near power in the lower part of the lens and the power in the upper portion of the lens is determined by the amount of power "degression" (decrease in plus power) relative to the near power. Independent measurements of the optical characteristics of these lenses have not been reported previously. Manufacturers of 7 different OPL designs provided sample lenses for a patient with +2.50 D add that were measured with a Rotlex Class Plus lens analyzer (Rotlex Inc., Israel). Power measurements were normalized to the location specified by the manufacturer, and the vertical location of each lens was normalized to pupil center based on manufacturer fitting guidelines. Large optical differences exist among the OPL designs. The results show clear differences between the designs in terms of the add powers, their vertical location, and zone width. The size and location of the near, near-intermediate, far-intermediate, and far viewing zones were determined. The literature and clinical experience support that OPLs are successful at meeting the computer, general office, and other intermediate viewing distance needs of many patients. However, because of the large differences in the several OPL designs, patient success can likely be enhanced by selecting the design that best suits his or her viewing needs.


Explainable semi-supervised deep learning shows that dementia is associated with small, avocado-shaped clocks with irregularly placed hands.
The clock drawing test is a simple and inexpensive method to screen for cognitive frailties, including dementia. In this study, we used the relevance factor variational autoencoder (RF-VAE), a deep generative neural network, to represent digitized clock drawings from multiple institutions using an optimal number of disentangled latent factors. The model identified unique constructional features of clock drawings in a completely unsupervised manner. These factors were examined by domain experts to be novel and not extensively examined in prior research. The features were informative, as they distinguished dementia from non-dementia patients with an area under receiver operating characteristic (AUC) of 0.86 singly, and 0.96 when combined with participants' demographics. The correlation network of the features depicted the "typical dementia clock" as having a small size, a non-circular or "avocado-like" shape, and incorrectly placed hands. In summary, we report a RF-VAE network whose latent space encoded novel constructional features of clocks that classify dementia from non-dementia patients with high performance.


Persistent phosphor SrAl₂O₄:Eu,Dy in outdoor conditions: saved by the trap distribution.
Persistent phosphors are a specific type of luminescent materials having the unique ability to emit light long after the excitation has ended. They are commonly used as emergency signage in near ideal, isothermal indoor situations. Recently, their energy storage capacity was relied on for outdoor situations, e.g. for glow-in-the-dark road marks and in combination with solar cells and photo catalytic processes. In this work the influence of temperature, illumination intensity and the duration of the night is critically evaluated on the performance of afterglow phosphors. The persistent luminescence of SrAl2O4:Eu,Dy green emitting phosphors is studied under realistic and idealized conditions. It is found that the light output profile is hardly influenced by the ambient temperature in a wide range. This is due to the presence of a broad trap depth distribution, which is beneficial to cover the longer and colder winter nights. Temperature drops during the night are however detrimental. For traffic applications, the total light output of glow-in-the-dark road marks at the end of the night is not sufficient for the studied compound, although re-charging by the car's headlamps partially alleviates this. For energy storage applications, the trap density should be improved and tunneling recombination processes might be needed to overcome overnight temperature drops.


L-Arginine modulates CXC chemokines in the human intestinal epithelial cell line HCT-8 by the NO pathway.
Arginine has immunomodulating properties in different animal models but its effects in human intestine remain unknown. This study examined whether arginine modulates inflammatory mediators as chemokines and nitric oxide (NO) in the human intestinal epithelial cell line HCT-8 induced by cytokines. Under basal conditions, arginine did not influence iNOS protein expression, NO and chemokine production and mRNA levels (P>0.05 for all). Stimulation with cytokines-induced a significant increase of NO and chemokine production, iNOS and chemokine mRNA level and iNOS protein expression. Under inflammatory conditions, arginine increased 30% NO production (P<0.05) but did not influence iNOS mRNA level or iNOS protein expression. Under stimulated conditions, arginine decreased IL-8 and Mig mRNA level (57% and 39%, for 0.1 vs. 2 mmol/l l-arginine, P<0.05, respectively), and production (respectively, 28 and 23%, both P<0.05). IP-10 and I-TAC mRNA level and production were not significantly influenced by arginine. Under inflammatory conditions, l-arginine as well as a NO donor (sodium nitroprusside (SNP)) increased NO production, which was inversely correlated with IL-8 production (r'=-0.66, P=0.007 for arginine; r'=-0.79, P<0.0001 for SNP). Use of NG-Methyl-l-arginine acetate, a NOS inhibitor which prevents arginine-induced NO production, suppressed the arginine-induced IL-8 inhibition (P<0.05). In HCT-8 cells, arginine enhanced cytokine-induced NO production, reduced IL-8 and Mig production and mRNA level and had no effects on other assessed chemokines. In conclusion, arginine-induced IL-8 inhibition in HCT-8 cells involves NO pathway under inflammatory conditions. These data suggest that arginine-enriched enteral nutrition may have significant influence on inflammatory response in human intestine.


Clinical evaluation of dithiothreitol in comparison with sonication for biofilm dislodgement in the microbiological diagnosis of periprosthetic joint infection.
Sonication of explanted devices is well investigated method and was shown to improve the microbiological diagnosis of impant-associated infections by physical removal of bacterial biofilms. Recently, novel approach with chemical agents have been investigated for biofilm dislodgement such as dithiothreitol (DTT). We compared the biofilm dislodgement efficacy of chemical method (dithiothreitol, DTT) compared to the sonication procedure in the diagnosis of prosthetic joint infections (PJI). In a prospective cohort, 187 patients undergoing hip and knee prostheses explantation were included, of whom 94 were assigned for sonication and 93 for DTT group. Sonication showed better sensitivity (73.8%) than DTT (43.2%) for the diagnosis of PJI and comparable specificity (98% and 94.6%, respectively). We concluded that sonication provides a more reliable diagnosis of PJI and detects about 30% more pathogens compared to DTT system. The study was registered at ClinicalTrials.gov (NCT02530229).


The age of stored red blood cell concentrates at the time of transfusion.
In the past decade, studies suggesting a reduced oxygen delivery by stored red blood cell concentrates (RBCCs) have initiated a discussion about the use of fresh versus old blood. We determined whether old RBCCs represent a significant part of the total of RBCCs issued. The age of RBCCs at the time of transfusion was determined in 74 084 units during a 5-year period in the Academic Medical Center, a main Dutch University Hospital. The mean (+/-SD) storage time of the total number of transfused RBCC was 19.4 +/- 7.0 days, and 37% were older than 3 weeks. As more than one-third of the transfused RBCC units are stored for longer than 3 weeks, the research examining differences in oxygen delivery between fresh and stored RBCC is relevant for packed RBC transfusion practice.


