Pedigree disequilibrium tests for multilocus haplotypes.
Association tests of multilocus haplotypes are of interest both in linkage disequilibrium mapping and in candidate gene studies. For case-parent trios, I discuss the extension of existing multilocus methods to include ambiguous haplotypes in tests of models which distinguish between the cis and trans phase. A likelihood-ratio test is proposed, using the expectation-maximization (E-M) algorithm to account for haplotype ambiguities. Assumptions about the population structure are required, but realistic situations, including population stratification, which violate the assumptions lead to conservative tests. I describe a permutation procedure for the null hypothesis of interest, which controls for violation of the assumptions. For general pedigrees, I describe extensions of the pedigree disequilibrium test to include uncertain haplotypes. The summary statistics are replaced by their expected values over prior distributions of haplotype frequencies. If prior distributions are not available, a valid test is possible by using the E-M algorithm to estimate the null distribution of haplotype frequencies. Similar methods are available for quantitative traits. Exact permutation tests are difficult to construct in small samples, but an approximate procedure is appropriate in large samples, and can be used to account for dependencies between tests of multiple haplotypes and loci.


Day type and the relationship between weight status and sleep duration in children and adolescents.
This study aimed to explore sleep duration in young Australians on different types of days across weight classes. Use of time and anthropometric data were collected on 8,866 nights from 3,884 9-18 year old Australians. The association between sleep duration and weight status was examined using factorial ANOVA for four day types: S-S (to bed and waking on school days); S-NS (to bed on school day and waking on non-school day); NS-NS (to bed and waking on non-school days); NS-S (to bed on non-school day and waking on school day). Sleep duration varied with weight status when all day types were considered together (p=0.0012). Obese adolescents slept less than normal and underweight adolescents. However, the relationship varied for different day types; with the strongest relationship for NS-S days (on which obese children slept 65 min less than very underweight children, p<0.0001). The association between weight status and sleep duration showed consistent gradients across weight categories, but only for certain day types. These patterns cast light on the direction of causation in the obesity-sleep duration relationship. Findings suggest that short sleep duration contributes to obesity, or that a third unidentified factor has an impact on both.


[Characteristics of stab wounds inflicted by knives with the gear-sharpened blade].
The authors present the results of an experimental study designed to estimate the damage to biological and non-biological objects inflicted by the knife blades having the gear-type sharpening. It was shown that a knife with such sharpening leaves edges of the damage of characteristic shape and outline. The results of the study testify to the expediency of further studies on the damaging action of knives considered in the present paper.


Phorbol esters activate the pathway for phosphatidylethanol synthesis in differentiating HL-60 cells.
12-O-Tetradecanoylphorbol 13-acetate (TPA) has been shown to induce the formation of an unusual acidic phospholipid, phosphatidylethanol, in HL-60 cells. The synthesis of this lipid is dependent upon the presence of ethanol in the culture medium of TPA-treated cells; however, other exogenous alcohols can substitute as headgroup precursors with the formation of the corresponding phosphatidyl alcohol. The activation of the pathway for phosphatidyl alcohol synthesis appears to be mediated through protein kinase C. Studies of the time-course for the synthesis and accumulation of phosphatidylethanol suggest a possible involvement of the pathway for phosphatidyl alcohol synthesis in the TPA-induced differentiation of HL-60 cells.


Biomarkers for the development of new medications for cocaine dependence.
There has been significant progress in personalized drug development. In large part, this has taken place in the oncology field and been due to the ability of researchers/clinicians to discover and develop novel drug development tools (DDTs), such as biomarkers. In cancer treatment research, biomarkers have permitted a more accurate pathophysiological characterization of an individual patient, and have enabled practitioners to target mechanistically the right drug, to the right patient, at the right time. Similar to cancer, patients with substance use disorders (SUDs) present clinically with heterogeneous symptomatology and respond variably to therapeutic interventions. If comparable biomarkers could be identified and developed for SUDs, significant diagnostic and therapeutic advances could be made. In this review, we highlight current opportunities and difficulties pertaining to the identification and development of biomarkers for SUDs. We focus on cocaine dependence as an example. Putative diagnostic, pharmacodynamic (PD), and predictive biomarkers for cocaine dependence are discussed across a range of methodological approaches. A possible cocaine-dependent clinical outcome assessment (COA)--another type of defined DDT--is also discussed. At present, biomarkers for cocaine dependence are in their infancy. Much additional research will be needed to identify, validate, and qualify these putative tools prior to their potential use for medications development and/or application to clinical practice. However, with a large unmet medical need and an estimated market size of several hundred million dollars per year, if developed, biomarkers for cocaine dependence will hold tremendous value to both industry and public health.


Exploring the interactions of antihistamine with retinoic acid receptor beta (RARB) by molecular dynamics simulations and genome-wide meta-analysis.
Kaposi sarcoma (KS) is one of the most common AIDS-related malignant neoplasms, which can leave lesions on the skin among HIV patients. These lesions can be treated with 9-cis-retinoic acid (9-cis-RA), an endogenous ligand of retinoic acid receptors that has been FDA-approved for treatment of KS. However, topical application of 9-cis-RA can induce several unpleasant side effects, like headache, hyperlipidemia, and nausea. Hence, alternative therapeutics with less side effects are desirable. There are case reports associating over-the-counter antihistamine usage with regression of KS. Antihistamines competitively bind to H1 receptor and block the action of histamine, best known for being released in response to allergens. Furthermore, there are already dozens of antihistamines that are FDA-approved with less side effects than 9-cis-RA. This led our team to conduct a series of in-silico assays to determine whether antihistamines can activate retinoic acid receptors. First, we utilized high-throughput virtual screening and molecular dynamics simulations to model high-affinity interactions between antihistamines and retinoic acid receptor beta (RARβ). We then performed systems genetics analysis to identify a genetic association between H1 receptor itself and molecular pathways involved in KS. Together, these findings advocate for exploration of antihistamines against KS, starting with our two promising hit compounds, bepotastine and hydroxyzine, for experimental validation study in the future.


Localization of the human UBC polyubiquitin gene to chromosome band 12q24.3.
The localization of specific human ubiquitin genes has not been straightforward because of the conservation of the ubiquitin coding sequence and the number of processed pseudogenes. An congruent to 1.4-kb sequence from the 5'-flanking region of the UBC gene has been shown to be unique to that locus and free from dispersed repeat elements. The cloned 5'-flanking fragment has been used to probe Southern blots of DNA obtained from somatic cell hybrid cell lines. These data indicate that the UBC gene is located on chromosome 12. In situ hybridization with the 5'-flanking probe has refined the assignment to the broad chromosomal subband 12q24.3. These data show that the active ubiquitin genes are not clustered and are located on separate chromosomes. In addition, these studies demonstrate the utility of intron or flanking sequence probes in the specific chromosomal assignment of members of highly conserved gene families.


VEGFR2 Trafficking, Signaling and Proteolysis is Regulated by the Ubiquitin Isopeptidase USP8.
Vascular endothelial growth factor A (VEGF-A) regulates many aspects of vascular function. VEGF-A binding to vascular endothelial growth factor receptor 2 (VEGFR2) stimulates endothelial signal transduction and regulates multiple cellular responses. Activated VEGFR2 undergoes ubiquitination but the enzymes that regulate this post-translational modification are unclear. In this study, the de-ubiquitinating enzyme, USP8, is shown to regulate VEGFR2 trafficking, de-ubiquitination, proteolysis and signal transduction. USP8-depleted endothelial cells displayed altered VEGFR2 ubiquitination and production of a unique VEGFR2 extracellular domain proteolytic fragment caused by VEGFR2 accumulation in the endosome-lysosome system. In addition, perturbed VEGFR2 trafficking impaired VEGF-A-stimulated signal transduction in USP8-depleted cells. Thus, regulation of VEGFR2 ubiquitination and de-ubiquitination has important consequences for the endothelial cell response and vascular physiology.


Increase of AMPA receptor glutamate receptor 1 subunit and B-cell receptor-associated protein 31 gene expression in hippocampus of fatigued mice.
Central fatigue is an indispensable biosignal for maintaining life, but the neuronal and molecular mechanisms involved remain unclear. In this study, we searched for genes differentially expressed in the hippocampus of fatigued mice to elucidate the mechanisms underlying fatigue. Mice were forced to swim in an adjustable-current water pool, and the maximum swimming time (endurance) until fatigue was measured thrice. Fatigued and nonfatigued mice with equal swimming capacity and body weight were compared. We found that the genes of GluR1 and B-cell receptor-associated protein 31 (Bap31), which acts as a transport molecule in the secretory pathway or as a mediator of apoptosis, were upregulated in the hippocampus of fatigued mice, and increases of GluR1 and Bap31 were confirmed by Northern blotting and real-time PCR. No change of gene expression of AMPA receptor subunits other than GluR1 was observed. These results suggest that a compositional change of AMPA receptor (increase of GluR1) and upregulation of the Bap31 gene may be implicated in fatigue in mice.


Comparison of effects of intraoperative esmolol and ketamine infusion on acute postoperative pain after remifentanil-based anesthesia in patients undergoing laparoscopic cholecystectomy.
Remifentanil is a short-acting drug with a rapid onset that is useful in general anesthesia. Recently, however, it has been suggested that the use of opioids during surgery may cause opioid-induced hyperalgesia (OIH). Researchers have recently reported that esmolol, an ultra-short-acing β1 receptor antagonist, reduces the postoperative requirement for morphine and provides more effective analgesia than the administration of remifentanil and ketamine. Hence, this study was conducted to determine whether esmolol reduces early postoperative pain in patients who are continuously infused with remifentanil for anesthesia during laparoscopic cholecystectomy. Sixty patients scheduled to undergo laparoscopic cholecystectomy were randomly divided into three groups. Anesthesia was maintained with sevoflurane and 4 ng/ml (target-controlled infusion) of remifentanil in all patients. Esmolol (0.5 mg/kg) was injected and followed with a continuous dosage of 10 µg/kg/min in the esmolol group (n = 20). Ketamine (0.3 mg/kg) was injected and followed with a continuous dosage of 3 µg/kg/min in the ketamine group (n = 20), while the control group was injected and infused with an equal amount of normal saline. Postoperative pain score (visual analog scale [VAS]) and analgesic requirements were compared for the first 6 hours of the postoperative period. The pain score (VAS) and fentanyl requirement for 15 minutes after surgery were lower in the esmolol and ketamine groups compared with the control group (P < 0.05). There were no differences between the esmolol and ketamine groups. Intraoperative esmolol infusion during laparoscopic cholecystectomy reduced opioid requirement and pain score (VAS) during the early postoperative period after remifentanil-based anesthesia.


