Crystallographic and thermodynamic evidence of negative cooperativity of flavin and tryptophan binding in the flavin-dependent halogenases AbeH and BorH.
The flavin-dependent halogenase AbeH produces 5-chlorotryptophan in the biosynthetic pathway of the chlorinated bisindole alkaloid BE-54017. We report that in vitro, AbeH (assisted by the flavin reductase AbeF) can chlorinate and brominate tryptophan as well as other indole derivatives and substrates with phenyl and quinoline groups. We solved the X-ray crystal structures of AbeH alone and complexed with FAD, as well as crystal structures of the tryptophan-6-halogenase BorH alone, in complex with 6-chlorotryptophan, and in complex with FAD and tryptophan. Partitioning of FAD and tryptophan into different chains of BorH and failure to incorporate tryptophan into AbeH/FAD crystals suggested that flavin and tryptophan binding are negatively coupled in both proteins. ITC and fluorescence quenching experiments confirmed the ability of both AbeH and BorH to form binary complexes with FAD or tryptophan and the inability of tryptophan to bind to AbeH/FAD or BorH/FAD complexes. FAD could not bind to BorH/tryptophan complexes, but FAD appears to displace tryptophan from AbeH/tryptophan complexes in an endothermic entropically-driven process.


Hydrogen-bonding and pi-pi interactions in 2-amino-4,6-dimethylpyrimidinium salicylate.
In the crystal structure of the title compound, C6H10N3+.C7H5O3-, the asymmetric unit contains four crystallographically independent 2-amino-4,6-dimethylpyrimidinium and salicylate ions (Z = 8). In each of these, one of the pyrimidine N atoms is protonated, and the carboxylate group of the salicylate ion interacts with the pyrimidine group through a pair of N-H...O hydrogen bonds, forming an R2(2)(8) motif. The pyrimidine cations also form base pairs via a pair of N-H...N hydrogen bonds (involving the amino group and the unprotonated ring N atom), forming another R2(2)(8) motif. Three such R2(2)(8) motifs, fused together, constitute a closed cyclic aggregate, and the linking of these aggregates, arranged in consecutive layers, can be analysed in terms of off-face stacking interactions.


Afatinib in Treatment-Naive Patients With EGFR-Mutated Lung Adenocarcinoma With Brain Metastasis: A Case Series.
Tyrosine kinase inhibitors (TKIs) of epidermal growth factor receptor (EGFR) were previously the standard first-line treatments for lung cancers with activating EGFR mutations. The first-generation reversible EGFR TKIs, gefitinib and erlotinib, demonstrated substantial efficacy in the treatment of brain metastases from EGFR-mutated lung adenocarcinoma. However, the efficacy of afatinib, the second-generation irreversible EGFR TKI, as the first-line treatment in lung adenocarcinoma patients with brain metastasis has yet to be evaluated.Here, we report cases of 3 patients who received afatinib alone as the first-line treatment in combination with whole-brain radiotherapy or following surgical resection of brain metastases. All 3 patients had EGFR L858R mutation. The first patient had lung adenocarcinoma with brain metastasis and no neurologic symptoms. After consultation, she received afatinib as a first-line treatment. Chest computed tomography and brain magnetic resonance imaging (MRI) showed partial response. The second patient had lung adenocarcinoma accompanied with a metastatic brain lesion associated with seizures. This patient received whole-brain radiotherapy and afatinib treatment following brain MRI and subsequently showed significant regression of the brain metastasis. The third patient had strabismus of the right eye, and brain MRI showed a single tumor at the cerebellar pontine angle. This patient underwent surgical resection of the tumor followed by afatinib treatment. He refused adjuvant radiotherapy after surgery for brain metastasis. The brain MRI showed no recurrent brain metastasis, and the patient had relatively less neurologic deficiency.This series of 3 cases indicate that afatinib may be an appropriate first-line treatment alternative in patients having lung adenocarcinoma with EGFR mutations. Further retrospective analyses and prospective clinical trials are required to substantiate the efficacy of afatinib in the treatment of brain metastases of lung adenocarcinoma.


ABCMdb reloaded: updates on mutations in ATP binding cassette proteins.
ABC (ATP-Binding Cassette) proteins with altered function are responsible for numerous human diseases. To aid the selection of positions and amino acids for ABC structure/function studies we have generated a database, ABCMdb (Gyimesi et al. , ABCMdb: a database for the comparative analysis of protein mutations in ABC transporters, and a potential framework for a general application. Hum Mutat 2012; 33:1547-1556.), with interactive tools. The database has been populated with mentions of mutations extracted from full text papers, alignments and structural models. In the new version of the database we aimed to collect the effect of mutations from databases including ClinVar. Because of the low number of available data, even in the case of the widely studied disease-causing ABC proteins, we also included the possible effects of mutations based on SNAP2 and PROVEAN predictions. To aid the interpretation of variations in non-coding regions, the database was supplemented with related DNA level information. Our results emphasize the importance of in silico predictions because of the sparse information available on variants and suggest that mutations at analogous positions in homologous ABC proteins have a strong predictive power for the effects of mutations. Our improved ABCMdb advances the design of both experimental studies and meta-analyses in order to understand drug interactions of ABC proteins and the effects of mutations on functional expression. http://abcm2.hegelab.org.


Cetylpyridinium chloride treatment of ready-to-eat Polish sausages: effects on Listeria monocytogenes populations and quality attributes.
Ready-to-eat Polish sausages were inoculated with Listeria monocytogenes at either low (3 log(10) CFU/g) or high (7 log(10) CFU/g) levels, treated with a 1% cetylpyridinium chloride (CPC) spray (20 psi, 25 degrees C, 30-sec exposure), vacuum packaged, and stored for 42 days at 0 degrees C or 4 degrees C. Non-inoculated samples were similarly treated, packaged, and stored to determine effects on color, firmness, and naturally occurring bacterial populations such as aerobic plate counts (APC). At the low inoculation level, L. monocytogenes populations were reduced by 1 log(10) CFU/g immediately after CPC treatment, and populations on treated samples remained approximately 2 log(10) CFU/g lower than non-treated samples throughout the 42-day storage period. At the high inoculation level, L. monocytogenes populations were reduced by 3 log(10) CFU/g immediately after treatment and, after 42 days of storage, populations on treated samples were 4 log(10) CFU/g lower than non-treated samples. Regardless of storage temperature, APC populations of CPC-treated samples were 1-2 log(10) CFU/g lower than non-treated samples throughout storage. An APC of 6 log(10) CFU/g was observed by day 7 of storage for non-treated samples, although not until day 21 of storage for CPC-treated samples. For samples stored at 4 degrees C, no significant differences (p > 0.05) were observed for L*, a*, or b* color values of treated versus non-treated samples. At 0 degrees C, the effects of CPC treatment on a* values were statistically significant (p < or = 0.05), although minor. Non-treated samples were somewhat firmer than CPC-treated samples, primarily at the 0 degrees C storage temperature, although the observed differences were of a magnitude unlikely to impact perceived product quality. CPC treatment appears to be a viable post-processing decontamination technology for eliminating and/or inhibiting L. monocytogenes on RTE meats during refrigerated storage without detrimentally impacting color and texture.


Recurrent painful perianal subcutaneous angiomatoid fibrous histiocytoma: a case report and review of the literature.
Angiomatoid fibrous histiocytoma (AFH) is a rare, low-grade malignant soft-tissue tumor most commonly occurring in the extremities of children and young adults and has a low potential of local recurrence and metastasis. Here, we present a case of recurrent subcutaneous perianal AFH. After an initial diagnosis as a sebaceous cyst, we were able to use immunohistochemical findings to correctly identify the mass as an AFH. The patient was effectively treated after 3 surgical resections. This case emphasizes the need to correctly diagnose soft-tissue tumors using a variety of diagnostic modalities to ensure that the patient receives proper treatment.


Participation in Dissection Affects Student Performance on Gross Anatomy Practical and Written Examinations: Results of a Four-Year Comparative Study.
The role of human dissection in modern medical curricula has been a topic of intense debate. In part, this is because dissection can be time-consuming and curricular hours are being monitored more carefully. This has led some to question the efficacy and importance of dissection as a teaching method. While this topic has received considerable attention in the literature, the question of how dissection impacts learning has been difficult to evaluate in a real-world, high-stakes setting since participation in dissection is often one of many variables. In this study, this challenge was overcome due to a change in the curriculum of a Special Master Program (SMP) that permitted a comparison between two years of students that learned anatomy using prosection only and two years of students that participated in dissection laboratories. Since each class of SMP students took courses in the medical school, and the medical school anatomy curriculum was constant, medical student performance served as a control throughout the study period. Results demonstrate that SMP students who learned through prosection had lower performance on anatomy practical and written examinations compared to medical students. When the SMP program changed and students started participating in dissection, there were measurable improvements in both practical and written examinations. These findings provide evidence of dissection's role in learning and applying anatomy knowledge both within and outside the gross anatomy laboratory.


MicroRNA‑601 serves as a potential tumor suppressor in hepatocellular carcinoma by directly targeting PIK3R3.
Recently, microRNAs (miRNAs) have been acknowledged as important regulators of hepatocarcinogenesis and tumor progression. Therefore, identifying the underlying molecular mechanisms of miRNAs in the occurrence and development of hepatocellular carcinoma (HCC) may be important for understanding the pathogenesis of HCC and aid the identification of potential therapeutic strategies. In the present study, miRNA (miR)‑601 was significantly downregulated in HCC tissues and cell lines; low miR‑601 expression was strongly associated with tumor, node and metastasis staging and lymph node metastasis of patients with HCC. In addition, the overexpression of miR‑601 expression significantly inhibited the proliferation and invasion of HCC cells. Regarding the underlying mechanism, phosphoinositide‑3‑kinase regulatory subunit 3 (PIK3R3) was predicted to be a direct target of miR‑601 in HCC cells. Furthermore, restoration of PIK3R3 expression in these cells counteracted the inhibitory effects of miR‑601 on cell proliferation and invasion in HCC. Notably, miR‑601 overexpression inhibited the protein kinase B (AKT)/mammalian target of rapamycin (mTOR) signaling pathway in HCC via the regulation of PIK3R3. Collectively, these results demonstrated that miR‑601 may inhibit the progression of HCC by directly targeting PIK3R3 and regulating the AKT/mTOR signaling pathway. Therefore, miR‑601 may be an effective therapeutic target for the treatment of patients with HCC.


