Automated analysis of bone-conduction cortical auditory evoked potential in normal-hearing neonates.
The cortical auditory evoked potential allows the possibility of objectively evaluating the entire auditory system, which is desirable in the pediatric population. Bone conduction auditory stimulation is recommended in the differential diagnosis of conductive hearing loss. However, there are not many studies of cortical auditory evoked potential using bone conduction. The aim of this study was to characterize the response of cortical auditory evoked potential through bone conduction in normal-hearing neonates using an automated response analysis equipment. This study included 30 normal-hearing neonates, without risk factors for hearing loss. The equipment used was the HEARlab automated response analysis and the cortical responses were evaluated at the frequencies of 500-4000Hz through bone conduction, at intensity ranging from 0 to 60dBnHL. The latencies and amplitudes were manually marked by experienced judges. Cortical auditory evoked potential responses were detected in 100% of the evaluated subjects and there was no difference regarding the cortical response of the neonates in relation to the variables of gender, ear and masking use. At an intensity of 60 dBnHL for the frequencies of 500, 1000, 2000 and 4000Hz the latencies were 234; 241; 239 and 253ms and the amplitudes were 15.6; 8.4; 6.2; 6.3μV. The mean thresholds were 23.6; 28; 31 and 33.1dBnHL, respectively. It was possible to measure the cortical auditory evoked potential response in the neonatal population using bone vibrator as sound transducer and to draw the profile of the cortical auditory evoked potential latencies and amplitudes by frequencies at the intensity of 60dBnHL and at the threshold.


Comprehensive control of PM 2.5 capture and ozone emission in two-stage electrostatic precipitators.
Indoor air purification is extremely urgent to eliminate the health threat of PM 2.5, VOCs and microbial aerosol for exposing people, for which ESPs enjoy exceptional advantage for its special high-voltage characteristic. However, the secondary air pollutant of ozone is produced to possibly cause potential risk. In this work, six kinds of two-stage ESPs containing various charger and collector units, whose structure and size design are determined according to the indoor application, are developed to investigate the comprehensive control of PM 2.5 capture and ozone emission. Responsive surface methodology is employed to explore the relationship among ozone concentration, wire number, charger current and airflow velocity, and obtain regression model for predicting ozone emission. The comprehensive evaluation standard considering efficiency-ozone double factors is proposed to optimize structure design and working conditions of two-stage ESPs. Experimental results show that two-stage ESPs with a unit ratio of >3/4 can keep relatively good stable state, whose current reduction is in around 10 μA, for preventing particle charging function of charger from basically affecting. For the two-stage ESP with Ra = 2/5, it finds the optimization of working conditions of collector can bring rapid improvement of collection efficiency for 0.25 μm particles, which reaches up to be >60 %, while the optimization of that of the charger can only result in an enhancement of <30 %. RSM analysis exhibits a strong connection between the interactive effect of charger current and airflow velocity for presenting a steep response surface. Based on comprehensive control of PM 2.5 and ozone pollutants, it suggests the two-stage ESP with Ra = 2/5 is selected at the first priority and then that with Ra = 1/6, while two-stage ESP with Ra = 4/3 is not recommended for unsatisfied consequence of both of PM 2.5 capture and ozone emission.


Neuroinflammation in Alzheimer's Disease: Current Progress in Molecular Signaling and Therapeutics.
Alzheimer's disease, a neurodegenerative disease with amyloid beta accumulation as a major hallmark, has become a dire global health concern as there is a lack of clear understanding of the causative agent. It is a major cause of dementia which is increasing exponentially with age. Alzheimer's disease is marked by tau hyperphosphorylation and amyloid beta accumulation that robs people of their memories. Amyloid beta deposition initiated a spectrum of microglia-activated neuroinflammation, and microglia and astrocyte activation elicited expressions of various inflammatory and anti-inflammatory cytokines. Neuroinflammation is one of the cardinal features of Alzheimer's disease. Pro-inflammatory cytokine signaling plays multifarious roles in neurodegeneration and neuroprotection. Induction of proinflammatory signaling leads to discharge of immune mediators which affect functions of neurons and cause cell death. Sluggish anti-inflammatory system also contributes to neuroinflammation. Numerous pathways like NFκB, p38 MAPK, Akt/mTOR, caspase, nitric oxide, and COX are involved in triggering brain immune cells like astrocytes and microglia to secrete inflammatory cytokines such as tumor necrosis factor, interleukins, and chemokines and participate in Alzheimer's disease pathology. PPAR-γ agonists tend to boost the phagocytosis of amyloid beta and decrease the inflammatory cytokine IL-1β. Recent findings suggest the cross-link between gut microbiota and neuroinflammation contributing in AD which has been explained in this study. The role of cellular, molecular pathways and involvement of inflammatory mediators in neuroinflammation has also been described; targeting them could be a potential therapeutic strategy for treatment of AD.


Effect of bromide and iodide on halogenated by-product formation from different organic precursors during UV/chlorine processes.
The effect of bromide and iodide on the transformation of humic acid (HA) and algal organic matter (AOM), and the formation of disinfection by-products (DBPs) during UV/chlorination were investigated. Experimental results indicated that the halides effectively inhibited mineralization, with multiple changes in organic molecule transformation due to differences in formation and speciation of reactive halogen species and free halogen. As a consequence, bromide and iodide also played important roles in DBP formation. The DBP yields in HA-containing water during UV/chlorination decreased in the order of iodide loaded > freshwater ≫ bromide loaded, whereas DBP formation in AOM-containing water decreased remarkably with halides added (freshwater > bromide loaded ≫ iodide loaded) at high UV fluence. Moreover, Pearson correlation analysis exhibited weaker correlation between DBPs and water parameters in AOM-containing water, while DBPs in HA-containing water exhibited better correlation with water parameters. For both simulated waters, the theoretical toxicity was calculated and peaked in bromide-containing water, whereas the calculated toxicity in iodide-containing water was comparable or slightly higher than that in freshwater. Therefore, UV/chlorine treatment may achieve good quality water with reduced DBP-associated toxicity in freshwater or iodide-containing water (iodide only), but careful consideration is needed when purifying source waters containing bromide (bromide only), especially for AOM/bromide-containing water.


Descending serotonergic modulation from rostral ventromedial medulla to spinal trigeminal nucleus is involved in experimental occlusal interference-induced chronic orofacial hyperalgesia.
Dental treatment associated with unadaptable occlusal alteration can cause chronic primary myofascial orofacial pain. The serotonin (5-HT) pathway from the rostral ventromedial medulla (RVM) exerts descending modulation on nociceptive transmission in the spinal trigeminal nucleus (Sp5) and facilitates chronic pain. The aim of this study was to investigate whether descending 5-HT modulation from the RVM to the Sp5 is involved in the maintenance of primary myofascial orofacial hyperalgesia after persistent experimental occlusal interference (PEOI) or after delayed removal of experimental occlusal interference (REOI). Expressions of 5-HT3A and 5-HT3B receptor subtypes in the Sp5 were assessed by immunofluorescence staining and Western blotting. The release and metabolism of 5-HT in the Sp5 were measured by high-performance liquid chromatography. Changes in the pain behavior of these rats were examined after specific pharmacologic antagonism of the 5-HT3 receptor, chemogenetic manipulation of the RVM 5-HT neurons, or selective down-regulation of 5-HT synthesis in the RVM. Upregulation of the 5-HT3B receptor subtype in the Sp5 was found in REOI and PEOI rats. The concentration of 5-HT in Sp5 increased significantly only in REOI rats. Intrathecal administration of Y-25130 (a selective 5-HT3 receptor antagonist) dose-dependently reversed the hyperalgesia in REOI rats but only transiently reversed the hyperalgesia in PEOI rats. Chemogenetic inhibition of the RVM 5-HT neurons reversed the hyperalgesia in REOI rats; selective down-regulation of 5-HT in advance also prevented the development of hyperalgesia in REOI rats; the above two manipulations did not affect the hyperalgesia in PEOI rats. However, chemogenetic activation of the RVM 5-HT neurons exacerbated the hyperalgesia both in REOI and PEOI rats. These results provide several lines of evidence that the descending pathway from 5-HT neurons in the RVM to 5-HT3 receptors in the Sp5, plays an important role in facilitating the maintained orofacial hyperalgesia after delayed EOI removal, but has a limited role in that after persistent EOI.


Small Animal Transfusion Medicine.
Transfusion medicine can be a lifesaving intervention. Component therapy has expanded the availability and blood products available. Patient safety and minimizing risk is important and can be accomplished through proper donor screening, collection, storage, compatibility testing, administration, and monitoring. The pros and cons of available products must be considered and tailored to each individual patient. Recent discoveries include new antigens and blood types, microbial effects on blood type, and the association between blood type and disease prevalence.


[Hospitalized psychiatric population in the Mexican Institute of the Social Security, 1971-1976].
This paper emphasizes the importance of having an objective registration system for clinical cases in a psychiatric hospital. For this purpose, special sheets were designed to register all cases comparing the years 1971 and 1976. During these years, 1 202 and 1 835 cases were obtained. Data included: age, sex, marital status, schooling, occupation, diagnosis, psychiatric family history and therapy. The results for those years are shown.


The role of mast cell in tissue morphogenesis. Thymus, duodenum, and mammary gland as examples.
Mast cells (MCs) are strategically located at host/environment interfaces like skin, airways, and gastro-intestinal and uro-genital tracts. MCs also populate connective tissues in association with blood and lymphatic vessels and nerves. MCs are absent in avascular tissues, such as mineralized bone, cartilage, and cornea. MCs have various functions and different functional subsets of MCs are encountered in different tissues. However, we do not' know exactly what is the physiological function of MC. Most of these functions are not essential for life, as various MC-deficient strains of mice and rats seems to have normal life spans. In this review article, we have reported and discussed the literature data concerning the role of MCs in tissue morphogenesis, and in particular their role in the development of thymus, duodenum, and mammary gland.


Photosensitized O2 enables intermolecular alkene cyclopropanation by active methylene compounds.
Cyclopropanes are key features in many preclinical, clinical, and commercial drugs, as well as natural products. The most prolific technique for their synthesis is the metal-catalyzed reaction of an alkene with a diazoalkane, a highly energetic reagent requiring stringent safety precautions. Discovery of alternative innocuous reagents remains an ongoing challenge. Herein, we report a simple photoredox-catalyzed intermolecular cyclopropanation of unactivated alkenes with active methylene compounds. The reaction proceeds in neutral solvent under air or dioxygen (O2) with a photoredox catalyst excited by blue light-emitting diode light and an iodine co-catalyst that is either added as molecular iodine or generated in situ from alkyl iodides. Mechanistic investigations indicate that photosensitized O2 plays a vital role in the generation of carbon-centered radicals for both the addition of active methylene compounds to alkenes and the ring closure.