Fracture incidence of WaveOne Gold files: a prospective clinical study.
This prospective clinical study evaluated the incidence of instrument fracture observed after single-file root canal treatment of molars using WaveOne Gold instruments. Three standardized, experienced and calibrated specialists treated 750 maxillary and mandibular molars with curvatures less than 45° (2691 root canals) over a 12-month period. All the treatments were performed in a single session. A total of 1104 WaveOne Gold instruments were used, including 38 small, 750 primary, 228 medium and 88 large instruments. Intracanal procedures were performed according to the manufacturer's recommendations, and each instrument was used in a single clinical case. The instruments were examined after their removal from the canal, under an operating microscope at 8× magnification. No fractures were observed in any of the 1104 instruments used. No fractures of WaveOne Gold reciprocating instruments occurred during root canal preparations performed in maxillary and mandibular molars with curvatures less than 45° when used strictly according to the manufacturer's recommendations and applied in a single clinical case.


MRI correlates of general intelligence in neurotypical adults.
There is growing interest in the neurobiological substrate of general intelligence. Psychometric estimates of general intelligence are reduced in a range of neurological disorders, leading to practical application as sensitive, but non-specific, markers of cerebral disorder. This study examined estimates of general intelligence in neurotypical adults using diffusion tensor imaging and resting-state functional connectivity analysis. General intelligence was related to white matter organisation across multiple brain regions, confirming previous work in older healthy adults. We also found that variation in general intelligence was related to a large functional sub-network involving all cortical lobes of the brain. These findings confirm that individual variance in general intelligence is related to diffusely represented brain networks.


Pulmonary Hypertension in Chronic Obstructive Pulmonary Disease and Pulmonary Fibrosis: Prevalence and Hemodynamic Differences in Lung Transplant Recipients at Transplant Center's Referral Time.
Single or bilateral lung transplantation is a therapeutic procedure for end-stage lung diseases. In particular, in cases of chronic obstructive pulmonary disease (COPD) and pulmonary fibrosis, patients can be referred to the transplant center late and with important comorbilities. Pulmonary hypertension (PH) associated with lung diseases not only is an index of poor outcome but also is an indication for bilateral procedure. We conducted a retrospective observational study. We analyzed right heart catheterization in a consecutive series of patients who underwent lung transplantation from 2006 to 2014 for end-stage COPD and pulmonary fibrosis. We included in the study 73 patients (35 with fibrosis and 38 with COPD); prevalence of PH was higher in the COPD group (84.3% vs 31.4%), and with worse hemodynamic parameters (mean pulmonary artery pressure [30.3 mm Hg vs 24.1 mm Hg]). The majority of COPD patients presented mild or moderate PH, and fibrosis patients showed normal pulmonary arterial pressures. COPD patients are referred to the Transplant Center with a higher prevalence of PH because of an echocardiographic screening or a late referral, but many patients survive on the waiting list and undergo the procedure. On the other hand, patients transplanted with interstitial diseases have a lower prevalence of PH; this can be explained by an earlier referral or a higher mortality on the waiting list and a more aggressive and rapidly progressing disease.


Ribozyme-based transfer RNA switches for post-transcriptional control of amino acid identity in protein synthesis.
Protein mutants are studied in a variety of contexts in the life sciences. However, individual mutations need to be generated in order to transcribe and translate the respective protein variants. Here, we introduce a novel strategy for controlling the incorporation of different amino acids in response to an amber stop codon by utilizing switchable designer transfer RNAs in Escherichia coli .


Chronic mild stress induces variations in locomotive behavior and metabolic rates in high fat fed rats.
Chronic mild stress (CMS) has been often associated to the pathogenesis of many diseases including obesity. Indeed, visceral obesity has been linked to the development of metabolic syndrome features and constitutes a serious risk factor for cardiovascular diseases and diabetes. In order to study possible mechanistic relationships between stress and the onset of obesity, we developed during 11 weeks a model of high-fat dietary intake (cafeteria diet) together with a CMS regimen in male Wistar rats. During the experimental period, basal metabolism by indirect calorimetry, rectal temperature, food intake, and locomotive markers were specifically analyzed. After 77 days, animals were sacrificed and body, adiposity and plasma biochemical profiles were also examined. As expected, cafeteria diet in unstressed animals induced a significative increase in body weight, adiposity, and insulin resistance markers. Locomotive variables, specifically distance, rearing and meander, were significantly increased by CMS on the first weeks of stress. Moreover, this model of CMS in Wistar rats increased significantly energy expenditure, and apparently interplayed with the dietary treatment on the muscle weight/fat weight ratio. In summary, this chronic stress model did not affected weight gain in control and high fat fed animals, but induced an interaction concerning the metabolic muscle/fat repartitioning.


Screening method for benzodiazepines and hypnotics in hair at pg/mg level by liquid chromatography-mass spectrometry/mass spectrometry.
A procedure is presented for the screening of 16 benzodiazepines and hypnotics in human hair by LC-MS/MS (alprazolam, 7-aminoclonazepam, 7-aminoflunitrazepam, bromazepam, clobazam, diazepam, lorazepam, lormetazepam, midazolam, nordiazepam, oxazepam, temazepam, tetrazepam, triazolam, zaleplon and zolpidem). The method involves decontamination of hair with methylene chloride, hair cut into small pieces, incubation of 20 mg in phosphate buffer (pH 8.4) in the presence of 1 ng diazepam-d5 used as internal standard, liquid-liquid extraction with diethyl ether/methylene chloride (10/90) and separation using liquid chromatography-tandem mass spectrometry. The limits of quantification for all benzodiazepines and hypnotics range from 0.5 to 5 pg/mg using a 20-mg hair sample. Linearity is observed from the limit of quantification of each compound to 200 pg/mg (r2 > 0.99). Coefficients of variation measured on six points and at two concentrations (10 and 50 pg/mg) range from 5 to 20% for all drugs but one. Extraction recovery, measured at the two same concentrations range from 32 to 76%. These results were found suitable to screen for 16 benzodiazepines in hair and detect them at very low concentrations, making this method suitable to monitor single dose.


Noneconomic and economic impacts of nurse turnover in hospitals: A systematic review.
To examine and synthesize the noneconomic and economic impacts of nurse turnover in acute hospitals. Nurse turnover occurs when nurses leave their jobs or the profession and is a major concern for the healthcare industry. Many studies have investigated the determinants of nurse turnover. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses checklist was utilized in the current review. Article search was conducted in June 2021. Research articles published since January 2000 were included. Eight databases (e.g., CINAHL, PubMed, PsycINFO, and Web of Science) were used. The following eligibility criteria were applied for inclusion: Articles that (1) were nonexperimental quantitative studies, (2) examined the impact of actual nurse turnover in acute hospitals, (3) were a peer-reviewed original research article, and (4) were written in English or Korean. Among 9,041 searched articles, 16 were included in the review. Seven studies investigated the association of nurse turnover with processes and outcomes (workgroup processes, nurse staffing, nurse outcomes, and patient outcomes), and partially supported the negative impact of turnover. Nine studies found that nurse turnover is very costly. Most studies investigated the turnover cost, which is costly. The negative noneconomic impact of nurse turnover was partially supported. To prevent the adverse noneconomic and economic impacts of nurse turnover and retain nurses, healthcare organizations, nurse managers, and hospital staff nurses need to develop and implement prevention strategies and policies to address nurse turnover. Efforts to address nurse turnover can increase hospital competency to improve the quality of nursing care services and patient safety.


AUTOLOGOUS NEUROSENSORY RETINAL TRANSPLANT TO TREAT REFRACTORY SEROUS RETINAL DETACHMENT SECONDARY TO OPTIC DISK COLOBOMA.
To describe a novel surgical technique to treat refractory serous retinal detachment in a patient with an optic disk coloboma. Case report. A 32-year-old male patient with an optic disk coloboma in his right eye was referred for recurrent retinoschisis and serous macular detachment despite multiple vitrectomies. Previous surgical procedures included peeling of internal limiting membrane and juxtapapillary laser as well as different tamponade agents such as sulfur hexafluoride gas, standard silicone oil, and heavy silicone oil. Our first approach to close the cavity using autologous platelet concentrate and gas tamponade was also unsuccessful with early recurrence of the submacular fluid. In a second attempt, an autologous neurosensory retinal transplant was used to cover the optic disk cavity. At 17-month follow-up, the macula was still attached. As a postoperative complication, the patient developed high intraocular pressure, for which laser cycloablation eventually was necessary. Autologous neurosensory retinal transplant may be a reasonable treatment option for patients with recurrent optic disk cavity-associated maculopathy.


Trailblazing New Paths to e-Learning Engagement.
E-learning modules are a common component of orientation and other education initiatives, but their usefulness can be limited by poor engagement. This article presents the results of an experimental cohort study testing interventions designed to improve learner engagement with e-learning modules.


EPR hyperthermia of S. cerevisiae using superparamagnetic Fe3O4 nanoparticles.
Presently we communicate a newly developed method of resonant radiofrequency heating, applicable in hyperthermal therapy. This method uses electron paramagnetic resonance (EPR) to transform the electromagnetic field energy into heat. We report the growth dynamics of the S. cerevisiae yeast cells exposed to EPR heating with superparamagnetic magnetite (Fe3O4) nanoparticles, with only 4% of yeast cells surviving hyperthermia. Given that EPR functions independently of type of the biologic species exposed, and produces spatially localized heating in conjunction with MRI hardware, it may be used in hyperthermal therapy of cancer and other diseases.


