Toward chronobiologic pattern discrimination of the risk of developing breast cancer and other diseases.
With a view of the prevention as well as treatment of cancer and other diseases, it is important to quantify health positively and on an individual basis by chronobiologic methods. These include the assessment of the characteristics of certain circadian, circannual and other endocrine rhythms and trends, for the recognition of risk (prior to the occurrence of a given disease) by an alteration of the same rhythm characteristics and even by a time-specified single sample. With this aim in mind, a small number of selected (rather than randomly picked) women of 3 age groups was extensively sampled for 12 plasma hormones around the clock and the calendar, in 2 geographic locations. Such data revealed correlations of the familial risk of developing breast cancer with the circannual amplitudes of circulating prolactin and TSH. The risk of several other conditions was also correlated with hormonal rhythm characteristics; for example, the risk of developing diseases associated with a high blood pressure was correlated with the circannual amplitude of plasma aldosterone. The mapping of circannual characteristics, however, is time-consuming and costly and may not be warranted as a first step, for example when a physician is not in a position to wait for a year to make a diagnosis. With the possibility in mind that sampling requirements may be reduced to one or at most two samples, a chronobiologic pattern discrimination analysis was undertaken on the original data from young adults. The results are presented to indicate the method and to suggest the singling-out of certain variables for further testing on a larger, properly stratified and randomized sample, rather than as definitive results. Different classifiers and different corresponding reference values from variables that undergo circadian and circannual rhythms may perhaps withstand the test (and, with Vergil, the tooth) of time. If so, reference values that are time-specified may well prove to be a sine qua non in the assessment of certain neuroendocrine aspects of developing certain diseases, including breast cancer.


Catalytic effects of ZnO nanorods grown by sonochemical decomposition of zinc acetate dihydrate.
In this study, we prepared ZnO nanorods by a sonochemical method using a zinc acetate dihydrate as a new precursor. Well-aligned high-quality ZnO nanorods were synthesized on FTO glass by the sonochemical decomposition of zinc acetate dihydrate using a ZnO thin-film as the catalytic layer. The ZnO thin-films were deposited on the FTO glass by a sputtering method. To investigate their catalytic effects on the ZnO nanorods, catalytic ZnO thin-films of 20 nm, 40 nm, and 60 nm thickness were prepared by adjusting the sputtering time. The ZnO nanorods grown on catalytic layers with different thicknesses were characterized by SEM, XRD, and PL. The ZnO nanorods grown on the catalytic layer of 40 nm thickness show the best crystal and spatial orientation and as a result display the best optical properties. It was found that a catalytic ZnO thin-film of 40 nm in thickness yields well-aligned high-quality ZnO nanorods, due to its small surface roughness and structural strain.


Pediatric AIDS in the United States: epidemiological reality versus government policy.
Pediatric AIDS cases constitute approximately 2 percent of total AIDS cases in the United States, but HIV infection and AIDS among children pose a growing concern. Government policies have failed to match the epidemiological reality of the disease. The powerful shapers of public opinion have dedicated their energies to a handful of cases, involving the school attendance of primarily middle-class children. Unfortunately, coverage of school placement issues has overshadowed both the demographically more serious issue of perinatally transmitted AIDS cases and the growing concern over adolescent AIDS. Seventy-five percent of perinatal AIDS sufferers are poor, urban minorities: the disease is clearly related to other indicators of poor child health--urban poverty and oppressive social conditions. School-based prevention efforts for adolescents have been rendered impotent because of moralistic obstacles to explicit education. Prevention of perinatal and adolescent HIV transmission must be both sensitive and relevant to communities in which the greatest threat to survival is poverty, not AIDS. Ultimately, issues surrounding pediatric AIDS only reinforce the long-term position of child health advocates: the best investment a society can make is a sincere commitment of resources to improve the health, education, and welfare of its children.


Ecological niche modelling and differentiation between Rhodnius neglectus Lent, 1954 and Rhodnius nasutus Stål, 1859 (Hemiptera: Reduviidae: Triatominae) in Brazil.
Ecological niche modelling was used to predict the potential geographical distribution of Rhodnius nasutus Stål and Rhodnius neglectus Lent, in Brazil and to investigate the niche divergence between these morphologically similar triatomine species. The distribution of R. neglectus covered mainly the cerrado of Central Brazil, but the prediction maps also revealed its occurrence in transitional areas within the caatinga, Pantanal and Amazon biomes. The potential distribution of R. nasutus covered the Northeastern Region of Brazil in the semi-arid caatinga and the Maranhão babaçu forests. Clear ecological niche differences between these species were observed. R. nasutus occurred more in warmer and drier areas than R. neglectus. In the principal component analysis PC1 was correlated with altitude and temperature (mainly temperature in the coldest and driest months) and PC2 with vegetation index and precipitation. The prediction maps support potential areas of co-occurrence for these species in the Maranhão babaçu forests and in caatinga/cerrado transitional areas, mainly in state of Piaui. Entomologists engaged in Chagas disease vector surveillance should be aware that R. neglectus and R. nasutus can occur in the same localities of Northeastern Brazil. Thus, the identification of bugs in these areas should be improved by applying morphometrical and/or molecular methods.


Maternal depressive symptoms and early childhood temperament before and during the COVID-19 pandemic in the United Kingdom.
The COVID-19 pandemic is an unexpected and major global event, with the potential to have many and varied impacts on child development. However, the implications of the pandemic for maternal depressive symptoms, early childhood temperament dimensions, and their associations, remain largely unknown. To investigate this, questionnaires were completed by mothers (N = 175) before and during the pandemic when their child was 10- and 16-months old (Study 1), and by an extended group of mothers with young children (6-48 months; 66 additional mothers) during the first and second national lockdowns in the United Kingdom in 2020 (Study 2). Results indicated that while maternal pandemic-related stress decreased over the first 6 months of the pandemic, there was an increase in mothers who reported feeling some level of pandemic-specific depression. Despite this, we did not observe an increase in the severity of global maternal depressive symptoms, or any negative impact of the pandemic on the development of temperament in infancy and early childhood.


Na2RE2TeO4(BO3)2 (RE = Y, Dy-Lu): luminescent and structural studies on a series of mixed metal borotellurates.
The first examples of metal borotellurates, namely, Na2RE2TeO4(BO3)2 (RE = Y, Dy-Lu) have been prepared by using solid-state reactions. They possess similar structures and crystallize in space group P21/c (No. 14). These compounds feature a novel [RE2TeO4(BO3)2](2-) 3D network structure composed of linear [TeO4(BO3)2](8-) anions interconnected by RE(3+) ions with the voids of the network filled by the Na(+) ions. They exhibit high thermal stability (higher than 800 °C). Results of magnetic measurements on Dy, Ho, and Er compounds indicate that they display weak antiferromagnetic interaction between RE(III) centers. Luminescent studies show that Na2Er2TeO4(BO3)2 has a strong emission at 1.562 μm with a wide fwhm (70 nm) and moderate lifetime (0.18 ms), whereas Na2Yb2TeO4(BO3)2 has a strong NIR region emission around 1.02 μm. Furthermore, UV-vis-NIR absorption spectra, infrared spectra, and DFT calculations for the Y compound as a representative were also accomplished.


Physical exam myths: listening for carotid artery bruits in stroke patients.
When a patient presents to the emergency department with a neurologic deficit and a cerebrovascular event is included in the differential diagnosis, the classic recommendation is to examine the carotid artery and assess for the presence of a bruit. The diagnostic yield and utility of this practice has seldom been called into question. This critical appraisal will review the practice of listening for a carotid artery bruit (CAB) in suspected stroke patients and analyze its clinical utility, including the sensitivity and specificity of a CAB for detecting a significant lesion and the potential impact a CAB may have on the investigation and disposition of such patients.


Stop Discussing New Medical Specialty Boards.
The Korean society is rapidly aging and the health care needs for aged people are increasing. In this context, some physicians claim to establish new medical specialty board (MSB) for geriatric medical experts but also MSB for primary medical care specialists, clinical pharmacologists, and public health experts. In Korea, basic concept for the specialty board system is still under debates and the legal support for the system is poor. At present, doctors with MSBs in private sectors supply 92.4% of primary medical care but the National Health Care System requires more primary care physicians than specialists in Korea. Therefore, the government must invest in the education of doctors more to improve the public health care system. The proposal of the new MSB for geriatric medicine must be gradually developed according to the national long-term health plan, social needs, and national budget for the public benefit. Please stop discussing unprepared new MSBs.


Identification of a region in protein C involved in thrombomodulin-stimulated activation by thrombin: potential repulsion at anion-binding site I in thrombin.
During coagulation human protein C is activated by thrombin; however, this cleavage reaction is slow unless thrombin is complexed with a cofactor, thrombomodulin. Near the thrombin cleavage site in protein C is a cluster of basic residues, at positions P5' (Lys-174), P8' (Arg-177) and P9' (Arg-178). We have explored the role of this basic cluster in the activation of protein C by thrombin, and by thrombin-thrombomodulin complex, by substitution of glutamic acid at each position to generate the acidic protein C derivative P'-EEE. The activation rate of P'-EEE by free alpha-thrombin was approx. 12-fold faster than that observed for wild-type (wt) human protein C zymogen (HPC) in the presence of calcium, but unchanged in the absence of calcium. While the thrombin-catalysed activation of wt-HPC was stimulated approx. 300-fold by thrombomodulin, we observed no effect of thrombomodulin on thrombin-catalysed activation of the P'-EEE derivative. Using synthetic peptides that bind to anion-binding site I of thrombin (thrombin-receptor sequence 52-66 and hirudin sequence 54-65 SO4 Tyr), we found that the rate of thrombin-catalysed activation of wt-HPC in the presence of calcium could be increased severalfold in a dose-dependent manner. However, the enhanced rate of thrombin-catalysed activation of P'-EEE could be progressively reduced to wt-HPC levels with increasing concentrations of both synthetic peptides. Our data suggest that the P' basic cluster in protein C reduces interaction with free alpha-thrombin through electrostatic repulsion with anion-binding site I, a site that is masked when thrombomodulin binds thrombin. Further, the lack of thrombomodulin cofactor activity with thrombin-catalysed activation of P'-EEE suggests that the basic cluster in protein C forms a contact site with thrombomodulin.


