Private body consciousness, anxiety and the perception of pain.
Two studies are described which present data consistent with Barsky and Klerman's hypothesis that people who report pain in the absence of an identifiable organic etiology may be attending to and amplifying normal bodily sensations. The results of these studies demonstrated that young college students with a predisposition toward focusing attention on somatic symptoms (high private body consciousness) and scoring high on State Anxiety reported more areas of aches and pains and rated these sensations as more noxious. Additionally, the most frequent areas of pain identified corresponded to the areas commonly seen in a chronic pain population. An attempt to manipulate self-focused attention with a mirror manipulation in Study 2 failed to produce reliable results.


Pseudo-Lyre Sign.
To study the causes of the Pseudo- Lyre sign which is radiologically demonstrated in tumours other than the carotid body tumour. The study is based on an unusual case of neurofibroma of the cervical sympathetic chain presenting as a pulsatile mass in the carotid triangle in a 34 years female. Radiological investigation pointed to a diagnosis of a carotid body tumour because of typical splaying of the internal and external arteries causing the Lyre sign. At surgery, the tumour which was arising from the cervical sympathetic chain (CSC) was excised with minimum blood loss and histopathology confirmed it to be neurofibroma. This, we presume is the first ever report of a neurofibroma of the cervical sympathetic chain causing Lyre sign which we have referred to as Pseudo-Lyre sign. The various investigations which help in diagnosing the cause of Pseudo-Lyre sign have been discussed. All tumours causing Lyre sign on radio-imaging are not carotid body tumours. Other masses mostly neurogenic can demonstrate this sign and an attempt should be made preoperatively to confirm the diagnosis.


Effect of clenbuterol on arterial oxygen tension in the anaesthetised horse.
In horses in dorsal recumbency, spontaneously breathing oxygen, with halothane at a constant end-tidal concentration, the arterial oxygen tension (PO2) increased from 9.9 +/- 0.3 SEM kPa to 21.7 +/- 4.0 kPa with 0.8 micrograms kg-1 clenbuterol and to 29.1 +/- 3.8 kPa with 2.4 micrograms kg-1 clenbuterol. In horses initially in dorsal recumbency then turned to sternal recumbency the PaO2 rose to 54.0 +/- 3.0 kPa, but this rise was unaffected by clenbuterol administration. The response in dorsal recumbency was consistent with clenbuterol counteracting the factor postulated to direct the pulmonary blood flow caudodorsally, but the response to clenbuterol in sternal recumbency was not. Although these results do not unequivocally characterise the postulated factor, the effect of the clenbuterol itself is of interest because of its potential as a treatment for the low PaO2 often observed in anaesthetised horses.


Management of thyroid nodules in children: a 20-year experience.
The medical records and surgical slides of 58 patients with the diagnosis of thyroid nodules (solitary nodule in 50 patients) are reviewed. The most common cause of thyroid nodules in this series is follicular adenoma (27 patients or 46%). A nuclear scan (technetium or radioactive iodine) was performed in 55 patients, of which 40 showed a cold nodule. Twelve of the 40 cold nodules were malignant (30%). However, for solitary nodules the incidence of cancer is 27%. This last figure is significantly greater than the one recently reported by Hung et al (18.5%). Available diagnostic methods are reviewed and the clinical management as derived from our experience is presented.


HEREDITARY ENDOCRINE TUMOURS: CURRENT STATE-OF-THE-ART AND RESEARCH OPPORTUNITIES: The state of science in medullary thyroid carcinoma: current challenges and unmet needs.
The 16th International Multiple Endocrine Neoplasia Workshop (MEN2019) held in Houston, TX, USA, focused on emerging topics in the pathogenesis and therapy of malignant endocrine tumors associated with MEN syndromes. With MEN-2 syndromes, the most common malignancy is medullary thyroid carcinoma (MTC). In the spirit of the original MEN meeting workshop model, the conference included didactic lectures and interactive working groups of clinicians and researchers focused on the state of science in MTC and ongoing challenges or unmet needs in the understanding of MTC and to develop strategies to address these issues.


A double blind placebo controlled trial of intravenous prostacyclin (PGI2) in 108 patients with ischaemic peripheral vascular disease.
108 patients with ischemic peripheral vascular disease were randomly allocated to receive infusion of either PGI2 (6 ng/kg/min over 8 hours daily for 5 consecutive days) or placebo in a double-blind manner. All patients had Stage II disease (Fontaine classification). One month after infusion the absolute and relative walking times were significantly (p less than 0.05) longer in the PGI2- than in the placebo-treated group. Patients were further classified as treatment responders or non-responders on the basis of increase of absolute and relative walking times. After one month 44% (24 out of 54) of the PGI2- and 15% (8 out of 54) of the placebo-treated patients were positive treatment-responders (p less than 0.01).


Comparison of hemagglutinin and agglutinin schemes for the serological classification of Haemophilus paragallinarum and proposal of a new hemagglutinin serovar.
Ninety-five isolates of Haemophilus paragallinarum were classified serologically by a hemagglutinin serotyping scheme, and the results were compared with results from agglutinin serotyping of the same isolates. Of the isolates, 65 were from Australia, 5 were from Japan, 6 were from the Federal Republic of Germany, 7 were from the United States, and 12 were from South Africa. Seven hemagglutinin serovars, HA-1 to HA-7, corresponding to agglutinin serovars A (HA-1, HA-2, and HA-3), C (HA-4, HA-5, and HA-6), and B (HA-7) have been described. Only one of the seven hemagglutinin serovars was found among the Australian isolates. This was serovar HA-5, comprising 49 isolates. Fifteen Australian isolates, all from southeast Queensland and northern New South Wales, were found to belong to a new hemagglutinin serovar. This was designated HA-8 and represented a fourth subgroup of agglutinin serovar A. Of the 95 isolates examined, only 1 did not produce a hemagglutinating antigen and was nonserotypeable by the hemagglutinin system. This compared favorably with the agglutinin scheme, which serotyped only 60 of the 95 isolates, with 29 nonserotypeable and 6 autoagglutinating.


Effect of diet and starvation on the activity state of branched-chain 2-oxo-acid dehydrogenase complex in rat liver and heart.
In rats fed a high-protein diet, the branched-chain 2-oxo-acid dehydrogenase complex in liver was essentially fully active and its activity state was unaffected by subsequent starvation for 48 h. Feeding with a low-protein diet led to a decrease in the activity state which was essentially reversed by 48 h of starvation. In heart, the enzyme was primarily inactive (activity state 18%) in rats fed a high-protein diet, with both low-protein diet and starvation leading to a further decrease in the activity state.


Vitamin D and PTH: data from a cross-sectional study in an equatorial population.
Investigate the prevalence of vitamin D deficiency in an equatorial population through a large-sample study. Cross-sectional study with 30,224 healthy individuals from the North Region, in Brazil (Amazônia - state of Pará), who had 25-hydroxy-vitamin D (25(OH)D) and intact parathyroid hormone (PTH) serum levels measured by immunoassay method. Those with history of acute or chronic diseases were excluded. Abnormal levels of calcium, creatinine, glycemia and albumin were also exclusion criteria. 25(OH)D levels were 29.1 ± 8.2 ng/mL and values <12.7 ng/mL were equal to < -2 s.d. below average. Hypovitaminosis D was present in 10% of subjects according to the Institute of Medicine (values <20 ng/mL) and in 59%, in consonance with Endocrine Society (values 20-30 ng/mL as insufficiency and <20 ng/mL as deficiency) criteria. Individuals were divided according to four age brackets: children, adolescents, adults and elderly, and their 25(OH)D levels were: 33 ± 9; 28.5 ± 7.4; 28.3 ± 7.7; 29.3 ± 8.5 ng/mL, respectively. All groups differed in 25(OH)D, except adolescents vs adults. Regression model showed BMI, sex, living zone (urban or rural) and age as independent variables to 25(OH)D levels. Comparing subjects with vitamin D deficiency (<20 ng/mL) to those with vitamin D insufficiency (20-30 ng/mL), a difference between PTH levels in these two groups was observed (95.9 ± 24.7 pg/mL vs 44.2 ± 64.5 pg/mL; P < 0.01). Additionally, the most accurate predictive vitamin D level for subclinical hyperparathyroidism in ROC curve was 26 ng/mL. Our equatorial population showed low prevalence of vitamin D hypovitaminosis ranging with age bracket. The insufficient category by Endocrine Society was corroborated by our PTH data.


Decline in Stroke Mortality Between 1997 and 2012 by Sex: Ecological Study in Brazilians Aged 15 to 49 Years.
This study aimed to analyse the time trends of stroke mortality between 1997 and 2012 according to sex in Brazilians aged 15 to 49 years. This ecological study used data obtained from the Mortality Information System, which is available from the National Health System Department of Informatics - DATASUS and maintained by the Brazilian Ministry of Health. Stroke definition included International Classification of Disease version 10 (ICD-10) codes I60, I61, I63, and I64. Crude and age-standardized mortality rates and respective 95% confidence intervals were estimated per 100,000 inhabitants and stratified by age, region, year, and sex. Linear regression models were used to analyse the time trends with a confidence level of 95%. The statistical program used was Stata 11.0. Between 1997 and 2012, there were 124,866 deaths due to stroke in Brazilians aged 15 to 49 years. There was a decreasing linear trend in stroke mortality among men (β = -0.46, p < 0.001, R2 = 0.95) and women (β = -0.40, p < 0.001, R2 = 0.98) during this period. Overall there was no significant difference in stroke mortality trends by sex, except with respect to the age group of 40 to 49 years where there was a difference in the decrease of stroke mortality between men and women (interaction sex * year: β = 0.238, p = 0.012, R² = 0.96). Mortality rates decrease significantly over time in men and women in the age group 15 to 49 years old, but there is only significant difference in the decrease of rates by sex only in the age group from 40 to 49 years old.


The use of ultrasound scanning in the management of developmental disorders of the hip.
Ultrasound was used, together with clinical examination, to help in the diagnosis and to evaluate the treatment of 48 babies with congenital disorders of the hip. The femoral head, and its relation to the acetabulum, can be demonstrated before it becomes visible on radiographs. Ionising radiation is avoided. Ultrasound scanning can be used to visualise the repositioning of the femoral head. It is also possible to examine babies on an abduction frame.


