Comparison of quantitative DNA measurements and cytomorphology in squamous cell carcinomas of the upper aerodigestive tract with and without lymph node metastases.
Cytologic smears of squamous cell carcinomas (UICC T2 through T4) from the mucosa of the upper aerodigestive tract without cervical lymph node metastases (n = 10) and with metastases (n = 20) were examined. Subsequently, the cytologic smears of the metastases (n = 20) obtained by fine-needle aspiration or following neck dissection were evaluated morphologically. Each specimen was then stained with Papanicolaou and Feulgen techniques, and quantitative DNA measurements were performed with an image analysis system. Morphologically, the primary tumors with metastases revealed an increased mean nuclear perimeter and mean nuclear area compared with tumors unassociated with metastases. On quantitative DNA measurements, the tumors with metastases had an increased DNA content, a higher 2c deviation index, and a higher DNA malignancy grade and increased number of aneuploid cells. The specimens obtained from the metastatic nodes yielded the highest values for mean DNA content, 2c deviation index, aneuploidy, and malignancy grade. The stem lines of metastasis were always nondiploid. These data indicate a positive correlation between aneuploid tumor cell clones in primary cancer and the manifestation of lymph node metastases.


Development of a Consistent and Reproducible Porcine Scald Burn Model.
There are very few porcine burn models that replicate scald injuries similar to those encountered by children. We have developed a robust porcine burn model capable of creating reproducible scald burns for a wide range of burn conditions. The study was conducted with juvenile Large White pigs, creating replicates of burn combinations; 50°C for 1, 2, 5 and 10 minutes and 60°C, 70°C, 80°C and 90°C for 5 seconds. Visual wound examination, biopsies and Laser Doppler Imaging were performed at 1, 24 hours and at 3 and 7 days post-burn. A consistent water temperature was maintained within the scald device for long durations (49.8 ± 0.1°C when set at 50°C). The macroscopic and histologic appearance was consistent between replicates of burn conditions. For 50°C water, 10 minute duration burns showed significantly deeper tissue injury than all shorter durations at 24 hours post-burn (p ≤ 0.0001), with damage seen to increase until day 3 post-burn. For 5 second duration burns, by day 7 post-burn the 80°C and 90°C scalds had damage detected significantly deeper in the tissue than the 70°C scalds (p ≤ 0.001). A reliable and safe model of porcine scald burn injury has been successfully developed. The novel apparatus with continually refreshed water improves consistency of scald creation for long exposure times. This model allows the pathophysiology of scald burn wound creation and progression to be examined.


Spinal ganglioneuroblastoma--complete response to chemotherapy alone.
Ganglioneuroblastoma in the spinal region is rare, the treatment of choice being surgical excision. We present a 21 year old male who was diagnosed to have this condition in the dorsolumbar spinal region. The tumour was extending intraspinally and was unresectable. Combination chemotherapy with Adriamycin (doxorubicin hydrochloride), vincristine, cyclophosphamide, etoposide, ifosfamide and cisplatin resulted in histologically proven complete remission. No radiotherapy or curative resection was done. The patient is alive without evidence of disease 24 months later. Never before has chemotherapy been successfully used as the sole modality of treatment in this condition. Our report raises important questions about the management of this rare condition, particularly in a situation of unresectability.


RHIOs--build in healthcare fraud management from the beginning.
This article presents the Department of Health and Human Services, Office of the National Coordinator for Health Information Technology's field-based research on the use of Health Information Technology to Advance and Expand Healthcare Anti-Fraud Activities.' The authors of this article directed and performed this research under contract to the Foundation of Research and Education of AHIMA. There is a tremendous potential to reduce healthcare fraud and achieve substantial financial benefits using a nationwide health information network with interoperable electronic health records. To achieve these benefits, there must be interoperability among providers and between providers and payers. The article will provide recommendations for regional health information organizations to incorporate healthcare fraud management in their early designs.


Organic contaminants in the Firth of Clyde following the cessation of sewage sludge dumping.
To assess contaminant concentrations in the Firth of Clyde in relation to the former sewage sludge dump site at Garroch Head, and investigate any temporal changes, fish have been sampled annually since 1992 and sediment since 1999. In addition, a further four locations in the Clyde (Holy Loch, Hunterston, Skelmorlie and Irvine Bay) have been sampled for fish and sediment since 1999. Chlorobiphenyls (CBs) were measured in fish samples and polycyclic aromatic hydrocarbons (PAHs) and CBs in sediment. Since sampling was initiated the concentration for the summation operatorICES7 CBs in fish liver has been consistently >500 microg kg(-1) lipid weight at Garroch Head and the other Clyde sites and lower at the reference sites (Pladda, Colonsay, Broad Bay). Although the lowest CB concentrations of the eleven year period in plaice liver from Garroch Head were found in 2002, CB concentrations were found not to have decreased significantly since sewage sludge dumping ceased in 1998. However, a change in CB profile was observed with fish liver collected between 1992 and 1998 from Garroch Head showing a lower proportion of the less chlorinated CBs compared to the 1999-2002 liver samples. Highest CB and PAH concentrations in sediment were found at Garroch Head and Holy Loch with concentrations at these sites being significantly higher than at all other sites.


Genomic selection: prediction of accuracy and maximisation of long term response.
Genomic selection refers to the use of dense markers covering the whole genome to estimate the breeding value of selection candidates for a quantitative trait. This paper considers prediction of breeding value based on a linear combination of the markers. In this case the best estimate of each marker's effect is the expectation of the effect conditional on the data. To calculate this requires a prior distribution of marker effects. If the marker effects are normally distributed with constant variance, BLUP can be used to calculate the estimated effects of the markers and hence the estimated breeding value (EBV). In this case the model is equivalent to a conventional animal model in which the relationship matrix among the animals is estimated from the markers instead of the pedigree. The accuracy of the EBV can approach 1.0 but a very large amount of data is required. An alternative model was investigated in which only some markers have non-zero effects and these effects follow a reflected exponential distribution. In this case the expected effect of a marker is a non-linear function of the data such that apparently small effects are regressed back almost to zero and consequently these markers can be deleted from the model. The accuracy in this case is considerably higher than when marker effects are normally distributed. If genomic selection is practiced for several generations the response declines in a manner that can be predicted from the marker allele frequencies. Genomic selection is likely to lead to a more rapid decline in the selection response than phenotypic selection unless new markers are continually added to the prediction of breeding value. A method to find the optimum index to maximise long term selection response is derived. This index varies the weight given to a marker according to its frequency such that markers where the favourable allele has low frequency receive more weight in the index.


Inter-individual and inter-regional variations in enteric drug metabolizing enzyme activities: Results with cryopreserved human intestinal mucosal epithelia (CHIM) from the small intestines of 14 donors.
We have previously reported successful isolation and cryopreservation of human intestinal mucosa (CHIM) with retention of viability and drug metabolizing enzyme activities. Here we report the results of the quantification of drug metabolizing enzyme activities in CHIM from different regions of the small intestines from 14 individual donors. CHIM were isolated from the duodenum, jejunum, and ileum of 10 individuals, and from 10 consecutive 12-inch segments starting from the pyloric sphincter of human small intestines from four additional individuals. P450 and non-P450 drug metabolizing enzyme activities (CYP1A2, CYP2A6, CYP2B6, CYP2C8, CYP2C9, CYP2C19, CYP2D6, CYP2E1, CYP3A, UGT, SULT, FMO, MAO, AO, NAT1, and NAT2) were quantified via incubation with pathway-selective substrates. Quantifiable activities were observed for all pathways except for CYP2A6. Comparison of the duodenum, jejunum, and ileum in 10 donors shows jejunum had higher activities for CYP2C9, CYP3A, UGT, SULT, MAO, and NAT1. Further definition of regional variations with CHIM from ten 12-inch segments of the proximal small intestine shows that the segments immediately after the first 12-inch segment (duodenum) had the highest activity for most of the drug metabolizing enzymes but with substantial differences among the four donors. Our overall results demonstrate that there are substantial individual differences in drug metabolizing enzymes and that jejunum, especially the regions immediately after the duodenum, had the highest drug metabolizing enzyme activities.


The efficacy and safety of oral immediate-release oxymorphone for postsurgical pain.
In this double-blind, parallel-group study, we compared 3 oxymorphone immediate-release (IR) doses with placebo for efficacy and with oxycodone IR and placebo for safety in patients with acute moderate-to-severe postsurgical pain. During the single-dose phase (n = 300), patients received oxymorphone IR 10, 20, or 30 mg; oxycodone IR 10 mg; or placebo. All oxymorphone IR doses were superior for providing pain relief for 8 h (P < 0.05), with a significant analgesic dose response (P < 0.001). Significant pain intensity differences occurred by 45 min (20- and 30-mg doses; P < 0.05). Discontinuations for lack of efficacy totaled 42% among placebo-treated patients and 27% among those treated with oxymorphone IR. Patients requiring rescue medication after 3 h were allowed to receive additional study drug every 4 to 6 h as needed for the multiple-dose phase (n = 164). All oxymorphone groups maintained analgesia for 48 h. The median dosing interval was >9.5 h for oxymorphone IR 30 mg and > or =7 h for the other groups. Opioid-related adverse events, similar among groups, were generally mild or moderate. Oxymorphone IR 10, 20, or 30 mg provided significant dose-related pain relief compared with placebo, and this relief was maintained over several days with a safety profile comparable to that of oxycodone IR.


Post-GWAS functional studies reveal an RA-associated CD40-induced NF-kB signal transduction and transcriptional regulation network targeted by class II HDAC inhibitors.
Currently, it remains difficult to identify which single nucleotide polymorphisms (SNPs) identified by genome-wide association studies (GWAS) are functional and how various functional SNPs (fSNPs) interact and contribute to disease susceptibility. GWAS have identified a CD40 locus that is associated with rheumatoid arthritis (RA). We previously used two techniques developed in our laboratory, single nucleotide polymorphism-next-generation sequencing (SNP-seq) and flanking restriction enhanced DNA pulldown-mass spectrometry (FREP-MS), to determine that the RA risk gene RBPJ regulates CD40 expression via a fSNP at the RA-associated CD40 locus. In the present work, by applying the same approach, we report the identification of six proteins that regulate RBPJ expression via binding to two fSNPs on the RA-associated RBPJ locus. Using these findings, together with the published data, we constructed an RA-associated signal transduction and transcriptional regulation network (STTRN) that functionally connects multiple RA-associated risk genes via transcriptional regulation networks (TRNs) linked by CD40-induced nuclear factor kappa B (NF-kB) signaling. Remarkably, this STTRN provides insight into the potential mechanism of action for the histone deacetylase inhibitor givinostat, an approved therapy for systemic juvenile idiopathic arthritis. Thus, the generation of disease-associated STTRNs based on post-GWAS functional studies is demonstrated as a novel and effective approach to apply GWAS for mechanistic studies and target identification.


