Absence of high-affinity binding of progesterone (R 5020) in human placenta and fetal membranes.
Increased levels of maternal serum progesterone occur during the last stages of human gestation. The function of the high level of this steroid is unknown. The presence of a progesterone receptor in the placenta was investigated to determine whether progesterone action on the placenta might serve as one function of the high level of this steroid. Cytosol and nuclear fractions, derived from human placentae and fetal membranes, were examined for the presence of progesterone receptors by conducting exchange assays, using tritiated R 5020 (17,21-dimethyl-19-norpregna-4,9-diene-3,20-dione) as the radiolabelled ligand. High-affinity, low-capacity binding, characteristic of steroid receptors, was estimated as the difference between binding of radiolabelled ligand in the presence of no unlabelled ligand and that in the presence of a 100-fold excess of unlabelled ligand. These exchange assays were conducted during a 24-hour period at 0 degrees C, to allow maximal stability of the receptor, and during a 3-hour period at 20 degrees C, to allow the rapid exchange of radiolabelled ligand for any bound endogenous progesterone. The assays of all fractions showed no specific binding of the R 5020, thus indicating the absence of progesterone receptors in the cytosol and nuclei of the human placenta and the fetal membranes.


A comparison of the Frisby, Random-Dot E, TNO, and Randot circles stereotests in screening and office use.
Three random-dot stereogram (RDS) tests, the Frisby, Random-Dot E (RDE), and TNO tests, and a stereotest with monocularly visible contours, the Randot circles test, were administered to two populations of 3- to 5-year-old children in vision screening settings and to a sample of patients with strabismus and amblyopia. The Frisby test missed (underreferred) cases of binocular dysfunction detected by the RDE and TNO tests, using a 250 seconds of arc (250") (Frisby and RDE) or 240" (TNO) thresholds as the pass-fail breakpoint. The TNO underreferred cases at 240" relative to the RDE, but underreferred none if the TNO's breakpoint was lowered to 120". The Randot circles test produced better-indicated stereoacuities than the RDS tests and was found able to reliably grade stereoacuity in patients with stereopsis too poor to be graded by RDS tests.


Biomarkers of response to ibrutinib plus nivolumab in relapsed diffuse large B-cell lymphoma, follicular lymphoma, or Richter's transformation.
We analyzed potential biomarkers of response to ibrutinib plus nivolumab in biopsies from patients with diffuse large B-cell lymphoma (DLBCL), follicular lymphoma (FL), and Richter's transformation (RT) from the LYM1002 phase I/IIa study, using programmed death ligand 1 (PD-L1) immunohistochemistry, whole exome sequencing (WES), and gene expression profiling (GEP). In DLBCL, PD-L1 elevation was more frequent in responders versus nonresponders (5/8 [62.5%] vs. 3/16 [18.8%]; p = 0.065; complete response 37.5% vs. 0%; p = 0.028). Overall response rates for patients with WES and GEP data, respectively, were: DLBCL (38.5% and 29.6%); FL (46.2% and 43.5%); RT (76.5% and 81.3%). In DLBCL, WES analyses demonstrated that mutations in RNF213 (40.0% vs. 6.2%; p = 0.055), KLHL14 (30.0% vs. 0%; p = 0.046), and LRP1B (30.0% vs. 6.2%; p = 0.264) were more frequent in responders. No responders had mutations in EBF1, ADAMTS20, AKAP9, TP53, MYD88, or TNFRSF14, while the frequency of these mutations in nonresponders ranged from 12.5% to 18.8%. In FL and RT, genes with different mutation frequencies in responders versus nonresponders were: BCL2 (75.0% vs. 28.6%; p = 0.047) and ROS1 (0% vs. 50.0%; p = 0.044), respectively. Per GEP, the most upregulated genes in responders were LEF1 and BTLA (overall), and CRTAM (germinal center B-cell-like DLBCL). Enriched pathways were related to immune activation in responders and resistance-associated proliferation/replication in nonresponders. This preliminary work may help to generate hypotheses regarding genetically defined subsets of DLBCL, FL, and RT patients most likely to benefit from ibrutinib plus nivolumab.


Scents boost preference for novel fruits.
When faced with a novel food, multisensory information that includes appearance and smell is a very important cue for preference, categorization, and the decision of whether or not to eat it. We elucidated whether olfactory information leads to biased visual categorization of and preference for fruits, even when odors are presented subliminally. We employed morphed images of strawberries and tomatoes combined with their corresponding odorants as stimuli. Participants were asked to categorize the images into either of two categories, to evaluate their preference for each visual image, and to judge the presence/absence of the odor. Results demonstrated that visual categorization was not affected by the odor manipulation; however, preference for uncategorizable images increased when odors were presented regardless of the participant's awareness of the odor. Our findings suggest that visual preference for novel fruits is based on both conscious and unconscious olfactory processing regarding edibility.


[Usefulness of a new fast technique for detection of pneumococcal antigen in the diagnosis of community pneumonia].
With the objective of analyzing the usefulness of a new technique of fast detection of pneumococcal antigen in urine (Binax NOW Streptococcus pneumoniae urinary antigen test) 163 community pneumonia episodes were reviewed. The test was positive in 30 cases, and gave rise to therapeutic implications in 12 patients. The global sensitivity was 57%, being superior in patients with HIV infection (70%), and the specificity was 91.6%. In 16 episodes it was the only diagnostic test of pneumococcal infection. The determination of pneumococcal antigen through this technique is a useful tool for the diagnosis of community pneumonia, mainly due its high specificity.


[Recognition of congenital endometrial carcinoma: the importance of family history and investigation of microsatellite instability in the tumour].
Endometrial cancer diagnosed at a relatively young age or in a patient with a medical history of colorectal cancer may be indicative of Lynch syndrome. Four women, aged 43, 60, 41 and 54 respectively, with a family history of endometrial or colorectal neoplasm were examined for microsatellite instability (MSI) in tumour tissue with positive results. Subsequently, a mutation was found in one of the DNA mismatch repair genes. Lynch syndrome, also known as hereditary non-polyposis colorectal cancer (HNPCC), is caused by a germline mutation in a mismatch repair gene and is an autosomal dominant disorder that is characterized by the development of carcinoma of the endometrium and colorectum at a relatively young age. Until recently, recognition of Lynch syndrome was mainly based on an, often incomplete, family history, but today the presence of MSI in tumour tissue can be used to identify patients at risk for Lynch syndrome. A pathologist can contribute to identifying a patient at risk for Lynch syndrome by initiating MSI testing when: (a) endometrial cancer is diagnosed under the age of 50, (b) a combination of endometrial cancer and colorectal cancer is diagnosed under the age of 70.


Antioxidative activities of aroma extracts isolated from natural plants.
Natural leaves and flowers containing numerous aroma chemicals are widely used in aromatherapy since ancient times. In addition to their pleasant smells, aroma chemicals might have some beneficial health effects. Aroma extracts, isolated from coffee beans, soybeans, and mung beans by steam distillation under mild conditions (55 degrees C and 85 mm Hg) were examined for their antioxidative activities. The inhibitory effect of these extracts toward hexanal/hexanoic acid conversion was measured in the testing solution over prolonged time periods. The inhibitory effects of these extracts toward malonaldehyde formation from lipids oxidized by Fenton's reagent were also measured. The antioxidative activity of these extracts, in particular coffee bean extract, was consistent with that of BHT or alpha-tocopherol (vitamin E). Soybeans and mung beans extract contained maltol, which inhibits hexanal oxidation significantly. Eugenol, which is one of the major constituents of mung bean extract, exhibited potent antioxidative activity in an aldehyde/carboxylic acid assay. Antioxidants such as eugenol and maltol may play an important role in the pharmaceutical activities of natural plant extracts used for aromatherapy.


Osteon cross-sectional size in the iliac crest: variation in normals and patients with osteoporosis, hyperparathyroidism, acromegaly, hypothyroidism and treated epilepsia.
Cross-sectional osteon size was measured in undecalcified stained sections of iliac crest bone specimens from normal individuals (n = 68) and from patients with spinal osteoporosis (n = 27), primary hyperparathyroidism (n = 23), epilepsia (receiving chronic anti-convulsant therapy) (n = 11), acromegaly (n = 18), and hypothyroidism (n = 12). In each individual the shortest osteon diameter (D) and the corresponding Haversian canal diameter (d) were measured in a minimum of 20 completed secondary osteons by means of a micrometer eyepiece. Among normal males the areas of bone resorbed and formed increased with age (p less than 0.01), owing to an increase in the thickness of bone resorbed (p less than 0.01) and an unchanged thickness of bone formed. Among the females, both the areas of bone resorbed and formed decreased with age (p less than 0.05), owing to a reduction in the thickness of bone resorbed (p less than 0.05) as well as formed (p less than 0.001). Resorbed and formed areas were reduced in the epileptic (p less than 0.01) and acromegalic (p less than 0.01) groups but increased in the hypothyroid group (p less than 0.01) compared to sex- and age-matched controls. Neither the osteoporotic nor the hyperparathyroid group showed any alterations in osteon size. The Haversian canal diameter was slightly increased in the epileptic group but normal in the other patient groups. The observed changes reflect variations in the amount of work performed by osteoclasts and osteoblasts during bone remodelling and may be explained by variations in cellular activity and bone turn-over rates.


Nonapoptotic caspases in neural development and in anesthesia-induced neurotoxicity.
Apoptosis, classically initiated by caspase pathway activation, plays a prominent role during normal brain development as well as in neurodegeneration. The noncanonical, nonlethal arm of the caspase pathway is evolutionarily conserved and has also been implicated in both processes, yet is relatively understudied. Dysregulated pathway activation during critical periods of neurodevelopment due to environmental neurotoxins or exposure to compounds such as anesthetics can have detrimental consequences for brain maturation and long-term effects on behavior. In this review, we discuss key molecular characteristics and roles of the noncanonical caspase pathway and how its dysregulation may adversely affect brain development. We highlight both genetic and environmental factors that regulate apoptotic and sublethal caspase responses and discuss potential interventions that target the noncanonical caspase pathway for developmental brain injuries.


