A deletion in the second exon of an HLA-DRB1 allele found in a DR2-negative narcolepsy patient.
In this report, we describe a new allele of the HLA-DRB 1 gene carrying a form of mutation that has not been observed before. It appeared in an HLA-DR2-negative narcolepsy patient who, besides HLA-DR4, revealed a serologic HLA-DR blank segregating with HLA-DQ1. Oligotyping showed that the new allele belongs to the HLA-DR8 group. Restriction analysis and DNA sequencing revealed the deletion of 12 bp as well as the substitution of 9 flanking base pairs between codons 36 and 43. The expression of the mutated gene was demonstrated by the presence of its messenger RNA and a few positive reactions with DR8 sera. Without interrupting the reading frame, the mutation leads to a gene product composed of a modified amino acid sequence. We anticipate that the mutation influences the conformation of the molecule with possible consequences concerning immune response.


The effect of a hand puppet-based therapeutic play for preschool children on the fear and pain associated with blood collection procedure.
The aim of this study was to determine the effects of a therapeutic play involving a hand puppet on the fear and pain associated with blood collection procedure in preschool children. The research was conducted as a randomised controlled experiment. The sample included children aged 3-6 years who attended the blood collection unit between July and October 2022 and met the study's inclusion criteria. The research was completed with a total of 120 children, divided evenly into one of two groups. The nursing intervention of the research was a therapeutic play applied with a hand puppet. Data were collected through face-to-face interviews using a Questionnaire Form, the Child Fear Scale and the Wong-Baker Faces Pain Rating Scale. Ethical principles were followed in the research. Differences between mean fear and pain level scores between the groups were statistically significant (p < 0.05). The therapeutic play applied with a hand puppet reduced the level of fear and pain associated with the blood collection process. Health professionals working in units related to paediatrics can use hand puppets, which are easy to use, inexpensive and practical, to reduce the fear and pain associated with blood collection from pre-school children.


Axillary Downstaging in Occult Primary Breast Cancer After Neoadjuvant Chemotherapy.
Neoadjuvant chemotherapy (NAC) is increasingly used for clinically node-positive (cN+) tumors with intact primary breast cancer (IPBC) to downstage the axilla, and those who convert to cN0 may be eligible for sentinel lymph node biopsy (SLNB). Rates of axillary downstaging in occult primary breast cancer (OPBC) are unknown. The aim of this study was to determine the frequency of nodal pathologic complete response (pCR) following NAC in a cohort of patients with OPBC. Twenty-eight patients with stage II/III OPBC treated between January 2008 and December 2019 were identified. Twenty patients had cN1-3 OPBC, pretreatment lymph node needle biopsy, and received NAC; these constituted the study population. Treatment factors and nodal pCR rates were summarized by tumor subtype. Median age at diagnosis was 54 years. Most patients presented with cN1 disease (75%) and ductal histology (80%). Nodal pCR was seen in 16/20 (80%) patients. Eight (40%) patients were triple negative, 6 (30%) were estrogen receptor-positive/human epidermal growth factor receptor 2-negative (ER +/HER2 -), and 6 (30%) were HER2 positive, with pCR rates of 88%, 50%, and 100%, respectively. Among the 15 patients who presented as cN1, 14 (93%) converted to cN0 following NAC. Of these, nine underwent SLNB and all achieved nodal pCR (100%). In this small series, 80% of OPBC patients achieved nodal pCR following NAC. pCR rates varied by receptor profile, being lowest in the ER positive/HER2 negative group and highest in the HER2 positive group (50-100%); however, these rates are excellent and numerically exceed those in the literature for IPBC. Given the pCR rate, SLNB may be an option in select OPBC patients who downstage following NAC.


Safety and clinical effectiveness of peginterferon beta-1a for relapsing multiple sclerosis in the real-world setting: Interim results from the Plegridy Observational Program.
The Plegridy Observational Program (POP) is an ongoing, 5-year, phase 4 real-world study of the safety and effectiveness of subcutaneous peginterferon beta-1a in patients with relapsing multiple sclerosis (RMS). This interim analysis from POP assessed the safety and effectiveness of peginterferon beta-1a, including subgroup analyses of patients aged < 50 and ≥ 50 years, newly diagnosed and non-newly diagnosed patients, and new and experienced peginterferon beta-1a users. A total of 1208 patients enrolled in POP. Mean (standard deviation) peginterferon treatment duration in the overall population was 757.0 (529.5) days. The overall incidence of treatment-emergent adverse events (AEs) was 65.5%, and the incidence was higher in new than experienced peginterferon beta-1a users (78.1 vs 52.4%). The overall incidence of treatment-emergent serious AEs was 7.6%, and the incidence was lower in younger than older patients (5.8 vs 11.1%). No new or unexpected safety signals were reported. Overall treatment discontinuation due to AEs occurred in 20.7% of patients, with a higher proportion of new than experienced peginterferon beta-1a users (27.0 vs 14.2%) discontinuing treatment due to AEs. Flu-like symptoms and injection site reactions were significant predictors of time to treatment discontinuation. The adjusted annualized relapse rate (ARR) was 0.12 (95% confidence interval 0.11-0.13) in the overall population and was similar across all subgroups. In the overall population at 4 years, 79.1% of patients were relapse free, the estimated cumulative proportion of patients with confirmed disability worsening was 1.8%, and > 67% of patients achieved clinical no evidence of disease activity (NEDA). Safety data of patients enrolled in POP are consistent with the established clinical safety profile of peginterferon beta-1a. In addition, the low ARR and high proportion of patients achieving clinical NEDA at 4 years across all subgroups indicates the effectiveness of peginterferon beta-1a in treating RMS in real-world clinical settings.


The use of transrectal ultrasound in the diagnosis, guided biopsy, staging and screening of prostate cancer.
In the authors' experience, transrectal sonography has the ability not only to stage prostatic cancer accurately, but also to detect such lesions before they become palpable.


A rapid method, using octadecasilyl-silica, for the extraction of certain peptides from tissues.
Peptides can be recovered from tissues by homogenization in a carefully selected extraction medium followed by adsorption from the supernatant on a small bed of octadecasilyl-silica. Recoveries of corticotropins and somatostatin added to a variety of tissues were quantitative, and the peptides undamaged as determined by high-pressure liquid chromatography.


Tongue lesions in children.
A review of tongue lesions in children showed that there is a great variety requiring operative intervention, often in infancy. While the presenting symptoms may be related to dysphagia and dyspnea, the aim of operative intervention should not only be to salvage life by restoration of breathing and swallowing, but also to leave a tongue capable of adequate speech, taste, sensation, and normal orofacial development. Intimate knowledge of lingual anatomy and function is necessary to allow selection of the ideal procedure and appropriate timing of the therapy. While careful observation and nonoperative approach may be indicated in non-neoplastic macroglossia, early intervention is often necessary in diffuse neoplastic lesions such as lymphangioma, fibromatosis, or fibrolipomatous dysplasia. While malignant tumors are rare in childhood, they do occur and have to ruled out.


Essential Newborn Care and Associated Factors Among Obstetrical Care Providers in Awi Zone Health Facilities, Northwest Ethiopia: An Institutional-Based Cross-Sectional Study.
Each year, millions of newborns die as a result of birth asphyxia, infections, and complications of preterm birth. This burden of death is disproportionately concentrated in low-income countries including Ethiopia. As a result, the care given immediately after birth is crucial for making a successful transition from intrauterine to extrauterine function and to reduce neonatal mortality. Facility-based cross-sectional study design was carried out on a sample size of 208 obstetrical care providers. A simple random sampling technique was used to select the study subjects. The data were collected through Interview-administered questionnaires and observational checklists. The data were entered into Epi-info version 7 and exported to SPSS 23 for analysis. A total of 201 obstetric care providers participated in the study, making a response rate of (96.6%). This study revealed that 62.7% of obstetric care providers practiced essential newborn care properly. The factors significantly associated were received in-service training (AOR = 2.7, 95% CI: 1.35, 5.51), level of education (AOR = 0.46, 95% CI: 0.22, 0.96), midwifery profession (AOR = 3.1, 95% CI: 1.35, 7.39), having good knowledge of essential newborn care (AOR = 2.1, 95% CI: 1.03, 4.49), availability of drugs for essential newborn care (AOR = 2.3, 95% CI: 1.16, 4.72), and availability of medical equipment to perform essential newborn care (AOR = 2, 95% CI: 1.01, 3.96). The practice of essential newborn care was generally low. Having in-service training, midwifery profession, a good knowledge of essential newborn care, availability of drugs, level of education, and availability of medical equipment for essential newborn care were the determinant factors for essential newborn care practice. Improvement in essential newborn care practices could be attained through modifiable proven interventions like provision of in-service training, availed drugs, and medical equipment for essential newborn care.


Measures of Comparative Behavior in Hearing Loss Patients with Cochlear Implant: Caretaker Assessment.
The aim of this study was to assess comparative behavior domain in patients with cochlear implants, using caretaker assessment. A prospective cross-sectional study was conducted. Of 106 patients with hearing loss and receiving cochlear implants were included along with their caretakers. The caretaker' perspective questionnaire-22 was implemented covering emotions, education, and social relationships domain. A repeated measure ANOVA was used to statistical analysis. The implantation elicited a slight reduction in emotions scores domain as well as slight increase in social relationships scores from pre-cochlear implants to 12 months in all aged (6-10 years: - 10.7, 95%CI - 8.4 to 12.9; 4.2, 95%CI 3.0-5.5, 11-20 years: - 8.6, 95%CI - 6.7 to 10.5; 2.5, 95%CI 1.6-3.3, 21-59 years: - 6.8, 95%CI - 4.9 to 8.6; 2.0, 95%CI 1.3-2.7, and older 60 years: - 12.1, 95%CI - 9.5 to 14.6; 3.6, 95%CI 2.7-4.5, respectively). However, the education scores domain has slight increase only in aged 21-59 years group (1.8, 95%CI 0.7-2.8). A long-term after cochlear implants (12 months), but not after only 6 months elicits a statistically significant increase the social relationships scores and the reduction in negative emotions scores in all aged at implantation. However, the education scores have slight increase only in aged 21-59.