Perspectives for the development of human papillomavirus vaccines and immunotherapy.
Human papillomavirus (HPV) is the most common sexually transmitted infection and is responsible for 90-99% of cervical cancer (CxCa) cases. Although effective screening programs have reduced the incidence of CxCa in developed countries, they are often not well organized. Prophylactic vaccination against HPV seems to be a good strategy for the prevention of CxCa. However, because millions of women are already infected with HPV, therapeutic HPV vaccines need to be developed further to treat these women. This review discusses the actual perspectives on both HPV vaccines and immunotherapy worldwide. In addition, some of the perspectives in France are also briefly discussed.


[Value of the injury severity score (ISS)].
The injury severity score (ISS) has been most widely accepted as a practicable method of classifying traumatised patients (ie., patients with accident injuries) according to the severity of their injuries, and has become more popular than all other comparable classification systems. By allocating the patients to different severity groups, it facilitates their classification in respect of prognosis. Over and above this, it enables comparison of patient groups of different hospitals. The authors investigated the validity of ISS classification by studying the case records of 432 patients in a traumatological intensive-care ward. They found good correlation between ISS score on the one hand, and lethality, requirements of banked blood during first-aid care and duration of treatment and artificial respiration of survivors on the other. However, the mean survival time of those patients who had died, did not reveal any connection with the severity of the injury. It is definitely impossible to arrive at any prognosis for an individual patient on the basis of his ISS classification. With increasing age, lethality after an accident increases even if the injury is less severe. The validity of ISS could be increased further if the age of the patients could be taken into account as well.


Hyskon complications in hysteroscopic surgery.
Hyskon (32 per cent dextran 70 in 10 per cent dextrose in water), a useful distension medium for hysteroscopic surgery, has significant side effects. A case of pulmonary edema following transcervical myoma resection is presented. Additional known side effects of Hyskon discussed include coagulation defects, spurious laboratory results, and anaphylaxis. Prevention and management of complications are described.


Autophagic/lysosomal dysfunction in Alzheimer's disease.
Autophagy serves as the sole catabolic mechanism for degrading organelles and protein aggregates. Increasing evidence implicates autophagic dysfunction in Alzheimer's disease (AD) and other neurodegenerative diseases associated with protein misprocessing and accumulation. Under physiologic conditions, the autophagic/lysosomal system efficiently recycles organelles and substrate proteins. However, reduced autophagy function leads to the accumulation of proteins and autophagic and lysosomal vesicles. These vesicles contain toxic lysosomal hydrolases as well as the proper cellular machinery to generate amyloid-beta, the major component of AD plaques. Here, we provide an overview of current research focused on the relevance of autophagic/lysosomal dysfunction in AD pathogenesis as well as potential therapeutic targets aimed at restoring autophagic/lysosomal pathway function.


Wnt affects symmetry and morphogenesis during post-embryonic development in colonial chordates.
Wnt signaling is one of the earliest and most highly conserved regulatory pathways for the establishment of the body axes during regeneration and early development. In regeneration, body axes determination occurs independently of tissue rearrangement and early developmental cues. Modulation of the Wnt signaling in either process has shown to result in unusual body axis phenotypes. Botryllus schlosseri is a colonial ascidian that can regenerate its entire body through asexual budding. This processes leads to an adult body via a stereotypical developmental pathway (called blastogenesis), without proceeding through any embryonic developmental stages. In this study, we describe the role of the canonical Wnt pathway during the early stages of asexual development. We characterized expression of three Wnt ligands (Wnt2B, Wnt5A, and Wnt9A) by in situ hybridization and qRT-PCR. Chemical manipulation of the pathway resulted in atypical budding due to the duplication of the A/P axes, supernumerary budding, and loss of the overall cell apical-basal polarity. Our results suggest that Wnt signaling is used for equivalent developmental processes both during embryogenesis and asexual development in an adult organism, suggesting that patterning mechanisms driving morphogenesis are conserved, independent of embryonic, or regenerative development.


Clinical Profile of Adult Patients Presenting With Renal Dysfunction to a Tertiary Hospital Emergency Department.
Background Renal dysfunction is a potentially life-threatening condition that is commonly encountered in the emergency department (ED). This study aimed to describe the clinical profile of patients presenting with renal dysfunction to a tertiary-level hospital ED. Methods Medical records of patients presenting to the ED with renal dysfunction over a six-month period (July-December 2017) were reviewed. A descriptive analysis of the data was performed. Results Serum creatinine levels were measured in 7,442 (69.9%) of the 10,642 patients that were triaged into the ED. Of these, 208 (2.8%) were identified with renal dysfunction, of which 192 consented to study participation. The median age of study subjects was 49.5 (IQR 38.8-63.0) years; 108 (56.3%) were male; proteinuria on urine dipsticks was demonstrated in 108 (56.3%); 72 (37.5%) were HIV-positive; 66 (39.6%) required dialysis; 11 (5.7%) were admitted to the ICU; and 59 (30.7%) died prior to hospital discharge. More patients presented with acute kidney injury (AKI) (46.9%) compared to chronic kidney disease (CKD) (27.6%) and acute on chronic kidney disease (AoCKD) (25.5%). Sepsis was the most common precipitant of AKI (42.2%) and AoCKD (30.6%), while chronic hypertension (35.8%) and diabetes mellitus (34.0%) were the most common comorbidities in subjects with CKD. Conclusion Patients presenting to the ED with various risk factors and comorbidities, including HIV, sepsis, hypertension, and diabetes mellitus, may have underlying renal dysfunction. ED clinicians should therefore adopt a low threshold to screen for renal dysfunction in these patients.


Validity and Reliability of the Korean Version of the Self-Care of Diabetes Inventory (SCODI-K).
This was a methodological study to evaluate the validity and reliability of the Korean version of the Self-Care of Diabetes Inventory (SCODI-K). A total of 210 patients with type 2 diabetes from a university hospital were enrolled. Content validity, construct validity, and criterion-related validity were evaluated. Cronbach's α was used to assess reliability. The SCODI-K consisted of 40 items in four dimensions (self-care maintenance, self-care monitoring, self-care management, and confidence). Four factors (activity-nutritional behavior, health-adherence behavior, health-promotion behavior, diet-restriction behavior) in the dimension of self-care maintenance, two factors (health status monitoring, symptom recognition) in the dimension of self-care monitoring, three factors (glucose self-control, problem-solving behavior, consultative self-care) in the dimension of self-care management, and one factor (self-care confidence) in the dimension of confidence were extracted. Confirmatory factor analysis supported a good fit with reliable scores for the SCODI-K model (normed chi-square(χ²/df) < 5, root mean square error of approximation (RMSEA) < 0.1, comparative fit index (CFI) ≥ 0.9, goodness-of-fit-index (GFI) ≥ 0.9). The SCODI-K showed a high positive correlation coefficient of 0.75 with the summary of diabetes self-care activities (SDSCA), confirming convergent validity. Cronbach's α was 0.92 for the overall scale and 0.69 to 0.90 for the four dimensions. Therefore, the SCODI-K is a valid and reliable instrument for assessing self-care of patients with type 2 diabetes in Korea.


Mutation detection in the promoter region of survivin gene on N-methyl-N-nitrosourea induced colon tumor model in experiment.
Survivin (also known as BIRC5) is one of the first reported inhibitors of apoptosis proteins (IAPs), which is an important family of proteins that regulate apoptosis. It is developmentally regulated and expressed during cell differentiation in humans, mice and rat. Survivin is expressed in a series of human cancers and it has been widely accepted that survivin is strongly related to the onset and development of cancer. In the present study, we tried to determine differences in the promoter region of survivin gene in colon tissue samples from N-methyl-N-nitrosourea (MNU) induced rat colon tumor model and control group. Polymerase chain reaction (PCR) - single strand conformation polymorphism (SSCP) analysis was used for this aim. No significant differences were found in the promoter region of survivin gene between the normal and tumor tissues (Tab. 2, Fig. 1, Ref. 16).


CSF-responsive bone marrow cells in liquid culture: characterization and screening applications.
In a previous study, colony-stimulating factor (CSF) activity assayed in colony culture correlated closely with 3HTdR uptake by human marrow cells depleted of adherent cells. To use this assay for screening media for CSF and immunotoxins for marrow toxicity, cells growing in liquid culture were compared to conventional granulocyte/macrophage (CFU-gm) colony assays. CSF dose-response relationships for liquid and colony-forming assays were nearly identical. 3HTdR uptake by nonadherent marrow cells was CSF dose-related, and there was a linear relationship between number of cells cultured and 3HTdR uptake. Ricin cytotoxicity curves for liquid cultures and CFU-gm were identical on day 7 but showed some disparity with day 14 cultures. Results with all cultures showed 3HTdR uptake to be most closely correlated with CFU-gm colony, rather than cluster, growth. Myeloid cell differentiation in liquid culture was similar to colony cultures, producing mixtures of granulocytes, macrophages and eosinophils. By combining cell and differential counts, production of various myeloid cells could be quantitated. Cytotoxicity of anti-Ia for CFU-gm and liquid culture cells was compared and the majority of both cell populations expressed Ia-like antigens. Simultaneous staining for surface antigens and DNA content was used to characterize proliferating marrow cells, and the vast majority of cells expressed myeloid markers. Transferrin receptors were displayed by cells in S/G2/M and appeared after CSF stimulation on G0/G1 cells. We conclude liquid cultures can be used to screen conditioned media for human CSF and to screen for cytotoxicity to normal myeloid precursor cells. Behavior of CSF-responsive cells in liquid culture appears most closely related to that of CFU-gm colony-forming cells, and characterization of CSF-stimulated cells allows quantitative as well as qualitative estimates of myeloid cell production.


Detecting positional vertigo using an ensemble of 2D convolutional neural networks.
The aim of the work presented here was to develop a system that can automatically identify attacks of dizziness occurring in patients suffering from positional vertigo, which occurs when sufferers move their head into certain positions. We used our novel medical device, CAVA, to record eye- and head-movement data continually for up to 30 days in patients diagnosed with a disorder called Benign Paroxysmal Positional Vertigo. Building upon our previous work, we describe a novel ensemble of five 2D Convolutional Neural Networks, using composite recognition features, including eye-movement data and three-channel accelerometer data. We achieve an F 1 score of 0.63 across an 11-fold cross-fold validation experiment, demonstrating that the system can detect a few seconds of motion provoked dizziness from within over a 100 h of normal eye-movement data. We show that the system outperforms our previous 1D Neural Network approach, and that our ensemble classifier is superior to each of the individual networks it contains. We also demonstrate that our composite recognition features provide improved performance over results obtained using the individual data sources independently.