Evaluating the Compliance, Efficacy, and Cost of Formulated Vitamins Versus Separate Supplements in Post-bariatric Surgery Patients.
Micronutrient deficiencies are common complications after bariatric surgery as alterations to the gastrointestinal tract change absorption. Patients are recommended to take supplements including multivitamins, B complex, calcium, vitamin D, and iron after bariatric surgery, and can take these as specifically formulated vitamins for post-bariatric patients or separate vitamin supplements. We investigated the compliance, efficacy, and cost of specifically formulated vitamins for post-bariatric patients in comparison to separate vitamin supplements. We surveyed 126 post-bariatric adult patients between February 1, 2022, and August 31, 2022, who had undergone bariatric surgery between 2014 and 2021 to assess the type of supplements taken, compliance, and cost. Demographics, type of bariatric surgery, and serum micronutrient levels were evaluated for all patients. There were 51 patients taking formulated vitamins and 75 patients taking separate vitamins. The formulated vitamin group demonstrated greater adherence to optimal vitamin dosage (formulated vitamin group, 76.5% vs. separate supplement group, 30.7%; p < 0.001) and higher compliance (formulated vitamin group, 90.2% vs. separate supplement group, 66.7%; p = 0.002). The costs associated with both groups were comparable. No significant difference was observed in the incidence of micronutrient deficiency between the groups. Our study shows that formulated vitamins do not offer significant difference in micronutrient levels or cost compared to separate standard vitamin supplements. However, formulated bariatric vitamins have improved compliance compared to separate vitamin supplements.


Germ-line transcription occurs on both the functional and the non-functional alleles of immunoglobulin constant heavy chain genes.
In B cells undergoing class switching, recombination is usually directed to the same switch sequences on both homologous chromosomes and is generally preceded by germ-line transcription initiated from I promoters upstream of immunoglobulin constant heavy chain genes. Whether germ-line transcription occurs on both alleles or is restricted to the productive one has not been directly addressed before. To clearly distinguish between these two possibilities, a system is needed in which one might detect allele-specific germ-line transcripts. We used homologous recombination to set up two in vivo systems in which one gamma3 allele was marked by a loxP sequence whereas the other allele was silenced by inhibiting mu heavy chain production. Here, we provide evidence that germ-line transcription occurs on both the functional and the non-functional alleles.


Risk modeling for ventricular assist device support in post-cardiotomy shock.
Post-cardiotomy shock (PCS) has a complex etiology. Although treatment with inotrops and intra-aortic balloon pump (IABP) support improves cardiac performance, end-organ injuries are common and lead to prolonged ICU stay, extended hospitalization and increased mortality. Early consideration of mechanical circulatory support may prevent such complications and improve outcome. Between January 1997 and January 2002, 321 patients required IABP and inotropic support for PCS following coronary artery bypass grafting (CABG) at our institution. Perioperative variables including age, mixed venous saturation (MVO2), inotropic requirements and LV function were analyzed using multivariate statistical methods. All explanatory variables with a univariate p value <0.10 were entered into a stepwise logistic regression model to predict hospital mortality. Odds ratios from significant variables (p < 0.05) in the regression model were used to compose a risk score. Overall hospital mortality was 16%. The independent risk factors for mortality in this population were: MVO2 < 60% (OR = 3.2), milrinone > 0.5 μg/kg/min (OR = 3.2), age > 75 (OR = 2.7), adrenaline > 0.1 μg/kg/min (OR = 1.5). A 15-point risk score was developed based on the regression model. Hospital mortality in patients with a score >6 was 46% (n = 13/28), 3-6 was 31% (n = 9/29) and <3 was 11% (n = 29/264). A significant proportion of patients with PCS continue to face high mortality despite IABP and inotropic support. Advanced age, heavy inotropic dependency and poor oxygen delivery all predicted increased risk for death. Further investigation is needed to assess whether early institution of VAD support could improve outcome in this high-risk group of patients.


Analysis of serum HE4 levels in various histologic subtypes of epithelial ovarian cancer and other malignant tumors.
The measurement of serum HE4 levels has emerged as a sensitive and specific biomarker for epithelial ovarian cancers (EOCs). However, serum levels in women diagnosed with various histologic subtypes of EOC and in women with metastatic non-ovarian primary malignancies have not been widely reported. The goal of this study was to identify how serum HE4 levels vary in women diagnosed with different histologic subtypes of EOC and non-ovarian malignancies. Data from six prospective pelvic mass clinical trials was combined and an evaluation of serum HE4 levels in women diagnosed with a malignancy was performed. For all patients, serum was obtained prior to surgery and final pathology, including primary tumor site, histologic subtype, grade and stage, were recorded. The mean, median, standard deviation, maximum, and minimum HE4 levels were determined for each group. A total of 984 patients were included in this study, with the average patient age being 60 years old. There were 230 premenopausal and 754 postmenopausal patients. Serum HE4 levels were elevated (≥70.0 pMol) in 85%of EOCs, 40%of LMP tumors, 21%of non-EOCs (germ cell tumors), 25%of cervical cancers, and 47%of non-gynecologic metastatic cancers. Analysis of histologic subtypes revealed 90%(n = 391) of serous, 85%(n = 73) of endometrioid, 45%(n = 42) of mucinous, 86%(n = 51) of mixed tumors, and 69%(n = 36) of clear cell tumors had elevated serum HE4 levels. Serum HE4 levels are most often elevated in women with high grade serous and endometrioid EOCs, and though serum elevations are seen more often with advanced stage disease, HE4 is also often elevated in early stage disease and lower grade tumors.


Criterion validity of responses to patient vignettes: an analysis based on management of female urinary incontinence.
Patient vignettes are often used for investigating the performance of physicians. The purpose of this study was to assess the criterion validity of vignettes. A random sample of incontinent women were interviewed, and vignettes depicting their cases were later presented to their own physicians. Questionnaires sent to the physicians included open questions about what drug treatment the doctor would give and a checklist (cueing items) for indicating other possible actions. Analysis compared actions taken with vignette patients and actual actions taken with the real patients. Thirty-two general practitioners and 32 patients were included in the study. When cueing items were provided, the physicians claimed more actions with vignettes than were actually performed. Mean difference was 1.9 actions per case (95% confidence interval 1.3 to 2.4). No such difference was found for the open question. When cues were provided, the likelihood ratio for reporting a vignette action in comparison with actually performing the action with a similar real patient was 2.8 (2.2 to 3.5), and Kappa .39. When no cues were provided, the likelihood ratio was 5.1 (2.6 to 10), and Kappa .45. Total number of actions with vignettes and real patients correlated significantly (r = .65, P < .001). Responses to vignettes with cueing items overestimate real performance. The agreement may be better when no cues are offered. The method may have acceptable validity for group comparisons.


Tissue-based stem cells: ABC transporter proteins take centre stage.
In adult tissues, with the notable exception of the haematopoietic system, the identity of somatic stem cells has often been inferred based on no more evidence than their location. Functional data (clonogenicity) to confirm such an appellation has been absent due to the inability to find appropriate cellular markers with which to isolate live stem cells. Flow cytometry has isolated haematopoietic stem cells based on their ability to exclude Hoechst dye. Named the side population (SP), this phenotype may be a universal marker of stem cells in adult tissues.


Partial monosomy 5p and partial trisomy 5q due to paternal pericentric inversion of chromosome 5.
A male infant with partial monosomy 5p and partial trisomy 5q due to paternal pericentric inversion of chromosome 5 (46,XY,rec(5), dup q,inv(5)(p15.1q35.1)pat) is reported together with the oral findings. The phenotype was chiefly the cri-du-chat syndrome. Severe retardation of mental and motor development, microencephaly, cardiac malformation, crying and facial appearance unique to the cri-du-chat syndrome were observed. Perioral and intraoral findings included thin upper lip, down-turning corners of mouth, micrognathia, shallow palate, and cleft of soft palate. Anterior deciduous teeth were small and canine deciduous teeth were conic. The row of deciduous teeth showed a flat arch-like shape that was very wide but short in length. No abnormality was noted in the number of deciduous teeth or the timing of eruption.


Efficacy and safety of MYL-1501D versus insulin glargine in people with type 1 diabetes mellitus: Results of the INSTRIDE 3 phase 3 switch study.
To assess the efficacy, insulin dose, safety and immunogenicity when people with type 1 diabetes mellitus switched between MYL-1501D and reference insulin glargine (Lantus®; Sanofi-Aventis US LLC, Bridgewater, New Jersey). Eligible participants from INSTRIDE 1 who completed 52 weeks of reference insulin glargine treatment were randomized 1:1 to the reference sequence (n = 63; reference insulin glargine for 36 weeks) or to the treatment-switching sequence (n = 64; MYL-1501D [weeks 0-12], reference insulin glargine [weeks 12-24] and MYL-1501D [weeks 24-36]). Change in glycated haemoglobin (HbA1c) from baseline to week 36 was the primary efficacy endpoint used to demonstrate equivalence between the two treatment sequences. Secondary endpoints included: change in fasting plasma glucose (FPG), self-monitored blood glucose (SMBG) and insulin dose; immunogenicity; and adverse events, including hypoglycaemia. Mean changes in HbA1c (least squares [LS] mean [SE]) from baseline to week 36 were -0.05 (0.032) and -0.06 (0.034) for the treatment-switching and reference sequences, respectively (LS mean difference 0.01 [95% CI -0.085 to 0.101]). Treatment sequences were comparable in terms of secondary endpoints, including FPG, SMBG and insulin dose, and the safety and immunogenicity profiles of the two sequences were similar. Switching participants between MYL-1501D and reference insulin glargine demonstrated equivalent efficacy and similar safety and immunogenicity, showing that people taking reference insulin glargine can safely switch to MYL-1501D.


Oxidative Stress and Pro-Inflammatory Status in Patients with Non-Alcoholic Fatty Liver Disease.
Nonalcoholic fatty liver disease (NAFLD) is characterized by excessive fat accumulation, especially triglycerides, in hepatocytes. If the pathology is not properly treated, it can progress to nonalcoholic steatohepatitis (NASH) and continue to fibrosis, cirrhosis or hepatocarcinoma. The aim of the current research was to identify the plasma biomarkers of liver damage, oxidative stress and inflammation that facilitate the early diagnosis of the disease and control its progression. Antioxidant and inflammatory biomarkers were measured in the plasma of patients diagnosed with NAFLD (n = 100 adults; 40-60 years old) living in the Balearic Islands, Spain. Patients were classified according to the intrahepatic fat content (IFC) measured by magnetic resonance imaging (MRI). Circulating glucose, glycosylated haemoglobin, triglycerides, low-density lipoprotein-cholesterol, aspartate aminotransferase and alanine aminotransferase were higher in patients with an IFC ≥ 2 of NAFLD in comparison to patients with an IFC of 0 and 1. The plasma levels of catalase, irisin, interleukin-6, malondialdehyde, and cytokeratin 18 were higher in stage ≥2 subjects, whereas the resolvin D1 levels were lower. No differences were observed in xanthine oxidase, myeloperoxidase, protein carbonyl and fibroblast growth factor 21 depending on liver status. The current available data show that the severity of NAFLD is associated with an increase in oxidative stress and proinflammatory status. It may be also useful as diagnostic purpose in clinical practice.