Economics of membrane occupancy and respiro-fermentation.
The simultaneous utilization of efficient respiration and inefficient fermentation even in the presence of abundant oxygen is a puzzling phenomenon commonly observed in bacteria, yeasts, and cancer cells. Despite extensive research, the biochemical basis for this phenomenon remains obscure. We hypothesize that the outcome of a competition for membrane space between glucose transporters and respiratory chain (which we refer to as economics of membrane occupancy) proteins influences respiration and fermentation. By incorporating a sole constraint based on this concept in the genome-scale metabolic model of Escherichia coli, we were able to simulate respiro-fermentation. Further analysis of the impact of this constraint revealed differential utilization of the cytochromes and faster glucose uptake under anaerobic conditions than under aerobic conditions. Based on these simulations, we propose that bacterial cells manage the composition of their cytoplasmic membrane to maintain optimal ATP production by switching between oxidative and substrate-level phosphorylation. These results suggest that the membrane occupancy constraint may be a fundamental governing constraint of cellular metabolism and physiology, and establishes a direct link between cell morphology and physiology.


[Cytotoxicity of chloramphenicol on cultured mammalian cells].
Cytotoxicity of chloramphenicol on cultured mammalian cells was studied. Growth of V79 cells, derived from Chinese hamster lung was inhibited by treatment with chloramphenicol at above 300 micrograms/ml for 24 to 48 hr. Inhibitory effect on survival of V79 cells was not observed in cultures treated with chloramphenicol at 300 to 1,000 micrograms/ml for 2 to 12 hr. Meanwhile, treatment with chloramphenicol at 3,000 micrograms/ml for 2 to 24 hr elicited a dose-related reduction of cell survival. Inhibition of cell survival was also observed in cultures treated with 300 to 3,000 micrograms/ml for 24 hr in a treatment time-dependent manner. Exposure of cells to chloramphenicol at 300 to 3,000 micrograms/ml for 2 hr resulted in an inhibition of DNA-, RNA-, and protein-syntheses of the cells, in a dose-related fashion.


Effects of insecticide-treated bednets during early infancy in an African area of intense malaria transmission: a randomized controlled trial.
Insecticide-impregnated bednets and curtains have been shown by many studies to be effective against malaria. However, because of possible interactions with immunity development, treated bednets may cause no effect at all or even an increase in malaria morbidity and mortality in areas of high transmission. To clarify this issue, we did a randomized controlled trial to assess the long-term effects of bednet protection during early infancy. A total of 3387 neonates from 41 villages in rural Burkina Faso were individually randomized to receive either bednet protection from birth (group A) or from age 6 months (group B). Primary outcomes were all-cause mortality in all study children and incidence of falciparum malaria in a representative subsample of the study population. After a mean follow-up of 27 months, there were 129 deaths in group A and 128 deaths in group B rate ratio (RR) 1.0 (95% confidence interval (CI): 0.78-1.27)). Falciparum malaria incidence was lower in group A than in group B, during early (0-5 months) and late infancy (6-12 months) (RR 3.1, 95% CI: 2.0-4.9; RR 1.3, 95% CI: 1.1-1.6) and rates of moderate to severe anaemia were significantly lower during late infancy (11.5% vs 23.3%, P = 0.008), but there were no differences between groups in these parameters in children older than 12 months. The findings from this study provide additional evidence for the efficacy of insecticide-treated nets in young children living in areas of intense malaria transmission.


Derivation of the Statistical Distribution of the Mass Peak Centroids of Mass Spectrometers Employing Analog-to-Digital Converters and Electron Multipliers.
The mass peak centroid is a quantity that is at the core of mass spectrometry (MS). However, despite its central status in the field, models of its statistical distribution are often chosen quite arbitrarily and without attempts at establishing a proper theoretical justification for their use. Recent work has demonstrated that for mass spectrometers employing analog-to-digital converters (ADCs) and electron multipliers, the statistical distribution of the mass peak intensity can be described via a relatively simple model derived essentially from first principles. Building on this result, the following article derives the corresponding statistical distribution for the mass peak centroids of such instruments. It is found that for increasing signal strength, the centroid distribution converges to a Gaussian distribution whose mean and variance are determined by physically meaningful parameters and which in turn determine bias and variability of the m/z measurements of the instrument. Through the introduction of the concept of "pulse-peak correlation", the model also elucidates the complicated relationship between the shape of the voltage pulses produced by the preamplifier and the mean and variance of the centroid distribution. The predictions of the model are validated with empirical data and with Monte Carlo simulations.


The effect of age at migration on cardiovascular mortality among elderly Mexican immigrants.
In this study, we evaluated the influence of age at migration on cardiovascular mortality among older Mexican Americans immigrants. A population-based cohort of Mexican-origin (N = 907) participants ages 60+ was followed up to 8 years. The association between migration before age 20 compared with after age 20 and mortality was analyzed with the use of multivariate Cox proportional models. Compared with those who migrated later, those who migrated before the age of 20 years had higher income and education, were more likely to speak English, were culturally more Anglo, and more likely to be men. Immigration before 20 years of age was associated with greater rates of cardiovascular mortality (hazard ratio, 2.39; 95% confidence interval, 1.16 - 4.94) compared with those migrating at older ages, even after adjustment for age, sex, education, income, and baseline cardiovascular health. No age at migration differences were observed for noncardiovascular deaths. Mexican Americans who migrated in early life experienced greater cardiovascular disease death rates than later migrants. Early experiences related to migration may have consequences for late-life disease that are not mitigated by the higher socioeconomic status achieved by early migrants. Health or economic selection related to migration may play a role although accounting for health and socioeconomic status actually increased differences between early and later migrants.


Multi-informant reports of psychiatric symptoms among high-functioning adolescents with Asperger syndrome or autism.
The aim of the study was to examine psychiatric symptoms in high-functioning adolescents with autism spectrum disorders reported by multiple informants. Forty-three 11- to 17-year-old adolescents with Asperger syndrome (AS) or high-functioning autism (HFA) and 217 typically developed adolescents completed the Youth Self-Report (YSR), while their parents completed the Child Behavior Checklist (CBCL). Teachers of adolescents with AS/HFA completed the Teacher Report Form (TRF). The informants reported significantly more psychiatric symptoms, especially withdrawn, anxious/depressed, social and attention problems, in adolescents with AS/HFA than in controls. In contrast to findings in the general population, the psychiatric problems of adolescents with AS/HFA are well acknowledged by multiple informants, including self-reports. However, anxiety and depressive symptoms were more commonly reported by adolescents with AS/HFA and their teachers than their parents, indicating that some emotional distress may be hidden from their parents.


Meta-analysis of diagnostic procedures for Pneumocystis carinii pneumonia in HIV-1-infected patients.
Sputum induction is a simple and noninvasive procedure for Pneumocystis carinii pneumonia (PCP) diagnosis in human immunodeficiency virus-1-positive patients, although less sensitive than bronchoalveolar lavage (BAL). In order to obtain an overview of the diagnostic accuracy of sputum induction, a systematic review and meta-analysis of studies reporting the comparative sensitivity and specificity of BAL (the "gold standard") and sputum induction was performed. The odds ratio and related 95% confidence interval were calculated using summary receiving operating characteristic curves as well as fixed-effect and random-effect models. Based on pooled data, the negative and positive predictive values were calculated for a range of PCP prevalence using a Bayesian approach. Seven prospective studies assessed the comparative accuracy of BAL and sputum induction. On the whole, sputum induction demonstrated 55.5% sensitivity and 98.6% specificity. The sensitivity of sputum induction was significantly higher with immunofluorescence than with cytochemical staining (67.1 versus 43.1%). In settings of 25-60% prevalence of PCP, the positive and negative predictive values ranged 86-96.7 and 66.2-89.8, respectively, with immunofluorescence, and 79-94.4 and 53-83.5% with cytochemical staining. In conclusion, in a setting of low prevalence of Pneumocystis carinii pneumonia, sputum induction, particularly with immunostaining, appears to be adequate for clinical decision-making.


A Systematic Review: Family Support Integrated with Diabetes Self-Management among Uncontrolled Type II Diabetes Mellitus Patients.
The rate of type-2 diabetes mellitus (T2D) is dramatically increasing worldwide. Continuing diabetes mellitus (DM) care needs effective self-management education and support for both patients and family members. This study aimed to review and describe the impacts of diabetes mellitus self-management education (DSME) that involve family members on patient outcomes related to patient health behaviors and perceived self-efficacy on self-management such as medication adherence, blood glucose monitoring, diet and exercise changes, health outcomes including psychological well-being and self-efficacy, and physiological markers including body mass index, level of blood pressure, cholesterol level and glycemic control. Three databases, PubMed, CINAHL, and Scopus were reviewed for relevant articles. The search terms were "type 2 diabetes," "self-management," "diabetes self-management education (DSME)," "family support," "social support," and "uncontrolled glycaemia." Joanna Briggs Institute (JBI) guidelines were used to determine which studies to include in the review. Details of the family support components of DSME intervention and the impacts of these interventions had on improving the health outcomes patients with uncontrolled glycaemia patients. A total of 22 intervention studies were identified. These studies involved different DSME strategies, different components of family support provided, and different health outcomes to be measured among T2D patients. Overall, family support had a positive impact on healthy diet, increased perceived support, higher self-efficacy, improved psychological well-being and better glycemic control. This systematic review found evidence that DSME with family support improved self-management behaviors and health outcomes among uncontrolled glycaemia T2D patients. The findings suggest DSME models that include family engagement can be a useful direction for improving diabetes care.


Technology insight: Image-guided therapies for hepatocellular carcinoma--intra-arterial and ablative techniques.
Locoregional techniques have become the mainstay of therapy for patients with unresectable hepatocellular carcinoma (HCC). Such image-guided interventions include catheter-based approaches (transarterial chemoembolization and yttrium-90 radiotherapy) and locoregional ablative techniques, either chemical (percutaneous ethanol injection), or thermal (radiofrequency ablation, laser ablation, microwave ablation and cryoablation). These therapies are mainly utilized for palliation, but have also been used with curative intent. In selected cases, percutaneous interventional treatments have shown good results (5-year survival 40-50%), but, even when chosen as first-line treatment, have not been able to achieve the response rates and outcomes achieved by surgical options (resection or transplantation). New promising image-guided therapies are continuously emerging, as we attempt to improve tumor targeting, minimize hepatic toxicity and ultimately improve quality of life and survival of patients with HCC. With new technologies in imaging and drug delivery becoming available, it is likely that, in the future, patients with HCC will be best treated by a multidisciplinary team approach, utilizing a combination of techniques to improve patient survival. This review outlines the current status of the most commonly used image-guided locoregional interventions in the treatment of patients with HCC, and describes recent research and advances related to image-guided interventions for liver cancer.