Sexual behavior among high school students in Brazil: alcohol consumption and legal and illegal drug use associated with unprotected sex.
Alcohol and other drug use appears to reduce decision-making ability and increase the risk of unsafe sex, leading to possible unplanned pregnancies, sexually transmitted diseases/human immunodeficiency virus/HIV transmission, and multiple sexual partners. This study aimed to test the hypothesis that risky sexual behaviors among adolescents are associated with legal and illegal drug use. A national cross-sectional survey of 17,371 high-school students was conducted in 2010. Students were selected from 789 public and private schools in each of the 27 Brazilian state capitals by a multistage probabilistic sampling method and answered a self-report questionnaire. Weighted data were analyzed through basic contingency tables and logistic regressions testing for differences in condom use among adolescents who were sexually active during the past month. Approximately one third of the high school students had engaged in sexual intercourse in the month prior to the survey, and nearly half of these respondents had not used a condom. While overall sexual intercourse was more prevalent among boys, unsafe sexual intercourse was more prevalent among girls. Furthermore, a lower socioeconomic status was directly associated with non-condom use, while binge drinking and illegal drug use were independently associated with unsafe sexual intercourse. Adolescent alcohol and drug use were associated with unsafe sexual practices. School prevention programs must include drug use and sexuality topics simultaneously because both risk-taking behaviors occur simultaneously.


Neurosyphilis presenting with status epilepticus.
Three patients with neurosyphilis are reported. The first and third patients presented with convulsive status epilepticus and the second with non-convulsive status after penicillin administration. In all cerebrospinal fluid and the serum Venereal Disease Research Laboratory Test (VDRL) and Treponema Pallidum hemagglutination (TPHA) or fluorescent treponemal antibody absorption test (FTA-ABS) were positive, but HIV serology was negative. Their EEGs showed periodic, lateralized, epileptiform discharges (PLEDs) just after SE. The first and third patients had no history of epilepsy. Seizures started as focal motor attacks but then secondarily generalized. The first patient's cranial MRI showed cerebral atrophy and hyperintensity involving bilateral medial and anterior temporal regions, more prominent on the left and which disappeared after penicillin treatment. The second case, after receiving penicillin, had nonconvulsive SE, a clinical presentation suggesting a Jarisch-Herxheimer reaction (JHR). Her cranial MR revealed moderate cortical atrophy and widespread confluent hyperintense foci mainly in both periventricular areas, corona radiata and centrum semiovale. MRI of the third case showed a large, left sylvian, arachnoid cyst without mass effect. Executive dysfunction was observed in follow-up neuropsychological tests in all patients. When investigating status epilepticus, neurosyphilis as a cause must not be forgotten.


Function and expression of renal epithelial sodium transporters in rats with thyroid dysfunction.
Thyroid disorders are accompanied by major changes in renal sodium handling and blood pressure. Sodium transporters play a crucial role in regulating sodium excretion. We determined the function and expression of type 3 Na/H (NHE3) exchanger, type 2 Na+K+2Cl co-transporter (NKCC2) co-transporter, NaCl co-transporter (NCC) cotransporter, and epithelial sodium channel (ENaC) in hypoand hyperthyroid rats at 6 weeks after each thyroid disorder induction. We measured the renal response to functional blockade of the tubular sodium transporters, using acetazolamide to inhibit the activity of NHE3, furosemide for NKCC2, hydrochlorotiazide for NCC, and amiloride for ENaC. Expression of sodium transporters was analyzed by measuring the protein abundance by Western blot. The responsiveness to NHE3 inhibition and NHE3 protein was lower in hypothyroid rats and higher in hyperthyroid rats vs controls. Hypothyroid rats showed greater diuretic and natriuretic responses to NKCC2 and ENaC blockade and higher protein abundance of NKCC2 vs controls. Hyperthyroid rats showed greater protein expression of NKCC2 and NCC vs controls. Groups did not differ in responsiveness to NCC blockade. The expression and activity of ENaC were lower in hyperthyroid rats. In conclusion, reduced NHE3 activity may participate in the low blood pressure of hypothyroid rats and elevated NHE3 activity in the high blood pressure of hyperthyroid rats. These proximal alterations are counter-balanced by functional upregulation of NKCC2 and ENaC in downstream nephron segments of hypothyroid rats and by downregulation of αENaC activity and expression in hyperthyroid rats.


Synthesis of a molecularly imprinted polymer for the isolation of 1-hydroxypyrene in human urine.
In the last decades, the assessment of polycyclic aromatic hydrocarbons' exposure has generated great interest and 1-hydroxypyrene (1-OHP) has been commonly used as a biological indicator of exposure to PAHs in many studies in environmental and occupational health. In this research, a molecularly imprinted polymer (MIP) was synthesised by precipitation polymerisation using 1-OHP as template, methacrylic acid (MAA) as functional monomer, ethylene glycol dimethacrylate (EGDMA) as cross-linker, and acetonitrile as porogen. MIP was used as solid-phase extraction (SPE) material for sample pretreatment and isolation of 1-OHP and posterior detection in a reversed-phase HPLC-FLD. Various parameters including washing solvent, elution solvent and volume affecting the extraction efficiency of the polymer have been evaluated to achieve the isolation of 1-OHP from urine samples and to reduce non-specific interactions. Cross-selectivity was studied in the presence of other structural analogues of the 1-OHP as hydroxyphenantrene isomers. The method was validated over a concentration range of 0.15-2.00 µg L(-1), R(2)>0.998. Recovery values were in the range of 78-90% and RSD <6.7%. The limits of detection and quantification were 0.05 µg L(-1) and 0.17 µg L(-1), respectively. In our knowledge, it is the first time that this methodology is applied for analysing urinary hydroxypyrene and it has been demonstrated that this specific MISPE-HPLC-FLD method offers a fast and simple alternative to determine 1-OHP in human urine samples.


Human analogue safe haven effect of the owner: behavioural and heart rate response to stressful social stimuli in dogs.
The secure base and safe haven effects of the attachment figure are central features of the human attachment theory. Recently, conclusive evidence for human analogue attachment behaviours in dogs has been provided, however, the owner's security-providing role in danger has not been directly supported. We investigated the relationship between the behavioural and cardiac response in dogs (N= 30) while being approached by a threatening stranger in separation vs. in the presence of the owner, presented in a balanced order. Non-invasive telemetric measures of heart rate (HR) and heart rate variability (HRV) data during the threatening approaches was compared to periods before and after the encounters. Dogs that showed distress vocalisation during separation (N = 18) and that growled or barked at the stranger during the threatening approach (N = 17) were defined as behaviourally reactive in the given situation. While characteristic stress vocalisations were emitted during separations, the absence of the owner did not have an effect on dogs' mean HR, but significantly increased the HRV. The threatening approach increased dogs' mean HR, with a parallel decrease in the HRV, particularly in dogs that were behaviourally reactive to the encounter. Importantly, the HR increase was significantly less pronounced when dogs faced the stranger in the presence of the owner. Moreover, the test order, whether the dog encountered the stranger first with or without its owner, also proved important: HR increase associated with the encounter in separation seemed to be attenuated in dogs that faced the stranger first in the presence of their owner. We provided evidence for human analogue safe haven effect of the owner in a potentially dangerous situation. Similarly to parents of infants, owners can provide a buffer against stress in dogs, which can even reduce the effect of a subsequent encounter with the same threatening stimuli later when the owner is not present.


The ethanolic fermentation pathway supports respiration and lipid biosynthesis in tobacco pollen.
Rapid pollen tube growth requires a high rate of sugar metabolism to meet energetic and biosynthetic demands. Previous work on pollen sugar metabolism showed that tobacco pollen carry out efficient ethanolic fermentation concomitantly with a high rate of respiration (Bucher et al., 1995). Here we show that the products of fermentation, acetaldehyde and ethanol, are further metabolised in a pathway that bypasses mitochondrial PDH. The enzymes involved in this pathway are pyruvate decarboxylase, aldehyde dehydrogenase and acetyl-CoA synthetase. Radiolabelling experiments show that during tobacco pollen tube growth label of 14C-ethanol is incorporated into CO2 as well as into lipids and other higher molecular weight compounds. A role for the glyoxylate cycle appears unlikely since activity of malate synthase, a key enzyme of the glyoxylate cycle, could not be detected.


Effectiveness of cervical epidural injections in the management of chronic neck and upper extremity pain.
Chronic persistent neck pain with or without upper extremity pain is common in the general adult population with prevalence of 48% for women and 38% for men, with persistent complaints in 22% of women and 16% of men. Multiple modalities of treatments are exploding in managing chronic neck pain along with increasing prevalence. However, there is a paucity of evidence for all modalities of treatments in managing chronic neck pain. Cervical epidural injections for managing chronic neck pain are one of the commonly performed interventions in the United States. However, the literature supporting cervical epidural steroids in managing chronic pain problems has been scant. A systematic review of cervical interlaminar epidural injections for cervical disc herniation, cervical axial discogenic pain, cervical central stenosis, and cervical postsurgery syndrome. To evaluate the effect of cervical interlaminar epidural injections in managing various types of chronic neck and upper extremity pain emanating as a result of cervical spine pathology. The available literature on cervical interlaminar epidural injections in managing chronic neck and upper extremity pain were reviewed. The quality assessment and clinical relevance criteria utilized were the Cochrane Musculoskeletal Review Group criteria as utilized for interventional techniques for randomized trials and the criteria developed by the Newcastle-Ottawa Scale criteria for observational studies. The level of evidence was classified as good, fair, and limited based on the quality of evidence developed by the U.S. Preventive Services Task Force (USPSTF). Data sources included relevant literature identified through searches of PubMed and EMBASE from 1966 to December 2011, and manual searches of the bibliographies of known primary and review articles. The primary outcome measure was pain relief (short-term relief = up to 6 months and long-term > 6 months). Secondary outcome measures were improvement in functional status, psychological status, return to work, and reduction in opioid intake. For this systematic review, 34 studies were identified. Of these, 24 studies were excluded and a total of 9 randomized trials, with 2 duplicate studies, met inclusion criteria for methodological quality assessment. For cervical disc herniation, the evidence is good for cervical epidural with local anesthetic and steroids; whereas, it was fair with local anesthetic only. For axial or discogenic pain, the evidence is fair for local anesthetic, with or without steroids. For spinal stenosis, the evidence is fair for local anesthetic, with or without steroids. For postsurgery syndrome, the evidence is fair for local anesthetic, with or without steroids. The limitations of this systematic review continue to be the paucity of literature. The evidence is good for radiculitis secondary to disc herniation with local anesthetics and steroids, fair with local anesthetic only; whereas, it is fair for local anesthetics with or without steroids, for axial or discogenic pain, pain of central spinal stenosis, and pain of post surgery syndrome.