Giant fibrolipoma in the mediastinum: an unusual case.
A 50-year-old man presented with a middle and posterior mediastinal mass on chest radiograph and computed tomography. Surgical exploration revealed a large dumbbell-shaped lipomatous lesion. Histologic examination confirmed this to be a fibrolipoma. This is the first reported case of fibrolipoma in the mediastinum but outside of the esophagus.


Relation of substance use disorders to mortality, accident and emergency department attendances, and hospital admissions: A 13-year population-based cohort study in Hong Kong.
The impact of substance use disorders (SUD) in an Asian population has not been fully explored. We aimed to assess the risk of mortality, accident and emergency (A&E) department attendances, and hospital admissions associated with SUD in a population-based cohort study. Patients diagnosed with SUD in public A&E departments from 2004 to 2016 (N = 8,423) were identified in the Clinical Database Analysis and Reporting System of the Hong Kong Hospital Authority and 1:1 matched to patients without SUD by propensity score (N = 6,074 in each group). Relative risks of mortality, A&E attendances and hospital admissions were assessed using Cox regression and Hurdle negative binomial regression. Patients with SUD had higher mortality (hazard ratio=1.43; 95% confidence interval [CI]=1.26-1.62) and more often died from poisoning or toxicity and injuries. The odds ratio (OR) for A&E attendances and all-cause hospital admissions associated with SUD were 2.80 (95% CI=2.58-3.04) and 3.54 (95% CI=3.26-3.83), respectively. The impact of SUD on the above outcomes was greatest among school-aged individuals (≤ 21 years) and decreased with age. The relative risk of mental disorder-related hospital admissions was much higher than that for infections, respiratory diseases, and cardiovascular diseases. In patients with SUD, ketamine and amphetamine use were associated with increased A&E attendances than opioid use. SUD was associated with increased mortality, A&E attendances and hospital admissions, especially in school-aged individuals. Our findings suggest prioritising early treatment and preventive interventions for school-aged individuals and focusing on the management of comorbid mental disorders and the use of ketamine and amphetamine.


Real-time transmission to real-time patient care: a tale of 4 devices.
We report a case in which a patient with dilated cardiomyopathy presented with syncope, terminated by a shock from his implantable cardioverter defibrillator. However, subsequent interrogation of the device revealed no tachycardia detection or treatment parameters. The mystifying details of the case were unravelled by remote consultation with the staff electrophysiologist and the use of smart phone-transmitted live images. This case highlights the use of mobile phone-facilitated video conferencing in urgent management of intracardiac device therapy. Judicious use of this technology has the potential to deliver effective and cost-effective solutions for many device-related emergencies in patients at remote settings.


Hydrocarbon bioremediation on Arctic shorelines: Historic perspective and roadway to the future.
Climate change has become one of the greatest concerns of the past few decades. In particular, global warming is a growing threat to the Canadian high Arctic and other polar regions. By the middle of this century, an increase in the annual mean temperature of 1.8 °C-2.7 °C for the Canadian North is predicted. Rising temperatures lead to a significant decrease of the sea ice area covered in the Northwest Passage. As a consequence, a surge of maritime activity in that region increases the risk of hydrocarbon pollution due to accidental fuel spills. In this review, we focus on bioremediation approaches on Arctic shorelines. We summarize historical experimental spill studies conducted at Svalbard, Baffin Island, and the Kerguelen Archipelago, and review contemporary studies that used modern omics techniques in various environments. We discuss how omics approaches can facilitate our understanding of Arctic shoreline bioremediation and identify promising research areas that should be further explored. We conclude that specific environmental conditions strongly alter bioremediation outcomes in Arctic environments and future studies must therefore focus on correlating these diverse parameters with the efficacy of hydrocarbon biodegradation.


Anaphylactoid reaction to mannitol.
A 16-year old boy with a lesion of the right eye developed, during the preoperative administration of a mannitol infusion, an anaphylactoid reaction characterized by hypotension, periorbital oedema and bronchospasm. This quickly resolved following cessation of the infusion and appropriate therapeutic measures. There were no long-lasting effects. We considered mannitol the causative agent because of its temporal relationship to the reaction and our inability to seriously implicate any other medication. A history of childhood atopy may have been a predisposing factor.


Quantitative assessment of motor speech abnormalities in idiopathic rapid eye movement sleep behaviour disorder.
Patients with idiopathic rapid eye movement sleep behaviour disorder (RBD) are at substantial risk for developing Parkinson's disease (PD) or related neurodegenerative disorders. Speech is an important indicator of motor function and movement coordination, and therefore may be an extremely sensitive early marker of changes due to prodromal neurodegeneration. Speech data were acquired from 16 RBD subjects and 16 age- and sex-matched healthy control subjects. Objective acoustic assessment of 15 speech dimensions representing various phonatory, articulatory, and prosodic deviations was performed. Statistical models were applied to characterise speech disorders in RBD and to estimate sensitivity and specificity in differentiating between RBD and control subjects. Some form of speech impairment was revealed in 88% of RBD subjects. Articulatory deficits were the most prominent findings in RBD. In comparison to controls, the RBD group showed significant alterations in irregular alternating motion rates (p = 0.009) and articulatory decay (p = 0.01). The combination of four distinctive speech dimensions, including aperiodicity, irregular alternating motion rates, articulatory decay, and dysfluency, led to 96% sensitivity and 79% specificity in discriminating between RBD and control subjects. Speech impairment was significantly more pronounced in RBD subjects with the motor score of the Unified Parkinson's Disease Rating Scale greater than 4 points when compared to other RBD individuals. Simple quantitative speech motor measures may be suitable for the reliable detection of prodromal neurodegeneration in subjects with RBD, and therefore may provide important outcomes for future therapy trials.


"Searching time aggregation" and density dependent parasitism in a laboratory host-parasitoid interaction.
Assuming random search by parasitoids within host-containing patches, and a constant search rate, current host-parasitoid models suggest that "searching time aggregation" by parasitoids in patches of high host density should tend to produce spatially density dependent parasitism at the patch level. It is not clear, however, that statistically significant "searching time aggregation" necessarily implies that significant density dependent parasitism will occur. In actual host-parasitoid systems the amounts of searching time allocated to patches of equal host density may vary a great deal from patch to patch. Such behavioral variability may be capable of obscuring an underlying density dependent trend, producing density independent parasitism at the patch level despite significant searching time aggregation in patches of high host density. This possibility is tested using data from an earlier laboratory study (Morrison and Lewis; Ent. exp. et appl. 30:31-39 [1981]) of the foraging behavior of Trichogramma pretiosum Riley, a generalist parasitoid of lepidopteran eggs. Searching time allocation is found to be highly variable among patches of equal host density, and significant density dependent parasitism does not occur despite significant searching time aggregation in patches of high host density. This suggests that in cases in which density independent or "density vague" patterns of parasitism are observed in field samples, direct field measurements of searching time allocation in patches of different host density may be necessary to demonstrate the presence or absence of significant searching time aggregation by foraging parasitoids.