[Tumors associated with nevus sebaceous].
Nevus sebaceus (NS) is a congenital hamartomatous lesion, usually involving the scalp or the face. Various benign and malignant neoplasms can develop in association with NS, the most common being trichoblastoma, syringocystadenoma papilliferum, viral warts and basal cell carcinoma (BCC). We retrospectively examined the clinical and histopathological records of 15 NS cases with an associated tumor which were diagnosed between 1996 and 2004. All cases were adults and 3 of them had more than one tumor. Six cases had BCC, which is a higher incidence of malignant tumor association with NS, than that reported in last years. Trichoblastoma was observed in 3 cases and was the most common benign tumor in our series. Filiform, hyperkeratotic, pigmented, pedunculated and/or eroded papulonodular changes were major clinical signs of secondary tumors on NS in our series. Clinical features are not sufficient enough to make an exact diagnosis of benign or malignant secondary tumors. Though prophylactic excision for NS is done less in last years, especially adult patients should closely be followed for any new changes evoking tumor development on this congenital lesion.


Nogo-A couples with Apg-1 through interaction and co-ordinate expression under hypoxic and oxidative stress.
Nogo-A is the largest isoform of the Nogo/RTN4 (reticulon 4) proteins and has been characterized as a major myelin-associated inhibitor of regenerative nerve growth in the adult CNS (central nervous system). Apart from the myelin sheath, Nogo-A is expressed at high levels in principal neurons of the CNS. The specificity of Nogo-A resides in its central domain, NiG. We identified Apg-1, a member of the stress-induced Hsp110 (heat-shock protein of 110 kDa) family, as a novel interactor of NiG/Nogo-A. The interaction is selective because Apg-1 interacts with Nogo-A/RTN4-A, but not with RTN1-A, the closest paralogue of Nogo-A. Conversely, Nogo-A binds to Apg-1, but not to Apg-2 or Hsp105, two other members of the Hsp110 family. We characterized the Nogo-A-Apg-1 interaction by affinity precipitation, co-immunoprecipitation and proximity ligation assay, using primary hippocampal neurons derived from Nogo-deficient mice. Under conditions of hypoxic and oxidative stress we found that Nogo-A and Apg-1 were tightly co-regulated in hippocampal neurons. Although both proteins were up-regulated under hypoxic conditions, their expression levels were reduced upon the addition of hydrogen peroxide. Taken together, we suggest that Nogo-A is closely involved in the neuronal response to hypoxic and oxidative stress, an observation that may be of relevance not only in stroke-induced ischaemia, but also in neuroblastoma formation.


Leeching as initial treatment in a cat with polycythaemia vera.
Polycythaemia vera was diagnosed in a three-year-old domestic shorthaired cat referred because of seizures and a high packed cell volume (PCV). Laboratory examination revealed severe erythrocytosis (PCV 79 per cent). Diagnosis was reached by excluding causes for relative and secondary absolute polycythaemia. As phlebotomy proved impossible for initial treatment due to hyperviscosity, four leeches were used to suck blood and the PCV was consequently reduced to 64 per cent. A further 24 hours later, when bleeding at the sites of sucking had stopped, the PCV was 56 per cent. Long-term management of the condition was achieved with hydroxyurea (100 mg/cat once daily) and intermittent phlebotomy. Initial treatment using leeches in cases of polycythaemia vera is a simple, non-invasive, well tolerated and effective method where phlebotomy is not possible.


Immediate and long-term results of carotid endarterectomy.
We review the long-term results of carotid endarterectomy in 200 consecutive patients operated on from 1980 to 1987. The patients were part of an ongoing study using duplex scanning to assess the status of the carotid bifurcation before and after endarterectomy. The average follow-up for the patients was 31 months. The indications for surgery were transient ischemic attacks in 87 (43.5%) and stroke in 36 (18%) patients; 77 patients (38.5%) were asymptomatic. In 176 sides (88%), the degree of stenosis exceeded 50% in terms of diameter reduction. The perioperative stroke rate was 2.3% in patients with transient ischemic attacks, 2.8% in patients with strokes, and 1.3% in asymptomatic patients. There was one perioperative death (0.5%). There were five occlusions of the internal carotid artery, one during the perioperative period and four after discharge; in three patients the occlusion was associated with the development of a stroke. There was a restenosis rate of 19.7% secondary to myointimal hyperplasia; such lesions did not appear to contribute to new ischemic events during or after their development. The mean stroke incidence after the decision was made for carotid endarterectomy was 2.8%/yr in the patients with transient ischemic attacks, 6.2%/yr in the patients with stroke, and 0.65%/yr in the asymptomatic patients. The annual death rate was 6% for the entire group, 5.5%/yr in the patients with transient ischemic attacks, 9.2%/yr in the patients with stroke, and 4.6%/yr in the asymptomatic patients.


Update on the role of endothelial lipase in high-density lipoprotein metabolism, reverse cholesterol transport, and atherosclerosis.
Endothelial lipase (EL) is a phospholipase that belongs to the lipoprotein lipase (LPL) family, which includes LPL and hepatic lipase (HL). Similar to LPL and HL, EL regulates lipoprotein metabolism, mainly high-density lipoprotein (HDL) metabolism and HDL cholesterol (HDL-C) levels in humans and mice. Existing data strongly suggest that inhibition of EL in humans would be expected to increase the HDL-C level. However, it has not been definitively established whether the effect of EL activity on HDL-C levels translates into effects on reverse cholesterol transport or atherosclerosis. The available data regarding the impact of EL expression and activity on HDL metabolism, reverse cholesterol transport, and atherosclerosis are reviewed.


The effects of a land-based home exercise program on surfing performance in recreational surfers.
Surfing has become a popular, non-age dependent sport that can be performed at most beaches. Hence, coaches and athletes have recognised the importance of physical preparation to enhance athletic performance. The purpose of this study was to investigate the effects of a sport-specific, land-based-home exercise programme (LB-HEP) on sport-specific assessments related to surfing performance in recreational surfers. Twenty-two year-round recreational surfers divided into two groups: the exercise group (EG) performed the LB-HEP 3 times a week for 8 weeks while the control group (CG) maintained their current exercise. Both groups were instructed to continue surfing during the study period. Each surfer completed sport-specific measurements related to surfing demands both pre-test and post-test (8 weeks). There was a significant interactive effect of time and group (p = .009, ηp2 =.298) on the surfer's performance questionnaire showing greater improvements in the EG. Additionally, the EG had an improvement on time to pop-up when compared to the CG (ηp2 =.160). Based on the results, the LB-HEP is an effective training programme for all experience levels of recreational surfers to improve surfing performance measures short term.


Toward Chromanes by de Novo Construction of the Benzene Ring.
The work describes three principal Diels-Alder cycloaddition approaches toward chromanes that are designed for the de novo construction of the benzene ring. This study specifically focuses on the potential exploitation in the total synthesis of chromane-bearing natural products such as cebulactam A.


RESULTS OF POSTERIOR MYECTOMY FOR THE TREATMENT OF CHILDREN WITH CHRONIC CONSTIPATION.
The aim of this study was to evaluate the result of posterior myectomy in children with chronic constipation who underwent to this surgery. Forty eight children with chronic constipation who did not respond to diet, laxative, or enema were included. Children with abnormal barium enema showing transitional zone were excluded. Children with documented metabolic disease diabetes, and hypothyroidism were also excluded. All patients underwent posterior myectomy. Children were followed during 1 year after surgery regarding frequency of fecal evacuation, fecal consistency, straining during defecation, and diameter of feces. Data was analyzed using SPSS version 13.0 (Chicago, IL, USA). Of 48 cases that underwent surgery, 21 were male and 27 were female. Age range was 1.5 to 11 years old. Mean duration of constipation before surgery was 22.79±17.08 (range 6-48 months). Mean duration of medical treatment was 14.90±10.31 (range= 6-48 months). Fecal consistency, feces diameter, number of bowel movements and straining during defecation were compared before and after surgery. The results were statistically significant ( P <0.001). Of all cases, 52% continued treatment of constipation after surgery for 1 year. Ganglion cells were absent in 32 cases. Ganglion cells were present in seven children. Proximal ganglion cell was found in nine cases Treatment response was not different between cases according to status of ganglion cell in biopsy. Fecal consistency, feces diameter, number of bowel movements, and straining for defecation were improved after posterior myectomy. Another study with more sample is required for better evaluation of treatment.


KL-6 as a Biomarker of Interstitial Lung Disease Development in Patients with Sjögren Syndrome: A Retrospective Case-Control Study.
Krebs von den Lungen-6 (KL-6) is expressed on regenerating type II pneumocytes and has been recognized as biomarkers in interstitial lung disease (ILD). We aim to identify the role of the serum KL-6 level in patients with newly diagnosed Sjögren syndrome (SS), as well as the correlation between the immunoassays. Patients with newly diagnosed SS and receiving HRCT for clinical reason during follow-up were included. Baseline KL-6 level was measured via enzyme-linked immunosorbent assay (ELISA) and latex particle-enhanced turbidimetric immunoassay (LETIA). Of the 39 patients, 21 (53.85%) developed interstitial lung disease (ILD) by the conclusion of the follow-up period. The median time to diagnosis of ILD was 2.24 years (IQR 1.15-4.34) in the ILD group. The median serum KL-6 level, measured using ELISA, was 1232 U/mL (IQR 937-2242) and 764.5 U/mL (IQR 503.25-1035.75) in the ILD group and the non-ILD group, respectively (p = 0.001). The median LETIA for serum KL-6 was 329 U/mL (IQR 235-619) and 245 U/mL (IQR 215.25-291) in the ILD group and the non-ILD group, respectively (p = 0.074). Serum KL-6 levels were higher in newly diagnosed SS patients with ILD diagnosis during follow-up. Thus, the serum KL-6 level can serve as a valuable biomarker to identify hidden ILD in patients with newly diagnosed SS patients. However, the immunoassay procedure may influence the efficacy of the prediction and its clinical association.


DFNA5 inhibits colorectal cancer proliferation by suppressing the mTORC1/2 signaling pathways via upregulation of DEPTOR.
The human deafness, autosomal dominant 5 gene (DFNA5), a newly discovered executor of pyroptosis, has been strongly implicated in the tumorigenesis of several human cancers. However, an understanding of the functional role of DFNA5 in the development and progression of colorectal cancer (CRC) is limited. In this study, we demonstrated that DFNA5 was downregulated in CRC tissues. Ectopic expression of DFNA5 inhibited tumor cell growth in vitro, retarded tumor formation in vivo, and blocked a cell-cycle transition from the G0/G1 to the S phase, whereas a DFNA5 knockdown promoted cell proliferation. Western blotting showed that the levels of cell cycle-related proteins, including cyclin D1, cyclin E, CDK2, and p21, were accordingly altered upon DFNA5 overexpression or DFNA5 knockdown. Mechanistic studies indicated that DFNA5 exerted its tumor suppressor functions by antagonizing mTORC1/2 signaling via upregulation of DEPTOR. In addition, blockage of mTORC1/2 signaling by Torin-1 abolished the accelerative proliferation by DFNA5 knockdown. In conclusion, these results indicated that DFNA5 inhibits the proliferation and tumor formation of colon cancer cells by suppressing mTORC1/2 signaling.