[Epidemiology, risk factors and current screening in rectal cancer].
Epidemiology, risk factors and current screening in rectal cancer. Incidence and survival data from the Francim Cancer Registry Network allowed an estimate of the national incidence of rectal cancer and its prognosis up to 20 years after diagnosis.In 2018, 13 744 new cases of rectal cancer were diagnosed in France. Its incidence slightly decreased since 1990. The M/F sex ratio has steadily decreased over time from 2.1 to 1.8. Forty-seven percent of cancers were diagnosed at a local extension stage, 20 % at a regional extension stage and 34 % at an advanced stage. Individuals of both sexes over 50 years of age are at medium risk for rectal cancer.Five-year net survival was 60 % in men and 59 % in women. At 10-year, it was 54 % for individuals aged 50 and 47 % for those aged 70 at time of diagnosis. Excess mortality related to cancer mostly occurred within the first year after diagnosis. It decreased up to 10 years after diagnosis and remained stable.The use of the immunological test for fecal occult bleeding in France is not efficient because of a participation too low, of the order of 30 %, well below the 45 % required to ensure the efficiency of the screening program.


COVID-19 and Fear, Which Comes First?
Today people have a few unanswered questions in their mind, such as "Do negative emotions will co-survive with the COVID-19 pandemic? Which one is worse? Which one will disappear quicker? Is there any connection between negative emotions and being infected by COVID-19 or the severity of infected individuals' symptoms? How are we supposed to live with COVID-19 and adapt our emotional system to the virus for more than one upcoming year?" These uncertainties could result in massive pressure on people. While there is no clear consensus regarding what establishes psychological stress on an individual, the effect of negative affect and psychological stress on increased susceptibility to disease due to altered immune functions is well established. Here we are going through the possible effect of emotions associated with the present pandemic on COVID-19 course of disease and severity of symptoms.


Effects of Probiotics on the Growth Performance, Antioxidant Functions, Immune Responses, and Caecal Microbiota of Broilers Challenged by Lipopolysaccharide.
We aimed to study the effects of dietary Bacillus coagulans (B. coagulans) and Lactobacillus plantarum (L. plantarum) on broilers challenged by Escherichia coli lipopolysaccharide (LPS). One-day-old Cobb 500 chicks (360) were divided randomly into three treatment groups for 47 days: no supplementation (control, CON), B. coagulans supplementation (BC), and L. plantarum supplementation (LA). Broilers were routinely fed for 42 days and intraperitoneally injected with 500 μg LPS per kg body weight at 43, 45, and 47 days of age, respectively. Samples were collected 3 h after the last injection. At 1-21 days of age, the ADG in the BC and LA groups was higher than that in the CON group, and the feed to gain ratio (F/G) in the BC group was significantly decreased (P < 0.05). Compared with that in CON birds, the ADG was increased and the F/G was decreased in the BC and LA birds at 22-42 and 1-42 days of age, respectively (P < 0.05). After LPS stimulation, the endotoxin (ET), diamine oxidase (DAO), and D-lactic acid (D-LA) levels in the BC group were lower than those in the CON group (P < 0.05). The IgY, IgA, and IgM contents in the BC group and the IgY and IgM contents in the LA group were higher than those in the CON group (P < 0.05). The pro-inflammatory factor and interferon-β (IFN-β) contents (P < 0.05) decreased, and the anti-inflammatory factor content in the serum (P < 0.05) increased in the BC and LA groups. Compared with the CON and LA treatments, the BC treatment increased the concentrations of glutathione peroxidase (GSH-Px), superoxide dismutase (SOD), and catalase (CAT), and decreased that of malondialdehyde (MDA) (P < 0.05). In contrast with the CON treatment, the BC and LA treatments increased the abundance of Ruminococcaceae and reduced that of Desulfovibrio (P < 0.05). Moreover, BC increased the abundance of beneficial bacteria. Overall, supplementation with B. coagulans and L. plantarum promoted the growth of broilers, improved their immunity and antioxidant capacity, and alleviated the LPS-stimulated inflammatory response by regulating the intestinal flora.


Bioactive electroconductive hydrogels: the effects of electropolymerization charge density on the storage stability of an enzyme-based biosensor.
Electrode-supported hydrogels were conferred with the biospecificity of enzymes during the process of electropolymerization to give rise to a class of bioactive, stimuli-responsive co-joined interpenetrating networks of inherently conductive polymers and highly hydrated hydrogels. Glucose responsive biotransducers were prepared by potentiostatic electropolymerization [750 mV vs. Ag/AgCl (3 M KCl)] of pyrrole at Poly(hydoxyethyl methacrylate)-based hydrogel-coated Pt micro-electrodes (Φ = 100 μm) from aqueous solutions of pyrrole and glucose oxidase (GOx; 0.4 M pyrrole, 1.0 mg/ml GOx) to 1.0 and 10.0 mC/cm². Polypyrrole was them over-oxidized by cyclic voltammetry (0-1.2 V vs. Ag/AgCl, 40 cycles in PBKCl, pH = 7.0). Biotransducers were stored at 4 °C in PBKCl for up to 18 days. Amperometric dose-response at 0.4 V vs. Ag/AgCl followed by Lineweaver-Burk analysis produced enzyme kinetic parameters as a function of electropolymerization charge density and storage time. Apparent Michaelis constant (K (Mapp)) increased from 18.6-152.0 mM (1.0 mC/cm²) and from 2.7-6.1 mM (10.0 mC/cm²). Biotransducer sensitivity increased to 21.2 nA/mM after 18 days and to 12.8 pA/mM after 10 days for the 1.0 and 10.0 mC/cm² membranes, respectively. Maximum current, I (max), also increased over time to 2.7 nA (1.0 mC/cm²) and to 170 pA (10.0 mC/cm²). Electropolymerization of polypyrrole is shown to be an effective means for imparting bioactivity to a hydrogel-coated microelectrode. GOx was shown to be stabilized and to increase activity over time within the electroconductive hydrogel.


Targeting endoplasmic reticulum stress in liver disease.
The accumulation of unfolded protein in the endoplasmic reticulum (ER) initiates an unfolded protein response (UPR) via three signal transduction cascades, which involve protein kinase RNA-like ER kinase (PERK), inositol requiring enzyme-1α (IRE1α) and activating transcription factor-6α (ATF6α). An ER stress response is observed in nearly all physiologies related to acute and chronic liver disease and therapeutic targeting of the mechanisms implicated in UPR signaling have attracted considerable attention. This review focuses on the correlation between ER stress and liver disease and the possible targets which may drive the potential for novel therapeutic intervention. Expert Commentary: We describe pathways which are involved in UPR signaling and their potential correlation with various liver diseases and underlying mechanisms which may present opportunities for novel therapeutic strategies are discussed.


Response of an Obstetric Unit during the Coronavirus Disease of 2019 (COVID-19) Pandemic: Experiences from a Tertiary Care Center.
Objective To describe our experiences in preparing our obstetric unit in Westchester County, New York, during the COVID-19 (coronavirus disease of 2019) pandemic. We focus on describing our timeline, continuously evolving actions, observations, and challenges. Methods With guidance from the New York State Department of Health (NYSDOH), our institutional epidemiologist, and key multidisciplinary faculty members, we evaluated emerging national data as well as expert opinions to identify issues and challenges to create action plans. Results We created and modified policies for our patients presenting for obstetrical care on the labor and delivery unit to accommodate their unique needs during this pandemic. Conclusion The COVID-19 pandemic has posed many unique challenges. Balancing communication, risks of infection to providers, patient autonomy and rights, and resources for testing and personal protective equipment were among the valuable lessons learnt. We have shared our experiences and described our observations and challenges in Westchester County, New York.


Synthesis, structure, and luminescent property of a heterometallic metal-organic framework constructed from rod-shaped secondary building blocks.
A new heterometallic MOF compound, [ZnNa(m-BDC)2].NH2(CH3)2 (MOF-CJ2), has been solvothermally synthesized and characterized by single-crystal X-ray diffraction, X-ray powder diffraction, ICP, TGA, IR, and photoluminescence spectroscopy analyses. It crystallizes in monoclinic space group C2/c (No. 15) with a=13.277(6) A, b=14.323(7) A, c=11.328(6) A, and beta=111.73(2) degrees. Its framework is constructed from M-O-C (M=Na and Zn) rods composed of alternating six-coordinated Na(I) centers and four-coordinated Zn(II) centers. These rods are linked by m-BDC links to form primitive cubic (pcu) type rod packing. This framework exemplifies the first open-framework heterometallic MOF structure based on the assembly of infinite rod building units.


A large-scale categorization of sites in San Francisco Bay, USA, based on the sediment quality triad, toxicity identification evaluations, and gradient studies.
Sediment quality was assessed in San Francisco Bay, California, USA, using a two-tiered approach in which 111 sites were initially screened for sediment toxicity. Sites exhibiting toxicity were then resampled and analyzed for chemical contamination, recurrent toxicity, and, in some cases, benthic community impacts. Resulting data were compared with newly derived threshold values for each of the metrics in a triad-based weight-of-evidence evaluation. Sediment toxicity test results were compared with tolerance limits derived from reference site data, benthic community data were compared with threshold values for a relative benthic index based on the presence and abundance of pollution-tolerant and -sensitive taxa, and concentrations of chemicals and chemical mixtures were compared with sediment quality guideline-based thresholds. A total of 57 sites exceeded threshold values for at least one metric, and each site was categorized based on triad inferences. Nine sites were found to exhibit recurrent sediment toxicity associated with elevated contaminant concentrations, conditions that met program criteria for regulatory attention. Benthic community impacts were also observed at three of these sites, providing triad evidence of pollution-induced degradation. Multi- and univariate correlations indicated that chemical mixtures, heavy metals, chlordanes, and other organic compounds were associated with measured biological impacts in the Bay. Toxicity identification evaluations indicated that metals were responsible for pore-water toxicity to sea urchin larvae at two sites. Gradient studies indicated that the toxicity tests and benthic community metrics employed in the study predictably tracked concentrations of chemical mixtures in Bay sediments.


Classification of familiarity based on cross-correlation features between EEG and music.
An approach to recognize the familiarity of a listener with music using both the electroencephalogram (EEG) signals and the music signal is proposed in this paper. Eight participants listened to melodies produced by piano sounds as simple natural stimuli. We classified the familiarity of each participant using cross-correlation values between EEG and the envelope of the music signal as features of the support vector machine (SVM) or neural network used. Here, we report that the maximum classification accuracy was 100% obtained by the SVM. These results suggest that the familiarity of music can be classified by cross-correlation values. The proposed approach can be used to recognize high-level brain states such as familiarity, preference, and emotion.