Intermittent hydrostatic pressure inhibits matrix metalloproteinase and pro-inflammatory mediator release from human osteoarthritic chondrocytes in vitro.
This study tested the hypothesis that intermittent hydrostatic pressure applied to human osteoarthritic chondrocytes modulates matrix metalloproteinase and pro-inflammatory mediator release in vitro. Human osteoarthritic articular chondrocytes were isolated and cultured as primary high-density monolayers. For testing, chondrocyte cultures were transferred to serum-free medium and maintained without loading or with exposure to intermittent hydrostatic pressure (IHP) at 10 MPa at a frequency of 1 Hz for periods of 6, 12 and 24 h. Levels of matrix metalloproteinase-2, -9 (MMP-2, -9), tissue inhibitor of metalloproteinase-1 (TIMP-1), and the pro-inflammatory mediators, interleukin-6 (IL-6) and monocyte chemoattractant protein-1 (MCP-1), released into the culture medium were assessed by ELISA. Matrix metalloproteinase activity was confirmed by zymographic analysis. In the absence of IHP, levels of MMP-2, TIMP-1, IL-6, and MCP-1 in the chondrocyte culture medium increased in a time-dependent manner. Application of IHP decreased MMP-2 levels at all time periods tested, relative to unloaded control cultures maintained for the same time periods. Although 84/82 kDa bands were faintly detectable by zymography, MMP-9 levels were not quantifiable in medium from loaded or unloaded cultures by ELISA. TIMP-1 levels were not altered in response to IHP at any time period tested. IL-6 and MCP-1 levels decreased in cultures exposed to IHP at 12 and 24 h, relative to unloaded control cultures maintained for the same time periods. IHP decreased release of MMP-2, IL-6 and MCP-1 by osteoarthritic chondrocytes in vitro suggesting that pressure influences cartilage stability by modulating chondrocyte expression of these degradative and pro-inflammatory proteins in vivo.


[How can the incidence of antibiotic residues in meat animals be minimized?].
The causes of the presence of antibiotic residues in slaughtered animals are analysed. The fact is stressed that the persistence of antibiotic residues in slaughtered animals varies, among other things, with the antibiotic itself, the pharmaceutical design and, in the case of subcutaneous or intramuscular injection, the site of injection and the severity of local irritation of the tissues. There are marked differences between the various antibiotic products as regards the local irritation induced and the residual persistence in organs at the site of injection. A selective use of antibiotics and forms of administration (so-called 'positive list') is advocated, by which the incidence of antibiotic residues in slaughtered animals can be restricted. Recommendations for drawing up a 'positive' list' are made.


FMR1 and Autism, an Intriguing Connection Revisited.
Autism Spectrum Disorder (ASD) represents a distinct phenotype of behavioral dysfunction that includes deficiencies in communication and stereotypic behaviors. ASD affects about 2% of the US population. It is a highly heritable spectrum of conditions with substantial genetic heterogeneity. To date, mutations in over 100 genes have been reported in association with ASD phenotypes. Fragile X syndrome (FXS) is the most common single-gene disorder associated with ASD. The gene associated with FXS, FMR1 is located on chromosome X. Accordingly, the condition has more severe manifestations in males. FXS results from the loss of function of FMR1 due to the expansion of an unstable CGG repeat located in the 5'' untranslated region of the gene. About 50% of the FXS males and 20% of the FXS females meet the Diagnostic Statistical Manual 5 (DSM-5) criteria for ASD. Among the individuals with ASD, about 3% test positive for FXS. FMRP, the protein product of FMR1, is a major gene regulator in the central nervous system. Multiple pathways regulated by FMRP are found to be dysfunctional in ASD patients who do not have FXS. Thus, FXS presents the opportunity to study cellular phenomena that may have wider applications in the management of ASD and to develop new strategies for ASD therapy.


The leukocyte common antigen-related protein LAR: candidate PTP for inhibitory targeting.
The leukocyte common antigen-related protein, LAR, is a receptor-like protein tyrosine phosphatase (PTP) which has a wide tissue distribution. Post-translational processing cleaves the proprotein into two non-covalently associated subunits, an extracellular subunit resembling a cell adhesion molecule with three immunoglobulin-like domains and eight fibronectin III-like domains, and a phosphatase subunit containing a short extracellular domain, a transmembrane segment, and tandem cytoplasmic PTP catalytic domains. Current evidence supports a role for LAR in cadherin complexes where it associates with and dephosphorylates beta-catenin, a pathway which may be critical for cadherin complex stability and cell-cell association. LAR also localizes to focal adhesions. Evidence strongly suggests that LAR is involved in axon guidance in the developing nervous system, being localized through association with alpha-liprins. Finally, considerable data support a role for LAR in negatively regulating the insulin receptor signaling. Now that targeting of specific PTPs for therapeutic inhibition is a reality, the clinically relevant pathways requiring LAR must be identified. Inhibition of LAR might improve insulin sensitivity in patients with insulin resistance and type 2 diabetes. Unfortunately, the LAR knockout mouse displays no improvement in insulin sensitivity but rather has defects in terminal mammary gland development and in basal forebrain cholinergic neurons. With LAR being implicated in diverse pathways, additional investigations are needed before clinical targets for therapeutic inhibition of LAR can be predicted. However, selective inhibitors of LAR would be valuable reagents to probe the function of LAR, particularly in animal studies where the most susceptible LAR-dependent pathway(s) must be determined.


Acute Pancreatitis in a Teenager With SARS-CoV-2 Infection.
The clinical manifestations of SARS-CoV-2 infection, the causative agent of COVID-19, mainly involve the respiratory system. However, there is increasing evidence that this virus can affect other organs causing a wide arrange of clinical symptoms. In this report, we present the case of 14-year-old boy with acute abdominal pain, with laboratory and radiologic findings consistent with acute pancreatitis, without any risk factors except for a SARS-CoV-2 infection.


[Pulmonary thromboendarterectomy].
Chronic thromboembolic pulmonary hypertension (CTEPH) is a rare disease characterized by the persistence of thromboemboli obstructing the pulmonary arteries as an organized tissue. The consequence is an increase in pulmonary vascular resistance resulting in pulmonary hypertension (PH) and progressive right heart failure. Pulmonary thromboendarterectomy (PTE) is the treatment of choice of chronic thromboembolic pulmonary disease. Pulmonary thromboendarterectomy is performed under hypothermia and total circulatory arrest. This procedure is associated with a low mortality rate in experienced centers and results in a dramatic improvement of hemodynamic parameters, functional status and survival rate. This surgery should be performed as early as possible in the history of this disease, preferentially before development of arteriolitis in the non obstructed territories. Because of the absence of clinically evident acute pulmonary embolism history in >50% of patients, the diagnosis of CTEPH can be difficult. Lung scintigraphic scan showing segmentary mismatched perfusion defects is the best diagnostic tool to detect CTEPH. Pulmonary angiography and high-resolution computerized tomography scan are required to establish the diagnosis and to assess the operability. A diagnostic right heart catheterization is required to confirm the diagnosis of PH and to determine the degree of hemodynamic impairment. If there is a good correlation between the pulmonary vascular resistance and the anatomical obstruction, pulmonary thromboendarterectomy should be proposed. Pulmonary or cardiopulmonary transplantation is indicated in this setting only when the lesions are too distal and thus inaccessible to endarterectomy.


The feasibility and utility of grocery receipt analyses for dietary assessment.
To establish the feasibility and utility of a simple data collection methodology for dietary assessment. Using a cross-sectional design, trained data collectors approached adults (approximately 20 - 40 years of age) at local grocery stores and asked whether they would volunteer their grocery receipts and answer a few questions for a small stipend (dollar 1). The grocery data were divided into 3 categories: "fats, oils, and sweets," "processed foods," and "low-fat/low-calorie substitutions" as a percentage of the total food purchase price. The questions assessed the shopper's general eating habits (eg, fast-food consumption) and a few demographic characteristics and health aspects (eg, perception of body size). Statistical Analyses Performed. Descriptive and analytic analyses using non-parametric tests were conducted in SAS. Forty-eight receipts and questionnaires were collected. Nearly every respondent reported eating fast food at least once per month; 27% ate out once or twice a day. Frequency of fast-food consumption was positively related to perceived body size of the respondent (p = 0.02). Overall, 30% of the food purchase price was for fats, oils, sweets, 10% was for processed foods, and almost 6% was for low-fat/low-calorie substitutions. Households where no one was perceived to be overweight spent a smaller proportion of their food budget on fats, oils, and sweets than did households where at least one person was perceived to be overweight (p = 0.10); household where the spouse was not perceived to be overweight spent less on fats, oils, and sweets (p = 0.02) and more on low-fat/low-calorie substitutions (p = 0.09) than did households where the spouse was perceived to be overweight; and, respondents who perceived themselves to be overweight spent more on processed foods than did respondents who did not perceive themselves to be overweight (p = 0.06). This simple dietary assessment method, although global in nature, may be a useful indicator of dietary practices as evidenced by its association with perceived weight status.


Hangings attended by emergency medical services: a scoping review.
In the United Kingdom (UK) there were 6507 deaths by suicide in 2018, with hanging being the most common method. Hanging will normally result in emergency medical services (EMS) being called and may result in resuscitation being attempted. Trauma audits conducted by North East Ambulance Service NHS Foundation Trust have identified an increased trend in hanging cases, which were also reported in national data. The aim of this scoping review was to explore the literature around EMS attendance at hangings to inform further research and clinical practice. A five-stage scoping review method was used. Relevant studies were identified by searching MEDLINE, CINAHL, EMBASE and EMCARE with the help of the Library and Knowledge Service for NHS Ambulance Services in England. Grey literature and reference lists were also searched. Studies were included based on relevance to hangings attended by EMS. Data were tabulated and narratively synthesised. Sixteen papers were included in the review. Australia was the most frequent source of studies (n = 5, 31%). Most studies (n = 11, 69%) were published in the past 10 years. The median sample size was 53 (IQR 41-988, range 10-3981). All papers included varying levels of patient characteristics, EMS input and patient outcomes. Hanging is a highly lethal method of suicide that is increasingly used in the UK. This scoping review found that there is scarce literature focused on hangings attended by EMS. Treatment of the hanging patient in cardiac arrest is described in many of the papers included. Hanging patients may benefit from the presence of specialist resources who can deliver interventions such as sedation and advanced airway management. The psychological impact of attending, or witnessing, hanging patients is an area that needs further consideration. Further research is needed to describe and improve EMS treatment of hangings.


