A pH sensitive thiolated β-cyclodextrin-modified nanoporous gold for controlled release of doxorubicin.
This article reports a novel thiolated β-cyclodextrin (HS-β-CD) modified nanoporous gold (NPG) wire for pH sensitive delivery of doxorubicin (DOX) in controlled manner. Nanoporous gold is a versatile material because of its three-dimensional nanoscale network of pores, facile surface functionalization, biocompatibility, and high capacity for the DOX payload. HS-β-CD can form supramolecular inclusion complexes with DOX affording the possibility of altering the controlled release behavior. DOX is one of the most potent anti-tumor drugs used in the treatment of different cancers. The binding of HS-β-CD and DOX was examined using UV-Vis spectroscopy. The prepared NPG structure exhibited excellent properties for controlled drug release outlining the potential of a pH sensitive drug implant for biomedical applications. This delivery system could improve local targeting of the drug as well as alter the rate of release of DOX near tumors.


The causes, impacts and countermeasures of COVID-19 "Infodemic": A systematic review using narrative synthesis.
An unprecedented infodemic has been witnessed to create massive damage to human society. However, it was not thoroughly investigated. This systematic review aims to (1) synthesize the existing literature on the causes and impacts of COVID-19 infodemic; (2) summarize the proposed strategies to fight with COVID-19 infodemic; and (3) identify the directions for future research. A systematic literature search following the PRISMA guideline covering 12 scholarly databases was conducted to retrieve various types of peer-reviewed articles that reported causes, impacts, or countermeasures of the infodemic. Empirical studies were assessed for risk of bias using the Mixed-Methods Appraisal Tool. A coding theme was iteratively developed to categorize the causes, impacts, and countermeasures found from the included studies. Social media usage, low level of health/eHealth literacy, and fast publication process and preprint service are identified as the major causes of the infodemic. Besides, the vicious circle of human rumor-spreading behavior and the psychological issues from the public (e.g., anxiety, distress, fear) emerges as the characteristic of the infodemic. Comprehensive lists of countermeasures are summarized from different perspectives, among which risk communication and consumer health information need/seeking are of particular importance. Theoretical and practical implications are discussed and future research directions are suggested.


SMARCB1 loss interacts with neuronal differentiation state to block maturation and impact cell stability.
Atypical teratoid rhabdoid tumors (ATRTs) are challenging pediatric brain cancers that are predominantly associated with inactivation of the gene SMARCB1, a conserved subunit of the chromatin remodeling BAF complex, which has known contributions to developmental processes. To identify potential interactions between SMARCB1 loss and the process of neural development, we introduced an inducible SMARCB1 loss-of-function system into human induced pluripotent stem cells (iPSCs) that were subjected to either directed neuronal differentiation or differentiation into cerebral organoids. Using this system, we identified substantial differences in the downstream effects of SMARCB1 loss depending on differentiation state and identified an interaction between SMARCB1 loss and neural differentiation pressure that causes a resistance to terminal differentiation and a defect in maintenance of a normal cell state. Our results provide insight into how SMARCB1 loss might interact with neural development in the process of ATRT tumorigenesis.


Increased circulating regulatory T cells (CD4(+)CD25 (+)CD127 (-)) contribute to lymphocyte anergy in septic shock patients.
Sepsis syndrome represents the leading cause of death in intensive care unit. Patients present features consistent with a decline in immune responsiveness potentially contributing to mortality. We investigated whether CD4(+)CD25(+) regulatory T cells (Treg) participate in the induction of lymphocyte anergy after sepsis. Observational study in septic shock patients and experimental study in mice. We took advantage of the recently described flow cytometric gating strategy using the measurement of CD25 and CD127 expressions for monitoring Treg (CD4(+)CD25(+)CD127(-)Foxp3(+)). In patients the increased circulating Treg percentage significantly correlated with a decreased lympho-proliferative response. In a murine model of sepsis mimicking these observations, the ex vivo downregulation of Foxp3 expression using siRNA was associated with a restoration of this response. The relative increase in circulating Treg might play a role in lymphocyte anergy described after septic shock and represent a standardizable surrogate marker of declining proliferative capacity after sepsis.