The influence of caffeine on voluntary muscle activation.
Caffeine is a very common CNS stimulant that has been of interest to physiologists because of its direct effects on skeletal muscle in vitro, as well as ergogenic effects on laboratory tests of human performance. While in vitro studies have clearly demonstrated the effects of the drug on the CNS, the effects of caffeine on the voluntary activation of muscle in humans are less defined. Voluntary as well as involuntary supraspinal input, alpha motor neuron membrane properties, and afferent feedback to spinal and supraspinal neurons all modulate voluntary muscle activation, and caffeine may therefore alter muscle activation at several sites along the motor pathway. This review explores the effects of caffeine on voluntary muscle activation that have been demonstrated in recent human studies and discusses the central mechanisms that may enhance activation. Evidence of caffeine's effects on the motor evoked potential, Hoffman reflex, self-sustained firing of the alpha motor neuron, and pain and force sensation are presented as well as limitations and considerations of using the drug in human neuromuscular studies.


The Effects of Intranasal Oxytocin Administration on Sensitive Caregiving in Mothers with Postnatal Depression.
Postnatal depression (PND) is common and negatively affects the mother-infant relationship; oxytocin (OT) has been found to have positive effects on parenting, although psychiatric disorders may reduce these effects. Thus, we explored the role of OT in mothers diagnosed with PND. A within-subject, randomized controlled double-blind design was used to test the effects of nasal administration of OT or placebo on sensitive caregiving. The outcome measures were perceptual and caregiving responses to prerecorded cry sounds, as well as observed maternal sensitivity. We found that in the OT condition mothers with PND were more likely to rate an infant cry as more urgent and they were more likely to indicate they would chose a harsh caregiving strategy in response. There was no effect of OT on maternal sensitive interaction with their own baby. Further research is required prior to consideration of OT administration in depressed mothers of infants.


Use of random systematic mutagenesis to generate viable human rhinovirus 14 chimeras displaying human immunodeficiency virus type 1 V3 loop sequences.
Random systematic mutagenesis was used to generate a library of human rhinovirus 14 chimeras that each display a segment from the V3 loop of human immunodeficiency virus type 1. The sequence XXIGPGRAXX, where X could be any of the 20 amino acids, was inserted at the neutralizing immunogenic site II of human rhinovirus 14 between VP2 residues 159 and 160. Twenty-five unique chimeric viruses were isolated, and the identity of their randomized residues was determined. A nonrandom amino acid distribution that may reflect structural requirements for viability was observed at the randomized positions. Fifteen of 25 chimeras were neutralized by one or more of a panel of four anti-human immunodeficiency virus type 1 V3 loop antibody preparations, indicating that antigenicity had been successfully transplanted. Libraries of chimeric viruses produced by using the techniques described may be a source of vaccines and other immunotherapeutic reagents. The random systematic mutagenesis methodology described should be generally useful for the rapid transplantation of foreign sequences into viral coat and other proteins to produce libraries containing members with the desired properties.


Horses for Courses in the Era of CARs: Advancing CAR T and CAR NK Cell Therapies.
The adoptive transfer of allogeneic CAR NK cells holds great promise as an anticancer modality due to the relative ease of manufacturing and genetic modification of NK cells, which translates into affordable pricing. Compared to the pronounced efficacy of CAR T cell therapy in the treatment of B cell malignancies, rigorous clinical and preclinical assessment of the antitumor properties of CAR NK cells has been lagging behind. In this brief review, we summarize the biological features of NK cells that may help define the therapeutic niche of CAR NK cells as well as create more potent NK cell-based anticancer products. In addition, we compare T cells and NK cells as the carriers of CARs using the data of single-cell transcriptomic analysis.


Watch and Wait Strategy for Rectal Cancer: How Long Should We Wait for a Clinical Complete Response?
The objective of this study was to determine how long to wait in locally advanced rectal tumor (LARC) patients who receive total neoadjuvant therapy (TNT) and achieve a clinical complete response (cCR), and to identify the clinical parameters that affect the waiting period for the watch-and-wait strategy (W &W). The data of patients who achieved cCR between February 2015 and June 2020 were examined retrospectively. The week in which patients with cCR at the end of TNT achieved clearance was determined by reanalyzing recorded endoscopy video images. In the assessment at the time of the initial diagnosis, tumor characteristics, such as digital rectal examination findings, MRI stage, location with respect to the puborectalis muscle, annularity, and tumor size, were recorded prospectively. A total of 54 patients were included in this study. According to the MRI-T stage, 14 cases were cT3a, 22 were cT3b, and 18 were cT3c-T4. Forty-four percent of the cases achieved cCR at 8-10 weeks, 19% at 12-16 weeks, 20% at 16-22 weeks, and 17% at 20-26 weeks. Patients with tumors that were early MRI-T stage (cT3a), negative clinical circumferential resection margin, mobile, small (≤4 cm), located above the puborectalis muscle and showed <180 degrees annularity achieved cCR significantly earlier than those with other tumors (p<0.05). In this study, cCR was achieved in less than half (44%) of the cases during the 8-10 week waiting period. In the W&W strategy, the initial assessment for cCR seems insufficient, and we may need to wait up to 26-30 weeks, especially in patients with advanced-stage tumors.


Cytogenetic analysis of the 18S, 5S rDNA and B chromosome of Iheringichthys labrosus (Lütken, 1874) (Siluriformes, Pimelodidae).
Cytogenetic analyses of the location of 18S and 5S ribosomal DNAs, and the base composition of B chromosomes of Iheringichthys labrosus from Tibagi River, Paraná, Brazil, are provided. AgNORs were observed in the terminal position on the long arm of a subtelocentric chromosome pair. CMA3-positive staining was observed in some chromosomes, which besides being associated with NORs, were all DAPI-negative. Chromosome B showed a strong fluorescence with CMA3. The concomitant use of 18S and 5S rDNA probes using the FISH technique revealed 18S ribosomal cistrons in a pair of subtelocentric chromosomes, on the long arm in the terminal position, coinciding with the AgNOR. The 5S sites were found in another subtelocentric pair, on the long arm in the interstitial region, near the centromere. The findings of the present study suggest that, although there are some more conserved cytogenetic characteristics, populations of I. labrosus may show their own characteristics.


Flow-cytometric study of granulocyte activation during hemodialysis with different membranes.
Flow cytometry allows an easy quantitation of reactive oxygen intermediate production and of C3bi receptor expression by granulocytes, thus providing a clinical tool to evaluate the hemodialysis-related granulocyte activation. In this flowcytometric study, we analyzed the effects of cellulosic, synthetic polyacrylonitrile, and ethylene-vinyl-alcohol dialyzers on granulocyte membrane and function. Our results confirmed the data reported in the literature on granulocyte activation secondary to cellulosic membranes and the better biocompatibility of synthetic dialyzers that did not increase C3bi receptor expression and reactive oxygen intermediate generation by granulocytes. The flow-cytometric analysis of granulocyte activation might be the method of choice to identify the best patient/membrane interaction in every single patient.


Diagnosis and phenotypic assessment of trimethylaminuria, and its treatment with riboflavin: 1H NMR spectroscopy and genetic testing.
Trimethylaminuria (TMAU) is a metabolic disorder characterized by the excessive excretion of the malodorous compound trimethylamine (TMA). The diagnosis of TMAU is challenging because this disorder is situated at the boundary between biochemistry and psychiatry. Here, we used nuclear magnetic resonance spectroscopy to assess TMAU in 13 patients. We also sequenced the FMO3 gene in 11 of these patients. Treatment with vitamin B2 was prescribed. Two patients (aged 3 and 9 years at the initial consultation) had a particularly unpleasant body odor, as assessed by their parents and the attending physicians. The presence of high urine TMA levels confirmed the presence of a metabolic disorder. The two (unrelated) children carried compound heterozygous variants in the FMO3 gene. In both cases, vitamin B2 administration decreased TMA excretion and reduced body odor. The 11 adults complained of an unpleasant body odor, but the physicians did not confirm this. In all adult patients, the urine TMA level was within the normal range reported for control (non-affected) subjects, although two of the patients displayed an abnormally high proportion of oxidized TMA. Seven of the 9 tested adult patients had a hypomorphic variant of the FMO3 gene; the variant was found in the homozygous state, in the heterozygous state or combined with another hypomorphic variant. All 11 adults presented a particular psychological or psychiatric phenotype, with a subjective perception of unpleasant odor. The results present the clinical and biochemical data of patients complaining of unpleasant body odor. Contrary to adult patients, the two children exhibited all criteria of recessively inherited trimethylaminuria, suspected by parents in infancy. B2 vitamin treatment dramatically improved the unpleasant body odor and the ratio of TMA/Cr vs TMAO/Cr in the urine in the children. Other patients presented a particular psychological or psychiatric phenotype.


Archaea, from obscurity to superhero microbes: 40 years of surprises and critical biological insights.
This issue of Emerging Topics in the Life Sciences highlights current areas of research in the field of archaeal biology and the following introductory editorial sets the stage by considering some of the key developments over the last four decades since the initial identification of the archaea as a unique form of life. Emerging topics from this vibrant and rapidly expanding field of research are considered and detailed further in the articles within this issue.


Application Effect of Whole-Process Seamless Nursing Model Based on Smart Healthcare Mode in Perioperative Period of Patients Undergoing Hematoma Removal.
To explore the application effect of a whole-process seamless nursing model based on the smart healthcare mode in the perioperative period of patients undergoing hematoma removal. In this retrospective study, 50 patients with hematoma removal admitted to our hospital from August 2018 to August 2019 were included as the control group (CG), while 50 patients with hematoma removal admitted to our hospital from September 2019 to September 2020 were included as the experimental group (EG). During the period of hematoma removal, CG received routine perioperative nursing, while EG received the whole-process seamless nursing model based on the smart healthcare mode. The perioperative indexes, hemodynamic indexes, and the incidence of postoperative complications were compared between the two groups, and the incidence of nursing staff's work omissions in different periods was analyzed. Notable differences were observed in surgical time, intraoperative blood loss, hematoma clearance rates, length of ICU stay, hospitalization time, removal time of ventricular drainage tube, and cerebral edema volume at 1 week after surgery between EG and CG (P < 0.05). Compared with CG, EG achieved obviously better hemodynamic indexes (P < 0.001) and a lower incidence of bedsore, muscle atrophy, and eating/swallowing disorders (P < 0.05). During the implementation of smart healthcare, the incidence of nursing staff's work omissions was remarkably reduced (P < 0.05). Under the smart healthcare, the incidence of nursing staff's work omissions is lower, and the effect of the whole-process seamless nursing is better, which can optimize the perioperative indexes of patients, stabilize the postoperative hemodynamics, and reduce the incidence of complications. Therefore, the whole-process seamless nursing model based on the smart healthcare mode has promotion value in clinic.