Clinical Efficacy of the Chinese Herbal Medicine Shumian Capsule for Insomnia: A Randomized, Double-Blind, Placebo-Controlled Trial.
Shumian capsule (SMC) is a patent Chinese herbal medicine that can soothe the liver and relieves depression, quiet the spirit. Here, we aimed to investigate the efficacy of SMC for treating insomnia using both scales and polysomnography (PSG). A randomized, double-blind, placebo-controlled trial was performed. Twenty-six insomnia patients randomly received SMC (n = 11) or placebo (n = 15) for four weeks. Pittsburgh Sleep Quality Inventory (PSQI), Insomnia Severity Index (ISI), 9-items Patient Health Questionnaire (PHQ-9), 7-items Generalized Anxiety Disorder (GAD-7), 17-item Hamilton Depression Rating Scale (HAMD-17), and Hamilton Anxiety Rating Scale (HAMA) were applied at the baseline and the 2nd, 4th week after treatment. Treatment Emergent Symptom Scale was used to assess adverse reactions. We used PSG to record and analyze sleep features at baseline and after four weeks. PSQI, ISI, PHQ-9, HAMD-17, and HAMA scores decreased significantly after SMC treatment. Also, the total sleep time, rapid-eye-movement (REM) sleep latency, stage 2 sleep, deep sleep, REM sleep, and sleep efficiency improved significantly after SMC treatment. In the placebo group, the only significant change was the decrease of PHQ-9 at week-2. Furthermore, both SMC and placebo reported no adverse events. SMC could safely improve sleep quality with depression and anxiety remission in insomnia patients.


Role of angiotensin modulation in primary headaches.
The renin-angiotensin system (RAS) is a major regulatory system controlling many different homeostatic mechanisms both within the brain and in the periphery. While it is primarily associated with blood pressure and salt/water regulation, increasing evidence points to the involvement of the RAS in both headache disorders specifically and pain regulation in general. Several publications have indicated that drugs blocking various elements of the renin-angiotensin system lead to a reduction in migraine. Additionally, interventions on different angiotensin peptides or their receptors have been shown to both reduce and increase pain in animal models. As such, modulation of the renin-angiotensin system is a promising approach to the treatment of headaches and other pain conditions.


Complex obstructive lung disease - A diagnostic and management conundrum.
Rheumatoid arthritis (RA) is a common autoimmune disease most well-known for its inflammatory, destructive polyarthropathy. Extraarticular manifestations of the disease may involve the respiratory system, including interstitial lung disease, pleural disease, pulmonary vascular abnormalities, and airways disease. Smoking is highly prevalent in the RA population, and may even have a synergistic effect in disease development and progression. In the diagnosis of pulmonary disease, this presents a unique diagnostic and therapeutic challenge. We present a case of a woman in her 50s who presented for evaluation of dyspnea and was found to have obstructive lung disease. In addition to RA, she had a significant smoking history and also owned pet birds, making definitive diagnosis difficult. Ultimately, chest imaging was crucial in identifying RA-related lung disease as the root cause of her symptoms, leading to successful treatment and symptom management.


Modulating arithmetic fact retrieval: a single-blind, sham-controlled tDCS study with repeated fMRI measurements.
Transcranial direct current stimulation (tDCS) is a non-invasive technique which has been used to modulate various cognitive functions in healthy participants as well as stroke patients. Despite the increasing number of tDCS studies, it still remains questionable whether tDCS is suitable for modulating performance in arithmetic tasks and whether a single tDCS session may cause brain activity changes that can be detected with functional magnetic resonance imaging (fMRI). We asked healthy participants to repeatedly solve simple multiplication tasks in three conditions: STIMULATION (anodal tDCS over the right angular gyrus, AG), SHAM (identical electrode set-up without stimulation), and CONTROL (no electrodes attached). Before and after tDCS, we used fMRI to examine changes in brain activity. Behavioural results indicate that a single session of tDCS did not modulate task performance significantly. However, fMRI measurements revealed that the neural correlates of multiplication were modified following a single session of anodal tDCS. In the bilateral AG, activity was significantly higher for multiplication problems rehearsed during active tDCS, as compared to multiplication problems rehearsed without tDCS or during sham tDCS. In sum, we present first neuro-functional evidence that tDCS modulates arithmetic processing. Implications of these findings for future tDCS studies and for the rehabilitation of acalculic patients with deficits in arithmetic fact retrieval are discussed.


Examining the Ensembles of Amyloid-β Monomer Variants and Their Propensities to Form Fibers Using an Energy Landscape Visualization Method.
The amyloid-β (Aβ) monomer, an intrinsically disordered peptide, is produced by the cleavage of the amyloid precursor protein, leading to Aβ-40 and Aβ-42 as major products. These two isoforms generate pathological aggregates, whose accumulation correlates with Alzheimer's disease (AD). Experiments have shown that even though the natural abundance of Aβ-42 is smaller than that for Aβ-40, the Aβ-42 is more aggregation-prone compared to Aβ-40. Moreover, several single-point mutations are associated with early onset forms of AD. This work analyzes coarse-grained associative-memory, water-mediated, structure and energy model (AWSEM) simulations of normal Aβ-40 and Aβ-42 monomers, along with six single-point mutations associated with early onset disease. We analyzed the simulations using the energy landscape visualization method (ELViM), a reaction-coordinate-free approach suited to explore the frustrated energy landscapes of intrinsically disordered proteins. ELViM is shown to distinguish the monomer ensembles of variants that rapidly form fibers from those that do not form fibers as readily. It also delineates the amino acid contacts characterizing each ensemble. The results shed light on the potential of ELViM to probe intrinsically disordered proteins.


Factors Affecting Neurological Deficits in Thoracic Tuberculous Spondylodiscitis.
Thoracic spinal tuberculosis (TB) causes destruction of the spine and compression of the adjacent spinal cord. This study aimed to identify the risk factors for neurological deterioration in patients with thoracic spinal TB to guide decision-making regarding immediate surgery before the onset of weakness. Demographic, clinical, laboratory, and radiologic (x-ray and magnetic resonance imaging) data of 115 patients with active thoracic spinal TB were retrospectively analyzed. Patients with neurological status categorized as Frankel grades A, B, or C (n = 71) were classified as the neurological deficit group, while those with neurological status categorized as Frankel grades D and E (n = 44) constituted the control group. Univariate and multivariate logistic regression analyses were used to predict the risk factors for neurological deficits. The mean patient age was 57.2 years. The most common lesion location was the distal thoracic region (T9-L1; 62.6%). Paradiscal involvement was the most common form of involvement (73%). In the univariate analysis, the significant risk factors associated with neurological worsening were overweight (body mass index [BMI] >25), C-reactive protein level > 20 mg/L, panvertebral involvement, loss of cerebrospinal fluid posterior to the cord, cord signal changes, and canal compromise. The multivariate analysis revealed that only BMI >25 (adjusted OR = 16.18; 95% CI 1.60-163.64; P = 0.018), cord signal changes (adjusted OR = 7.42; 95% CI 1.85-29.74; P = 0.005), and canal encroachment >50% ( adjusted OR = 51.86; 95% CI 5.53-486.24; P = 0.001) were independent risk factors for predicting the risk of neurological deficits. Overweight (BMI >25), cord signal changes, and canal compromise >50% significantly predicted neurological deficits in patients with thoracic spinal TB. Prompt spinal surgery should be considered before progressive worsening of the neurological condition in patients with all of these risk factors. Predictive factors for neurological deficits in thoracic spinal TB were determined. Overweight, cord signal changes, and canal compromise >50% showed predictive value. These factors can help identify patients who require early surgical intervention.


Survival data on breast cancer patients accepted for radiotherapy, 1966-1977.
The survival data presented here include the stage of breast cancer, location of the primary cancer in the breast, type of surgery, and dose and location of radiotherapy.


Brain structural and functional alterations in individuals with combined overweight/obesity and mood disorders: A systematic review of neuroimaging studies.
Growing evidence suggests there is a bidirectional relationship between depression and obesity, which are associated with structural and functional brain abnormalities. However, the underlying neurobiological mechanisms subserving the foregoing associations have yet to be characterized. It is necessary to summarize the neuroplastic brain changes in relation to depression and obesity. We systematically searched articles from 1990 to November 2022 on databases including MEDLINE/PubMed, Web of Science, PsycINFO. Only neuroimaging studies within the scope of potential differences in brain function and structure in individuals with depression and obesity/ BMI changes were included. Twenty-four eligible studies were included in the review herein, consisting of 17 studies reporting changes in brain structure, 4 studies reporting abnormal brain function, and 3 studies reporting both changes in brain structure and function. Results indicated an interaction between depression and obesity on brain functions, and their influence on brain structure is both extensive and specific. Overall, reduced whole brain, intracranial, and gray matter volume (e.g. frontal, temporal gyri, thalamic, and hippocampal) and impaired white matter integrity was observed in persons with depression and obesity comorbidity. Additional evidence on resting state fMRI reveals select brain regions associated with cognitive control, emotion regulation, and reward functions. Due to the diversity of tasks in task fMRI, the distinct neural activation patterns are revealed separately. The bidirectional relationship between depression and obesity reflects different characteristics in brain structure and function. Longitudinal designs should be reinforced in follow-up studies.


An enzymatic biosensor for hydrogen peroxide based on CeO2 nanostructure electrodeposited on ITO surface.
In this study, an enzymatic biosensor for amperometric detection of hydrogen peroxide was developed based on the direct electrochemistry of myoglobin (Mb) on a porous cerium dioxide (CeO2) nanostructured film. The developed film accomplished with large surface area was electrodeposited on an indium tin oxide (ITO) substrate. Surface morphological studies revealed that the formed CeO2 film has a large specific surface area with a unique nanostructure on the ITO surface. Cyclic voltammetry (CV) and differential pulse voltammetry (DPV) were employed to demonstrate the electrochemical behavior of Mb immobilized on the fabricated film, which exhibited facile, direct electrochemistry and good electrocatalytic performance without any electron mediator. The electrode displayed a pair of quasi-reversible reduction-oxidation peaks at -0.3 and -0.2V, respectively, due to the Mb [Fe(3+)/Fe(2+)] redox couple, which is a surface-controlled electrochemical process with one electron transfer. This reagent-less biosensor showed good stability and high sensitivity for detecting H2O2 without any influence of intermediate compounds. This protein-based biosensor was capable of detecting H2O2 as low as 0.6μM with linearity up to 3mM and a response time of ~8s, compared to those of other modified electrodes. Hence, porous CeO2 is a possible candidate material for fabricating enzymatic sensors or devices.


Symptoms preceding sudden cardiac death in the young are common but often misinterpreted.
To identify patients at risk of sudden cardiac death (SCD) by analysis of clinical history. A retrospective study of the Swedish cohort of 15-35 year olds having suffered an SCD during 1992-1999 and having undergone a forensic autopsy (162 individuals). We sought information in forensic, police and medical records and from interviews with family members. Syncope/presyncope, chest pain, palpitations or dyspnoea were present in 92/162, unspecific symptoms such as fatigue, influenza, headache or nightmares in 35/162. Syncope/presyncope was most common (42/162). In 74 seeking medical attention, 32 had an ECG recorded (24 pathological). In 26 subjects there was a family history of SCD. The patient seeking medical advice before suffering an SCD is characterized by one to three of the following: 1) cardiac-related symptoms or non-specific symptoms often after an infectious disease, 2) a pathological ECG, 3) a family history of SCD. In 6 out of 10 a cardiac diagnosis was not considered. We conclude that symptoms preceding SCD were common but often misinterpreted.