Physical human locomotion prediction using manifold regularization.
Human locomotion is an imperative topic to be conversed among researchers. Predicting the human motion using multiple techniques and algorithms has always been a motivating subject matter. For this, different methods have shown the ability of recognizing simple motion patterns. However, predicting the dynamics for complex locomotion patterns is still immature. Therefore, this article proposes unique methods including the calibration-based filter algorithm and kinematic-static patterns identification for predicting those complex activities from fused signals. Different types of signals are extracted from benchmarked datasets and pre-processed using a novel calibration-based filter for inertial signals along with a Bessel filter for physiological signals. Next, sliding overlapped windows are utilized to get motion patterns defined over time. Then, polynomial probability distribution is suggested to decide the motion patterns natures. For features extraction based kinematic-static patterns, time and probability domain features are extracted over physical action dataset (PAD) and growing old together validation (GOTOV) dataset. Further, the features are optimized using quadratic discriminant analysis and orthogonal fuzzy neighborhood discriminant analysis techniques. Manifold regularization algorithms have also been applied to assess the performance of proposed prediction system. For the physical action dataset, we achieved an accuracy rate of 82.50% for patterned signals. While, the GOTOV dataset, we achieved an accuracy rate of 81.90%. As a result, the proposed system outdid when compared to the other state-of-the-art models in literature.


A Chlorine-Free Electrolyte Based on Non-nucleophilic Magnesium Bis(diisopropyl)amide and Ionic Liquid for Rechargeable Magnesium Batteries.
The electrolyte based on magnesium bis(diisopropyl)amide (MBA), a low-cost and non-nucleophilic organic magnesium salt, is proposed to be an admirable alternative for rechargeable magnesium batteries but suffers from limited ionic conductivity and an inferior electrochemical window in the commonly used ether solvents. In this work, the 1-butyl-1-methylpiperidinium bis(trifluoromethyl sulfonyl)imide (PP14TFSI) ionic liquid as the cosolvent of tetrahydrofuran (THF) in chlorine-free MBA-based electrolytes has been first demonstrated to remarkably improve the ionic conductivity and broaden the oxidative stable potential (2.2 V vs Mg/Mg2+) on stainless steel. Reversible Mg electrochemical plating/stripping with a low overpotential below 200 mV and ca. 90% Coulombic efficiency are obtained. The current density of Mg plating/stripping is increased 238 times after the addition of PP14TFSI, where the mechanism of competitive coordination of TFSI- making an easier Mg plating/stripping is proposed theoretically. The MBA-2AlF3 electrolyte with a ratio-optimized THF/PP14TFSI cosolvent exhibits good compatibility with the Mo6S8 cathode. Furthermore, the Se@pPAN|Mg full cell exhibits an initial capacity of 447.8 mAh g-1 and as low as ∼0.66% capacity decay per cycle for more than 70 cycles at 0.2 C with the synergy of LiTFSI additives. The facile modification strategy of ionic liquid in the MBA-based electrolyte sheds inspiring light on exploring non-nucleophilic and chlorine-free electrolytes for practical rechargeable magnesium batteries.


Influence of polyelectrolyte coating conditions on capillary coating stability and separation efficiency in capillary electrophoresis.
Polyelectrolytes are widely used in capillary electrophoresis as coating agents of silica capillaries to prevent adsorption phenomena and improve the repeatability of peptide and protein analysis. A systematic study of the coating experimental conditions has been carried out to optimize coating stability and performance. The main experimental parameters studied were the type and concentration of polyelectrolytes used in several monolayer and multilayer coatings, the ionic strength of coating and stabilizing solutions, and the procedures used for coating and capillary storage. Electroosmotic flow magnitude, direction and repeatability were used to monitor coating stability. Coating ability to limit adsorption was investigated by monitoring variations of migration times, time-corrected peak areas and separation efficiency of test peptides. Capillary-to-capillary and batch-to-batch reproducibility was also studied. In addition, the separation performance of polyelectrolyte coatings were compared to those obtained with bare silica capillaries.


Hypoxia induces autophagy in human vascular endothelial cells in a hypoxia-inducible factor 1‑dependent manner.
Hypoxia has been widely implicated in numerous pathological conditions, including those associated with inflammation and tumorigenesis. A number of recent studies have implicated hypoxia in the control of microvascular damage, the basis for which is not fully understood. In the present study, it was identified that autophagy was induced in human umbilical vein endothelial cells (HUVECs) post treatment with hypoxia, and the induction of autophagy by hypoxia was enhanced by hypoxia‑inducible factor 1 (HIF‑1) gene overexpression and inhibited by HIF‑1 knockout. Furthermore, the autophagy induced by overexpression of HIF‑1 was associated with a reduction of HUVEC cell viability. Therefore, HIF‑1 reduced HUVEC cell viability by inducing autophagy. These findings provide evidence of an important link between hypoxia and microvascular damage associated with HIF‑1‑related autophagy.


Research progress on the correlation between platelet aggregation and tumor progression.
Platelets are generally considered as the main functional unit of the coagulation system. However, more and more studies have confirmed that platelets also have an important relationship with tumor progression. Tumor cells can utilize platelets to promote their own infiltration and hematogenous metastasis, and platelets are activated and aggregated in this process. Therefore, platelet aggregation may be a concomitant marker of tumor progression. This is of great significance for predicting tumor metastasis before timely treatments.


A diffusional alternative to the Marcus free energy gap law.
The results of the precise kinetic fitting of the highly exergonic electron transfer from excited perylene to tetracyanoethylene in acetonitrile were used to estimate the Stern-Volmer constant of perylene quenching by double channel electron transfer (to the ground and excited states of the radical ion pair). It appears that the Stern-Volmer constant is exactly the same as the diffusional height of the Rehm-Weller plateau, substituting the exergonic wing of the Marcus free energy gap law. Even the single channel transfer is shown to be fast enough that the quenching should be under true diffusional control at the highest available exergonicity.


Cholesterol Protects the Oxidized Lipid Bilayer from Water Injury: An All-Atom Molecular Dynamics Study.
In an effort to delineate how cholesterol protects membrane structure under oxidative stress conditions, we monitored the changes to the structure of lipid bilayers comprising 30 mol% cholesterol and an increasing concentration of Class B oxidized 1-palmitoyl-2-oleoylphosphatidylcholine (POPC) glycerophospholipids, namely, 1-palmitoyl-2-(9'-oxo-nonanoyl)-sn-glycero-3-phosphocholine (PoxnoPC), and 1-palmitoyl-2-azelaoyl-sn-glycero-3-phosphocholine (PazePC), using atomistic molecular dynamics simulations. Increasing the content of oxidized phospholipids (oxPLs) from 0 to 60 mol% oxPL resulted in a characteristic reduction in bilayer thickness and increase in area per lipid, thereby increasing the exposure of the membrane hydrophobic region to water. However, cholesterol was observed to help reduce water injury by moving into the bilayer core and forming more hydrogen bonds with the oxPLs. Cholesterol also resists altering its tilt angle, helping to maintain membrane integrity. Water that enters the 1-nm-thick core region remains part of the bulk water on either side of the bilayer, with relatively few water molecules able to traverse through the bilayer. In cholesterol-rich membranes, the bilayer does not form pores at concentrations of 60 mol% oxPL as was shown in previous simulations in the absence of cholesterol.


The role of nasendoscopy in the fabrication of a palatopharyngeal obturator - a case report.
Defects confined to the hard palate can be managed with relative ease because it is a static shelf creating oro- nasal separation. Since the soft palate is a dynamic separator between the oral and nasal cavities, defects involving the soft palate require careful consideration. Instrumental visualization methods can aid the fabrication of obturators in patients with such defects and prevent problems of under or over obturation. This case report presents the prosthodontic management of a patient with a Veau class II cleft palate using a palatopharyngeal obturator in order to re-establish normal functions of deglutition and speech. Nasendoscopy was used as an adjunctive procedure to assess velopharyngeal function with the prosthesis.


Signaling by Steroid Hormones in the 3D Nuclear Space.
Initial studies showed that ligand-activated hormone receptors act by binding to the proximal promoters of individual target genes. Genome-wide studies have now revealed that regulation of transcription by steroid hormones mainly depends on binding of the receptors to distal regulatory elements. Those distal elements, either enhancers or silencers, act on the regulation of target genes by chromatin looping to the gene promoters. In the nucleus, this level of chromatin folding is integrated within dynamic higher orders of genome structures, which are organized in a non-random fashion. Terminally differentiated cells exhibit a tissue-specific three-dimensional (3D) organization of the genome that favors or restrains the activity of transcription factors and modulates the function of steroid hormone receptors, which are transiently activated upon hormone exposure. Conversely, integration of the hormones signal may require modifications of the 3D organization to allow appropriate transcriptional outcomes. In this review, we summarize the main levels of organization of the genome, review how they can modulate the response to steroids in a cell specific manner and discuss the role of receptors in shaping and rewiring the structure in response to hormone. Taking into account the dynamics of 3D genome organization will contribute to a better understanding of the pleiotropic effects of steroid hormones in normal and cancer cells.


A qualitative review of instrumental activities of daily living in dementia: what's cooking?
The measurement of instrumental activities of daily living (IADL) is common in clinical practice and research into dementia. IADL are cognitively complex daily activities, such as cooking and doing finances. Their measurement is required for the diagnostic process of dementia, and also useful for the monitoring of disease progression. Since problems in IADL contribute to the disease burden of both patient and caregiver, it is a relevant outcome measure for disease-modifying and non-pharmacological interventions. Despite the widespread use of IADL instruments, an overview of its theoretical background, measurement methods, and potential sources of bias is lacking. In the current manuscript, we therefore aim to provide a selective overview of these topics.


Methamphetamine-induced apoptosis in a CNS-derived catecholaminergic cell line.
Methamphetamine (METH) causes neurotoxic damages to the dopaminergic system in mammals, but whether it exerts toxicity to dopamine cells in culture has not been fully explored. In order to develop an in vitro model of METH-induced dopamine neurotoxicity toward more systemical examination of the mechanism, we investigated METH toxicity in a clonal dopamine producing cell line (CATH.a). We show in the present study that METH produces a time- and dose-dependent increase in cell death via a process similar to apoptosis. The METH toxicity seems to be produced by oxidative stress, as it was attenuated by the antioxidant glutathione, and to involve dopamine because dopamine release and synthesis inhibitors attenuated the toxicity. This catecholaminergic cell line derived from the central nervous system may become a useful in vitro model to elucidate the mechanism underlying the METH-induced dopaminergic neuronal damage.