Pattern of the heart rate performance curve in maximal graded treadmill running from 1100 healthy 18-65 Years old men and women: the 4HAIE study.
Introduction: The heart rate performance curve (HRPC) in maximal incremental cycle ergometer exercise demonstrated three different patterns such as downward, linear or inverse versions. The downward pattern was found to be the most common and therefore termed regular. These patterns were shown to differently influence exercise prescription, but no data are available for running. This study investigated the deflection of the HRPC in maximal graded treadmill tests (GXT) of the 4HAIE study. Methods: Additional to maximal values, the first and second ventilatory thresholds as well as the degree and the direction of the HRPC deflection (kHR) were determined from 1,100 individuals (489 women) GXTs. HRPC deflection was categorized as downward (kHR < -0.1), linear (-0.1 ≤ kHR ≤ 0.1) or inverse (kHR > 0.1) curves. Four (even split) age- and two (median split) performance-groups were used to investigate the effects of age and performance on the distribution of regular (= downward deflection) and non-regular (= linear or inverse course) HR curves for male and female subjects. Results: Men (age: 36.8 ± 11.9 years, BMI: 25.0 ± 3.3 kg m-2, VO2max: 46.4 ± 9.4 mL min-1. kg-1) and women (age: 36.2 ± 11.9 years, BMI: 23.3 ± 3.7 kg m-2, VO2max: 37.4 ± 7.8 mL min-1. kg-1) presented 556/449 (91/92%) downward deflecting, 10/8 (2/2%) linear and 45/32 (7/6%) inverse HRPC´s. Chi-squared analysis revealed a significantly higher number of non-regular HRPC´s in the low-performance group and with increasing age. Binary logistic regression revealed that the odds ratio (OR) to show a non-regular HRPC is significantly affected by maximum performance (OR = 0.840, 95% CI = 0.754-0.936, p = 0.002) and age (OR = 1.042, 95% CI = 1.020-1.064, p < 0.001) but not sex. Discussion: As in cycle ergometer exercise, three different patterns for the HRPC were identified from the maximal graded treadmill exercise with the highest frequency of regular downward deflecting curves. Older subjects and subjects with a lower performance level had a higher probability to show a non-regular linear or inverted curve which needs to be considered for exercise prescription.


Prevalence and Predictors of Complementary and Alternative Medicine Use in a Large Insured Sample of Children with Autism Spectrum Disorders.
The purpose of the present study was to examine the prevalence and predictors of complementary and alternative medicine (CAM) use as well as parental perceptions of CAM efficacy in a large, geographically diverse sample of children with Autism Spectrum Disorders (ASD). Data were obtained from a web-based survey administered to parents of children with ASD at four sites participating in the Mental Health Research Network (MHRN). The web survey obtained information about services and treatments received by children with ASD as well as the caregivers' experiences with having a child with ASD. Approximately 88% of the sample had either used CAM in the past or had recently used some type of CAM. The following characteristics were associated with CAM use: greater parental education, younger child age, a mix of regular and special classroom settings and prescription drug use in the past three months. The use of CAM was very prevalent in this large, geographically diverse sample of children with ASD. It is critical that providers be prepared to discuss the advantages and potential side effects with families to help them make well-informed health care decisions and prevent possible CAM-drug interactions.


Measurement of the respiratory burst in human monocytes and polymorphonuclear leukocytes by nitro blue tetrazolium reduction and chemiluminescence.
We compared measurements of chemiluminescence (CL) assessing the rate of production of oxygen intermediates at a given instance, and of nitro blue tetrazolium (NBT) reduction detecting total superoxide produced during the assay period, for the assessment of the respiratory burst of both human monocytes (M phi) and polymorphonuclear leukocytes (PMN). In the CL experiments, opsonized and non-opsonized zymosan was used to stimulate peripheral blood M phi and PMN. Opsonized zymosan yielded an earlier and 2-fold higher peak response than non-opsonized zymosan. The stimulatory action of zymosan in CL varied with the time of incubation and depended on the concentration of cells and zymosan. No light generation was observed in the absence of viable cells. In contrast to NBT reduction, incubation of PMN with dextran sulfate did not result in increased light generation but rather in a quenching of the response in CL. Opsonized zymosan also yielded a higher level of NBT reduction than non-opsonized zymosan. Comparing NBT reduction with CL in 21 healthy individuals, with 2 X 10(5) M phi and 2.5 X 10(5) PMN for NBT and 5 X 10(5) PMN for CL tests, we found that NBT brings about spontaneous oxidative metabolism, possibly reflecting the intracellular compartment, the chemiluminescent response of resting cells being only marginal. The data suggest higher sensitivity of the CL method. These results provide useful comparative data for 2 established methods used to document the respiratory burst in phagocytic cells.


Sclerosing stromal tumour--a rare ovarian benign neoplasm: description of three cases.
Sclerosing stromal tumour is a rare benign usually unilateral ovarian tumour. We present three cases of this neoplasm in young females, including one bilateral case. All tumours were composed of cellular areas forming pseudolobular patterns, as well as vascular, fibrous, and myxoid areas. The characteristic feature of tumours was cellular heterogenity. All tumours revealed negative immunostaining for cytokeratin, and intense positive immunostaining for vimentin, and smooth muscle actin. Immunostaining for desmin and progesterone receptors was weakly positive.


A Comparison of Salmonella Survival and Detection Using an Enrichment Technique in Dry- and Wet-Inoculated Rendered Chicken Fat Treated with Sodium Bisulfate.
The differences in the recovery of Salmonella from rendered chicken fat treated with sodium bisulfate (SBS) when inoculated with a dry versus wet inoculum were evaluated. Food-grade rendered chicken fat was inoculated with a dry inoculum and a wet inoculum containing a cocktail of Salmonella serovars (Enteritidis, Heidelberg, and Typhimurium). In addition, the effect of an antimicrobial treatment (SBS) against Salmonella in both the aqueous phase and fat phase of the chicken fat was evaluated. The untreated control samples in the aqueous phase had a consistent level of Salmonella (∼7 log) when both the dry and wet inocula were used. In the SBS-treated aqueous phase, Salmonella pathogens were not detectable after 6 h when the wet inoculum was used; when the dry inoculum was used, Salmonella pathogens were not detectable at 24 h. Salmonella pathogens were detected for up to 6 h in the SBS-treated fat phase when the dry inoculum was used compared with 2 h with the wet inoculum. The 24-h fat samples that failed to show growth on Trypticase soy agar were enriched for Salmonella isolation, followed by confirmation by PCR using primers for the invA gene. SBS-treated and control samples from the dry-inoculated rendered chicken fat and the inoculated control from the wet-inoculated rendered chicken fat tested positive for Salmonella. However, the SBS-treated sample from the wet-inoculated fat was negative for Salmonella. The use of dry SBS powder against dry Salmonella inoculum in the fat matrix caused only ∼2.8-log reduction after 24 h compared with ∼2.2-log reduction in the positive control. However, the recovery of Salmonella from untreated control fat was lower and was not different (P > 0.05) from that recovered from the SBS-treated fat. The results suggest that viable but nonculturable states of Salmonella may develop in rendered chicken fat or that injured cells may be present, which indicates that testing should include an enrichment and appropriate molecular confirmation instead of agar plating alone.


Examining the psychometric properties of the Norwegian version of the Social Aptitudes Scale in two clinical samples.
Few studies have examined the psychometric properties of the Social Aptitudes Scale (SAS). The study aims of the current paper were to examine the internal consistency and the validity of the Norwegian SAS. Parents of children from a clinical neuropediatric sample (N = 257) and from a clinical sample from child and adolescent's mental health services (N = 804) filled in the SAS. Internal consistency for the SAS were good in both samples and correlations between the SAS and different scales were in the expected directions. The results from the Confirmatory Factor Analyses indicated poor model fit. Future validity studies should investigate whether SAS is suitable as a screening instrument for detecting autism spectrum disorder.


Scp3 expression in relation to the ovarian differentiation in the protogynous hermaphroditic ricefield eel Monopterus albus.
Synaptonemal complex protein 3 (Scp3), which is encoded by scp3, is a meiotic marker commonly used to trace the timing of gonadal differentiation in vertebrates. In the present study, the ricefield eel scp3 cDNA was cloned, and a fragment encoding amino acids 49 to 244 was overexpressed. The recombinant Scp3 polypeptide was purified and used to generate a rabbit anti-Scp3 polyclonal antiserum. In adult ricefield eels, scp3 mRNA was predominantly detected in the gonads and faintly detected in discrete brain areas. In the gonads, Scp3 immunoreactivities were shown to be localized to the germ cells, including meiotic primary growth oocytes, spermatocytes, and pre-meiotic spermatogonia. During early ovarian differentiation, immunoreactive Scp3 was not detected in the gonads of ricefield eels at 6 days post-hatching (dph) but was found to be abundantly localized in the cytoplasm of some oogonia at 7 dph, coinciding with the appearance of the ovarian cavity and ovarian differentiation. At 14 dph, strong Scp3 immunostaining was detected on one side of the nucleus with a distinct polarity in some germ cells, presumably at the leptotene stage. Consistent with these results, the expression of scp3 mRNA was faintly detected in the gonads of ricefield eels at 6 dph, increased at 8 dph, and then remained relatively high thereafter. Taken together, these results suggest that the appearance of immunoreactive Scp3 in oogonia could be a marker for early ovarian differentiation in ricefield eels. The translocation of the Scp3 protein from the cytoplasm to the nucleus in the oogonium of ricefield eels appears to be a controlled process that warrants further study.


Aerobic sn-glycerol-3-phosphate dehydrogenase from Escherichia coli binds to the cytoplasmic membrane through an amphipathic alpha-helix.
sn-Glycerol-3-phosphate dehydrogenase (GlpD) from Escherichia coli is a peripheral membrane enzyme involved in respiratory electron transfer. For it to display its enzymic activity, binding to the inner membrane is required. The way the enzyme interacts with the membrane and how this controls activity has not been elucidated. In the present study we provide evidence for direct protein-lipid interaction. Using the monolayer technique, we observed insertion of GlpD into lipid monolayers with a clear preference for anionic phospholipids. GlpD variants with point mutations in their predicted amphipathic helices showed a decreased ability to penetrate anionic phospholipid monolayers. From these data we propose that membrane binding of GlpD occurs by insertion of an amphipathic helix into the acyl-chain region of lipids mediated by negatively charged phospholipids.


Neurological changes in brain structure and functions among individuals with a history of childhood sexual abuse: A review.
Review literature focused on neurological associations in brain structure among individuals with a history of childhood sexual abuse (CSA). A review of literature examining physiological irregularities in brain structures of individuals with a history of CSA was conducted. Results revealed that a history of CSA was associated with irregularities in the cortical and subcortical regions of the brain. These irregularities have been recognized to contribute to various cognitive, behavioral, and psychological health outcomes later in life. Age of CSA onset was associated with differential neurological brain structures. Mental and behavioral health problems such as anxiety, depression, substance abuse, dissociative disorders, and sexual dysfunction are associated with CSA and may persist into adulthood. Research depicting the associations of CSA on neurological outcomes emphasizes the need to examine the biological and subsequent psychological outcomes associated with CSA. Early intervention is imperative for CSA survivors.