Value of integrated pulmonary index to predict exacerbation of chronic obstructive pulmonary Disease's severity.
In this study, we aimed to examine the correlation between current prognostic scores and the integrated pulmonary index (IPI) in patients admitted to the emergency department (ED) with exacerbation of chronic obstructive pulmonary disease (COPD), and the diagnostic value of using the IPI in combination with other scores in determining patients who can be discharged safely. This study was conducted as a multicenter and prospective observational study between August 2021 and June 2022. Patients diagnosed with COPD exacerbation (eCOPD) at the ED were included in the study and they were grouped according to the Global Initiative for Chronic Obstructive Lung Disease (GOLD) classification. The CURB-65 (Confusion, Urea, Respiratory rate, Blood pressure, and age older than 65 years), BAP-65 (Blood urea nitrogen, Altered mental status, Pulse rate, and age older than 65 years), and DECAF (Dyspnea, Eosinopenia, Consolidation, Academia, and atrial Fibrillation) scores and IPI values of the patients were recorded. The correlation between the IPI and the other scores and its diagnostic value in detecting mild eCOPD were examined. The diagnostic value of CURB-IPI, a new score created by the combination of CURB-65 and IPI, in mild eCOPD was examined. The study was carried out with 110 patients (49 female and 61 male), mean age of 67 (min/max: 40/97). The IPI and CURB-65 had better predictive value in detecting mild exacerbations than DECAF and BAP-65 scores [Area under curves (AUC) were 0.893, 0.795, 0.735, 0.541 respectively]. The CURB-IPI score, on the other hand, had the best predictive value for detecting mild exacerbations (AUC 0.909). We found that the IPI has good predictive value in the detection of mild COPD exacerbations, and its predictive value increases when used in combination with CURB-65. We think that the CURB-IPI score can be a guide when deciding whether patients with exacerbation of COPD can be discharged.


Patterns of Eating Disorder Pathology are Associated with Weight Change in Family-Based Behavioral Obesity Treatment.
Children with overweight or obesity have elevated eating disorder (ED) pathology, which may increase their risk for clinical EDs. The current study identified patterns of ED pathology in children with overweight or obesity entering family-based behavioral weight loss treatment (FBT) and examined whether children with distinct patterns differed in their ED pathology and BMI z score (zBMI) change across FBT. Before participating in a 16-session FBT, children (N = 241) completed surveys or interviews assessing ED pathology (emotional eating, shape/weight/eating concerns, restraint, and loss of control [LOC]). Shape and weight concerns (SWC) and LOC were also assessed post treatment. Child height and weight were measured at baseline and post treatment. Latent class analysis identified patterns of ED pathology. Repeated-measures ANOVA examined changes in zBMI and ED pathology. Four patterns of ED pathology were identified: low ED pathology, SWC, only loss of control, and high ED pathology. SWC decreased across treatment, with the highest decreases in patterns characterized by high SWC. All groups experienced significant decreases in zBMI; however, children with the highest ED pathology did not achieve clinically significant weight loss. ED pathology decreased after FBT, decreasing ED risk. While all children achieved zBMI reductions, further research is needed to enhance outcomes for children with high ED pathology.


Specific purine N7-nitrogens are critical for high affinity binding by the trp repressor.
We have analysed the interaction of the trp repressor with the trpEDCBA operator using a series of modified trp operator sequences incorporating two isosteric purine analogues that lack N7-nitrogens. Our results suggest that as well as the direct contact between Arg69 and G-9, three additional purine N7-nitrogens, implicated in specific, water-mediated contacts to the repressor, are critical for formation of the high-affinity repressor-operator complex. We conclude that the crystal structure obtained by Otwinowski et al. reflects high-affinity sequence-specific binding of the trp repressor to the trp operator, and that in some cases proteins can use water molecules to extend amino acid side chains in order to derive favorable binding energy in complex formation.


Association of epicardial and intramyocardial fat with ventricular arrhythmias.
Among patients with ischemic cardiomyopathy (ICM) and nonischemic cardiomyopathy (NICM), myocardial fibrosis is associated with an increased risk for ventricular arrhythmia (VA). Growing evidence suggests that myocardial fat contributes to ventricular arrhythmogenesis. However, little is known about the volume and distribution of epicardial adipose tissue and intramyocardial fat and their relationship with VAs. The purpose of this study was to assess the association of contrast-enhanced computed tomography (CE-CT)-derived left ventricular (LV) tissue heterogeneity, epicardial adipose tissue volume, and intramyocardial fat volume with the risk of VA in ICM and NICM patients. Patients enrolled in the PROSE-ICD registry who underwent CE-CT were included. Intramyocardial fat volume (voxels between -180 and -5 Hounsfield units [HU]), epicardial adipose tissue volume (between -200 and -50 HU), and LV tissue heterogeneity were calculated. The primary endpoint was appropriate ICD shocks or sudden arrhythmic death. Among 98 patients (47 ICM, 51 NICM), LV tissue heterogeneity was associated with VA (odds ratio [OR] 1.10; P = .01), particularly in the ICM cohort. In the NICM subgroup, epicardial adipose tissue and intramyocardial fat volume were associated with VA (OR 1.11, P = .01; and OR = 1.21, P = .01, respectively) but not in the ICM patients (OR 0.92, P =.22; and OR = 0.96, P =.19, respectively). In ICM patients, increased fat distribution heterogeneity is associated with VA. In NICM patients, an increased volume of intramyocardial fat and epicardial adipose tissue is associated with a higher risk for VA. Our findings suggest that fat's contribution to VAs depends on the underlying substrate.


Molecular analysis of a mutation conferring the high-lysine phenotype on the grain of barley (Hordeum vulgare).
We have analyzed the molecular nature of the Riso 56 mutation that occurs in barley. This mutation results in a depression of hordein accumulation in the grain and consequently in a higher overall lysine content. In particular, the amount of B hordein, which is encoded by the complex locus Hor-2, is decreased by about 75% because of the absence of the major components. The synthesis of certain minor polypeptides, with properties similar to the major B hordeins, remains unaffected. Analysis of endosperm RNA, by in vitro translation and hybridization to various cloned cDNAs derived from hordein mRNA, shows that mRNA for the major B hordeins is not present in the endosperm. Hybridization of a B hordein cDNA clone to gel-fractionated restriction digests of mutant and wild-type DNA indicates that at least 85 kb of DNA has been deleted from the Hor-2 locus in the high-lysine mutant.


Antimicrobial photodynamic therapy (aPDT) induction of biofilm matrix architectural and bioadhesive modifications.
Dental implants are commonly used today for the treatment of partially and fully edentulous patients. Despite the high success rate they are not resistant to complications and failure due to a variety of problems including peri-implantitis or peri-mucositis due to bacterial biofilm formation on the implant surface. The use of non-surgical and surgical treatment procedure to promote healing in cases with peri-implantitis have limited efficacy. Here we studied the ability of photodynamic therapy to destroy a known bacterial pathogen and the extracellular matrix architecture of biofilm attached to titanium plates and germanium prisms. Titanium plates or germanium prisms were incubated for 24h with Fusobacterium nucleatum a fusiform, gram-negative bacterium was used to enable biofilm formation. Photodynamic therapy was carried out by incubating the biofilm samples on each substrata with porfimer sodium. Treatment was carried out using a diode laser at 630nm, 150mW/cm(2) for light doses ranging from 25-100J/cm(2). Evaluation of killing efficacy was done by counting colony forming units compared to controls. Multiple attenuated internal reflection-infrared spectroscopy (MAIR-IR) and SEM were used to analyze the samples pre and post PDT for validation. F. nucleatum was significantly reduced in a dose dependent manner by treatment with PDT. Changes in biofilm components and strength of bioadhesion were examined with MAIR-IR following jet impingement using calibrated water jets. SEM demonstrates significant morphological alterations in the bacteria, consistent with damage associated with exposure to reactive oxygen species. The results are indicative that aPDT is a method that can be used to eradicate micro-organisms associated with biofilm in peri-implantitis on relevant substrata. Data shows that the slime layer of the biofilm is removed and that further methods need to be employed to completely remove weakened or destroyed biofilm matrix components. Reactive oxygen species (ROS) mediated oxidative damage results in morphologic changes as a consequence of changes in cell membrane integrity.


Insertion of dominant selectable markers into the human genome.
In the above discussion, I have outlined the current status of our efforts to use retroviral vectors to introduce selectable markers into the human genome and to use these markers for mapping specific chromosomal regions. I have not reviewed in detail the extensive characterization of the mouse H-2 region carried out by David Nelson and John Weis based on the insertion of a single retroviral element. This analysis has provided a model for the application of retroviral elements into various regions of the human genome. The prospects for increasing the resolution of the human genetic map and identifying many genes relevant to human health and development are likely to be enhanced by increasing the precision of this methodology.


[Gastric resection with preservation of the pyloric sphincter in treating patients with duodenal ulcer].
An experience with pylorus-preserving resections of the stomach in 27 patients with duodenal ulcer and very high acid production is described. Specific technical features of this operation, immediate and long-term results are analyzed. Rhythmic evacuation was preserved in addition to a reliable drop of the acid production. Gastroduodenal reflux was prevented. Positive results were noted in all the examined patients in the remote follow-up.


Antibiotic residues and mycotoxins in raw milk in Punjab (India): a rising concern for food safety.
The present study was envisaged with an aim to determine the occurrence of antibiotic residues; enrofloxacin, oxytetracycline, penicillin G, sulphamethoxazole and chloramphenicol as well as mycotoxins; aflatoxin M1 and ochratoxin A in raw milk samples collected from individual animals from dairy farms located in 9 districts of Punjab, India. A total of 168 raw milk samples were collected and analysed using commercially available competitive Enzyme linked immunosorbent assay kits. Out of these, 19 (11.3%) and 9 (5.4%) samples were found positive for antibiotic residues and mycotoxins, respectively. The milk samples were positive for enrofloxacin (4.8%), oxytetracycline (3.0%), penicillin G (3.0%) and sulphamethoxazole (0.6%) residues. The percentage of samples found above maximum residue limit established by Europen Union (EU)/Codex Alimentarius Commission (CAC) were 1.7%, 1.2% and 0.6% for enrofloxacin, oxytetracycline and penicillin G residues, respectively. Aflatoxin M1 was detected in 5.4% of monitored milk samples with 1.2% samples exceeded the established maximum levels of EU but were below the maximum levels established by CAC. The occurrence of antibiotic residues and mycotoxins in raw milk samples above maximum limits is a rising concern for food safety due to possibility of health risks to the consumers.