Investigation of cancer epidemiology and study of carcinogenic agents in the Shanghai Rubber Industry.
Preliminary studies on crude cancer incidences among workers from 89 factories in Shanghai revealed excessive risk of cancer for workers in certain workshops of rubber tire factories. Chronic in situ animal exposures showed that compounding and Banbury mills for mastication and mixing were origins of carcinogenic contaminants. Various chronic experiments indicated the carcinogenicity of PBNA in rats and mice, especially with regard to the lungs. The high concentration of PBNA in the atmosphere of the work area seemed to be related to the excessive incidence of lung cancer among the workers. Epidemiological investigation showed that there was an excessive number of cases of lung cancer in the workshop of rubber tire factories where compounding, mixing, and milling took place.


[Application of Preschool Auditory Processing Assessment Scale in children with attention deficit hyperactivity disorder].
To investigate the characteristics of auditory processing (AP) in preschool children with attention deficit hyperactivity disorder (ADHD) using Preschool Auditory Processing Assessment Scale (hereafter referred to as "auditory processing scale"). A total of 41 children with ADHD and 41 typically developing (TD) children were assessed using the auditory processing scale, SNAP-IV rating scale, and Conners' Kiddie Continuous Performance Test (K-CPT). The auditory processing scale score was compared between the TD and ADHD groups. The correlations of the score with SNAP-IV and K-CPT scores were assessed. Compared with the TD group, the ADHD group had significantly higher total score of the auditory processing scale and scores of all dimensions except visual attention (P<0.05). In the children with ADHD, the attention deficit dimension score of the SNAP-IV rating scale was positively correlated with the total score of the auditory processing scale (rs30=0.531, P<0.05; rs27=0.627, P<0.05) as well as the scores of its subdimensions, including auditory decoding (rs=0.628, P<0.05), auditory attention (rs=0.492, P<0.05), and communication (rs=0.399, P<0.05). The hyperactivity-impulsivity dimension score of the SNAP-IV rating scale was positively correlated with the hyperactivity-impulsivity dimension score of the auditory processing scale (rs=0.429, P<0.05). In the children with ADHD, the attention deficit dimension score of the K-CPT was positively correlated with the total score (rs30=0.574, P<0.05; rs27=0.485, P<0.05) and the hyperactivity-impulsivity dimension score (rs=0.602, P<0.05) of the auditory processing scale. Preschool children with ADHD have the risk of AP abnormalities, and the auditory processing scale should be used early for the screening and evaluation of AP abnormalities in children.


Recent progress in vertebrate limb morphogenesis.
Morphogenesis of vertebrate limb, specifically that of the chick wing, has been recognized as a suitable model to study the cellular and molecular mechanisms of pattern formation. The importance of cellular inductive phenomena and the relevance of the processes such as cell division and cell death in the above model are discussed. These studies have revealed the retinoic acid (RA) and retinols as convincing candidates for vertebrate morphogens. The recent discovery that the RA receptors belong to the steroid hormone receptor superfamily might indicate the universality of the RA morphogen and might enlighten the possible mode of its action. Identification and characterization of the 1d locus genes associated with the mouse limb morphogenesis and the possible involvement of the homeobox proteins in chick wing development have opened new prospects in understanding the molecular mechanisms of vertebrate morphogenesis.


Comparing depression diagnostic symptoms across younger and older adults.
Depression in later life has potential grave implications and contributes to heavy emotional, medical, and economic burdens. Therefore, it is not surprising that identifying depression and its symptoms in later life has remained a sustained concern for professionals who treat older patients. Despite this concern, the current diagnostic gold standard may not identify depression symptoms equally well in older and younger adults. The objective of this analysis is to determine whether older and younger adults with equivalent levels of latent depression are equally likely to endorse particular DSM diagnostic symptoms. We analyzed DSM depression data using Item Response Theory (IRT)-based differential item functioning analyses. The data came from 1808 older adults (age 65-98 years) and 3734 younger adults (age 18-34 years) who participated in the National Epidemiological Survey on Alcoholism and Related Conditions. The analyses confirmed our hypothesis. The DSM items identify depression differently in younger and older adults. Specifically, results showed that older adults were more likely to endorse somatic items and less likely to endorse cognitive and suicide items than their younger counterparts with equivalent levels of depression. These findings provide evidence that the DSM depression items work differently across age groups when controlling for latent depression. It is important to consider, however, that these findings are limited by the sampling methodology and the particular protocol implemented.


Risk Factors for Prevertebral Soft Tissue Swelling Following Single-Level Anterior Cervical Spine Surgery.
Anterior cervical spine surgery (ACSS) is a common surgical procedure used to treat cervical spinal degenerative diseases. One of the complications associated with ACSS is prevertebral soft tissue swelling (PSTS), which can result in airway obstruction, dysphagia, and other adverse outcomes. This study aims to investigate the correlation between various cervical sagittal parameters and PSTS following single-level ACSS, as well as to identify independent risk factors for PSTS. A retrospective study conducted at a single institution. The study population included all patients who underwent single-level ACSS between January 2014 and December 2022. Patients with a history of cervical spine surgery or trauma were excluded from the study. The presence and severity of PSTS was assessed by reviewing pre- and postoperative imaging studies. The potential risk factors for PSTS that were examined include patient age, sex, body mass index, tobacco use, comorbidities, serum albumin levels, operative time, implant type, implanted level, and various cervical spine sagittal parameters. Multivariate linear regression analysis was performed to identify the independent risk factors for PSTS. A total of 62 consecutive patients who underwent single-level ACSS over a 8-year period at a single institution were enrolled in this study. Only preoperative segmental angle showed positive correlation with PSTS among various cervical spine sagittal parameters (r=0.36, p=0.005). Artificial disc replacement showed a negative correlation with PSTS (β=-0.38, p=0.002), whereas the use of demineralized bone matrix (DBM) had a positive impact on PSTS (β=0.33, p=0.009). We found that male sex, lower preoperative serum albumin, and implantation of upper cervical level (above C5) were independent predictors for PSTS after single-level ACSS (β=1.21; 95% confidence interval [CI], 0.27 to 2.15; p=0.012; β=-1.63; 95% CI, -2.91 to -0.34; p=0.014; β=1.44; 95% CI, 0.38 to 2.49; p=0.008, respectively). Our study identified male sex, lower preoperative serum albumin levels, and upper cervical level involvement as independent risk factors for PSTS after single-level ACSS. These findings can help clinicians monitor high-risk patients and take preventive measures to reduce complications. Further research with larger sample sizes and prospective designs is needed to validate these findings.


Social implications of behavioral interventions for persons with mental retardation.
The influence of type of behavioral program and program outcome on university students' perceptions of a hypothetical 17-year-old boy with mental retardation who exhibited severe self-injury was examined. A positive program was viewed as more acceptable and effective than were other programs (extremely aversive, mildly aversive, positive combined with extremely aversive, and control). Successful programs were also judged more acceptable and effective than were unsuccessful ones. When a program succeeded the individual was also seen as more likable, competent, adjusted, capable of learning, responsible, and problem-free. These preliminary findings point to the merits of considering the individual's social image in evaluating treatment acceptability.


Oral health policy and programmatic implications: lessons from ICS-II.
The conceptual model used in the ICS-II USA Ethnicity and Aging project helps to identify who among the elderly should be targeted for oral health promotion initiatives and the kinds of initiatives most likely to promote positive oral health outcomes. Outcomes have been measured in this study as perceived by the individual and as clinically assessed by the oral epidemiologists. For policy purposes, achieving both types of outcomes is important. A typology of oral health promotion priorities is used to rank the diverse racial-ethnic groups. In the analysis, groups with both low perceived and low evaluated oral health status receive highest priority. By these criteria, the older Native American populations have the highest priority, followed, in order, by Hispanics, African-Americans, and non-Hispanic Whites. Policy implications of the empirical analyses presented in earlier articles are discussed by use of the conceptual model and the typology of oral health promotion priorities. Having a usual source of care and/or regular dental visits appears to be a promising avenue for the promotion of better-perceived oral health status among most older ethnic groups. Improved oral hygiene practices, as represented by both regular toothbrushing and dental floss use, promote better clinically evaluated oral health status among many older ethnic groups.


Dynamic associations among alcohol use and anxiety symptoms in early adolescence.
The relationship between anxiety and alcohol use in adolescence remains unclear, with evidence for no association and for risk and protective effects of anxiety. Considering developmental trajectories may be important for understanding the association between anxiety and alcohol use and may help clarify prior mixed findings. The present study examined trajectories of alcohol use, social anxiety symptoms, and general anxiety symptoms in early to middle adolescence through the use of univariate and parallel process growth models. Social anxiety and general anxiety symptoms declined, while alcohol use increased with age. Parallel process growth models suggested that less rapid declines in social anxiety and general anxiety symptoms were associated with more rapid escalation in alcohol use. These results suggest that young adolescents who do not show normative declines in social anxiety or general anxiety symptoms may be at risk for more rapid increases in alcohol use.


Direct observation of G-protein binding to the human delta-opioid receptor using plasmon-waveguide resonance spectroscopy.
Using a recently developed method (Salamon, Z., Macleod, H. A., and Tollin, G. (1997) Biophys. J. 73, 2791-2797), plasmon-waveguide resonance spectroscopy, we have been able, for the first time, to directly measure the binding between the human brain delta-opioid receptor (hDOR) and its G-protein effectors in real-time. We have found that the affinity of the G-proteins toward the receptor is highly dependent on the nature of the ligand pre-bound to the receptor. The highest affinity was observed when the receptor was bound to an agonist ( approximately 10 nm); the lowest when receptor was bound to an antagonist ( approximately 500 nm); and no binding at all was observed when the receptor was bound to an inverse agonist. We also have found direct evidence for the existence of an additional G-protein binding conformational state that corresponds to the unliganded receptor, which has a G-protein binding affinity of approximately 60 nm. Furthermore, GTP binding to the receptor.G-protein complex was only observed when the agonist was pre-bound. Similar studies were carried out using the individual G-protein subtypes for both the agonist and the unliganded receptor. Significant selectivity toward the different G-protein subtypes was observed. Thus, the unliganded receptor had highest affinity toward the Galphao (Kd approximately 20 nm) and lowest affinity toward the Galphai2 ( approximately 590 nm) subtypes, whereas the agonist-bound state had highest affinity for the Galphao and Galphai2 subtypes (Kd approximately 9 nm and approximately 7 nm, respectively). GTP binding was also highly selective, both with respect to ligand and G-protein subtype. We believe that this methodology provides a powerful new way of investigating transmembrane signaling.