MiR-103a-3p aggravates renal cell carcinoma by targeting TMEM33.
We investigated the mechanism of miR-103a-3p-mediated renal cell carcinoma (RCC) progression. The miR-103a-3p expressions were measured in clinical samples and in two RCC cell lines. MiR-103a-3p was inhibited or over-expressed in the 786-O and UO31 cell lines, respectively. We found that miR-103a-3p is closely related to the development of RCC cells. A bioinformatics analysis and a dual-luciferase reporter gene assay revealed that there is a direct interaction between TMEM33 and miR-103a-3p. Moreover, a rescue assay further confirmed that TMEM33 overexpression can attenuate miR-103a-3p-induced RCC cell development. miR-103a-3p exerts a carcinogenic function in RCC by regulating TMEM33, a finding that may provide new insights into the development of prognostic markers and therapeutic targets for RCC.


Thiamine-responsive, life-threatening, pulmonary hypertensive crisis with encephalopathy in young infants: A case series.
Thiamine (Vitamin B1) deficiency (TD), although reduced in incidence, is still seen in infants. We describe a rarely reported form of infantile TD with life-threatening pulmonary hypertensive crisis and severe encephalopathy, with dramatic response to thiamine supplementation. Study design: Descriptive case series. Six young infants with mean age 76 days (range 1-3 months), manifesting rapidly progressive encephalopathy and cardio-pulmonary arrest were included. All infants underwent cardiac, neuroimaging and metabolic evaluations. All six infants had similar presentation with severe pulmonary arterial hypertension (PAH), hypotensive shock, metabolic acidosis and severe encephalopathy. All infants were exclusively breast-fed. Thiamine treatmwnt resulted in dramatic improvement in haemodynamic and neurological function in all the infants. There were no major neurological deficits on follow up. A high index of suspicion is warranted for this rarely described form of TD, as early identification helps in preventing mortality and morbidity.


Effects of propolis from Brazil and Bulgaria on fungicidal activity of macrophages against Paracoccidioides brasiliensis.
Paracoccidioidomycosis is the most important systemic mycosis in Latin America. Its etiological agent, Paracoccidoides brasiliensis, affects individuals living in endemic areas through inhalation of airborne conidia or mycelial fragments. The disease may affect different organs and systems, with multiple clinical features, with cell-mediated immunity playing a significant role in host defence. Peritoneal macrophages from BALB/c mice were stimulated with Brazilian or Bulgarian propolis and subsequently challenged with P. brasiliensis. Data suggest an increase in the fungicidal activity of macrophages by propolis stimulation, independently from its geographic origin.


Analyzing inherent biases in SARS-CoV-2 PCR and serological epidemiologic metrics.
Prospective observational data show that infected persons with the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) remain polymerase chain reaction (PCR) positive for a prolonged duration, and that detectable antibodies develop slowly with time. We aimed to analyze how these effects can bias key epidemiological metrics used to track and monitor SARS-CoV-2 epidemics. An age-structured mathematical model was constructed to simulate progression of SARS-CoV-2 epidemics in populations. PCR testing to diagnose infection and cross-sectional surveys to measure seroprevalence were also simulated. Analyses were conducted on simulated outcomes assuming a natural epidemic time course and an epidemic in presence of interventions. The prolonged PCR positivity biased the epidemiological measures. There was a lag of 10 days between the true epidemic peak and the actually-observed peak. Prior to epidemic peak, PCR positivity rate was twofold higher than that based only on current active infection, and half of those tested positive by PCR were in the prolonged PCR positivity stage after infection clearance. Post epidemic peak, PCR positivity rate poorly predicted true trend in active infection. Meanwhile, the prolonged PCR positivity did not appreciably bias estimation of the basic reproduction number R0. The time delay in development of detectable antibodies biased measured seroprevalence. The actually-observed seroprevalence substantially underestimated true prevalence of ever infection, with the underestimation being most pronounced around epidemic peak. Caution is warranted in interpreting PCR and serological testing data, and any drawn inferences need to factor the effects of the investigated biases for an accurate assessment of epidemic dynamics.


Litter chemical traits strongly drove the carbon fractions loss during decomposition across an alpine treeline ecotone.
The decomposition of litter carbon (C) fraction is a major determinant of soil organic matter pool and nutrient cycling. However, knowledge of litter chemical traits regulate C fractions release is still relatively limited. A litterbag experiment was conducted using six plant functional litter types at two vegetation type (coniferous forest and alpine shrubland) in a treeline ecotone. We evaluated the relative importance of litter chemistry (i.e. Nutrient, C quality, and stoichiometry) on the loss of litter mass, non-polar extractables (NPE), water-soluble extractables (WSE), acid-hydrolyzable carbohydrates (ACID), and acid-unhydrolyzable residue (AUR) during decomposition. Litter nutrients contain nitrogen (N), phosphorus (P), potassium (K), calcium (Ca), sodium (Na), magnesium (Mg), aluminium (Al), manganese (Mn), zinc (Zn), iron (Fe) and copper (Cu), litter C quality contains C, WSE, NPE, ACID, and AUR, and stoichiometry was defined by C:N, C:P; N:P, ACID:N, and AUR:N. The results showed single exponential model fitted decomposition rates of litter mass and C fractions better than double exponential or asymptotic decomposition, and the decomposition rates of C fractions were strongly correlated with initial litter nutrients, especially K, Na, Ca. Furthermore, the temporal dynamics of litter nutrients (Ca, Mg, Na, K, Zn, and Fe) strongly regulated C fractions loss during the decomposition process. Changes in litter C quality had an evident effect on the degradation of ACID and AUR, supporting the concept of "priming effect" of soluble carbon fraction. The significant differences were found in the release of NPE, WSE, and ACID rather than AUR among coniferous forest and alpine shrubland, and the vegetation type effects largely depend on the changes in litter stoichiometry, which is an important implication for the change in plant community abundance regulate decay. Collectively, elucidating the hierarchical drivers of litter chemistry on decomposition is critical to soil C sequestration in alpine ecosystems.


Kawasaki disease shock syndrome or toxic shock syndrome in children and the relationship with COVID-19.
Most pediatric patients with COVID-19 are asymptomatic or show only mild symptoms. However, in the last two months, first in Europe and recently in the United States, a small number of children have developed a more severe inflammatory syndrome associated with COVID-19, which often leads to hospitalization and sometimes requires intensive care. A potential relationship was observed, especially between the occurrence of the Kawasaki disease and viral upper respiratory tract infections.


Retrospective comparison of traditional and artificial intelligence-based heart failure phenotyping in a US health system to enable real-world evidence.
Quantitatively evaluate the quality of data underlying real-world evidence (RWE) in heart failure (HF). Retrospective comparison of accuracy in identifying patients with HF and phenotypic information was made using traditional (ie, structured query language applied to structured electronic health record (EHR) data) and advanced (ie, artificial intelligence (AI) applied to unstructured EHR data) RWE approaches. The performance of each approach was measured by the harmonic mean of precision and recall (F1 score) using manual annotation of medical records as a reference standard. EHR data from a large academic healthcare system in North America between 2015 and 2019, with an expected catchment of approximately 5 00 000 patients. 4288 encounters for 1155 patients aged 18-85 years, with 472 patients identified as having HF. HF and associated concepts, such as comorbidities, left ventricular ejection fraction, and selected medications. The average F1 scores across 19 HF-specific concepts were 49.0% and 94.1% for the traditional and advanced approaches, respectively (p<0.001 for all concepts with available data). The absolute difference in F1 score between approaches was 45.1% (98.1% relative increase in F1 score using the advanced approach). The advanced approach achieved superior F1 scores for HF presence, phenotype and associated comorbidities. Some phenotypes, such as HF with preserved ejection fraction, revealed dramatic differences in extraction accuracy based on technology applied, with a 4.9% F1 score when using natural language processing (NLP) alone and a 91.0% F1 score when using NLP plus AI-based inference. A traditional RWE generation approach resulted in low data quality in patients with HF. While an advanced approach demonstrated high accuracy, the results varied dramatically based on extraction techniques. For future studies, advanced approaches and accuracy measurement may be required to ensure data are fit-for-purpose.


Covalent allosteric modulation: An emerging strategy for GPCRs drug discovery.
Designing covalent allosteric modulators brings new opportunities to the field of drug discovery towards G-protein-coupled receptors (GPCRs). Targeting an allosteric binding pocket can allow a modulator to have protein subtype selectivity and low drug resistance. Utilizing covalent warheads further enables the modulator to increase the binding potency and extend the duration of action. This review starts with GPCR allosteric modulation to discuss the structural biology of allosteric binding pockets, the different types of allosteric modulators, as well as the advantages of employing allosteric modulation. This is followed by a discussion on covalent modulators to clarify how covalent ligands can benefit the receptor modulation and to illustrate moieties that can commonly be used as covalent warheads. Finally, case studies are presented on designing class A, B, and C GPCR covalent allosteric modulators to demonstrate successful stories on combining allosteric modulation and covalent binding. Limitations and future perspectives are also covered.


Anti-aggressive effect of a new phenylpiperazine compound (DU27716) on hypothalamically induced behavioural activities.
Using the same hypothalamic electrodes, the following behaviour was evoked in male rats by electrical stimulation at roughly equal current intensities: attacks on a partner, teeth-chattering, switch-off behaviour and locomotion. Current thresholds were determined for each behaviour following the intraperitoneal administration of saline or DU27716, a new phenylpiperazine compound with interesting inhibitory effects on territorial and intermale aggression. DU27716 raised current thresholds for attack and teeth-chattering beginning at the lowest dose (4 mg/kg), whereas there was no effect on switch-off behaviour, and only a slight but significant effect on locomotion thresholds at the highest dose (8 mg/kg). The results provide support for the hypothesis that DU27716 possesses behaviourally selective, anti-aggressive properties, and illustrate the usefulness of hypothalamically induced behaviours as a pharmacological model.


Reliability of physical examination in penetrating chest injuries.
The decision to insert an intercostal drain in chest injury must occasionally be made without a chest radiograph. A prospective analysis of the reliability of physical examination in penetrating pleural injuries was undertaken. A total of 51 consecutive patients were examined before obtaining a chest radiograph. The presumptive diagnosis and decision to institute intercostal drainage were compared with the radiological diagnosis and the actual decision in each patient. A policy of selective drainage of large pleural collections was employed. The series consisted mainly of stab injuries in young men. Physical examination accurately diagnosed 13 of the 14 large pneumo- or haemothoraces. This reliability combined with the selective drainage policy showed that physical examination accurately predicted the need for tube thoracostomy with a sensitivity of 96 per cent and a specificity of 93 per cent. This study suggests that experienced clinicians should not hesitate to institute immediate life-saving intercostal drainage when needed, before a chest radiograph is obtained.