Effect of selenium on testicular damage induced by varicocele in adult male Wistar rats.
Varicocele is an abnormal tortuosity and distension of the veins of the pampiniform plexus in the spermatic cord. It is the most common surgically correctable cause of male infertility. Several studies have revealed the effects of increased oxidative stress on serum, semen, and testicular tissues in patients with varicocele or in animal models. The aim of this study was to investigate the effects of sodium selenite on testicular damage induced by experimental left varicocele in male Wistar rats. In the present study, the effects of oral administration of sodium selenite (at doses of 0.05, 0.1, 0.2, and 0.4mg/kg bw) were assessed in normal and varicocelized rats. The varicocelized control rats showed decrease in sperm quality parameters, decreased activity of testes CAT, GPX and SOD, increased levels of MDA, and damage in testicular architecture. Administration of sodium selenite significantly reduced these changes to nearly normal levels, but did not change these parameters in normal rats. Histopathological studies further confirmed the protective effects of sodium selenite on varicocele-induced testicular damage in rats. Administrations of sodium selenite did not change these parameters in normal rats. Taken together, the results of this study suggest that sodium selenite treatment may have beneficial effect on the testes of varicocelized rats.


Targeting invading macrophage-derived PGE2, IL-6 and calcitonin gene-related peptide in injured nerve to treat neuropathic pain.
Immune and inflammatory responses occurring in an injured nerve have been generally believed to contribute to the generation and maintenance of neuropathic pain. In this review, the authors demonstrate the upregulation of COX-2/prostaglandin E2, IL-6 and calcitonin gene-related peptide in invading macrophages and discuss possible mechanisms involved in their upregulation and how they contribute to the maintenance of neuropathic pain. By acting on nociceptors in dorsal root ganglion and local inflammatory cells via autocrine or paracrine pathways, these inflammatory mediators facilitate spontaneous ectopic activity and sustain nociceptive responses, an important mechanism underlying both ongoing and evoked neuropathic pain state. Targeting these mediators in injured nerve may provide novel therapeutic avenues to more successfully treat nerve injury-associated neuropathic pain.


Immunization of mice with urease vaccine affords protection against Helicobacter pylori infection in the absence of antibodies and is mediated by MHC class II-restricted responses.
We examined the roles of cell- and antibody-mediated immunity in urease vaccine-induced protection against Helicobacter pylori infection. Normal and knockout mice deficient in major histocompatibility complex (MHC) class I, MHC class II, or B cell responses were mucosally immunized with urease plus Escherichia coli heat-labile enterotoxin (LT), or parenterally immunized with urease plus aluminum hydroxide or a glycolipid adjuvant, challenged with H. pylori strain X47-2AL, and H. pylori organisms and leukocyte infiltration in the gastric mucosa quantified. In an adjuvant/route study in normal mice, there was a direct correlation between the level of protection and the density of T cells recruited to the gastric mucosa. In knockout studies, oral immunization with urease plus LT protected MHC class I knockout mice [beta2-microglobulin (-/-)] but not MHC class II knockout mice [I-Ab (-/-)]. In B cell knockout mice [microMT (-/-)], vaccine-induced protection was equivalent to that observed in immunized wild-type (+/+) mice; no IgA+ cells were detected in the stomach, but levels of CD4(+) cells equivalent to those in the wild-type strain (+/+) were seen. These studies indicate that protection of mice against H. pylori infection by immunization with the urease antigen is dependent on MHC class II-restricted, cell-mediated mechanisms, and antibody responses to urease are not required for protection.


Hair cell regeneration.
The mammalian inner ear largely lacks the capacity to regenerate hair cells, the sensory cells required for hearing and balance. Recent studies in both lower vertebrates and mammals have uncovered genes and pathways important in hair cell development and have suggested ways that the sensory epithelia could be manipulated to achieve hair cell regeneration. These approaches include the use of inner ear stem cells, transdifferentiation of nonsensory cells, and induction of a proliferative response in the cells that can become hair cells.


The Role of Inflammatory Phenotype in Patients With Exacerbation-prone Asthma and Ongoing Therapy.
The risk factors for having frequent exacerbations are not well documented in cohort studies of patients with asthma on existing therapy. The objective of the present study was to compare the clinical and inflammatory characteristics of patients with exacerbation-prone asthma (EPA) with a history of two or more exacerbations in the previous year with those who had presented just one or no exacerbation. An ambispective observational study was conducted in a tertiary hospital. Patients diagnosed with moderate or severe asthma and ongoing therapy, whose inflammatory profile was determined by means of allergy and atopy status, blood eosinophilia and induced sputum were included. Patients were classified according to the number of asthma exacerbations in EPA (≥2 exacerbations in the previous year) vs. non-exacerbators (≤1 exacerbation in the previous year). Clinical, lung function and inflammatory characteristics of the two groups were compared. Three hundred ten patients were visited in the Asthma Unit in 2018 and the combination of atopy and allergy status, blood eosinophilia and induced sputum was obtained in 96 (31%) patients. Of this latter group, 46 patients (47%) presented EPA compared to 50 (53%) non-exacerbators. Airway and blood eosinophilic inflammation did not differ between EPA and non-exacerbators in patients with asthma and ongoing therapy, and it was not a risk factor for EPA in our cohort. Airway or blood type 2 inflammation status is not a valid tool for recognizing EPA or predicting asthma exacerbations in asthma patients following controller therapy.


Procalcitonin and mortality in status epilepticus: an observational cohort study.
Acute-phase proteins, such as procalcitonin (PCT), C-reactive protein (CRP) and albumin, may relate with course and outcome in status epilepticus (SE), as seizures bring about inflammation, changes of cytokine levels and blood-brain barrier breakdown. We aimed to determine the predictive value of serum levels of PCT at SE onset for the emergence of infections and unfavorable outcome in adult patients with SE. Furthermore, we sought to compare the predictive value of PCT, CRP and albumin for death. This observational cohort study was performed in the intensive care units of the University Hospital Basel (Switzerland), a university-affiliated tertiary care center. Adult patients with SE admitted from 2005 to 2012 were included. Serum levels of PCT, CRP and albumin were assessed at SE onset. Unfavorable outcome (i.e., death and a Glasgow Outcome Score of 1 to 3) during hospital stay and mortality after 30 days were considered the primary and infections as the secondary outcome measures. In 91 SE patients, mortality was 23.1 % during hospital stay and at 30-days follow-up. Infections emerged in 30.8 % of patients. In the multivariable analysis, PCT predicted unfavorable outcome independently from possible confounders such as acute etiology, infections during SE, the Charlson Comorbidity Index, and the Status Epilepticus Severity Score (hazard ratio 1.44 per every increasing ug/L, 95 % confidence interval 1.11-1.87). Additional multivariable analysis including serum levels of PCT, CRP and albumin revealed PCT as the only biomarker independently associated with an increased hazard for unfavorable outcome. PCT levels at SE onset were not related to infections during SE. Serum PCT levels measured at SE onset are independently associated with unfavorable outcome but do not predict the emergence of infections during SE. Procalcitonin may increase the predictive value of clinical scoring systems allowing for rapid risk stratification early in the course of SE.