On decoding and rewriting genomes: a psychoanalytical reading of a scientific revolution.
In various documents the view emerges that contemporary biotechnosciences are currently experiencing a scientific revolution: a massive increase of pace, scale and scope. A significant part of the research endeavours involved in this scientific upheaval is devoted to understanding and, if possible, ameliorating humankind: from our genomes up to our bodies and brains. New developments in contemporary technosciences, such as synthetic biology and other genomics and "post-genomics" fields, tend to blur the distinctions between prevention, therapy and enhancement. An important dimension of this development is "biomimesis": i.e. the tendency of novel technologies and materials to mimic or plagiarize nature on a molecular and microscopic level in order to optimise prospects for the embedding of technological artefacts in natural systems such as human bodies and brains. In this paper, these developments are read and assessed from a psychoanalytical perspective. Three key concepts from psychoanalysis are used to come to terms with what is happening in research laboratories today. After assessing the general profile of the current revolution in this manner, I will focus on a particular case study, a line of research that may serve as exemplification of the vicissitudes of contemporary technosciences, namely viral biomaterials. Viral life forms can be genetically modified (their genomes can be rewritten) in such a manner that they may be inserted in human bodies in order to produce substances at specific sites such as hormones (testosterone), neurotransmitters (dopamine), enzymes (insulin) or bone and muscle tissue. Notably, certain target groups such as top athletes, soldiers or patients suffering from degenerative diseases may become the pioneers serving as research subjects for novel applications. The same technologies can be used for various purposes ranging from therapy up to prevention and enhancement.


Status epilepticus leads to the degradation of the endogenous inhibitor of caspase-activated DNase in rats.
Specific biochemical hallmarks of apoptosis, namely internucleosomal DNA fragmentation and caspase-3 activation, appear in the aftermath of status epilepticus (SE). This led us to hypothesize that caspase-activated DNase (CAD) is involved in DNA fragmentation and apoptotic neuronal cell death following SE. The present study aimed to determine whether SE is associated with an activation of CAD, as reflected in the degradation of the CAD inhibitor, ICAD. SE was induced in adult male Sprague-Dawley rats by kainic acid (12 mg/kg i.p.) and seizures were terminated with diazepam after 2 h. At 24, 48, or 72 h after SE termination, protein levels of CAD and ICAD were measured by Western blotting (after sodium dodecyl sulfate-polyacrylamide gel electrophoresis) using specific antibodies. At 48 and 72 h after SE termination, ICAD protein levels significantly decreased (by more than 60%) in rhinal cortex and hippocampus as compared with those in the same tissue from animals not experiencing SE. No changes were detected in total CAD protein levels at any time point, resulting in an increase in the ratio of CAD to its inhibitor. The loss of ICAD following SE is indicative of a disinhibition of CAD, leading to DNA fragmentation. Consistent with this, we observed that the decrease in ICAD between 24 and 48 h was accompanied by a marked increase in DNA fragmentation. Our results support the proposal that CAD participates in caspase-3-mediated internucleosomal DNA fragmentation in the aftermath of SE.


The population dynamics of acquired immunity to helminth infection: experimental and natural transmission.
Recently we described a mathematical model of the role of acquired immunity in host-helminth interactions. The model gives a good quantitative description of the results of experiments involving the nematode Heligmosomoides polygyrus in laboratory mice. Here we apply the model to the results of two further laboratory studies of the same parasite-host interaction: (i) the repeated experimental infection of a genetically heterogeneous host population, and (ii) the natural transmission of the parasite within mouse populations under different dietary conditions. Numerical simulation again reveals good quantitative agreement between the model predictions and laboratory data. Finally, the model is extended to give a preliminary description of the dynamics of helminth-host interactions of medical and ecological significance in the real world.


Computer-assisted solid lung nodule 3D volumetry on CT: influence of scan mode and iterative reconstruction: a CT phantom study.
To evaluate the effect of high-resolution scan mode and iterative reconstruction on lung nodule 3D volumetry. Solid nodules with various sizes (5, 8, 10 and 12 mm) were placed inside a chest phantom. CT images were obtained with various tube currents, scan modes (conventional mode, high-resolution mode) and iterative reconstructions [0, 50 and 100 % blending of adaptive statistical iterative reconstruction (ASiR) and filtered back projection]. The nodule volumes were calculated using semiautomatic software and compared with the assumed volume from the nodules. The mean absolute and relative percentage error improved when using iterative reconstruction especially when using the conventional scan mode; however, this effect was not significant. Significant reduction in volume overestimation was observed when using high-resolution scan mode (P = 0.011). The high-resolution mode significantly reduces the volume overestimation of 3D volumetry. Iterative reconstruction shows a reduction in volume overestimation and error margin especially with the conventional scan mode; however, this effect was not significant.


Testimony method to ameliorate post-traumatic stress symptoms. Community-based intervention study with Mozambican civil war survivors.
The effectiveness of the testimony method has not been established in rural communities with survivors of prolonged civil war. To examine the effectiveness and feasibility of a testimony method to ameliorate post-traumatic stress symptoms. Participants (n=206) belonged to former war zones in Mozambique. They were divided into a case (n=137) and a non-case group (n=69). The case group was randomly divided into an intervention (n=66) and a control group (n=71). Symptoms were measured during baseline assessment, post-intervention and at an 11-month follow-up. Post-intervention measurements demonstrated significant symptom reduction in both the intervention and the control group. No significant differences were found between the intervention and the control group. Follow-up measurements showed sustained lower levels of symptoms in both groups, and some indications of a positive intervention effect in women. A remarkable drop in symptoms could not be linked directly to the intervention. Feasibility of the intervention was good, but controlling the intervention in a small rural community appeared to be a difficult task to accomplish.


Effect of adrenalin, insulin and contractions on the content of the free fatty acid fraction in skeletal muscle.
The fraction of free fatty acids (FFA) is present in skeletal muscles. However, there is almost no data regarding regulation in the content of this intramuscular lipid pool. We took advantage of the isolated muscle preparation to examine whether: a) increasing exogenous concentration of FFA (500microM or 700microM, 30min) b) insulin (10.00 I.U./L, 30min), c) adrenalin (4.4 nM, 30 min), or d) contractions (200ms, tetani, 1Hz, 30min), affect the FFA content inside myocytes. Incubation of soleus (S) and extensor digitorum longus (EDL) with increasing concentrations of exogenous FFA (from 500microM to 700microM) resulted in an increase in the total FFA fraction in both muscles studied (by 280.2% and 259.1%, respectively). In contracting muscles FFA pool was significantly reduced both in S (by 73.1%) and in EDL (by 31.1%). Neither stimulation by adrenalin nor insulin affected the total content of FFA fraction in the muscles examined. We conclude that a) increased availability of exogenous FFA at the sarcolemma level results in an increase in the size of intramuscular FFA fraction b) the intracellular FFA fraction is utilized by contracting muscles with regard to the fiber composition and to a greater extent in more oxidative muscles, c) FFA fraction remains stable upon stimulation by insulin or adrenalin.


Patterns of failure in Ionescu-Shiley bovine pericardial bioprosthetic valves.
The experience of the University of Ottawa Heart Institute with valvular replacement by Ionescu-Shiley bovine pericardial bioprostheses has been recently reviewed. The focus of the present study is to examine the patterns of valve failure in a subgroup of these prostheses, those that required explanation for valve failure caused specifically by cusp wear and tears. A total of 22 aortic and six mitral standard-profile valves failed in this way. Twenty-five of these valves were reassessed and are the subject of this paper. Twenty-eight holes and 56 cusp tears occurred in these valves in locations which, along with coexistent pathologic findings, suggested that the cusp commissural suture/alignment stitch was the point of their origin. The importance of this observation and postulation about the genesis of these cases of valve failure lies in the potential for improvement of this valve's performance by modifications of its manufacture.


Real-time intrafraction prostate motion during linac based stereotactic radiotherapy with rectal displacement.
Kilovoltage Intrafraction Monitoring (KIM) is a method which determines the three-dimensional position of the prostate from two-dimensional kilovoltage (kV) projections taken during linac based radiotherapy treatment with real-time feedback. Rectal displacement devices (RDDs) allow for improved rectal dosimetry during prostate cancer treatment. This study used KIM to perform a preliminary investigation of prostate intrafraction motion observed in patients with an RDD in place. Ten patients with intermediate to high-risk prostate cancer were treated with a Rectafix RDD in place during two boost fractions of 9.5-10 Gy delivered using volumetric modulated arc therapy (VMAT) on Clinac iX and Truebeam linacs. Two-dimensional kV projections were acquired during treatment. KIM software was used following treatment to determine the displacement of the prostate over time. The displacement results were analyzed to determine the percentage of treatment time the prostate spent within 1 mm, between 1 and 2 mm, between 2 and 3 mm and greater than 3 mm from its initial position. KIM successfully measured displacement for 19 prostate stereotactic boost fractions. The prostate was within 1 mm of its initial position for 84.8%, 1-2 mm for 14%, 2-3 mm 1.2% and ≥3 mm only 0.4% of the treatment time. In this preliminary study using KIM, KIM was successfully used to measure prostate intrafraction motion, which was found to be small in the presence of a rectal displacement device. The Hunter New England Human Research Ethics Committee reference number is 14/08/20/3.01.


The influence of obesity and age at diagnosis on the estrogen receptor status of breast cancers. Perimenopausal predominance of estrogen receptor negative tumors.
Estrogen receptor (ER) status of 763 primary breast cancers was analyzed by host age and obesity. Tumors from women less than 40 years of age were found to be ER negative (ERN) predominantly. Tumors from women greater than 40 years of age demonstrated increasingly higher median values for ER protein and were ER positive (ERP) predominantly except for those presenting among nonobese women 45 to 49 years of age and obese women 50 to 54 years of age. Tumors from these two subgroups were more frequently ERN than those from women of similar habitus who were immediately younger (P less than 0.05) or older (P less than 0.02), or than those from women of the same age and differing obesity status (45 to 49 years of age P less than 0.01; 50 to 54 years of age P greater than 0.05). This altered pattern of estrogen binding in perimenopausal tumors likely results from the hormonal changes of the menopausal and late premenopausal years. Recognition of their varied patterns of estrogen binding should assist in understanding the behavior of these perimenopausal tumors and in the selection of optimal antitumor therapy for their hosts.


Functional grouping of similar genes using eigenanalysis on minimum spanning tree based neighborhood graph.
Gene expression data clustering is an important biological process in DNA microarray analysis. Although there have been many clustering algorithms for gene expression analysis, finding a suitable and effective clustering algorithm is always a challenging problem due to the heterogeneous nature of gene profiles. Minimum Spanning Tree (MST) based clustering algorithms have been successfully employed to detect clusters of varying shapes and sizes. This paper proposes a novel clustering algorithm using Eigenanalysis on Minimum Spanning Tree based neighborhood graph (E-MST). As MST of a set of points reflects the similarity of the points with their neighborhood, the proposed algorithm employs a similarity graph obtained from k(') rounds of MST (k(')-MST neighborhood graph). By studying the spectral properties of the similarity matrix obtained from k(')-MST graph, the proposed algorithm achieves improved clustering results. We demonstrate the efficacy of the proposed algorithm on 12 gene expression datasets. Experimental results show that the proposed algorithm performs better than the standard clustering algorithms.