Undescribed C-Glycosylflavones from Corn Silk and Potential Anti-inflammatory Activity Evaluation of Isolates.
Phytochemical investigation of corn silk resulted in isolation and characterization of four flavone C-glycosides, chrysoeriol 6-C-β-oliopyranosyl-7-O-β-D-glucopyranoside (1: ), 3'-methoxycassiaoccidentalin A (2: ), chrysoeriol 6-C-β-boivinopyranosyl-7-O-β-D-glucopyranoside (3: ), and ax-4″-OH-3'-methoxymaysin (4: ), a triterpenoid, friedelin (5: ), two sterols, (22E)-5α,8α-epidioxyergosta-6,22-dien-3β-ol (6: ) and 6β-hydroxystigmasta-4,22-diene-3-one (7: ), and a mixture of β-sitosterol and stigmasterol. Compounds 1: and 2: were previously undescribed. Structure elucidation of the isolated compounds was attained using spectral data including 1D and 2D NMR and HRESIMS. Compounds1, 2, 5: , and 6: inhibited iNOS activity in LPS-induced macrophages and decreased nitrite levels by 68.64 ± 4.46, 65.67 ± 6.47, 88.50 ± 0.50, and 94.00 ± 4.00%, respectively, at 50 µM. Compound 5: also showed inhibition of NF-κB (51.00 ± 1.50%). Compounds 1: and 2: induced NAG-1 activity in chondrocytes by 1.80 ± 0.05 and 2.00 ± 0.13 fold, respectively. The extract of corn silk, however, did not exhibit inhibition of iNOS or NF-κB but induced NAG-1 by 1.80 ± 0.51 fold.


Whole-brain changes in white matter microstructure after radiotherapy for nasopharyngeal carcinoma: a diffusion tensor imaging study.
Radiation-induced local white matter (WM) damage has been observed by diffusion tensor imaging (DTI) within a priori-defined regions of interest following radiotherapy (RT) for nasopharyngeal carcinoma (NPC). In this study, we aimed to detect WM changes throughout the brain of NPC patients by DTI. Tract-based spatial statistics (TBSS) was used to analyze DTI data from 81 NPC patients. Fractional anisotropy (FA) and mean diffusivity (MD) were quantified across the whole brain in separate groups: pre-RT, and <6, 6-12, and >12 months post-RT. We found that fractional anisotropy values were significantly lower in the right frontal, parietal, and occipital WM <6 months post-RT compared with pre-RT and remained significantly lower in the right frontal and parietal WM at >12 months. MD values were significantly higher in the right occipital, bilateral temporal, right occipital-temporal junction, left parietal, left centrum semiovale, and left frontal-parietal junction WM <6 months post-RT and remained higher in the right occipital WM at >12 months. This study suggests that changes in white matter microstructure following RT for NPC were widespread, complex, and dynamic. Diffusion tensor imaging with TBSS analysis allows for early non-invasive detection of RT-induced WM damage.


Draft Genome Sequence of Labrys okinawensis, Isolated from Acaciella sp. Nodules in Mexico.
A new plant-associated bacterium, Labrys okinawensis strain LIt4, was isolated from root nodules of wild Acaciella sp. in Morelos, Mexico. The 6,499,737-bp genome sequence provides opportunities to investigate a new reference strain to add information about the species L. okinawensis.


Are tyrosine kinase inhibitors still active in patients with metastatic renal cell carcinoma previously treated with a tyrosine kinase inhibitor and everolimus? Experience of 36 patients treated in France in the RECORD-1 Trial.
Because the response to treatment is limited, patients with metastatic renal cell carcinoma (mRCC) typically receive multiple treatments. Guidelines recommend everolimus for patients previously treated with tyrosine kinase inhibitors (TKI) sunitinib or sorafenib. This study evaluated the efficacy of TKI re-treatment in patients with disease progression after a TKI-everolimus sequence. Data were reviewed for patients enrolled in RECORD-1 (Renal Cell Cancer Treatment With Oral RAD001 Given Daily) at French sites. Response, progression-free survival (PFS), and overall survival were evaluated in patients treated with a TKI-everolimus-TKI sequence. Thirty-six patients received a TKI after everolimus: sunitinib in 17 patients, sorafenib in 15, and dovitinib (TKI258) in 4. The response rate with TKI re-treatment was 8%, and the disease-control rate (response plus stable disease) was 75%. The median PFS with each component of the TKI-everolimus-TKI sequence was 10.7 months (95% CI, 1.8-28.5 months), 8.9 months (95% CI, 1.7-34.6 months), and 8.2 months (95% CI, 5.2-11.9 months), respectively. The median overall survival from the start of everolimus was 29.1 months (95% CI 21.1 to not reached months), which suggests a benefit in using TKI in this setting. Administration of a TKI-everolimus-TKI sequence may be associated with clinical benefit and should be prospectively investigated.


Pallamins A-C, ent-labdane and pallavicinin based dimers from the Chinese liverwort Pallavicinia ambigua (mitt.) stephani.
Three unprecedented ent-labdane and pallavicinin based dimers pallamins A-C formed via [4 + 2] Diels-Alder cycloaddition, together with eight biosynthetically related monomers were isolated from Pallavicinia ambigua. Their structures were determined by the extensive analysis of HRESIMS and NMR spectra. The absolute configurations of the labdane dimers were determined by single crystal X-ray diffraction of the homologous labdane units, and 13C NMR and ECD calculations. Moreover, a preliminary evaluation of the anti-inflammatory activities of the isolated compounds was performed using the zebrafish model. Three of the monomers demonstrated significant anti-inflammatory activity.


Polymer-surfactant systems in bulk and at fluid interfaces.
The interest of polymer-surfactant systems has undergone a spectacular development in the last thirty years due to their complex behavior and their importance in different industrial sectors. The importance can be mainly associated with the rich phase behavior of these mixtures that confers a wide range of physico-chemical properties to the complexes formed by polymers and surfactants, both in bulk and at the interfaces. This latter aspect is especially relevant because of the use of their mixture for the stabilization of dispersed systems such as foams and emulsions, with an increasing interest in several fields such as cosmetic, food science or fabrication of controlled drug delivery structures. This review presents a comprehensive analysis of different aspects related to the phase behavior of these mixtures and their intriguing behavior after adsorption at the liquid/air interface. A discussion of some physical properties of the bulk is also included. The discussion clearly points out that much more work is needed for obtaining the necessary insights for designing polymer-surfactant mixtures for specific applications.


Amplitude and phase dynamics in oscillators with distributed-delay coupling.
This paper studies the effects of distributed-delay coupling on the dynamics in a system of non-identical coupled Stuart-Landau oscillators. For uniform and gamma delay distribution kernels, the conditions for amplitude death are obtained in terms of average frequency, frequency detuning and the parameters of the coupling, including coupling strength and phase, as well as the mean time delay and the width of the delay distribution. To gain further insights into the dynamics inside amplitude death regions, the eigenvalues of the corresponding characteristic equations are computed numerically. Oscillatory dynamics of the system is also investigated, using amplitude and phase representation. Various branches of phase-locked solutions are identified, and their stability is analysed for different types of delay distributions.


New simple spectrophotometric assay of total carotenes in margarines.
Direct and reliable spectrophotometric method for assaying total carotenes (TC) in margarines with the minimum of sample manipulation is proposed. For the first time saponification step used in determination of carotenes in margarines was omitted leading to a substantial cost saving and reduction of time needed to complete the analysis. The resulting analytical procedure is characterized in details in terms of the figures of merit. The method is sensitive, precise and accurate; for both, standard additions and calibration in soybean oil, recovery ranges between 98 and 102%. For the most accurate analyses the approach of standard additions is preferred but for quick routine analyses this latter can be replaced by the calibration in soybean oil. Limit of detection value (LOD=3S.D.(B)/a, where S.D.(B) is the standard deviation of the blank, "a" is the slope of calibration line) as low as 12 microg TC/100 g was achieved in soybean oil enabling the sensitive detection. Concentration of TC in margarines declared as being coloured with beta-carotene (carotene) ranges between 0.3 and 0.9 mg/100 g while in carrot extract-coloured margarine TC is 0.2 mg/100 g.


The person of the analyst: interpreting, not interpreting, and countertransference.
The author focuses on the person of the analyst and particularly how it helps shape two key factors in psychoanalysis: clinical narration and the analyst's interpretations. Freud's comments on how treatment is influenced by the analyst's individuality are briefly reviewed; and Winnicott's notion of how the individual analyst relates to the patient--including how he does and does not interpret--is also discussed. Following a detailed description of an analytic treatment, the author discusses various aspects of the analyst's attitude and functioning, including countertransference, and how these are affected by the person of the analyst.


Incidence of tuberculosis in mountain areas and surrounding townships: dose-response relationship by geographic analysis.
The incidence of tuberculosis (TB) in Taiwan is known to be high in aboriginal mountain areas and low in the surrounding non-mountain areas. The aim of this study was to assess whether TB incident cases in the surroundings of mountain areas decreased with distance from foci of mountain areas. The mountain areas in Taiwan are adjacent to each other and divided into four geographic groups. Townships with high TB incidence in each group were treated as the foci of TB infection. The surrounding townships were then classified, by distance away from foci, into three levels: < 20 km, 20 to 40 km, and 40 to 60 km. Data were obtained on a total of 84,366 TB cases from 1991 to 1997 from the Taiwan Tuberculous Disease Registry Center. The incidence of TB in each of the four groups was significantly higher in the mountain areas compared with non-mountain areas, with relative risks ranging from 8.4 (95% confidence interval [CI], 7.8-9.1) for the southern group to 15.0 (95% CI, 13.4-16.9) for the northern group. Relative risks for surrounding townships decreased with distance in all four groups. Such a gradient relationship was statistically significant. A significant dose-response relationship between distance from townships with a high incidence of TB and the incidence of TB in the surrounding areas has been demonstrated.


Toxicity of epoxy trichothecenes in cultured mammalian cells.
With four established cell lines, cytotoxicity of 23 epoxy trichothecenes was tested. Three cell lines from human origin have been found to have a similar degree of sensitivity to trichothecenes. A pig kidney cell line had a higher sensitivity to NT-1 toxin, neosolaniol, tetraacetyl T-2, and iso-T-2 toxin. The potential cause for discrepancies in literature were discussed. Activity of esterases in calf serum used for cell cultures should be recorded whenever conducting toxicity tests in cell cultures with trichothecenes.Relations of chemical structures of toxins to their biological activities were investigated. With verrucarol (scirpendiol), scirpentriol, and T-2 tetraol analogues the esters generally showed significantly higher cytotoxicity. But, loss of acetyl groups at single positions did not necessarily mean decline in toxicity. With macrocyclic trichothecenes minor differences in the side chain of verrucarol esters were found to contribute to differences in biological activity.


The human milk microbiome and factors influencing its composition and activity.
Beyond its nutritional aspects, human milk contains several bioactive compounds, such as microbes, oligosaccharides, and other substances, which are involved in host-microbe interactions and have a key role in infant health. New techniques have increased our understanding of milk microbiota composition, but few data on the activity of bioactive compounds and their biological role in infants are available. Whereas the human milk microbiome may be influenced by specific factors - including genetics, maternal health and nutrition, mode of delivery, breastfeeding, lactation stage, and geographic location - the impact of these factors on the infant microbiome is not yet known. This article gives an overview of milk microbiota composition and activity, including factors influencing microbial composition and their potential biological relevance on infants' future health.