Treatment patterns and health care resource utilization in a 1-year observational cohort study of outpatients with schizophrenia at risk of nonadherence treated with long-acting injectable antipsychotics.
To describe (1) the clinical profiles and the patterns of use of long-acting injectable (LAI) antipsychotics in patients with schizophrenia at risk of nonadherence with oral antipsychotics, and in those who started treatment with LAI antipsychotics, (2) health care resource utilization and associated costs. A total of 597 outpatients with schizophrenia at risk of nonadherence, according to the psychiatrist's clinical judgment, were recruited at 59 centers in a noninterventional prospective observational study of 1-year follow-up when their treatment was modified. In a post hoc analysis, the profiles of patients starting LAI or continuing with oral antipsychotics were described, and descriptive analyses of treatments, health resource utilization, and direct costs were performed in those who started an LAI antipsychotic. Therapy modifications involved the antipsychotic medications in 84.8% of patients, mostly because of insufficient efficacy of prior regimen. Ninety-two (15.4%) patients started an LAI antipsychotic at recruitment. Of these, only 13 (14.1%) were prescribed with first-generation antipsychotics. During 1 year, 16.3% of patients who started and 14.9% of patients who did not start an LAI antipsychotic at recruitment relapsed, contrasting with the 20.9% who had been hospitalized only within the prior 6 months. After 1 year, 74.3% of patients who started an LAI antipsychotic continued concomitant treatment with oral antipsychotics. The mean (median) total direct health care cost per patient per month during the study year among the patients starting any LAI antipsychotic at baseline was €1,407 (€897.7). Medication costs (including oral and LAI antipsychotics and concomitant medication) represented almost 44%, whereas nonmedication costs accounted for more than 55% of the mean total direct health care costs. LAI antipsychotics were infrequently prescribed in spite of a psychiatrist-perceived risk of nonadherence to oral antipsychotics. Mean medication costs were lower than nonmedication costs.


Egg predation in forest bird communities on islands and mainland.
To examine if differences in egg predation rates could explain differences in bird community composition, egg predation was studied in two years on small islands in a South Swedish lake and on the nearby mainland using both natural and artificial nests.In plots with similar vegetation, the combined density of ground- and tree-nesting bird species did not differ between the islands and the mainland. Egg predation rates were similar on islands and the mainland for natural Turdus nests in two years, and for artificial Turdus and Phylloscopus nests. Unmarked and unvisited experimental nests suffered similar rate of egg predation as marked and visited nests. Egg predation rates were higher on natural nests when artificial nests were also put out, increasing the total nest density. Initial egg predation rates in artificial nests were also higher than later when nest density had decreased by 75%.The egg predators involved differed for artificial Phylloscopus nests between the islands and the mainland. Small mammals were apparently responsible for 29% of the predation on the mainland, but none on the islands. Artificial Turdus nests near crow nests suffered from a higher egg predation rate than nests further away from crow nests. Daily survival rates of Turdus nests increased from the laying to the incubation and further to the fledging state.Egg predation can not explain differences in bird community composition between islands and mainland in the present case.


Mutational analysis of cell wall biosynthesis in Mycobacterium avium.
The cell wall of the environmental pathogen Mycobacterium avium is important to its virulence and intrinsic antimicrobial resistance. To identify genes involved in cell wall biosynthesis, "transposome" insertion libraries were screened for mutants with altered colony morphology on medium containing the lipoprotein stain Congo red. Nineteen such mutants were isolated and mapped, including 10 with insertions in a functional island of cell wall biosynthetic genes that spans approximately 40 kb of the M. avium genome.