Interlaminar Fracture Behavior of Carbon Fiber/Polyimide Composites Toughened by Interleaving Thermoplastic Polyimide Fiber Veils.
Carbon fiber reinforced thermosetting polyimide (CF/TSPI) composites were interleaved with thermally stable thermoplastic polyimide (TPPI) fiber veils in order to improve the interlaminar fracture toughness without sacrificing the heat resistance. Both of the mode I and mode II interlaminar fracture toughness (GIC and GIIC) for the untoughened laminate and TPPI fiber veils interleaved laminates were characterized by the double cantilever beam (DCB) test and end notch flexure (ENF) test, respectively. It is found that the TPPI fiber veils interleaved laminates exhibit extremely increased fracture toughness than the untoughened one. Moreover, the areal density of TPPI greatly affected the fracture toughness of laminates. A maximum improvement up to 179% and 132% on GIC and GIIC is obtained for 15 gsm fiber veils interleaved laminate, which contributes to the existence of bicontinuous TPPI/TSPI structure in the interlayer according to the fractography analysis. The interlaminar fracture behavior at elevated temperatures for 15 gsm fiber veils interleaved laminate were also investigated. The results indicated that the introduction of thermally stable TPPI fiber veils could enhance the fracture toughness of CF/TSPI composites by exceeding 200% as compared to the untoughened one even as tested at 250 °C.


Isolation and characterization of six new genome types of human adenovirus types 1 and 2.
Several of the 41 types of human adenovirus have been divided into genome types based on aberrant restriction endonuclease digestion patterns of viral DNA. In the process of screening a large number of clinical adenovirus isolates by restriction endonuclease digestion of viral DNA, we have identified nine isolates from eight patients which were identified by neutralization as adenovirus type 1 or 2 but had aberrant cleavage patterns. Cleavage sites for the enzymes SmaI, EcoRI, HindIII, KpnI, and HpaI were mapped. The variants could be placed in six distinct groups based on cleavage patterns. The designation genome types 1a, 1b, 1c, 2b, 2c, and 2d are proposed for these isolates.


Binuclear half-sandwich cobalt(III) and rhodium(III) ortho-carboranedichalocogenolato complexes with ether chain-bridged bis(cyclopentadienyl) ligand.
1, 1'-(3-Oxapentamethylene)dicyclopentadiene [O(CH(2)CH(2)C(5)H(5))(2)], containing a flexible chain-bridged group, was synthesized by the reaction of sodium cyclopentadienide with bis(2-chloroethyl) ether through a slightly modified literature procedure. Furthermore, the binuclear cobalt(III) complex O[CH(2)CH(2)(eta(5)-C(5)H(4))Co(CO)I(2)](2) and insoluble polynuclear rhodium(III) complex {O[CH(2)CH(2)(eta(5)-C(5)H(4))RhI(2)](2)}(n) were obtained from reactions of with the corresponding metal fragments and they react easily with PPh(3) to give binuclear metal complexes, O[CH(2)CH(2)(eta(5)-C(5)H(4))Co(PPh(3))I(2)](2) and O[CH(2)CH(2)(eta(5)-C(5)H(4))Rh(PPh(3))I(2)](2), respectively. Complexes react with bidentate dilithium dichalcogenolato ortho-carborane to give eight binuclear half-sandwich ortho-carboranedichalcogenolato cobalt(III) and rhodium(III) complexes O[CH(2)CH(2)(eta(5)-C(5)H(4))Co(PPh(3))(E(2)C(2)B(10)H(10))](2) (E = S and Se), O[CH(2)CH(2)(eta(5)-C(5)H(4))](2)Co(2)(E(2)C(2)B(10)H(10)) (E = S and Se), O[CH(2)CH(2)(eta(5)-C(5)H(4))Co(E(2)C(2)B(10)H(10))](2) (E = S and Se and O[CH(2)CH(2)(eta(5)-C(5)H(4))Rh(PPh(3))(E(2)C(2)B(10)H(10))](2) (E = S and Se). All complexes have been characterized by elemental analyses, NMR spectra ((1)H, (13)C, (31)P and (11)B NMR) and IR spectroscopy. The molecular structures were determined by X-ray diffractometry.


Electronic Health Record: a systematic review of the implementation under the National Humanization Policy guidelines.
As part of the evaluability study of the implementation of the Electronic Patient Record (EPR) evaluation, the aim of this Systematic Review (SR) was to identify the evaluation domains to be addressed. This SR, aligned with the Cochrane Handbook for Systematic Reviews of Interventions and the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) encompassed articles published from 2006 to 2019. The search was carried out in the electronic databases SciELO, Oasis IBICT, BVS Regional and Scopus. The search resulted in 1,178 articles, 42 of which met the inclusion criteria. Most studies used qualitative methods for the analyses. The publications took place between 2006 and 2019, with a concentration in 2017 with 9 (21%) articles published in that year. No studies were published in 2008 and 2009. Only 10 studies included the description, analysis or results related to the domains of implementation. The main domains in which the EPR was problematized were: underutilization; professionals' resistance to its use; emphasis on usability; and EPR as an information source. Despite the inclusion of all studies that covered the principles and guidelines of the National Humanization Policy (NHP), they are still incipient.


Inhibition of nonspecific defenses by soil infection potentiating factors.
This study was undertaken to examine the effect of soil infection potentiating factors on the defense system of the tissue. Using an in vitro model, leukocyte phite. This damaging effect on leukocyte function was a result of an interaction between the leukocyte and the clay particles. Montmorillonite also interfered with nonspecific humoral defenses. Exposure of serum to clay rapidly eliminated its bactericidal bodies occurred without any damage to the serum opsonins.


Effect of Prolonged Anti-HM1: IMSS Entamoeba histolytica Antibody Activity in Humoral and Cellular Immunity of Experimentally Induced Animal Model.
The Cellular immunity plays an important role in amoebic infections, whereas humoral immune responses have little influence on the outcome of the disease. Chronic infestation with Entameoba histolytica, a common protozoan parasite, has been associated with autoimmune phenomena, including the appearance of antibodies to colonic epithelial cells. The mechanism whereby the protozoan parasite E. histolytica causes suppression of the immune response to allow it to survive in humans is unclear. Both parasite and parasite-induced host factors appear to be important in immunoregulation. This study was designed to evaluate prolonged antibody response to E. histolytica (HM1: IMSS) which may contribute and might identify antigens implicated in the disease pathology and throw light on the massive T-cell infiltration causing inflammation. An in vivo study was undertaken against experimentally induced animal model by evaluating total protein, Radial Immunodiffusion and Antiamoebic IgG antibody detection by ELISA using serum samples from rabbit collected weekly from day 7-28th (RS1: day-7; RS2: day-14, RS3: day-21 and RS4: day-28) which were immunized with amoebic antigen. Serological and cytokines profile- like interleukin- 6 (IL-6), IL-10 and tumor necrosis factor-α (TNF-α) were also analyzed. Our result indicated that RS4 showed a significant 167.3 ± 0.333 mg/dl value for IgG antibodies whereas, RS3 showed significant elevated 0.57 ± 0.033mg/dL C' reactive protein and 7.6667 ± 0.333 IU/mL Rheumatoid factor level. Similarly, RS3 775.00 ± 0.57 pg/ml showed maximum significant values for TNF-α, whereas IL-6 level was higher in RS4 701.00 ±0.577 pg/ml but IL-10 level was found low in RS1 62.33 ± 0.33 pg/ml, respectively. Thus, our study demonstrated the efficacy of amoebic antigen in immune response mechanism and how they provoked inflammation and acted as an immunomodulator. This article also summarized some relevant patents with respect to E. histolytica against inflammation and other diseases.


Coherent and incoherent specular inverse Faraday effect: chi((3)) measurements in opaque materials.
We report what is to our knowledge the first observation of coherent and incoherent terms of the specular inverse Faraday effect. The specular inverse Faraday effect is treated as a four-wave mixing phenomenon, and the role of the phase-conjugated wave in the polarization-altering interaction is disclosed. Several components of the nonresonant cubic susceptibility tensor in InSb and GaAs are measured and found to be in the 10(-7)-10(-6)-esu range.


TT dinucleotides containing an isoxazoline moiety: synthesis and binding affinity study.
We have prepared four diastereomers of TT dinucleotides containing an isoxazoline moiety and four dodecanucleotides incorporating these TT dinucleotides in the middle of the DNA sequence. We also have determined the melting temperatures of these modified oligonucleotides (Tm values) by measuring change in UV absorbance.


Abnormal gray matter asymmetry in alcohol dependence.
Previous voxel-based morphometry studies have provided evidence that patients with alcohol dependence (AD) have widespread gray matter morphological abnormalities. However, brain structural asymmetry in AD has not been assessed to date. Here, we aimed to use a recently developed voxel-based morphometry-based approach to investigate global and regional gray matter asymmetry alterations in AD. A total of 39 male individuals, including 19 AD patients and 20 age-matched healthy controls, underwent high-resolution structural MRI. Global and voxel-wise gray matter asymmetries were measured separately by the Dice coefficient and the asymmetry index, which were compared between the two groups. We found no difference in the global gray matter asymmetry between AD patients and healthy controls. However, voxel-wise gray matter asymmetry analysis showed that AD patients and healthy controls had different distribution patterns of brain regions with a rightward asymmetry and a leftward asymmetry Furthermore, we observed an increased rightward asymmetry of gray matter in the hemispheric I-IV and V of the cerebellum and lingual gyrus in AD patients. These findings suggest that abnormal structural asymmetry in the cerebellum and the primary visual cortex may be the neural mechanisms contributing toward motor and visual impairments in AD.


The Social Negotiation of People's Views on the Causes of Illness.
Over the last two decades increasing attention has been given to lay views of health and illness. An important area within this research is the views that different socioeconomic groups hold on the causes of illness. Generally it is concluded that people of lower socioeconomic status are more likely than those of more affluent standing to talk about the causes of illness in lifestyle rather than structural terms that involve overt connections with the material impact of social inequality. We draw on 20 semi-structured interviews with New Zealanders of lower socioeconomic status to explore the ways various causes are assigned to illness. Our participants voice multiple and often contradictory views when assigning cause, and include references to structural issues in addition to lifestyle risk factors and medical ideas about biological functioning and disease. There appears to be a range of sociocultural explanations available for these people to draw on when making sense of illness. We argue that the prevalence of structural explanations may be due, in part, to cultural shifts and increased critical reaction to various social reforms. Our findings support the idea that people's views are socially constructed to account for the complexities of health and illness as part of everyday life.