Off-label prescribing in oncology.
Off-label prescribing occurs when a practitioner prescribes a drug for a use, or in a manner, not listed in the 'approved product information' (API) for that drug. The literature suggests that this is a frequent occurrence in many areas of medicine, but data are limited in the hospitalized oncology setting. The aim of this study was to quantify the extent of off-label prescribing in a hospitalized oncology population in Australia. The study was conducted at Peter MacCallum Cancer Centre, Australia. On a single day the medication charts of all hospitalized patients were prospectively reviewed. Drug prescribing was assessed for licensing status by comparison with the API as approved by the Therapeutic Goods Administration of Australia. Prescriptions were classified as licensed, off-label or unlicensed. Medication charts of 130 patients were assessed. There were 1351 prescriptions. In 293 (22%) of the prescriptions the drug was either off-label (242, 18%) or unlicensed (51, 4%). Among the 130 patients, 110 (85%) received at least one drug that was prescribed off-label or that was unlicensed. Off-label dosing was the most frequent reason for a drug being off-label (139, 10% of all prescriptions). Off-label due to use for an unapproved indication was found in 118 prescriptions (9%), and off-label due to an unapproved route of administration was found in 38 prescriptions (3%). Off-label prescribing is widespread in the acute hospitalized oncology population, with approximately 22% of all prescriptions being for off-label or unlicensed medication. Such prescribing affects a significant proportion of patients.


A novel alphapartitivirus detected in Japanese pear.
Pyrus pyrifolia cryptic virus (PpCV) had been previously reported from Japanese pear (Pyrus pyrifolia). In analyses of Japanese pear, two other double-stranded (ds) RNA molecules (dsRNA4 and 5) were observed along with the three dsRNA segments from PpCV on an electrophoretic profile of isolated dsRNA. When the purified dsRNA sample was deep sequenced by a next-generation sequencer, two de novo assembled contigs corresponding to dsRNA4 and 5, with predicted amino acid sequences showing homologies to the RNA-dependent RNA polymerase and the capsid protein of Rose partitivirus, respectively, were found by BLAST analysis. The relationships between the two contigs and dsRNA4, 5 were confirmed by northern blot analyses with probes amplified using primers designed from the contigs. Terminal sequence analyses by rapid amplification of cDNA ends revealed that dsRNA4 and 5 were 1945 and 1788 bp long, respectively. The 5' terminal sequences (GUCAAAUU) of dsRNA4 and 5 were conserved. Based on genome size and phylogenetic analyses, the newly found virus is thought to be a member of the genus Alphapartitivirus. Thus, it has been designated as Pyrus pyrifolia partitivirus 2.


Bombesin-induced hypothermia and hypophagia are associated with plasma metabolic fuel alterations in the rat.
Microinfusion of bombesin into the preoptic area (POA) has previously been shown to reduce core body temperature and feeding in rats that are food-deprived or made hypoglycemic with insulin. The present study determined the metabolic fuel state of rats under these experimental conditions. In addition, changes in plasma metabolic fuels following the microinfusion of bombesin (50 ng/0.25 microliters) into the POA were evaluated. Rats (n = 8) were tested under conditions of food satiation, food deprivation (20 h), and insulin pretreatment (10 U/kg). Prior to peptide infusion, food-deprived rats exhibited the expected elevation in free fatty acids coupled with a small decline in plasma glucose. Insulin treatment resulted in hypoglycemia which persisted for at least 120 min. Following bombesin infusion, free fatty acids and corticosterone levels were elevated in food-sated rats. Food-deprived rats exhibited elevation in plasma glucose, free fatty acids, and corticosterone following peptide infusion. In insulin-treated rats, bombesin attenuated the hypoglycemia observed in controls and increased corticosterone levels. These findings suggest that bombesin-like peptides localized within the POA may participate in the regulation of metabolic fuels.


A Study on Emotional-Affective Aspects and the Perception of General Health in Kidney Transplant Subjects.
Transplantation has profound psychological implications. Psychodiagnostic assessments with structured instruments (scales, questionnaires) may be insufficient for bringing out the deeper aspects of the personality. Thirty kidney transplant recipients underwent the Thematic Apperception Test to detect significant variables hypothetically related to characteristics of the study sample and the SF-36 to assess quality of life. The variable of Thematic Apperception Test (TAT) "communication difficulties" was significantly correlated with the dimensions of the SF-36 "emotional role functioning," "social activities," and "mental health." The dimension of SF-36 "general health" did not interfere with the variable of TAT "constricted effect." This study is considered to be particularly useful in detecting the emergence of "removed difficulties" that transplanted subjects are not inclined to recognize. The analysis of these aspects is necessary to plan individualized psychotherapy pathways.


Thyroid hormone-induced alterations in membrane structure-function relationships: studies on kinetic properties of rat kidney microsomal Na(+),K (+)-ATPase and lipid/phospholipid profiles.
The effects of thyroidectomy (Tx) and subsequent treatment with 3,5,3'-triiodothyronine (T(3)) or combined replacement therapy (T(R)) with T(3 )and thyroxine (T(4)) on the substrate and temperature kinetics properties of Na+,K+-ATPase and lipid/phospholipid makeup of rat kidney microsomes were examined. Enzyme activity was somewhat high in the hypothyroid (Tx) animals and increased significantly following T(3) treatment, while T(R) treatment caused a decrease. In the Tx and T(3) groups enzyme activity resolved in two kinetic components, while in the T(R) group the enzyme showed allosteric behavior up to 0.5 mM: ATP concentration. The K(m) and V(max) values of both the components decreased in Tx animals without affecting the catalytic efficiency. T(3) treatment caused a significant increase in the V(max) of both the components, with a significant increase in the catalytic efficiency, while the K(m) values were not upregulated. The T(R) regimen lowered the K(m) and V(max) of component II but improved the catalytic efficiency. Thyroid status-dependent changes were also noted in the temperature kinetics of the enzyme. Regression analysis revealed that changes in the substrate and temperature kinetics parameters correlated with specific phospholipid components.


Aronia melanocarpa juice, a rich source of polyphenols, induces endothelium-dependent relaxations in porcine coronary arteries via the redox-sensitive activation of endothelial nitric oxide synthase.
This study examined the ability of Aronia melanocarpa (chokeberry) juice, a rich source of polyphenols, to cause NO-mediated endothelium-dependent relaxations of isolated coronary arteries and, if so, to determine the underlying mechanism and the active polyphenols. A. melanocarpa juice caused potent endothelium-dependent relaxations in porcine coronary artery rings. Relaxations to A. melanocarpa juice were minimally affected by inhibition of the formation of vasoactive prostanoids and endothelium-derived hyperpolarizing factor-mediated responses, and markedly reduced by N(ω)-nitro-l-arginine (endothelial NO synthase (eNOS) inhibitor), membrane permeant analogs of superoxide dismutase and catalase, PP2 (Src kinase inhibitor), and wortmannin (PI3-kinase inhibitor). In cultured endothelial cells, A. melanocarpa juice increased the formation of NO as assessed by electron paramagnetic resonance spectroscopy using the spin trap iron(II)diethyldithiocarbamate, and reactive oxygen species using dihydroethidium. These responses were associated with the redox-sensitive phosphorylation of Src, Akt and eNOS. A. melanocarpa juice-derived fractions containing conjugated cyanidins and chlorogenic acids induced the phosphorylation of Akt and eNOS. The present findings indicate that A. melanocarpa juice is a potent stimulator of the endothelial formation of NO in coronary arteries; this effect involves the phosphorylation of eNOS via the redox-sensitive activation of the Src/PI3-kinase/Akt pathway mostly by conjugated cyanidins and chlorogenic acids.


The ethics of maternal-fetal surgery.
Maternal-fetal surgery is performed on two patients, the pregnant patient and the fetal patient. Ethics is therefore an essential dimension of maternal-fetal surgery. From its beginnings in only a few centers, various procedures have become available in highly specialized centers in developed countries. Innovation and research have played an indispensable role in the development of maternal-fetal surgery and will continue to do so. In this article we present ethically justified criteria, based on the ethical concept of the fetus as a patient, for clinical innovation and research of maternal-fetal surgery and for the professionally responsible transition from innovation and research into clinical practice. These criteria are designed to be used by clinical innovators, clinical investigators, and by oversight committees.


Postprandial lipemia in men with metabolic syndrome, hypertensives and healthy subjects.
The metabolic syndrome (MetS), as well as postprandial hypertriglyceridemia, is associated with coronary heart disease. This study aimed to evaluate the postprandial lipemia after oral fat tolerance test (OFTT) in subjects with MetS and compare them to hypertensive (HTN) and healthy subjects. OFTT was given to 33 men with MetS (defined by the Adult Treatment Panel III), 17 HTN and 14 healthy men. The MetS group was further divided according to fasting triglycerides (TG) into TG > or = 150 [MetS+TG, (n = 22)] or < 150 mg/dl [MetS-TG (n = 11)], and into those with or without hypertension [MetS+HTN (n = 24), MetS-HTN (n = 9), respectively]. TG concentrations were measured before and at 4, 6 and 8 h after OFTT and the postprandial response was quantified using the area under the curve (AUC) for TG. The postprandial response was significantly higher in MetS compared to HTN and healthy men [AUC (SD) in mg/dl/h; 2534 +/- 1016 vs. 1620 +/- 494 and 1019 +/- 280, respectively, p < or = 0.001]. The TG levels were increased significantly in MetS+TG compared to MetS-TG subjects at 4 (p = 0.022), 6 (p < 0.001) and 8 hours (p < 0.001). The TG were increased significantly in MetS-TG compared to healthy subjects at 4 (p = 0.011), 6 (p = 0.001) and 8 hours (p = 0.015). In linear regression analysis only fasting TG levels were a significant predictor of the AUC (Coefficient B = 8.462, p < 0.001). Fasting TG concentration is the main determinant of postprandial lipemia. However, an exaggeration of TG postprandialy was found in normotriglyceridemic MetS and HTN compared to healthy subjects. This suggests that intervention to lower fasting TG levels should be recommended in MetS subjects.


Cocaine and lidocaine as topical urethral anesthetics.
To evaluate the efficacy of topical cocaine combined with lidocaine as a urethral anesthetic, a double-blind, randomized, prospective study was performed comparing lidocaine combined with cocaine or placebo in male outpatient cystoscopy. Evaluations were based on a scale of 1 to 10, with 1 representing no discomfort and 10 extreme discomfort as judged by the patient, and 1 representing the best tolerance and 10 extreme intolerance as judged by the physician. Patients who received lidocaine plus cocaine reported a mean score of 3.33 for over-all discomfort of cystoscopy. This was not significantly different than for lidocaine alone. This finding indicates a lack of a summation effect in combining topical anesthetics. Patients undergoing repeat examinations were no more comfortable than those undergoing initial cystoscopy but older patients tolerated the procedure significantly better than younger patients.