Cost-Effectiveness of Tucatinib in Human Epidermal Growth Factor Receptor 2-Positive Metastatic Breast Cancer From the US and Chinese Perspectives.
Background: The clinical evaluation of HER2CLIMB trial showed a 21. 9-month median overall survival with the triplet regimens of tucatinib, capecitabine, and trastuzumab (TXT) for patients with human epidermal growth factor receptor 2 (HER2) -overexpressing metastatic breast cancer. From the payer's perspective of the United States and China, a cost-effectiveness analysis was conducted to evaluate the costs and benefits of adding tucatinib in this study. Methods: We constructed a Markov model for the economic evaluation of adding tucatinib to trastuzumab plus capecitabine in patients with HER-2 positive metastatic breast cancer in the United States and China. The model was conducted with a 10-year time horizon, and the health status was divided into three states: progression-free survival, progressing disease, and death. The health utility scores were consistent with published literature with similar patient status. The transition probabilities were derived from the survival data of the HER2CLIMB study. The unit prices of medicines were obtained from the West China Hospital, Red Book, and published literature. Outcomes were measured in quality-adjusted life-years (QALYs), and incremental cost-effectiveness ratio, which robustness was evaluated by deterministic and probabilistic sensitivity analyses. Results: Compared with the two-drug regimen of trastuzumab plus capecitabine (TX), the addition of tucatinib increased 0.21 QALY, with an increasing cost of $146,995.05 and $19,022.97 in the United States and China, respectively. The incremental cost-effectiveness ratios (ICERs) for the TXT versus TX was $699,976.43 in the U.S. and $90,585.57 in China, both of which are higher than their respective threshold of willingness to play. Deterministic sensitivity analysis shows that the price of tucatinib is the parameter that has the most significant impact on ICERs, but it does not change the results of the model. Probability sensitivity analysis shows that the probability of cost-effective for TXT is 0 in the base case. Conclusion: In the United States and China, tucatinib combined with trastuzumab and capecitabine is not cost-effective for patients with HER-2 positive metastatic breast cancer.


Cost analysis in a population based screening programme for colorectal cancer: comparison of immunochemical and guaiac faecal occult blood testing.
To compare the costs of colorectal cancer (CRC) screening by two faecal occult blood tests (FOBT)-namely, Hemoccult (guaiac based) and reversed passive haemagglutination (RPHA) tests. RPHA was interpreted according to two positivity thresholds (+ or +/-). Attenders performed both tests. Subjects with a positive FOBT test were invited to have a complete exploration of the colon. The total costs for every 10,000 screened subjects and costs for each unit of result (screened subject, or patient with adenoma/s or cancer detected) were calculated for both tests. 8353 subjects were enrolled. A total of 2109 repeated screening after two years. RPHA(+ and +/-) showed the highest and RPHA(+) the lowest positivity rate at first screening. The Hemoccult positivity rate was highest at repeat screening. Total costs of screening by RPHA(+ and +/-) were highest as this method had the highest recall rate. Screening by RPHA(+) was the least costly. Costs for each screened subject were highest for RPHA(+ and +/-) and lowest for RPHA(+). Costs for each cancer detected were lowest for RPHA(+) and highest for Hemoccult or RPHA(+ and +/-) in subjects aged > 49 or < 50, respectively. Costs for subjects with detected adenoma/s of > 9 mm were lowest for RPHA(+ and +/-) and highest for Hemoccult. At repeat screening total costs of RPHA(+ and +/-) were lower than at first screening, whereas for each subject with cancer or adenoma/s costs were increased. Our data confirm that screening by RPHA is more cost effective than by Hemoccult.


Arcanobacterium pyogenes septicemia in a southern pudu (Pudu puda) following uterine prolapse.
A 14-year-old female pudu (Pudu puda) developed a uterine prolapse after unassisted parturition. The length of time between the prolapse and replacement of the organ was not known but was less than 24 hr. When the prolapse was first noticed, uterine tissue appeared undamaged and was immediately cleaned with antiseptic solution, handled carefully during replacement, and prophylactic antibiotic and anti-inflammatory drugs were given. The pudu appeared clinically normal until 4 days postpartum, when she developed clinical signs of tenesmus, dysuria, and a purulent discharge from the vulva. Despite further treatment, the animal was found dead 10 days postpartum, even though it had not shown any other signs of systemic illness. Gross and histologic lesions supported a diagnosis of septicemia secondary to metritis. Arcanobacterium pyogenes was isolated from lung, liver, and uterine exudate.


Profile of early occurring spontaneous tumors in Han Wistar rats.
It is sometimes difficult to assess the relevance of tumors that occur in treated animals in short-term studies. This report is intended to establish a general profile of tumor occurrence in young Han Wistar rats. Data were collected and evaluated from 29 rat carcinogenicity studies and from a few 2-, 4-, 13-, and 26-week studies conducted between 1995 and 2009 at Huntingdon Life Sciences, UK. The route of administration was dietary, oral gavage, or inhalation, and the analysis was confined to sporadic deaths (decedents) in carcinogenicity studies. In Han Wistar rats, the most common and earliest occurring tumor was malignant lymphoma in both sexes, the earliest being seen in the 16th and 26th week in males and females, respectively. The incidence of malignant lymphoma was slightly higher in males than in females. The second most common type of tumor was brain tumors in males and mammary tumors in females. Compared with Sprague-Dawley rats, where the most common early tumor was pituitary tumor in females, the most common early tumor in Han Wistar rats was malignant lymphoma in both sexes. These early tumor profiles are consistent with the lifetime tumor occurrence in these strains.


Implementation of reperfusion therapy in acute myocardial infarction. A policy statement from the European Society of Cardiology.
Reperfusion therapy in ST-segment elevation myocardial infarction (STEMI) is the most important component of treatment, as it strongly influences short- and long-term patient outcome. The main objective of healthcare providers should be to achieve at least 75% of reperfusion therapy applied to patients suffering from STEMI in a timely manner, and preferably within the first 3 h after onset of symptoms. Establishing networks of reperfusion at regional and national level, implying close collaboration between all the actors involved in reperfusion therapy, namely hospitals, departments of cardiology, PCI centres, emergency medical systems (EMS), (para)medically staffed ambulances, private cardiologists, primary care physicians, etc., is a key issue. All forms of reperfusion, depending on local facilities, need to be available to patients. Protocols must be written and agreed for the strategy of reperfusion to be applied within a network. Early diagnosis of STEMI is essential and is best achieved by rapid ECG recording and interpretation at first medical contact, wherever this contact takes place (hospital or ambulance). Tele-transmission of ECG for immediate interpretation by experienced cardiologists is an alternative. Primary PCI is the preferred reperfusion option if it can be performed by experienced staff within 90 min after first medical contact. Thrombolytic treatment, administered if possible in the pre-hospital setting, is a valid option if PCI cannot be performed in a timely manner, particularly within the first 3 h following onset of symptoms. Thrombolysis is not the end of the reperfusion therapy. Rescue PCI must be performed in the case of thrombolysis failure. Next-day PCI after successful thrombolysis has been proven efficacious. Quality control is important for monitoring the efficacy of networks of reperfusion. All elements that influence time to reperfusion must be taken into account, particularly transfer delays, in-hospital delays, and door-to-balloon or door-to-needle times. The rate of reperfusion achieved must also be taken into consideration. Professional organizations such as the European Society of Cardiology (ESC) have the responsibility to impart this message to the cardiology community, and inform politicians and health authorities about the best possible strategy to achieve reperfusion therapy.


[Case control study on risk factors of congenital microtia].
To identify the risk factors associated with congenital microtia. A case-control, retrospective study was performed. A total of 207 cases of congenital microtia and 209 age-frequently-matched controls were interviewed individually according to the uniform questionnaire. The questionnaire included: (1) Essential information about patients and their parents. (2) First trimester diseases and medication of mother. (3) Past gestation history of mother. (4) Family history and life style of the parent. The available data were analyzed by chi-square test and multivariate Logistic regression model. The factors, such as gender (OR = 5.893), first trimester disease of mother (OR = 34.49) and medication (OR = 4.299), excessive drinking and smoking of father (OR = 4. 347, OR = 4.304), non-primiparous parity (OR = 9.524), abortion (spontaneous and induced, OR = 1.723), low-education of mother (OR = 2.275) were risk factors contributing to microtia in multivariate study. The factors, such as tea (OR = 0.179) were protective factors in multivariate study. Multi-risks factors are contributing to microtia. Preventive measures according to risk factors should be put forward.


The use of indwelling pleural catheters for the management of malignant pleural effusion--direct costs in a Dutch hospital.
Indwelling pleural catheters (IPCs) are increasingly used in the treatment of malignant pleural effusion (MPE). In general, these catheters have been reported to manage MPE efficiently. Unfortunately, insurance companies in the Netherlands do not reimburse these catheters in either first-line treatment or following failed talc pleurodesis. Investigation of direct costs of IPC placement. Retrospective analysis of a prospectively collected database. Direct costs for both catheters and vacuum bottles were calculated. Indicators for indirect costs such as adverse events and complications and the need for additional home care for drainage were registered. Mean costs for IPC amounted to EUR 2,173 and were different between tumor types - mesothelioma: EUR 4,028, breast: EUR 2,204, lung: EUR 1,146 and other: EUR 1,841; p = 0.017. Four patients were admitted to hospital for treatment of complications. Mean costs for IPC placement was similar when inserted as frontline treatment and after failed pleurodesis. Approximately 75% of patients did not need any help from specialized home care. Direct costs for IPC placement turn out to be acceptable when compared with estimated hospitalization costs for pleurodesis treatment. Randomized controlled trials have to be performed to compare the cost-effectiveness of IPCs compared to pleurodesis.