Prediction of survival in patients with femoral neck fractures.
A prospective study of factors which might help to predict mortality in patients with intracapsular fractures of the femoral neck has been undertaken. A multivariate analysis technique was used to analyse the collected data, and it was found that mental ability was the most significant variable; this factor had the greatest effect on outcome.


Lipid membrane polarity profiles by high-field EPR.
Profiles of polarity across biological membranes are essential determinants of the cellular permeability barrier and of the stability of transmembrane proteins. High-field electron paramagnetic resonance of systematically spin-labeled lipid chains is used here to determine the polarity profiles of cholesterol-containing phospholipid membranes. The polarity dependence of the g(xx)-tensor element is opposite to the dependence on chain dynamics, and additionally has enhanced sensitivity to hydrogen bonding. Both features make high-field measurements superior to conventional determinations of local polarity from spin-label hyperfine couplings. The profile of g(xx) in dimyristoyl phosphatidylcholine membranes with 5 or 40 mol% cholesterol is established with eleven positional isomers of phosphatidylcholine, spin labeled at positions n = 4-14 in the sn-2 chain. A sigmoidal barrier, centered about chain position n(o) approximately 8, mirrors the corresponding sigmoidal trough obtained from the spin-label hyperfine coupling, A(zz). For the different positions, n, it is found that partial differential g(xx)/ partial differential A(zz) = -2.4 T(-1), a high value that is characteristic of hydrogen-bonded spin labels. This demonstrates that the transmembrane polarity profile registered by spin labels corresponds to water penetration into the membrane. Inhomogeneous broadening of the g(xx)-spectral feature demonstrates heterogeneities of the water distribution in the regions of higher intramembrane polarity defined by n < 8. In the transition region between high- and low-polarity regions (n approximately 8), the g(xx)-feature consists of two components characteristic of coexisting hydrated and nonhydrated states.


[Laryngopharyngeal Reflux (LPR) in patients with persistent hoarseness].
In 2006 The Global Consensus Group in Montreal pointed out that chronic laryngitis is highly associated with gastroesophageal reflux disease (GERD). To evaluate the frequency of LPR in a selected group of patients with chronic hoarseness. We were also interested in assessment of the relationship between Reflux Symptoms Index (RSI) scores, Ryan scores from the pharyngeal pH monitoring and the morphological changes in the larynx according to Reflux Findings Score (RFS). In addition, we wanted to assess the frequency of various clinical symptoms included in the RSI questionnaire among patients with LPR. 42 patients from an outpatient ENT clinic with chronic hoarseness and RSI ≥ 13. All subjects underwent pharyngeal pH monitoring with the Dx-pH System Restech ™ and laryngoscopy. Among 42 patients with chronic hoarseness, LPR was confirmed in 35 patients (83.33%). In 7 subjects pharyngeal pH monitoring was normal. Among all patients with confirmed LPR, only 5 out of 8 elements of RFS laryngoscopic changes were observed. The most frequent inflammatory changes noticed included erythema of the arytenoids and interarytenoid regions (posterior laryngitis). These findings were found in 30 out of 35 patients with LPR. Median value of RFS in patients with LPR was 4.45, which is lower than the cut off value of 7 necessary for recognition of LPR. There is statistically significant positive correlation between Ryan scores and the RFS scale results (correlation coefficient 0.91, p<0.001). Pharyngeal pH monitoring confirmed LPR in 83.33% selected group of patients with chronic hoarseness and RSI ≥ 13. Isolated erythema of arytenoid and interarytenoid region was the most frequent inflammatory abnormality found in the larynx. RFS values below 7 do not exclude the diagnosis of LPR. We can use RFS scales as a prognostic test of severity of LPR - due to statistically significant positive correlation between Ryan score and RFS values. The use of RSI scale revealed that the most frequent symptom among patient with LPR was throat clearing followed by hoarseness.


Self-stimulation at the lateral hypothalamus and locus coeruleus after specific unilateral lesions of the dopamine system.
A group of rats was trained to press levers for electrical stimulation from bipolar electrodes aimed at the lateral hypothalamus (LH), and another group was trained to self-stimulate from electrodes in the locus coeruleus (LC). All rats in both groups were subjected to unilateral injections of 6-hydroxydopamine into the substantia nigra and midbrain ventral tegmentum. The lesions produced profound depletions of dopamine from the ipsilateral frontal cortex, nucleus accumbens/olfactory tubercle, and corpus striatum. Pretreatment with desmethylimipramine prevented loss of noradrenaline in excess of that caused by electrode implantation. The destruction of the dopamine projections produced a persistent and pronounced deficit in intracranial self-stimulation from ipsilateral electrodes in both the LH and LC groups, but only transient effects on self-stimulation from contralateral electrodes at these sites. These results suggest that an intact dopamine system is required for the expression of self-stimulation behaviour.


Monoclonal antibody on-rate constant determined from time-course data of ligand binding by capture ELISA: Evaluation of eight data analysis methods.
We describe an ELISA method with which to determine monoclonal antibody (mAb) on-rate constants (k+1) based on time-course data of ligand (L) binding to plate-bound mAb. The assay was performed in pseudo-first order kinetic conditions ([L] > > [mAb]) and at various starting ligand concentrations. Time-course initial velocity was analyzed by several methods to derive the pseudo-first order (kobs) and second order (k+1) association rate constants of the antibody; the methods included i) an exponential first order rate equation, ii) reaction half-time from the Michaelis-Menten relationship, iii) the Vmax/Km tangent of the time-course curve, iv) Boeker's extrapolated-vo method, v-vi) modified Hanes-Woolf and Lineweaver-Burk linear plots, vii) a LOS plot, and viii) initial velocity gradient. Due to k+1 value dispersion associated with the methods of analysis, the on-rate constant of mAb SIM 253-19 anti-cholera toxin was estimated as an average value of 1.79 ± 0.11 × 106 M-1 s-1, 95% CL (1.68-1.89) and 5.8 (%CV [coefficient of variation]), which is similar to the k+1 obtained by surface plasmon resonance, 1.60 ± 0.17 × 106 M-1 s -1 (mean ± half range). This kinetic ELISA is a sensitive, quantitative method by which to determine antibody association rate constants.