Clinical relevance of comorbidity in anxiety disorders: a report from the Netherlands Study of Depression and Anxiety (NESDA).
To study the clinical relevance of type of comorbidity and number of comorbid disorders in anxiety disorders. Four groups were compared according to sociodemographic-, vulnerability- and clinical factors: single anxiety disorder, anxiety-anxiety comorbidity, anxiety-depressive comorbidity and "double" comorbidity (i.e. anxiety and depressive comorbidity). Data were obtained from the Netherlands Study of Anxiety and Depression (NESDA). A sample of 1004 participants with a current anxiety disorder was evaluated. As compared with single anxiety, anxiety-anxiety comorbidity was associated with higher severity, greater chronicity and more treatment. Anxiety-anxiety comorbidity was associated with an earlier age of onset and a more chronic course compared with anxiety-depressive comorbidity, while anxiety-depressive comorbidity was associated with more severe symptoms and more impaired functioning than anxiety-anxiety comorbidity. "Double" comorbidity was associated with higher severity, greater chronicity, more treatment and increased disability. Sociodemographic and vulnerability factors were comparable among the four groups. Limitations A prospective design would be more appropriate to study the outcome. In this study no distinction was made between whether depression or anxiety disorder preceded the current anxiety disorder. It is clinical relevant to diagnose and treat comorbidity among anxiety disorders as it is associated with higher severity and more chronicity. Whereas anxiety-anxiety comorbidity has an earlier age of onset and a more chronic course, anxiety-depressive comorbidity leads to more treatment and impaired functioning. "Double" comorbidity leads to even more severity, chronicity and impairment functioning compared with both anxiety-anxiety and anxiety-depressive comorbidity.


The G-308A promoter variant of the tumor necrosis factor-alpha gene is associated with hypertension in adolescents harboring the metabolic syndrome.
Tumor necrosis factor-alpha (TNF-alpha) has been associated with obesity, obesity-related hypertension, and metabolic syndrome. We investigated the possible contribution of the G-308A TNF-alpha mutant to explain variables of the metabolic syndrome. Data and blood samples were used from the 175 adolescents that satisfied the criterion of having systolic or diastolic blood pressures (BP) more than the 80th or less than the 20th percentiles, out of a cross-sectional, population-based study of 934 high school students. Genotyping for the polymorphism was performed by polymerase chain reaction-based restriction fragment length polymorphism analysis. In univariate analysis, we found that there was no difference between A allele carriers and noncarriers in most of the clinical characteristics of the metabolic syndrome such as body mass index (BMI), waist-to-hip ratio, plasma leptin levels, total cholesterol, HDL- and LDL-cholesterol, triglycerides, plasma fasting glucose, insulin, and homocysteine levels. However, we found a significantly (P = .015) higher age- and sex-adjusted systolic BP (Z score) in the A allele carriers, and A allele carriers also showed an elevated homeostasis model assessment of insulin resistance (HOMA) index with respect to noncarriers. Logistic regression analysis indicates that A allele carriers had a 2.8-fold higher probability of being hypertensive independent of BMI, waist-to-hip ratio, and HOMA index. In this report we found a positive association between the G-308A TNF-alpha variant and systolic arterial BP Z score and HOMA index in adolescents harboring features of metabolic syndrome. Therefore, the A allele may predispose to hypertension and insulin resistance in youth.


Comparison of acral nevomelanocytic proliferations in Japanese and whites.
The preponderance of malignant melanomas that occur in the Japanese population affect the palmar and plantar areas, in contrast to those of whites, which occur predominantly on the head, neck, and trunk. Furthermore, a precursor lesion, the dysplastic nevus, has been well defined in nonacral white skin but not in the Japanese. In this paper, a similarity between benign and atypical acral nevomelanocytic proliferations in Japanese and whites is described. However, it appears that in the Japanese group the melanocytes in benign and atypical proliferations are less dendritic than those noted in whites, and, in both groups, extensive pigmentation was noted in both the epidermal and dermal components of benign and malignant lesions in this limited review. A practical approach to classifications of atypism is, likewise, offered.


Immunochemical and proteomic technologies as tools for unravelling toxins involved in envenoming by accidental contact with Lonomia obliqua caterpillars.
The accidental contact with Lonomia obliqua caterpillar causes local and systemic symptoms (such as fibrinogen depletion), leading, in some cases, to serious clinical complications (acute renal failure and intracranial haemorrhage). Fortunately, a successful therapeutical approach using anti-Lonomic serum, produced in horses against L. obliqua's bristle extract, has already been put in place. However, a global view of immunogenic toxins involved in the coagulation disorders could help to elucidate the envenoming process. In the present study, our aim was to identify bristle extract's immunogenic components, especially those related to the haemostasis, coupling proteomics and immunochemical approaches (bidimensional electrophoresis, mass spectrometry and immunoblotting). The bidimensional map of bristle extract showed a broad profile of 157 silver-stained spots, where at least 153 spots were immunochemically revealed. Twenty-four of these spots were submitted to sequencing by mass spectrometry and three different categories of proteins were identified: lipocalins, cuticle proteins and serpins. From these protein families, it was observed that the most abundant was the lipocalin family, specifically represented by different isoforms of Lopap (a prothrombin activator protein), reinforcing its relevance during envenoming. Peptide sequences of several other immunochemically revealed spots showed no correspondence to any known sequence and were classified as unknown proteins. These proteins could represent new immunogenic molecules and/or toxins. The sequences presented in this article can be used for oligonucleotide design aiming the amplification of cDNAs coding for new molecules using L. obliqua bristles' cDNA libraries or isolated RNAs as template.


Diagnosis of Coma.
The differential diagnosis for the comatose patient is includes structural abnormality, seizure, encephalitis, metabolic derangements, and toxicologic etiologies. Identifying and treating the underlying pathology in a timely manner is critical for the patient's outcome. We provide a structured approach to taking a history and performing a physical examination for this patient population. We discuss diagnostic testing and treatment methodologies for each of the common causes of coma. Our current understanding of the mechanisms of coma is insufficient to accurately predict the patient's clinical trajectory and more work needs to be done to investigate potential treatments for this often fatal disorder.


Clinico-pathological correlation of non specific inflammation in bowel histology with joint manifestation in a tertiary center in South India.
The aim of our study was to determine whether the pattern of arthropathy in patients with suspected enteropathic arthritis bore any relation to their gut histology and specifically to chronic nonspecific gut inflammation. Records of 39 patients with suspected enteropathic arthritis from rheumatology clinic between January 2006 and December 2008 who had undergone ileocolonoscopic biopsy were analyzed retrospectively. Patients were grouped into 3 categories, namely those with normal bowel histology, those with mild nonspecific chronic changes, and those with histology suggestive of inflammatory bowel disease. Patients with nonspecific chronic gut inflammation had higher occurrence of axial involvement with or without peripheral articular involvement as compared to those with normal gut histology (8/9 vs. 10/21, P = 0.049), and this pattern was similar to that in patients with IBD. Wrist joint involvement was more common in patients with normal bowel histology (12/21) than the other two groups (P = 0.003). All groups had fared well on follow up while taking treatment with sulphasalazine and methotrexate.


Proliferative epidermis of essential fatty acid deficient mice has reduced cyclic AMP content.
We have simultaneously measured epidermal DNA synthesis, epidermal thickness and cyclic nucleotide levels in essential fatty acid (EFA) deficient hairless mice skin. In vitro epidermal DNA synthesis and epidermal thickness were significantly increased in EFA deficient epidermis. Cyclic AMP levels were significantly reduced when expressed using three different data bases. Cyclic GMP levels were increased using two data bases but these increases were not statistically significant; Cyclic AMP/cyclic GMP ratios were significantly decreased in the EFA deficient skin. The results provide evidence that cyclic nucleotide levels are altered in an animal model of benign epidermal proliferation.


A case of septic arthritis in multiple joints due to Bacteroides fragilis in a patient with rheumatoid arthritis.
A case of arthritis in multiple joints due to B. fragilis ssp. fragilis is described. The patient was a 55-year-old man badly disabled by rheumatoid arthritis. The patient's immune response to the isolated strain was studied and a significant titre reduction during the course of the disease was observed. The serum antibodies of the patient cross-reacted with heterologous strains of B. fragilis ssp. fragilis. It is suggested that indirect immunofluorescence tests against a certain number of B. fragilis strains could be performed with serum from a patient in whom an infection with B. fragilis is suspected.


Identification of two new HLA-A*0201-restricted cytotoxic T lymphocyte epitopes from colorectal carcinoma-associated antigen PLAC1/CP1.
To explore the potential application of placenta-specific PLAC1/Cancer Placenta (CP) 1 antigen for immunotherapy in CRC patients, further identification of the cytotoxic T lymphocyte epitopes from this antigen is necessary. We assessed the protein expression of PLAC1/CP1 using a tissue chip and immunochemistry staining in CRC samples. Simultaneously, we predicted four PLAC1/CP1-derived HLA-A*0201-restricted peptides by using reverse immunology methods. Peptide-specific CD8(+) T cell responses were assessed by an IFN-γ release ELISPOT assay. Effector CD8(+) T cells lyse HLA-A*0201 CRC cell line SW620 was detected in a granzyme-B release ELISPOT cytotoxicity assay. Our results indicated that PLAC1/CP1 was highly expressed in 56.7 % (55/97) of adenocarcinomas. PLAC1/CP1 protein expression was associated with CRC tumor differentiation, the tumor/node/metastasis stage, and lymph node metastasis. Two of four peptides showed high affinities in an HLA-A2 binding assay. In 66.7 % (6/9) of peripheral blood mononuclear cells of CRC samples with PLAC1/CP1 protein-positive expression, these two peptides, PLAC1/CP1 p41-50 (FMLNNDVCV) and PLAC1/CP1 p69-77 (HAYQFTYRV), were immunogenic in the induction of peptide-specific CD8(+) T cell responses as assessed by an IFN-γ release ELISPOT assay. Furthermore, the generated effector CD8(+) T cells could specifically lyse the PLAC1/CP1 HLA-A*0201 CRC cell line SW620 in a granzyme-B release ELISPOT cytotoxicity assay. These results show that the PLAC1/CP1 antigen is a possible prognostic marker of CRC and that PLAC1/CP1 p41-50 and PLAC1/CP1 p69-77 are novel HLA-A*0201-restricted CD8(+) T cell epitopes and potential targets for peptide-based immunotherapy in CRC patients.