[CA 125 expression in cervical and vaginal secretions in women in normal reproductive period].
To investigate the tumor-associated antigen CA125 expression in the serum and cervical and vaginal secretions in women during normal reproductive period, and explore the clinical value of detecting tumor markers in the cervical and vaginal secretions. A total of 145 women in reproductive period were divided into 3 age groups (20-29 years, 30-39 years, and over 40 years), and their CA125 levels in cervical secretion, vaginal secretion and serum were detected by automatic electro-chemiluminescent immunoassay. CA125 levels in the cervical secretion, vaginal secretion and serum showed no significant difference between the 3 age groups (P>0.05). In each group, CA125 levels differed significantly between the cervical secretion, vaginal secretion and serum (P<0.001). In the 145 women, the average CA125 level was 497.82 - or + 75.29 U/ml in the cervical secretion, 114.66 - or + 26.40 U/ml in vaginal secretion and 18.06 - or + 3.35 U/ml in serum, showing significant differences between them (P<0.001). CA125 expression level is significantly higher in the cervical and vaginal secretions than in the serum in women in normal reproductive period, and its levels in cervical and vaginal secretions can be more sensitive and convenient for early detection of related diseases.


Landauer-type transport theory for interacting quantum wires: application to carbon nanotube y junctions.
We propose a Landauerlike theory for nonlinear transport in networks of one-dimensional interacting quantum wires (Luttinger liquids). A concrete example of current experimental focus is given by carbon nanotube Y junctions. Our theory has three basic ingredients that allow one to explicitly solve this transport problem: (i) radiative boundary conditions to describe the coupling to external leads, (ii) the Kirchhoff node rule describing charge conservation, and (iii) density matching conditions at every node.


Screening a wide host-range, waste-water metagenomic library in tryptophan auxotrophs of Rhizobium leguminosarum and of Escherichia coli reveals different classes of cloned trp genes.
A metagenomic cosmid library was constructed, in which the insert DNA was derived from bacteria in a waste-water treatment plant and the vector was the wide host-range cosmid pLAFR3. The library was screened for clones that could correct defined tryptophan auxotrophs of the alpha-proteobacterium Rhizobium leguminosarum and of Escherichia coli. A total of 26 different cosmids that corrected at least one trp mutant in one or both of these species were obtained. Several cosmids corrected the auxotrophy of one or more R. leguminosarum trp mutants, but not the corresponding mutants in E. coli. Conversely, one cosmid corrected trpA, B, C, D and E mutants of E. coli but none of the trp mutants of R. leguminosarum. Two of the Trp+ cosmids were examined in more detail. One contained a trp operon that resembled that of the pathogen Chlamydophila caviae, containing the unusual kynU gene, which specifies kynureninase. The other, whose trp genes functioned in R. leguminosarum but not in E. coli, contained trpDCFBA in an operon that is likely co-transcribed with five other genes, most of which had no known link with tryptophan synthesis. The sequences of these TRP proteins, and the products of nine other genes encoded by this cosmid, failed to affiliate them with any known bacterial lineage. For one metagenomic cosmid, lac reporter fusions confirmed that its cloned trp genes were transcribed in R. leguminosarum, but not in E. coli. Thus, rhizobia, with their many sigma-factors, may be well-suited hosts for metagenomic libraries, cloned in wide host-range vectors.


Perfused murine heart optical transmission spectroscopy using optical catheter and integrating sphere: Effects of ischemia/reperfusion.
Tissue transmission optical absorption spectroscopy provides dynamic information on metabolism and function. Murine genetic malleability makes it a major model for heart research. The diminutive size of the mouse heart makes optical transmission studies challenging. Using a perfused murine heart center mounted in an integrating sphere for light collection with a ventricular cavity optical catheter as an internal light source provided an effective method of optical data collection in this model. This approach provided high signal to noise optical spectra which when fit with model spectra provided information on tissue oxygenation and redox state. This technique was applied to the study of cardiac ischemia and ischemia reperfusion which generates extreme heart motion, especially during the ischemic contracture. The integrating sphere reduced motion artifacts associated with a fixed optical pickup and methods were developed to compensate for changes in tissue thickness. During ischemia, rapid decreases in myoglobin oxygenation occurred along with increases in cytochrome reduction levels. Surprisingly, when ischemic contracture occurred, myoglobin remained fully deoxygenated, while the cytochromes became more reduced consistent with a further, and critical, reduction of mitochondrial oxygen tension during ischemic contraction. This optical arrangement is an effective method of monitoring murine heart metabolism.


[Efficacy of magnetolaser therapy of patients with an inflammatory form of chronic abacterial prostatitis].
To assess efficacy of magnetolaser therapy (KAP-ELM-01 Andro-Gin unit) in the treatment of inflammatory chronic abacterial prostatitis (ICAP), 68 ICAP patients were divided into 2 groups. Group 1 patients (n = 33) received standard therapy. Group 2 patients received standard therapy plus magnetolaser (ML) therapy. The effect was assessed by the symptoms scale and indices of kallirrein-kinin system. After treatment pain relieved by 36,9%, on the average, in group 1 and by 63.1% in group 2. Lower urinary tract symptoms regressed insignificantly in both groups: by 4.8% and 7.1%, respectively. Quality of life improved by 27.6 and 65.5%, respectively. Kallikrein activity in prostatic secretion remained high in both groups. A 21.7% rise (p < 0.05) of prokallikrein level was seen after treatment only in group 2. Activity of KKS inhibitors (alpha2-MG and alphal-PI) in prostatic secretion normalized in group 2. Total activity of serin proteinases lowered in both groups (p < 0.05). High activity of alphal-PI (8.21 + 1.97 U/ml) persisted in group 1. Thus, standard treatment of ICAP does not result in biochemical normalization of prostatic secretion. ML therapy is more effective.


[Study of mixed dry binders in directly compressible lactoses and microcrystalline cellulose].
The paper evaluated the compressibility of dry binders prepared in the ratios of 3:1, 1:1, and 1:3 from Pharmatosa DCL 15 and DCL 21 and Avicel PH 200, and the sensitivity of the mixtures to an addition of the lubricant magnesium stearate from the standpoint of the effect on the strength of tablets. Mixtures of lactoses with Avicel PH -200 in a ratio of 3:1 proved to be most advantageous. The strengths of tablets made of these mixtures oscillated in the optimal range and they showed the least sensitivity to the added lubricant. An increase in stearate concentration did not result in a marked decrease in the strength of compacts. Pharmatosa DCL 21 in a mixture with Avicel PH 200 yielded stronger compacts at lower compression force than Pharmatosa DCL 15.


Use of a rapid, sensitive immunoradiometric assay for thyrotropin to distinguish normal from hyperthyroid subjects.
Using a new three-site immunoradiometric assay for thyrotropin (TSH), we measured concentration of this hormone in the serum of 47 patients with hyperthyroidism and 46 controls. The mean and range of serum TSH concentration was significantly lower in thyrotoxic than in control subjects, and it was possible to correctly identify 96% of thyrotoxic patients on the basis of a serum TSH concentration less than 0.5 milli-int. unit/L. We conclude that such measurement is highly sensitive for distinguishing hyperthyroid from normal subjects, and that the lower limit of normal for TSH in serum is about 0.5 milli-int. unit/L.


A tandem of alpha-tubulin genes preferentially expressed in radicular tissues from Zea mays.
The identification of a cDNA (MR19) corresponding to a maize alpha-tubulin and homologous genomic clones (MG19/6 and MG19/14) is described. The cDNA has been isolated by differential screening of a cDNA maize root library. We have found two alpha-tubulin genes in a tandem arrangement in the genomic clones, separated by approximately 1.5 kbp. One of the genes (gene I) contains an identical nucleotide sequence which corresponds to the cDNA clone. The two deduced proteins from DNA sequences are very similar (only two conservative replacements in 451 amino acids) and they share a high homology as compared with the published alpha-tubulin sequences from other systems and in particular with the Arabidopsis thaliana and Chlamydomonas reinhardtii sequences reported. The structure of both genes is also very similar; it includes two introns, of 1.7 kbp and 0.8 kbp respectively, in each gene and only one intron placed at a homologous position in relation to Arabidopsis thaliana genes. By using specific 3' probes it appears that both genes are preferentially expressed in the radicular system of the plant. The alpha-tubulin gene family of Zea mays seems to be represented by at least 3 or 4 members.


Biomechanical evaluation of braces used for the treatment of epicondylitis.
The purpose of the study was to investigate the biomechanical effects of different types of braces that are used in the treatment of patients with epicondylitis radialis. Vibration and acceleration of the forearm and the elbow were measured with sensors taped to defined anatomic points on the skin surface. The impact-induced vibration of the racket-arm system was analyzed while the subjects were playing tennis. Different designed brace systems were investigated with respect to acceleration amplitudes and acceleration integrals. Clasp-based brace systems showed a slight reduction of acceleration amplitudes (-6%) and acceleration integrals (-8%). Braces with pads at the lateral epicondyle reduced acceleration amplitudes by 20% and acceleration integrals by 22%. Braces with pads placed at the forearm showed the highest reduction of acceleration amplitudes (-46%) and acceleration integrals (-42%). Overload of the wrist extensors, which is considered to be a major pathogenic factor in lateral epicondylitis, can be reduced by braces. There is a significant difference in the effects among different biomechanical principles of braces.


Synthesis of Suberin during Wound-healing in Jade Leaves, Tomato Fruit, and Bean Pods.
The structure and composition of the aliphatic monomers of the polymeric material deposited during wound-healing of tomato fruit, bean pods, and Jade leaves were examined. After removing the cuticle-containing layer of tissue, the wounds were healed for 14 days and the resulting surface layer was excised, lyophilized, solvent-extracted, and depolymerized by hydrogenolysis with LiAlH(4) or transesterified with BF(3) in methanol. The products obtained by the chemical depolymerization were subjected to thin layer chromatography and combined gas chromatography and mass spectrometry. The major aliphatic components isolated from the hydrogenolysate of the wound polymer produced by tomato fruit were hexadecane-1,16-diol and octadec-9-ene-1,18-diol, which were shown to be derived from a 1:1 mixture of omega-hydroxy and dicarboxylic acids of the appropriate chain length by LiAlH(4) reduction. Also identified in the wound polymer were long chain (>C(20)) fatty acids and alcohols. This monomer composition is typical of suberin polymers and is in sharp contrast with that of the cutin of tomato fruit which contains dihydroxy C(16) acid as the major aliphatic component. The hydrogenolysis of the wound material from bean pods gave octadecene-1,18-diol as the major aliphatic component, and smaller amounts of hexadecane-1,16-diol and long chain alcohols. Similar treatment of the normal cuticular tissue of these pods gave hexadecane triol, as well as C(16) and C(18) alcohols. Hydrogenolysis of wound material from the Jade leaves gave octadecene-1,18-diol, C(16) and C(22) diols, as well as alcohols from C(16) to C(26), whereas similar treatment of the cutin-containing tissue from these leaves gave C(16) triol as the major aliphatic component. Thus, the major aliphatic monomers of the polymeric material deposited during the wound-healing of bean pods and Jade leaves are very similar to those of suberin, although the natural protective polymer of these tissues is cutin. From these results, it is concluded that suberization is a fundamental process involved in wound-healing in plants, irrespective of the chemical nature of the natural protective polymer of the tissue.