A short receptor downregulates JAK/STAT signalling to control the Drosophila cellular immune response.
The posterior signalling centre (PSC), a small group of specialised cells, controls hemocyte (blood cell) homeostasis in the Drosophila larval hematopoietic organ, the lymph gland. This role of the PSC is very reminiscent of the "niche," the micro-environment of hematopoietic stem cells in vertebrates. We have recently shown that the PSC acts in a non-cell-autonomous manner to maintain janus tyrosine kinase/signal transducers and activators of transcription (JAK/STAT) signalling in hematopoietic progenitors (prohemocytes), thereby preserving the multipotent character necessary for their differentiation into lamellocytes, a cryptic and dedicated immune cell type required to fight specific immune threats such as wasp parasitism. In this report, on the basis of a knock out generated by homologous recombination, we show that a short type I cytokine-related receptor CG14225/Latran is required for switching off JAK/STAT signalling in prohemocytes. This is a prerequisite to massive differentiation of lamellocytes upon wasp parasitisation. In vivo and cell culture assays indicate that Latran forms heteromers with Domeless, the Drosophila type I cytokine signalling receptor related to mammalian GP130, and antagonises Domeless activity in a dose-dependent manner. Our analysis further shows that a primary immune response to wasp parasitism is a strong decrease in cytokine mRNA levels in the lymph gland, followed by an increase in the latran/domeless ratio. We propose that this sequence of events culminates in the complete inhibition of residual JAK/STAT signalling by Latran. JAK/STAT activity has been associated with several human diseases including leukaemia while knock-out studies in mice point to a central role of this pathway in hematopoiesis and regulation of immune functions. The specific function of Drosophila Latran is, to our knowledge, the first in vivo example of a role for a nonsignalling receptor in controlling a dedicated immune response, and thus raises the question of whether short, nonsignalling receptors also control specific aspects of vertebrate cellular immunity.


Heavy-tailed phase-space distributions beyond Boltzmann-Gibbs: Confined laser-cooled atoms in a nonthermal state.
The Boltzmann-Gibbs density, a central result of equilibrium statistical mechanics, relates the energy of a system in contact with a thermal bath to its equilibrium statistics. This relation is lost for nonthermal systems such as cold atoms in optical lattices, where the heat bath is replaced with the laser beams of the lattice. We investigate in detail the stationary phase-space probability for Sisyphus cooling under harmonic confinement. In particular, we elucidate whether the total energy of the system still describes its stationary state statistics. We find that this is true for the center part of the phase-space density for deep lattices, where the Boltzmann-Gibbs density provides an approximate description. The relation between energy and statistics also persists for strong confinement and in the limit of high energies, where the system becomes underdamped. However, the phase-space density now exhibits heavy power-law tails. In all three cases we find expressions for the leading-order phase-space density and corrections which break the equivalence of probability and energy and violate energy equipartition. The nonequilibrium nature of the steady state is corroborated by explicit violations of detailed balance. We complement these analytical results with numerical simulations to map out the intricate structure of the phase-space density.


The influence of footwear on the electromyographic activity of selected lower limb muscles during walking.
The purpose of this study was to compare the effects of a standard flexible shoe and a stability running shoe on lower limb muscle activity during walking. Twenty-eight young asymptomatic adults with flat-arched feet were recruited. While walking, electromyographic (EMG) activity was recorded from tibialis posterior and peroneus longus via intramuscular electrodes; and from tibialis anterior and medial gastrocnemius via surface electrodes. Three experimental conditions were assessed: (i) barefoot, (ii) a standard flexible shoe, (iii) a stability running shoe. Results showed significant differences for the peak amplitude and the time of peak amplitude for tibialis anterior, peroneus longus and medial gastrocnemius when comparing the three experimental conditions (p < 0.05). Significant differences were detected primarily between the barefoot and shoe conditions and with relatively small effect sizes for peroneus longus, tibialis anterior and medial gastrocnemius. Few significant differences were found between the two shoe styles. We discuss how these changes are most likely associated with the shoe upper bracing the foot, the shape of the shoe outer-sole and weight of the shoes. Further research is needed to investigate differences between these shoe styles when participants walk for longer distances (i.e. over 1000 m) and following fatigue.


Generalized three-dimensional lattice Boltzmann color-gradient method for immiscible two-phase pore-scale imbibition and drainage in porous media.
This article presents a three-dimensional numerical framework for the simulation of fluid-fluid immiscible compounds in complex geometries, based on the multiple-relaxation-time lattice Boltzmann method to model the fluid dynamics and the color-gradient approach to model multicomponent flow interaction. New lattice weights for the lattices D3Q15, D3Q19, and D3Q27 that improve the Galilean invariance of the color-gradient model as well as for modeling the interfacial tension are derived and provided in the Appendix. The presented method proposes in particular an approach to model the interaction between the fluid compound and the solid, and to maintain a precise contact angle between the two-component interface and the wall. Contrarily to previous approaches proposed in the literature, this method yields accurate solutions even in complex geometries and does not suffer from numerical artifacts like nonphysical mass transfer along the solid wall, which is crucial for modeling imbibition-type problems. The article also proposes an approach to model inflow and outflow boundaries with the color-gradient method by generalizing the regularized boundary conditions. The numerical framework is first validated for three-dimensional (3D) stationary state (Jurin's law) and time-dependent (Washburn's law and capillary waves) problems. Then, the usefulness of the method for practical problems of pore-scale flow imbibition and drainage in porous media is demonstrated. Through the simulation of nonwetting displacement in two-dimensional random porous media networks, we show that the model properly reproduces three main invasion regimes (stable displacement, capillary fingering, and viscous fingering) as well as the saturating zone transition between these regimes. Finally, the ability to simulate immiscible two-component flow imbibition and drainage is validated, with excellent results, by numerical simulations in a Berea sandstone, a frequently used benchmark case used in this field, using a complex geometry that originates from a 3D scan of a porous sandstone. The methods presented in this article were implemented in the open-source PALABOS library, a general C++ matrix-based library well adapted for massive fluid flow parallel computation.


Porphyria cutanea tarda and AIDS.
Two male patients, each of whom had one or more risk factors for human immunodeficiency virus, subsequently developed findings of porphyria cutanea tarda preceding diagnosis of acquired immune deficiency syndrome (AIDS).


Trans-Cricothyroid Membrane Injection of Local Anesthesia Attenuates Cough Response and Postoperative Sore Throat to the Nasotracheal Tube.
This study aims to investigate the effects of trans-cricothyroid membrane injection of local anesthesia on cough response and postoperative sore throat to the nasotracheal tube. Patients who require general anesthesia with nasotracheal tube for oral and maxillofacial surgery were randomised divided into groups L and C. The patients in group L received trans-cricothyroid membrane injection of 2% lidocaine (3 mL) before anesthesia. Meanwhile, the same volume of 0.9% saline was administered to group C. The incidences of cough response, mean arterial pressure (MAP) and heart rate (HR) were recorded during emergency from general anesthesia. Postoperative sore throat (POST) was assessed at 1, 6, 12 and 24 h after surgery. The data of 60 patients in group L and 61 in group C were included in this study. The incidence of cough was lower in group L than in group C, ie, 41.7% vs 67.2% upon extubation (P=0.006) and 20.0% vs 41.0% at five minutes after extubation (P=0.018). MAP and HR in group L were significantly lower than in group C during emergency from general anesthesia (P<0.05). POST incidence was significantly reduced in group L at 1 and 6 h after surgery, ie, 35.0% vs 55.7% at 1 h after surgery (P=0.029) and 20.0% vs 37.7% at 6 h after surgery (P=0.044). Trans-cricothyroid membrane injection of local anesthesia is a simple and effective method to attenuate the incidence of cough response during emergency from general anesthesia. This technique can reduce the incidence of POST after surgery.


Effect of piplartine and cinnamides on Leishmania amazonensis, Plasmodium falciparum and on peritoneal cells of Swiss mice.
Plants of the Piperaceae family produce piplartine that was used to synthesize the cinnamides. To assess the effects of piplartine (1) and cinnamides (2-5) against the protozoa responsible for malaria and leishmaniasis, and peritoneal cells of Swiss mice. Cultures of Leishmania amazonensis, Plasmodium falciparum-infected erythrocytes, and peritoneal cells were incubated, in triplicate, with different concentrations of the compounds (0 to 256 μg/mL). The inhibitory concentration (IC50) in L. amazonensis and cytotoxic concentration (CC50) in peritoneal cell were assessed by the MTT method after 6 h of incubation, while the IC50 for P. falciparum-infected erythrocytes was determined by optical microscopy after 48 or 72 h of incubation; the Selectivity Index (SI) was calculated by CC50/IC50. All compounds inhibited the growth of microorganisms, being more effective against P. falciparum after 72 h of incubation, especially for the compounds 1 (IC50 = 3.2 μg/mL) and 5 (IC50 = 6.6 μg/mL), than to L. amazonensis (compound 1 = 179.0 μg/mL; compound 5 = 106.0 μg/mL). Despite all compounds reducing the viability of peritoneal cells, the SI were <10 to L. amazonensis, whereas in the cultures of P. falciparum the SI >10 for the piplartine (>37.4) and cinnamides 4 (>10.7) and 5 (= 38.4). The potential of piplartine and cinnamides 4 and 5 in the treatment of malaria suggest further pre-clinical studies to evaluate their effects in murine malaria and to determine their mechanisms in cells of the immune system.


Pseudo-stir bar hollow fiber solid/liquid phase microextraction combined with anodic stripping voltammetry for determination of lead and cadmium in water samples.
A new procedure is presented for the determination of low concentrations of lead and cadmium in water samples. Ligand assisted pseudo-stir bar hollow fiber solid/liquid phase microextraction using sol-gel sorbent reinforced with carbon nanotubes was combined with differential pulse anodic stripping voltammetry for simultaneous determination of cadmium and lead in tap water, and Darongar river water samples. In the present work, differential pulse anodic stripping voltammetry (DPASV) using a hanging mercury drop electrode (HMDE) was used in order to determine the ultra trace level of lead and cadmium ions in real samples. This method is based on accumulation of lead and cadmium ions on the electrode using different ligands; Quinolin-8-ol, 5,7-diiodo quinoline-8-ol, 4,5-diphenyl-1H-imidazole-2(3H)-one and 2-{[2-(2-Hydroxy-ethylamino)-ethylamino]-methyl}-phenol as the complexing agent. The optimized conditions were obtained. The relationship between the peak current versus concentration was linear over the range of 0.05-500 ng mL(-1) for Cd (II) and Pb (II). The limits of detection for lead and cadmium were 0.015 ng mL(-1) and 0.012 ng mL(-1), respectively. Under the optimized conditions, the pre-concentration factors are 2440 and 3710 for Cd (II) and Pb (II) in 5 mL of water sample, respectively.