Blood selenium in chronic spinal muscular atrophy.
The spinal muscular atrophies (SMA) of childhood comprise the second most common fatal recessive disease after cystic fibrosis, yet the nature of the biochemical defect causing the anterior horn cell degeneration is totally unknown. Recent reports of a cluster of adult motor neurone disease cases from a high seleniferous area in South Dakota have prompted the study of blood selenium in children with SMA in Australia. Eight children with chronic SMA were tested, in addition to 9 obligate heterozygote carriers of the gene. Blood selenium levels of patients and carriers did not differ significantly from that observed in controls. The mammalian effects of selenium toxicity are discussed.


[Diagnosis and specifics of the clinical course of acute surgical sepsis].
The results of observations on 176 patients with sepsis are presented. Criteria for diagnosis of acute surgical sepsis are substantiated, it symptoms, peculiarities of the course and outcome described. The criteria for differential diagnosis of diffuse purulent peritonitis and peritoneal sepsis on the basis of a mechanism of the polyorganic failure syndrome development are presented.


Laparoscopic left hepatectomy with intraoperative biliary exploration for hepatolithiasis.
Major liver resections remain a challenge for liver surgeons. This video illustrates, step by step, a totally laparoscopic technique for left hepatectomy with intraoperative exploration of the remaining biliary tree in a patient with unilateral hepatolithiasis.


Statin prescribing in Australia: socioeconomic and sex differences. A cross-sectional study.
To assess if there are any differences in statin prescribing across Australia by socioeconomic status or sex and to relate prescribing rates to coronary heart disease (CHD) mortality rates. Cross-sectional study using data on statin prescribing by age, sex and patient postcode for the period May to December 2002. The Australian population, stratified by sex and quintile of Index of Relative Socio-Economic Disadvantage (IRSD). Age-standardised rates of statin scripts per 1000 population per month for each sex and IRSD quintile. 9.1 million prescriptions for statins were supplied between May and December 2002, for a total cost of 570 million dollars. The age-standardised rates for statin prescribing in women varied from 56.9 (95% CI, 56.6-57.2) scripts per 1000 population per month in the most disadvantaged socioeconomic quintile through 53.4 (95% CI, 53.0-53.7), 50.3 (95% CI, 50.0-50.6), 48.4 (95% CI, 48.1-48.7) to 46.3 (95% CI, 46.0-46.6) in the least disadvantaged quintile. For men the figures were 52.6 (95% CI, 52.3-52.9), 50.9 (95% CI, 50.6-51.2), 48.8 (95% CI, 48.6-49.1), 47.7 (95% CI, 47.4-47.9), and 51.9 (95% CI, 51.6-52.2). There was a significant linear association between statin prescribing and CHD mortality by quintile of socioeconomic disadvantage in women (weighted least squares slope, 0.380; 95% CI, 0.366 to 0.395; P < 0.0001), but not in men (slope, -0.002; 95% CI, -0.010 to 0.006; P = 0.65). Our results suggest that in men there is either overprescribing of statins in the highest socioeconomic quintile or underprescribing in the lowest. Furthermore, contrary to expectation, women - relative to men - are prescribed statins at higher rates at lower levels of risk (using CHD deaths as a proxy measure of risk).


Comparative immunomodulatory effects in mice and in human dendritic cells of five bacterial strains selected for biocontrol of leafy green vegetables.
The market for ready-to eat vegetables is increasing, but unfortunately so do the numbers of food-borne illness outbreaks related to these products. A previous study has identified bacterial strains suitable for biocontrol of leafy green vegetables to reduce the exposure to pathogens in these products. As a tentative safety evaluation, five selected strains (Rhodococcus cerastii MR5x, Bacillus coagulans LMG P-32205, Bacillus coagulans LMG P-32206, Pseudomonas cedrina LMG P-32207 and Pseudomonas punonensis LMG P-32204) were individually compared for immunomodulating effects in mice and in human monocyte-derived dendritic cells (MoDCs). Mice receiving the two B. coagulans strains consistently resemble the immunological response of the normal control, and no, or low, cell activation and pro-inflammatory cytokine expression was observed in MoDCs exposed to B. coagulans strains. However, different responses were seen in the two models for the Gram-negative P. cedrina and the Gram-positive R. cerastii. Moreover, P. punonensis and B. coagulans increased the microbiota diversity in mice as seen by the Shannon-Wiener index. In conclusion, the two strains of B. coagulans showed an immunological response that indicate that they lack pathogenic abilities, thus encouraging further safety evaluation and showing great potential to be used as biocontrol agents on leafy green vegetables.


Effect of a new squalene synthase inhibitor on an ApoE-/- mouse model of atherosclerosis.
Ηypercholesterolemia/hyperlipidemia in conjunction with oxidative stress and inflammatory processes contribute synergistically to the pathogenesis of atherosclerosis. We hereby evaluated the antiatherosclerotic effect of the multi-target derivative 4-methyl-2-(10H-phenothiazin-3-yl)morpholin-2-ol hydrobromide 1 in apoE-/- mice; compound 1 is a potent antihyperlipidemic agent acting through Squalene Synthase inhibition, while it has exhibited an outstanding antioxidant and anti-inflammatory activity in various experimental animal models. The new analogue was evaluated in terms of its antiatherosclerotic/antioxidant effect in the ApoE-/- transgenic mouse model. Its toxicity profile was also assessed by measuring the levels of four sensitive indicators of liver toxicity. Prolonged administration of 1 in ApoE-/- mice fed with a western-type (wt) diet efficiently reduced the aortic atheromatic lesions, an effect that took place through a cholesterol lowering independent manner. In addition, 1 displayed a significant reduction not only of glucose but also of oxidative stress levels, while it did not cause any toxicity. To the best of our knowledge this is the first time that the antiatherosclerotic effect of a Squalene Synthase inhibitor is studied in this specific atherosclerosis mouse model. As a result, compound 1 may serve as a promising starting point towards developing new bioactive analogues against the onset and subsequent development of atherosclerosis.


Real-time demultiplexing Nanopore barcoded sequencing data with npBarcode.
The recent introduction of a barcoding protocol for Oxford Nanopore sequencing has increased the versatility of the technology. Several bioinformatics tools have been developed to demultiplex barcoded reads, but none of them supports streaming analysis. This limits the use of multiplexed sequencing in real-time applications, which is one of the main advantages of the technology. We introduced npBarcode, an open source and cross-platform tool for barcode demultiplexing in streaming fashion that can be used to pipe data to further real-time analyses. The tool also provides a friendly graphical user interface by integrating the module into npReader, making possible to monitor the progress concurrently when the sequencing is still in progress. We show that our algorithm achieves accuracies at least as good as competing tools. npBarcode is bundled in Japsa-a Java tools kit for genome analysis, and is freely available at https://github.com/mdcao/japsa. email@example.com or firstname.lastname@example.com. Supplementary data are available at Bioinformatics online.


Alterations of cellular redox homeostasis in cultured fibroblast-like renal cells upon exposure to low doses of cytochrome bc1 complex inhibitor kresoxim-methyl.
In this paper we elucidate the effects of the cytochrome bc1 inhibitor, strobilurin fungicide kresoxim-methyl, on the redox balance of a mammalian renal cell line. To explore whether mammalian exposure to sub-nephrotoxic concentrations of kresoxim-methyl induces cellular and biochemical mechanisms of toxicity, its effects on cellular viability and, in particular, several parameters related to oxidative stress, mitochondrial respiratory function and apoptosis were examined in fibroblast-like renal Vero cells. Elevation of mitochondrial superoxide generation, together with a concomitant decrease in mitochondrial transmembrane potential was indicative of mitochondrial dysfunction. Losses on antioxidant enzyme activities and GSH, along with increased H2O2 and nitrite release were associated with oxidative stress and induced impaired cellular migration. Raise of intracellular calcium was also observed, while no experimental evidence of apoptosis was found. Our findings suggest that sub-nephrotoxic concentrations of kresoxim-methyl cause perturbation of multiple pathways in renal mammalian cellular redox homeostasis.


Clinical characteristics and outcomes of patients with COVID-19 and tuberculosis coinfection.
Data on the coincidence of Tuberculosis (TB) and Coronavirus disease 2019 (COVID-19) are limited. We sought to investigate the clinical characteristics and outcomes of coinfected patients in Henan and identify whether TB disease is associated with an increased risk of intensive care unit (ICU) admission and mortality. We conducted a retrospective matched cohort study of COVID-19 inpatients involving 41 TB-positive patients with 82 patients without TB. Leveraging data was collected from electronic medical records. There were no significant differences in clinical manifestations, the need for mechanical ventilation and vasopressors, ICU admission, or in-hospital mortality between 2 groups. TB-positive patients had a lower lymphocyte counts (1.24 ± 0.54 vs. 1.59 ± 0.58, p = 0.01), B cells (99/µl vs. 201/µl, p < 0.01), CD4+ T cells (382/µl vs. 667/µl, p < 0.01), CD8+ T cells (243/µl vs. 423/µl, p < 0.01), NK cells (145/µl vs. 216/µl, p = 0.01), IL-2 (14.18 ± 11.23 vs. 31.86 ± 34.55, p < 0.01) and TNF-α (3.42 ± 2.93 vs. 5.62 ± 3.69, p < 0.01). Notably, the TB-positive group had a longer duration of SARS-CoV-2 shedding (67 days vs. 22 days, p < 0.01). Concomitant TB does not significantly impact clinical outcomes of hospitalised patients with acute COVID-19. However, TB-positive patients had longer duration of SARS-COV-2-RNA positivity.