Usefulness of pediatric colonoscopes in adult colonoscopy.
Use of small diameter, extraflexible pediatric colonoscopes has proved to be valuable in adult endoscopy practice, not only for passing strictures and stomas but also where either fixation due to diverticular disease or postoperative adhesions, or unavoidably painful looping made passage of adult colonoscopes impossible. In 70 of 78 (92%) of the cases where the adult colonoscope could not be passed through the sigmoid colon by an expert endoscopist, the pediatric colonoscope passed through, often very easily. Fifteen of these patients were considered to have been saved surgery by successful passage. The "failure" rate for all colonoscopy examinations was only 2%; this low failure rate was attributable to the use of pediatric instruments whenever passage through the sigmoid colon proved to be impossible with standard colonoscopes. In our opinion every unit performing frequent colonoscopies should have a pediatric colonoscope available for selected adult patients as well as for use in children.


[Bacteriorhodopsin retains the conformation of Val69-Gly72 fragment during functioning].
Effect of the monoclonal antibody (MAb) 5B6 produced to the solubilized preparation of bacteriorhodopsin on the protein photocycle was studied to examine conformational rearrangements on the surface of functioning bacteriorhodopsin molecule. Using the methods of solid phase enzyme immunoassay, peptide phage display, and 1H NMR spectroscopy, we demonstrated that the epitope recognized by MAb 5B6 is the Val69-Pro-Phe-Gly72 fragment of the protein, with the aromatic ring of Phe71 and the methyl groups of Val69 participating in the binding. MAb 5B6 exerted no significant effect on the photocycle of bacteriorhodopsin solubilized in Triton X-100 at pH 6.2 and 7.4, which suggested that, when functioning, bacteriorhodopsin retains the conformation and position of its Val69-Pro-Phe-Gly72 fragment.


Attention based parameter estimation and states forecasting of COVID-19 pandemic using modified SIQRD Model.
In this work, we propose a new mathematical modeling of the spread of COVID-19 infection in an arbitrary population, by modifying the SIQRD model as m-SIQRD model, while taking into consideration the eight governmental interventions such as cancellation of events, closure of public places etc., as well as the influence of the asymptomatic cases on the states of the model. We introduce robustness and improved accuracy in predictions of these models by utilizing a novel deep learning scheme. This scheme comprises of attention based architecture, alongside with Generative Adversarial Network (GAN) based data augmentation, for robust estimation of time varying parameters of m-SIQRD model. In this regard, we also utilized a novel feature extraction methodology by employing noise removal operation by Spline interpolation and Savitzky-Golay filter, followed by Principal Component Analysis (PCA). These parameters are later directed towards two main tasks: forecasting of states to the next 15 days, and estimation of best policy encodings to control the infected and deceased number within the framework of data driven synergetic control theory. We validated the superiority of the forecasting performance of the proposed scheme over countries of South Korea and Germany and compared this performance with 7 benchmark forecasting models. We also showed the potential of this scheme to determine best policy encodings in South Korea for 15 day forecast horizon.


Circadian rhythms in the urinary excretion of heavy metals and organic substances in metal workers in relation to renal excretory mechanism: profile analysis.
Circadian rhythms in the urinary excretion of eleven heavy metals and organic substances were examined under free, water-restrictive and water-loading conditions for 6 d (2 d for each of the three conditions) in twenty metal workers exposed to lead, zinc and copper. Circadian rhythms were found for all heavy metals and organic substances as well as for urinary flow (UF) rate, creatinine (Cn) and total urinary solutes (TUS). The Cn rhythm was significantly unparallel to the UF rhythm under the water-loading condition, indicating that the two rhythms were essentially different from each other. Circadian rhythms of the eleven urinary substances were then related to the Cn and UF rhythms, using profile analysis. The results indicated that the rhythms in the manganese, chromium, copper and beta-2-microglobulin excretion depend on the Cn rhythm, i.e. the rhythm of glomerular filtration; the rhythms in the hippuric acid, delta-aminolevulinic acid and TUS excretion are on the UF rhythm, i.e. the rhythm of reabsorption by the distal tubule and collecting duct. On the other hand, the rhythms in the lead, inorganic mercury, cadmium, zinc and coproporphyrin excretion were considered as reflecting complex renal excretory mechanisms.


The (cost-)effectiveness of combined lifestyle interventions for people with persistent low-back pain who are overweight or obese: A systematic review.
Lifestyle factors are expected to contribute to the persistence and burden of low-back pain (LBP). However, there are no systematic reviews on the (cost-)effectiveness of combined lifestyle interventions for overweight or obese people with LBP. To assess whether combined lifestyle interventions are (cost-)effective for people with persistent LBP who are overweight or obese, based on a systematic review. Systematic review METHOD: PubMed, Cochrane, Embase, CINAHL, PsycINFO and the Wiley/Cochrane Library were searched from database inception till January 6th 2023. Two independent reviewers performed study selection, data-extraction and risk of bias scoring using the Cochrane RoB tool 2 and/or the Consensus Health Economic Criteria list. GRADE was used to assess the level of certainty of the evidence. In total 2510 records were screened, and 4 studies on 3 original RCTs with 216 participants were included. Low certainty evidence (1 study) showed that combined lifestyle interventions were not superior to usual care for physical functioning, pain and lifestyle outcomes. Compared to usual care, moderate certainty evidence showed that healthcare (-$292, 95%CI: 872; -33), medication (-$30, 95% CI -65; -4) and absenteeism costs (-$1000, 95%CI: 3573; -210) were lower for the combined lifestyle interventions. There is low certainty evidence from 3 studies with predominantly small sample sizes, short follow-up and low intervention adherence that combined lifestyle interventions are not superior to physical functioning, pain and lifestyle outcomes compared to usual care, but are likely to be cost-effective.


[Runa soncco: Manuel Núñez Butron and his health education project].
Runa soncco, a Quechua term for "Indian heart", is the title of a magazine published between 1935 and 1948, which articles reveal the intention to integrate the Andean culture with Western public health on-site. It also turned into a key tool for the dissemination of the sanitation and education message and the indigenous movement led by Dr. Manuel Núñez Butrón, one of the first experiences in promotional preventive care in Peru and in the world - a pioneer of what four decades later would be called "primary health care".


A prospective follow-up study of panretinal photocoagulation in preventing neovascular glaucoma following ischaemic central retinal vein occlusion.
Fifteen consecutive eyes with central retinal vein occlusion (CRVO) and extensive capillary non-perfusion were treated by panretinal photocoagulation using argon laser. Of these eyes six had chronic glaucoma and one had acute angle-closure glaucoma when first seen. One developed neovascular glaucoma before treatment. After photocoagulation iris new vessels appeared in two eyes with pre-existing glaucoma. In one case the new vessels later regressed without further treatment. The prevalence of neovascular glaucoma was considerably less than has been reported in untreated eyes with ischaemic-type CRVO. Poor dilatation of the pupil due to pre-existing glaucoma, cataract and/or massive retinal oedema put a limit on the extent of treatment.