[Remission of a complex periodic catatonic syndrome under electroconvulsive therapy].
This article is reporting about a spontaneous occurred catatonic syndrome in a 52 years old female patients with no prior psychiatric illness record. The catatonia followed a severe depressive episode with psychotic symptoms. At the beginning additionally to the catatonic-symptoms severe disorientation and memory disturbances were prominent in a way it can be seen in neurodegenerative diseases like Lewy-Body-Dementia and Creutzfeldt-Jacob-Disease. The patient didn't respond on any medication or showed severe side-effects which led to discontinue the medication. After applying widespread somatic diagnostics, which has excluded a neurodegenerative disease a electroconvulsive therapy was applied. During this treatment the patient showed a recurrence of her catatonic symptoms but they remitted if there was a too long period between the convulsive treatments. After establishing a sufficient period between the convulsive treatments the symptoms remitted totally.


Myogenous phenotype of epithelial-like areas in endometrial stromal sarcomas.
Approximately 25% of low-grade endometrial stromal sarcomas of the uterus contain areas of epithelial-like differentiation, which are often reminiscent of ovarian sex-cord tumors. It has been suggested that these areas may represent attempted differentiation toward either uterine glands or smooth muscle. To investigate these two possibilities, we examined the histologic and immunohistochemical features of 26 low-grade endometrial stromal sarcomas. Eight tumors had epithelial-like differentiation, which in some tumors was so prominent as to suggest a purely epithelial neoplasm. Areas typical of endometrial stromal sarcoma were vimentin positive, whereas epithelial-like differentiation expressed vimentin and the muscle markers muscle-specific actin and desmin, as well as cytokeratin, but not the epithelial marker epithelial membrane antigen. Epithelial-like differentiation in low-grade endometrial stromal sarcoma is not uncommon and, based on our immunohistochemical results after comparison with normal controls, epithelial-like differentiation has a myogenous rather than an epithelial phenotype.


Structure of a liquid/liquid interface during solvent extraction combining X-ray and neutron reflectivity measurements.
We have resolved the molecular structure of a bulk oil/water interface that contains amphiphilic ligand molecules using a combination of X-ray and neutron reflectivity measurements for the first time. This new capability can greatly impact future work in the field of ion separation by phase transfer, i.e. liquid/liquid extraction.


Downregulation and growth inhibitory role of FHL1 in lung cancer.
Four and a half Lin-11, Isl-1, Mac-3 (LIM) protein 1 (FHL1) has been linked to carcinogenesis. However, the role of FHL1 in lung cancer remains unclear and the detailed mechanism underlying its tumor suppressive role is poorly understood. The purpose of this study was to examine FHL1 expression in lung cancer patients and to investigate how it was associated with lung cancer cell growth. Immunoblotting and immunohistochemistry showed that FHL1 protein was downregulated in over 90% of 80 lung cancer patients. FHL1 expression was strongly correlated with tumor histological types (p < 10(-4) ) and the differentiation of the tumor (p = 0.002). FHL1 inhibited anchorage-dependent and -independent growth of human lung cancer cell lines. The inhibitory effects of FHL1 on lung cancer cell growth were associated with both the G1 and the G2/M cell cycle arrest concomitant with a marked inhibition of cyclin A, cyclin B1 and cyclin D as well as the induction of the cyclin dependent kinase inhibitors p21 (WAF1/CIP1) and p27 (Kip1). Direct intratumoral injection of an adenovirus expressing FHL1 dramatically suppressed the growth of A549 lung cancer cells in nude mice. Our data suggest that reduced expression of FHL1 may play an important role in the development and progression of lung cancer and that FHL1 may be a useful target for lung cancer gene therapy.


Beyond Hemostasis: Platelet Innate Immune Interactions and Thromboinflammation.
There is accumulating evidence that platelets play roles beyond their traditional functions in thrombosis and hemostasis, e.g., in inflammatory processes, infection and cancer, and that they interact, stimulate and regulate cells of the innate immune system such as neutrophils, monocytes and macrophages. In this review, we will focus on platelet activation in hemostatic and inflammatory processes, as well as platelet interactions with neutrophils and monocytes/macrophages. We take a closer look at the contributions of major platelet receptors GPIb, αIIbβ3, TLT-1, CLEC-2 and Toll-like receptors (TLRs) as well as secretions from platelet granules on platelet-neutrophil aggregate and neutrophil extracellular trap (NET) formation in atherosclerosis, transfusion-related acute lung injury (TRALI) and COVID-19. Further, we will address platelet-monocyte and macrophage interactions during cancer metastasis, infection, sepsis and platelet clearance.


Speech perception and functional benefit after cochlear implantation: a multicentre survey in Finland.
This study was done to survey the effect of cochlear implantation on hearing level, speech perception and listening performance in Finnish-speaking adults. The subjects of the study comprise 67 adults. Pure-tone thresholds (0.125-8 kHz), word recognition and listening performance were studied before and after implantation. After switch-on of the implant, the median values of PTA(0.5-4 kHz) in the sound field were fairly stable across the evaluation period. Three months after switch-on of the implant, the mean word recognition score was 54%. There was clear improvement in the mean word recognition scores over a longer period of time, the mean score being 71% 24 months after switch-on. Six months after switch-on, the majority of subjects (40/48) were able to recognize some speech without speechreading, and 26 of these 48 subjects were able to use the telephone with a known speaker, gaining good functional benefit from the implantation.


The specific binding of nuclear protein(s) to the cAMP responsive element (CRE) sequence (TGACGTCA) is reduced by the misincorporation of U and increased by the deamination of C.
Point mutations in the cAMP-responsive element (CRE) of the rat somatostatin gene promoter/enhancer sequence (TGACGTCA) were used as a model for assessing the effect of uracil, deriving either from misincorporation during DNA synthesis (T----U) or cytosine deamination (C----U), on the binding of sequence/specific regulatory proteins. The results show that the T----U conversion in both strands of the CRE palindromic sequence reduces its affinity for the CRE binding factor(s), suggesting the crucial role of the methyl group contributed by T for the correct recognition of the sequence. On the other hand, deamination of C in the CpG central dinucleotide (CpG----UpG) causes an increase of binding affinity which is further enhanced by the contemporary deamination in both strands. Then, both uracil misincorporation and cytosine deamination alter the binding to CRE sequence in vitro, suggesting that uracil, if not removed by uracil DNA-glycosylase, could be dangerous for cellular functions.


Exo-zodi detection capability of the Ground-Based European Nulling Interferometry Experiment (GENIE) instrument.
The Ground-Based European Nulling Interferometry Experiment (GENIE) is intended as an Earth-based precursor for the European Darwin mission that will prepare the Darwin science program and demonstrate the required technology at system level. We propose a compact nulling interferometer design consisting of a two-telescope aperture configuration, an optional split-pupil add-on, and only four active control loops for counteracting environmentally induced disturbances. We show by simulation that the proposed instrument is able to detect, within a few minutes of observation time, exo-zodiacal dust clouds around Sunlike stars at 20 parsecs that are 20 times stronger than the local zodiacal dust cloud density.


Feeding habits and ontogenic changes in digestive enzyme patterns in five freshwater teleosts.
Feeding habits and the activity of digestive enzymes (total alkaline proteases, α-amylase and lipase) from dace Leuciscus leuciscus, roach Rutilus rutilus, Prussian carp Carassius auratus gibelio, perch Perca fluviatilis and pikeperch Sander lucioperca fry were studied in the Malye Chany Lake-Kargat Estuary (western Siberia, Russia). The diet of fry from all studied species was mainly composed of chironomid larvae and zooplanktonic organisms (i.e. cladocera and copepoda), whereas carnivorous species such as P. fluviatilis and S. lucioperca also preyed on fry from other fishes while detritus and microalgae were also important in the diet of ommivorous species. When comparing diet similarity (Sørensen-Dice index, Q(S)) among fry at different stages of development, both omnivorous and carnivorous species showed a high level of similarity (0.67 < Q(S) < 0.89 and 0.73 < Q(S)< 0.89, respectively). Diet similarity values were in agreement with the overall digestive activity profile analysed by cluster analysis. Diet similarity suggested potential trophic competition when zooplanktonic and benthic prey began to decline towards autumn. The analysis of pancreatic digestive enzymes revealed a correlation among their activities and fry feeding habits with α-amylase:total proteases (A:P) values higher than 1 in omnivorous species and lower (A:P ≤ 1) in carnivorous species.


Identification of hepatitis C virus transmission using a next-generation sequencing approach.
Here, we describe a transmission event of hepatitis C virus (HCV) among injection drug users. Next-generation sequencing (NGS) was used to assess the intrahost viral genetic variation. Deep amplicon sequencing of HCV hypervariable region 1 allowed for a detailed analysis of the structure of the viral population. Establishment of the genetic relatedness between cases was accomplished by phylogenetic analysis. NGS is a powerful tool with applications in molecular epidemiology studies and outbreak investigations.


Arthroscopy of the shoulder joint--a cadaver and clinical study. Part 2: Clinical study.
Shoulder arthroscopy was carried out 56 times on 50 patients. Different types of arthroscopes were employed. Anterior and posterior approaches were used. Diagnoses were 21 cases of glenohumeral instability including 17 of recurrent anterior dislocation and subluxation; 2 of voluntary anterior subluxation and 2 of habitual posterior dislocation, 13 of rotator cuff tear, 6 of chronic subacromial bursitis, 2 of fracture-dislocation, 2 of frozen shoulder, 2 of baseball shoulder, one of rheumatoid arthritis, and 3 miscellaneous. The arthroscopic findings in the instability group and rotator cuff tear group were verified. Bankart lesion and Hill-Sachs lesion were identified arthroscopically. The indications for shoulder arthroscopy are outlined. There was no significant morbidity with this procedure.


Subcritical water extraction for the remediation of phthalate ester-contaminated soil.
Subcritical water has been used as an environment-friendly extraction fluid for many classes of organic compounds. It was used for the removal of phthalate esters (PEs), such as di-methyl phthalate, DMP; di-ethyl phthalate, DEP; di-iso-propyl phthalate, DIPP; di-n-butyl phthalate, DBP; benzyl butyl phthalate, BBP; di-n-pentyl phthalate, DpentP; di-n-hexyl phthalate, DHXP; di-heptyl phthalate, DheptP; di-2-ethylhexyl phthalate, DEHP; di-n-nonyl phthalate, DNP; di-n-octyl phthalate, DOP; di-n-decyl phthalate, DDP, in soil samples under the optimum condition of 250 °C and 10 MPa in our study. The soil samples cleaned with subcritical water were extracted by homemade accelerated solvent extraction system (ASE) and analyzed by HPLC-UV to check for soil remediation efficiency. Three types of soil collected at different sites in Taiwan have been tested. Although at higher PEs concentration levels, the modification of treatments may be necessary for satisfactory removal of the contaminants, soil samples of different PEs levels treated with subcritical water extraction (SCWE) were analyzed and the results indicated removal efficiency ranges of 80-90% for PEs spiked in soil samples. Soil samples contaminated with native DEHP were treated and gave comparable recovery efficiencies. Our results indicate that the applications of subcritical water as soil remediation for removal of PEs contaminant are feasible.