Genetic diversity in Italian Lactobacillus sanfranciscensis strains assessed by multilocus sequence typing and pulsed-field gel electrophoresis analyses.
Lactobacillus sanfranciscensis is a lactic acid bacterium that characterizes the sourdough environment. The genetic differences of 24 strains isolated in different years from sourdoughs, mostly collected in Italy, were examined and compared by PFGE and multilocus sequence typing (MLST). The MLST scheme, based on the analysis of six housekeeping genes (gdh, gyrA, mapA, nox, pgmA and pta) was developed for this study. PFGE with the restriction enzyme ApaI proved to have higher discriminatory power, since it revealed 22 different pulsotypes, while 19 sequence types were recognized through MLST analysis. Notably, restriction profiles generated from three isolates collected from the same firm but in three consecutive years clustered in a single pulsotype and showed the same sequence type, emphasizing the fact that the main factors affecting the dominance of a strain are correlated with processing conditions and the manufacturing environment rather than the geographical area. All results indicated a limited recombination among genes and the presence of a clonal population in L. sanfranciscensis. The MLST scheme proposed in this work can be considered a useful tool for characterization of isolates and for in-depth examination of the strain diversity and evolution of this species.


HO‑1 alleviates cholesterol‑induced oxidative stress through activation of Nrf2/ERK and inhibition of PI3K/AKT pathways in endothelial cells.
Heme oxygenase‑1 (HO‑1), as an inducible and cytoprotective enzyme, has a protective effect against cellular oxidative stress. In the present study, cholesterol was used to induce lipid overload and increase reactive oxygen species (ROS), leading to oxidative stress in EA.hy926 cells. In the present study, western blotting and immunofluorescence analysis were used to detect the expression level of important molecules in the metabolism process of cholesterol. It was confirmed that cholesterol stimulation upregulated the expression of HO‑1 in a time‑dependent manner via the activation and translocation of nuclear factor erythroid 2‑related factor 2 (Nrf2), activation of the mitogen‑activated protein kinase (MAPK)/extracellular signal‑regulated kinase (ERK) signaling pathway and increasing intercellular Ca2+ ([Ca2+]i) concentration. The results showed that increasing the expression of HO‑1 decreased activation of the phosphoinositide 3‑kinase (PI3K)/AKT signaling pathway and inhibited the expression of c‑Myc. It was confirmed that cholesterol‑mediated oxidative damage in vascular endothelial cells induced an increase in the expression of HO‑1 via the activation of Nrf2 and the MAPK/ERK signaling pathway, and increasing the [Ca2+]i concentration. The overexpression of HO‑1 alleviated oxidative damage through inhibition of the PI3K/AKT signaling pathway and downregulation of the expression of c‑Myc.


Delta opioids reduce the neurotransmitter release probability by enhancing transient (KV4) K+-currents in corticostriatal synapses as evaluated by the paired pulse protocol.
Field recordings were used to determine the influence of delta-opioid receptor activation on corticostriatal synaptic transmission. Application of the selective delta-opioid receptor agonist, [Tyr-D-Pen-Gly-Phe-D-Pen]-enkephalin (DPDPE, 1 microM), decreased the amplitude of the field-excitatory synaptic potential and at the same time increased the paired pulse ratio (PPR) suggesting a presynaptic site of action. This response reversed rapidly when DPDPE was washed and blocked by 1 nM of the selective delta-receptor antagonist naltrindole. Neither omega-conotoxin GVIA (1 microM) nor omega-agatoxin TK (400 nM), blockers of N- and P/Q-type Ca2+-channels, respectively, nor TEA (1 mM), blocker of some classes of K+-channels, occluded the effects of DPDPE. Instead, 1 mM 4-AP or 400 microM Ba2+ occluded completely the effects of DPDPE. Therefore, the results suggest that the modulation by delta opioids at corticostriatal terminals is mediated by transient (KV4) K+-conductances.


Viruses and pemphigus: an intriguing never-ending story.
Virus infections and autoimmunity have long been linked. As to pemphigus, many studies have been directed to prove or rule out the possibility of viral induction. Herpesviruses have often been related to the onset or reactivation of pemphigus. The association may be (i) casual, (ii) due to the iatrogenic immunosuppression facilitating opportunistic viral infections or (iii) based on a pathogenic link between the viral presence and the host's dysregulated immune response leading to autoimmunity. Japanese researchers, using real-time polymerase chain reaction, lately detected herpes simplex virus DNA in the saliva from pemphigus patients at the earliest stage of the disease and with no signs or history of herpetic infection, thus confirming the possible existence of cases of pemphigus induced by herpesviruses. These selected cases could be included into the innovative concept of 'paraviral eruptions', where an inciting role for induction may be played by the concomitant intake of certain drugs.


Cooperative Resonances in Light Scattering from Two-Dimensional Atomic Arrays.
We consider light scattering off a two-dimensional (2D) dipolar array and show how it can be tailored by properly choosing the lattice constant of the order of the incident wavelength. In particular, we demonstrate that such arrays can operate as a nearly perfect mirror for a wide range of incident angles and frequencies, and shape the emission pattern from an individual quantum emitter into a well-defined, collimated beam. These results can be understood in terms of the cooperative resonances of the surface modes supported by the 2D array. Experimental realizations are discussed, using ultracold arrays of trapped atoms and excitons in 2D semiconductor materials, as well as potential applications ranging from atomically thin metasurfaces to single photon nonlinear optics and nanomechanics.


New Insights into Butyrylcholinesterase Activity Assay: Serum Dilution Factor as a Crucial Parameter.
Butyrylcholinesterase (BChE) activity assay and inhibitor phenotyping can help to identify patients at risk of prolonged paralysis following the administration of neuromuscular blocking agents. The assay plays an important role in clinical chemistry as a good diagnostic marker for intoxication with pesticides and nerve agents. Furthermore, the assay is also commonly used for in vitro characterization of cholinesterases, their toxins and drugs. There is still lack of standardized procedure for measurement of BChE activity and many laboratories use different substrates at various concentrations. The purpose of this study was to validate the BChE activity assay to determine the best dilution of human serum and the most optimal concentration of substrates and inhibitors. Serum BChE activity was measured using modified Ellman's method applicable for a microplate reader. We present our experience and new insights into the protocol for high-throughput routine assays of human plasma cholinesterase activities adapted to a microplate reader. During our routine assays used for the determination of BChE activity, we have observed that serum dilution factor influences the results obtained. We show that a 400-fold dilution of serum and 5mM S-butyrylthiocholine iodide can be successfully used for the accurate measurement of BChE activity in human serum. We also discuss usage of various concentrations of dibucaine and fluoride in BChE phenotyping. This study indicates that some factors of such a multicomponent clinical material like serum can influence kinetic parameters of the BChE. The observed inhibitory effect is dependent on serum dilution factor used in the assay.


Integrated prediction of water pollution and risk assessment of water system connectivity based on dynamic model average and model selection criteria.
In recent years, with the rapid development of economy and society, river water environmental pollution incidents occur frequently, which seriously threaten the ecological health of the river and the safety of water supply. Water pollution prediction is an important basis for understanding development trends of the aquatic environment, preventing water pollution incidents and improving river water quality. However, due to the large uncertainty of hydrological, meteorological and water environment systems, it is challenging to accurately predict water environment quality using single model. In order to improve the accuracy and stability of water pollution prediction, this study proposed an integrated learning criterion that integrated dynamic model average and model selection (DMA-MS) and used this criterion to construct the integrated learning model for water pollution prediction. Finally, based on the prediction results of the integrated learning model, the connectivity risk of the connectivity project was evaluated. The results demonstrate that the integrated model based on the DMA-MS criterion effectively integrated the characteristics of a single model and could provide more accurate and stable predictions. The mean absolute percentage error (MAPE) of the integrated model was only 11.1%, which was 24.5%-45% lower than that of the single model. In addition, this study indicates that the nearest station was the most important factor affecting the performance of the prediction station, and managers should pay increased attention to the water environment of the control section that is close to their area. The results of the connectivity risk assessment indicate that although the water environment risks were not obvious, the connectivity project may still bring some risks to the crossed water system, especially in the non-flood season.


Timing, rates, and causes of death in a large South African tuberculosis programme.
Tuberculosis (TB) mortality remains high across sub-Saharan Africa despite integration of TB and HIV/ART programmes. To inform programme design and service delivery, we estimated mortality by time from starting TB treatment. Routinely collected data on TB treatment, vital status, and the timing and causes of death, were linked to cardio-respiratory autopsy data, from 1995-2008, from a cohort of male platinum miners in South Africa. Records were expanded into person-months at risk (pm). 4162 TB episodes were registered; 3170 men were treated for the first time and 833 men underwent retreatment. Overall, 509 men died, with a case fatality of 12.2% and mortality rate of 2.0/100 pm. Mortality was highest in the first month after starting TB treatment for first (2.3/100 pm) and retreatment episodes (4.8/100 pm). When stratified by HIV status, case fatality was higher in HIV positive men not on ART (first episode 14.0%; retreatment episode 26.2%) and those on ART (12.0%; 22.0%) than men of negative or unknown HIV status (2.6%; 3.6%). Mortality was also highest in the first month for each of these groups. Mortality risk factors included older age, previous TB, HIV, pulmonary TB, and diagnostic uncertainty. The proportion of deaths attributable to TB was consistently overestimated in clinical records versus cardio-respiratory autopsy. Programme mortality was highest in those with HIV and during the first month of TB treatment in all groups, and many deaths were not caused by TB. Resource allocation should prioritise TB prevention and accurate earlier diagnosis, recognise the role of HIV, and ensure effective clinical care in the early stages of TB treatment.


Tomato Wall-Associated Kinase SlWak1 Depends on Fls2/Fls3 to Promote Apoplastic Immune Responses to Pseudomonas syringae.
Wall-associated kinases (Waks) are important components of plant immunity against various pathogens, including the bacterium Pseudomonas syringae pv. tomato (Pst). However, the molecular mechanisms of their role(s) in plant immunity are largely unknown. In tomato (Solanum lycopersicum), wall-associated kinase 1 (SlWak1), has been implicated in pattern recognition receptor (PRR)-triggered immunity (PTI) because its transcript abundance increases significantly after treatment with the flagellin-derived, microbe-associated molecular patterns flg22 and flgII-28, which activate the PRRs Fls2 and Fls3, respectively. We generated two SlWak1 tomato mutants (Δwak1) using CRISPR/Cas9 gene editing technology and investigated the role of SlWak1 in tomato-Pst interactions. Late PTI responses activated in the apoplast by flg22 or flgII-28 were compromised in Δwak1 plants, but PTI at the leaf surface was unaffected. The Δwak1 plants developed fewer callose deposits than wild-type plants, but retained early PTI responses such as generation of reactive oxygen species and activation of mitogen-activated protein kinases upon exposure to flg22 and flgII-28. Induction of Wak1 gene expression by flg22 and flgII-28 was greatly reduced in a tomato mutant lacking Fls2 and Fls3, but induction of Fls3 gene expression by flgII-28 was unaffected in Δwak1 plants. After Pst inoculation, Δwak1 plants developed disease symptoms more slowly than Δfls2.1/2.2/3 mutant plants, although ultimately, both plants were similarly susceptible. SlWak1 coimmunoprecipitated with both Fls2 and Fls3, independently of flg22/flgII-28 or of BRASSINOSTEROID INSENSITIVE1-ASSOCIATED RECEPTOR KINASE1. These observations suggest that SlWak1 acts in a complex with Fls2/Fls3 and is important at later stages of PTI in the apoplast.