Is a surgical approach justified for octogenarians with pancreatic carcinoma? Projecting surgical decision making for octogenarian patients.
In recent years, more elderly patients have undergone surgery for pancreatic cancer, although the safety and efficacy of performing complex pancreatic resections in patients older than 80 years remain controversial. Patients with pancreatic cancer who underwent curative surgical treatment were divided into 2 subgroups: the younger group (<80 years) and the octogenarian group (≥80 years). From March 2005 to December 2013, 194 consecutive surgically curable patients with diagnosed pancreatic cancer were studied, among which 34 (17.5%) were of 80 years or older. There were no significant differences in postoperative severe complication rates for younger and octogenarian groups (16% vs 20%, respectively) or perioperative mortality rates (1.3% vs .0%). The incidence of postoperative delirium in the octogenarian group was greater than that in the younger group (23.5% vs 3.8%). Octogenarian pancreatic cancer patients should not be denied a priori the opportunity for surgery, particularly if the patient represents an ideal candidate and if the co-operation of the family can be obtained.


Investigating the nucleic acid interactions and antimicrobial mechanism of buforin II.
Buforin II (BF2) is an antimicrobial peptide that is hypothesized to kill bacteria by entering cells and binding nucleic acids. To further investigate this proposed mechanism, we used computer modeling and experimental measurements to consider the interactions between BF2 and DNA. Computational and experimental results imply that the peptide forms specific interactions with DNA. Moreover, we observe a general correlation between DNA affinity and antimicrobial activity for a series of BF2 variants. Thus, our results support the proposed mechanism for BF2 and provide a useful approach for evaluating the nucleic acid interactions of other antimicrobial peptides.


Synergism of cell adhesion regulatory genes and instant air pollutants on blood pressure elevation.
Accumulating evidence suggests that an instant exposure to particulate matter (PM) may elevate blood pressure (BP), where cell-adhesion regulatory genes may be involved in the interplay. However, few studies to date critically examined their interaction, and it remained unclear whether these genes modified the association. To assess the association between instant PM exposure and BP, and to examine whether single-nucleotide polymorphisms (SNPs) mapped in four cell adhesion regulatory genes modify the relationship, a cross-sectional study was performed, based on the baseline of an ongoing family-based cohort in Beijing, China. A total of 4418 persons from 2089 families in Northern China were included in the analysis. Four tagged SNPs in cell adhesion regulatory genes were selected among ZFHX3, CXCL12, RASGRP1 and MIR146A. A generalized additive model (GAM) with a Gaussian link was adopted to estimate the change in blood pressure after instant PM2.5 or PM10 exposure. A cross-product term of PM2.5/PM10 and genotype was incorporated into the GAM model to test for interaction. The study observed that an instant exposure to either PM2.5 or PM10 was found to be associated with elevated systolic blood pressure (SBP). On average, a 10 μg/m3 increase in instant exposure to PM2.5 and PM10 concentration corresponded to 0.140% (95% CI: 0.014%-0.265%, P = 0.029) and 0.173% (95% CI: 0.080%-0.266%, P < 0.001) higher SBP. However, diastolic blood pressure (DBP) was not elevated as the PM2.5 or PM10 concentration increased (P > 0.05). A synergetic interaction on SBP was observed between SNPs in four cell adhesion regulatory genes (rs2910164 in MIR146A, rs2297630 in CXCL12, rs7403531 in RASGRP1, and rs7193343 in ZFHX3) and instant PM2.5 exposure (Pfor interaction <0.05). Briefly, as carriers of risk alleles in each of these four genes increased, an enhanced association was found between instant PM2.5 exposure and SBP.


Rethinking work with "multicultural populations".
This article examines the importance of ethnic and cultural factors in mental health and mental illness, through consideration of race and culture in the diagnosis and treatment of mental illness, by examining patterns of service utilization by multicultural populations, and by advocating for policies which support multicultural initiatives in public mental health.


The Dutch patients' perspective on oculopharyngeal muscular dystrophy: A questionnaire study on fatigue, pain and impairments.
Research on oculopharyngeal muscular dystrophy focuses mainly on genetic and pathophysiological aspects. Clinically, oculopharyngeal muscular dystrophy is often considered as a disease with a relatively mild initial disease course with no or only mild functional disabilities. However the occurrence of fatigue, pain and functional impairments other than dysphagia has never been studied systematically. The aim of this study is therefore to assess the prevalence of fatigue, pain, and functional limitations, and the social participation and psychological well-being of oculopharyngeal muscular dystrophy patients. We performed a questionnaire study on fatigue, pain, functional impairments, social participation and psychological distress in 35 genetically confirmed oculopharyngeal muscular dystrophy patients with an average disease duration of 11.6 years. We showed that 19 (54%) of the patients experienced severe fatigue and also 19 (54%) experienced pain. Limitations in daily life activities and social participation were detected in 33 (94%) of the patients. Many patients reported pelvic girdle weakness and limitations in ambulation. Fatigue severity was related to functional impairments, while pain and disease duration were not. Psychological distress was not different from healthy adults. In conclusion, fatigue and pain are present among approximately half of the patients, and almost all patients are impaired in daily life activities, social participation and ambulation. These data should be taken into account in symptomatic management of oculopharyngeal muscular dystrophy.


Is higher nursing home quality more costly?
Widespread issues regarding quality in nursing homes call for an improved understanding of the relationship with costs. This relationship may differ in European countries, where care is mainly delivered by nonprofit providers. In accordance with the economic theory of production, we estimate a total cost function for nursing home services using data from 45 nursing homes in Switzerland between 2006 and 2010. Quality is measured by means of clinical indicators regarding process and outcome derived from the minimum data set. We consider both composite and single quality indicators. Contrary to most previous studies, we use panel data and control for omitted variables bias. This allows us to capture features specific to nursing homes that may explain differences in structural quality or cost levels. Additional analysis is provided to address simultaneity bias using an instrumental variable approach. We find evidence that poor levels of quality regarding outcome, as measured by the prevalence of severe pain and weight loss, lead to higher costs. This may have important implications for the design of payment schemes for nursing homes.


A method for the analysis of sigmoid stimulus-response curves.
This paper describes a method, using an interactive computer programme, for fitting a curve to data which is expected to assume a sigmoid form. The programme is specifically designed to generate best estimates of the limits and maximum slope of stimulus-response curves for the carotid sinus baroreceptor reflex, but is applicable to curve-fitting tasks in other fields such as immunology, pharmacology, biochemistry and neurophysiology.


First record of Pomacanthus maculosus (Perciformes, Pomacanthidae) in the south-western Atlantic Ocean.
A single Pomacanthus maculosus was filmed during a scuba diving survey on a rocky reef from southern Brazil. The body shape and coloration pattern confirmed the species identification. The biological and ecological characteristics of P. maculosus and the long distance of Brazil from its original distribution strongly suggest of an anthropogenic pathway of dispersion.


[Analysis of a novel delta gene during the formation of cortical layers].
The preplate is composed of earliest-generated neurons, including Cajal-Retzius cells and prospected subplate neurons which together play a critical role in the formation of cortical layers. Additionally, Notch and Delta have been identified as key components that mediate the lateral specification and fate of numerous cells during development. Here, we demonstrate that a divergent type of Delta (D113) is expressed transiently and specifically in a set of earliest generated neurons in the neural tube. Moreover, in developing cerebrum, D113 is specifically and transiently expressed in prospected subplate neurons. Thus, our results suggest that D113 mediates the specification of cell fate in the earliest stage of neurogenesis including the neurons that compose preplate, leading to the mechanism of genesis of cortical layers.


The safety of Ramadan Fasting following Percutaneous Coronary Intervention.
This work aimed to assess the safety of Ramadan Fasting following the Percutaneous Coronary Intervention. In our two centers' Prospective Cohort Study, We included 303 patients who had successful Percutaneous Coronary Intervention before the first day of Ramadan. We advised the patients that recent Percutaneous Coronary Intervention could be a valid excuse for not fulfilling Ramadan Fasting. However, many patients intended to fast the following Ramadan, and we included them in the fasting Group I. We added the patients who decided not to fast the following Ramadan as a control Group II. We followed all the patients during Ramadan and for 6 months after Ramadan. The demographic data of both groups and the complexity of the coronary anatomy showed no statistically significant difference. Group I (n = 153) showed a statistically significant difference in the incidence of Major Adverse Cardiac Events compared to Group II with a P value (0.005). The logistic multivariate regression analysis showed that the duration from index PCI till the start of RF, SYNTAX score > 22, and Complex procedure were independent predictors of Major Adverse Cardiac Events in the fasting Group I with {P = 0.001, OR (2.302), P = 0.026, OR (2.419), and P = 0.032 OR (1.952)}, respectively. Major Adverse Cardiac Events in Group I occurred mainly during Ramadan Fasting, with 19 patients having Major Adverse Cardiac Events during Ramadan and four patients during the remaining of the follow-up period. The Receiver Operating Characteristic curve analysis showed the decline of the incidence of Major Adverse Cardiac Events after 90 days from Percutaneous Coronary Intervention till the start of Ramadan Fasting with Sensitivity and specificity (90% and 65%), respectively. We suggest that low-risk patients with a normal systolic function who underwent Percutaneous Coronary Intervention may safely fast Ramadan. At the same time, Ramadan Fasting during the first 3 months following the Percutaneous Coronary Intervention may not be safe.


Brain delivery of camptothecin by means of solid lipid nanoparticles: formulation design, in vitro and in vivo studies.
For the purpose of brain delivery upon intravenous injection, formulations of camptothecin-loaded solid lipid nanoparticles (SLN), prepared by hot high pressure homogenisation, were designed. Incorporation of camptothecin in the hydrophobic and acidic environment of SLN matrix was chosen to stabilise the lactone ring, which is essential for its antitumour activity, and for avoiding premature loss of drug on the way to target camptothecin to the brain. A multivariate approach was used to assess the influence of the qualitative and quantitative composition on the physicochemical properties of camptothecin-loaded SLN in comparison to plain SLN. Mean particle sizes of ≤200 nm, homogenous size distributions and high encapsulation efficiencies (>90%) were achieved for the most suitable formulations. In vitro release studies in plasma, showed a prolonged release profile of camptothecin from SLN, confirming the physical stability of the particles under physiological pH. A higher affinity of the SLN to the porcine brain capillary endothelial cells (BCEC) was shown in comparison to macrophages. MTT studies in BCEC revealed a moderate decrease in the cell viability of camptothecin, when incorporated in SLN compared to free camptothecin in solution. In vivo studies in rats showed that fluorescently labelled SLN were detected in the brain after i.v. administration. This study indicates that the camptothecin-loaded SLN are a promising drug brain delivery system worth to explore further for brain tumour therapy.