[The influence of an overdose of vitamin A on the rat fetal membranes in the last third of the pregnancy (author's transl)].
The ultrastructure of the rat fetal membranes (yolk-sac) was examined following an intrauterine overdose of vitamin A (Retinol palmitate). Three and six hours after the injection drastic lesions of the yolk-sac surface cells were to be seen, obviously mainly due to the numerous leaky lysosomes present in the yolk-sac epithelium.


Application of Nipple Aspirate Fluid miRNA Profiles for Early Breast Cancer Detection and Management.
The authors of the recently published review, "Why the Gold Standard Approach by Mammography Demands Extension by Multiomics [...].


Temporal alterations in vascular angiotensin receptors and vasomotor responses in offspring of protein-restricted rat dams.
Examine temporal alterations in vascular angiotensin II receptors (AT(1)R and AT(2)R) and determine vascular response to angiotensin II in growth-restricted offspring. Offspring of pregnant rats fed low-protein (6%) and control (20%) diet were compared. Prenatal protein restriction reprogrammed AT(1a)R messenger RNA expression in male rats' mesenteric arteries to cause 1.7- and 2.3-fold increases at 3 and 6 months of age associated with arterial pressure increases of 10 and 33 mm Hg, respectively; however, in female rats, increased AT(1a)R expression (2-fold) and arterial pressure (15 mm Hg) occurred only at 6 months. Prenatal protein restriction did not affect AT(2)R expression. Losartan abolished hypertension, suggesting that AT(1a)R plays a primary role in arterial pressure elevation. Vasoconstriction to angiotensin II was exaggerated in all protein-restricted offspring, with greater potency and efficacy in male rats. Prenatal protein restriction increased vascular AT(1)R expression and vasoconstriction to angiotensin II, possibly contributing to programmed hypertension.


Encouraging visual outcomes in children with idiopathic and JIA associated uveitis: a population-based study.
Pediatric uveitis is typically asymptomatic and may become chronic affecting ocular structures and vision. We evaluated visual outcomes, clinical features, medication, and uveitis activity in children with either idiopathic uveitis (idio-U) or juvenile idiopathic arthritis associated uveitis (JIA-U). A longitudinal, population-based cohort study of children with uveitis in 2008-2017. The data included parameters for age, gender, age at diagnosis, laterality, chronicity, anatomical distribution, etiology, systemic association, uveitis activity, medication, and visual outcomes. A total of 119 patients aged < 16 years with uveitis were included. Uveitis was idio-U in 23% and associated with JIA in 77% of cases. 37% of the patients in the idio-U group and 65% in the JIA-U were girls (p = 0.014). The mean age at first uveitis was 10.0 (SD 3.4) years in idio-U and 5.5 (SD 3.3) years in JIA-U (p < 0.001). Anterior location of uveitis was noted in 74% in idio-U and 99% in JIA-U (p < 0.001). Mostly, uveitis was chronic (59% in idio-U and 75% in JIA-U) and bilateral (56% in idio-U and 64% in JIA-U). Topical corticosteroids were initially used by 89% and 100%, systemic corticosteroids by 30% and 27% in some extent during the follow-up, disease-modifying antirheumatic drugs (DMARDs) by 33% and 85% (p < 0.001) of the patients in idio-U and JIA-U, respectively. Biologic disease-modifying antirheumatic drugs (bDMARDs) were more common in JIA-U (55% vs. 15% in idio-U, respectively, p < 0.001). Most patients had normal visual acuity (Snellen > 0.8, [6/7.5]) in the affected eye and bilaterally in 85% idio-U and 70% JIA-U. Only 5 patients (4%) had visual impairment in one, but none in both eyes. Uveitis activity by SUN classification was 0 + in 81% and 72%, 0.5 + in 19% and 25%, and 1 + in 0% and 3% in the idio-U and JIA-U, respectively. Children with uveitis have good visual acuity and a low rate for visual impairment. In addition, modern treatment with DMARDs and bDMARDs seems to save vision.


Ultrastructural organization of normal and transplanted rat fascia dentata: I. A qualitative analysis of intracerebral and intraocular grafts.
Few studies have dealt with the general ultrastructure and synaptic organization of grafted brain tissue. This study was therefore performed to extend current light microscopic observations on intracerebral and intraocular grafts of hippocampal tissue to the ultrastructural level. Blocks of tissue containing the hippocampus and fascia dentata from day 21 embryonic rats were grafted into the brain of developing and adult rats and to the anterior eye chamber of adult rats. After 100 or 200 days of survival the recipient rat brains or eyes were processed for electron microscopy. Tissue containing the graft dentate molecular layer and adjacent granule cell layer was selected for ultrastructural analysis, together with a few samples of the hilus and CA3. Normal dentate tissue was analyzed as control. At the light microscopic level most intracerebral and intraocular grafts displayed an organotypic organization with clearly recognizable cell and neuropil layers. Under the electron microscope the grafted granule cells had normal-appearing dendrites bearing the normal types of spines and forming the normal types of synapses. This was the case even in the absence of the normal major extrinsic afferents like the perforant path. The graft dentate granule cells formed axons and terminals with characteristics of the normal mossy fiber system in the hilus and CA3, in addition to aberrant supragranular mossy fiber terminals known from light microscopic studies of dentate transplants. Abnormal structures included a few dendritic growth cones and an increased occurrence of polyribosomes in spines. Their occurrence indicates ongoing dendritic plasticity even 100 days after transplantation. There was also an increased density of glial elements, particularly in the intraocular grafts. In some of these grafts the granule cells displayed immature traits in terms of nuclear indentations. Dentate interneurons of the basket cell type were present in both the intracerebral and the intraocular grafts. We conclude that grafted dentate granule cells, in different surroundings and without the normal, major perforant path input, can develop a basically normal cellular morphology, which includes the normal ultrastructural characteristics of the dendrites with spines and synapses, and the mossy fibers and its terminals.


Screening for resistance to Aspergillus flavus and aflatoxin production in groundnut.
All the varieties, advanced breeding lines, germplasm lines, and wild species used in the experiments differed significantly for their ability to allow invasion and aflatoxin production by an aflatoxigenicAspergillus flavus strain. Infection and colonisation were strongly correlated (r = 0.82), while there was no relation between infection and aflatoxin content or colonisation and aflatoxin content (r = 0.15). The varieties ICGS11 and S 206 supported less infection and colonisation (range 35 to 40%). Lowest aflatoxin content was recorded in Chitra (3,200 ppb), while it was highest in Kaushal (38,250 ppb). A cross derivative of GAUG1 × NC Ac 17133 R F showed lowest infection and colonisation (86,3 and 25,28%, respectively), and also supported moderate aflatoxin production (4,000 ppb). Among germplasm lines spancross supported lowest aflatoxin production (2,026 ppb) while both the wild species vz. ICG 8127 and ICG 8128 were highly susceptible to infection, colonisation, and aflatoxin production.


A vector for recombinant DNA in Staphylococcus aureus.
Staphylococcal plasmids pS194 and pSC194 which confer streptomycin and streptomycin-chloramphenicol resistance respectively have been used as vectors for construction of recombinant DNA, since they each carry one single recipient site for endonuclease EcoRI. Hybrid DNA does not express streptomycin resistance, a marker which is present in both vectors, presumably because the marker gene is cleaved by EcoRI. A chloramphenicol marker present in pSC194 was used for positive hybrid selection. Hybrid plasmids generated by joining pSC194 with one or more of the four EcoRI fragments of the large (18.1-10(6) daltons) staphylococcal plasmid pI258 were constructed and permitted us to develop a physical map for pI258.


Amplification of DNA encoding entire type I polyketide synthase domains and linkers from streptomyces species.
Polyketides are a group of bioactive compounds from bacteria, plants, and fungi. To increase the availability of analogs for testing, the active sites of polyketide synthases are often substituted with homologous domains having altered substrate specificities. This study reports the design of polymerase chain reaction primers that enables isolation of entire active site domains from type I polyketide synthases with native interdomain linkers. This bypasses the need for further genetic screening to obtain functional units for use in genetic engineering. This is especially important in bioprospecting projects exploring new environments for bioresources.


Pulmonary Toxicities of Gefitinib in Patients With Advanced Non-Small-Cell Lung Cancer: A Meta-Analysis of Randomized Controlled Trials.
Gefitinib is a selective tyrosine kinase inhibitor of the epidermal growth factor receptor (EGFR) used to treat adults with EGFR mutation-positive non-small-cell lung cancer (NSCLC). Clinical benefits of gefitinib administration in NSCLC patients have been observed in clinical practice, but the extent of the pulmonary toxicity of gefitinib in patients with advanced NSCLC remains unclear. The aim of this systematic review was to evaluate the overall incidence and risk of gefitinib-related pulmonary toxicity in advanced NSCLC patients. Relevant trials were identified from the databases of Pubmed, Embase, Cochrane Library, and the clinicaltrials.gov of the U.S. National Institutes of Health. The outcomes included the overall incidence, odds ratios (ORs), and 95% confidence intervals (CIs). Fixed-effects models were used in the statistical analyses according to the heterogeneity of the included studies. According to the data from the included trials, the overall incidence of high-grade hemoptysis, pneumonia, pneumonitis, and interstitial lung disease (ILD) was 0.49% (95% CI: 0.24%-0.99%), 2.33% (95% CI: 1.47%-3.66%), 2.24% (95% CI: 1.34%-3.72%), and 1.43% (95% CI: 0.98%-2.09%), respectively. The pooled ORs of high-grade hemoptysis, pneumonia, pneumonitis, and ILD were 1.73 (95% CI: 0.46-6.52; P = 0.42), 0.99 (95% CI: 0.66-1.49; P = 0.95), 4.70 (95% CI: 1.48-14.95; P = 0.0087), and 2.64 (95% CI: 1.22-5.69; P = 0.01), respectively. Gefitinib was associated with a significantly increased risk of high-grade/fatal ILD and pneumonitis compared with the controls, whereas the risk of other high-grade pulmonary events (pneumonia and hemoptysis) was not significant. Careful surveillance of gefitinib-related pulmonary toxicity is critical for the safe use of this drug.