Three New Lanostanoids with Anti-HCV Effects from Abies nukiangensis.
Three new lanostane derivatives (1-3) and twelve known triterpenoids (4-15) were isolated from the twigs and leaves of Abies nukiangensis. The structures of the new compounds were elucidated mainly by detailed analysis of their NMR and HR-ESI-MS spectroscopic data. Evaluation of the anti-HCV effects of all isolates showed that 3 exhibited moderate effect with the EC50 value of 11.09 μM.


Manipulations of 5-HT activity and memory in the rat.
The activity of 5-HT was manipulated by means of the peripheral injection of 5-HT reuptake inhibitors, fenfluramine and fluoxetine. These drug treatments, at doses higher than 1 mg/kg, produced retrograde amnesia in a one-trial appetitive learning task in rats. A non-specific inhibitor of 5-HT reuptake, imipramine, did not produce this amnesic effect, nor did the combination of fenfluramine with the MAOI tranylcypromine, although it produced, as expected, the "serotonergic syndrome." Results for the metabolic precursor of 5-HT, 5-HTP, also administered peripherally, were inconsistent, with amnesic effects seen at 5 and 20 mg/kg but none at 10 mg/kg.


The longitudinal effects of chronotype on chemotherapy-induced nausea and vomiting in patients with breast cancer receiving neoadjuvant chemotherapy.
The object of this longitudinal cohort study was to investigate whether chronotype affects the incidence of chemotherapy-induced nausea and vomiting (CINV) among patients with breast cancer. The study included a total of 203 breast cancer patients who received neoadjuvant chemotherapy using a regimen of doxorubicin and cyclophosphamide with high emetogenicity. Patients received four cycles of chemotherapy in approximately three months. Patients completed questionnaires including the Munich Chronotype Questionnaire (MCTQ) before the first chemotherapy and the Multinational Association of Supportive Care in Cancer Antiemesis Tool (MAT) after each of the four chemotherapy sessions. To confirm the effect of chronotype on CINV during the four cycles, we performed statistical analyses using a generalized estimating equation (GEE). CINV occurred in 108 (53.2%), 112 (55.2%), 102 (50.3%), and 62 (30.5%) patients during four cycles of treatment. In the GEE approach, late and early chronotypes (vs. intermediate chronotype) were associated with an increased risk of CINV (late chronotype: odds ratio [OR], 2.06; 95% confidence interval [CI], 1.41-2.99; p < 0.001, early chronotype: OR, 1.84; CI, 1.25-2.73; p = 0.002), which remained significant even after adjusting for age, BMI, antiemetic treatment, history of nausea and vomiting, anxiety, and sleep quality. Chronotype affected CINV across the four cycles of neoadjuvant chemotherapy in patients with breast cancer, suggesting the need to consider chronotype in predicting and managing CINV.


Contribution of HLA-G and FOXP3 genes and proteins in the severity of cervical intraepithelial neoplasia during HPV infection.
Human Papillomavirus (HPV) persistence leads to the chronification of cervical inflammation, where HLA-G and Foxp3; immunomodulatory molecules, may contribute to the aggravation of the lesion and cancerization. Here, we evaluated the synergic effect of these two molecules in the worsening of the lesion in presence of HPV infection. Hundred and eighty (180) women cervical cells and biopsies were collected for (i) HLAG Sanger sequencing and gene expression, and (ii) HLA-G and Foxp3 molecule expressions by immunohistochemistry. 53 women were HPV+ against 127 women HPV-. HPV+ women were more at risk of having cytological changes (p ≤ 0.0123), histological changes (p < 0.0011), and cervical lesion (p = 0.0004). The HLA-G + 3142CC genotype predisposed women to infection (p = 0.0190), while HLA-G + 3142C and +3035 T alleles were associated with HLA-G5 transcript expression. Both sHLA-G (p = 0.030) and Foxp3 (p = 0.0002) proteins were higher in cervical lesion as well as in high-grade lesion. In addition, sHLA-G+ cells were positively correlated to Foxp3+ cells in presence of HPV infection and in cervical grade II/III injuries. In conclusion, HPV may use HLA-G and Foxp3 as a way of host immune escape contributing to the persistence of infection and inflammation, leading to the cervical lesion and the worsening of lesions.


Coexistent pulmonary and portal hypertension: morphologic and clinical features.
Patients with portal hypertension of varying etiology may develop pulmonary artery hypertension. In the present autopsy study, pulmonary and hepatic tissue was studied in 12 patients in whom pulmonary and portal hypertension coexisted. Plexogenic pulmonary arteriopathy was present in 10 patients, 7 of whom had coexistent thromboembolic lesions. One patient had isolated medial hypertrophy, which may be an early stage in the plexogenic category, whereas isolated thromboembolic pulmonary vascular disease was observed in one subject. Hepatic disease was consistent with alcoholic cirrhosis in seven patients, cryptogenic cirrhosis in four and extrahepatic portal hypertension without cirrhosis in one. Thrombocytopenia was present in all 10 patients whose platelet count was determined. This study suggests that pulmonary hypertension associated with portal hypertension commonly has a plexogenic appearance on histologic examination. However, thrombosis (whether embolic or in situ) may also contribute to vascular obstruction.


An autonomous, multi-agent, IoT-empowered space logistics system for mission-critical inventory packing.
In recent aerospace missions, space logistics have proven essential in storing, delivering and returning crew and materials between terrestrial facilities and space stations. Unlike classical commercial logistics, space logistics operations are cost-prohibitive and mission-driven, and its replenishment cycle for essential materials is relatively long. Therefore, the complete utilisation of spacecraft payload is of utmost importance. The theory of the inventory packing problem is extended in this study to build autonomous agents that interact with one another within a space logistics decision support system to reinforce the replenishment decision, chunk loading optimisation, and quality inspection. With the long replenishment cycle time, an agent embedded with interval type-2 fuzzy logic is explored to support chaotic time-series demand forecasting to derive re-order quantities in the desired period. Afterwards, the second agent solves the space chunk loading problem using the differential evolution algorithm to utilise payloads and capacities, particularly cylindrical chunks fully. The third agent measures actual item dimensions and quality to deploy the three-dimensional object scanning devices. Feedback is provided to the second agent to derive optimal chunk-loading instructions. Thanks to the autonomous interactions among the above agents, mission-critical decisions for space logistics are supported to achieve operational excellence.


Untangling causes of variation in mercury concentration between flight feathers.
Bird feathers are one of the most widely used animal tissue in mercury biomonitoring, owing to the ease of collection and storage. They are also the principal excretory pathway of mercury in birds. However, limitations in our understanding of the physiology of mercury deposition in feathers has placed doubt on the interpretation of feather mercury concentratoins. Throughout the literature, moult sequence and the depletion of the body mercury pool have been taken to explain patterns such as the decrease in feather mercury from the innermost (P1) to the outermost primary feather (P10) of the wing. However, it has been suggested that this pattern is rather a measurement artefact as a result of the increased feather mass to length ratio along the primaries, resulting in a dilution effect in heavier feathers. Here, we attempt to untangle the causes of variation in feather mercury concentrations by quantifying the mercury concentration as μg of mercury (i) per gram of feather, (ii) per millimetre of feather, and (iii) per day of feather growth in the primary feathers of Bulwer's Petrel Bulweria bulwerii chicks, effectively controlling for some of the axes of variation that may be acting in adults, and monitoring the growth rate of primary feathers in chicks. The mercury concentration in Bulwer's Petrel chicks' primaries increased from the innermost to the outermost primary for all three concentration measures, following the order of feather emergence. These observations confirm that the pattern of mercury concentration across primary feathers is not an artefact of the measure of concentration, but is likely an effect of the order of feather growth, whereby the earlier grown feathers are exposed to higher blood mercury concentrations than are later moulted feathers as a result of blood mercury depletion.


Patient and mentor language style matching as a predictor of working alliance, engagement with treatment as usual, and eating disorders symptoms over the course of an online guided self-help intervention for anorexia nervosa.
The aim of this study was to examine the processes involved in a guided self-help (GSH) pre-treatment intervention (RecoveryMANTRA) for patients with anorexia nervosa (AN), by measuring the levels of patient/mentor Language Style Matching (LSM). RecoveryMANTRA was supported by student mentors or peer mentors (recovered individuals) over six weekly chat-based sessions. We examined whether LSM during RecoveryMANTRA predicted patients'working alliance with the clinic therapist, motivation, eating disorder (ED) and general psychopathology. A further aim was to examine differences in LSM between student mentors and peer mentors. 87 AN adults received RecoveryMANTRA plus treatment as usual. The LSM algorithm was used to calculate verbal attunement between patient and mentor. Participants were assessed at baseline and at the end of the intervention. Both early (1st session) and late (6th session) LSM predicted higher working alliance with the clinic therapist. Moreover, late LSM predicted lower EDs symptoms at the end of the RecoveryMANTRA intervention. Patient/peer mentor dyads showed higher late verbal attunement than patient/student mentor dyads. These findings suggests that in the early phase of treatment relational aspects can impact on engagement with treatment. Verbal attunement in a GSH for AN is associated with working alliance and better clinical outcome.


Combination therapy in stage C and D prostatic cancer: rationale and five year clinical experience.
In 1941, Huggins and his colleagues discovered that testicular androgens exert a stimulatory effect on prostate cancer growth. Our group has made the key observations that the human adrenals, in addition to the tests, also secrete important amounts of androgens and cancer cells exhibit a marked heterogeneity of androgen sensitivity. In fact, human adrenals secrete large amounts of precursor steroids that are converted into active androgens in peripheral tissues (including the prostate), thus providing 40% to 50% of total androgens in adult men. The action of these androgens remaining after castration can be inhibited in prostatic cancer tissue by administering a pure antiandrogen that also decreases the local concentration of dihydrotestosterone (DHT). The castration levels of serum testosterone left in men after castration have an important stimulatory activity on the growth of androgen-sensitive normal as well as cancer tissues. Cancer cells have markedly different requirements for androgens. Some cell clones can grow in the presence of minimal amounts of androgens, requiring more complete androgen blockade and more potent antiandrogens for inhibiting growth. Among the compounds recommended as antiandrogens, the most unexpected finding is that many of them are devoid of any antiandrogenic activity. In fact, medroxyprogesterone acetate, chlormadinone acetate, and megestrol acetate have androgenic activity, but do not inhibit the peripheral action of DHT in prostatic tissue. These compounds should not be classified as antiandrogens. Cyproterone acetate, on the other hand, is a mixed agonist-antagonist. The only compounds showing pure antiandrogenic activity are Flutamide and its analogues. There is thus a need for a more complete blockade of androgens of both testicular and adrenal origins in order to exert a maximal inhibitory effect on cancer growth. We have therefore performed clinical studies in previously untreated stage D2 and C prostate cancer patients with the combination therapy using the LHRH agonist [D-Trp6, des Gly NH2(10)] LHRH ethylamide and the antiandrogen Flutamide. There was a significant increase in patients with a complete response, as compared with studies limited to the removal or blockade of testicular androgens. There was also a significant decrease in the number of non-responders, an increased duration of positive response, and a decrease in the death rate. This was achieved with minimal or no side effects, thus preserving a good quality of life.