300-MHz-repetition-rate, all-fiber, femtosecond laser mode-locked by planar lightwave circuit-based saturable absorber.
We show the implementation of fiber-pigtailed, evanescent-field-interacting, single-walled carbon nanotube (CNT)-based saturable absorbers (SAs) using standard planar lightwave circuit (PLC) fabrication processes. The implemented PLC-CNT-SA device is employed to realize self-starting, high-repetition-rate, all-fiber ring oscillators at telecommunication wavelength. We demonstrate all-fiber Er ring lasers operating at 303-MHz (soliton regime) and 274-MHz (stretched-pulse regime) repetition-rates. The 303-MHz (274-MHz) laser centered at 1555 nm (1550 nm) provides 7.5 nm (19 nm) spectral bandwidth. After extra-cavity amplilfication, the amplified pulse train of the 303-MHz (274-MHz) laser delivers 209 fs (178 fs) pulses. To our knowledge, this corresponds to the highest repetition-rates achieved for femtosecond lasers employing evanescent-field-interacting SAs. The demonstrated SA fabrication method, which is based on well-established PLC processes, also shows a potential way for mass-producible and lower-cost waveguide-type SA devices suitable for all-fiber and waveguide lasers.


Management Protocols of the Hot Tooth-A KAP Survey among General Dentists and Endodontists.
Pain management is a cornerstone in the practice of endodontics. However, optimum pain control has been a challenge in cases of symptomatic irreversible pulpitis resulting in a "hot tooth." Thus, the objective of the study is to assess the knowledge and attitude and to determine the clinical protocols of "hot tooth" management followed among general practitioners and specialists. The KAP questionnaire contained 05 knowledge, 04 attitudes, and 06 practice-related items. The questionnaire was pretested among 10 randomly selected general dentists and endodontists. Testing-retesting was also performed. The questionnaire was self-administered and the acceptance to answer the questionnaire was considered consent to participate in the study. The sample size was calculated to be 200 with a 95% level of confidence. Descriptive statistics were used. For significance level, P < 0.05 was considered statistically significant. The Chi-square test was used for comparison between the endodontists and the general dentists. The anesthetic techniques that clinicians are most skilled in are infiltration and inferior alveolar nerve block (IANB) - 96.6% and 98.5% respectively. The intraosseous technique (IO) was the least preferred technique (6.8%). The most common supplementary injection used among both the BDS and MDS graduates was intrapulpal anesthesia. In cases of acute pulpitis, 54% of the respondents prescribed NSAIDs as a pre-anesthetic medication. The current study shows that supplemental injections like intraosseous and intraligamental techniques are underutilized. Also, the benefits of preanesthetic medication for hot tooth management are not harnessed among clinicians despite the sufficient body of evidence.


In situ quantitative analysis of etching process of human teeth by atomic force microscopy.
Etching is one of the most fundamental steps in the restoration of teeth by adhesion of composite resin in dental clinics. Atomic force microscope (AFM) was used for the in situ observation of the etching process of human enamel, dentin and synthetic hydroxyapatite in the three different acid agents, 2% phosphoric acid, 10% citric acid and 10% polyacrylic acid. To measure the absolute depth from the initial level before etching and to correlate the surface height between the changing AFM images obtained, the depth profiles were recorded with etching time by carrying out the line scan consecutively at the representative place of the observed area. These chronological series of depth profiles enabled us to perform quantitative analysis of etched amount in addition to the surface roughness obtained from relative depth profile within one image. The course of etching process from the dissolution of smear layer, appearance of enamel prizms or dentinal tubules to progress of demineralization could clearly be observed. The depth profile, surface roughness, etching amount, etching rate and smear layer thickness could then be evaluated. The different etching characteristics of three acid agents and the effect of surface roughness produced by different mechanical prepolish were compared and discussed.


Epidemic neuropathy in Cuba: a plea to end the United States economic embargo on a humanitarian basis.
During 1992-1993, an epidemic of neurologic disease in Cuba affected 50,862 patients with optic neuropathy, sensorineural deafness, predominantly sensory peripheral neuropathy, and dorsolateral myelopathy. The clinical syndromes were identical to those of prisoners of war subjected to nutritional restriction in tropical prison camps during World War II (Strachan's disease). A dietary deficiency of group B vitamins and sulfur-containing amino acids appears to have been the primary cause of the epidemic. This was a consequence of economic and political events in Cuba linked to the collapse of the Soviet Union and socialist countries. The recently toughened 30-year-old US economic embargo on Cuba contributed to these problems and hampered the investigation, treatment, and prevention of the epidemic. A plea is made to the neurologic community to request the lifting of the trade blockade on a humanitarian basis.


Non-invasive score system for fibrosis in chronic hepatitis: proposal for a model based on biochemical, FibroScan and ultrasound data.
We elaborate a non-invasive score system for liver fibrosis (NISF), exploring its diagnostic performance and comparing its accuracy to FibroScan in patients with chronic viral hepatitis (CH) and non-alcoholic fatty liver disease (NAFLD). Clinical, biochemical, elastographic and ultrasound parameters derived from patients with CH (n = 83) or NAFLD (n = 58), undergoing liver biopsy for fibrosis assessment, were prospectively collected as potential predictors of fibrosis. Each parameter was evaluated for its correlation with the liver biopsy (Gold Standard). Candidate predictors with good interobserver agreement and correlation with histological stages were combined into two algorithms (NISF) to predict fibrosis in chronic viral hepatitis and NAFLD. The CH-NISF included six parameters: bluntness of liver edges, irregularity of left lobe surface, diameter of segment 4, liver stiffness measurement, platelet count and ALT values. The ability of the model to discriminate F3-F4 vs F0-F1 stages and F2 vs F0-F1 was high (AUROC of 0.95 and 0.83 respectively) and better than FibroScan alone, especially in intermediate stages (F2 vs F0-F1), AUROC 0.83 vs 0.57 (P = 0.003). The resulting algorithm is available as mathematical formula, nomogram or free online link. [http://health.mafservizi.it/NISF_Calculator/liver.htm] The NAFLD-NISF included liver stiffness, platelet count and AST levels, had good ability to discriminate F0-F1 vs F2-F3-F4 stages (AUROC 0.86), however, not significantly higher than FibroScan. CH-NISF can be proposed as preliminary and easily available staging tool, superior to FibroScan alone in predicting histological fibrosis, especially in intermediate stages. Further validations are needed to improve NISF accuracy in NAFLD.


Customized Allogeneic Bone Augmentation Improves Esthetic Outcome in Anteromaxillary Dental Implantation.
In cases of severe atrophic maxilla or maxillary involution, augmentation is necessary for implant-supported prosthetics. Using bone grafts is a standard procedure, and using customized allogeneic bone blocks may be a predictable alternative before dental implantation. Clinical Findings. This case study shows the digital workflow, including a preimplantological augmentation by a customized allogeneic block, followed by soft tissue optimization and template-based dental implantation, after six months of healing. It is part of a three-year follow-up study on the resorption rate of allogeneic bone blocks. Outcomes. Allogeneic bone augmentation is an alternative treatment option to autologous bone grafts. It allows predictable advanced backward planning (ABP) even in the maxillary esthetic zone. Diameter-reduced implants show long-term stability of a minimum of three years after loading and excellent results of prosthetic fixtures. Prefabricated customized allogeneic blocks for augmentation may increase the fitting accuracy of the graft, decrease morbidity, and reduce the operation time in esthetic maxillary rehabilitation.


Discrete Solvent Reaction Field Calculations for One- and Two-Photon Absorptions of Solution-Phase Dimethylaminonitrostilbene Molecule.
Based on the configurations generated by molecular dynamics (MD) simulations using the on-the-fly density-functional tight-bonding (DFTB) force field, we investigated performance of the discrete solvent reaction field (DRF) model coupled to time-dependent density functional theory (TD-DFT) for solvatochromic effect of one- and two-photon absorption phenomena. Dimethylaminonitrostilbene (DANS) molecule solvated in chloroform, dichloromethane, and dimethyl sulfoxide solvents was selected as a model system for our research purpose. For every selected MD/DFTB configuration, within the context of the DRF, solute molecule is represented by TD-DFT and solvent molecules are described by atomic charges and polarizabilities. The calculated one-photon absorption energies reproduce well the positive solvatochromic behavior of solvated DANS and are in good agreement with available experimental data. For the two-photon absorption cross section, even though our approach overshot the experimental data by about 20% in absolute magnitude, experimentally observed solvatochromic change was captured qualitatively in this work. At last, we examined the contributions of atomic charges and polarizabilities of solvent molecules to the solvatochromic shifts of properties of interest.


Risk factors for anastomotic leakage after laparoscopic surgery for rectal cancer using a stapling technique.
This study evaluated the risk factors for anastomotic leakage after laparoscopic surgery for rectal cancer using a stapling technique. The total prospective registry of 111 patients with rectal cancer who initially underwent laparoscopic low anterior resection using a stapling technique was reviewed. Univariate and multivariate analyses were carried out to identify relevant risk factors. Overall anastomotic leakage rate was 5.4% (6/111). Univariate analysis demonstrated that body mass index (BMI) (P=0.0377) was significantly associated with anastomotic leakage. After univariate analysis, the variables of BMI and the size of the circular stapler (P=0.0923) were selected for multivariate analysis, as their P values were <0.2, and multivariate analysis demonstrated that BMI was independently predictive of developing anastomotic leakage (P=0.0458). Laparoscopic surgery for rectal cancer using a stapling technique can be performed safely without increasing the risk of anastomotic leakage, and increased BMI might be a potential risk factor for anastomotic leakage.