The Cedar Project: sexual vulnerabilities among Aboriginal young people involved in illegal drug use in two Canadian cities.
Very few studies in Canada address the sexual health of young Aboriginal people who use drugs; the focus in established literature has been on parenteral risks. This study sought to identify the risk factors associated with inconsistent condom use in a cohort of young Aboriginal people who live in British Columbia and use drugs. This analysis includes baseline questionnaire data from October 2003 to April 2005. Multivariable modeling stratified by gender identified independent demographic, traumatic, sex and drug use risk factors associated with inconsistent condom use. Of the 292 women and 313 men at baseline, prevalence of inconsistent condom use during insertive sex was 59% and 46%, respectively. In multivariable logistic regression, after adjusting for age and location, inconsistent condom use among women was significantly associated with ever being enrolled in a drug/alcohol treatment program (AOR: 1.95, 95% CI: 1.06-3.60), and ever being sexually abused (AOR: 1.80, 95% CI: 1.01-3.20). Among men, inconsistent condom use was significantly associated with having more than 20 lifetime sex partners (AOR: 2.06, 95% CI: 1.24-3.44). Our study demonstrates high rates of inconsistent condom use among young Aboriginal people who use drugs, highlighting their vulnerability to contracting sexually transmitted infections. Culturally tailored sexual health interventions must be made a priority and need to incorporate the reality of gendered differences in the context of multigenerational trauma, including non-consensual sex.


Influence of Calcineurin Inhibitors and Genetic Polymorphism of Transporters on Enterohepatic Circulation and Exposure of Mycophenolic Acid in Chinese Adult Renal Allograft Recipients.
There is significant enterohepatic circulation (EHC) during the disposition of mycophenolic acid (MPA). The aim of this study was to elucidate factors influencing the EHC of MPA in Chinese adult renal allograft recipients. After 2 weeks of therapy with mycophenolate mofetil or enteric-coated mycophenolate sodium, blood samples were collected from 125 patients at 0 to 12 hours post-administration and MPA concentrations were determined. The influence of calcineurin inhibitors (CNIs) and genetic polymorphisms on MPA exposure and EHC was studied. The Shapley additive explanations method was used to estimate the impact of various factors on the area under the plasma drug concentration-time curve (AUC0-12h ) for MPA. An extreme gradient boosting (XGboost) machine learning-based model was established to predict AUC0-12h . Results showed that the dose-normalized AUC6-12h (dn-AUC6-12h ) of MPA was significantly lower in patients co-administered with cyclosporine (CsA) than in patients co-administered with tacrolimus (TAC) (P < .05). For patients co-administered with TAC, patients with ABCC2 C-24T CC or SLCO1B1 T521C TT genotypes had significantly higher values of dn-AUC6-12h (P < .05). Patients with SLCO1B3 334T/699G alleles had significantly lower dn-AUC6-12h values than homozygotes (P < .05). By introducing body weight, age, and EHC-related factors, including co-administered CNIs and genetic polymorphism of drug transporters, as covariates in the XGboost machine learning model, the prediction performance of AUC0-12h for MPA in Chinese adult renal allograft recipients can be improved.


Substituted ammonium ions as allergenic determinants in drug allergy.
Serious, and occasionally fatal, anaphylactic-like (anaphylactoid) reactions may occur when a patient is exposed to a drug for the first time. Apart from the penicillins, nothing is known of the nature of antigenic or sensitizing drug determinants and, as yet, there is no evidence for the involvement of IgE antibodies in most drug reactions. Muscle relaxants such as alcuronium have been implicated in many life-threatening anaphylactoid reactions but the mechanisms remain unclear. We have now investigated the possibility that drug-specific IgE antibodies are involved by using an alcuronium-carrier complex in a radioimmunoassay with patients' sera. Alcuronium-reactive antibodies were found in five drug-sensitive subjects and most of the antibodies cross-reacted with other muscle relaxants and with a variety of apparently structurally unrelated drugs. Structure-activity studies designed to explore the molecular basis of the antibody binding established that quaternary and tertiary ammonium ions were the complementary allergenic sites on the reactive drugs. These structures occur widely in many drugs but also in foods, cosmetics, disinfectants and industrial materials. Hence, there would seem to be ample opportunity for sensitive individuals to come into contact with and synthesize IgE antibodies to these unusual, and previously unsuspected, antigenic determinants.


Use of combined oral contraceptives alters metabolic determinants and genetic regulation of C-reactive protein. The Cardiovascular Risk in Young Finns Study.
Use of combined oral contraceptives (COCs) is known to increase concentrations of C-reactive protein (CRP), an important predictor of cardiovascular disease. The inflammatory nature of the disease is well acknowledged. The aim of this study was to find out whether the metabolic, lifestyle and genetic determinants of CRP differ between women who use COCs and those who do not use any hormonal contraceptives (non-users). A total of 1,257 women (24-39 years) participated in the ongoing Cardiovascular Risk in Young Finns Study, a population based cross-sectional follow-up study. Use of hormonal contraceptives was determined by questionnaire. Plasma CRP and other cardiovascular risk factors were measured; five CRP gene polymorphisms were genotyped (-717A>G, -286C>T>A, +1059G>C, +1444C>T and +1846G>A) and CRP haplotypes were constructed. Multivariate regression analysis revealed that BMI and leptin were the main determinants of CRP in non-users, whereas in COC users the main determinants were BMI, leptin and triglycerides. The median CRP and triglyceride values were significantly higher in COC users than in non-users. The correlations between triglyceride and CRP were tested separately in different COC users in accordance with progestagen content and dosage, the analysis revealing significant association only in women using a high dosage of progestagen or cyproterone. The haplotypes of CRP gene had no significant association with CRP concentration in COC users, while independent effects on CRP were found in non-users. Our study suggests that use of COCs alters the metabolic determinants and genetic regulation of CRP.


Dietary marine-derived ingredients for stimulating hair cell cycle.
In normal condition human hair growth occurs through three phases, anagen (growth phase included about 85 % of hairs, last from 2 to 6 years), catagen (transitional phase lasting up to 2 weeks) and telogen (resting phase which last from 1 to 4 months). Natural dynamics of the hair growth process can be impaired by several factors, such as genetic predisposition, hormonal disorders, aging, poor nutrition or stress, which can lead to the slowdown in the growth of hair or even hair loss. The aim of the study was to assess the hair growth promotion effect of marine-derived ingredients, hair supplement Viviscal® and its raw components (marine protein complex AminoMarC®, shark and oyster extract). Cytotoxicity, production of alkaline phosphatase and glycosaminoglycans, as well as expression of genes involved in hair cycle-related pathways were investigated using dermal papilla cells, both immortalized and primary cell lines. Tested marine compounds showed no evidence of cytotoxicity under in vitro conditions. Viviscal® significantly increased proliferation of dermal papilla cells. Moreover, tested samples stimulated cells to produce alkaline phosphatase and glycosaminoglycans. Increased expression of hair cell cycle-related genes was also observed. The obtained results indicate that marine-derived ingredients stimulate hair growth through anagen activation.


Inhibitory effect of two Indian medicinal plants on aldose reductase of rat lens in vitro.
To assesse the inhibitory effect of alcoholic extract of two Indian medicinal plants namely Ceasalpinia digyna Rottler and, Alangium lamarckii Thwaits on aldose reductase (AR) of rat lens. Rats lens were enucleated through posterior approach and their homogenate was prepared and centrifuged to obtain a clear supernatant for the determination of AR activity and protein content. The alcoholic extract of Ceasalpinia digyna and Alangium lamarckii had a potent inhibitory effect on the lens AR enzyme. The IC(50) values of alcoholic extract of the selected plants were calculated and were (46.29±11.17) and (106.00±5.11) μg/mL, respectively. Quercetin was used as a positive control and its IC(50) value was (2.95±1.53) μg/mL. Thus, it is concluded that alcoholic extracts of the selected plant exhibit significant inhibitory effects on AR in the rat lens in vitro.


Impact of new International Association of Diabetes and Pregnancy Study Groups (IADPSG) diagnostic criteria on perinatal outcomes in a regional tertiary hospital in New South Wales, Australia.
We compared the impact of new gestational diabetes (GDM) diagnostic criteria by IADPSG with previous criteria to ascertain concordance between the two criteria; and whether women discordant for GDM between the old and new criteria had increased pregnancy complications. Oral glucose tolerance tests of pregnant women across time periods using old criteria and new criteria were collected. Maternal data and perinatal outcomes were compared between diagnostic concordant and discordant women. In total, 666/5178 (12.9%) women were diagnosed and treated for GDM. There was a significant increase in odds of any complication in concordant positive women (OR 3.91 95%CI 2.71-5.63, p<.0001); in women only positive by new GDM criteria (OR 2.06, 95% CI 1.41-2.99, p=.0002); and women only positive by old GDM criteria (OR 2.28, 95% CI 1.42-3.66, p=.0006); compared to concordant negative women. This is mainly due to macrosomia and nursery admissions. This study confirms that women diagnosed with GDM on both old and new criteria have a higher rate of birth complications than women without GDM. Women who have been missed out due to new criteria may still be at risk. Therefore, combination of both old and new criteria may be optimal for identifying high-risk pregnancies.