Entry of blood-borne cytokines into the central nervous system: effects on cognitive processes.
Blood-borne cytokines affect many aspects of the central nervous system (CNS). One of the more dramatic effects is the induction of sickness behavior. Impairments in learning and memory are an important component of sickness behavior and are largely mediated by IL-1. Many mechanisms have been proposed by which a cytokine circulating in the blood can affect functions within the CNS. We review here the role one of those mechanisms, that of transport of cytokines across the blood-brain barrier (BBB), plays in induction of the memory impairments of sickness behavior. We have shown that the posterior division of the septum (PDS) plays a key role in mediating the effects of interleukin-1alpha (IL-1alpha) on memory. Furthermore, this effect at the PDS is largely mediated by circulating IL-1alpha acting directly at the PDS which, in turn, depends on the ability of IL-1alpha to cross the BBB.


Lateral pressure profiles in cholesterol-DPPC bilayers.
By means of atomistic molecular dynamics simulations, we study cholesterol-DPPC (dipalmitoyl phosphatidylcholine) bilayers of different composition, from pure DPPC bilayers to a 1:1 mixture of DPPC and cholesterol. The lateral pressure profiles through the bilayers are computed and separated into contributions from the different components. We find that the pressure inside the bilayer changes qualitatively for cholesterol concentrations of about 20% or higher. The pressure profile in the inside of the bilayer then turns from a rather flat shape into an alternating sequence of regions with large positive and negative lateral pressure. The changes in the lateral pressure profile are so characteristic that specific interaction between cholesterol and molecules such as membrane proteins mediated solely via the lateral pressure profile might become possible.


The effect of dietary protein restriction on high dose gentamicin nephrotoxicity in rats.
Gentamicin (120 mg/kg/day) was administered for 10 days to Sprague-Dawley rats given either a low (5% w/w) or normal (18% w/w) protein diet. Serum protein concentrations remained normal in all rats during the study. Nephrotoxicity was slightly less severe in rats fed a low protein diet as shown by: (i) a mean creatinine clearance rate (14 +/- 4 ml/min) which was significantly greater than that (8 +/- 3 ml/min) recorded from the rats maintained on the normal diet (P less than 0.05); (ii) lower activities of urinary N-acetyl-beta-D glucosaminidase (NAG); and (iii) less marked histological changes. Mean tissue concentrations of gentamicin were considerably lower in both renal cortex and medulla from rats maintained on the low protein diet than from those animals on the normal diet (P less than 0.01 and P less than 0.05, respectively). These differences were, however, not reflected in the mean trough serum gentamicin concentrations which were not significantly different between the two groups. These results are discussed in relation to the proposed mechanisms involved in gentamicin-induced nephrotoxicity.


Thoracic surgery manpower: the fourth manpower study of thoracic surgery: 1985 report of the Ad Hoc Committee on Manpower of The American Association for Thoracic Surgery and The Society of Thoracic Surgeons.
Responding to a survey about their practice in 1985, 2,969 (70%) Board-certified thoracic surgeons provided data that were compared with data from manpower surveys in 1980 and 1976. (table; see text) Thoracic surgeons were most active between ages 35 and 54 years when they accomplished 61% of all general thoracic and 85% of cardiac operations. Surgeons older than 50 years performed significantly more general thoracic operations than younger surgeons, and the younger group performed significantly more cardiac operations than their older counterparts. Solo practice continued to decline. In smaller referral areas, the number of general thoracic procedures per surgeon increased, but the number of cardiac operations have decreased compared with 1980. Overall, general thoracic and cardiac operations increased, but peripheral vascular procedures and pacemaker insertions decreased in almost all nine census regions. Fewer general thoracic and cardiac operations were performed per thoracic surgeon in the western United States than in central and eastern regions. In response to questions about work load, 55% believed that their clinical activity was satisfactory, 42% operated too little, and 3% operated too much. The 363 non-Thoracic Board-certified surgeons who responded performed 14% of general thoracic and 8% of cardiac surgery in 1985. During the first half of the 1980s, our specialty certified an average of 134 thoracic surgeons annually, which is higher than the 120 surgeons per year estimated to meet the projected demand.


Hydrofluoroalkane-134a beclomethasone dipropionate extrafine aerosol provides equivalent asthma control to chlorofluorocarbon beclomethasone dipropionate at approximately half the total daily dose.
The mandatory requirement to eliminate chlorofluorocarbons (CFCs) as propellants in pharmaceutical aerosols has provided the opportunity to enhance significantly the delivery of aerosol drugs to the respiratory tract. This randomized, parallel-group, double-blind, double-dummy, multicentre study was undertaken to assess whether beclomethasone dipropionate (BDP) in hydrofluoroalkane-134a (HFA) provided equivalent control of moderately severe asthma to BDP in CFC but at approximately half the total daily dose, as might be expected from the improved lung deposition of the HFA-BDP extrafine aerosol. The novel study design included a 10-12 day run-in period to confirm that patients met established criteria of moderately severe asthma and were symptomatic on current therapy (inhaled beta-agonist plus CFC-BDP 400-800 micrograms day-1). This run-in period was followed by a short course of oral steroid therapy (prednisolone 30 mg day-1 for 7-13 days) to demonstrate steroid responsiveness [> or = 15% improvement in morning peak expiratory flow (PEF)] and to provide a within-study baseline of improved asthma control. A total of 233 patients were randomized to treatment for 12 weeks with HFA-BDP 800 micrograms day-1 (116 patients) or CFC-BDP 1500 micrograms day-1 (117 patients). The mean change from oral steroid treatment in morning PEF with HFA-BDP was equivalent to that seen with CFC-BDP at all time intervals. Changes in other measures of pulmonary function, asthma symptom scores and beta-agonist use were equivalent in the two treatment groups throughout the 12 week treatment period. The safety profile of HFA-BDP compared favourably with that of CFC-BDP with no unexpected adverse events reported. Fewer patients on HFA-BDP than on CFC-BDP had plasma cortisol levels below the normal reference range after 12 weeks of therapy (5.1% vs. 17.3%, respectively). In conclusion, HFA-BDP extrafine aerosol was found to provide equivalent control of moderately severe asthma to CFC-BDP at approximately half the daily dose with a favourable safety profile, suggesting an improved therapeutic ratio.


High failure rate associated with 180 degrees selective laser trabeculoplasty.
To determine the efficacy of selective laser trabeculoplasty (SLT) in a tertiary care referral center. In this retrospective study of selective laser trabeculoplasty performed by five physicians, 94 eyes from 94 patients were included. A majority (83/92, 90%) underwent 180 degrees selective laser trabeculoplasty. Selective laser trabeculoplasty failure was defined in two ways: (1) IOP decrease <3 mm Hg (definition one), or (2) IOP decrease <20% (definition two), on two successive visits > or =4 weeks after SLT. Overall failure rates were 68% (64/94) and 75% (70/94) (by definitions one and two, respectively). By survival/life-table analysis, mean time to failure was 6 months and 5.5 months, by definitions one and two, respectively. By the end of the study (14.5 months), the failure rates were 86% and 92% by definitions one and two, respectively. By each definition, in both univariable and multivariable analysis, only lower baseline IOP was a significant predictor of failure. Selective laser trabeculoplasty had an overall low success rate in our tertiary clinic population, with overall failure rates of 68% to 74% in those who underwent 180 degrees selective laser trabeculoplasty.


Poly(silsesquioxanes) and poly(siloxanes) grafted with N-acetylcysteine for eradicating mature bacterial biofilms in water environment.
Bacteria adapt to their living environment forming organised biofilms. The survival strategy makes them more resistant to disinfectants, which results in acute biofilm-caused infections, secondary water pollution by biofilm metabolites and bio-corrosion. New, efficient and environmentally friendly strategies must be developed to solve this problem. Water soluble N-acetyl derivative of L-cysteine (NAC) is a non-toxic compound of mucolytic and bacteriostatic properties that can interfere with the formation of biofilms. However, it can also be a source of C and N for undesired microorganisms, as well as a reason for some adverse human health effects. Consequently, novel procedures are required, that would decrease the take-up of NAC but not reduce its antibacterial properties. We have grafted N-acetyl-l-cysteine onto linear poly(vinylsilsesquioxanes) and poly(methylvinylsiloxanes) via thiol-ene addition. Antibacterial activity of the obtained hybrid materials (respectively, NAC-Si-1 and NAC-Si-2) was determined against Escherichia coli, Pseudomonas aeruginosa and Staphylococcus aureus strains. Native NAC inhibited growth of planktonic cells for the tested bacteria at concentration 0.25% w/v. Inhibition with equivalent solutions of the polymer derivatives was less effective due to the lack of SH groups. However, the tested polymers proved to be quite effective in eradication of mature biofilms. Treatment with 1% w/v emulsions of the hybrid polymers resulted in a significant reduction of viable cells in biofilm matrix despite the absence of thiol moieties. The effect was most pronounced for mature biofilms of S. aureus eradicated with NAC-Si-2.


Presence of the P2X(7) purinergic receptor on immune cells that invade the rat endometrium during oestrus.
Eosinophils, macrophages and other leucocytes invade the uterine endometrium during oestrus and play a role in the tissue remodeling and immune responses that occur prior to implantation of the fertilized ovum. Adenosine 5'-triphosphate (ATP) and its metabolites influence uterine function via ATP receptors. In this study, we investigated the presence and localisation of the P2X(7) nucleotide receptor in the cells that infiltrate the uterine endometrium of adult female rats during oestrus at the electron microscope level, using gold-silver pre-embedding immunocytochemical techniques. P2X(7) receptor expression was found in the cytoplasm and the cell membrane of eosinophils, macrophages and fibroblasts in the endometrium during oestrus. These results suggest that ATP-mediated responses may be important in uterine preparation and remodeling before implantation and that this may involve several types of cells. In particular, the presence of P2X(7) receptors on endometrial stromal cells may indicate their involvement in apoptosis and immune and inflammatory responses.