Dynamicity of early and late phases of repolarization in patients with remote anterior myocardial infarction: the interlead differences.
Repolarization dynamicity (QT/RR) is supposed to be a prognostic marker in post-MI patients. However, data on the relationships between early and late phases of QT and RR intervals (QT peak/RR and T peak-T end/RR) are insufficient, and which ECG lead should be used for the analysis is unclear. We analyzed repolarization dynamicity in patients after anterior MI with and without VT/VF history using two leads of Holter recordings- modified V(5) and V(3) . The daytime and nighttime periods were also analyzed. Cohort of 88 patients after anterior MI (>6 months) consisted of 43 patients without VT/VF (33 males; 59 ± 12 years; LVEF: 41 ± 7%; NoVT/VF), and 45 patients with VT/VF history- ICD implanted as secondary prevention (40 males; 64 ± 10 years; LVEF: 32 ± 8%; VT/VF). QT/RR, QT peak/RR and T peak-T end/RR were calculated from 24-hour ECG for the entire recording, daytime and nighttime periods, from V(5) and V(3) leads, respectively. VT/VF patients had lower LVEF (P = 0.001). There were no differences in age and gender. VT/VF group had steeper QT/RR, QT peak/RR, and T peak-T end/RR in V(5) : 0.233 ± 0.04 versus 0.150 ± 0.05, P = 0.0001, 0.181 ± 0.04 versus 0.120 ± 0.04, P = 0.0001, 0.052 ± 0.02 versus 0.030 ± 0.02, P = 0.0001, and in V(3) : 0.201 ± 0.04 versus 0.149 ± 0.05, P = 0.0001, 0.159 ± 0.03 versus 0.118 ± 0.04, P = 0.0001, and 0.042 ± 0.02 versus 0.031 ± 0.02, P = 0.004; respectively. VT/VF patients had higher indices in V(5) than in V(3) lead (P = 0.001). QT/RR and QT peak/RR were steeper at daytime period in both leads. It was not found for T peak-T end/RR. Patients with VT/VF history are characterized by steeper relationships between repolarization duration and RR intervals. These findings are more evident in modified V(5) lead.


Sensitivity of Countermovement Jump Variables in Professional Rugby Union Players Within a Playing Season.
Howarth, DJ, McLean, BD, Cohen, DD, and Coutts, AJ. Sensitivity of countermovement jump variables in professional rugby union players within a playing season. J Strength Cond Res 37(7): 1463-1469, 2023-The aim of this study was to explore the measurement sensitivity of a wide range of countermovement jump (CMJ) variables to a full European professional rugby union season. A secondary purpose was to compare 3 different data treatment methods for the calculation of CMJ variables. Twenty-nine professional rugby union players (mean ± SD; age 24 ± 4 years, height 183.7 ± 8.0 cm, body mass 101.6 ± 10.7 kg) completed a minimum of 12 CMJ testing sessions on Thursdays-a day preceded by a rest day and a minimum of 96 hours after a match-throughout a season. Measurement sensitivity, quantified by signal-to-noise ratio (SNR), was determined for 74 CMJ variables and was calculated by dividing the signal, (week-to-week variation expressed as a coefficient of variation [CV%]) by the noise (interday test/retest reliability expressed as CV%). We also identified variables which had no overlap between the 95% confidence intervals (CIs) for the signal and the noise. The 3 data treatment methods for comparison were (a) mean output across 3 jump trials (Mean3), (b) single output from the trial with the highest jump (BestJH), and (c) the trial with the highest flight time to contraction time ratio (BestFTCT). Most variables had an SNR >1.0 (Mean3 = 60/74; BestFTCT = 59/74; BestJH = 48/74). Fewer variables displayed a nonoverlap of 95% CIs (Mean3 = 23/60; BestFTCT = 22/59; BestJH = 16/48). Most CMJ variables during a professional rugby season demonstrated a signal that exceeded measured noise (SNR > 1.0) and that using the Mean3 or BestFTCT data treatment methods yields a greater number of variables considered sensitive within a season (i.e., SNR > 1.0) than when using BestJH. We also recommend the calculation of the 95% CIs for both signal and noise, with nonoverlap indicative of a greater probability that the responsiveness of the variable at team level (i.e., SNR) also applies at the individual level. As sensitivity analysis is cohort and environment specific, practitioners should conduct a sensitivity analysis using internal signal and noise data to inform their own monitoring protocols.


Ortho-methylated tribenzotriquinacenes--paving the way to curved carbon networks.
The synthesis of sterically crowded tribenzotriquinacenes with complete and partial methylation of the ortho-positions has been achieved using the double cyclodehydration strategy. This leads to a twisted tribenzotriquinacene core and enables further functionalization for the future synthesis of curved model compounds for defective carbon networks.


Nest-plugging: interference competition in desert ants (Novomessor cockerelli and Pogonomyrmex barbatus).
Pogonomyrmex barbatus and Novomessor cockerelli, sympatric species of harvester ants in the Lower Sonoran desert, compete for seed resources. This study reports on a method of interference competition. Early in the morning, before P. barbatus' activity period, N. cockerelli fills the nest entrances of P. barbatus with sand. This delays the beginning of the P. barbatus activity period for 1-3 h. P. barbatus colonies near N. cockerelli nests were more likely to be plugged. Nest-plugging shifts the typical daily sequence of P. barbatus activities, including the onset of foraging, forward towards midday, when high temperatures force the colony back inside the nest. P. barbatus colonies do not compensate for late emergence or events impeding foraging by increasing foraging rate. Thus nest-plugging by N. cockerelli decreases the foraging capacity of P. barbatus colonies.


Reconstitution of EPA and DHA biosynthesis in arabidopsis: iterative metabolic engineering for the synthesis of n-3 LC-PUFAs in transgenic plants.
An iterative approach to optimising the accumulation of non-native long chain polyunsaturated fatty acids in transgenic plants was undertaken in Arabidopsis thaliana. The contribution of a number of different transgene enzyme activities was systematically determined, as was the contribution of endogenous fatty acid metabolism. Successive iterations were informed by lipidomic analysis of neutral, polar and acyl-CoA pools. This approach allowed for a four-fold improvement on levels previously reported for the accumulation of eicosapentaenoic acid in Arabidopsis seeds and also facilitated the successful engineering of the high value polyunsaturated fatty acid docosahexaenoic acid to 10-fold higher levels. Our studies identify the minimal gene set required to direct the efficient synthesis of these fatty acids in transgenic seed oil.


Genetic Landscape of Multistep Hepatocarcinogenesis.
Hepatocellular carcinoma (HCC) is a major cause of cancer-related death worldwide. Although several targeted therapy agents are available for advanced HCC, their antitumor efficacy remains limited. As the complex genetic landscape of HCC would compromise the antitumor efficacy of targeted therapy, a deeper understanding of the genetic landscape of hepatocarcinogenesis is necessary. Recent comprehensive genetic analyses have revealed the driver genes of HCC, which accumulate during the multistage process of hepatocarcinogenesis, facilitating HCC genetic heterogeneity. In addition, as early genetic changes may represent key therapeutic targets, the genetic landscapes of early HCC and precancerous liver tissues have been characterized in recent years, in parallel with the advancement of next-generation sequencing analysis. In this review article, we first summarize the landscape of the liver cancer genome and its intratumor heterogeneity. We then introduce recent insight on early genetic alterations in hepatocarcinogenesis, especially those in early HCC and noncancerous liver tissues. Finally, we summarize the multistep accumulation of genetic aberrations throughout cancer progression and discuss the future perspective towards the clinical application of this genetic information.


[The modern approaches to the choice of infusion agents used in the treatment of severe injuries and burns].
The article presents an analytical review of modern possibilities of the complex pathogenic treatment for severe traumas and injuries at the expense of systemic use of infusion drugs with antihypoxic and antioxidant effects. It is shown that hypoxia and oxidative stress is the typical; pathologic process that accompanies the development of traumatic disease during severe surgical pathology. One of the effective ways to correct the developing disorders is to use the regulatory or substrate antihypoxants as well as the drugs with antioxidant effect.


Catheter-associated bloodstream infection after bowel surgery in patients with inflammatory bowel disease.
Catheter-associated bloodstream infections (CABSIs) are a leading cause of nosocomial infections. The objectives of this study were to establish the incidence of CABSIs after bowel surgery and to identify the risk factors. We reviewed the prospectively collected data of patients who underwent abdominal surgery with central venous catheter (CVC) insertion between March, 2006 and September, 2009. We analyzed all possible variables, including age, sex, disease, CVC duration, insertion frequency, CVC site, infliximab, corticosteroid, and immunosuppressant administration, preoperative serum albumin level, surgical wound class, and emergency surgery. A total of 1261 patients were prospectively surveyed. The underlying diseases comprised ulcerative colitis (UC; n = 428), Crohn's disease (CD; n = 334), colorectal cancer (CA; n = 344), esophageal cancer (ESO; n = 28), gastric cancer (GAST; n = 44), and others (n = 83). The incidences of CABSI were 6.9/1000 catheter days for UC, 7.4 for CD, 4.3 for CA, 3.7 for ESO, 3.7 for GAST, and 5.1 for others. CD patients had the highest rate of CABSI. The risk factors for CABSI were CD with an odds ratio (OR) of 1.63, dirty/infected wound class (OR 3.34), and CVC insertion via the internal jugular vein (OR 9.89). A high CABSI incidence was found in association with CD, especially in dirty/infected surgery. Thus, the use of CVCs should be restricted in the presence of these risk factors.


Pregnancy in patients with Sydenham's Chorea.
Sydenham's Chorea is a frequent cause of chorea during pregnancy, chorea gravidarum. The aim of this article is to describe the effect of pregnancy in a consecutive series of patients with diagnosis of Sydenham's Chorea. A chart review was performed of all patients with the diagnosis of Sydenham's Chorea followed up at our institution from 07/1993 through 08/2010 and who became pregnant. From 66 patients, 20 became pregnant. Of these 20 patients, 15 (75%) developed chorea gravidarum. Generalized chorea was found in 67% of these 15 patients, focal or multifocal chorea was identified in 20% and 13.4% developed hemichorea. In 80% of cases chorea began in the first 6 months of gestation. Three women with previous persistent chorea experienced worsening of the movement disorder during pregnancy. Remission occurred after delivery in 11 patients whereas the other four remained with non-disabling chorea during the first 12 months after delivery. Abortion occurred in two patients (13%). All patients with chorea gravidarum subsequently treated with oral contraceptives developed recurrence of chorea. Chorea gravidarum is a frequent complication of pregnancy in patients with previous history of Sydenham's Chorea and an increased risk of miscarriage should be considered. Our findings confirm the notion that chorea gravidarum results from hormonal changes acting on previously dysfunctional basal ganglia.


Analysis of type II collagen RNA localization in chick wing buds by in situ hybridization.
Type II collagen is a major component of cartilage extracellular matrix. Differentiation of mesenchyme into cartilage involves the cessation of type I collagen synthesis and the onset of type II collagen synthesis. Solution hybridization of mRNA isolated from chick limb buds with a cDNA probe to type II collagen mRNA showed the presence of small amounts of type II collagen message in mesenchymal chick limbs. We have examined the localization of type II collagen mRNA in mesenchymal chick wing buds by in situ hybridization using single stranded RNA probes. Our results show a small but detectable amount of type II collagen RNA distributed uniformly in early limbs until the first precartilage condensations form at stage 22. This is interesting because it is known that mesenchyme isolated from chick wing buds has the capacity to undergo chondrogenesis in culture, even if taken from nonchondrogenic areas of the limb. At stage 23, type II collagen mRNA is found at significantly increased levels in the cells of the precartilage condensation when compared to the other limb cells. As chondrogenesis proceeds, the amount of type II collagen RNA increases even more in cells of the cartilage elements. The signal in the peripheral tissue is indistinguishable from background. These results show that type II collagen message exists at low levels in cells throughout the mesenchymal chick wing bud, until the formation of the condensation results in an elevation of type II mRNA in the prechondrogenic cells found in the core of the limb.