Innate Response to Human Cancer Cells with or without IL-2 Receptor Common γ-Chain Function in NOD Background Mice Lacking Adaptive Immunity.
Immunodeficient hosts exhibit high acceptance of xenogeneic or neoplastic cells mainly due to lack of adaptive immunity, although it still remains to be elucidated how innate response affects the engraftment. IL-2R common γ-chain (IL-2Rγc) signaling is required for development of NK cells and a subset of dendritic cells producing IFN-γ. To better understand innate response in the absence of adaptive immunity, we examined amounts of metastatic foci in the livers after intrasplenic transfer of human colon cancer HCT116 cells into NOD/SCID versus NOD/SCID/IL-2Rγc (null) (NOG) hosts. The intravital microscopic imaging of livers in the hosts depleted of NK cells and/or macrophages revealed that IL-2Rγc function critically contributes to elimination of cancer cells without the need for NK cells and macrophages. In the absence of IL-2Rγc, macrophages play a role in the defense against tumors despite the NOD Sirpa allele, which allows human CD47 to bind to the encoded signal regulatory protein α to inhibit macrophage phagocytosis of human cells. Analogous experiments using human pancreas cancer MIA PaCa-2 cells provided findings roughly similar to those from the experiments using HCT116 cells except for lack of suppression of metastases by macrophages in NOG hosts. Administration of mouse IFN-γ to NOG hosts appeared to partially compensate lack of IL-2Rγc-dependent elimination of transferred HCT116 cells. These results provide insights into the nature of innate response in the absence of adaptive immunity, aiding in developing tumor xenograft models in experimental oncology.


The risk of hepatotoxicity during long-term and low-dose flutamide treatment in hirsutism.
Flutamide is an effective drug in treatment of hirsutism. Hepatotoxicity occasionally may occur with therapeutic doses (750-1500 mg/day), 3 months after initiation of treatment. Monitoring of serum aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels is recommended to obviate serious hepatotoxicity. Two hundred and fourteen patients with mean age of 20.9+/-2.34 years suffering from hirsutism were included in the study. Of these 214 women, 117 had diagnosis of polycystic ovarian syndrome (PCOS), and 97 had diagnosis of idiopathic hirsutism. Thirty age-matched (mean age 20.3+/-2.0 years) normal women without signs of hirsutism and with normal menstrual cycle served as control group. Hirsutism was assessed using modified Ferriman-Gallwey method at the beginning and at the end of the treatment. Serum levels of luteinizing hormone (LH), follicle stimulant hormone (FSH), prolactin (PRL), estradiol (E2), androstenodion (A), testosterone (T), dehydrotestosterone (DHT), dehydroepiandrosterone sulfate (DHEAS), dehydroepiandrosterone (DHEA), 17-hydroxyprogesterone (17-P), sex hormone binding protein (SHBG), and ACTH were measured. Pelvic ultrasonography was performed for diagnosis of PCOS. Fifty-seven patients with PCOS (group 1) were given flutamide 125 mg/day + oral contraceptive. Sixty patients with PCOS (group 2) were given flutamide 250 mg/day + oral contraceptive. Forty-seven patients with IH (group 3) were given flutamide 125 mg/day alone, and 50 patients with IH (group 4) were given flutamide 250 mg alone. Thirty women in control group (group 5) were given placebo only. ALT and AST levels were measured in the beginning of the treatment, and repeated after 3, 6, 9 and 12 months. No incidence of increase in AST or ALT levels (>or= 45 U/L) was observed in any of the groups. No evidence of hepatotoxicity in any of the 214 hyperandrogenic women was observed on low-dose flutamide for 1 year. We conclude that flutamide in a dosage of 125 or 250 mg daily is a safe drug in the long-term treatment of hirsutism. The follow-up of patients receiving flutamide can be done by monitoring AST or ALT levels for hepatotoxicity.


In Situ and In Vitro Effects of Two Bleaching Treatments on Human Enamel Hardness.
The aim of this study was to evaluate in vitro and in situ the effects of two bleaching treatments on human enamel surface microhardness. Sixty enamel slabs from recently extracted thirty molars were used. The specimens were polished with sandpapers under water-cooling. The enamel samples were randomly divided in four groups, treated with 10% hydrogen peroxide (HP) or Whitening Strips (WS) containing 10% hydrogen peroxide and using two conditions: in vitro or in situ model. For in situ condition, six volunteers wore an intra-oral appliance containing enamel slabs, while for in vitro condition the specimens were kept in deionized water after the bleaching protocols. The bleaching treatments were applied one-hour daily for 14 days. Similar amounts of bleaching agents were used in both conditions. Before and after bleaching treatments, microhardness was measured. Statistical analysis (ANOVA and Tukey test) showed that in the in situ condition there was no statistically significant microhardness reduction in the bleached enamel (p>0.05). Significant decrease in hardness was observed for enamel slabs bleached with both treatments in the in vitro condition (p<0.05). Regarding the bleaching agents, in situ results showed no difference between HP and WS, while in vitro WS produced the lowest hardness value. It could be concluded that there was no deleterious effect on enamel produced by any of the bleaching protocols used in the in situ model. The reduction of hardness was only observed in vitro.


Quality of life assessment in HIV clinical research in resource-limited settings: better late than never.
Comprehensive and sustained optimal care for patients infected with HIV can now be achieved in resource-constrained settings, thanks to the sustainability of programs providing antiretroviral therapy (ART). But the primary goals of HIV virological suppression and improved survival need to be accompanied by a substantial improvement in patient's experience with HIV care and treatment. An assessment of both patients' quality of life and perceived toxicity and symptoms should now be systematically integrated into HIV clinical research in resource-constrained countries. This will allow treatment strategies aimed at optimizing the durability of response to ART in these settings to be properly evaluated and compared.


qUVR-10, a major quantitative trait locus for ultraviolet-B resistance in rice, encodes cyclobutane pyrimidine dimer photolyase.
Rice qUVR-10, a quantitative trait locus (QTL) for ultraviolet-B (UVB) resistance on chromosome 10, was cloned by map-based strategy. It was detected in backcross inbred lines (BILs) derived from a cross between the japonica variety Nipponbare (UV resistant) and the indica variety Kasalath (UV sensitive). Plants homozygous for the Nipponbare allele at the qUVR-10 locus were more resistant to UVB compared with the Kasalath allele. High-resolution mapping using 1850 F(2) plants enabled us to delimit qUVR-10 to a <27-kb genomic region. We identified a gene encoding the cyclobutane pyrimidine dimer (CPD) photolyase in this region. Activity of CPD photorepair in Nipponbare was higher than that of Kasalath and nearly isogenic with qUVR-10 [NIL(qUVR-10)], suggesting that the CPD photolyase of Kasalath was defective. We introduced a genomic fragment containing the CPD photolyase gene of Nipponbare to NIL(qUVR-10). Transgenic plants showed the same level of resistance as Nipponbare did, indicating that the qUVR-10 encoded the CPD photolyase. Comparison of the qUVR-10 sequence in the Nipponbare and Kasalath alleles revealed one probable candidate for the functional nucleotide polymorphism. It was indicated that single-base substitution in the CPD photolyase gene caused the alteration of activity of CPD photorepair and UVB resistance. Furthermore, we were able to develop a UV-hyperresistant plant by overexpression of the photolyase gene.


Focus cardiac ultrasound: the European Association of Cardiovascular Imaging viewpoint.
The concept of point-of-care, problem-oriented focus cardiac ultrasound examination (FoCUS) is increasingly applied in the settings of medical emergencies, including cardiac diseases. The European Association of Cardiovascular Imaging (EACVI) recognizes that cardiologists are not the only medical professionals dealing with cardiovascular emergencies. In reality, emergency cardiac diagnostics and treatment are also carried out by a wide range of specialists. For the benefit of the patients, the EACVI encourages any medical professional, sufficiently trained to obtain valuable information from FoCUS, to use it in emergency settings. These medical professionals need to have the necessary knowledge to understand the obtained information entirely, and to use it correctly, thoughtfully and with care. In this document, the EACVI underlines major differences between echocardiography and FoCUS, and underscores the need for specific education and training in order to fully utilize advantages and minimize drawbacks of this type of cardiac ultrasound examination in the critically ill patients.


[Maternal hemoglobin in Peru: regional differences and its association with adverse perinatal outcomes].
To evaluate hemoglobin (Hb) levels in pregnant women from different geographical regions from Peru; to establish anemia and erythrocytocis rates and to establish the role of Hb on adverse perinatal outcomes using the Perinatal Information System (PIS) database of Peruvian Ministry of Health. Data were obtained from 379,816 births of 43 maternity care units between 2000 and 2010. Anemia and erythrocytocis rates were determined in each geographical region as well as rates of adverse perinatal outcomes. To analyze data the STATA program (versión 10.0,Texas, USA) was used. The results were considered significant at p<0.01. Mild anemia rate was higher in the coast (25.8%) and low forest (26.2%). Moderate/severe anemia rate in low forest was 2.6% and at the coast was 1.0%. In the highland, the highest rate of moderate/severe anemia was in the southern highlands (0.6%). The highest rate of erythrocytocis was found in the central highland (23.7%), 11.9% in the southern highland and 9.5% in the north highland. Severe anemia and erythrocytocis were associated with adverse perinatal outcomes. There are differences by Peruvian geographical region in anemia rates. In the central highlands were found the highest rates of erythrocytocis due to hypoxia effect in the high altitudes; however in the southern highlands, erythrocytocis was lower. Severe anemia and erythrocytosis were associated with increased adverse perinatal outcomes.


Cytotoxic activity of IMMUNEPOTENT CRP against non-small cell lung cancer cell lines.
IMMUNEPOTENT-CRP® (I-CRP) is a bovine dialyzable leukocyte extract containing transfer factor. It is a cost-effective, unspecific active immunotherapy that has been used in patients with non-small cell lung cancer (NSCLC) as an adjuvant to reduce the side-effects of chemotherapy and radiotherapy, and has shown cytotoxic activity in vitro on different cancer cell lines. However, its mechanism of action against lung cancer cells has not been assessed. Therefore, the objective of this work was to assess the cytotoxic mechanism of I-CRP on lung cancer cell lines. We assessed cell viability through MTT assay on the NSCLC cell lines A549, A427, Calu-1, and INER-51 after treatment with I-CRP. To further understand the mechanisms of cell viability diminution we used fluorescence-activated cell sorting to evaluate cell death (annexin-V and propidium iodide [PI] staining), cell cycle and DNA degradation (PI staining), mitochondrial alterations (TMRE staining), and reactive oxygen species (ROS) production (DCFDA staining). Additionally, we evaluated caspase and ROS dependence of cell death by pretreating the cells with the pan-caspase inhibitor Q-VD-OPH and the antioxidant N-acetylcysteine (NAC), respectively. Our data shows that I-CRP is cytotoxic to NSCLC cell lines in a dose and time dependent manner, without substantial differences between the four cell lines tested (A549, A427, Calu-1, and INER-51). Cytotoxicity is induced through regulated cell death and cell cycle arrest induction. I-CRP-induced cell death in NSCLC cell lines is characterized by DNA degradation, mitochondrial damage, and ROS production. Moreover, cell death is independent of caspases but relies on ROS production, as it is abrogated with NAC. Altogether, these results improve the knowledge about the cytotoxic activity of I-CRP on NSCLC cells, indicating that cell death, cell cycle arrest, DNA degradation and mitochondrial damage are important features, while ROS play the main role for I-CRP mediated cytotoxicity in lung cancer cells.