Cocaine acutely increases rat myometrial contractile activity by mechanisms other than potentiation of adrenergic pathways.
We hypothesized that cocaine acutely increases contractile activity in isolated rat myometrium and that this effect is solely caused by potentiation of adrenergic pathways. Isometric contractions were measured in myometrium isolated from virgin and day-18 pregnant Sprague-Dawley rats. Frequency, duration, amplitude, and integrated area were compared before and after the addition of cocaine (10(-6) to 10(-4) mol/L) by means of analysis of variance and Duncan's multiple-range test. The effects of alpha-adrenergic receptor antagonists (prazosin 10(-6) mol/L and yohimbine 10(-6) mol/L) and beta-adrenergic receptor antagonist (DL-propranolol 2 x 10(-6) mol/L) were assessed. Contraction duration, expressed relative to control, increased acutely after cocaine (10(-5) mol/L) administration in pregnant (1.70 +/- 0.20) and nonpregnant (1.36 +/- 0.24) myometrium (mean +/- SE, p < 0.05), as did integrated area (pregnant 3.47 +/- 0.97, nonpregnant 2.48 +/- 0.66) (mean +/- SE, p < 0.05). These effects were not completely inhibited by adrenergic blockade. Cocaine acutely increases the duration and integrated area of spontaneous contractions in isolated rat myometrium by mechanisms not completely explained by inhibition of catecholamine reuptake and potentiation of adrenergic pathways.


A new phenolic glycoside from Spiraea prunifolia var. simpliciflora twigs.
The phytochemical investigation of the methanol extract from the twigs of Spiraea prunifolia var. simpliciflora (Rosaceae) using column chromatography led to the isolation of a new phenol glycoside, 1-O-(E)-caffeoyl-2-O-p-(E)-coumaroyl-β-D-glucopyranose (1), together with 16 known phenolic compounds (2-17). The structure of this new compound was elucidated by analysis of spectroscopic data including 1D, 2D nuclear magnetic resonance and HR-FAB-MS data. The isolated compounds were tested for cytotoxicity against four human tumor cell lines in vitro using the sulforhodamine B bioassay.


Growth properties and hydrogen yield in green microalga Parachlorella kessleri: Effects of low-intensity electromagnetic irradiation at the frequencies of 51.8 GHz and 53.0 GHz.
The current research reports the effects of low-intensity extremely high frequency electromagnetic irradiation (EMI) of 51.8 GHz and 53.0 GHz on green microalga Parachlorella kessleri RA-002 isolated in Armenia. EMI demonstrated different effects on the growth properties of microalgae under various conditions. Under aerobic conditions a positive effect of EMI on the growth rate of P. kessleri and the content of photosynthetic pigments were observed. The data obtained indicates a significant role of O2, since the enhancing effect of EMI was determined only under aerobic conditions. Meanwhile under anaerobic conditions EMI with both frequencies caused inhibition of algal growth and a decrease in the amount of photosynthetic pigments. EMI also inhibited the yield of H2 production in P. kessleri, which was partially restored after 5-day cultivation due to the existence of protective mechanisms in this alga. The results might indicate membrane-bound mechanisms of EMI action on algae, which can be associated with the effects on photosynthetic pigments and membrane-associated enzymes responsible for H2 production. The results are useful for the development of algae biotechnology and the possibility of using EMI as a factor which regulates the production of biomass and biohydrogen by green microalgae.


Infection surveillance in cardiac transplantation.
Infections are a major cause of morbidity and mortality in cardiac transplantation. There is little information describing screening and prospective surveillance of heart recipients. We describe a surveillance program that was used for 35 patients, which screens and follows recipients through serologic, virologic, and immunologic parameters. Pretransplantation surveillance identified four (11.4%) patients whose skin tests with purified protein derivative (PPD) were positive, one patient with giardiasis, and seven (20%) recipients who were susceptible to cytomegalovirus (CMV). Twelve (34.3%) patients had CMV infections, only one of which was primary and involved a seropositive donor. The low rate of primary infection (14%) may result from our use of CMV-negative blood products. Seven (20%) recipients who were seronegative for toxoplasmosis received seropositive hearts, and disseminated toxoplasmosis developed in one of them. Eight (22.8%) patients had asymptomatic significant increases in Epstein-Barr virus antibody titers, without evidence of lymphoma. Fifteen (42.8%) recipients had at least one herpes simplex virus reactivation. Preventive, diagnostic, and early therapeutic interventions should occur as a result of infection surveillance, thus leading to a reduced risk of infection during the period after cardiac transplantation.


Modes and impact of coercive inpatient treatment for drug-related conditions in Switzerland.
Two forms of institutionalized pressure to treatment can be distinguished in Switzerland: civil commitment and court referral. In court referral, the referred patient has the right to refuse treatment. To compare court referrals for inpatient treatment to voluntary therapy. Comparison of interviews at treatment entry and discharge records. There were few systematic differences at entry except for voluntary subjects having had less contact with the legal system before treatment, independently of the specific court referral. At discharge, voluntary patients had a better social integration and fewer legal problems. Legal problems waiting for court referrals at discharge may be a significant handicap for reintegration. Otherwise, voluntary patients and court referrals showed few systematic differences in inpatient treatment.


Intracellular delivery of nanoparticles of an antiasthmatic drug.
The aim of the investigation was to prepare and characterize wheat germ agglutinin(WGA)-conjugated poly(D: ,L-lactic-co-glycolic) acid nanoparticles encapsulating mometasone furoate (MF) as a model drug and assess changes in its fate in terms of cellular interactions. MF loaded nanoparticles were prepared using emulsion-solvent evaporation technique. WGA-conjugation was done by carbodiimide coupling method. The nanoparticles were characterized for size, zeta potential, entrapment efficiency and in-vitro drug release. The intracellular uptake of nanoparticles, drug cellular levels, and anti-proliferative activity studies of wheat germ agglutinin-conjugated and unconjugated nanoparticles were assessed on alveolar epithelial (A549) cells to establish cellular interactions. Prepared nanoparticles were spherical with 10-15 microg/mg of WGA conjugated on nanoparticles. The size of nanoparticles increased after conjugation and drug entrapment and zeta potential reduced from 78 +/- 5.5% to 60 +/- 2.5% and -15.3 +/- 1.9 to -2.59 +/- 2.1 mV respectively after conjugation. From the cellular drug concentration-time plot, AUC was found to be 0.4745, 0.6791 and 1.24 for MF, MF-nanoparticles and wheat germ agglutinin-MF-nanoparticles respectively. The in-vitro antiproliferative activity was improved and prolonged significantly after wheat germ agglutinin-conjugation. The results conclusively demonstrate improved availability and efficacy of antiasthmatic drug in alveolar epithelial cell lines. Hence, a drug once formulated as mucoadhesive nanoparticles and incorporated in dry powder inhaler formulation may be used for targeting any segment of lungs for more improved therapeutic response in other lung disorders as well.