[Prophylactic treatment of cluster headache with verapamil].
Verapamil is the preventive therapy of choice for cluster headache. The recommended dose ranges from 240-720 mg/day. In a retrospective study nine patients with episodic and three patients with chronic cluster headache were analyzed. In episodic cluster headache early treatment onset stopped attacks within 20 days in 80%, late treatment onset was successful within ten days in 67%. Early treatment onset shortens episode duration by four times. The recommended dose is 360 mg/day. Chronic cluster headache probably requires higher doses.


Nuclear mutations in Saccharomyces cerevisiae conferring multiple sensitivity to petite-inducing treatments.
Eighteen EMS-induced mutant strains of S. cerevisiae with increased sensitivity to petite induction by sulfanilamide-aminopterin treatment have been isolated. Four of these strains demonstrated a concomitant increase in sensitivity to the petite-inducing effects of u.v. irradiation and of growth at an elevated temperature. Of these, two were shown to be a consequence of recessive nuclear mutations at one gene (sas1-1 and sas1-2). Expression of the two remaining mutations was too low to permit genetic analysis. All three petite-inducing treatments used in this study are known to reduce the hydrogen bond strength between the two strands of double stranded DNA, and the existence of multiple sensitivity is discussed in terms of an alteration of a mitochondrial endonuclease which acts preferentially at sites of reduced attraction.


Lamellar stack formation and degradative behaviors of hydrolytically degraded poly(ε-caprolactone) and poly(glycolide-ε-caprolactone) blended fibers.
Electrospun fibrous mats have gained popularity in bioengineering over the past decade, but few papers detail their degradative mechanisms. To address this, blends of hydrophobic poly(ε-caprolactone) (PCL) and hydrophilic PGA-PCL-PGA triblock copolymer were electrospun into aligned fibrous mats to assess the copolymers' mechanical and degradative properties. Increased hydrophilic triblock content led to enhanced morphological uniformity of fiber, tightening of fiber diameters, increased storage and Young's modulus, and decreased elongation. The corresponding decrease in hydrophobic PCL content led to faster hydrolytic degradation rate, as reflected by enhanced decrease in mass, molecular weight, and modulus loss at 25, 37, and 45°C. The activation energy for hydrolytic degradation for 15:85 PCL: triblock copolymer was approximately half that of 85:15 PCL: triblock copolymer. Detailed examination of fiber morphology and crystallinity revealed initial surface erosion followed by the evolution of crystalline lamellar stacks and bulk degradation at 37°C. Because of the high surface to volume and short diffusion length scale of the small diameter fibers, surface and bulk degradation may both contribute to the hydrolytic degradative behavior of these electrospun fibrous mats. Electrospun mats' distinct architecture that embodies high specific surface to volume and interfiber porous ultrastructures that lead to their unique degradative behaviors hold much potential for significant impact in the field of tissue engineering and controlled drug delivery.


Rates and roles of cyclic and alternative electron flow in potato leaves.
Measurements of 810 nm transmittance changes in leaves, simultaneously with Chl fluorescence, CO(2) uptake and O(2) evolution, were carried out on potato (Solanum tuberosum L.) leaves with altered expression of plastidic NADP-dependent malate dehydrogenase. Electron transport rates were calculated: J(C) from the CO(2) uptake rate considering ribulose-1,5-bisphosphate (RuBP) carboxylation and oxygenation, J(O) from the O(2) evolution rate, J(F) from Chl fluorescence parameters and J(I) from the post-illumination re-reduction speed of PSI donors. In the absence of external O(2), J(O) equaled (1.005 +/- 0.003) J(C), independent of the transgenic treatment, light intensity and CO(2) concentration. This showed that nitrite and oxaloacetate reduction rates were very slow. The Mehler-type O(2) reduction was evaluated from the rate of electron accumulation at PSI after the O(2) concentration was decreased from 210 to 20 mmol mol(-1), and resulted in <1% of the linear flow. J(F) and J(I) did not differ from J(C) while photosynthesis was light-limited, but considerably exceeded J(C) at saturating light. Then, typically, J(F) = 1.2 J(C) and J(I) = 1.3 J(C), and J(F) -J(C) and J(I) -J(C) depended little on CO(2) and O(2) concentrations. The results showed that the alternative and cyclic electron flow necessary to compensate variations in the ATP/NADPH ratio were only a few percent of the linear flow. The data do not support the requirement of 14H(+)/3ATP by the chloroplast ATP synthase. We suggest that the fast PSI cyclic electron flow J(I) - J(C), as well as the fast J(F) - J(C) are energy-dissipating cycles around PSI and PSII at light saturation.


Placental tissue metabolome analysis by GC-MS: Oven-drying is a viable sample preparation method.
Analysis of the human placenta metabolome has great potential to advance the understanding of complicated pregnancies and deleterious fetal outcomes in remote populations, but samples preparation can present unique challenges. Herein, we introduce oven-drying as a simple and widely available method of sample preparation that will facilitate investigations of the placental metabolome from remote and under-studied populations. Placentae from complicated and uncomplicated pregnancies were prepared in three ways (oven-dried at 60 °C, fresh, lyophilized) for metabolome analysis via gas chromatography-mass spectrometry (GC-MS). Multiple computer models (e.g. PLS-DA, ANN) were employed to classify and determine if there was a difference in placentae metabolome and a group of metabolites with high variable importance in projection scores across the three preparations and by complicated vs. control groups. The analyses used herein were shown to be thorough and sensitive. Indeed, significant differences were detected in metabolomes of complicated vs. uncomplicated pregnancies; however, there were no statistical differences in the metabolome of placentae prepared by oven-drying vs. lyophilization vs. fresh placentae. Oven-drying is a viable sample preparation method for placentae intended for use in metabolite analysis via GC-MS. These results open many possibilities for researching metabolome patterns associated with fetal outcomes in remote and resource-poor communities worldwide.


Influence of varying protein and starch degradabilities on performance of lactating cows.
A milk production and digestibility trial with 32 cows (2 X 2 factorial with 8 cows per treatment) was conducted to test animal response to varying rumen degradation of dietary starch and protein. Four rations (barley-cottonseed, barley-brewers dried grains, milo-cottonseed, and milobrewers dried grains) were compared in early lactation cows fed 65% concentrate and 35% forage for 60 d. Digestibilities of starch were higher for barley than milo diets; whereas, those for organic matter were higher for cottonseed meal than brewers dried grains. Milk production was highest on barley-cottonseed with mean adjusted values of (kg/d): 37.4, 34.9, 34.2, and 34.6 for respective treatments. Dry matter intakes were not different among rations. Milk fat was higher on milo than barley with respective diets averaging (%): 3.1, 2.9, 3.4, and 3.6, and resulting in lowest FCM for the barley-brewers dried grains diet. Milk protein was not altered by treatment. These data suggest that responses to varying protein degradability can be altered by rate of starch breakdown in the rumen.


Differential effects of cytokines and corticosteroids on toll-like receptor 2 expression and activity in human airway epithelia.
The recognition of microbial molecular patterns via toll-like receptors (TLRs) is critical for mucosal defenses. Using well-differentiated primary cultures of human airway epithelia, we investigated the effects of exposure of the cells to cytokines (TNF-alpha and IFN-gamma) and dexamethasone (dex) on responsiveness to the TLR2/TLR1 ligand Pam3CSK4. Production of IL-8, CCL20, and airway surface liquid antimicrobial activity were used as endpoints. Microarray expression profiling in human airway epithelia revealed that first response cytokines markedly induced TLR2 expression. Real-time PCR confirmed that cytokines (TNF-alpha and IFN-gamma), dexamethasone (dex), or cytokines + dex increased TLR2 mRNA abundance. A synergistic increase was seen with cytokines + dex. To assess TLR2 function, epithelia pre-treated with cytokines +/- dex were exposed to the TLR2/TLR1 ligand Pam3CSK4 for 24 hours. While cells pre-treated with cytokines alone exhibited significantly enhanced IL-8 and CCL20 secretion following Pam3CSK4, mean IL-8 and CCL20 release decreased in Pam3CSK4 stimulated cells following cytokines + dex pre-treatment. This marked increase in inflammatory gene expression seen after treatment with cytokines followed by the TLR2 ligand did not correlate well with NF-kappaB, Stat1, or p38 MAP kinase pathway activation. Cytokines also enhanced TLR2 agonist-induced beta-defensin 2 mRNA expression and increased the antimicrobial activity of airway surface liquid. Dex blocked these effects. While dex treatment enhanced TLR2 expression, co-administration of dex with cytokines inhibited airway epithelial cell responsiveness to TLR2/TLR1 ligand over cytokines alone. Enhanced functional TLR2 expression following exposure to TNF-alpha and IFN-gamma may serve as a dynamic means to amplify epithelial innate immune responses during infectious or inflammatory pulmonary diseases.


Effects of LDL, cholesterol, and their oxidized forms on the precipitation kinetics of calcium phosphates.
LDL, cholesterol, and their oxidized forms are known cardiovascular risk factors and are often found in atherosclerotic lesions of various stages. Little is known, however, about whether they are directly involved in the formation of calcium phosphate compounds. We used the pH-stat technique to follow the kinetics of calcium phosphate precipitation at pH 7.4, 37 degrees C, and ionic strength 0.150 mol/L, in the presence or absence of LDL, oxidized LDL, cholesterol, cholestane-3beta,5alpha,6beta-triol, and cholesteryl linoleate. The precipitates were characterized by x-ray diffraction, scanning and transmission electronic microscopy coupled with energy-dispersion x-ray analysis, and inductively coupled plasma atomic emission spectroscopy. Under the experimental conditions, LDL (14.8 and 43.1 mg/L protein) had no significant effect on the precipitation kinetics. Oxidized LDL (14.8 and 43.1 mg/L protein) prolonged the nucleation phase and diminished the amount of total precipitate, and both the extent of oxidation and the concentration of the protein affected the kinetics. Cholesterol microcrystals (71.4 and 143 mg/L) made the nucleation phase shorter (300 min vs 390 min for the control), and the precipitated particles had an organic core and a shell composed of calcium phosphates. L-alpha-Phosphatidylcholine vesicles (143 mg/L), cholesterol (71.4 mg/L)/phospholipid (143 mg/L) mixed vesicles, cholesteryl linoleate (143 mg/L), and cholestane-3beta,5alpha,6beta-triol (71.4 mg/L) prolonged the nucleation phase. LDL is not involved directly in the precipitation of calcium phosphates. Oxidized LDL inhibits both nucleation and crystal growth, possibly by attracting calcium ions in the solution and thus reducing supersaturation. Cholesterol microcrystals serve as seeds for the precipitation of hydroxyapatite, whereas L-alpha-phosphatidylcholine, cholesteryl linoleate, and cholestane-3beta,5alpha,6beta-triol exhibit inhibitive effects on the nucleation of calcium phosphates.