Herminiimonas contaminans sp. nov., isolated as a contaminant of biopharmaceuticals.
A Gram-staining-negative, rod-shaped, non-spore-forming bacterium isolated as a contaminant from a biopharmaceutical process (strain CCUG 53591(T)) was studied for its taxonomic allocation. On the basis of 16S rRNA gene sequence similarity data, this strain was clearly allocated to the genus Herminiimonas. Herminiimonas saxobsidens was shown to be the most closely related species on the basis of 16S rRNA gene sequence similarity (99.9 %), followed by Herminiimonas glaciei (99.6 %) and Herminiimonas arsenicoxydans (98.8 %). Strain ND5, previously reported as H. glaciei, but showing 100 % 16S rRNA gene sequence similarity to strain CCUG 53591(T), was included in the comparative study. Similarities to all other species of the genus Herminiimonas were below 98.0 %. Chemotaxonomic data (major ubiquinone, Q-8; major polar lipids, phosphatidylethanolamine, phosphatidylglycerol and diphosphatidylglycerol; and major fatty acids, C(17 : 0) cyclo, C(19 : 0) cyclo ω8c and C(16 : 0,) with C(10 : 0) 3-OH as hydroxylated fatty acid) supported the affiliation of the isolate to the genus Herminiimonas. DNA-DNA hybridization results (mean values) for strain CCUG 53591(T) with H. saxobsidens CCUG 59860(T) (34 %), H. glaciei DSM 21140(T) (57 %), H. arsenicoxydans DSM 17148(T) (17 %) and Herminiimonas fonticola S-94(T) (11 %) clearly supported the separate taxonomic position of this strain. Strain ND5 showed DNA-DNA similarities of 78, 56 and 52 % to strain CCUG 53591(T), H. glaciei DSM 21140(T) and H. saxobsidens CCUG 59860(T), respectively. Phenotypic differentiation of the isolate from the most closely related species was possible by various features. Hence, strain CCUG 53591(T) represents a novel species, for which the name Herminiimonas contaminans sp. nov. is proposed, with the type strain CCUG 53591(T) ( = CCM 7991(T)). Strain ND5 is a second strain of this species.


Epidemiological evaluation of cytogenetic biomarkers as potential surrogate end-points for cancer.
Various occupational exposures have been monitored by chromosomal aberrations, sister chromatid exchanges and micronuclei in peripheral blood lymphocytes. During the last decade, epidemiological studies have evaluated whether any of these markers foreshadows cancer risk. Results from Nordic, Italian and Czech cohorts support an approximately twofold cancer risk among subjects with high frequencies of chromosomal aberrations, but no such association was seen for any of the other biomarkers. The estimated attributable proportion of high frequencies of chromosomal aberrations for overall cancer risk is 0.25, which gives a quantitative estimate of the chromosomal aberration assay as a surrogate endpoint of cancer. The results from the different cohort studies are contradictory in terms of whether or not the predictive value of the chromosomal aberration assay for cancer is differential with respect to occupational exposure to clastogens. Genetic susceptibility factors are known to affect the frequency of chromosomal aberrations in peripheral blood lymphocytes. It is quite possible that such factors might also affect the frequency of chromosomal aberrations directly or might modify the impact of exposures to clastogen. There is no other biomarker for general cancer risk that is applicable to healthy subjects from the general population with such a high attributable proportion. However, at present only a simplified and tentative model can be proposed for the role of the chromosomal aberration marker in the pathogenesis of cancer.


Anti-proliferative effect of rhein, an anthraquinone isolated from Cassia species, on Caco-2 human adenocarcinoma cells.
In recent years, the use of anthraquinone laxatives, in particular senna, has been associated with damage to the intestinal epithelial layer and an increased risk of developing colorectal cancer. In this study, we evaluated the cytotoxicity of rhein, the active metabolite of senna, on human colon adenocarcinoma cells (Caco-2) and its effect on cell proliferation. Cytotoxicity studies were performed using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT), neutral red (NR) and trans-epithelial electrical resistance (TEER) assays whereas (3)H-thymidine incorporation and Western blot analysis were used to evaluate the effect of rhein on cell proliferation. Moreover, for genoprotection studies Comet assay and oxidative biomarkers measurement (malondialdehyde and reactive oxygen species) were used. Rhein (0.1-10 microg/ml) had no significant cytotoxic effect on proliferating and differentiated Caco-2 cells. Rhein (0.1 and 1 microg/ml) significantly reduced cell proliferation as well as mitogen-activated protein (MAP) kinase activation; by contrast, at high concentration (10 microg/ml) rhein significantly increased cell proliferation and extracellular-signal-related kinase (ERK) phosphorylation. Moreover, rhein (0.1-10 microg/ml): (i) did not adversely affect the integrity of tight junctions and hence epithelial barrier function; (ii) did not induce DNA damage, rather it was able to reduce H(2)O(2)-induced DNA damage and (iii) significantly inhibited the increase in malondialdehyde and reactive oxygen species (ROS) levels induced by H(2)O(2)/Fe(2+). Rhein was devoid of cytotoxic and genotoxic effects in colon adenocarcinoma cells. Moreover, at concentrations present in the colon after a human therapeutic dosage of senna, rhein inhibited cell proliferation via a mechanism that seems to involve directly the MAP kinase pathway. Finally, rhein prevents the DNA damage probably via an anti-oxidant mechanism.


Technique for inguino-femoral lymph node dissection in vulvar cancer: an international survey.
Vulvar cancer is a rare disease and despite broad adoption of sentinel lymph node mapping to assess groin metastases, inguino-femoral lymph node dissection still plays a role in the management of this disease. Inguino-femoral lymph node dissection is associated with high morbidity, and limited research exists to guide the best surgical approach. To determine international practice patterns in key aspects of the inguino-femoral lymph node dissection technique and provide data to guide future research. A survey addressing six key domains of practice patterns in performing inguino-femoral lymph node dissection was distributed internationally to gynecologic oncology surgeons between April and October 2020. The survey was distributed using the British Gynecological Cancer Society, the Society of Gynecologic Oncology, authors' direct links, the UK Audit and Research in Gynecology Oncology group, and Twitter. A total of 259 responses were received from 18 countries. The majority (236/259, 91.1%) of respondents reported performing a modified oblique incision, routinely dissecting the superficial and deep inguino-femoral lymph nodes (137/185, 74.1%) with sparing of the saphenous vein (227/258, 88%). Most respondents did not routinely use compression dressings/underwear (169/252 (67.1%), used prophylactic antibiotics at the time of surgery only (167/257, 65%), and closed the skin with sutures (192 74.4%). Also, a drain is placed at the time of surgery by 243/259 (93.8%) surgeons, with most practitioners (144/243, 59.3%) waiting for drainage to be less than 30-50 mL in 24 hours before removal; most respondents (66.3%) routinely discharge patients with drain(s) in situ. Our study showed that most surgeons perform a modified oblique incision, dissect the superficial and deep inguino-femoral lymph nodes, and spare the saphenous vein when performing groin lymphadenectomy. This survey has demonstrated significant variability in inguino-femoral lymph node dissection in cases of vulvar cancer among gynecologic oncology surgeons internationally.


A role for flavin monooxygenase-like enzymes in auxin biosynthesis.
Although auxin is known to regulate many processes in plant development and has been studied for over a century, the mechanisms whereby plants produce it have remained elusive. Here we report the characterization of a dominant Arabidopsis mutant, yucca, which contains elevated levels of free auxin. YUCCA encodes a flavin monooxygenase-like enzyme and belongs to a family that includes at least nine other homologous Arabidopsis genes, a subset of which appears to have redundant functions. Results from tryptophan analog feeding experiments and biochemical assays indicate that YUCCA catalyzes hydroxylation of the amino group of tryptamine, a rate-limiting step in tryptophan-dependent auxin biosynthesis.


Metabolism, Nutrition, and Redox Signaling of Hydroxyproline.
Hydroxyproline is a structurally and physiologically important imino acid in animals. It is provided from diets and endogenous synthesis, and its conversion into glycine enhances the production of glutathione, DNA, heme, and protein. Furthermore, oxidation of hydroxyproline by hydroxyproline oxidase (OH-POX) plays an important role in cell antioxidative reactions, survival, and homeostasis. Understanding the mechanisms whereby hydroxyproline participates in metabolism and cell signaling can improve the nutrition and health of animals and humans. Recent Advances: Hydroxyproline is highly abundant in milk and is utilized for renal synthesis of glycine to support neonatal growth, development, and survival. The oxidation of hydroxyproline by mitochondrial OH-POX generates reactive oxygen species (ROS). Enhanced ROS production contributes to the regulation of oxidative defense, apoptosis, angiogenesis, tumorigenesis, hypoxic responses, and cell survival in animals. Although dietary hydroxyproline enters the portal circulation, its utilization by the portal-drained viscera is unknown. Pathways for hydroxyproline metabolism and their regulation at the molecular, cellular, and whole-body levels remain to be defined. Furthermore, the mechanisms responsible for hydroxyproline-derived ROS and related metabolites to induce cell survival or apoptosis are unknown. Interorgan metabolism of hydroxyproline (including synthesis, catabolism, and flux) in animals must be quantified using isotope technologies. Efforts should also be directed toward studying dietary, hormonal, and epigenetic regulation of OH-POX expression at transcriptional and translational levels. Another emerging research need is to understand the roles of cellular redox and signaling networks involving both ROS and Δ1-pyrroline-3-hydroxy-5-carboxylate in nutrition, health, and disease.