Sesquiterpene glycosides from Calendula arvensis.
The extract of the aerial parts of Calendula arvensis afforded four new sesquiterpene glycosides 1-4 in addition to three known compounds. The structures of the new compounds were established by high field 1H-nmr spectroscopy.


Qualitative and quantitative prediction of food allergen epitopes based on machine learning combined with in vitro experimental validation.
An allergen epitope is a part of molecules that can specifically bind to immunoglobulin E (IgE), causing an allergic reactions. To predict protein epitopes and their binding ability to IgE, quantitative structure-activity relationship (QSAR) models were established using four algorithms combined with the selected chemical descriptors. The model predicted the binding capabilities of the epitopes to IgE with the R2 and root mean squared error (RMSE) as 0.7494 and 0.2375, respectively. The model's performance was validated using an enzyme-linked immunosorbent assay (ELISA). The results showed that the established QSAR model could efficiently and accurately predict the allergic reaction of food protein epitopes. The prediction results of the model and the experimental results were consistent, with a Pearson correlation coefficient of 0.8956. The results from both the QSAR model and in vitro experiments indicated that amino acid sequence 116-130 was a novel IgE-binding epitope of β-LG.


If You Have to Ask How Much It Costs, You Probably Can't Afford It.
In health care, the cost of surgical procedures and medications often come across as items listed at market price, which is indicated as "MP" on menus of many upscale restaurants.


Determination of regulatory phosphorylation sites in nanogram amounts of a synthetic fragment of ZAP-70 using microprobe NMR and on-line coupled capillary HPLC-NMR.
The protein kinase ZAP-70 is involved in T-cell activation and interacts with tyrosine-phosphorylated peptide sequences known as immunoreceptor tyrosine activation motifs (ITAMs). We have studied the regulatory phosphorylation sites in the tryptic fragment containing amino acids 485-496 (ALGADDSYYTAR). The four possible peptides with phosphorylation at none, one, or both of the Y-492 and Y-493 tyrosines were specifically synthesized and analyzed by (1)H/(13)C-NMR at 600 MHz using a capillary HPLC-NMR microprobe. Unambiguous discrimination of the peptides was possible via effect of chemical shifts of phosphorylation on the aromatic tyrosine protons. With the microprobe and the detection volume of 1.5 microl, it was possible to perform structure elucidation with the very small amounts available for the various peptides. For the syringe injection, 15 microg of the analyte were used (corresponding to ca 2 mg in classical 5-mm tubes). Capillary HPLC-NMR spectra were recorded in the stopped-flow mode from less than 400 ng of each peptide, using 1D and 2D techniques ((1)H,(1)H-COSY-90, (1)H/(13)C-HSQC, and (1)H/(13)C-HMBC).


De Novo Shoot Regeneration Controlled by HEN1 and TCP3/4 in Arabidopsis.
Plants have the ability to regenerate whole plant body parts, including shoots and roots, in vitro from callus derived from a variety of tissues. However, the underlying mechanisms for this de novo organogenesis, which is based on the totipotency of callus cells, are poorly understood. Here, we report that a microRNA (miRNA)-mediated posttranscriptional regulation plays an important role in de novo shoot regeneration. We found that mutations in HUA ENHANCER 1 (HEN1), a gene encoding a small RNA methyltransferase, cause cytokinin-related defects in de novo shoot regeneration. A hen1 mutation caused a large reduction in the miRNA319 (miR319) level and a subsequent increase in its known target (TCP3 and TCP4) transcript levels. TCP transcription factors redundantly inhibited shoot regeneration and directly activated the expression of a negative regulator of cytokinin response ARABIDOPSIS THALIANA RESPONSE REGULATOR 16 (ARR16). A tcp4 mutation at least partly rescued the shoot-regeneration defect and derepression of ARR16 in hen1. These findings demonstrate that the miR319-TCP3/4-ARR16 axis controls de novo shoot regeneration by modulating cytokinin responses.


Occupational exposure to potentially toxic elements alters gene expression profiles in formal and informal Brazilian workers.
Chemical elements, such as toxic metals, have previously demonstrated their ability to alter gene expression in humans and other species. In this study, microarray analysis was used to compare the gene expression profiles of different occupational exposure populations: a) informal workers who perform soldering of jewelry inside their houses (n = 22) in São Paulo (SP) State; and b) formal workers from a steel company (n = 10) in Rio de Janeiro (RJ) state, Brazil. Control participants were recruited from the same neighborhoods without occupational chemical exposure (n = 19 in SP and n = 8 in RJ). A total of 68 blood samples were collected and RNA was extracted and hybridized using an Agilent microarray platform. Data pre-processing, statistical and pathway analysis were performed using GeneSpring software. Different expression was detected by fold-change analysis resulting in 16 up- and 33 down-regulated genes in informal workers compared to the control group. Pathway analysis revealed genes enriched in MAPK, Toll-like receptor, and NF-kappa B signaling pathways, involved in inflammatory and immune responses. In formal workers, 20 up- and 50 down-regulated genes were found related to antimicrobial peptides, defensins, neutrophil degranulation, Fc-gamma receptor-dependent phagocytosis, and pathways associated with atherosclerosis development, which is one of the main factors involved in the progression of cardiovascular diseases. The gene IFI27 was the only one commonly differentially expressed between informal and formal workers and is known to be associated with various types of cancer. In conclusion, differences in gene expression related to occupational exposure are mainly associated with inflammation and immune response. Previous research has identified a link between inflammation and immune responses and the development of chronic diseases, suggesting that prolonged occupational exposures to potentially toxic elements in Brazilian metal workers could lead to negative health outcomes. Further analysis should be carried out to investigate its direct effects and to validate causal associations.


[Bone tumour register and therapeutic centres (author's transl)].
This report deals with bone tumour centres in Dresden and Cottbus (G.D.R.). The data registered were computerized. A reference centre as suggested by the WHO is described with respect to the tumours of bones.


Intercellular transport of Tau protein and β-amyloid mediated by tunneling nanotubes.
Tunneling nanotubes (TNTs) are thin channel-like structures connecting distant cells, providing a route for intercellular communication. In this study, we investigated the physical properties, including the cytoskeletal components, length and diameter, of the TNTs formed by HEK293T, U87 MG, and U251 cell lines. We found that organelles such as lysosomes, mitochondria, and Golgi bodies can be transported through TNTs, indicating that TNTs can mediate material transport. Moreover, we investigated the transport of the Tau protein and β-amyloid (Aβ), which are both closely related to Alzheimer's disease (AD) pathology, through TNTs. The results showed that TNTs formed by various neuronal cell lines can mediate the transport of different forms of the Tau protein and fluorescently labeled Aβ and that this transport is bidirectional, with different velocities in various cell lines. Our results confirmed the transport of the Tau protein and Aβ between cells and provided a possible explanation for the cascade of cell death in specific brain regions during the progression of AD. Our findings suggest new possibilities for the treatment of AD.


Neuromedin: An insight into its types, receptors and therapeutic opportunities.
Neuropeptides are small protein used by neurons in signal communications. Neuromedin U was the first neuropeptide discovered from the porcine spinal and showed its potent constricting activities on uterus hence was entitled with neuromedin U. Following neuromedin U another of its isoform was discovered neuromedin S which was observed in suprachiasmatic nucleus hence was entitled neuromedin S. Neuromedin K and neuromedin L are of kanassin class which belong to tachykinin family. Bombesin family consists of neuromedin B and neuromedin C. All these different neuromedins have various physiological roles like constrictive effects on the smooth muscles, control of blood pressure, pain sensations, hunger, bone metastasis and release and regulation of hormones. Over the years various newer physiological roles have been observed thus opening ways for various novel therapeutic treatments. This review aims to provide an overview of important different types of neuromedin, their receptors, signal transduction mechanism and implications for various diseases.


Detection of circulating immune complexes in human sera by simplified assays with polyethylene glycol.
The search for circulating immune complexes by precipitation tests using polyethylene glycol (PEG) was performed on a series of normal and pathological sera. Various factors affecting PEG precipitation were studied. Immunoglobulins and complement factors percipitated by PEG (3.5%) were quantified and their significance was discussed in relation to serum levels. The PEG test was compared to labeled C1q binding test with a fairly good correlation. The direct evaluation of the amount of C4 precipitated with IgG by 3% PEG (C4 test) provided a simpler routine assay than the C1q binding test for detecting complement-fixing immune complexes. The direct PEG test and the C4 tests gave positive results in patients with diseases generally presumed to be associated with immune complexes including systemic lupus erythematosus, acute glomerulonephritis, bacterial sub-acute endocarditis and chronic acitve hepatitis. The demonstration of HBs antigen and antibody after acid dissociation of PEG precipitates from hepatitis B seronegative sera illustrated the fact that PEG does precipitate and thus concentrates circulating immune complexes.


Effects of preeclampsia on the yield of hematopoietic stem cells obtained from umbilical cord blood at delivery.
To compare the numbers of cord blood CD34(+) hematopoietic stem cells (HSC) between preeclampsia (PE) and control (non-PE) subjects and to determine the factors that may influence this observation. Umbilical cord blood was collected from 28 PE and 19 non-PE subjects. Nucleated and CD34(+) cell counts were derived using the Trucount tube-based stem cell enumeration kit on BD FACSCalibur. The cord blood volume, nucleated and CD34(+) cell counts were significantly reduced in PE subjects compared to non-PE subjects. Among the PE subjects, systolic and diastolic blood pressure demonstrated a negative correlation with total nucleated and CD34(+) cell counts. Gestational age at delivery influenced cord blood volume and nucleated cell counts, but not CD34(+) cell counts. Birth weight and placental weight correlated strongly with cord blood volume, and nucleated and CD34(+) cell counts. There were no correlations observed between cord blood parameters and maternal age, maternal white cell count, gravidity, route of delivery or neonatal gender among PE subjects. Preeclampsia has a negative impact on the yield of HSC obtained from cord blood at delivery. Maternal blood pressure, neonatal birth weight and placental weight are important factors influencing the numbers of cord blood HSC. These findings should be taken into consideration when selecting cord blood units from mothers with PE for banking. Selecting the heaviest term neonate might improve the yield of cord blood HSC obtained from PE mothers.


Primary leiomyoma of the ovary: a case report.
The imaging features of primary ovarian leiomyoma have seldom been described because of the very low prevalence of the tumor. Herein we present a case report on its magnetic resonance imaging features. Both T1- and T2-weighted images revealed a low-signal-intensity mass, which was well circumscribed and sharply demarcated from the uterus. Magnetic resonance imaging was useful in distinguishing it from a malignant ovarian tumor and uterine leiomyoma.