Invasive findings in patients with angina equivalent symptoms but no coronary artery disease; results from the heart quest cohort study.
The cause of angina in patients presenting at coronary angiography without significant coronary artery disease (CAD) has not been systematically assessed in a large prospective cohort. This study is aimed to identify the cause of angina in these patients. This prospective cohort comprised 718 consecutive patients with angina equivalent symptoms and no CAD (defined as no coronary stenosis ≥ 50%) between January 1st 1997 and July 31st 2008. All patients underwent additional invasive testing (intracoronary acetylcholine administration, fast atrial pacing). Small vessel and vasospastic diseases were diagnosed according to symptoms and vessel reaction during testing. Mean age was 56.3 ± 11.0 years (range 15 to 81 years). A majority of 431 patients (60.0%) had small vessel and/or vasospastic disease (233 patients had small vessel disease, 145 vasospastic disease and 53 a combination of both). Additional 87 patients (12.1%) had another cardiac disease. Only in a minority of 200 study participants (27.9%) that the symptoms were attributed to an extracardiac problem. Patients with small vessel disease were more likely to be female, to have hypertension, to have a family history of CAD and to have effort-related symptoms. Patients with vasospastic disease were more likely to be current smokers, to have angina at rest or to present as myocardial infarction, and to have coronary sclerosis and/or endothelial dysfunction. In a majority of patients with angina but no significant CAD, a cardiac cause of their symptoms can be found. Systematical invasive testing may help optimizing the medical management of these patients.


Regulation of chromosome segregation in Escherichia coli.
Cell division is tightly coupled to DNA replication in Escherichia coli, as evidenced by the rarity of anucleate cells in steady state cultures. When DNA synthesis is arrested, cell division also comes to a halt and filamentous growth ensues, again with little formation of anucleate cells. To test the precise role of the SfiA division inhibitor during filamentous growth, we compared sfiA+ and sfiA- strains in their response to thymine starvation. More residual division was observed in the sfiA mutant culture, and autoradiographic analysis revealed that 13% of the final population consisted of cells of normal size containing no DNA compared to 0.9% in the thymine-starved sfiA+ culture. The SfiA division inhibitor is known to be synthesized massively during thymine starvation as part of the inducible SOS response. We conclude that it prevents aberrant division and formation of anucleate cells, thus assuring proper segregation when DNA synthesis is perturbed. The SfiC division inhibition mechanism, also associated with the SOS response, does not affect cell division during thymine starvation. On the other hand, an SOS-independent mechanism of division arrest clearly comes into play during thymine starvation of a sfiA sfiC mutant: although considerable aberrant division took place, the majority of the cells formed long filaments with 1 or 2 masses of DNA. Thus, E. coli assures proper chromosome segregation by two systems when DNA replication is perturbed: the rapid, efficient SfiA division inhibitor and a less stringent SOS-independent mechanism.


A new technique for trans-perirectal iodine-125 seed implantation in prostatic cancer guided by CT and 3D printed template: Two case reports.
Low-dose-rate prostate brachytherapy with permanent iodine-125 is an important curative treatment for low-risk prostate cancer, and it has been demonstrated that brachytherapy with permanent seeds is an effective treatment. However, differences in prostate volume, spatial location, and gland deformation between images obtained in the pre-planning phase and those obtained during the implantation procedure affect accurate delivery of the pre-planned dose. Furthermore, the complicated procedure could be a burden to elderly patients, for example, the risks associated with general anesthesia. In addition, ultrasound images are not as clear as computed tomography (CT) images with regard to identifying the location of seeds. Therefore, a new method for guidance during the procedure is urgently needed. Here, we have described a new method for precise trans-perirectal insertion of radioactive iodine-125 seeds in patients with prostate cancer under the guidance of CT and a 3D-printed template. These are some of the advantages of this technique over the standard procedure for seed implantation in the prostate: It requires only local anesthesia, the pre-planning phase can be completed before the procedure, and the operation time is considerably shorter. This report describes trans-pararectal iodine-125 seed brachytherapy for prostate cancer under local anesthesia and the guidance of a 3D printed template in two elderly patients. The dose parameters determined in the preoperative planning phase were verified postoperatively and found to be consistent. Further, the procedure was completely successfully with no major complications in both cases, and the patients' prostate-specific antigen levels were normal at the most recent follow-up conducted 50 months after the procedure. Therefore, this technique seems promising for prostate cancer brachytherapy, and its application needs to be researched and extended further in the future.


Disease course and prognosis of pleuroparenchymal fibroelastosis compared with idiopathic pulmonary fibrosis.
Idiopathic pleuroparenchymal fibroelastosis (iPPFE) is a rare interstitial lung disease characterized by unique radiological and pathological findings. However, pathological evaluations are available only in a limited number of patients. Therefore, several clinical diagnostic criteria have been proposed. Nevertheless, the applicability of these criteria has not yet been validated. Moreover, the clinical course of iPPFE and its prognosis have not yet been completely elucidated. The present study assessed previously proposed clinical diagnostic criteria by comparing the clinical features between pathologically diagnosed iPPFE (p-iPPFE) and clinically diagnosed iPPFE (c-iPPFE). Subsequently, the clinical features of iPPFE were characterized and compared with those of idiopathic pulmonary fibrosis (IPF, n = 323). Clinical characteristics of c-iPPFE (n = 27) and p-iPPFE (n = 35) were similar. No significant difference was observed in terms of prognosis between c-iPPFE and p-iPPFE. The number of patients with iPPFE (both c-iPPFE and p-iPPFE) who developed lung cancer was significantly lower than that of patients with IPF. However, acute exacerbation (AE) showed similar incidence in patients with iPPFE and IPF. Survival of patients with iPPFE was significantly worse than that of patients with IPF (5-year survival rate: 38.5% vs. 63.5%, p < 0.0001), and the most common cause of death was chronic respiratory failure (73.8%), followed by AE (14.3%). Male gender was the only poor prognostic factor of iPPFE. The present study demonstrated efficiency of clinical diagnosis and also revealed clinically important characteristics of iPPFE that should be considered for management of iPPFE.


Extreme sensitivity of staphylococcal enterotoxin B and C production to inhibition by cerulenin.
Production of staphylococcal enterotoxins B and C was completely inhibited by concentrations of cerulenin (4 mug/ml and 2 mug/ml, respectively) that did not affect either growth rate or final growth density. Type A toxin formation was not similarly inhibited.


Cyclosporine pharmacokinetics and effect in the type I diabetic rat model.
Recent clinical studies have demonstrated the potential benefit of the T-cell-specific immunosuppressant, cyclosporine, in the treatment of Type I insulin-dependent diabetes. In the present study, steady-state cyclosporine pharmacokinetics, fasting glucose and insulin levels and renal function were examined in stable insulin-dependent diabetic rats and compared to non-diabetic rats. Mean creatinine clearance 30 days following diabetes induction was not significantly different from saline controls. Cyclosporine treatment (5 mg/kg/day i.v. for 13 days) did not significantly alter creatinine clearance in either group; however, renal function of vehicle-treated diabetic rats was markedly reduced compared to other groups. Serum insulin concentrations were significantly greater in diabetic rats treated with cyclosporine compared to the control group (35.1 +/- 22.7 vs. 16.0 +/- 8.1 microU/ml; P less than 0.05). Glucose levels were proportionately reduced in diabetic rats treated with cyclosporine. Area under the concentration-time curve, half-life and volume of distribution of cyclosporine were significantly reduced in diabetic rats compared to non-diabetic controls. In summary, the pharmacokinetics and pharmacodynamics of cyclosporine were significantly different in the insulin-dependent diabetic rat model compared to normal controls. Furthermore, short-term cyclosporine therapy reduced the extent of experimental diabetic nephropathy observed in this model.


A human-in-the-loop deep learning paradigm for synergic visual evaluation in children.
Visual development during early childhood is a vital process. Examining the visual acuity of children is essential for early detection of visual abnormalities, but performing visual examination in children is challenging. Here, we developed a human-in-the-loop deep learning (DL) paradigm that combines traditional vision examination and DL with integration of software and hardware, thus facilitating the execution of vision examinations, offsetting the shortcomings of human doctors, and improving the abilities of both DL and doctors to evaluate the vision of children. Because this paradigm contains two rounds (a human round and DL round), doctors can learn from DL and the two can mutually supervise each other such that the precision of the DL system in evaluating the visual acuity of children is improved. Based on DL-based object localization and image identification, the experiences of doctors and the videos captured in the first round, the DL system in the second round can simulate doctors in evaluating the visual acuity of children with a final accuracy of 75.54%. For comparison, we also assessed an automatic deep learning method that did not consider the experiences of doctors, but its performance was not satisfactory. This entire paradigm can evaluate the visual acuity of children more accurately than humans alone. Furthermore, the paradigm facilitates automatic evaluation of the vision of children with a wearable device.


Relationships Among Disease, Social Support, and Perceived Health: A Lifespan Approach.
We examined the relationship between the cumulative presence of major disease (cancer, stroke, diabetes, heart disease, and hypertension), social support, and self-reported general and emotional well-being in a community representative sample of predominantly White and African American respondents (N = 1349). Across all ages, greater presence of disease predicted poorer reported general health, and predicted lower emotional well-being for respondents 40 and above. In contrast, social support predicted better-reported general and emotional well-being.We predicted that different types of social support (blood relatives, children, friends, community members) would be relatively more important for health in different age groups based on a lifespan or life stage model. This hypothesis was supported; across all ages, social support was related to better reported general and emotional health, but sources of support differed by age. Broadly, those in younger age groups tended to list familial members as their strongest sources of support, whereas older group members listed their friends and community members. As a whole, social support mediated the effect of disease on reported wellbeing,however, moderated mediation by type of support was not significant. The results are consistent with a lifespan approach to changing social ties throughout the life course.


Different risk-increasing drugs in recurrent versus single fallers: are recurrent fallers a distinct population?
Polypharmacy, and specifically the use of multiple fall-risk-increasing drugs (FRID), have been associated with increased risk of falling in older age. However, it is not yet clear whether the known set of FRIDs can be extrapolated to recurrent fallers, since they form a distinct group of more vulnerable older persons with different characteristics. We aim to investigate which classes of medications are associated with recurrent falls in elderly patients visiting the Emergency Department (ED) after a fall. This study had a cross-sectional design and was conducted in the ED of an academic medical center. Patients who sustained a fall, 65 years or older, and who visited the ED between 2004 and 2010 were invited to fill in a validated fall questionnaire designed to assess patient and fall characteristics (CAREFALL Triage Instrument [CTI]). We translated self-reported medications to anatomical therapeutic chemical (ATC) codes (at the second level). Univariate logistic regression analysis was performed to explore the association between medication classes and the outcome parameter (recurrent fall). Multivariate logistic regression was used to assess the associations after adjustment to potential confounders. In total 2,258 patients participated in our study, of whom 39 % (873) had sustained two or more falls within the previous year. After adjustment for the potential confounders, drugs for acid-related disorders (adjusted odds ratio [aOR] 1.29; 95 % CI 1.03–1.60), analgesics (aOR 1.22; 95 % CI 1.06–1.41), anti-Parkinson drugs (aOR 1.59; 95 % CI 1.02–2.46), nasal preparations (aOR 1.49; 95 % CI 1.07–2.08), ophthalmologicals (aOR 1.51; 95 % CI 1.10–2.09); antipsychotics (aOR 2.21; 95 % CI 1.08–4.52), and antidepressants (aOR 1.64; 95 % CI 1.13–2.37) remained statistically significantly associated with an ED visit due to a recurrent fall. Known FRIDs, such as psychotropic drugs, also increase the risk of recurrent falls. However, we found four relatively new classes that showed significant association with recurrent falls. In part, these classes may act as markers of frailty and comorbidity, or they may reflect differences in the risk factors affecting the older, frailer population that tends to sustain recurrent falls. Further investigation is needed to elucidate causes and ways to prevent recurrent falls.