[Effect of measured chemical sympathectomy on the dynamics of the chromatin functional indices of rat sympathetic neurocytes during their differentiation].
Differences have been found between age-related shifts of DNA template activity of sympathetic neuron chromatin of normal and guanethidine-desympathized rats. The mean level of DNA template activity in mature neurons was the higher the heavier the desympathization of rat. In the ganglia of guanethidine-treated rats a subpopulation of neurocytes was revealed with an unusually high nucleolar-to-nucleoplasmic label ratio, never observed in control rats. The maturational disturbances in the course of alterations in histones visualized by ammoniacal silver, as well as shifts in the percentage of specifically stained nuclei are proportional to the level of desympathization. These changes in histones can be interpreted as a preliminary acceleration and aging of guanethidine-treated rat ganglia which are proportional to the number of destructed cells.


Comparative efficacy of the Cognitive Behavioral Analysis System of Psychotherapy versus supportive psychotherapy for early onset chronic depression: design and rationale of a multisite randomized controlled trial.
Effective treatment strategies for chronic depression are urgently needed since it is not only a common and particularly disabling disorder, but is also considered treatment resistant by most clinicians. There are only a few studies on chronic depression indicating that traditional psycho- and pharmacological interventions are not as effective as in acute, episodic depression. Current medications are no more effective than those introduced 50 years ago whereas the only psychotherapy developed specifically for the subgroup of chronic depression, the Cognitive Behavioral Analysis System of Psychotherapy (CBASP), faired well in one large trial. However, CBASP has never been directly compared to a non-specific control treatment. The present article describes the study protocol of a multisite parallel-group randomized controlled trial in Germany. The purpose of the study is to estimate the efficacy of CBASP compared to supportive psychotherapy in 268 non-medicated early-onset chronically depressed outpatients. The intervention includes 20 weeks of acute treatment with 24 individual sessions followed by 28 weeks of continuation treatment with another 8 sessions. Depressive symptoms are evaluated 20 weeks after randomisation by means of the 24-item Hamilton Rating Scale of Depression (HRSD). Secondary endpoints are depressive symptoms after 12 and 48 weeks, and remission after 12, 20, and 48 weeks. Primary outcome will be analysed using analysis of covariance (ANCOVA) controlled for pre-treatment scores and site. Analyses of continuous secondary variables will be performed using linear mixed models. For remission rates, chi-squared tests and logistic regression will be applied. The study evaluates the comparative effects of a disorder-specific psychotherapy and a well designed non-specific psychological approach in the acute and continuation treatment phase in a large sample of early-onset chronically depressed patients. ClinicalTrials.gov (NCT00970437).


Hard-to-Reach Populations and Administrative Health Data: A Serial Cross-sectional Study and Application of Data to Improve Interventions for People Experiencing Homelessness.
Intervention studies with vulnerable groups in the emergency department (ED) suffer from lower quality and an absence of administrative health data. We used administrative health data to identify and describe people experiencing homelessness who access EDs, characterize patterns of ED use relative to the general population, and apply findings to inform the design of a peer support program. We conducted a serial cross-sectional study using administrative health data to examine ED use by people experiencing homelessness and nonhomeless individuals in the Niagara region of Ontario, Canada from April 1, 2010 to March 31, 2018. Outcomes included number of visits; unique patients; group proportions of Canadian Triage and Acuity Scale (CTAS) scores; time spent in emergency; and time to see an MD. Descriptive statistics were generated with t tests for point estimates and a Mann-Whitney U test for distributional measures. We included 1,486,699 ED visits. The number of unique people experiencing homelessness ranged from 91 in 2010 to 344 in 2017, trending higher over the study period compared with nonhomeless patients. Rate of visits increased from 1.7 to 2.8 per person. People experiencing homelessness presented later with higher overall acuity compared with the general population. Time in the ED and time to see an MD were greater among people experiencing homelessness. People experiencing homelessness demonstrate increasing visits, worse health, and longer time in the ED when compared with the general population, which may be a burden on both patients and the health care system.


Radiation-induced inhibition of tumor growth as monitored by PET using L-[1-11C]tyrosine and fluorine-18-fluorodeoxyglucose.
The potential use of PET to monitor radiotherapeutic effects on tumors has been evaluated with L-[1-11C]tyrosine and 18FDG. Single x-ray doses of 10, 30, or 50 Gy have been applied to rhabdomyosarcoma tumors growing in the flank of rats. Dose-dependent reductions of tracer uptake were registered by PET 4 and 12 days after treatment. These later effects on tracer uptake appeared to correlate with changes in tumor volume. Therefore, PET using L-[1-11C]tyrosine and 18FDG is suitable to monitor kinetics of tumor growth and tumor regression after radiotherapy. Direct effect on tracer uptake was not observed within 8 hr after irradiation. This indicates that, using PET, early predictions on the outcome of radiotherapy are not possible. When combining a radiation treatment with hyperthermia, radiation-induced inhibition of tumor growth was clearly enhanced. Tracer uptake remained at the pretreatment value, possibly due to invasion of host cells. From these experiments, it can be concluded that it is difficult to monitor a combined treatment of radiation and hyperthermia by PET.


Heat stress on microbiota composition, barrier integrity, and nutrient transport in gut, production performance, and its amelioration in farm animals.
Livestock species experience several stresses, particularly weaning, transportation, overproduction, crowding, temperature, and diseases in their life. Heat stress (HS) is one of the most stressors, which is encountered in livestock production systems throughout the world, especially in the tropical regions and is likely to be intensified due to global rise in environmental temperature. The gut has emerged as one of the major target organs affected by HS. The alpha- and beta-diversity of gut microbiota composition are altered due to heat exposure to animals with greater colonization of pathogenic microbiota groups. HS also induces several changes in the gut including damages of microstructures of the mucosal epithelia, increased oxidative insults, reduced immunity, and increased permeability of the gut to toxins and pathogens. Vulnerability of the intestinal barrier integrity leads to invasion of pathogenic microbes and translocation of antigens to the blood circulations, which ultimately may cause systematic inflammations and immune responses. Moreover, digestion of nutrients in the guts may be impaired due to reduced enzymatic activity in the digesta, reduced surface areas for absorption and injury to the mucosal structure and altered expressions of the nutrient transport proteins and genes. The systematic hormonal changes due to HS along with alterations in immune and inflammatory responses often cause reduced feed intake and production performance in livestock and poultry. The altered microbiome likely orchestrates to the hosts for various relevant biological phenomena occurring in the body, but the exact mechanisms how functional communications occur between the microbiota and HS responses are yet to be elucidated. This review aims to discuss the effects of HS on microbiota composition, mucosal structure, oxidant-antioxidant balance mechanism, immunity, and barrier integrity in the gut, and production performance of farm animals along with the dietary ameliorations of HS. Also, this review attempts to explain the mechanisms how these biological responses are affected by HS.


The human papillomavirus 16 E6 protein binds to tumor necrosis factor (TNF) R1 and protects cells from TNF-induced apoptosis.
High risk strains of human papillomavirus (HPV), such as HPV 16, cause human cervical carcinoma. The E6 protein of HPV 16 mediates the rapid degradation of p53, although this is not the only function of E6 and cannot completely explain its transforming potential. Previous work in our laboratory has demonstrated that transfection of HPV 16 E6 into the tumor necrosis factor (TNF)-sensitive LM cell line protects expressing cells from TNF-induced apoptosis in a p53-independent manner, and the purpose of this study was to determine the molecular mechanism underlying this protection. Caspase 3 and caspase 8 activation were significantly reduced in E6-expressing cells, indicating that E6 acts early in the TNF apoptotic pathway. In fact, E6 binds directly to TNF R1, as shown both by co-immunoprecipitation and mammalian two-hybrid approaches. E6 requires the same C-terminal portion of TNF R1 for binding as does TNF R1-associated death domain, and TNF R1/TNF R1-associated death domain interactions are decreased in the presence of E6. HA-E6 also blocked cell death triggered by transfection of the death domain of TNF R1. Together, these results provide strong support for a model in which HPV E6 binding to TNF R1 interferes with formation of the death-inducing signaling complex and thus with transduction of proapoptotic signals. They also demonstrate that HPV, like several other viruses, has developed a method for evading the TNF-mediated host immune response.


Estimation of manganese daily intake among adults in Korea.
The purpose of this study was to estimate daily intake of manganese in Korean adults. Manganese intake was estimated through the use of the database of manganese content in frequently consumed Korean foods after first conducting anthropometric measurement and a survey on dietary intake with 354 Korean adults. Average age, height, weight and body mass index were 54.6 years, 165.7 cm, 67.2 kg and 24.5 kg/m(2) in males and 53.8 years, 153.7 cm, 59.1 kg and 24.9 kg/m(2) in females. The daily energy intakes of subjects were 1740.1 kcal in males and 1432.6 kcal in females. Male and female subjects recorded, respectively, 5.2 mg and 4.1 mg in manganese intake indicating that the male subjects consume more manganese (p<0.001). And they posted, respectively, 3.0 mg and 2.9 mg in manganese intake per 1000 kcal of energy consumption; it turned out that there was no significant difference. Daily manganese intake of both males and females posted, respectively, 148.8% and 135.2% of the adequate intake, and 8 males and 3 females surpassed the tolerable upper intake level. It is suggested that the study for accurate determination of manganese consumption needs to be more diversified based on the database of manganese content in Korean foods.


Activation of phosphodiesterase in frog rod outer segment by an intermediate of rhodopsin photolysis I.
Guanosine 3',5'-cyclic monophosphate phosphodiesterase (EC 22.214.171.124) in frog rod outer segment prepared by a sucrose stepwise density gradient method was activated by light in the presence of GTP. Rhodopsin in rod outer segment was solubilized with sucrose laurylmonoester and then purified by concanavalin A-Sepharose column. Addition of photo-bleached preparation of the purified rhodopsin to the crude rod outer segment, which had been prepared by 43% (w/w) sucrose floatation, caused the activation of phosphodiesterase in the dark, while each component of the photo-product eluted from the column (all-trans retinal and opsin) did not. Regenerated rhodopsin prepared from 11-cis retinal and purified opsin activated phosphodiesterase when it was bleached. From these facts it is suggested that an intermediate or a process of photolysis of rhodopsin causes activation of phosphodiesterase.