Delta9-tetrahydrocannabinol (THC) and AM 404 protect against cerebral ischaemia in gerbils through a mechanism involving cannabinoid and opioid receptors.
It has been suggested that the endocannabinoid system elicits neuroprotection against excitotoxic brain damage. In the present study the therapeutic potential of AM 404 on ischaemia-induced neuronal injury was investigated in vivo and compared with that of the classical cannabinoid receptor type 1 (CB1) agonist, delta 9-tetraydrocannabinol (THC), using a model of transient global cerebral ischaemia in the gerbil. The effects of AM 404 (0.015-2 mg kg(-1)) and THC (0.05-2 mg kg(-1)), given 5 min after ischaemia, were measured from 1 h to 7 days in terms of electroencephalographic (EEG) total spectral power, spontaneous motor activity, memory function, rectal temperature and hippocampal CA1 neuronal count. Over the dose range tested, AM 404 (2 mg kg(-1)) and THC (1 mg kg(-1)) completely reversed the ischaemia-induced behavioural, EEG and histological damage. Only THC (1 and 2 mg kg(-1)) induced a decrease of body temperature. Pretreatment with the selective CB1 receptor antagonist, AM 251 (1 mg kg(-1)) and the opioid antagonist, naloxone (2 mg kg(-1)) reversed the protective effect induced by both AM 404 and THC while the TRPV1 vanilloid antagonist, capsazepine (0.01 mg kg(-1)), was ineffective. Our findings demonstrate that AM 404 and THC reduce neuronal damage caused by bilateral carotid occlusion in gerbils and that this protection is mediated through an interaction with CB1 and opioid receptors. Endocannabinoids might form the basis for the development of new neuroprotective drugs useful for the treatment of stroke and other neurodegenerative pathologies.


Upregulation of hepcidin by interleukin-1beta in human hepatoma cell lines.
Anemia of chronic disease (ACD) is commonly observed in chronic inflammation, although its pathogenesis is poorly understood. Hepcidin is thought to be a key regulator in iron metabolism and has been implicated in ACD. Although the induction of hepcidin by an inflammatory cytokine interleukin-6 (IL-6) seems to have been confirmed, it is still controversial whether interleukin-1beta (IL-1beta), also known as an inflammatory cytokine, regulates hepcidin expression. We demonstrated that hepcidin mRNA was upregulated by IL-1beta in human hepatoma-derived HuH-7 cells, particularly at low concentrations of IL-1beta, while high concentrations of IL-6 were needed for the upregulation of hepcidin mRNA. Therefore, IL-1beta might be more important for the upregulation of hepcidin in physiological conditions than IL-6. Although IL-1beta induces IL-6 production in hepatocytes, our data indicate that the effect of IL-1beta on hepcidin expression is independent from that of IL-6. In conclusion, IL-1beta might have an important role in ACD.


Pathogens susceptible to tetracycline are also susceptible to omadacycline: tetracycline as a one-sided surrogate to predict omadacycline susceptible pathogens.
This study used surveillance data from a global program of clinical bacterial isolates to determine whether a tetracycline susceptible result can be used to predict an omadacycline susceptible result. Categorical agreement, very major error rates, and minor error rates were calculated for Staphylococcus aureus (MSSA and MRSA; n=38,364), S. lugdunensis (n=335), Streptococcus pneumoniae (n=11,725), S. pyogenes (n=3,390), S. anginosus group (n=622), Haemophilus spp. (n=6,419), Enterococcus faecalis (n=7,065), Klebsiella pneumoniae (n=10,313), and Enterobacter cloacae (n=4,418). Across the organisms, for which omadacycline has an FDA breakpoint established, a tetracycline susceptible result showed ≥96.3% categorical agreement in predicting an omadacycline susceptible result. The rates of very major errors were below the guideline-suggested level (<1.5%). Omadacycline retained activity against most (88.7-100% Gram-positive and 54-98.6% Gram-negative) tetracycline-resistant isolates. For laboratories that do not have the capability to perform susceptibility testing for omadacycline, one-sided surrogate testing for tetracycline can be a practical alternative.


One hundred years of Golgi's "perineuronal net": history of a denied structure.
Perineuronal nets are reticular structures enwrapping cell bodies and the largest dendrites of several neuronal populations. Discovered by Camillo Golgi, who described them in detail in 1898, they were intensely studied by the most famous contemporary neurohistologists for about twenty years. The opinion of Ramon y Cajal that perineuronal nets were a fixation artifact ended the first period of studies. Only a few researchers, among whom the Italian neurologists Besta and Belloni, went on with their studies up to the 1930s documenting the morphology of perineuronal nets of different mammals and of man both in normal and in pathological conditions. Only after about fifty years, the advances in the field of cytochemistry allowed the elucidation of not only the actual existence of perineuronal nets, but also their chemical nature, showing conclusively that they are complex organisations of extracellular matrix molecules, namely glycoproteins and proteoglycans. The research on perineuronal nets today involves several groups engaged to elucidate their biological properties and functional role.


Aerobic exercise improves motor function and striatal MSNs-Erk/MAPK signaling in mice with 6-OHDA-induced Parkinson's disease.
In Parkinson's disease (PD) state, with progressive loss of dopaminergic neurons in the substantia nigra, the striatal dopamine (DA) and glutamate (Glu) levels change, resulting in dysfunction of basal ganglia motor regulation. The PD patient presents motor dysfunction such as resting tremor, bradykinesia, and muscular rigidity. To investigate the mechanism of aerobic exercise to improve PD-related motor dysfunction, in the current study, 6-hydroxydopamine (6-OHDA) was used to induce the PD mice model, and the motor function of PD mice was comprehensively evaluated by open-field test, rotarod test, and gait test. The co-expression of prodynorphin (PDYN) and proenkephalin (PENK) with extracellular signal-regulated kinase (Erk1/2) and phosphorylation Erk1/2 (p-Erk1/2) were detected by double-labeling immunofluorescence. The results showed that a 4-week aerobic exercise intervention could effectively improve the motor dysfunction of PD mice. Moreover, it was found that the expressions of Erk1/2 and p-Erk1/2 in the dorsal striatum (Str) of PD mice were significantly increased, and the number of positive cells co-expressed by Erk1/2, p-Erk1/2, and PENK was significantly higher than PDYN. The above phenomenon was reversed by a 4-week aerobic exercise intervention. Therefore, this study suggests that the mechanism by which aerobic exercise improves PD-related motor dysfunction may be related to that the aerobic exercise intervention alleviates the activity of extracellular signal-regulated kinase/mitogen-activated protein kinases (Erk/MAPK) signaling pathway in striatal medium spiny neurons expressing D2-like receptors (D2-MSNs) of PD mice by regulating the striatal DA and Glu signaling.


Computational study of effects of tension imbalance on phonation in a three-dimensional tubular larynx model.
The present study explores the use of a continuum-based computational model to investigate the effect of left-right tension imbalance on vocal fold (VF) vibrations and glottal aerodynamics, as well as its implication on phonation. The study allows us to gain new insights into the underlying physical mechanism of irregularities induced by VF tension imbalance associated with unilateral cricothyroid muscle paralysis. A three-dimensional simulation of glottal flow and VF dynamics in a tubular laryngeal model with tension imbalance was conducted by using a coupled flow-structure interaction computational model. Tension imbalance was modeled by reducing by 20% the Young's modulus of one of the VFs, while holding VF length constant. Effects of tension imbalance on vibratory characteristic of the VFs and on the time-varying properties of glottal airflow as well as the aerodynamic energy transfer are comprehensively analyzed. The analysis demonstrates that the continuum-based biomechanical model can provide a good description of phonatory dynamics in tension imbalance conditions. It is found that although 20% tension imbalance does not have noticeable effects on the fundamental frequency, it does lead to a larger glottal flow leakage and asymmetric vibrations of the two VFs. A detailed analysis of the energy transfer suggests that the majority of the energy is consumed by the lateral motion of the VFs and the net energy transferred to the softer fold is less than the one transferred to the normal fold.


Characterization of lung-delivered in-situ forming controlled release formulations.
This study investigated the controlled drug release potential of formulations revealing temperature-induced sol-gel transition following administration to the respiratory tract. Diverse sildenafil-containing aqueous poloxamer 407 preparations were evaluated for critical gelation temperature and rheological properties. The in-vitro drug release profiles of the in-situ forming formulations were studied in a Franz type cell, while the drug absorption characteristics were determined in an isolated lung model. Furthermore, the weight gain of isolated lungs was monitored and the bronchoalveolar lavage fluid was analysed for the total protein content. Poloxamer 407 solutions with concentrations of >12 wt.% revealed gelation upon temperature increase (>20°C). Compared with free sildenafil solution, sildenafil-containing polymer formulations showed a prolonged in-vitro drug release profile. Likewise, 17 and 21 wt.% of poloxamer 407 were characterized by a sustained sildenafil transfer from the lung into the perfusate. However, a 10 wt.% polymer solution displayed an immediate sildenafil absorption. Interestingly, increasing the poloxamer 407 concentration (21 and 17 vs. 10 wt.%) led to decreased organ weight gain kinetics and a lower total protein content found in the bronchoalveolar lavage fluid. In-situ forming controlled release hydrogels represent a viable approach for inhalative therapy.


Formulation and Drug Loading Features of Nano-Erythrocytes.
Nano erythrocyte ghosts have recently been used as drug carriers of water-soluble APIs due to inherit biological characteristics of good compatibility, low toxicity, and small side-effect. In this study, we developed a novel drug delivery system based on nano erythrocyte ghosts (STS-Nano-RBCs) to transport Sodium Tanshinone IIA sulfonate (STS) for intravenous use in rat. STS-Nano-RBCs were prepared by hypotonic lysis and by extrusion methods, and its biological properties were investigated compared with STS injection. The results revealed that STS-Nano-RBCs have narrow particle size distribution, good drug loading efficiency, and good stability within 21 days. Compared with STS injection, STS-Nano-RBCs extended the drug release time in vitro and in vivo with better repairing effect on oxidative stress-impaired endothelial cells. These results suggest that the nano erythrocyte ghosts system could be used to deliver STS.


Influence of genetic polymorphisms on frequency of micronucleated buccal epithelial cells in leukoplakia patients.
Micronuclei (MN) are extensively used as an indicator of chromosomal damage and early biomarker of cancer risk. The genetic host factors are known to influence the level of chromosomal alterations consequently affecting MN frequencies. Hence, in the present study, we investigated the extent of chromosomal damage by analyzing micronucleated cell (MNC) frequency in exfoliated buccal epithelial cells (BEC) and its possible relationship with genetic polymorphisms in patients with oral leukoplakia (OL). The study group comprised of habit-free (NHC, n=39), habit controls (HC, n=62) and OL patients (n=66). Micronucleus assay was carried out to determine the MNC frequency and the genotyping was performed by PCR-RFLP for metabolizing (CYP1A1, GSTM1, GSTT1, GSTP1) and DNA repair (hOGG1, XRCC1, XPD) genes. The correlation between MNC frequency and genetic polymorphisms was analyzed. We found significant increase in overall MNC frequency in OL patients as compared to habit-matched controls (p=0.01). The higher proportion of multiple micronucleated cells (>5 MN per cell) indicate increased DNA damage in the buccal mucosa of OL patients than the controls (p=0.004). The polymorphic alleles of XPD751 and hOGG1 showed significant association with total MNC frequency in OLs (p=0.034 and p=0.03 respectively). In conclusion, the extent of chromosomal damage in target tissues is higher in patients with OL. MNC frequency in combination with genetic polymorphisms in DNA repair genes may serve as better predicator of risk.