Ecological risks of home and personal care products in the riverine environment of a rural region in South China without domestic wastewater treatment facilities.
Home and personal care products (HPCPs) including biocides, benzotriazoles (BTs) and ultraviolet (UV) filters are widely used in our daily life. After use, they are discharged with domestic wastewater into the receiving environment. This study investigated the occurrence of 29 representative HPCPs, including biocides, BTs and UV filters, in the riverine environment of a rural region of South China where no wastewater treatment plants were present, and assessed their potential ecological risks to aquatic organisms. The results showed the detection of 11 biocides and 4 BTs in surface water, and 9 biocides, 3 BTs and 4 UV filters in sediment. In surface water, methylparaben (MeP), triclocarban (TCC), and triclosan (TCS) were detected at all sites with median concentrations of 9.23 ng/L, 2.64 ng/L and 5.39 ng/L, respectively. However, the highest median concentrations were found for clotrimazole (CLOT), 5-methyl-1H-benzotriazole (MBT) and carbendazim (CARB) at 55.6 ng/L, 33.7 ng/L and 13.8 ng/L, respectively. In sediment, TCC, TCS, and UV-326 were detected with their maximum concentrations up to 353 ng/g, 155 ng/g, and 133 ng/g, respectively. The concentrations for those detected HPCPs in surface water and sediment were generally lower in the upper reach (rural area) of Sha River than in the lower reach of Sha River with close proximity to Dongjiang River (Pt-test<0.05), indicating other input sources of HPCPs in the lower reach. Biocides showed significantly higher levels in surface water in the wet season than in the dry and intermediate seasons. Preliminary risk assessment demonstrated that the majority of HPCPs monitored represented low risk in surface waters. There are potentially greater risks to aquatic organisms from the use of TCS and TCC in the wet season than in dry and intermediate seasons in surface waters. This preliminary assessment also indicates potential concerns associated with TCC, TCS, DEET, CARB, and CLOT in sediments, although additional data should be generated to assess this fully. Thus future research is needed to investigate ecological effects of these HPCPs on benthic organisms in sediment of rural rivers receiving untreated wastewater discharge.


Differential effects of methoxyamine on doxorubicin cytotoxicity and genotoxicity in MDA-MB-231 human breast cancer cells.
Pharmacological inhibition of DNA repair is a promising approach to increase the effectiveness of anticancer drugs. The chemotherapeutic drug doxorubicin (Dox) may act, in part, by causing oxidative DNA damage. The base excision repair (BER) pathway effects the repair of many DNA lesions induced by reactive oxygen species (ROS). Methoxyamine (MX) is an indirect inhibitor of apurinic/apyrimidinic endonuclease 1 (APE1), a multifunctional BER protein. We have evaluated the effects of MX on the cytotoxicity and genotoxicity of Dox in MDA-MB-231 metastatic breast cancer cells. MX has little effects on the viability and proliferation of Dox-treated cells. However, as assessed by the cytokinesis-block micronucleus assay (CBMN), MX caused a significant 1.4-fold increase (P<0.05) in the frequency of micronucleated binucleated cells induced by Dox, and also altered the distribution of the numbers of micronuclei. The fluorescence probe dihydroethidium (DHE) indicated little production of ROS by Dox. Overall, our results suggest differential outcomes for the inhibition of APE1 activity in breast cancer cells exposed to Dox, with a sensitizing effect observed for genotoxicity but not for cytotoxicity.


[SMILE - Small Incision Lenticule Extraction].
Refractive lenticule extraction is a corneal surgical technique that uses a femtosecond laser exclusively to create an intrastromal refractive lenticule for the correction of myopia and myopic astigmatism. In small incision lenticule extraction (SMILE) the generated refractive lenticule is subsequently extracted through a small incision. The reported efficacy, predictability and safety of the flap-less SMILE procedure is similar to those of femtosecond laser in situ keratomileusis (LASIK). Advantages of SMILE over LASIK include less iatrogenic dry eye, fewer induced higher-order aberrations, and potentially less biomechanical weakening of the cornea. However, there is a steeper surgeon learning curve for SMILE as the procedure is technically more challenging than LASIK. Furthermore, the current SMILE laser platform cannot use cyclotorsion control or eye-tracking technology and retreatment options are more complex compared to LASIK. This review looks at patient selection, surgical method, possible complications, retreatment options, and postoperative outcome of the SMILE technique.


Gastric teratomas in infants: report of two cases.
Gastric teratoma is a rare benign tumor with a striking male predominance in patients under one year of age. The common presenting features are a palpable mass producing gastro-intestinal hemorrhage or respiratory distress. Approximately 50% of gastric teratomas may show calcification on plain abdominal roentgenograms. Two cases in newborns are reported, and the clinical and radiologic features of gastric teratomas reviewed.


Concurrent determination of brain dopamine and 5-hydroxytryptamine turnovers in individual freely moving rats using repeated sampling of cerebrospinal fluid.
5-Hydroxytryptamine (5-HT) turnover and dopamine (DA) turnover values were obtained in individual conscious rats by measuring the rates of accumulation of 5-hydroxyindoleacetic acid (5-HIAA), 3,4-dihydroxyphenylacetic acid (DOPAC), and homovanillic acid (HVA) in cisternal CSF samples taken from each rat at 0, 30, and 60 min after probenecid (200 mg/kg i.p.) administration. In a separate experiment, 5-HT and DA turnover values were determined in CSF, striatum, and rest of brain of groups of rats killed 0, 30, or 60 min after probenecid. Whole brain turnover values were calculated from striatal and rest of brain values. Mean turnover values using CSF were comparable with both procedures. DA turnover values were greater when based on total (i.e., free + conjugated) DA metabolites than when based on free metabolites. After partial inhibition of monoamine synthesis with the decarboxylase inhibitor DL-alpha- monofluoromethyl -DOPA ( MFMD , 100 mg/kg p.o.) DA and 5-HT turnover values were comparably reduced in whole brain, rest of brain, and CSF but more markedly reduced in the striatum. Mean DA and 5-HT turnover values obtained using CSF were similar with probenecid doses over the range 150-250 mg/kg i.p. but were variable when repeatedly determined in the same rats after administration of 200 mg/kg probenecid. Results in general show that the CSF procedure may be used to determine concurrently both 5-HT and DA turnover (when estimated from the sum of total but not free metabolites) and that it provides a good index of whole brain turnover of these transmitters in the conscious individual rat.


Unexpected Bradycardia Related to Surgical Manipulation During Thoracolumbar Spinal Surgery.
Although spinal surgery can offer pain relief and functional improvements in daily life, it is often associated with various perioperative complications. The incidence of cardiac complications associated with spinal surgery is relatively low. We evaluated frequency and causes for bradycardia incidents in posterior thorocolumbar spinal surgeries. We retrospectively evaluated posterior thoracolumbar spinal surgeries between 2018-2022 for bradycardic events in our tertiary general hospital. Patients operated for degenerative changes or disk herniations are included, other cases for tumors, trauma, arteriovenous (AV) fistulae or previously operated are excluded. The study reached 6 eligible patients (4 female and 2 male) aged between 45-75 years (mean: 63.3) among 550 patients operated between 2018-2022. The rate of bradycardia was 1.09%. Of these, 5 patients (lumbar discectomy: one; posterior stabilization:4) exhibited it following L2 and L3 root manipulation and one presented it following L4-5 discectomy. In each of these cases, bradycardia occurred during surgical manipulation and ceased upon removal of the insult. None of the cases exhibited accompanying hypotension. The patient's heart rates were seen to drop to lowest the of 30 beats/min, and all patients exhibited favorable outcomes and no postoperative cardiac complications over a mean follow-up period of 20 months (range: 10-40 months). The current study examines the occurrence of unexpected bradycardia events associated with thoracolumbar spinal surgery during surgical handling of the dura mater. Awareness of such incidents among surgeons and anesthesiologists can help prevent catastrophic outcomes caused by adverse cardiac events.


Ablation of murine jejunal crypts by alkylating agents.
The gut microcolony assay has been used to measure damage to intestinal crypts by single and split doses of 3 alkylating agents: mechlorethamine hydrochloride (HN2), bis-chloroethyl-nitrosourea (BCNU) and isopropyl methane sulphonate (IMS). The single-dose survival curves for whole crypts were distinguished by extrapolation numbers (3.0, 176 and 1.5 respectively) that were lower than most previously published values for assay by irradiation. Significant sparing of crypts occurred when doses of HN2 or BCNU, but not IMS, were given in 2 equal fractions separated by more than 2 h. Deduced D0 values for those cells from which crypts regenerate were 1.9 mg/kg HN2, 19 mg/kg BCNU and 487 mg/kg IMS.


Suppressive effects of Ixodes persulcatus sialostatin L2 against Borrelia miyamotoi-stimulated immunity.
Borrelia miyamotoi infection is an emerging tick-borne disease that causes hard tick-borne relapsing fever. B. miyamotoi is transmitted through the bite of ticks, including Ixodes persulcatus. Although accumulating evidence suggests that tick salivary proteins enhance the infectivity of other tick-borne pathogens, the association of B. miyamotoi with tick-derived proteins remains unknown. In this study, the effect of I. persulcatus sialostatin L2 (Ip-sL2), a tick-derived cystatin, on specific immunity to B. miyamotoi was preliminarily investigated in vitro. Mice were immunized with heat-killed B. miyamotoi and in vitro analyses of the splenocytes of the immunized mice indicated that the expression levels of the activation markers of CD11c+ and CD3+ cells were significantly upregulated by B. miyamotoi stimulation. Spleen cells from B. miyamotoi-immunized mice were used to determine whether Ip-sL2 regulates murine immune responses against B. miyamotoi. Treatment with Ip-sL2 in vitro inhibited the activation of CD11c+ and CD3+ cells as well as inflammatory cytokine production by cultured splenocytes. These findings show that Ip-sL2 has modulatory effects on murine immune responses to B. miyamotoi. Therefore, it is necessary to clarify in the future whether Ip-sL2 is involved in the enhanced infectivity of B. miyamotoi.