CD4+/CD8+ Ratio and Growth Differentiation Factor 8 Levels in Peripheral Blood of Large Canine Males Are Useful Parameters to Build an Age Prediction Model.
To build an age prediction model, we measured CD4+ and CD8+ cells, and humoral components in canine peripheral blood. Large Belgian Malinois (BGM) and German Shepherd Dog (GSD) breeds (n=27), aged from 1 to 12 years, were used for this study. Peripheral bloods were obtained by venepuncture, then plasma and peripheral blood mononuclear cells (PBMCs) were separated immediately. Six myokines, including interleukin (IL)-6, IL-8, IL-15, leukemia inhibitory factor (LIF), growth differentiation factor 8 (GDF8), and GDF11 were measured from plasma and CD4+/CD8+ T-lymphocytes ratio were measured from PBMC. These parameters were then tested with age prediction models to find the best fit model. We found that the T-lymphocyte ratio (CD4+/CD8+) was significantly correlated with age (r=0.46, p=0.016). Among the six myokines, only GDF8 showed a significant correlation with age (r=0.52, p=0.005). Interestingly, these two markers showed better correlations in male dogs than females, and BGM breed than GSD. Using these two age biomarkers, we could obtain the best fit in a quadratic linear mixed model (r=0.77, p=3×10-6). Age prediction is a challenging task because of complication with biological age. Our quadratic linear mixed model using CD4+/CD8+ ratio and GDF8 level showed a meaningful age prediction.


Effect of various essential oils isolated from Douglas fir needles upon sheep and deer rumen microbial activity.
The effects of essential oils isolated from Douglas fir needles on sheep and deer rumen microbial activity were tested by use of an anaerobic manometric technique. Rumen microorganisms were obtained from a sheep which had been fed mainly on alfalfa hay and dried range grass. One deer used in this study had access to Douglas fir trees the year around, whereas the other deer had no access to Douglas fir. All of the monoterpene hydrocarbons isolated from Douglas fir needles-alpha-pinene, beta-pinene, limonene, myrcene, camphene, Delta(3)-carene, and terpinolene-promoted only slightly or had no effect on deer rumen microbial activity, whereas all of them promoted activity in sheep rumen microbes, except Delta(3)-carene and terpinolene, which inhibited activity. Of the oxygenated monoterpenes, all monoterpene alcohols-alpha-terpineol, terpinen-4-ol, linalool, citronellol, and fenchyl alcohol-strongly inhibited the rumen microbial activity of both sheep and deer. Monoterpene esters (bornyl acetate) produced mild inhibition for both sheep and deer microbes, and citronellyl acetate inhibited rumen microbial activity in sheep, whereas it promoted activity in both deer. Monoterpene aldehyde (citronellal) inhibited the activity of rumen microbes from both sheep and deer having no access to Douglas fir from the Hopland Field Station, whereas they produced no effect upon the deer having access to Douglas fir from the Masonite forest. Rumen microbial activity for sheep and deer was promoted slightly with aliphatic ester (ethyl-n-caproate). There was a marked difference between sheep and deer rumen microbes as affected by addition of the various essential oils. The monoterpene hydrocarbons promoted activity more on sheep rumen microbes than on deer, and the monoterpene alcohols inhibited sheep rumen microbial activity more than that of deer. Furthermore, the deer rumen microbes from Hopland Field Station were affected more than the deer from Masonite forest.


16S-23S rDNA internal transcribed spacer sequences for analysis of the phylogenetic relationships among species of the genus Fusobacterium.
The 16S-23S rDNA internal transcribed spacer (ITS) regions of all currently defined Fusobacterium species and related taxa such as Leptotrichia buccalis, Sebaldella termitidis and Streptobacillus moniliformans, were analysed to examine inter- and intraspecies as well as subspecies relationships. For the ITS-amplification, a new eubacterial universal primer pair was designed and used. The majority of the Fusobacterium strains, along with L. buccalis showed one major, and two to three weaker, distinct bands (short and long versions) with lengths of 800-830 bp and 1000-1100 bp. Nevertheless, six other patterns were also found within the genus Fusobacterium, demonstrating its heterogeneity. The ITS region was sequenced and found to consist both of conserved motifs, which functioned as a framework for alignment, and of variable sites, which provided high phylogenetic resolution. Analyses of the ITS-DNA sequences and ITS relative length (short version) allowed species and subspecies differentiation in most cases. The results confirmed the strikingly distant relationship between Fusobacterium prausnitzii and the genus Fusobacterium. Fusobacterium nucleatum subspecies, along with Fusobacterium naviforme, Fusobacterium simiae and Fusobacterium periodonticum, formed a cluster with an inherently high potential for diversification. Other clusters were formed by Fusobacterium necrophorum subspecies with Fusobacterium gonidaformans and by Fusobacterium varium with Fusobacterium mortiferum and Fusobacterium ulcerans. Fusobacterium russii as well as Fusobacterium perfoetens formed separate branches. Fusobacterium necrophorum subspp. necrophorum and funduliforme on the one hand, and Fusobacterium varium and Fusobacterium mortiferum on the other, were found to be very similar, even at the high-resolution ITS level.


Accuracy of duplex ultrasound in evaluating carotid artery anatomy before endarterectomy.
Anatomic features, such as a high carotid bifurcation (< 1.5 cm from the angle of the mandible), excessive distal extent of plaque (> 2.0 cm above the carotid bifurcation), or a small diameter (< or = 0.5 cm) redundant or kinked internal carotid artery can complicate carotid endarterectomy. In the past, arteriography was the only preoperative study capable of imaging these features. This study assessed the ability of duplex ultrasound to evaluate their presence before surgery. A consecutive series of 20 patients who underwent 21 carotid endarterectomies had preoperative duplex ultrasound evaluations of these anatomic features. These evaluations were correlated with operative measurements from an observer blinded to the duplex findings. The mean difference between duplex and operative measurements for the distance between the carotid bifurcation and the angle of the mandible, the distal extent of plaque, and the internal carotid artery diameter was 0.9 cm, 0.3 cm, and 0.8 mm, respectively. The correlation coefficient between the two methods was 0.86, 0.75, and 0.59, respectively. Duplex ultrasound predicted a high carotid bifurcation, excessive distal extent of plaque, or a redundant or kinked internal carotid artery with 100% sensitivity (p < 0.05, p < 0.01, and p < 0.001, respectively). The sensitivity of duplex ultrasound in predicting a small internal carotid artery diameter was 80%. The specificity of duplex ultrasound for predicting excessive distal extent of plaque, small internal carotid artery diameter, high carotid bifurcation, and a coiled or kinked carotid artery was 92%, 56%, 100%, and 100%, respectively. Duplex ultrasound can predict the presence of anatomic features that may complicate carotid endarterectomy. Preoperative duplex imaging of these features may be helpful in patients who undergo carotid endarterectomy without preoperative arteriography.


Long-term outcome after venom immunotherapy.
There have been a limited number of studies examining the outcome after discontinuing venom immunotherapy (VIT), all of which showed continued protection in the great majority of patients. Several different criteria have been proposed to select patients to stop treatment based on immunologic and clinical factors. Specific high-risk factors have been reported from these published reports. There have been very few reports of the outcome more than 5 years after stopping VIT and virtually none on patients who had discontinued treatment for more than 10 years. This review will summarize the published evidence for current guidelines and recommendations, with emphasis on long-term outcomes. There has been a paucity of studies of VIT in recent years, particularly regarding long-term outcomes. These studies have raised questions about whether the long-term outcome is different with less than 3 years than with more than 3 years of treatment. Recent studies have confirmed the roughly 15% chance of systemic reaction to a sting after stopping VIT and the low risk (<3%) of a severe reaction. New and meaningful observations have been made in several reports regarding the increased risk of relapse, and even death, in patients with mastocytosis or elevated baseline serum tryptase, who had discontinued VIT. This review incorporates old and new observations that provide the basis for the guidelines and practice parameters on discontinuing VIT.


Balloon atrial septostomy through internal jugular vein in a 45-day-old child with transposition of great arteries.
Balloon atrial septostomy is a common palliative procedure in D-transposition of great arteries. It is technically easy before 2-3 weeks of age when the septum primum is thin. Femoral vein or umbilical vein, when available, is the common access used for this procedure. In situations when these accesses are not available or in case of inferior vena cava interruption, trans-hepatic access is used. Internal jugular vein (IJV) access is not used as it is difficult to enter the left atrium through this route. We describe a case of successful Balloon atrial septostomy done through IJV in a 45-day-old child with emphasis on the technique, hardware and precautions necessary during the procedure.


Tibiofemoral joint kinetics during squatting with increasing external load.
There is limited information about the effects of increasing load while squatting. To quantify tibiofemoral joint kinetics during squatting with variable loads. Research laboratory. 20 male students. Tibiofemoral joint kinetics and electromyographic (EMG) activity of four involved muscles were determined by recording the half squat with variable external loads. Tibiofemoral joint force and external moment components and EMG activity of four involved muscles. Throughout the exercise, a posterior direction for the antero-posterior shear force and a net extension for the external moment were observed. They increased with knee flexion reaching peak force of 29% of the subject body weight (BW) and moment of 88Nm (without external load). All force and moment components and muscle activities increased as the external load increased. These findings suggest that half squat may be safe to use for quadriceps strengthening with very low potential loading on the anterior cruciate ligament (ACL). Our data can help clinicians choose the appropriate external load.


The effects of accelerated growth rates and estrogen implants in prepubertal Holstein heifers on estimates of mammary development and subsequent reproduction and milk production.
The objectives of this study were to determine the effects of accelerating growth rates and of imposing estrogen implants in prepubertal heifers on mammary development and subsequent reproduction and milk production. Sixty-eight Holstein heifers were assigned to 1 of 4 treatment groups by using a randomized complete block design in a 2 x 2 factorial arrangement. The treatments were standard growth rate (700 g/d) or accelerated growth rate (1000 g/d) and estrogen implant or no estrogen implant. The treatments were imposed over 20 wk, beginning at 4.5 mo of age and 130 kg of body weight (BW). During the treatment period, all heifers were fed individually and received the same diet, but the dry matter intake of each heifer was adjusted weekly to achieve the designated growth rate. The estrogen implants were removed at the end of the treatment period at 9.5 mo of age. After the treatment period, the heifers were group fed according to BW and age to allow the heifers to have a similar BW and age at calving. The accelerated growth regimen decreased age at puberty by 32 d. Age, BW, and body condition scores at calving were not significantly different among treatments. The accelerated prepubertal growth regimen decreased first lactation fat-corrected milk yield 7.1%. Prepubertal heifers given estrogen implants produced 5.2% less fat-corrected milk during first lactation than did heifers not implanted with estrogen. Estrogen implants stimulated a large increase in teat length growth during the treatment period, but the advantage was lost posttreatment. Over both the treatment and posttreatment periods, the estrogen implants reduced teat length growth by 30%. Accelerated growth rates from 700 to 1000 g/d and estrogen implants in prepubertal heifers decreased first lactation milk production.