Analysis of the prognostic value of emergency blood tests in ischaemic stroke.
This study aims to evaluate the prognostic value of emergency blood test results in patients with acute ischaemic stroke. We evaluated 592 prospectively patients with neuroimaging-confirmed ischaemic stroke admitted to our stroke unit between 2015 and 2018. We gathered emergency blood test results and calculated the neutrophil-to-lymphocyte ratio and the neutrophil-to-platelet ratio (neutrophils × 1.000/platelets). The association between blood test results and functional prognosis (as measured with the modified Rankin Scale) and such complications as haemorrhagic transformation was evaluated by logistic regression analysis. The additional predictive value of blood test parameters was assessed with receiver operating characteristic curves and the net reclassification index. An neutrophil-to-lymphocyte ratio ≥ 3 at admission was associated with a two-fold increase in the risk of functional dependence at 3 months (OR: 2.24; 95% CI: 1.35-3.71) and haemorrhagic transformation (OR: 2.11; 95% CI: 1.09-4.05), while an neutrophil-to-lymphocyte ratio ≥ 3.86 resulted in an increase of 2.4 times in the risk of mortality at 3 months (OR: 2.41; 95% CI: 1.37-4.26) after adjusting for the traditional predictors of poor outcomes. Patients with neutrophil-to-platelet ratio ≥ 32 presented 3 times more risk of haemorrhagic transformation (OR: 3.17; 95% CI: 1.70-5.92) and mortality at 3 months (OR: 3.07; 95% CI: 1.69-5.57). Adding these laboratory parameters to standard clinical-radiological models significantly improved discrimination and prognostic accuracy. Basic blood test parameters provide important prognostic information for stroke patients and should therefore be analysed in combination with standard clinical and radiological parameters to optimise ischaemic stroke management.


Risk assessment of accidental falls in patients taking trazodone, quetiapine, or risperidone for insomnia: A single-center, case-control study.
No consensus has been reached on the association between the risk of falls and antipsychotic and antidepressant drug use. In this study, we evaluated the risk of falls with trazodone, risperidone, and quetiapine, which are recommended for use at Kanazawa Medical University Hospital. We reviewed all patients who were admitted to Kanazawa Medical University Hospital between January 1st and December 31st, 2018. We excluded those aged <20 years and those admitted to pediatric, intensive care, and psychiatric wards. Finally, 9273 patients were included. We reviewed the incidence in these patients of accidental falls reported to the medical safety department. We noted whether these patients received trazodone, quetiapine, or risperidone. We also observed whether they were taking a benzodiazepine receptor agonist, which is a known risk factor. We further examined each patient's age, sex, the department they were visiting, and their diseases. Patients were considered to have taken medication if it was administered within 24 hours before an accidental fall. Multiple logistic regression analysis was used to evaluate the risk of accidental fall. Multivariate analysis showed that the adjusted odds ratios (OR) for each medication (with 95% confidence intervals) were: trazodone (OR, 0.47 [0.27-0.80]), quetiapine (OR, 1.06 [0.46-2.46]), and risperidone (OR, 0.82 [0.41-1.63]). The association of risperidone and quetiapine with accidental falls was unclear. Interestingly, however, trazodone may help reduce the risk, which makes it a potential pharmacologic treatment option for insomnia in patients at high risk for accidental falls.


Stable Full-Inkjet-Printed Solid-State Ag/AgCl Reference Electrode.
With a growing demand for the availability of inexpensive, simple, and rapid prototyped devices, the prospect of miniaturization of the reference electrodes using printing techniques becomes promising. A stable and reusable full-inkjet-printed solid-state reference electrode (IPRE) was developed. The reference electrode was fully produced by consecutive inkjet printing of several layers. Ag ink was printed and chlorinated by NaClO printing, forming a Ag/AgCl pseudoreference electrode. Then a surface protection by printing a Cl--saturated polyvinyl butyral membrane finally gave a reference electrode that demonstrated an outstanding performance comparable to commercial ones. This full inkjet printing fabrication strategy will improve the viability of producing low-cost miniaturized reference electrodes with interest in many electrochemical sensor-dependent areas.


Concentration and characteristics of dissolved carbon in the Sanjiang Plain influenced by long-term land reclamation from marsh.
Since the 1960s, the marshes in the Sanjiang Plain, Northeast China, which are an important reservoir for dissolved carbon, have undergone long-term reclamation to farmland, resulting in elevated marsh loss and degradation on a large scale. This study compared the concentrations of dissolved carbon, as well as the chemical characteristics of dissolved organic carbon (DOC), in natural marshes, a degraded marsh, and drainage ditches sampled during the growing seasons between 2008 and 2010 to clarify the temporal-spatial variability of the dissolved carbon in the fluvial system influenced by the long-term reclamation. The results show that the average concentrations of total dissolved carbon (TDC) and DOC are considerably greater in the natural marshes than in the degraded marsh and drainage ditches. The average DOC concentration for the natural marshes, approximately 35.53 ± 5.15 mg L(-1), is approximately 2.39 times that in the degraded marsh (14.84 ± 4.21 mg L(-1)) and 2.77 times the average value in the ditches (12.84 ± 4.49 mg L(-1)). The dissolved inorganic carbon (DIC) exhibits increased trends in the drainage ditches compared with the natural marshes, whereas the hydrophobic fraction of DOC is present at lower concentrations in the degraded marsh and ditches. Fluorescence indices also indicate that the DOC in the degraded marsh and ditches has a simpler humification structure. In total, the long-term reclamation has led to great variability in the DOC concentration and chemical characteristics in the fluvial system. Changes in the DOC production potential and hydrological regimes due to sustained reclamation are deemed the predominant causes of this effect. The continuously decreased DOC concentration and high variability of DOC in the surface fluvial systems are inevitable if reclamation continues in the Sanjiang Plain. More importantly, the presence of tyrosine and tryptophan-like substances in the ditches indicates that there has been extensive agricultural organic pollution in the fluvial systems. This pollution could lead to more unexpected impacts on the downriver aquatic system. To avoid a destructive ecological crisis in the future, adjustment of the reclamation policy and agricultural management measures in the Sanjiang Plain is urgently needed.


Adolescent and pediatric sports injuries.
With the ever increasing number of boys and girls participating in organized sports, specific injury patterns, often dependent upon sport and gender, have been identified. This article identifies the most common sports injuries, focusing on mechanisms of injury, pathoanatomy, the history and physical findings, as well as recommendations, for the primary care physician, for initial diagnostic studies and treatment.


Crossed, non-fused renal ectopia and ipsilateral ureteral carcinoma. A case report.
A man with crossed, non-fused renal ectopia had carcinoma of the distal ureter, leading to hydro-ureter, hydronephrosis and urinary infection. Crossed ectopic kidneys are more disease-prone than are normal kidneys. Complicating disorders are discussed, the value of thorough urologic investigation is stressed and the incidence of tumour of the upper urinary tract in crossed renal ectopia without fusion is reviewed.


Characterization of the sand fly fauna in Barbalha, one of the municipalities with the highest leishmaniasis rates in Brazil.
Leishmaniases are a complex of sand fly-borne diseases that are considered a public health issue in several countries. Brazil presents high leishmaniases rates. The South of Ceará State, known as Cariri region, shows worrying statistics mainly on American tegumentary leishmaniasis. In Barbalha, which is one of the municipalities in this region, there is still a lack of studies regarding the local phlebotomine (Diptera: Psychodidae) fauna in order to help clarify the high rates. This study aimed to characterize such fauna by capturing sand flies with light traps during a four-year period. A total of 3730 sand flies were captured, of which 37.8% were females. Fourteen species were found: 13 of the Lutzomyia genus and one of the Brumptomyia genus. Of the Lutzomyia species, four were proven and five had potential involvement in leishmaniasis transmission. Lutzomyia longipalpis was the most common species (66.97%). This predominance, especially in the urban area, indicates its epidemiological importance and adaptation to environmental conditions modified by human activity. In fact, further studies are still required to accurately determine the behavioral features of these vectors in order to guide public health measurements towards its control and prevention.


Decreased Expression of Peroxiredoxin in Patients with Ovarian Endometriosis Cysts.
Endometriosis (EMT) is a common occurrence in women of reproductive age. Since oxidative stress has been associated with the development and/or progression of the disease, the present study was conducted to detect the expression of peroxiredoxin (PRX) isoforms, including PRX1, PRX2, and PRX3. Fifty-two patients with ovarian endometriosis cysts and 47 controls were included in the study. Serum levels of PRXs were detected by enzyme-linked immunosorbent assay, and the expression of PRX in the endometrium was examined by immunohistochemistry. Serum PRX1, PRX2, and PRX3 were significantly lower in EMT patients than in controls. The expression of the three isoforms was significantly decreased in ectopic endometrium compared to that in eutopic or control endometrium. There was no difference in PRX expression between eutopic endometrium of EMT patients and control endometrium, and no association was found between serum PRX levels and immunostaining scores. Our results are the first report that PRXs are downregulated in EMT patients, which suggests that PRXs are involved in the oxidative state of the disease.


Giga-voxel computational morphogenesis for structural design.
In the design of industrial products ranging from hearing aids to automobiles and aeroplanes, material is distributed so as to maximize the performance and minimize the cost. Historically, human intuition and insight have driven the evolution of mechanical design, recently assisted by computer-aided design approaches. The computer-aided approach known as topology optimization enables unrestricted design freedom and shows great promise with regard to weight savings, but its applicability has so far been limited to the design of single components or simple structures, owing to the resolution limits of current optimization methods. Here we report a computational morphogenesis tool, implemented on a supercomputer, that produces designs with giga-voxel resolution-more than two orders of magnitude higher than previously reported. Such resolution provides insights into the optimal distribution of material within a structure that were hitherto unachievable owing to the challenges of scaling up existing modelling and optimization frameworks. As an example, we apply the tool to the design of the internal structure of a full-scale aeroplane wing. The optimized full-wing design has unprecedented structural detail at length scales ranging from tens of metres to millimetres and, intriguingly, shows remarkable similarity to naturally occurring bone structures in, for example, bird beaks. We estimate that our optimized design corresponds to a reduction in mass of 2-5 per cent compared to currently used aeroplane wing designs, which translates into a reduction in fuel consumption of about 40-200 tonnes per year per aeroplane. Our morphogenesis process is generally applicable, not only to mechanical design, but also to flow systems, antennas, nano-optics and micro-systems.


CCR5, MCP-1 and VDR Gene Polymorphisms Are Associated with the Susceptibility to HBV Infection.
Genetic variants of chemokine and regulatory cytokines play functional roles in chronic HBV infection. The objective of the study, was to evaluate the association between the CCR5D32, CCR5-2459A/G, MCP-1-2518A/G, VDR-APa1A/C, VDR-Taq1T/C SNPs and HBV susceptibility, in samples of Iranian populations. The CCR5D32, CCR5-2459A/G, MCP1-2518A/G, VDR-APa1A/C, VDR-Taq1T/C polymorphisms were analyzed by polymerase chain reaction and PCR-RFLP using 100 chronic HBV infected (HBV) patients, 40 spontaneously recovered HBV (SR) subjects and 100 healthy controls (C). Also, serum levels of protein were monitored. The study showed that the existence of CCR5-2459A, MCP1-2518G and VDR-CC alleles significantly increased risk of chronic HBV infection. In addition, WtAGCC haplotype had a higher frequency in HBV patients than C and SR groups and might relate to the natural history of the infection. Statistical analysis indicated positive correlations between CCR5-2459A/G, MCP1-2518A/G, VDR-APa1A/C, VDR-Taq1T/C genotypes and serum levels of the CCR5, MCP-1 and VDR in HBV patients. According to the statistical analysis, significant associations with susceptibility to chronic HBV infection was observed with CCR5-2459A/G, MCP1-2518A/G, VDR-APa1A/C, VDR-Taq1T/C polymorphisms. In addition, no association of the CCR5D32 SNP with the disease was found.