Rapid, activity-guided isolation of sex-limited protein (Slp) from mouse serum by fractionated precipitation and high-performance liquid chromatography.
We have recently demonstrated that sex-limited protein (Slp) plays a key role in an EDTA-resistant mouse complement activation pathway. A rapid procedure, utilizing classical chromatography methods on an FPLC system, was developed for the isolation of functionally active Slp. The method is based on the fractionated precipitation of serum by polyethylene glycol 6000, followed by heparin Sepharose Cl-6B affinity chromatography, Mono Q anion exchange and Superose 12 gel filtration. The isolation of Slp was monitored by a hemolytic assay. The procedure resulted in the purification of Slp, which by SDS-PAGE gave a single band of M(r) 2000,000 under non-reducing conditions, and under reducing conditions three bands corresponding to M(rs) of 105,000, 76,000 and 37,000.


MR outcome parameters in multiple sclerosis: comparison of surface-based thresholding segmentation and magnetization transfer ratio histographic analysis in relation to disability (a preliminary note).
MR imaging is now widely used to monitor disease progression in patients with multiple sclerosis (MS). The purpose of this study was to explore the relationship between disability status and existing and new MR parameters in MS patients. Forty-one patients with clinically definitive MS were studied. MR imaging included T2- and T1-weighted imaging as well as gradient-echo imaging with and without magnetization transfer contrast. We used surface-based thresholding segmentation techniques to obtain T2 and T1 lesion load, T1/T2 ratio, and several magnetization transfer ratio (MTR) lesion load parameters. MTR histographic analysis included measurements of absolute peak height (aHp), relative peak height (rHp), MTR of the peak (MTRp), mean MTR (MTRm), and MTR25, MTR50, and MTR75, relating to the integrals of the histogram at 25%, 50%, and 75%, respectively, of the total area under the curve. All MR parameters were correlated with Expanded Disability Status Scale (EDSS) score, disease duration, and patient's age. Using surface-based thresholding segmentation techniques, we found relatively low correlations with EDSS. T1 lesion load and T1/T2 ratios correlated most strongly. Regarding MTR histographic parameters, EDSS correlated best with rHp but only weakly with others. Similar correlations were found with disease duration, but not with age. The best MR correlations with disability were several MTR histographic parameters. Our findings may favor the use of these MR parameters over T2 lesion load to monitor disease progression in patients with MS, findings that should be explored further in longitudinal studies.


Molecular cloning and mRNA expression of cathepsin C gene in black tiger shrimp (Penaeus monodon).
Cathepsin C (dipeptidyl-peptidase I, DPPI) is a lysosomal cysteine proteinase belonging to the papain superfamily, which is capable of removing dipeptides sequentially from the amino terminus of peptide and protein substrates. In the present study, the cDNA of a cathepsin C was cloned from black tiger shrimp Penaeus monodon (designated PmcathepsinC) by homology cloning and rapid amplification of cDNA ends (RACE) approaches. The full-length cDNA of PmcathepsinC consisted of 2051 nucleotides with a canonical polyadenylation signal sequence AATAAA and a poly(A) tail, and an open reading frame (ORF) of 1350 bp encoding a polypeptide of 449 amino acid residues with a predicted molecular weight of 50.0 kDa and theoretical isoelectric point of 5.65. The high identity of PmcathepsinC with Cathepsin C in other organisms indicated that PmcathepsinC should be a new member of the Cathepsin C family. By fluorescent quantitative real-time PCR, mRNA transcript of PmcathepsinC was detectable in all the examined tissues with higher level in ovary and heart. The temporal expression of PmcathepsinC mRNA in the hepatopancreas was up-regulated by lipopolysaccharide (LPS) stimulation and reached the maximum level at 4 h post-stimulation, and then dropped back to the original level gradually. These results indicated that PmcathepsinC was a constitutive and inducible acute-phase protein that perhaps involved in the immune defense of P. monodon.


Induction of lipolysis in vitro and loss of body fat in vivo by zinc-alpha2-glycoprotein.
Loss of adipose tissue in cancer cachexia has been associated with tumour production of a lipid-mobilizing factor (LMF) which has been shown to be homologous with the plasma protein zinc-alpha(2)-glycoprotein (ZAG). The aim of this study was to compare the ability of human ZAG with LMF to stimulate lipolysis in vitro and induce loss of body fat in vivo, and to determine the mechanisms involved. ZAG was purified from human plasma using a combination of Q Sepharose and Superdex 75 chromatography, and was shown to stimulate glycerol release from isolated murine epididymal adipocytes in a dose-dependent manner. The effect was enhanced by the cyclic AMP phosphodiesterase inhibitor Ro20-1724, and attenuated by freeze/thawing and the specific beta3-adrenoreceptor antagonist SR59230A. In vivo ZAG caused highly significant, time-dependent, decreases in body weight without a reduction in food and water intake. Body composition analysis showed that loss of body weight could be attributed entirely to the loss of body fat. Loss of adipose tissue may have been due to the lipolytic effect of ZAG coupled with an increase in energy expenditure, since there was a dose-dependent increase in expression of uncoupling protein-1 (UCP-1) in brown adipose tissue. These results suggest that ZAG may be effective in the treatment of obesity.


Intestinal lactase deficiency in Ceylon (Sri Lanka).
Lactose tolerance tests (LTT) in 200 normal adult Ceylonese have shown that 145 (72.5%) had a flat LTT, indicating a population prevalence of lactase deficiency of 66.2 to 78.8%. Jejunal lactase estimations in a smaller sample (41) confirmed this. Twelve of 55 subjects (21.8%) with a normal LTT had intestinal symptoms after lactose and intestinal lactase was low in most of them. It is suggested that little lactase is required to elevate the blood sugar but that more may be required to prevent diarrhea. On the other hand, 65.5% had no symptoms despite a flat LTT, and the possible reasons for this are considered.


Sonochemical formation of peroxynitrite in water: Impact of ultrasonic frequency and power.
There is a lack of literature on peroxynitrite formation due to sonolysis of aerated water. In this work, the impact of sonication parameters, frequency and power, on ultrasonic peroxynitrite production in aerated alkaline water was investigated. Peroxynitrite formation was clearly established with undeniable evidence at all the tested frequencies in the range of 516-1140 kHz with a typical G-value (energy-specific yield) of 0.777 × 10-10, 0.627 × 10-10, 0.425 × 10-10 and 0.194 × 10-10 mol/J at 516, 558, 860 and 1140 kHz, respectively. The ultrasonication frequency has a direct impact on the sonochemical peroxynitrite production. Increasing the ultrasonication frequency in the interval 321-1140 kHz reduces peroxynitrite formation. The most practical sonochemistry dosimetries, including hydrogen peroxide production, triiodide dosimetry, Fricke dosimetry, and 4-nitrocatechol formation, were compared with the sonochemical efficiency of the reactors used to produce peroxynitrite. The G-value, energy specific yield, for the tested dosimetries was higher than that for peroxynitrite formation, regardless of frequency. For all chemical dosimetries investigated, the same trend of frequency dependence was found as for peroxynitrite generation. The influence of ultrasonication power on peroxynitrite formation by sonication at diverse frequencies in the interval 585-1140 kHz was studied. No peroxynitrite was formed at lower acoustic power levels, regardless of frequency. As the frequency increases, more power is required for peroxynitrite formation. The production of peroxynitrite increased as the acoustic power increased, despite the frequency of ultrasonic waves. Ultrasonic power is a key factor in the production of peroxynitrite by sonolysis. Since peroxynitrite is uniformly distributed in the bulk solution, peroxynitrite-sensitive solutes can be transformed both in the bulk of the solution and in the surfacial region (shell) of the cavitation bubble. The formation of peroxynitrite should be taken into account in sonochemistry, especially at higher pH values. Ultrasonic peroxynitrite formation in alkaline solution (pH 12) can be considered as a kind of chemical dosimetry in sonochemistry.


The effect of portacaval shunting in the alcoholic cirrhotic on serum cholesterol concentration. A retrospective study.
Preoperative and postoperative cholesterol levels were obtained by retrospective analysis of 28 patients subjected to successful portalsystemic decompression. The average cholesterol values showed a statistically significant decline from 189-161 mg.%.


Photobiochemistry without light.
Efficient excited state formation - much higher than that hitherto expected - may occur in organelles and in intact cells. Excited triplet states can be enzymatically generated in high yields by different routes. An example is the oxidation of isobutanal to acetone and formic acid, catalyzed by horseradish peroxidase. Other enzymatic systems that generate triplet carbonyls are linear aliphatic aldehydes when oxidized by peroxidase/O2, or the indole-3-acetic acid/peroxidase/O2-reaction. The latter is widespread in plants. This new field - photobiochemistry without light - has led to a growing awareness of the idea that cells may utilize excited states to trigger photochemical processes even in the dark. Such phenomena are of considerable importance, also for the understanding of weak photon emission from biological systems.


Percutaneous hallux valgus surgery: comparison between mini-invasive Chevron and Bosch osteotomies.
Through percutaneous approaches, hallux valgus corrections can be performed with minimal soft tissue injury, less postoperative pain and good cosmetic results. Bosch osteotomy and MICA (Minimally Invasive Chevron Akin) have shown to be effective techniques for the correction of hallux valgus, although there are currently no publications comparing each other. The aim of this study is to compare the radiological and functional results of both techniques. A retrospective, comparative study was carried out on patients with moderate hallux valgus. They were divided into two groups according to the percutaneous technique performed: Chevron osteotomy and Bosch osteotomy with screw fixation. The metatarsophalangeal, intermetatarsal, and distal articular veneer declination angles of the first metatarsal and the bone consolidation time were evaluated radiologically. The American Orthopaedic Foot and Ankle Surgery (AOFAS) score was used for functional assessment. Complications were registered during the first year. Thirty-eight patients in each group were included for the study. In each of the groups, the radiological angles were compared preoperatively and at final follow-up, showing statistically significant changes in the three variables considered; but no differences were obtained by comparing them with each other. The time of consolidation was also similar in both groups. As for the AOFAS scale, an improvement was obtained with both techniques, but the difference was not significant when comparing them. Both Bosch and MICA techniques showed comparable results at the end of the follow-up. Further work is needed to determine the advantages of each in the immediate postoperative time.