Interleukin-7 and interleukin-15 as prognostic biomarkers in sepsis and septic shock: Correlation with inflammatory markers and mortality.
Sepsis is a life-threatening organ dysfunction caused by a dysregulated host response to infection and a syndrome shaped by pathogen and host factors evolving over time. During sepsis, the absolute number of lymphocytes decreases. CD4+ and CD8+ T cells, B cells, and NK cells are reduced. Lymphocytes are an essential element of the body's defence against pathogens. Interleukin 7 has strong anti-apoptotic properties and induces the proliferation of CD4+ and CD8+ T lymphocytes. IL-15 prompts the generation of mature NK cells in the bone marrow, plays an important role in the generation, cytotoxicity, and survival of CD8+ T lymphocytes, and is essential for the survival of natural killer T (NKT) and intestinal intraepithelial lymphocytes (IELs). The study highlights the importance of monitoring IL-7 levels in patients with sepsis and septic shock, as low levels of this cytokine were associated with an increased risk of mortality. Physicians should consider using IL-7 levels as a biomarker to identify patients who are at higher risk of mortality and may require more aggressive treatment.


Application of dynamic laser scattering to the quality control of injectable drugs: polymer formation in ampicillin solution.
To assess the usefulness of dynamic laser scattering for monitoring the stability of ampicillin after reconstitution from commercially available vials with respect to the polymer formation and potency. Polymer formation and the remaining potency of the reconstituted ampicillin solution were estimated using dynamic laser scattering and high-performance liquid chromatography. The laser light-scattering submicron particle analyser was sufficiently sensitive for detecting both monomer and polymer aggregates with the average diameter of 1.1 +/- 0.2 and 7.3 +/- 1.7 nm, respectively, in the ampicillin solution. Polymer formation was dependent on both the storage temperature and the storage period, but it was detected, even when no precipitates were visible and when loss of potency was less than 10% of the initial value following storage at 4 or -15 degrees C. Submicron particle analysis using scanning electron microscopy, when used in combination with high-performance liquid chromatography, provides a useful method for studying polymer formation in antibiotic solutions and for the quality control of antibiotic injections during storage.


IgG and FcγR genotypes and humoral immunity to mucin 1 in prostate cancer.
Immunoglobulin GM and KM allotypes-hereditary antigenic determinants of γ and κ chains, respectively-and Fcγ receptor IIa (FcγRIIa) and FcγRIIIa genes are associated with the immunobiology of several malignant diseases, but their role in humoral immunity to the tumor-associated antigen mucin 1 (MUC1) in prostate cancer has not been examined. This investigation aimed to determine whether these genes-individually or in particular epistatic combinations-contribute to the inter-individual variability in the magnitude of antibody responsiveness to MUC1 in patients with prostate cancer. We genotyped DNA from 127 Caucasian American (CA) and 76 African American (AA) patients with histologically verified adenocarcinoma of the prostate for several GM, KM, FcγRIIa, and FcγRIIIa alleles by molecular methods. We also quantitated antibodies to MUC1 in the plasma from these patients by ELISA. In CA patients, homozygosity for the valine allele at the FcγRIIIa locus was significantly associated with low antibody responsiveness to MUC1 (p=0.029). In AA patients, the KM 1/3 heterozygotes had significantly higher anti-MUC1 antibody levels than 1/1 and 3/3 homozygotes (p=0.044). These results, the first to implicate FcγRIIIa and KM loci in humoral immunity to MUC1 in prostate cancer, might be relevant to MUC1-based immunotherapy of this malignancy.


Success of ChatGPT, an AI language model, in taking the French language version of the European Board of Ophthalmology examination: A novel approach to medical knowledge assessment.
The purpose of this study was to evaluate the performance of ChatGPT, a cutting-edge artificial intelligence (AI) language model developed by OpenAI, in successfully completing the French language version of the European Board of Ophthalmology (EBO) examination and to assess its potential role in medical education and knowledge assessment. ChatGPT, based on the GPT-4 architecture, was exposed to a series of EBO examination questions in French, covering various aspects of ophthalmology. The AI's performance was evaluated by comparing its responses with the correct answers provided by ophthalmology experts. Additionally, the study assessed the time taken by ChatGPT to answer each question as a measure of efficiency. ChatGPT achieved a 91% success rate on the EBO examination, demonstrating a high level of competency in ophthalmology knowledge and application. The AI provided correct answers across all question categories, indicating a strong understanding of basic sciences, clinical knowledge, and clinical management. The AI model also answered the questions rapidly, taking only a fraction of the time needed by human test-takers. ChatGPT's performance on the French language version of the EBO examination demonstrates its potential to be a valuable tool in medical education and knowledge assessment. Further research is needed to explore optimal ways to implement AI language models in medical education and to address the associated ethical and practical concerns.


Surgery vs radiation for localized prostate cancer.
With the increased incidence of prostate cancer, decisions regarding its treatment are now both complex and frequent. Accurate staging is crucial. Then appropriate treatment can be decided on, using nondogmatic common sense.


Cover Crop Yield, Nutrient Storage and Release under Different Cropping Technologies in the Sustainable Agrosystems.
Due to short post-harvest seasons, it is not always possible to grow worthy cover crops (CCs). This research aims to clarify the impact of undersown red clover (Trifolium pratense L., RC) and post-sown white mustard (Sinapis alba L., WM) management on their biomass, accumulated nitrogen (N), phosphorus (P), and potassium (K) content and the nutrient release to subsequent main crops. During the study period, RC mass yields varied from 220 to 6590 kg ha-1 DM and those of WM from 210 to 5119 kg ha-1 DM. WM shoot biomass increased with the increase in rainfall in August and the average daily temperature of the post-harvest period. CC productivity and efficiency were higher when growing short-season spring barley than winter wheat. In the warm and rainy post-harvest period, undersown WM after winter wheat increased the biomass by 34.1% compared to post-harvest sowing. The application of straw (+N) increased the accumulation of nutrients in WM biomass. The intensive fertilization of the main crop had a negative effect on RC yield and NPK accumulation. RC shoot biomass was characterized by a higher N content and WM by a higher P concentration. Well-developed CCs could reduce soil mineral nitrogen content by 28.5-58.8% compared to a plot without CCs. Nutrient transfer to spring barley was dependent on the N content of CC biomass and the carbon and nitrogen ratio (C:N < 20). We conclude that CC growth and efficiency were enhanced by the investigated measures, and in interaction with meteorological conditions.