British and West African facial form in ideal occlusion.
True lateral cephalometric radiographs of 20 adult male British subjects and 20 Nigerian adult males were collected. All subjects showed an ideal occlusion of the teeth. These radiographs were analysed using a facial polygon joining the points Nasion, Sella, Articulare, Gonion and Menton. Additionally, measurements were made of the axial inclination of the incisor teeth and the distances from the incisal edges and apices of the teeth to the facial plane. Statistical examination of the results using "t" tests revealed that the average British mandible had a longer ramus but shorter body joined at a wider angle than the Negro, that the nasal part of the face was longer on average in the British group and that the incisor teeth, on average, projected further and were inclined further forward in the Nigerian group. A linear discriminant function in only three variables predicted with 100 per cent accuracy membership of the two groups. The three variables were the mandibular body length, the height of the nasal part of the face, and the amount by which the incisal edges of the lower incisor teeth projected beyond the facial plane.


Pediatric Liver Transplant For Hepatoblastoma: A Single-Center Experience.
Our aim was to analyze our experience with orthotopic liver transplant for hepatoblastoma patients. We performed a single-center retrospective analysis of 6 orthotopic liver transplant cases in children with hepatoblastoma from 2001 to March 2015. We evaluated patient demographic features, pretreatment extent of disease stage, type of transplant, change in serum alpha-fetoprotein levels, complications, and follow-up results. Orthotopic liver transplant was performed for pretreatment extent of disease stage III with a central location (n = 3) and pretreatment extent of disease stage IV (n = 3). All children underwent living-donor orthotopic liver transplant. Postoperative serum alpha-fetoprotein levels remained below 10 ng/mL during the follow-up period in 3 patients who were free of recurrences or metastases. Five patients were free of tumor recurrences at a median follow-up of 29.9 months. The limited number of cases we present without long-term follow-up of orthotopic liver transplant for unresectable hepatoblastoma seemed to show good clinical results.


Single-cell T cell receptor sequencing of paired tissue and blood samples reveals clonal expansion of CD8+ effector T cells in patients with calcific aortic valve disease.
Calcific aortic valve disease (CAVD) is a complex cardiovascular pathology, culminating in aortic stenosis, heart failure and premature mortality, with no comprehensive treatment strategy, except valve replacement. While T cells have been identified within the valve, their contribution to pathogenesis remains unclear. To elucidate the heterogenous phenotype of the immune populations present within patients with CAVD, deep phenotypic screens of paired valve and peripheral blood cells were conducted via flow cytometry (n=20) and immunohistochemistry (n=10). Following identification of a significant population of memory T cells; specifically, CD8+ T cells within the valve, single cell RNA sequencing and paired single T cell receptor sequencing was conducted on a further 4 patients on CD45+ CD3+, CD4+ or CD8+ T cells. Through unsupervised clustering, 7 T cell populations were identified within the blood and 10 identified within the valve. Tissue resident memory (T RM ) T cells were detected for the first time within the valve, exhibiting a highly cytotoxic, activated, and terminally differentiated phenotype. This pan-pro-inflammatory signal was differentially identified in T cells originating from the valve, and not observed in the blood, indicative of an adaptive, local not-systemic inflammatory signature in CAVD patients. T cell receptor analysis identified hyperexpanded clones within the CD8+ T cell central memory (T CM ) population, with T RM cells comprising the majority of large and medium clonal expansion within the entire T cell population. Clonal interaction network analysis demonstrated the greatest proportion of clones originating from CD8+ T cell effector memory (T EM ) and CD4+ naïve / T CM populations and ending in the CD8+ T RM and CD8+ T CM clusters, suggesting a clonal expansion and predicted trajectory of T cells towards a tissue resident, cytotoxic environment within the valve. CDR3 epitope predictive analysis identified 7 potential epitope targets, of which GALNT4 and CR1L have previously been implicated in a cardiovascular context as mediators of inflammation. Taken together, the data identified T cell sub-populations within the context of CAVD and further predicted possible epitopes responsible for the clonal expansion of the valvular T cells, which may be important for propagating inflammation in CAVD.


Biofilm formation on voice prostheses: in vitro influence of probiotics.
In order to determine the influence of probiotic bacteria on biofilm formation on Groningen and Provox 2 voice prostheses in an artificial throat, we grew biofilms on both types of voice prostheses and exposed them 3 times daily to a probiotic bacterial suspension. As a control, we perfused an artificial throat with phosphate-buffered saline solution. Perfusion with Lactococcus lactis 53 suspension reduced the percentage numbers of bacteria and yeasts, respectively, on the Groningen prostheses to 17% and 22% and on the Provox 2 prostheses to 19% and 45%, compared to the number of colony-forming units on the control prosthesis, which was set at 100%. A suspension of Streptococcus thermophilus B reduced the percentage numbers of bacteria and yeasts, respectively, on the Groningen prostheses to 53% and 33% and on the Provox 2 prostheses to 14% and 0%, as compared to the control prosthesis. All other probiotic strains tested caused some reduction in the percentages of bacteria or yeasts, but strong differences between the types of prostheses were observed. In conclusion, L. lactis 53 and S. thermophilus B strongly reduce the occurrence of yeasts and bacteria in voice prosthetic biofilms.


New indices for thyroid functional status, hormone binding, and peripheral hormone metabolism. Principal component analysis of 24,000 clinical data.
Principal component analysis of three thyroid function tests, thyroxine (T4), 3,5,3'-triiodothyronine (T3), and T3 uptake (T3U), was done using 24,000 data obtained from patients with a wide range of pathophysiologic conditions related to the thyroid. The three component scores were obtained as follows: Z1 = 2.62 square root T4 + 0.63 square root T3 + 3.18 square root T3U - 32.43; Z2 = 0.91 square root T4 + 0.24 square root T3 - 4.68 square root T3U + 20.14; and Z3 = 3.94 square root T4 + 0.95 square root T3 + 0.18 square root T3U - 1.53 (T4 micrograms/dL, T3 ng/dL, T3U%). The first component (Z1) represents an apparent axis to the direction of thyroid functional status. It provides a new metabolic index putting conventional free T4 and free T3 indices together. The second component (Z2) was found to be a sensitive indicator of abnormal hormone binding. It showed a close correlation with serum concentration of thyroxine-binding globulin. The third component (Z3) represents the degree of T3 predominance over T4. Computation of these scores will facilitate the diagnosis of atypical cases in which hyper-or hypothyroidism is complicated by abnormal peripheral hormone binding and/or metabolism.


A combined passive and active musculoskeletal model study to estimate L4-L5 load sharing.
A number of geometrically-detailed passive finite element (FE) models of the lumbar spine have been developed and validated under in vitro loading conditions. These models are devoid of muscles and thus cannot be directly used to simulate in vivo loading conditions acting on the lumbar joint structures or spinal implants. Gravity loads and muscle forces estimated by a trunk musculoskeletal (MS) model under twelve static activities were applied to a passive FE model of the L4-L5 segment to estimate load sharing among the joint structures (disc, ligaments, and facets) under simulated in vivo loading conditions. An equivalent follower (FL), that generates IDP equal to that generated by muscle forces, was computed in each task. Results indicated that under in vivo loading conditions, the passive FE model predicted intradiscal pressures (IDPs) that closely matched those measured under the simulated tasks (R2=0.98 and root-mean-squared-error, RMSE=0.18MPa). The calculated equivalent FL compared well with the resultant force of all muscle forces and gravity loads acting on the L4-L5 segment (R2=0.99 and RMSE=58N). Therefore, as an alternative approach to represent in vivo loading conditions in passive FE model studies, this FL can be estimated by available in-house or commercial MS models. In clinical applications and design of implants, commonly considered in vitro loading conditions on the passive FE models do not adequately represent the in vivo loading conditions under muscle exertions. Therefore, more realistic in vivo loading conditions should instead be used.


Prevalence and Comorbidities of Adult Attention-deficit/hyperactivity Disorder in a Community Sample from Korea.
: Attention-deficit/hyperactivity disorder (ADHD) is prevalent in adults, and psychiatric comorbidities are common in adults with ADHD. We aimed to examine the prevalence of adult ADHD with several common psychiatric conditions in a community sample in Korea and the association between adult ADHD and risk of psychiatric comorbidities. : This study used a cross-sectional survey design. We provided supplementary and optional self-report questionnaires, including the Korean version of the World Health Organization Adult ADHD Self-Report Scale (ASRS) short screening scale, Patient Health Questionnaire-9 for screening for depression, Alcohol Use Disorders Identification Test alcohol consumption questions, and the Korean version of the Mood Disorders Questionnaire, to Korean adults who visited one of six centers of a large private healthcare company for the National General Health Examination. : A total of 17,799 subjects included in this study, and 430 (2.4%) were positive on the ASRS screen. ADHD was significantly associated with the 19-30-year-old age group (odds ratio [OR] = 3.938), lower income (OR = 1.298), depression (OR = 11.563), and bipolar disorder (OR = 3.162). : Adult ADHD was highly associated with depression and bipolar disorder, suggesting that clinicians should carefully evaluate and treat such psychiatric disorders in adults with ADHD symptoms.


Genetic factors influencing age at onset in LRRK2-linked Parkinson disease.
Patients with Leucine-rich repeat kinase 2 (LRRK2) linked Parkinson's disease (PD) clinically present with typical idiopathic PD. However, LRRK2-linked PD displays a pleomorphic neuropathology and high variability in age at disease onset (AAO) which suggests that environmental and/or genetic factors other than the mutation itself influence the course of the disease. We investigated the modulation of AAO by genetic factors including the mutation-containing domain and PD associated polymorphisms in the gene coding alpha-synuclein (SNCA) and tau (MAPT) in 44 patients from 19 affected families. Using this limited number of available LRRK2 mutation carriers, we provide evidence that mutations in the kinase domain of Lrrk2 significantly decrease AAO compared to mutations in the ROC (Ras/GTPase of complex proteins) domain. Furthermore, polymorphic variations in MAPT show a significant association with AAO in individuals with LRRK2 mutations. Our results await replication in future studies with a larger number of LRRK2 mutation carriers, but indicate an association of mutation-affected protein domain and mutation-extrinsic genetic factors with AAO and suggest that these factors could contribute to explain the phenotypic heterogeneity observed in LRRK2-linked PD.


Demonstration of antigenic sites in glomeruli of patients with acute poststreptococcal glomerulonephritis by immunofluorescein and immunoferritin technics.
The presence and localization of antigenic sites in glomeruli of 14 patients with acute poststreptococcal glomerulonephritis (AGN) were studied by immunofluorescein and immunoferritin technics. Labeled IgG fractions from the same patients were used for the identification of antigenic sites. The staining capacity of these IgG fractions depended on the time when sera were obtained. Staining was minimal during the first week, and increased up to the fourth or fifth week. Glomeruli, however, stained only when renal tissue was obtained during the early phase of the disease. Precise localization of antigenic sites was determined with ferritin-conjugated patients' IgG. Segmental deposition of ferritin was observed in the mesangial matrix and on the endothelial side of the glomerular basement membrane. Subepithelial electron-dense deposits contained no or very few ferritin particles. In contrast, ferritin-conjugated antihuman IgG was distributed diffusely in the mesangial matrix, on the endothelial side of the basement membrane and in subepithelial deposits. These findings suggest that, during the early stage of acute poststreptococcal glomerulonephritis, free antigen is present in the glomeruli of patients with this disease.