Effect of a single ingestion of alcohol on iron absorption.
The effect of alcohol on inorganic and organic iron absorption was studied in 70 subjects, using a whole-body counter technique. The mean iron absorption of a test dose was 24.44%, while in the presence of whisky, absorption fell to 9.73% (P less than 0.0001). Absorption of a test dose in the presence of whisky without alcohol was 10.14% (P less than 0.0001). The alcohol in whisky, therefore, was not responsible for the diminished iron absorption (P greater than 0.20). The absorption of the iron contained in wine with alcohol was 73.31 microgram and wine without alcohol was 67.50 microgram. The difference was not statistically significant (P greater than 0.20). The absorption of inorganic iron contained in a test meal was 165.55 microgram and was not changed in the presence of ethanol (151.35 microgram) (P greater than 0.10). However, the presence of ethanol affected the absorption of heme iron: 538.68 microgram compared with 442.41 microgram with ethanol (P less than 0.0001). These studies show that the acute ingestion of ethanol does not influence the absorption of inorganic iron, while it does diminish the absorption of the organic form.


The phylogenetic affinities and morphological peculiarities of the bird-like dinosaur Borogovia gracilicrus from the Upper Cretaceous of Mongolia.
Borogovia gracilicrus is a small-bodied theropod dinosaur from the Maastrichtian (Upper Cretaceous) Nemegt Formation of southern Mongolia. The taxon is based on a single fragmentary specimen preserving only the distal part of the hindlimbs. The morphology of Borogovia shows a peculiar combination of features, some of which are traditionally considered troodontid synapomorphies and others which are unusual for Troodontidae but are shared with other maniraptoran clades. In particular, the second toe of B. gracilicrus differs from other troodontids in lacking some of the features which contribute to the specialized 'sickle-clawed' second toe, here termed the 'falciphoran condition', shared with dromaeosaurids and some other paravians, such as the strongly compressed and falciform ungual. Phylogeny reconstructions intended to explore the affinities of Borogovia consistently support its referral within a subclade of troodontids including all Late Cretaceous taxa. The placement of Borogovia is not significantly affected by its unusual combinations of hindlimb features or by the homoplasy of the elements forming the falciphoran condition. Borogovia is supported as a valid taxon and is distinct from the other Nemegt troodontids, Tochisaurus and Zanabazar. The lack of a falciform ungual, and the distinctive morphology of the second toe in B. gracilicrus are interpreted as a derived specialization among Troodontidae and not as retention of the plesiomorphic condition of non-paravian theropods.


EXOSC10/Rrp6 is essential for the eight-cell embryo/morula transition.
The conserved 3'-5' exoribonuclease EXOSC10/Rrp6 is required for gametogenesis, brain development, erythropoiesis and blood cell enhancer function. The human ortholog is essential for mitosis in cultured cancer cells. Little is known, however, about the role of Exosc10 during embryo development and organogenesis. We generated an Exosc10 knockout model and find that Exosc10-/- mice show an embryonic lethal phenotype. We demonstrate that Exosc10 maternal wild type mRNA is present in mutant oocytes and that the gene is expressed during all stages of early embryogenesis. Furthermore, we observe that EXOSC10 early on localizes to the periphery of nucleolus precursor bodies in blastomeres, which is in keeping with the protein's role in rRNA processing and may indicate a function in the establishment of chromatin domains during initial stages of embryogenesis. Finally, we infer from genotyping data for embryonic days e7.5, e6.5 and e4.5 and embryos cultured in vitro that Exosc10-/- mutants arrest at the eight-cell embryo/morula transition. Our results demonstrate a novel essential role for Exosc10 during early embryogenesis, and they are consistent with earlier work showing that impaired ribosome biogenesis causes a developmental arrest at the morula stage.


Oncological and aesthetic considerations of skin-sparing mastectomy.
To review the oncological safety and aesthetic value of skin-sparing mastectomy (SSM) for invasive breast cancer (IBC) and ductal carcinoma in-situ (DCIS). Controversies including the impact of radiotherapy (RT) on immediate breast reconstruction (IBR), preservation of the nipple-areola complex (NAC) and the role of endoscopic mastectomy are also considered. Literature review facilitated by Medline and PubMed databases. SSM is an oncologically safe technique in selected cases, including IBC <5 cm, multi-centric tumours, DCIS and prophylactic risk-reduction surgery. The high risk of local recurrence (LR) excludes inflammatory breast cancers and tumours with extensive involvement of the skin. SSM can facilitate IBR and is associated with an excellent aesthetic result. Prior breast irradiation or the need for post-mastectomy radiotherapy (PMR) do not preclude SSM, however the cosmetic outcome may be affected. Nipple/areola preservation is possible for remote tumours, employing a frozen section protocol for the retro-areolar tissue. There is limited data available for endoscopic mastectomy and superiority over conventional SSM has not been established. In appropriately selected cases SSM is oncologically adequate. There are several patient centred advantages over conventional mastectomy, including aesthetic outcome and the avoidance of multiple staged procedures. Despite widespread uptake into surgical practice, validation of these techniques from randomised controlled trials is lacking.


Monoclonal antibodies against microorganisms.
The recent spread of hybridoma technology among laboratories has promoted the development of monoclonal antibodies against a wide variety of infectious disease agents. While monoclonal antibodies theoretically represent an excellent (perhaps superior) alternative to conventional antisera as diagnostic, therapeutic or laboratory reagents, traditional antisera may be preferable to monoclonal antibody in some circumstances because of the fixed affinity and specificity as well as the limited functional capacities of some antibodies. The acceptance of monoclonal antibodies by the clinical microbiologist and physician must await proof of their reliability, safety and efficacy.


Quality of life in patients operated on for digestive neoplasia: a prospective study.
The aim of this study was to evaluate the quality of life in patients having surgery for a digestive neoplasm and to monitor how the patient's perception evolves during the first 6 months after surgery. A prospective study was carried out on the pre and postoperative quality of life of patients undergoing surgery for a digestive system neoplasm between May 2009 and December 2010. Patients were asked to complete the Short Form (36) Health Survey questionnaire (SF-36; spanish version 1.4). The study included 80 patients. At 1 month after surgery there was a statistically significant improvement in some domains of the SF-36. At 6 months, a statistically significant improvement was seen in physical functioning, social functioning, mental health and in the two physical and mental domains. We also found statistically significant differences, with women having a worse quality of life. Comparison of quality of life before and 6 months after surgical intervention showed improvement in both the psychological and the physical elements. This can be attributed to the fact that the patients have had time to recover from the surgery.


Application of ionic liquid-based microwave-assisted extraction of flavonoids from Scutellaria baicalensis Georgi.
In the present work, a rapid ionic liquid-based microwave-assisted extraction (ILMAE) method was successfully applied to simultaneous extraction of baicalin, wogonoside, baicalein and wogonin from Scutellaria baicalensis Georgi. A series of 1-alkyl-3-methylirnidazolium ionic liquids with different anions and cations were assessed for extraction efficiency, and 1-octyl-3-methylimidazolium bromide was selected as the optimal solvent. In addition, the parameters of ILMAE procedure for the four flavonoids were optimized, and the optimal ILMAE method was validated in the linearity, stability, precision and recovery. Meanwhile, the microstructures of S. baicalensis powders were observed before and after extraction with the help of a scanning electron microscope (SEM) in order to explore the extraction mechanism, and the activity of the crude enzyme solution from S. baicalensis was determined through the hydrolysis of baicalin. Finally, the extraction yields and extraction time of WaterHRE, WaterMAE, ILHRE and Chp were 5.18% (30min), 8.77% (90s), 16.94% (30min) and 18.58% (3h), respectively. The results indicated that compared with the conventional extraction approaches, ILMAE possessed great advantages in extracting flavonoids, such as the highest extraction yield (22.28%), the shortest extraction time (90s), etc.


Is Morton's neuroma in a pes planus or pes cavus foot lead to differences in pressure distribution and gait parameters?
Morton's neuroma (MN) is a compressive neuropathy of the common digital plantar nerve causing forefoot pain. Foot posture and altered plantar pressure distribution have been identified as predispoing factors, however no studies have compared individuls with different foot postures with MN. Thus, we aimed to compare the effect of MN on spatiotemporal gait parameters and foot-pressure distribution in individuals with pes planus and pes cavus. Thirty-eight patients with unilateral MN were evaluated between June and August 2021. Nineteen patients with bilateral pes planus and 19 age and gender-matched patients with pes cavus who had no prior surgery were recruited. A Zebris FDM-THM-S treadmill system (Zebris Medical GmbH, Germany) was used to evaluate step length, stride length, step width, step time, stride time, cadence, velocity, foot-pressure distribution, force and whole stance phase, loading response, mid stance, pre-swing and swing phase percentages. There were no significant differences between the groups in spatiotemporal gait parameters (p > 0.05). Patients with pes planus displayed the following results for step length (49.36 ± 8.38), step width (9.05 ± 2.12), stance phase percentage (65.92 ± 2.11), swing phase percentage (34.08 ± 2.12), gait speed (2.96 ± 0.55), and cadence (100.57 ± 8.84). In contrast, patients with pes cavus displayed the following results for step length (49.06 ± 8.37), step width (8.10 ± 2.46), stance phase percentage (64.96 ± 1.61), swing phase percentage (34.79 ± 1.60), gait speed (2.95 ± 0.65), and cadence (99.73 ± 13.81). Foot-pressure distribution values showed no differences were detected in force, forefoot, and rearfoot pressure distribution, except for midfoot force (p < 0.05). The forefoot, midfoot, and rearfoot pressure values for the pronated group were 32.14 ± 10.90, 13.80 ± 3.03, and 22.78 ± 5.10, and for the supinated group were 33.50 ± 11.49, 14.23 ± 3.11 and 24.93 ± 6.52. MN does not significantly affect spatiotemporal gait parameters or foot-pressure distribution in patients with pes cavus or pes planus.


Malignant transformation of endometriosis in a laparoscopic trocar site a case report.
Malignant transformation of endometriosis is infrequent at the laparoscopic trocar site. Although malignant transformation is uncommon, it must be acknowledged in order to achieve radical resection. We report on a 54-year-old woman with trocar site endometriosis 2 years after laparoscopic ovarian endometrial resection. Physical examination revealed a subcutaneous solid tumor with a diameter of 3 cm surrounding the scar of laparoscopic surgery in the right lower abdomen. Transabdominal ultrasonography showed a cystic tumor in the subcutaneous adipose layer of the right lower abdomen. The pathological diagnosis was poorly differentiated endometrioid carcinoma. Hysterectomy, bilateral salpingo-oophorectomy and pelvic lymphadenectomy were then performed. Histological examination revealed mixed endometrioid carcinoma and clear cell carcinoma. After six cycles of chemotherapy, computed tomography showed no signs of recurrence. Malignant transformation of laparoscopic endometriosis is very uncommon, and the diagnosis and stage are determined by clinical manifestations and imaging examination. The main therapy methods are radical surgery combined with neoadjuvant chemotherapy and adjuvant radiotherapy. At the same time, reducing iatrogenic abdominal incision implantation is an effective prevention method.