E-Cigarette Use in Young Adult Never Cigarette Smokers with Disabilities: Results from the Behavioral Risk Factor Surveillance System Survey.
Young adult never cigarette smokers with disabilities may be at particular risk for adopting e-cigarettes, but little attention has been paid to these people. This study examines the associations between different types of disability and e-cigarette use in this population. Young adult never-smokers from the 2016-2017 Behavioral Risk Factor Surveillance System (BRFSS) survey who were either never or current e-cigarette users (n = 79,177) were selected for the analysis. The Least Absolute Shrinkage and Selection Operator (LASSO) algorithm was used to select confounders for multivariable logistic regression models. Multivariable logistic regression models were used to determine the associations between current e-cigarette use and different types of disability after incorporating BRFSS survey design and adjusting for confounders. Young adult never-smokers who reported any disability had increased odds (OR 1.44, 95% CI 1.18-1.76) of e-cigarette use compared to those who reported no disability. Young adult never-smokers who reported self-care, cognitive, vision, and independent living disabilities had higher odds of e-cigarette use compared to those who reported no disability. There was no statistically significant difference in the odds of e-cigarette use for those reporting hearing and mobility disabilities compared to those who reported no disability. This study highlights the need for increased public education and cessation programs for this population.


Building the green way.
Just five or six years ago, the term "green building" evoked visions of barefoot, tie-dyed, granola-munching denizens. There's been a large shift in perception. Of course, green buildings are still known for conserving natural resources by, for example, minimizing on-site grading, using alternative materials, and recycling construction waste. But people now see the financial advantages as well. Well-designed green buildings yield lower utility costs, greater employee productivity, less absenteeism, and stronger attraction and retention of workers than standard buildings do. Green materials, mechanical systems, and furnishings have become more widely available and considerably less expensive than they used to be-often cheaper than their standard counterparts. So building green is no longer a pricey experiment; just about any company can do it on a standard budget by following the ten rules outlined by the author. Reliable building-rating systems like the U.S. Green Building Council's rigorous Leadership in Energy and Environmental Design (LEED) program have done much to underscore the benefits of green construction. LEED evaluates buildings and awards points in several areas, such as water efficiency and indoor environmental quality. Other rating programs include the UK's BREEAM (Building Research Establishment's Environmental Assessment Method) and Australia's Green Star. Green construction is not simply getting more respect; it is rapidly becoming a necessity as corporations push it fully into the mainstream over the next five to ten years. In fact, the author says, the owners of standard buildings face massive obsolescence. To avoid this problem, they should carry out green renovations. Corporations no longer have an excuse for eschewing environmental and economic sustainability. They have at their disposal tools proven to lower overhead costs, improve productivity, and strengthen the bottom line.


Exosomal Vaccine Loading T Cell Epitope Peptides of SARS-CoV-2 Induces Robust CD8+ T Cell Response in HLA-A Transgenic Mice.
Current vaccines for the SARS-CoV-2 virus mainly induce neutralizing antibodies but overlook the T cell responses. This study aims to generate an exosomal vaccine carrying T cell epitope peptides of SARS-CoV-2 for the induction of CD8+ T cell response. Thirty-one peptides presented by HLA-A0201 molecule were conjugated to the DMPE-PEG-NHS molecules, and mixed with DSPE-PEG to form the peptide-PEG-lipid micelles, then fused with exosomes to generate the exosomal vaccine, followed by purification using size-exclusion chromatography and validation by Western blotting, liquid nuclear magnetic resonance (NMR) test and transmission electron microscopy. Furthermore, the exosomal vaccine was mixed with Poly (I:C) adjuvant and subcutaneously administered for three times into the hybrid mice of HLA-A0201/DR1 transgenic mice with wild-type mice. Then, the epitope-specific T cell responses were detected by ex vivo ELISPOT assay and intracellular cytokine staining. The exosomal vaccine was purified from the Peak 2 fraction of FPLC and injected into the hybrid mice for three times. The IFN-γ spot forming units and the frequencies of IFN-γ+/CD8+ T cells were 10-82-fold and 13-65-fold, respectively, higher in the exosomal vaccine group compared to the Poly (I:C) control group, without visible organ toxicity. In comparison with the peptides cocktail vaccine generated in our recent work, the exosomal vaccine induced significantly stronger T cell response. Exosomal vaccine loading T cell epitope peptides of SARS-CoV-2 virus was initially generated without pre-modification for both peptides and exosomes, and elicited robust CD8+ T cell response in HLA-A transgenic mice.


Statins for the prevention and treatment of infections: a systematic review and meta-analysis.
Emerging epidemiological evidence suggests that statin use may reduce the risk of infections and infection-related complications. Our objective was to examine the association between statin use and the risk of infections and related outcomes. We searched several electronic databases from inception through December 2007 for randomized trials and cohort studies that examined the association between statin use and the risk or outcome of infections. Data on study characteristics, measurement of statin use, outcomes (adjusted for potential confounders), and quality assessment were extracted. Sixteen cohorts were eligible and differed in representativeness, outcome assessment, and comparability of exposed (statin) and unexposed (nonstatin) groups. Nine cohorts addressed the role of statins in treating infections: bacteremia (n = 3), pneumonia (n = 3), sepsis (n = 2), and bacterial infection (n = 1). The pooled adjusted effect estimate was 0.55 (95% confidence interval, 0.36-0.83; I(2) = 76.5%) in favor of statins. Seven cohorts addressed infection prevention in patients with vascular diseases (n = 3), chronic kidney disease (n = 1), diabetes (n = 1), intensive care unit-acquired infections (n = 1), and in general practice (n = 1). The pooled effect estimate was 0.57 (95% confidence interval, 0.43-0.75; I(2) = 82%) in favor of statin use; there was some evidence of publication bias for this analysis (Egger test; P = .07). Meta-regression did not identify potential effect modifiers that explain the between-study heterogeneity. Results for our meta-analysis suggest that statin use may be associated with a beneficial effect in treating and preventing different infections. Given the presence of heterogeneity and publication bias, there is a need for randomized trials to confirm the benefit of statin use in this context.


Determinants of scholarly project completion in a paediatric resident program in Canada.
The primary aims of this study were to: 1) assess barriers and facilitators of completing scholarly projects from residents and faculty mentor perspectives, 2) determine the perceived value of new initiatives designed to support resident scholarly projects and 3) determine if these initiatives led to changes in resident publications. Between June and September 2014, we surveyed 18 paediatric residents and 41 faculty mentors regarding barriers to resident scholarly project completion and the value of new initiatives to support scholarly activity. We also tracked scientific publications by residents before and after implementation of these initiatives. The primary perceived barriers to research for residents and faculty were lack of protected time (64.3% versus 68.6%, respectively), lack of resident interest in scholarly activity (50.0% versus 60.0%, respectively) and lack of mentor motivation. Mentors and residents did not agree that lack of proper training in research (29% versus 54%, respectively) and faculty motivation (29% versus 17%, respectively) were barriers to completing a project. A dedicated research coordinator (71.4% versus 70.6%, respectively), a revised research curriculum (71.4% versus 41.2%, respectively) and works in progress sessions (50.0% versus 61.8%, respectively) were perceived as valuable initiatives to the program. These initiatives were not associated with changes in annual resident publication rates. Lack of time and competing clinical training are primary barriers to scholarly project completion for residents in addition to a lack of motivation on the part of faculty members. Improving program support was perceived as positive changes to address these barriers but did not increase resident publication rates. The information provided here could be used to tailor future resident research programs and highlight the value of gathering input from resident and faculty when designing initiatives to enhance resident research productivity.


Function and Regulation of ALDH1A1-Positive Nigrostriatal Dopaminergic Neurons in Motor Control and Parkinson's Disease.
Dopamine is an important chemical messenger in the brain, which modulates movement, reward, motivation, and memory. Different populations of neurons can produce and release dopamine in the brain and regulate different behaviors. Here we focus our discussion on a small but distinct group of dopamine-producing neurons, which display the most profound loss in the ventral substantia nigra pas compacta of patients with Parkinson's disease. This group of dopaminergic neurons can be readily identified by a selective expression of aldehyde dehydrogenase 1A1 (ALDH1A1) and accounts for 70% of total nigrostriatal dopaminergic neurons in both human and mouse brains. Recently, we presented the first whole-brain circuit map of these ALDH1A1-positive dopaminergic neurons and reveal an essential physiological function of these neurons in regulating the vigor of movement during the acquisition of motor skills. In this review, we first summarize previous findings of ALDH1A1-positive nigrostriatal dopaminergic neurons and their connectivity and functionality, and then provide perspectives on how the activity of ALDH1A1-positive nigrostriatal dopaminergic neurons is regulated through integrating diverse presynaptic inputs and its implications for potential Parkinson's disease treatment.


[Acupuncture Analgesia-Panorama Multi-dimensional Treatment of Pain].
Along with advances in pain medicine, people have a deep understanding about pain. It is now considered that pain is a complex activity of the nerve system, particularly the high nerve centers, and is composed of sensory, affective, cognitive, and social interaction. By the help of new techniques and instruments of brain science, the neural circuits involved in pain generation have been understood intensively, partially explaining why pain is composed of multiple components and how the sensation, emotion and cognition of pain are influenced each other. Acupuncture analgesia is widely used in clinical treatment and has a definite therapeutic effect. Along with the revision of definition of pain, the research of acupuncture analgesia needs to accommodate the so-called multiple dimensions and their interactions, will effectively deepen its connotation and denotation, and expand its application range, opening up a wider clinical prospect.