Interrater variability of EEG interpretation in comatose cardiac arrest patients.
EEG is widely used to predict outcome in comatose cardiac arrest patients, but its value has been limited by lack of a uniform classification. We used the EEG terminology proposed by the American Clinical Neurophysiology Society (ACNS) to assess interrater variability in a cohort of cardiac arrest patients included in the Target Temperature Management trial. The main objective was to evaluate if malignant EEG-patterns could reliably be identified. Full-length EEGs from 103 comatose cardiac arrest patients were interpreted by four EEG-specialists with different nationalities who were blinded for patient outcome. Percent agreement and kappa (κ) for the categories in the ACNS EEG terminology and for prespecified malignant EEG-patterns were calculated. There was substantial interrater agreement (κ 0.71) for highly malignant patterns and moderate agreement (κ 0.42) for malignant patterns. Substantial agreement was found for malignant periodic or rhythmic patterns (κ 0.72) while agreement for identifying an unreactive EEG was fair (κ 0.26). The ACNS EEG terminology can be used to identify highly malignant EEG-patterns in post cardiac arrest patients in an international context with high reliability. The establishment of strict criteria with high transferability between interpreters will increase the usefulness of routine EEG to assess neurological prognosis after cardiac arrest.


Chemical Visualization of a GaN p-n junction by XPS.
We report on an operando XPS investigation of a GaN diode, by recording the Ga2p3/2 peak position under both forward and reverse bias. Areal maps of the peak positions under reverse bias are completely decoupled with respect to doped regions and allow a novel chemical visualization of the p-n junction in a 2-D fashion. Other electrical properties of the device, such as leakage current, resistivity of the domains are also tapped via recording line-scan spectra. Application of a triangular voltage excitation enables probing photoresponse of the device.


Effects of a one-year exercise training program in adults over 70 years old: a study with a control group.
Exercise training is known to improve exercise tolerance in elderly subjects. Therefore the present study aimed at investigating the effects of one year of combined endurance and resistance training in healthy older people. After baseline evaluation, subjects were assigned to either the training group (n=24, age 77.2+/-3.6) or the control group (n=16, age 76.1+/-4.8). Subjects in the control group did not change anything in their everyday activities, whereas subjects in the training group underwent moderately intensive combined exercise training, 3 hours a week over the course of one year. Breath-by-breath oxygen uptake and heart rate were measured at each workload during the symptom-limited cardiopulmonary exercise test. Performance on the 6-minute (6-MWT) and 200-meter (200-MWT) walk tests was registered and maximal strength was measured on knee extensor and plantar flexor muscles. After training, oxygen uptake was significantly increased, both at the ventilatory threshold (+11.6%, p<0.01) and at the end of exercise (+14.8%, p<0.001). The distance walked in 6 min (+10%, p<0.001), the time required to cover 200 m (-7.3%, p<0.001) and the maximal muscle strength (+15.2% and +17.4% for knee extensors and plantar flexors respectively, p<0.05) also improved after training. All these parameters had not significantly changed in the control group after the one-year period. The results of the present study show that one year of combined exercise training is well-tolerated and improves aerobic capacity, performance on field tests and muscle strength in healthy subjects over 70 years old.


Quadruplex PCR for simultaneous detection of serotype, biotype, toxigenic potential, and central regulating factor of Vibrio cholerae.
A quadruplex PCR was developed for the simultaneous detection of genes specific for Vibrio cholerae O1 and/or O139 serogroup (wbe and/or wbf), cholera toxin A subunit (ctxA), toxin-coregulated pilus (tcpA), and central regulating protein ToxR (toxR) in a single tube reaction. This is a simple, rapid, and accurate approach for the detection of toxigenic V. cholerae O1 and/or O139 and can prevent the rapid spread of the disease by early detection.


CPAP-induced mania in bipolar disorder: a case report.
In this case report we present our clinical observations of two patients with bipolar disorder with comorbid obstructive sleep apnea (OSA) who were treated with continuous positive airway pressure (CPAP) for their sleep apnea. Bipolar disorder is a psychiatric disorder characterized by the presence of one or more episodes of mania and frequent episodes of depression. This disorder affects approximately 0.8% of the adult population, with estimates from community samples ranging between 0.4% and 1.6%. OSA syndrome is a severe sleep disorder with a prevalence of 2-4% in the general population, the risk of which is increased by obesity. The prevalence of OSA is expected to be high in bipolar disorder due to high comorbid obesity. It is expected that improvement in OSA in patients with bipolar disorder with CPAP will improve mood and other symptoms of bipolar disorder. However, there is a relative lack of data examining this aspect. In both cases of bipolar disorder, CPAP was started after a polysomnographic diagnosis of OSA and CPAP titration study indicating that most of the apneas/hypopneas were eliminated with a significant improvement in oxygen saturation. To our surprise, we noted that in both of these cases initiation of CPAP resulted in manic symptoms. Clinicians need to monitor patients with bipolar disorder closely for worsening of manic symptoms when they are started on CPAP for underlying OSA.


Potential for improvement in radiation therapy.
A successful strategy for improving the efficacy of radiation therapy has been to improve dose distribution, that is, reduce treatment volume toward target volume. This is so as the smaller treatment volume has permitted a higher dose to the target (hence a high tumor control probability) and a lesser volume of non-target tissues being irradiated (consequently a reduced frequency and severity of treatment related morbidity). There are in place several important means for further improvements in dose distributions. These include: (a) 3D graphic reconstruction of the affected part with definition of the position of the tumor vis-a-vis the adjacent normal structures; (b) explicit inclusion in the treatment plan of the uncertainty band around each isodose contour; (c) on-line contrast enhanced visual monitoring of the target tissue during the individual treatment session; (d) gating of treatment so as to reduce the impact of patient motion on the needed treatment volume; (e) use of computer control systems to execute the treatment; and (f) use of treatment methods which achieve a reduced treatment volume. In an examination for sites for which treatment volumes might be decreased by a substantial factor we have compared treatment volumes for radical surgical and radiation therapy. Results are presented for carcinomas of the cervix (Stage IB), breast (Stage II), floor of mouth (Stage II). We describe a system developed here for on-line visual monitoring of the tissues covered by the treatment field. Brief descriptions are given of results of low LET charged particle radiation therapy and of intraoperative electron beam therapy. Also, the program developed here to use computer graphic techniques to display tumor and normal structures and isodose countours with uncertainty bands around each contour is mentioned.


A further failure to replicate an effect of oral anesthesia on alcohol consumption by rats.
Oral anesthesia by lidocaine has been reported to increase alcohol consumption in food-restricted rats by a substantial degree. Described herein is a second unsuccessful attempt to replicate the finding.