A bisexually reproducing all-triploid vertebrate.
Green toads are common in the Palaearctic region, where they have differentiated into several taxa. The toads exist with variable amounts of ploidy, similar to other anuran species or reptiles. In vertebrate biology, the very rare occurrence of triploidy is coupled with infertility or unisexuality, or requires the coexistence of individuals of different ploidy in a reproductive community. The reproduction of naturally occurring triploids has been reported to occur only through parthenogenesis, gynogenesis or hybridogenesis. The bisexual reproduction of pure triploids has been considered to be impossible because of the problem of equally distributing three chromosome sets in meiosis. Here we report geographically isolated populations of green toads (Bufo viridis complex) that are all-triploid and reproduce bisexually.


Incremental value of arterial wave reflections in the determination of left ventricular diastolic dysfunction in untreated patients with essential hypertension.
Systemic arterial stiffness is an indicator of cardiovascular disease and an independent marker of morbidity and cardiovascular mortality. We investigated the association of arterial wave reflections with left ventricular (LV) diastolic dysfunction and their incremental value to other determinants of LV diastolic dysfunction in patients with essential hypertension. In total 143 patients and 20 controls with similar atherosclerotic risk factors were examined by applanation tonometry of the radial artery (Sphygmocor) and echocardiography. Central augmentation index (CAI%) of reflected arterial waves as well as aortic strain (AoS) assessed by echocardiography were estimated. Doppler diastolic abnormalities were defined as proposed by the European Study Group on diastolic heart failure by measurement of E/A ratio (the ratio of the mitral inflow velocities), isovolumic relaxation time, deceleration time and flow propagation velocity. AoS and CAI were impaired in patients compared with controls (4.67 +/- 2.94 vs 6.06 +/- 4.91% and 145.8 +/- 22.7 vs. 135.7 +/- 20.3%, P < 0.01) as well as in patients with LV diastolic dysfunction compared to patients without, (5.52 +/- 4.29 vs. 10.73 +/- 5.77% and 139.5 +/- 21.7 vs. 124.5 +/- 17.0%, P < 0.05). The odds ratio (OR) of AoS and CAI for diastolic dysfunction was OR:0.918, 95% confidence interval (CI):0.837-0.99, P = 0.04 and OR:1.023, 95% CI: 1.023-1.040 P = 0.010, respectively. The addition of CAI to the multivariable model including age, LV mass index, AoS and mean arterial pressure increased the power of the model for determination of LV diastolic dysfunction (-2 log likelihood = 139.368, change of chi2 = 4.2, P-value for change=0.04). In untreated patients with newly diagnosed essential hypertension, wave reflections are independent and additive determinants of LV diastolic dysfunction.


The taxonomic status of Rhodococcus equi.
The species Corynebacterium equi was proposed for strains isolated from foals suffering from purulent pneumonia. The taxon has had a confused history and is currently listed under both Corynebacterium and Rhodococcus in the Approved Lists of Bacterial Names. Data from modern taxonomic studies indicate that Corynebacterium equi Magnusson 1923 should be reduced to a synonym of Rhodococcus equi (Magnusson) Goodfellow and Alderson 1980. Rhodococcus equi has repeatedly been shown to be a good species on the basis of chemical, molecular biological, numerical phenetic and serological data. Improved methods are needed to differentiate Rhodococcus equi from closely related species of Rhodococcus.


Female urethral stricture from chronic graft-versus-host disease.
Female urethral strictures are rare with limited literature to guide management. We present a case of a 27 year old female diagnosed with a urethral stricture secondary to chronic graft-versus-host disease. This diagnosis should be considered in females presenting with obstructive voiding symptoms and have risk factors for stricture development.


Independent measurement of oxygen consumption and oxygen delivery.
This experiment investigated the relationship between oxygen consumption and oxygen delivery (cardiac output X arterial oxygen content) in an acute canine model. Previous studies investigating this relationship have largely utilized methods in which oxygen consumption and oxygen delivery were each calculated using the same measured variables resulting in mathematical coupling of variables. In this study, oxygen consumption was measured directly by closed-circuit spirometry. Oxygen delivery was independently controlled using right atrial bypass. These techniques assured that the values for oxygen consumption and oxygen delivery were derived entirely independently. In our study using 11 dogs, we found that oxygen consumption was constant and independent of oxygen delivery at oxygen delivery levels greater than 8.0 cc/kg/min (normal canine oxygen delivery 20-25 cc/kg/min). Oxygen consumption was linearly related to oxygen delivery at oxygen delivery levels less than or equal to 8.0 cc/kg/min. Below this critical level of oxygen delivery, animals were more acidotic and hypotensive than at higher delivery levels.


The natural history of halo nevi: a retrospective case series.
The time period between onset of depigmentation around the halo nevus (HN) to complete resolution of the nevus and halo has not been well studied. We sought to better understand the natural history of the HN. A retrospective chart review of patients with a clinical diagnosis of HN selected from a private practice database (1994-2010) was performed. In all, 52 patients with 80 HN were identified. The current stage of the HN was determined by a follow-up questionnaire and physical examination of 36 patients with 56 HN. Seven HN were excised. Of the remaining 49 HN, 51% (25) demonstrated no change in the halo or nevus after an average of 4.2 years; 14.3% (7) demonstrated partial nevus regression with persistence of the halo after an average of 6.7 years; 4.1% (2) demonstrated complete involution of the nevus with persistent halo depigmentation after an average of 7.7 years; 8.2% (4) demonstrated complete nevus involution with some repigmentation of the halo after an average of 11.8 years; 22.4% (11) demonstrated complete resolution of the nevus with complete repigmentation of the halo after an average of 7.8 years. Some subjects were lost to follow-up. The time of initial HN onset was dependent on patient recall. These results demonstrate that HN typically persist for a decade or longer. A subgroup may progress through stages of involution with a return to normal-appearing skin, but even these lesions persisted for an average of 7.8 years. Education about the prolonged natural history of HN may reassure patients and avoid unnecessary excision.


One year of laboratory-based COVID-19 surveillance system in Belgium: main indicators and performance of the laboratories (March 2020-21).
With the spread of coronavirus disease 2019 (COVID-19), an existing national laboratory-based surveillance system was adapted to daily monitor the epidemiological situation of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in the Belgium by following the number of confirmed SARS-CoV-2 infections, the number of performed tests and the positivity ratio. We present these main indicators of the surveillance over a one-year period as well as the impact of the performance of the laboratories, regarding speed of processing the samples and reporting results, for surveillance. We describe the evolution of test capacity, testing strategy and the data collection methods during the first year of the epidemic in Belgium. Between the 1st of March 2020 and the 28th of February 2021, 9,487,470 tests and 773,078 COVID-19 laboratory confirmed cases were reported. Two epidemic waves occurred, with a peak in April and October 2020. The capacity and performance of the laboratories improved continuously during 2020 resulting in a high level performance. Since the end of November 2020 90 to 95% of the test results are reported at the latest the day after sampling was performed. Thanks to the effort of all laboratories a performant exhaustive national laboratory-based surveillance system to monitor the epidemiological situation of SARS-CoV-2 was set up in Belgium in 2020. On top of expanding the number of laboratories performing diagnostics and significantly increasing the test capacity in Belgium, turnaround times between sampling and testing as well as reporting were optimized over the first year of this pandemic.


Water and sodium balance: the effect of the air-fluidized bed on burned patients.
Five patients with burned areas from 20 to 40 per cent BSA were studied in the air-fluidized bed during the first 2-week period post burn. Patients with abnormal renal and intestinal functions and with previous pathological history were not incorporated in the study. The patients were treated by the exposure method, and no surgical procedure was carried out during the study. The water and sodium balances were calculated from intravenous and oral intakes, urine-outflow, urinary sodium excretion and weight changes. In addition measurements of the sodium space were performed in two patients, using Sodium. Evaporative water loss was calculated during the first week, the sodium loss during the first and second weeks. As a result of the study the average daily evaporative water loss could be defined as: 0.81 ml/cm2 burned area +/- 0.07 ml. We compared the actual evaporative water loss with two classical formulas: --Davies, Lamke, Liljedahl (1974) (D.L.L.) min: 0.3 ml X cm2 burned area = ml/day = D.L.L. (0.3) Max: 0.45 ml X cm2 burned area = ml/day = D.L.L. (0.45) --Scott, McDougall, Slade, Pruitt (1978) (S.M.S.P.) (25 + %) X BSA = ml/h = S.M.S.P. --Scott, McDougall, Slade, Pruitt (1978) (S.M.S.P.) (25 + %) X BSA = ml/h = S.M.S.P. The average calculated daily evaporative water was: D.L.L. (0.3) + 5 litre/m2 burned area D.L.L. (0.45) + 3.5 l/m2 burned area S.M.S.P. + 4 litre/m2 burned area. This 'extra' evaporative water loss was closely related to the body burned surface. Correlation coefficient: D.L.L. (0.3) = 0.99 D.L.L. (0.45) = 0.98 S.M.S.P. = 0.97. Day 2 and day 3 showed the most important water loss per cm2 burned area. On the other hand, the sodium loss was found to be as expected: daily average: 0.02 mmol/cm2 burned area.


Surgically assisted rapid palatal expansion for transverse maxillary discrepancy in adults - Case report.
Transverse maxillary deficiency is one of the most detrimental problems to midfacial growth and the integrated dentoalveolar structures. Early diagnosis and proper treatment of such cases is most important to maintain the balance between the basal bones and stable occlusion. In our case, a 17-year-old male had irregular upper front teeth with an unpleasant smile. Detail examination revealed a symmetrical face with an orthognathic profile, mild malar deficiency, competent lips, asymmetrical arches, Class I molar and canine relationships bilaterally. Crowding was present in the upper anterior arch with 2 mm of anterior open bite and posterior cross bite present in the premolar region and molar region bilaterally. Lefort-1 osteotomy, midpalatal split, pterygomandibular disjunction without down fracture was done. The HYRAX appliance was cemented. Distraction started after four days of surgery. One mm distraction per day was done for 10 days. The patient was transferred to fixed orthodontic treatment to relive the anterior crowding. Records were taken after 1 year of follow up and analyzed. Skeletal relationships were in harmony. Dental crowding, anterior open bite and posterior crossbite were corrected. The zygomatic buttress and the pterygomaxillary junction are considered as the critical areas of resistance for maxillary expansion. Literature claims lefort-1 osteotomy in combination with palatal distraction results in more displacement and less stress in the maxilla. SARPE has proved to be clinically effective and stable for the correction of transversely deficient maxilla after cessation of growth in adult patients.