Water-soluble contrast medium (gastrografin) value in adhesive small intestine obstruction (ASIO): a prospective, randomized, controlled, clinical trial.
Patients with adhesive small intestine obstruction (ASIO) are difficult to evaluate and to manage and their treatment is still controversial. The diagnostic and therapeutic role of water-soluble contrast medium (Gastrografin) in ASIO is still debated. This study was designed to determine the therapeutic role of Gastrografin in patients with ASIO. The study was a multicenter, prospective, randomized, controlled investigation. The primary end points were the evaluation of the operative rate reduction and shortening the hospital stay after the use of Gastrografin. A total of 76 patients were randomized into two groups: the control group received traditional treatment (TT), whereas the study group (GG) received in addition a Gastrografin meal and follow-through study immediately. Patients with Gastrografin in the colon within 36 hours were considered to be partially obstructed and submitted to nonoperative management. If after 36 hours, the Gastrografin had not entered the colon, the subjects were submitted to laparotomy. No significant differences were found in age, sex, intravenous administration of prokinetics, incidence and characteristics of the previous procedures in surgical history of the patients, previous episodes of ASIO and surgery for adhesiolysis, or duration of symptoms before admission. In the GG group obstruction resolved subsequently in 31 of 38 cases (81.5%) after a mean time of 6.4 hours. The remaining seven patients were submitted to surgery, and one of them needed bowel resection for strangulation. In the control group, 21 patients were not submitted to surgery (55%), whereas 17 showed persistent untreatable obstruction and required laparotomy: 2 of them underwent bowel resection for strangulation. The difference in the operative rate between the two treatment groups reached statistical significance (p = 0.013). The time from the hospital admission for obstruction to resolution of symptoms was significantly lower in the GG group (6.4 vs. 43 hours; p < 0.01). The length of hospital stay revealed a significant reduction in the GG group (4.7 vs. 7.8 days; p < 0.05). This reduction was more evident in the subset of patients who did not require surgery (3 vs. 5.1 days; p < 0.01). No GG-related complications or significant differences in major complications and the relapse rate were found (relapse rate, 34.2% after a mean time to relapse of 6.3 months in the GG group vs. 42.1% after 7.6 months in the TT; p = not significant). Data showed that the use of Gastrografin in ASIO is safe and reduces the operative rate and the time to resolution of obstruction, as well as the hospital stay.


Social Pavlovian conditioning: Short- and long-term effects and the role of anxiety and depressive symptoms.
Today's stressors largely arise from social interactions rather than from physical threat. However, the dominant laboratory model of emotional learning relies on physical stimuli (e.g. electric shock) whereas adequate models of social conditioning are missing, possibly due to more subtle and multilayered biobehavioral responses to such stimuli. To fill this gap, we acquired a broad set of measures during conditioning to negative social unconditioned stimuli, also taking into account long-term maintenance of conditioning and inter-individual differences. Fifty-nine healthy participants underwent a classical conditioning task with videos of actors expressing disapproving (US-neg) or neutral (US-neu) statements. Static images of the corresponding actors with a neutral facial expression served as CS+ and CS-, predicting US-neg and US-neu, respectively. Autonomic and facial-muscular measures confirmed differential unconditioned responding whereas experiential CS ratings, event-related potentials, and evoked theta oscillations confirmed differential conditioned responding. Conditioning was maintained at 1 month and 1 year follow-ups on experiential ratings, especially in individuals with elevated anxiety and depressive symptoms, documenting the efficiency of social conditioning and its clinical relevance. This novel, ecologically improved conditioning paradigm uncovered a remarkably efficient multi-layered social learning mechanism that may represent a risk factor for anxiety and depression.


[Prevalence of Chlamydia trachomatis and Neisseria gonorrhoea infections in sexual actives young women at a southern Brazilian city].
to determine the prevalence of Chlamydia and gonorrhea in a sample of women from Curitiba. this was a cross-sectional study with a sample of sexually active non-pregnant women aged between 16 and 23 years-old, with an intact uterus, with up to four sexual partners, without evidence of fever or purulent cervicitis, submitted to pelvic examination and PCR-based urine- testing for Chlamydia and gonorrhea. Exclusion criteria included: vaccination for HPV, vaccination history for the past 21 days, previous abnormal cytology, history of genital warts, splenectomy, immune disorders, and use of immunosuppressive drugs. An interview regarding sociodemographic and obstetric data and gynecological risk behavior for sexual transmitted diseases was applied. For statistical analysis, we used the χ(2) or Fisher's exact test to assess the association between variables. the prevalence of Chlamydia and gonorrhea infection in the study group was 10.7 and 1.5%, respectively, and the rate of coinfection was 0.9%. No correlation was found between the age range of the volunteers, the onset of sexual activity, the number of sexual partners and of new sexual partners in the last six months, and the presence of Chlamydia or gonorrhea. In women who had vaginal discharge or ectropion, the prevalence of Chlamydia infection was two times higher than in those without such signs. the results of this study were similar to national studies using PCR in urine samples for the detection of Chlamydia and gonorrhea in samples of non-pregnant women of the same age groups and with the same background. Since the volunteers with more than four sexual partners and those who had purulent endocervicitis were excluded, it is believed that the prevalence of Chlamydia and gonorrhea infection could have been greater in this population.


Why is the Implementation of Beta-Lactam Therapeutic Drug Monitoring for the Critically Ill Falling Short? A Multicenter Mixed-Methods Study.
Beta-lactam therapeutic drug monitoring (BL TDM; drug level testing) can facilitate improved outcomes in critically ill patients. However, only 10%-20% of hospitals have implemented BL TDM. This study aimed to characterize provider perceptions and key considerations for successfully implementing BL TDM. This was a sequential mixed-methods study from 2020 to 2021 of diverse stakeholders at 3 academic medical centers with varying degrees of BL TDM implementation (not implemented, partially implemented, and fully implemented). Stakeholders were surveyed, and a proportion of participants completed semistructured interviews. Themes were identified, and findings were contextualized with implementation science frameworks. Most of the 138 survey respondents perceived that BL TDM was relevant to their practice and improved medication effectiveness and safety. Integrated with interview data from 30 individuals, 2 implementation themes were identified: individual internalization and organizational features. Individuals needed to internalize, make sense of, and agree to BL TDM implementation, which was positively influenced by repeated exposure to evidence and expertise. The process of internalization appeared more complex with BL TDM than with other antibiotics (ie, vancomycin). Organizational considerations relevant to BL TDM implementation (eg, infrastructure, personnel) were similar to those identified in other TDM settings. Broad enthusiasm for BL TDM among participants was found. Prior literature suggested that assay availability was the primary barrier to implementation; however, the data revealed many more individual and organizational attributes, which impacted the BL TDM implementation. Internalization should particularly be focused on to improve the adoption of this evidence-based practice.


Role of the p53 tumor suppressor gene in cell cycle arrest and radiosensitivity of Burkitt's lymphoma cell lines.
We have assessed the role of the p53 tumor suppressor gene in cell cycle arrest and cytotoxicity of ionizing radiation in 17 Burkitt's lymphoma and lymphoblastoid cell lines. Cell cycle arrest was assessed by flow cytometry of cells 16 h following irradiation. In addition to the usual G2 arrest, the cell lines exhibited three types of responses in G1: Class I, strong arrest in G1 following radiation; Class II, minimal arrest; and Class III, an intermediate response. All Class I cells contained normal p53 genes. Of the ten lines that showed minimal G1 arrest, eight had mutant p53 alleles, and two lines were heterozygous for p53 mutations. Both of the lines showing an intermediate response contained wild-type p53. Our results are consistent with the view that mutations abrogate the ability of p53 to induce G1 arrest following radiation. Studies with the heterozygotes showed that the mutant protein can have a dominant negative influence upon wild-type p53, and the reduced ability of two normal p53 lines to arrest in G1 indicated that p53 function can be impaired by other mechanisms. The radiosensitivity of most of the lines appeared to depend on the ability of p53 to induce a G1 arrest. The mean radiation dose that inhibited proliferation of the Class I lines by 50% was 0.98 Gy. Of the eight p53 mutant cell lines tested, five lines required approximately 2.9 Gy to cause a 50% inhibition of cell proliferation. The two heterozygotes were also more resistant to radiation than the Class I cells (50% inhibitory dose, 2.1 and 2.9 Gy). Our results suggest that radioresistance is afforded by a loss of function of wild-type p53, which would normally induce a G1 arrest and promote cell death in the presence of DNA damage.


An oceanographic radiance distribution camera system.
An oceanographic optical instrument has been designed and constructed to record the radiance distribution of natural radiant energy underwater. The instrument contains two cameras placed back-to-back, each equipped with a fisheye (180 degrees field of view) lens and is fabricated so that film can be exposed by remote control. The instrument is designed to operate at depths up to 100 m. Values of underwater radiance can be obtained from the exposed films by means of photographic photometry. Radiance distributions obtained in natural waters will provide basic information needed for the study and solution of several problems in optical oceanography. First, the radiance distribution is an important input for the study of the interaction of electromagnetic radiation with the sea. From the distribution of radiance in the natural light fields in the ocean, many of the important optical properties which relate to radiative transfer processes in the ocean can be calculated. Second, from these optical properties one can compute the magnitude of the deterioration of image contrast of submerged objects and thus furnish information for the study and solution of underwater visibility problems, which include problems in underwater television and photography. Finally, since radiant energy is critical to the beginning of the marine food chain through photosynthetic plankton, radiance distribution measurements will provide information of fundamental importance to the problem of primary productivity in natural waters.


Activity of minocycline against Toxoplasma gondii infection in mice.
The chemotherapeutic activity of minocycline, a semi-synthetic tetracycline analogue, was evaluated in a murine model of toxoplasmosis. A lethal acute toxoplasmosis was produced by injecting 10(5) tachyzoites of the RH strain of Toxoplasma gondii into the peritoneal cavities of Swiss-Webster mice. When infected mice were treated once daily for 12 days, starting 2 h after challenge, the survival and cure rates were 100% and 40% respectively after minocycline alone (100 mg/kg per day), 0% and 0% after pyrimethamine alone (8.5 mg/kg per day), and 100% and 50% after combination of the two drugs at the same dosages. Absolute survival and cure with minocycline were observed when mice were treated with two daily doses of 100 mg/kg for 12 days. Mice chronically infected with a low virulent strain of T. gondii (Me49) showed a significant reduction in the number of brain cysts after three weeks of treatment with 50 mg/kg per day of minocycline. Minocycline serum levels after a single oral administration of 50 mg/kg or 100 mg/kg to normal mice, peaked at 1.8 mg/l and 10 mg/l after 1 h, respectively, and showed an extended half-life.