The effects of hormone replacement therapy on autoimmune disease: rheumatoid arthritis and systemic lupus erythematosus.
Autoimmune diseases are generally more common in women than men; however, there is no simple explanation for this. Sex hormones, especially estrogen (but also prolactin and testosterone), play important roles in these diseases. Estrogens are generally considered to enhance autoimmunity and have multiple effects on the immune system through various cell types and molecular pathways. There is much evidence supporting the role of estrogen in the pathogenesis of systemic lupus erythematosus (SLE): the disease occurs much more frequently in women, especially during the years of child-bearing potential, and commonly flares during pregnancy. The relationship between estrogen and the development of SLE is complex, however. Exogenous estrogens have been historically avoided in women with SLE due to the widely held view that they could activate disease and their use remains controversial. Current evidence from prospective trials suggests that there may be a small increased risk of mild/moderate flares in women with SLE taking hormone replacement therapy (HRT), but the risk of major flare does not appear to be increased. In rheumatoid arthritis, HRT does not appear to be associated with an increased risk of disease flare and may actually improve disease activity. In all individuals with autoimmune disease, the risk of venous thrombosis associated with oral HRT is an important factor that should also be considered.


miR-1236 down-regulates alpha-fetoprotein, thus causing PTEN accumulation, which inhibits the PI3K/Akt pathway and malignant phenotype in hepatoma cells.
Alpha fetoprotein (AFP) is a clinical biomarker of hepatocellular carcinoma (HCC). Here, we found that miR-1236 is down-regulated, whereas AFP is highly expressed in HCC tissues and cells. We demonstrated that miR-1236 directly targets the 3'UTR of AFP and down-regulates its expression. Also, miR-1236 inhibited and AFP stimulated proliferation, migration, invasion and vasculogenic mimicry (VM) of HCC. In agreement, AFP over-expression counteracted the inhibitory effect of miR-1236. We demonstrated that AFP promoted the ubiquitination of PTEN, thus decreasing PTEN levels, while miR-1236 inhibited the PI3K/Akt pathway.


Resistance and the management of complicated skin and skin structure infections: the role of ceftobiprole.
Antimicrobial resistant bacteria are an increasing concern due to the resulting increase in morbidity, mortality, and health-care costs associated with the administration of inadequate or delayed antimicrobial therapy. The implications of inadequate antimicrobial therapy in complicated skin and skin structure infections (cSSSIs) have gained more attention recently, most likely due to the recent emergence of community-acquired methicillin resistant Staphylococcus aureus (MRSA) and the already high prevalence of MRSA in the nosocomial setting. Due to the continuous threat of resistance arising and the limitations of currently available agents for the treatment of cSSSIs, it is necessary to develop new antimicrobials for this indication. Ceftobiprole medocaril, the prodrug of ceftobiprole, is a parental investigational cephalosporin for the treatment of cSSSIs displaying a wide-spectrum of activity against both Gram-positive and Gram-negative species, including MRSA. Ceftobiprole displays noncomplex linear pharmacokinetics, is eliminated primarily by glomerular filtration, and distributes to extracellular fluid. Additionally, it has been shown that the extent of distribution to the site of action with regard to cSSSIs, ie, the extracellular space fluid of subcutaneous adipose tissue and skeletal muscle, is expected to be efficacious, as free concentrations meet efficacy targets for most pathogens. Similar to other beta-lactams, it displays an excellent safety and tolerability profile with the primary adverse events being dysgeusia in healthy volunteers, resulting from the conversion of the prodrug to the active, and nausea in patients. Ceftobiprole has demonstrated noninferiority in two large-scale pivotal studies comparing it to vancomycin, clinical cure rates 93.3% vs 93.5%, respectively, or vancomycin plus ceftazidime, clinical cure rates 90.5% vs 90.2%, respectively. Given the pharmacokinetic and pharmacodynamic properties, ceftobiprole is a promising new agent for the treatment of cSSSIs and has the potential to be used as a single agent for empiric treatment.


Giving intravenous iron to patients with symptomatic heart failure is safe and cost effective.
Heart failure affects approximately 1 million people in the UK, adversely affecting quality of life, functional capacity and cognitive health. Iron deficiency complicates heart failure in approximately 50% of patients. Giving intravenous ferric carboxymaltose has been shown to improve quality of life in patients with heart failure (New York Heart Association class and Kansas City Cardiomyopathy Questionnaire). A quality improvement project was designed to assess the feasibility, safety and cost implications of establishing an intravenous iron service in the authors' centre. Between July and December 2019 61 patients who were screened met the inclusion criteria and were administered intravenous ferric carboxymaltose. There were statistically significant improvements in ferritin levels (83.3 ug/litre to 433 ug/litre; P<0.0001), transferrin saturation (18% to 30% P<0.0001) and haemoglobin levels (126 g/litre to 135 g/litre; P<0.01). No demonstrable changes in New York Heart Association class or quality of life scores were noted. The overall financial impact for the trust was income generation of £14 665, a net income of £240 per patient. Intravenous iron replacement with ferric carboxymaltose is safe and cost effective, and should be considered in eligible iron-deficient patients with symptomatic heart failure. Integration with another day case intravenous service represented the most logistically simple and economically viable method of service delivery.


Treatment of female urethral syndrome refractory to antibiotics.
Various methods of treatment, other than antibiotic therapy, have been proposed for the treatment of female urethral syndrome; however, the results of these treatment methods are disappointing, due perhaps to the use of the wrong treatment approach. The aim of this study was to evaluate the effectiveness of external sphincter relaxant and biofeedback (BFB) with electrical stimulation therapy (EST) in patients who do not respond well to antibiotics. One hundred and five patients with a diagnosis of female urethral syndrome were entered into this study. Antibiotics were given as a first-line therapy for about 3 months. In cases of recurrent or incurable urethral syndrome, antibiotic therapy combined with external sphincter relaxant or BFB with EST were performed. External sphincter relaxant group was composed of 31 patients (29.5%) who showed functional urethral obstruction. Biofeedback group was composed of 41 patients (39.0%) who had severe pain or discomfort with irritative voiding symptoms. Subjective symptom was measured before and after therapy using the Bristol Female Lower Urinary Tract Symptoms questionnaire. Thirty-three patients (31.4%) were treated with antibiotic therapy alone and 7 (21.2%) of these patients recurred. The symptom score of this group changed from 10.51 to 2.85. In the antibiotics plus external sphincter relaxant group (N=31), the symptom score changed from 12.39 to 3.96. Five (16.1%) of these patients recurred and 3 of these 5 underwent urethral dilatation. In the antibiotics plus biofeedback group (N=41), the average urinary frequency changed from 12.2 to 7.7 times a day and nocturia changed from 2.4 to 0.6 times a night. The symptom score improved from 15.22 to 4.69 and the overall satisfaction rate was 87.8% (41.5%: very satisfied, 46.3%: satisfied, 12.2%: no response). Female urethral syndrome is not due to a single factor but is a complex disease due to various combined symptoms and mechanisms. This condition needs to be treated with an appropriate treatment protocol. We believe that satisfactory results could be obtained in female urethral syndrome, which has shown poor prognosis until now, by appropriately combining treatment methods, which include the use of external sphincter relaxants, biofeedback therapy and bladder training, according to indication, and depending on whether symptoms continue after initial antibiotic therapy.


Decreased S100A9 expression alleviates Clostridium perfringens beta2 toxin-induced inflammatory injury in IPEC-J2 cells.
S100 calcium-binding protein A9 (S100A9) is a commonly known pro-inflammatory factor involved in various inflammatory responses. Clostridium perfringens (C. perfringens ) type C is known to cause diarrhea in piglets. However, the role of S100A9 in C. perfringens type C-induced infectious diarrhea is unclear. Here, the S100A9 gene was overexpressed and knocked down in the IPEC-J2 cells, which were treated with C. perfringens beta2 (CPB2) toxin. The role of S100A9 in CPB2 toxin-induced injury in IPEC-J2 cells was assessed by measuring the levels of inflammatory cytokines, reactive oxygen species (ROS), lactate dehydrogenase (LDH), cell proliferation, and tight junction-related proteins. The results showed elevated expression of S100A9 in diarrhea-affected piglet tissues, and the elevation of S100A9 expression after CPB2 toxin treatment of IPEC-J2 was time-dependent. In CPB2 toxin-induced IPEC-J2 cells, overexpression of S100A9 had the following effects: the relative expression of inflammatory factors IL-6, IL8, TNF-α, and IL-1β was increased; the ROS levels and LDH viability were significantly increased; cell viability and proliferation were inhibited; the G0/G1 phase cell ratio was significantly increased. Furthermore, overexpression of S100A9 reduced the expression of tight junction proteins in CPB2-induced IPEC-J2 cells. The knockdown of S100A9 had an inverse effect. In conclusion, our results confirmed that S100A9 exacerbated inflammatory injury in CPB2 toxin-induced IPEC-J2 cells, inhibited cell viability and cell proliferation, and disrupted the tight junctions between cells. Thus, decreased S100A9 expression alleviates CPB2 toxin-induced inflammatory injury in IPEC-J2 cells.


Direct percutaneous carotid artery stenting for a patient with absence of the common carotid artery.
A 54-year-old man with symptomatic internal carotid artery stenosis with absence of the common carotid artery (CCA), who had been treated with surgery and postoperative radiotherapy for tonsillar carcinoma, underwent direct percutaneous carotid artery stenting (CAS). To our knowledge, this is the first report of direct percutaneous carotid artery stenting (CAS) for a patient with absent CCA.


Occupational Experience Effects on Physiological and Perceptual Responses of Common Soldiering Tasks.
Cohen BS, Redmond JE, Haven CC, Foulis SA, Canino MC, Frykman PN, Sharp MA. Occupational Experience Effects on Physiological and Perceptual Responses of Common Soldiering Tasks. J Strength Cond Res 37(4): 894-901, 2023-This study measured the impact of occupational experience (i.e., time spent deployed, in military service, and in job and task performance frequency in training, deployment, and study practice) on the physiological (heart rate [HR] and oxygen consumption [VO 2 ]) and perceptual (rate of perceived exertion [RPE]) responses to performance of critical physically demanding tasks (CPDTs). Five CPDTs (road march, build a fighting position, move under fire, evacuate a casualty, and drag a casualty to safety), common to all soldiers, were performed by 237 active duty soldiers. Linear regression models examined the association between measures of experience and physiological and perceptual performance responses to task demands. The level of significance was adjusted for multiple comparisons and set at ρ ≤ 0.0125 for this study. Significant and notable effect sizes included the impact of time spent deployed on the physiological measures of the road march (PostHR F = 24.84, p < 0.0001, β=-9.65), sandbag fill (PostHR F = 8.26, p = 0.005, β = -2.83), and sandbag carry (MeanHR F = 7.51, p = 0.007, β = -1.12; PostHR F = 7.35, p = 0.007, β = -0.87). For the road march task, there was a nearly 10 bpm decrease in postperformance HR for every year spent deployed. Road march, sandbag fill, and sandbag carry tasks PostHRs were also notably negatively associated with the experience measures of time in their MOS (job and time in military service but not for other physiological and perceptual responses, including VO 2 and RPE. Frequency of task performance in training, deployment, and study practice was not meaningfully associated with experience. The results suggest that increasing task familiarization through on-the-job occupational operational experience may result in greater proficiency and reduced physiological effort.