Luteinizing hormone-releasing factor-like immunoreactivity in islet cells and insulomas of the human pancreas.
Luteinizing hormone-releasing factor (LRF)-like immunoreactivity was demonstrated by a three-layer immunoperoxidase method in the islet cells of human pancreas and in the neoplastic cells of insulomas. Adenocarcinomas originating in the exocrine pancreas were LRF-negative. The results demonstrate another hypothalamic peptide-like material in the gastrointestinal tract, the biological role of which remains to be clarified.


Occlusion of the central retinal artery after retrobulbar corticosteroid injection.
Occlusion of the central retinal artery with loss of all vision occurred in a 38-year-old white woman given a retrobulbar injection of betamethasone acetate and betamethasone disodium phosphate (Celestone Soluspan) for the treatment of a retrobulbar neuritis. Ophthalmoscopy revealed embolic, whitish material within several of the small retinal arterioles and capillaries. This, together with the absence of any signs of retrobulbar hemorrhage, suggested that the corticosteroid material was accidentally injected into a branch of the central retinal artery and subsequently passed into the main vessel.


Isolated cerebellar tuberculoma mimicking a malignant posterior cranial fossa tumor in a healthy child: A rare case report from Tanzania.
Tuberculosis (TB) is one of the leading causes of mortality and morbidity in the world, especially in developing countries that account for 98 % deaths among TB cases. Although TB is primarily a disease of the lungs, extrapulmonary manifestations have been reported. Although CNS tuberculoma mostly affects immunocompromised people, it also affects healthy people at extremes of age. Imaging of intracranial tuberculoma may look like neurocysticercosis, and other ring-enhancing lesions hence imposing a diagnosis dilemma. A 13-year-old female presented with headache, convulsions, blurry vision, and gait disturbance for six months. Brain imaging showed a left cerebellar lesion with obstructive hydrocephalus. She underwent ventriculoperitoneal shunting on admission, then sub-occipital craniotomy with tumor resection one week later. Histology confirmed a diagnosis of tuberculoma. She was given anti-tuberculosis medications and she was discharged home healthy without any of the symptoms she had on admission. Although only about 1 % of active tuberculosis cases presents as CNS TB, 5-10 % of intracranial space-occupying lesions in developing countries are tuberculomas. Provisional diagnosis of tuberculoma can be made through clinical history, examination, and neuroimaging. However, it is challenging because neurocysticercosis also appears as a ring-enhancing lesion in the brain and has almost similar prevalence in low-income settings. Being immunocompetent with no history of tuberculosis or constitutional symptoms, a diagnosis of tuberculoma was only confirmed by histology. A high index of suspicion for CNS tuberculomas in TB endemic areas should be kept in patients presenting with features of intracranial space-occupying lesions regardless of the absence of risk factors.


Precursor-directed biosynthesis: biochemical basis of the remarkable selectivity of the erythromycin polyketide synthase toward unsaturated triketides.
The structural basis for the striking stereochemical discrimination among triketide analogs has been investigated by incubating a series of N-acetyl cysteamine (-SNAC) esters of unsaturated triketides with DEBS module 2+TE. The triketide analogs were first screened under a standard set of short-term incubation conditions in the presence of the extender substrate methylmalonyl-CoA and NADPH. For those triketide analogs that served as substrates for module 2+TE, the relative specificity, represented by the k(cat)/K(M) values, was quantitated. Triketide diastereomers that were converted in precursor-directed biosynthesis experiments to unsaturated 16-membered ring macrolides by DEBS(KS1(0)) were good to excellent substrates for DEBS module 2+TE, whereas analogs that were converted to the 14-membered ring analogs of 10,11-dehydro-6-deoxyerythronolide B by DEBS(KS1(0)) were not turned over at all by module 2+TE.


Ultrasound-guided periradicular injections in the middle to lower cervical spine: an imaging study of a new approach.
The objective of this study was to show the efficacy of ultrasound in facilitating the performance of a simulated cervical periradicular injection in cadavers. A total of 40 ultrasound-guided examinations at 4 levels (C3 to C7) were performed on 4 embalmed cadavers. The cervical spinal nerves were located with ultrasound. First, the transverse process of each level was taken as a sonoanatomic landmark. The most lateral aspect of the transverse process of the seventh cervical vertebra was then established as the reference point. Ipsilateral distances (A, B, C, and D) between this point and each one of the transverse processes of the cervical spine up to the third vertebra were then computed. Subsequently, coronal computed tomography (CT) scans were taken to verify these distances. In a second part, a spinal needle was advanced under ultrasound guidance to the spinal nerves C5 to C8 on both sides of one cadaver. The exact placement of the needle tips was checked by CT. The transverse processes were identified in all cadavers. In 5 attempts, a depiction of the spinal nerves was not possible. Ultrasound and CT provided the same mean measurements of 1.1 cm, 2.1 cm, 3.1 cm, and 4.1 cm for distances A, B, C, and D, respectively. All 8 needle tips were placed within 5 mm dorsal to the spinal nerve and less than 5 mm away from the posterior tubercle of each level's transverse process, as also verified by CT. This preclinical study suggests that ultrasound is a useful guiding tool for periradicular injections in the cervical spine.


One-step immunopurification and lectinochemical characterization of the Duffy atypical chemokine receptor from human erythrocytes.
Duffy antigen/receptor for chemokines (DARC) is a glycosylated seven-transmembrane protein acting as a blood group antigen, a chemokine binding protein and a receptor for Plasmodium vivax malaria parasite. It is present on erythrocytes and endothelial cells of postcapillary venules. The N-terminal extracellular domain of the Duffy glycoprotein carries Fy(a)/Fy(b) blood group antigens and Fy6 linear epitope recognized by monoclonal antibodies. Previously, we have shown that recombinant Duffy protein expressed in K562 cells has three N-linked oligosaccharide chains, which are mainly of complex-type. Here we report a one-step purification method of Duffy protein from human erythrocytes. DARC was extracted from erythrocyte membranes in the presence of 1% n-dodecyl-β-D-maltoside (DDM) and 0.05% cholesteryl hemisuccinate (CHS) and purified by affinity chromatography using immobilized anti-Fy6 2C3 mouse monoclonal antibody. Duffy glycoprotein was eluted from the column with synthetic DFEDVWN peptide containing epitope for 2C3 monoclonal antibody. In this single-step immunoaffinity purification method we obtained highly purified DARC, which migrates in SDS-polyacrylamide gel as a major diffuse band corresponding to a molecular mass of 40-47 kDa. In ELISA purified Duffy glycoprotein binds anti-Duffy antibodies recognizing epitopes located on distinct regions of the molecule. Results of circular dichroism measurement indicate that purified DARC has a high content of α-helical secondary structure typical for chemokine receptors. Analysis of DARC glycans performed by means of lectin blotting and glycosidase digestion suggests that native Duffy N-glycans are mostly triantennary complex-type, terminated with α2-3- and α2-6-linked sialic acid residues with bisecting GlcNAc and α1-6-linked fucose at the core.


Muscle Hypertrophy Responses to Changes in Training Volume: A Retrospective Analysis.
This study assessed associations between changes in the weekly number of sets performed and the percentage change in muscle thickness of the biceps (MTBB) and triceps (MTTB) brachii muscles. Through a retrospective analysis, sixty-eight resistance-trained subjects that participated in previous studies had their previous training volumes analyzed and compared to the volume imposed during each individual study. The relationship between variables was determined through Spearman correlation and a k-cluster analysis was performed to subdivide the participants into three groups and classified as:<0%; 0-50%, and >50% increase in the number of sets for both muscle groups. Moderate and weak correlations were observed between the alterations in training volume and changes in MTBB (rs=0.44, p=0.001) and MTTB (rs=0.35, p=0.002), respectively. A significant difference was noted between<0% to >50% for MTBB and MTTB (p=0.017; p=0.042, respectively), while no significant difference was observed between<0% to 0-50% and 0-50% to >50% (both p >0.05) for both muscle groups. In conclusion, muscle hypertrophy of the upper limbs is only weakly to moderately associated with changes in training volume of trained subjects.


Comparative gene expression analysis in melanocytes driven by tumor cell-derived exosomes.
Abundant with organelle-like membranous structures, the tumor microenvironment is composed of cancer cells that secrete exosomes. Studies have shown that these secreted exosomes transport RNA and active molecules to other cells to reshape the tumor microenvironment and promote tumor growth. In fact, we found that exosomes derived from melanoma cells drive pre-malignant transition in primary melanocytes. However, there is little available in the scientific literature on how exosomes modulate melanocytes in the microenvironment to optimize conditions for tumor progression and metastasis. We therefore focused this current study on identifying these conditions genetically. Through RNA sequencing, we analyzed gene expression levels of melanocytes driven by exosomes derived from melanoma and lung cancer cells compared with those without exosome controls. Significant differences were found in gene expression patterns of melanocytes driven by exosomes derived from melanoma and lung cancer cells. In the melanocytes responding to exosomes derived from melanoma cells, genes of lipopolysaccharide and regulation of leukocyte chemotaxis were predominant. In the melanocytes responding to exosomes derived from lung cancer cells, genes of DNA replication and mitotic nuclear division played an important role. These results provide further mechanistic understanding of tumor progression promoted by tumor-derived exosomes. This will also help identify potential therapeutic targets for melanoma progression.


Levels of PCDD/Fs, PCBs and PBDEs in breast milk of women living in the vicinity of a hazardous waste incinerator: assessment of the temporal trend.
The concentrations of polychlorinated dibenzo-p-dioxins and dibenzofurans (PCDD/Fs), polychlorinated biphenyls (PCBs) and polybrominated diphenyl ethers (PBDEs) were determined in breast milk from women living in the vicinity of a hazardous waste incinerator (HWI) in Catalonia, Spain. The results were compared with the levels obtained in previous surveys carried out in the same area in 1998 (baseline study), 2002 and 2007. The current total concentrations of 2,3,7,8-chlorinated PCDD/Fs in breast milk ranged from 18 to 126 pg g(-1)fat (1.1-12. 3 pg WHO2005-TEQPCDD/F), while the total levels of PCBs ranged from 27 to 405 pg g(-1)fat(0.7-5.3 pg WHO2005-TEQPCB). In turn, PBDE concentrations (sum of 15 congeners) ranged 0.3-5.1 g g(-1)fat, with a mean value of 1.3 ng g(-1)fat. A general decrease in the concentrations for PCDD/Fs, both planar and total PCBs, and PBDEs in breast milk was observed. The levels of PCDD/Fs, PCBs, and PBDEs in milk of women living in urban zones were higher than those corresponding to industrial zones (41%, 26%, and 8%, respectively). For PCDD/Fs and PCBs, the current decreases are in accordance with the reduction in the dietary intake of these pollutants that we have also observed in recent studies carried out in the same area of study.