Efferent arterioles exclusively express the subtype 1A angiotensin receptor: functional insights from genetic mouse models.
Angiotensin (ANG) type 1A (AT(1A)) receptor-null (AT(1A)(-/-)) mice exhibit reduced afferent arteriolar (AA) constrictor responses to ANG II compared with wild-type (WT) mice, whereas efferent arteriolar (EA) responses are absent (Harrison-Bernard LM, Cook AK, Oliverio MI, and Coffman TM. Am J Physiol Renal Physiol 284: F538-F545, 2003). In the present study, the renal arteriolar constrictor responses to norepinephrine (NE) and/or ANG II were determined in blood-perfused juxtamedullary nephrons from kidneys of AT(1A)(-/-), AT(1B) receptor-null (AT(1B)(-/-)), and WT mice. Baseline AA diameter in AT(1A)(-/-) mice was not different from that in WT mice (13.1 +/- 0.9 and 12.6 +/- 0.9 microm, n = 7 and 8, respectively); however, EA diameters were significantly larger (17.3 +/- 1.4 vs. 11.7 +/- 0.4 microm, n = 10 and 8) in AT(1A)(-/-) than in WT mice. Constriction of AA (-40 +/- 8 and -51 +/- 6% at 1 microM NE) and EA (-29 +/- 6 and -38 +/- 3% at 1 microM NE) in response to 0.1-1 microM NE was similar in AT(1A)(-/-) and WT mice. Baseline diameters of AA (13.5 +/- 0.7 and 14.2 +/- 0.9 microm, n = 9 and 10) and EA (15.4 +/- 1.0 and 15.0 +/- 0.7 microm, n = 11 and 9) and ANG II (0.1-10 nM) constrictor responses of AA (-25 +/- 4 and -31 +/- 5% at 10 nM) and EA (-32 +/- 6 and -35 +/- 7% at 10 nM) were similar in AT(1B)(-/-) and WT mice, respectively. ANG II-induced constrictions were eliminated by AT(1) receptor blockade with 4 microM candesartan. Taken together, our data demonstrate that AA and EA responses to NE are unaltered in the absence of AT(1A) receptors, and ANG II responses remain intact in the absence of AT(1B) receptors. Therefore, we conclude that AT(1A) and AT(1B) receptors are functionally expressed on the AA, whereas the EA exclusively expresses the AT(1A) receptor.


A new species abundance distribution model based on model combination.
Species abundance distribution (SAD) is one of the important measures of biodiversity and one of the most significant concepts in ecology communities. Using this concept, the biologists can infer a lot of information from their collected data. In this article, we proposed a new method for predicting SAD. This method is based on the combination of several measures parameterized by machine learning techniques and decomposition of the model in sub-ranges having their proper combination. The goal is to use the combination of several individual models to design a better and more informative model. We show in this article by using many datasets representing different ecological situations that our new method is more robust and outperforms the predictive capacity of the other existing models.


Down-Regulation of Phosphoenolpyruvate Carboxylase Kinase in Grapevine Cell Cultures and Leaves Is Linked to Enhanced Resveratrol Biosynthesis.
In grapevine, trans-Resveratrol (tR) is produced as a defence mechanism against stress or infection. tR is also considered to be important for human health, which increases its interest to the scientific community. Transcriptomic analysis in grapevine cell cultures treated with the defence response elicitor methyl-β-cyclodextrin (CD) revealed that both copies of PHOSPHOENOLPYRUVATE CARBOXYLASE KINASE (PPCK) were down-regulated significantly. A role for PPCK in the defence response pathway has not been proposed previously. We therefore analysed the control of PPCK transcript levels in grapevine cell cultures and leaves elicited with CD. Moreover, phosphoenolpyruvate carboxylase (PPC), stilbene synthase (STS), and the transcription factors MYB14 and WRKY24, which are involved in the activation of STS transcription, were also analysed by RT-qPCR. The results revealed that under CD elicitation conditions PPCK down-regulation, increased stilbene production and loss of PPC activity occurs in both tissues. Moreover, STS transcripts were co-induced with MYB14 and WRKY24 in cell cultures and leaves. These genes have not previously been reported to respond to CD in grape leaves. Our findings thus support the hypothesis that PPCK is involved in diverting metabolism towards stilbene biosynthesis, both for in vitro cell culture and whole leaves. We thus provide new evidence for PEP being redirected between primary and secondary metabolism to support tR production and the stress response.


The export of pesticides: shipments from U.S. ports, 1995-1996.
In 1995-96, 21 million pounds of pesticides that were forbidden to be used in the United States were exported from U.S. ports. This total, which includes domestically-banned and never-registered products, is on average 14 tons per day. In addition, more than 48 million pounds (24,000 tons) of extremely toxic pesticides were exported. Most of these pesticides were shipped to developing countries, despite extensive evidence of the need to restrict the export of hazardous pesticides from the United States to these countries to protect their workers' health and their environments. The National Environmental Protection Act presents a sensible and manageable policy that, if followed, could considerably alleviate the problem. Specifics are provided.


Sleep disordered breathing in Parkinson's disease: a critical appraisal.
Parkinson's disease (PD) is the second most common neurodegenerative disorder, characterized by resting tremor, rigidity, bradykinesia and postural instability, and is associated with non-motor features, including sleep abnormalities. The high prevalence of excessive daytime sleepiness and snoring in PD patients has led to the suggestion that sleep disordered breathing (SDB) is more common in these individuals than in normal subjects. We aimed to review the literature on SDB prevalence and its clinical repercussions in PD. A PubMed search was performed to identify controlled studies, published from January 1990 through October 2012, which addressed the prevalence of SDB diagnosed by polysomnography in idiopathic PD. From the seven studies included, five reported similar or lower prevalence of SDB in patients when compared to healthy age-matched controls. Two studies reported less oxyhemoglobin desaturation during sleep among patients. These results did not support the idea that PD patients are at increased risk of SDB and indicate that they may not present significant hypoxemia. The prevalence of obstructive sleep apnea syndrome and the long-term outcomes of disordered breathing events during sleep have not been adequately studied in PD.


Harmonized procedures lead to comparable quantification of total oxylipins across laboratories.
Oxylipins are potent lipid mediators involved in a variety of physiological processes. Their profiling has the potential to provide a wealth of information regarding human health and disease and is a promising technology for translation into clinical applications. However, results generated by independent groups are rarely comparable, which increases the need for the implementation of internationally agreed upon protocols. We performed an interlaboratory comparison for the MS-based quantitative analysis of total oxylipins. Five independent laboratories assessed the technical variability and comparability of 133 oxylipins using a harmonized and standardized protocol, common biological materials (i.e., seven quality control plasmas), standard calibration series, and analytical methods. The quantitative analysis was based on a standard calibration series with isotopically labeled internal standards. Using the standardized protocol, the technical variance was within ±15% for 73% of oxylipins; however, most epoxy fatty acids were identified as critical analytes due to high variabilities in concentrations. The comparability of concentrations determined by the laboratories was examined using consensus value estimates and unsupervised/supervised multivariate analysis (i.e., principal component analysis and partial least squares discriminant analysis). Interlaboratory variability was limited and did not interfere with our ability to distinguish the different plasmas. Moreover, all laboratories were able to identify similar differences between plasmas. In summary, we show that by using a standardized protocol for sample preparation, low technical variability can be achieved. Harmonization of all oxylipin extraction and analysis steps led to reliable, reproducible, and comparable oxylipin concentrations in independent laboratories, allowing the generation of biologically meaningful oxylipin patterns.


Diet restriction inhibits apoptosis and HMGB1 oxidation and promotes inflammatory cell recruitment during acetaminophen hepatotoxicity.
Acetaminophen (APAP) overdose is a major cause of acute liver failure and serves as a paradigm to elucidate mechanisms, predisposing factors and therapeutic interventions. The roles of apoptosis and inflammation during APAP hepatotoxicity remain controversial. We investigated whether fasting of mice for 24 h can inhibit APAP-induced caspase activation and apoptosis through the depletion of basal ATP. We also investigated in fasted mice the critical role played by inhibition of caspase-dependent cysteine 106 oxidation within high mobility group box-1 protein (HMGB1) released by ATP depletion in dying cells as a mechanism of immune activation. In fed mice treated with APAP, necrosis was the dominant form of hepatocyte death. However, apoptosis was also observed, indicated by K18 cleavage, DNA laddering and procaspase-3 processing. In fasted mice treated with APAP, only necrosis was observed. Inflammatory cell recruitment as a consequence of hepatocyte death was observed only in fasted mice treated with APAP or fed mice cotreated with a caspase inhibitor. Hepatic inflammation was also associated with loss in detection of serum oxidized-HMGB1. A significant role of HMGB1 in the induction of inflammation was confirmed with an HMGB1-neutralizing antibody. The differential response between fasted and fed mice was a consequence of a significant reduction in basal hepatic ATP, which prevented caspase processing, rather than glutathione depletion or altered APAP metabolism. Thus, the inhibition of caspase-driven apoptosis and HMGB1 oxidation by ATP depletion from fasting promotes an inflammatory response during drug-induced hepatotoxicity/liver pathology.


Copper elicits an increase in cytosolic free calcium in cultured tobacco cells.
At concentrations greater than 0.1 mM, CuSO(4) provoked a rapid and sustained increase in the cytosolic free Ca(2+) concentration ([Ca(2+)](cyt)), in tobacco suspension culture cells expressing apoaequorin, a Ca(2+)-sensitive photoprotein. The increase was suppressed by treatment with LaCl(3), indicating that the increase is due to an influx of Ca(2+) from the apoplast through plasma membrane Ca(2+) channels. Although stimulation of H(2)O(2) production upon the CuSO(4) treatment (0.1 mM) was observed, treatment with catalase did not inhibit the increase in [Ca(2+)](cyt), and treatment with H(2)O(2) dose-dependently suppressed or delayed the increase. These results suggested that active oxygen species generated through copper-mediated reactions, or copper-mediated oxidative damages to plasma membrane, are not responsible for the increase. Treatment with sulfhydryl reagents, which alkylate or oxidize thiol groups, or acidification of the culture medium suppressed the increase in [Ca(2+)](cyt). These results demonstrated that copper causes an influx of Ca(2+) through plasma membrane Ca(2+) channels, and that plasma membrane thiol groups play an important role in activating the Ca(2+) channels.