Mutation-selection dynamics and error threshold in an evolutionary model for Turing machines.
We investigate the mutation-selection dynamics for an evolutionary computation model based on Turing machines. The use of Turing machines allows for very simple mechanisms of code growth and code activation/inactivation through point mutations. To any value of the point mutation probability corresponds a maximum amount of active code that can be maintained by selection and the Turing machines that reach it are said to be at the error threshold. Simulations with our model show that the Turing machines population evolve toward the error threshold. Mathematical descriptions of the model point out that this behaviour is due more to the mutation-selection dynamics than to the intrinsic nature of the Turing machines. This indicates that this result is much more general than the model considered here and could play a role also in biological evolution.


Idiotypic and anti-idiotypic determinants on lymphocytes during anti-Rh immunization.
Evolution of idiotypic determinants on lymphocytes membrane and presence of other lymphocytes carrying anti-idiotypic determinants, were studied in Rh negative human volunteer blood donors during immunization towards Rh factor. For this purpose E-Rh Rosettes, direct immunofluorescence, inhibition of E-Rh Rosettes by anti-idiotypic sera as well as EA-Rh Rosettes--induced with Fab'2 fragments from anti-Rh antibodies and lymphocytes from the same subject--were examined and compared to the evolution of circulating antibodies. E-Rh Rosettes preceded or accompanied production of anti-Rh antibodies; their frequency decreased after the fifth month following immunization, meanwhile EA-Rh Rosettes increased in parallel with antibody decrease. The direct immunofluorescence and the inhibition of E-Rh Rosettes, by anti-idiotypic sera, show the presence of idiotypic determinants on lymphocyte membranes; the presence of EA-Rh Rosettes, coinciding with the decrease in antibodies demonstrate the existence of lymphocytes bearing auto-anti-idiotypic determinants.


Pelvic sidewall adenocarcinoma after definitive therapy for cervical adenocarcinoma in situ.
Traditionally, hysterectomy is considered definitive therapy for cervical adenocarcinoma in situ (AIS) in women beyond childbearing. A 45-year-old gravida 2, para 2 patient presented with cervical dysplasia and on pathology review of the large loop excision procedure cervical adenocarcinoma in situ was diagnosed. She underwent extrafascial hysterectomy and bilateral salpingo-oophorectomy. Final pathology revealed adenocarcinoma in situ with negative margins. Twenty-eight months later, she presented with right lower extremity deep venous thrombosis. A computed tomography (CT) scan of the abdomen and pelvis showed a pelvic sidewall mass. A CT-guided biopsy of the mass was consistent with invasive adenocarcinoma of the endocervical type. She underwent combination therapy with weekly cisplatin and extended field radiation therapy. This case depicts another example of the unpredictable nature of cervical AIS. Despite undergoing definitive surgery, a residual focus of disease may remain leading to invasive adenocarcinoma. Close follow-up is required of all patients diagnosed with AIS because the disease is poorly understood.


Long term adherence to dietary recommendations after inpatient rehabilitation: prospective follow up study of patients with coronary heart disease.
To evaluate the adherence to nutritional recommendations in inpatient rehabilitation and the long term maintenance of dietary changes among patients with coronary heart disease. Prospective cohort study. Two rehabilitation clinics in Germany. A cohort of 1206 patients undergoing inpatient rehabilitation after an acute manifestation of coronary heart disease. Self reported dietary intake before, during, and one and three years after rehabilitation measured with a semiquantitative food frequency questionnaire and summarised to a nutritional index, which was used to categorise patients as having a poor, fair, or good diet. During rehabilitation the proportion of patients whose dietary intake was categorised as good increased strongly from 30% to 91%. One and three years after rehabilitation a still increased proportion of 49% and 42%, respectively, in the good category was observed. The strong increase in intake of low fat and wholemeal products that was achieved during rehabilitation was followed after rehabilitation discharge by a backslide to the intake observed before rehabilitation admission. The avoidance of unfavourable food items, such as French fries or eggs, was at least partly maintained during the follow up period. During inpatient rehabilitation most patients do have to make major changes in their dietary intake to comply with recommendations. Although some proportion of patients continue to adhere to dietary recommendations in the long run, further research into strategies to improve maintenance of dietary changes is needed to enhance further the long term benefits from cardiac rehabilitation.


Nuclear translocation of H2RSP is impaired in regenerating intestinal epithelial cells of murine colitis model.
Hepatocyte growth factor activator inhibitor type 2-related small peptide (H2RSP) is a recently identified nuclear peptide that is abundantly expressed in the gastrointestinal tract. In this study, we analyzed the expression of H2RSP in normal and injured intestinal mucosa in a murine experimental colitis induced by oral administration of 2.5% dextran sodium sulfate. Results of immunohistochemistry and in situ hybridization showed that H2RSP was expressed predominantly in the epithelium of normal intestine. Whereas H2RSP was localized in the cytoplasm of cells in the crypt, it was translocated into the nuclei of the surface epithelial cells. In injured intestine, H2RSP was detected in the cytoplasm of regenerating epithelial cells, and the nuclear translocation was impaired even in the surface epithelium. However, the mRNA level was not significantly altered in these cells by real-time reverse transcription-polymerase chain reaction using total RNAs obtained from the fractionated mucosal tissue samples prepared by laser-captured microdissection technique. On the other hand, H2RSP mRNA was significantly upregulated in the stromal cells of injured intestinal mucosa compared with those in normal mucosa, which shows cytoplasmic localization of H2RSP. These circumstantial evidences suggest that the nuclear translocation of H2RSP may be related to a signaling involved in the transition from cellular proliferation to differentiation.


[Diabetes mellitus and changes in hemostasis: study of the fibrinolytic response of insulin-dependent patients without vascular disease].
Diabetes mellitus (DM) is characterized by a hypercoagulability state and many of these disorders are corrected with adequate metabolic control. The goal of this study was to assess diverse hemostatic and fibrinolytic parameters in 12 insulin-dependent (IDDM) metabolically controlled patients without vascular lesions and in a group of 12 healthy volunteers. A significant difference was observed in the euglobulin lysis time (ELT), after a stress test, since only 3 patients had an adequate fibrinolytic response. These results suggest that the fibrinolytic alterations found in DM are not secondary to metabolic disorders caused by the disease and we can consider that the existence of subclinical alterations of the vascular endothelium would be responsible for these alterations.


Laparoscopic "single knot-single running" suture vesico-urethral anastomosis with posterior musculofascial reconstruction.
To describe results of a simplified technique to configure the vesicourethral anastomosis and to restore posterior musculofascial plate during laparoscopic radical prostatectomy with a "single knot-single running" suture. Between December 2006 and 2009, a conventional Van Velthoven anastomosis (group A) was applied in 125 cases while the novel anastomosis was applied in 155 consecutive patients (group B). A between group comparison of continence recovery was performed with log-rank test and Chi-square test. Continuous variables were compared with Wilcoxon's test and categorical ones with Chi-square test. Median operative time and median time to configure the anastomosis were comparable between two groups. Proportions of patients using 0 pad, 1 pad and >1 pad per day were statistically different between groups at 1 month (54.4%, 14.4%, 31.2% vs. 52.3%, 27.7%, 20%, in group A and group B, respectively; p = 0.01), at 3 months (73.6%, 8.8%, 17.6% vs. 86.5%, 7.1%, 6.5%; p = 0.01) and at 6 months (80.8%, 12.8%, 6.4% vs. 92.3%, 6.5%, 1.2%; p = 0.01). At log-rank test, continence recovery between two groups was statistically different (p = 0.008). The excellent outcome together with the easiness of performing this novel anastomosis compared to the traditional Van Velthoven make it widely reproducible.


Prognostic Significance of Proliferative Markers: Cyclin D1 and CENPF in Oral Squamous Cell Carcinoma Patients-A Cohort Study.
Oral cancer ranks sixth place worldwide among other cancers and is known for its high morbidity and mortality rates. Among oral cancer, oral squamous cell carcinomas (OSCC) remains the most common. Expression of specific biomarkers are known to be related to the prognosis of the OSCC. An immunohistochemistry study was performed to evaluate the expression of Cyclin D1 and CENPF for their prognostic significance in twenty OSCC patients. The follow-up period ranged from 10 to 18 months. The expression of these proliferative markers was correlated with demographic, clinical and histopathological grade of the disease. The results revealed 28% mortality rates in relation to OSCC involving retro-molar trigone. Based on the Cyclin D1 and CENPF expression, high mortality rate (Pearson coefficient = 0.800) was seen with grade 3 and 4 expressions of the markers. Decreased survival rates (Pearson coefficient = 0.824) were observed with stage III and IV disease with grade 3 and 4 expressions of the markers. Cyclin D1 and CENPF have shown promising results as proliferative markers which can be linked with prognosis of OSCC in this study. Further studies with larger sample size are needed to extrapolate our findings.


Corneal power after refractive surgery for myopia: contact lens method.
To clarify the theoretical background of the rigid contact lens overrefraction (CLO) method to determine corneal power after corneal refractive surgery. University Eye Clinic, University of Würzburg, Würzburg, Germany. Using paraxial geometrical optics, the measurement situation for the contact lens method was analyzed and the definitions of corneal refractive power were reviewed. Based on the theoretical Gullstrand eye, model eyes were constructed, representing 1 emmetropic and 2 myopic eyes (primary refraction -5.21 diopters [D] and -10.25 D, respectively) before and after photorefractive keratectomy and laser in situ keratomileusis. In these eyes, the application of the CLO was mathematically simulated using Gaussian thick-lens optics and commercial ray-tracing software. The CLO method measured neither the equivalent (total) power nor the vertex (back) power of the cornea but rather the quantity 336/R(1C) (R(1C) = anterior corneal radius). Based on these results and the Gullstrand eye, new formulas are proposed to derive the equivalent power and vertex power of the cornea by the CLO method. Depending on whether intraocular lens calculation formulas are based on equivalent (total) corneal power or vertex corneal power, the respective new formulas for the CLO method should be applied in patients after corneal refractive surgery. An increase in prediction accuracy of the refractive outcome is expected.