[Japan children's cancer registry and strategy for children's cancer epidemiology].
A registry of 19,853 children with various types of cancer has been made during 1969-1984 in Japan. The advantages and methods of database control in setting up the strategy for prevention of children's cancer were described. Several procedures of statistical analysis were treated, along with the discussion of data search mode, medical record linkage technique, recent trends in medical care facilities, and study of high-risk conditions for cancer.


Effects of high-dose simvastatin therapy on glucose metabolism and ectopic lipid deposition in nonobese type 2 diabetic patients.
Statins may exert pleiotropic effects on insulin action that are still controversial. We assessed effects of high-dose simvastatin therapy on peripheral and hepatic insulin sensitivity, as well as on ectopic lipid deposition in patients with hypercholesterolemia and type 2 diabetes. We performed a randomized, double-blind, placebo-controlled, single-center study. Twenty patients with type 2 diabetes received 80 mg simvastatin (BMI 29 +/- 4 kg/m2, age 55 +/- 6 years) or placebo (BMI 27 +/- 4 kg/m2, age 58 +/- 8 years) daily for 8 weeks and were compared with 10 healthy humans (control subjects; BMI 27 +/- 4 kg/m2, age 55 +/- 7 years). Euglycemic-hyperinsulinemic clamp tests combined with D-[6,6-d2]glucose infusion were used to assess insulin sensitivity (M) and endogenous glucose production (EGP). 1H magnetic resonance spectroscopy was used to quantify intramyocellular and hepatocellular lipids. High-dose simvastatin treatment lowered plasma total and LDL cholesterol levels by approximately 33 and approximately 48% (P < 0.005) but did not affect M, intracellular lipid deposition in soleus and tibialis anterior muscles and liver, or basal and insulin-suppressed EGP. In simvastatin-treated patients, changes in LDL cholesterol related negatively to changes in M (r = -0.796, P < 0.01). Changes in fasting free fatty acids (FFAs) related negatively to changes in M (r = -0.840, P < 0.01) and positively to plasma retinol-binding protein-4 (r = 0.782, P = 0.008). High-dose simvastatin treatment has no direct effects on whole-body or tissue-specific insulin action and ectopic lipid deposition. A reduction in plasma FFAs probably mediates alterations in insulin sensitivity in vivo.


Two concurrent appendiceal neoplasms in an elderly patient: A case report.
Acute appendicitis, one of the commonest surgical diagnoses, is rare and more complex presentation in the elderly. Physicians must consider atypical causes appendicitis in this population, which could affect the management of the patient. An elderly female presented with a two-day history of lower abdominal pain, associated with low-grade fevers and chills. Studies showed leukocytosis and computed tomography (CT) findings consistent with appendicitis. She underwent laparoscopic appendectomy. Intra-operatively, the Appendix had an unusual appearance, so a frozen-section was obtained, suggestive of a mucinous neoplasm with grossly clear margins. Despite the possibility that she may require a more extensive cancer operation pending the final Pathology results, the decision was made to complete the operation at this stage, and return at a later date if needed, after completing the patient's work-up with a colonoscopy to rule out any synchronous colonic lesions that could alter her surgical management. Final Pathology revealed both a low-grade appendiceal mucinous neoplasm, as well as a tip carcinoid tumor, both of which were adequately treated with appendectomy alone. Physicians treating elderly patients with appendicitis should suspect an atypical etiology, such as appendiceal cancer. Early identification and appropriate pre-operative counseling may alter the surgical management. The role and timing of right hemicolectomy in treating appendiceal cancers remain controversial, and should be evaluated on a case by case basis.


Fronto-temporal brain activity and connectivity track implicit attention to positive and negative social words in a novel socio-emotional Stroop task.
Previous inconsistencies on the effects of implicitly processing positively - vs. negatively - connotated emotional words might reflect the influence of uncontrolled psycholinguistic dimensions, and/or social facets inherent in putative "emotional" stimuli. Based on the relevance of social features in semantic cognition, we developed a socio-emotional Stroop task to assess the influence of social vs. individual (non-social) emotional content, besides negative vs. positive valence, on implicit word processing. The effect of these variables was evaluated in terms of performance and RTs, alongside associated brain activity/connectivity. We matched conditions for several psycholinguistic variables, and assessed a modulation of brain activity/connectivity by trial-wise RT, to characterize the maximum of condition- and subject-specific variability. RTs were tracked by insular and anterior cingulate activations likely reflecting implicit attention to stimuli, interfering with task-performance based on condition-specific processing of their subjective salience. Slower performance for negative than neutral/positive words was tracked by left-hemispheric structures processing negative stimuli and emotions, such as fronto-insular cortex, while the lack of specific activations for positively-connotated words supported their marginal facilitatory effect. The speeding/slowing effects of processing positive/negative individual emotional stimuli were enhanced by social words, reflecting in specific activations of the right anterior temporal and orbitofrontal cortex, respectively. RTs to social positive and negative words modulated connectivity from these regions to fronto-striatal and sensorimotor structures, respectively, likely promoting approach vs. avoidance dispositions shaping their facilitatory vs. inhibitory effect. These results might help assessing the neural correlates of impaired social cognition and emotional regulation, and the effects of rehabilitative interventions.


MicroRNA-455-3p regulates proliferation and osteoclast differentiation of RAW264.7 cells by targeting PTEN.
Macrophages are one of the important cells in immune system. In this article, we aim to explore the regulatory role of miR-455-3p on proliferation and osteoblast differentiation of RAW264.7 cells. Expression levels of genes and proteins in cells were tested via qRT-PCR and western blot. The targeted correlation between miR-455-3p and PTEN was identified by luciferase analysis. MTT assay and flow cytometry were applied to detect the proliferation and apoptosis of cells. Osteoclastogenesis was completed by stimulating RAW 264.7 cells with RANKL. Tartrate-resistant acid phosphatase (TRAP) activity in different groups of cells were assessed. Firstly, we determined that up-regulation of miR-455-3p promoted the proliferation and inhibited apoptosis of RAW 264.7 cells. MiR-455-3p deficiency played opposite effect in RAW 264.7 cells. Additionally, osteoclastogenesis-related factors (TRAP, CTSK and NFATc1) expression levels were remarkably up-regulated in miR-455-3p-mimic group of RAW264.7 cells treated with RANKL, but decreased in inhibitor group. Luciferase assay proved that miR-455-3p targeted PTEN. We took a further step and found overexpression of PTEN significantly inhibited the increased proliferation and osteoblast differentiation of RAW264.7 cells induced by miR-455-3p. Our findings supported basic to explore the molecular mechanism of proliferation and osteoblast differentiation of RAW264.7 cells.


Total invasion of the pancreatic gland by a rare aggressive IPMN: Report of a case.
The intraductal papillary mucinous neoplasms (IPMNs) are increasingly diagnosed entities with high potential of malignancy and significant recurrence rates. In this case report a rare mixed IPMN with full invasion of the pancreatic ducts was identified. Difficulties in determining the grade of pancreatic duct involvement make the surgical management tough. In multifocal IPMNs the management of the patients is even more challenging. In this case the patient was treated successfully with total pancreatectomy.


Empirical solvent-mediated potentials hold for both intra-molecular and inter-molecular inter-residue interactions.
Whether knowledge-based intra-molecular inter-residue potentials are valid to represent inter-molecular interactions taking place at protein-protein interfaces has been questioned in several studies. Differences in the chain connectivity effect and in residue packing geometry between interfaces and single chain monomers have been pointed out as possible sources of distinct energetics for the two cases. In the present study, the interfacial regions of protein-protein complexes are examined to extract inter-molecular inter-residue potentials, using the same statistical methods as those previously adopted for intra-molecular residue pairs. Two sets of energy parameters are derived, corresponding to solvent-mediation and "average residue" mediation. The former set is shown to be highly correlated (correlation coefficient 0.89) with that previously obtained for inter-residue interactions within single chain monomers, while the latter exhibits a weaker correlation (0.69) with its intra-molecular counterpart. In addition to the close similarity of intra- and inter-molecular solvent-mediated potentials, they are shown to be significantly more residue-specific and thereby discriminative compared to the residue-mediated ones, indicating that solvent-mediation plays a major role in controlling the effective inter-residue interactions, either at interfaces, or within single monomers. Based on this observation, a reduced set of energy parameters comprising 20 one-body and 3 two-body terms is proposed (as opposed to the 20 x 20 tables of inter-residue potentials), which reproduces the conventional 20 x 20 tables with a correlation coefficient of 0.99.


[Methodological aspects of assessing chitin utilization by soil microorganisms].
A computational method for estimating specific activity of chitin decomposition by microorganisms is proposed. Spectrophotometric and gas chromatographic methods have been used to determine the rates of chitinase production, biomass accumulation, and carbon dioxide emission by pure cultures of microorganisms grown on a chitin-containing medium. Among dominants of the chitinolytic community of chernozem (Trichoderma viride, Stretomyces albolongus, Alcaligenes, and Arthrobacter), the highest chitinolytic activity is characteristic of prokaryotes. In brown desert-steppe soil, the main destructor prokaryotes are actinomycetes (S. roseolilacinus). The biomass of the fungus T. viride growth on the chitin-containing medium markedly exceeds that of prokaryotes, but the specific activity of respiration and chitinase production in actinomycetes S. roseolilacinus and S. albolongus is an order of magnitude higher than in T. viride.


Variation in reversal learning by three generalist mesocarnivores.
Urbanization imposes novel challenges for wildlife, but also provides new opportunities for exploitation. Generalist species are commonly found in urban habitats, but the cognitive mechanisms facilitating their successful behavioral adaptations and exploitations are largely under-investigated. Cognitive flexibility is thought to enable generalists to be more plastic in their behavior, thereby increasing their adaptability to a variety of environments, including urban habitats. Yet direct measures of cognitive flexibility across urban wildlife are lacking. We used a classic reversal-learning paradigm to investigate the cognitive flexibility of three generalist mesocarnivores commonly found in urban habitats: striped skunks (Mephitis mephitis), raccoons (Procyon lotor), and coyotes (Canis latrans). We developed an automated device and testing protocol that allowed us to administer tests of reversal learning in captivity without extensive training or experimenter involvement. Although most subjects were able to rapidly form and reverse learned associations, we found moderate variation in performance and behavior during trials. Most notably, we observed heightened neophobia and a lack of habituation expressed by coyotes. We discuss the implications of such differences among generalists with regard to urban adaptation and we identify goals for future research. This study is an important step in investigating the relationships between cognition, generalism, and urban adaptation.