Evaluation of the effect of granule size of raw tableting materials on critical quality attributes of tablets during the continuous tablet manufacturing process using near-infrared spectroscopy.
The effects of granule size of raw materials on tablet hardness (TH) and weight (TW) in the continuous tablet manufacturing process (CTMP) were investigated using near-infrared spectroscopy (NIRS). Granule materials of different sizes were prepared by extrusion granulation from a standard granule formula powder containing lactose/starch and 4.5% acetaminophen. Large-, small-, and medium-sized granules were sequentially filled in a hopper, and tablets were produced continuously using a single-shot tableting machine. After arranging approximately 500 tablets in order, the tablets were subjected to NIRS. A total of 450 NIRS datasets were divided into three groups of 150 each (calibration, validation 1, and validation 2 datasets). The best fitted calibration models for predicting TH and TW were obtained, with sufficient accuracy, based on NIRS using the partial least squares regression, and comprised both physical and chemical information. The regression and loading vectors of the calibration models suggested that the models used to predict TH and TW involve physical information based on geometrical factors of the tablet and chemical information related to binder-related intermolecular interactions. The changes in the predicted value profiles of TH and TW using NIRS reflected the changes in the measured values depending on the raw granule size during CTMP.


Mathermycin, a Lantibiotic from the Marine Actinomycete Marinactinospora thermotolerans SCSIO 00652.
Lantibiotics are antimicrobial peptides belonging to the family of ribosomally synthesized and posttranslationally modified peptides (RiPPs) and feature thioether linkages in their structures. In this study, we identified the biosynthetic gene cluster of a cinnamycin analog, named mathermycin, from Marinactinospora thermotolerans SCSIO 00652 and reconstituted its biosynthesis in Streptomyces lividans and Escherichia coli Key posttranslational modification enzymes of mathermycin were characterized. Mathermycin exhibited antimicrobial activity and therefore represents an example of cinnamycin-like lantibiotics from Marinactinospora species.IMPORTANCE The discovery of new antimicrobial compounds that can be used as potential drugs is in urgent need due to increasing bacterial resistance to current antibiotics. Lantibiotics are important antimicrobial compounds that have found applications in both the clinic setting and food industry. We report here the discovery of a new lantibiotic, mathermycin, from a marine-derived Marinactinospora thermotolerans strain and elucidation of its biosynthesis. We also demonstrate that mathermycin possesses antimicrobial activity toward a Bacillus strain.


Extraintestinal manifestations of inflammatory bowel disease.
Inflammatory bowel disease (IBD) is associated with a variety of extraintestinal manifestations (EIMs) that may produce greater morbidity than the underlying intestinal disease and may even be the initial presenting symptoms of the IBD. As many as 36% of patients with IBD have at least one EIM. Some are more common related to active colitis (joint, skin, ocular, and oral manifestations). Others are especially seen with small bowel dysfunction (cholelithiasis, nephrolithiasis, and obstructive uropathy), and some are nonspecific disorders (osteoporosis, hepatobiliary disease, and amyloidosis). Patients with perianal Crohn's disease are at higher risk for developing EIMs than other IBD patients. Also the presence of one EIM appears to confer a higher likelihood of developing other manifestations than would be expected by chance alone. The identified pathogenetic autoimmune mechanisms include genetic susceptibility antigenic display of autoantigen, aberrant self-recognition, and immunopathogenetic autoantibodies against organ-specific cellular antigen(s) shared by colon and extra-colonic organs. Microbes may play an important role, probably by molecular mimicry. Early recognition of these extraintestinal manifestations should help guide therapy that will reduce overall morbidity in affected patients. This paper reviews the diagnosis, therapy and management of the more common EIMs.


ADCYAP1R1 and asthma in Puerto Rican children.
Epigenetic and/or genetic variation in the gene encoding the receptor for adenylate-cyclase activating polypeptide 1 (ADCYAP1R1) has been linked to post-traumatic stress disorder in adults and anxiety in children. Psychosocial stress has been linked to asthma morbidity in Puerto Rican children. To examine whether epigenetic or genetic variation in ADCYAP1R1 is associated with childhood asthma in Puerto Ricans. We conducted a case-control study of 516 children ages 6-14 years living in San Juan, Puerto Rico. We assessed methylation at a CpG site in the promoter of ADCYAP1R1 (cg11218385) using a pyrosequencing assay in DNA from white blood cells. We tested whether cg11218385 methylation (range, 0.4-6.1%) is associated with asthma using logistic regression. We also examined whether exposure to violence (assessed by the Exposure to Violence [ETV] Scale in children 9 yr and older) is associated with cg11218385 methylation (using linear regression) or asthma (using logistic regression). Logistic regression was used to test for association between a single nucleotide polymorphism in ADCYAP1R1 (rs2267735) and asthma under an additive model. All multivariate models were adjusted for age, sex, household income, and principal components. EACH 1% increment in cg11218385 methylation was associated with increased odds of asthma (adjusted odds ratio, 1.3; 95% confidence interval, 1.0-1.6; P = 0.03). Among children 9 years and older, exposure to violence was associated with cg11218385 methylation. The C allele of single nucleotide polymorphism rs2267735 was significantly associated with increased odds of asthma (adjusted odds ratio, 1.3; 95% confidence interval, 1.02-1.67; P = 0.03). Epigenetic and genetic variants in ADCYAP1R1 are associated with asthma in Puerto Rican children.


Insulin-like growth factor binding proteins in human breast cancer cells: relationship to hIGFBP-2 and hIGFBP-3.
Human breast cancer cells (HBCC) secrete at least four different forms of IGFBPs. We have previously demonstrated that hIGFBP-1 is a minor component of IGFBPs secreted by Hs578T cells and is absent in CM from MCF-7 cells. In our present report, we describe the immunological and structural relationship of HBCC IGFBPs to hIGFBP-2 and hIGFBP-3. Analysis of conditioned media (CM) from Hs578T by Western ligand blotting revealed three IGFBPs of apparent Mr = 38K, 28K, and 24K; CM from MCF-7 revealed only two IGFBPs, of apparent Mr = 31K and 24K. Immunoprecipitation studies with polyclonal antibodies raised against hIGFBP-2 and hIGFBP-3 demonstrated that the 38K IGFBP in Hs578T CM is immunologically related to hIGFBP-3, while the 31K IGFBP in MCF-7 cells is related to the hIGFBP-2. Analysis by Northern blot demonstrated that MCF-7 cells contained mRNA for hIGFBP-2, while Hs578T cells contained the mRNA characteristic of the hIGFBP-3. The identity of the 24K IGFBP remains unknown, and may represent a distinct IGFBP. Of note, assay of CM following removal of BPs by acid chromatography demonstrated no detectable IGF-I or -II. The role of these IGFBPs in HBCC is of interest in view of the potential modulation of IGF actions by these proteins.


Medicinal plants for the treatment of neuropathic pain: A review of randomized controlled trials.
Neuropathic pain is a disabling condition caused by various diseases and can profoundly impact the quality of life. Unfortunately, current treatments often do not produce complete amelioration and can be associated with potential side effects. Recently, herbal drugs have garnered more attention as an alternative or a complementary treatment. In this article, we summarized the results of randomized clinical trials to evaluate the effects of various phytomedicines on neuropathic pain. In addition, we discussed their main bioactive components and potential mechanisms of action to provide a better view of the application of herbal drugs for treating neuropathic pain.


Flourishing Beyond Borders: Facilitating the Well-Being of Accompanying Expatriate Partners.
One of the leading causes for failing at expatriate assignments is the accompanying expatriate partners' (AEPs) unhappiness with life abroad or inability to adjust to the challenges of the host country. Strength-based therapeutic interventions have the potential to increase individuals' mental health and well-being. The current study formed part of a multimethod study consisting of three related but independent sub-studies. The first sub-study identified the strengths of Gratitude, Curiosity and Hope to be positively associated with AEPs' resilience and well-being. These results were used to construct a quantitative model that illustrates the interplay between these constructs. In the second sub-study, the proposed model was qualitatively reviewed by a smaller group of AEPs to inform and enrich our understanding of AEPs' personal experiences of these constructs. In the current study, a panel of practicing psychologists who provide counselling services for South African expatriates and AEPs were asked to qualitatively review a proposed quantitative model. A cross-sectional, interpretive descriptive research design, applying purposive sampling was used to identify and recruit participants. The objective for the current study was firstly to ascertain why participants thought strengths of Gratitude, Curiosity and Hope featured so prominently in the model. Secondly, the study aimed to determine how these participants would, from their experience in working with AEPs, enhance these strengths and AEPs' resilience in therapy, and ultimately facilitate greater well-being and successful adjustment abroad. Participants completed an online questionnaire consisting of two semi-structured, open-ended questions. The data were analyzed using primary and secondary cycle coding to ultimately develop themes. Results indicated that strengths of Curiosity, Gratitude and Hope featured prominently because these strengths include elements that form part of the process of expatriation. Participants were able to suggest practical strength-based therapeutic techniques which would assist in enhancement of strengths, resilience and ultimately well-being. It is proposed that the therapeutic techniques and approaches suggested in this study could contribute to the success rate of expatriate assignments.


Recently Approved and Under Investigation Drugs for Treating Patients with Heart Failure.
Heart Failure (HF) represents a leading cause of morbidity and mortality worldwide. Despite the recent advances in the treatment of this condition, patients´ prognosis remains unfavorable in most cases. Sacubitril/valsartan and ivabradine have been recently approved to improve clinical outcomes in patients with HF with reduced ejection fraction. Drugs under investigation for treating patients with HF encompass many novel mechanisms including vasoactive peptides, blocking inflammatory- mediators, natriuretic peptides, selective non-steroidal mineralocorticoid-receptor antagonists, myocardial β3 adrenoreceptor agonists, inhibiting the cytochrome C/cardiolipin peroxidase complex, neuregulin-1/ErbB signaling and inhibiting late inward sodium current. The aim of this manuscript is to review the main drugs under investigation for the treatment of patients with HF and give perspectives for their implementation into clinical practice.


Electrochemical detection of oligopeptides at silicon-fabricated micro-liquid/liquid interfaces.
The detection of peptides is an important bioanalytical challenge, as they are a generic class of potent molecules of biomedical and biopharmaceutical significance. In this work, the electrochemistry of seven oligopeptides at microscaled interfaces between two immiscible electrolyte solutions (microITIES) was investigated. Their transfer across the polarized interface was assisted by dibenzo-18-crown-6 (DB18C6). The ion transfer potentials of these oligopeptides were dependent on their hydrophobicities and their interaction with DB18C6. Micropore arrays, which were fabricated in silicon by a combination of wet and dry etch techniques, were used to enhance mass transfer and thus analytical sensitivities. The use of a gellified organic phase allowed the implementation of voltammetric stripping techniques at the liquid-organogel interface. The combination of interface miniaturization and stripping voltammetry provided limits of detection at submicromolar concentration levels. The sensitivities (calibration graph slopes) were -3205 nA microM(-1) cm(-2) for Phe-Phe, -1791 nA microM(-1) cm(-2) for Leu-Leu, -6014 nA microM(-1) cm(-2) for Lys-Lys, and -9611 nA microM(-1) cm(-2) for Lys-Lys-Lys. Mixtures of peptides were also investigated with this technique, illustrating the possibility to detect certain mixture combinations.


Mode-resolved frequency comb interferometry for high-accuracy long distance measurement.
Optical frequency combs have developed into powerful tools for distance metrology. In this paper we demonstrate absolute long distance measurement using a single femtosecond frequency comb laser as a multi-wavelength source. By applying a high-resolution spectrometer based on a virtually imaged phased array, the frequency comb modes are resolved spectrally to the level of an individual mode. Having the frequency comb stabilized against an atomic clock, thousands of accurately known wavelengths are available for interferometry. From the spectrally resolved output of a Michelson interferometer a distance is derived. The presented measurement method combines spectral interferometry, white light interferometry and multi-wavelength interferometry in a single scheme. Comparison with a fringe counting laser interferometer shows an agreement within <10(-8) for a distance of 50 m.


Intermittent Dieting: Theoretical Considerations for the Athlete.
Athletes utilise numerous strategies to reduce body weight or body fat prior to competition. The traditional approach requires continuous energy restriction (CER) for the entire weight loss phase (typically days to weeks). However, there is some suggestion that intermittent energy restriction (IER), which involves alternating periods of energy restriction with periods of greater energy intake (referred to as 'refeeds' or 'diet breaks') may result in superior weight loss outcomes than CER. This may be due to refeed periods causing transitory restoration of energy balance. Some studies indicate that intermittent periods of energy balance during energy restriction attenuate some of the adaptive responses that resist the continuation of weight and fat loss. While IER-like CER-is known to effectively reduce body fat in non-athletes, evidence for effectiveness of IER in athletic populations is lacking. This review provides theoretical considerations for successful body composition adjustment using IER, with discussion of how the limited existing evidence can be cautiously applied in athlete practice.


Dependency of resonance frequencies and effective coupling coefficients of piezoceramic rectangular bars and plates on aspect ratio.
The resonance frequencies and effective coupling coefficients of piezoceramic rectangular plates polarized through their width and transversely polarized bars are presented as functions of their lateral aspect ratios. The results are obtained by employing the coupled vibration analysis technique that was previously illustrated for rectangular plates polarized through the thickness [J. Acoust. Soc. Am. 126(6), 2983-2990 (2009)]. The results of calculations show good agreement with experimental data. Conclusions are made on preferable values of the aspect ratios in terms of the effective coupling coefficients.


Medial Sural Artery Perforator Flap for Leg and Knee Coverage: Extended Skin Paddle With 2 Perforators.
For soft-tissue defect coverage in the lower leg and around the knee joint, the gastrocnemius muscle flap is the most commonly used. Having constant anatomy, a long pedicle, and decreased donor site morbidity, the medial sural artery perforator (MSAP) flap may represent a good reconstructive alternative. The aim of this report was to present the experience of using a dual perforator MSAP pedicled flap. Nineteen patients underwent soft-tissue reconstruction by MSAP flap in the one third of the lower leg and around the knee joint. Eleven patients were injured in traffic accidents. Exposure of a knee prosthesis required flap coverage in 4 cases. The other defect etiologies were a gunshot wound, bone abscess due to a sickle cell anemia, bone exposure due to a full thickness burn, and sarcoma resection. Defect dimensions ranged from 7 × 5 cm to 15 × 8 cm. Seventeen flaps were harvested with 2 perforators. Donor sites were closed primary in 16 of the 19 cases. The sizes of the MSAP flaps ranged from 7 to 22 cm × 5 to 8 cm. The procedure was uneventful in 17 cases. The 2 unsuccessful flaps developed a distal necrosis, for which an excision with direct suture was made secondary. Complete healing was achieved in all cases. The pedicled MSAP flap represents a versatile option in soft-tissue defect coverage of the lower leg and around the knee joint. Inclusion of 2 perforators could render the flap safer and increase its skin paddle, making it suitable for larger defects.


Effect of temperature on survival of free-living stages of Haemonchus contortus.
One percent or more unembryonated eggs of Haemonchus contortus survived in sheep fecal pellets less than 0.5 hour at -95 C, 2 hours at -28 C, 1 hour at -10 C, 4 days at 4 C, and 1 hour at 45 C. One percent or more embryonated eggs survived 1 hour at -95 and -28C, 12 hours at -10 C, 64 days at 4 C, and 12 hours at 45 C. Over half the unembryonated and embryonated eggs survived only 1 and 4 days, respectively, at 4 C. One percent or more 1st-stage larvae did not survive 0.5 hour at -95 C but did survive 0.5 hour at -28 C, 8 hours at -10 C, 16 days at 4 C, and 1 hour at 45 C. Less than 1% of 2nd-stage larvae survived up to 2 days at -95 C; all were dead by 4 days. Second-stage larvae survived 32 days at -28 C, 8 days at -10 C, 64 days at 4 C, and 2 hours at 45 C. One percent or more 3rd-stage larvae survived 256 days at -95 C, 16 days at -28 C, 32 days at -10 C, more than 256 days at 4 C, 128 days at 20 C, 64 days at 25 and 35 C, and 4 days at 45 C. Thus, the increasing order of survival was unembryonated eggs, 2nd-stage larvae, 1st-stage larvae, embryonated eggs, and 3rd-stage larvae.


Balanced high fat diet reduces cardiovascular risk in obese women although changes in adipose tissue, lipoproteins, and insulin resistance differ by race.
We previously reported that consuming a balanced high fat diet (BHFD) wherein total saturated fat was reduced and total unsaturated fat increased by proportionately balancing the type of fat (1/3 saturated, 1/3 monounsaturated, 1/3 polyunsaturated) led to significant improvements in inflammatory burden, blood pressure, and vascular function in obese premenopausal European American (EA) and African American (AA) women. Here we compared changes in adipose tissue, lipoproteins, insulin resistance, and cardiovascular risk between EA and AA women. Dietary intakes, plasma fatty acids, lipids, apolipoproteins, lipoproteins, HOMA-IR and ASCVD risk was measured in 144 women who consumed BHFD for 16 weeks. Generalized linear modeling was performed while controlling for change in body weight. EA women had greater reductions in visceral adipose tissue. Only EA women had significant reductions in fasting insulin levels (↓24.8%) and HOMA-IR (↓29%) scores. In EA women, the most significant improvements occurred in VLDL particle size (↑), apolipoprotein B levels (↑), serum TG (↓), number of plasma LDL particles (↓), and serum LDL-cholesterol (↓). In AA women, significant improvements occurred in HDL particle size (↑), number of large HDL particles (↑), and apolipoprotein AI levels (↑). Consequently, both groups had improved ASCVD risk scores (↓5.5%). Consuming the balanced high fat diet led to significant reduction in cardiovascular risk factors in both groups. However, the pattern of response to BHFD differed with EA women responding more in components of the apolipoprotein B pathway versus AA women responding more in components of the apolipoprotein AI pathway.


Aneurysmal subarachnoid hemorrhage models: do they need a fix?
The discovery of tissue plasminogen activator to treat acute stroke is a success story of research on preventing brain injury following transient cerebral ischemia (TGI). That this discovery depended upon development of embolic animal model reiterates that proper stroke modeling is the key to develop new treatments. In contrast to TGI, despite extensive research, prevention or treatment of brain injury following aneurysmal subarachnoid hemorrhage (aSAH) has not been achieved. A lack of adequate aSAH disease model may have contributed to this failure. TGI is an important component of aSAH and shares mechanism of injury with it. We hypothesized that modifying aSAH model using experience acquired from TGI modeling may facilitate development of treatment for aSAH and its complications. This review focuses on similarities and dissimilarities between TGI and aSAH, discusses the existing TGI and aSAH animal models, and presents a modified aSAH model which effectively mimics the disease and has a potential of becoming a better resource for studying the brain injury mechanisms and developing a treatment.


Stimulation of ovarian follicle growth after AMPK inhibition.
Previous studies showed that the protein kinase B (Akt)-mammalian target of rapamycin (mTOR) and Hippo signaling Yes-associated protein (YAP) pathways play important roles in promoting follicle growth. Additionally, other studies demonstrated that 5' adenosine monophosphate-activated protein kinase (AMPK) is an upstream regulatory element of mTOR and YAP. Here, we used AMPK inhibitor (Compound C) to in vitro cultured ovaries from 10-day-old mice followed by in vivo grafting into adult hosts or to in situ treated ovaries of 3-week-old mice by intrabursal injection followed by gonadotropin stimulation. We found that the phosphorylation of ovarian mTOR and downstream proteins (ribosomal protein S6 (S6) and eukaryotic translation initiation factor 4B (eIF4B)) was upregulated following Compound C administration, whereas tuberous sclerosis complex 2 (TSC2) phosphorylation was downregulated. Additionally, treatment with Compound C increased hypoxia-inducible factor 1-alpha (Hif1a), vascular endothelial growth factor A (Vegfa), VEGF receptor 2 (Vegfr2) and connective tissue growth factor (Ctgf) mRNA levels. Furthermore, treatment of 10-day-old mice with Compound C promoted the growth of preantral and antral follicles accompanied by enhanced angiogenesis. In situ intrabursal injection with Compound C, followed by controlled ovarian hyperstimulation, increased the number of ovulated oocytes in 3-week-old mice, and these oocytes could be successfully fertilized, leading to the delivery of healthy pups. Our results demonstrated that treatment with AMPK inhibitor resulted in the activation of the mTOR signaling pathway, increases in Ctgf expression in mouse ovaries, stimulation of follicle development and promotion of ovarian angiogenesis for ovary growth.