Long-term air pollution, noise, and structural measures of the Default Mode Network in the brain: Results from the 1000BRAINS cohort.
While evidence suggests that long-term air pollution (AP) and noise may adversely affect cognitive function, little is known about whether environmental exposures also promote structural changes in underlying brain networks. We therefore investigated the associations between AP, traffic noise, and structural measures of the Default Mode Network (DMN), a functional brain network known to undergo specific changes with age. We analyzed data from 579 participants (mean age at imaging: 66.5 years) of the German 1000BRAINS study. Long-term residential exposure to particulate matter (diameter ≤10 μm [PM10]; diameter ≤2.5 μm [PM2.5]), PM2.5 absorbance (PM2.5abs), nitrogen dioxide (NO2), and accumulation mode particulate number concentration (PNAM) was estimated using validated land use regression and chemistry transport models. Long-term outdoor traffic noise was modeled at participants' homes based on a European Union's Environmental Noise Directive. As measures of brain structure, cortical thickness and local gyrification index (lGI) values were calculated for DMN regions from T1-weighted structural brain images collected between 2011 and 2015. Associations between environmental exposures and brain structure measures were estimated using linear regression models, adjusting for demographic and lifestyle characteristics. AP exposures were below European Union standards but above World Health Organization guidelines (e.g., PM10 mean: 27.5 μg/m3). A third of participants experienced outdoor 24-h noise above European recommendations. Exposures were not consistently associated with lGI values in the DMN. We observed weak inverse associations between AP and cortical thickness in the right anterior DMN (e.g., -0.010 mm [-0.022, 0.002] per 0.3 unit increase in PM2.5abs) and lateral part of the posterior DMN. Long-term AP and noise were not consistently associated with structural parameters of the DMN in the brain. While weak associations were present between AP exposure and cortical thinning of right hemispheric DMN regions, it remains unclear whether AP might influence DMN brain structure in a similar way as aging.


[Sudden death of a young man as late sequelae complicating a pediatric disease: About a case].
In France, sudden death is responsible every year for 40,000 deaths. The most frequent etiology is cardiac disease. Atheromatous-related pathology is the most common etiology beyond 35, but cardiomyopathies and channelopathies are responsible for a significant number of deaths in young adults. Some acquired disorders can also cause sudden cardiac death. We report the case of a 17-year-old man who died suddenly after sport. Autopsy and pathological study found multiple giant coronary aneurysms. Thrombosis and fibrous scar of myocardial ischemic events were observed. These lesions were in favor of late sequelae of Kawasaki disease. Kawasaki disease is a rare but not exceptional cause of sudden cardiac death in young adults. In the lack of known clinical history, some aspects, even not specific, should evoke this diagnosis. Even in front of apparent good clinical tolerance, these sequelae require appropriate follow-up because of a significant risk of sudden death.


The Problem of Neurovascular Uncoupling.
Neurovascular uncoupling (NVU) is one of the most important confounds of blood oxygen level dependent (BOLD) functional magnetic resonance imaging (fMR imaging) in the setting of focal brain lesions such as brain tumors. This article reviews the assessment of NVU related to focal brain lesions with emphasis on the use of cerebrovascular reactivity mapping measurement methods and resting state BOLD fMR imaging metrics in the detection of NVU, as well as the use of amplitude of low-frequency fluctuation metrics to mitigate the effects of NVU on clinical fMR imaging activation.


In vitro effects of Cytochalasin B on TA3 tumor cells.
We studied the effect of Cytochalasin B (CB) on two lines of the ascites tumor TA3 by microcinematography and scanning electron microscopy. CB induces a dose dependent and reversible cell paralysis. One microgram CB/ml causes a pronounced but incomplete paralysis. The cells retain their general shape but develop numerous blebs. Ten microgram CB/ml causes a complete cell paralysis and a retraction of pseudopods and microvilli. When CB is removed, the cells rapidly regain their original form and motility. The recovery process starts within minutes after CB removal and is almost completed in 15 min.


[Damage to intra- and extrahepatic bile duct after hepatic artery embolization].
To study the pathogenesis, treatment and prevention of bile duct damage arising from hepatic artery embolization. Five patients with intra- and extrahepatic biliary damage resulting from hepatic artery embolization. Of these patients, 4 were due to hepatic artery embolization for hepatic haemangioma, and 1 was due to injecting TH (methacrylate) compound into the hepatic artery during operation. The hepatic artery was injected with ethanol so as to evaluate liver damage in experimental rats. All patients were found to have damage to intra- and extrahepatic bile duct at the hilum with biliary hepatocirrhosis; 4 of them received intrahepatic bile duct jejunal anastomosis and bile duct stent. Experiment result revealed obliteration of the bile duct and necrosis of the liver around the portal tract area. Arterial embolization of hepatic haemangioma may cause severe biliary damage.


Cardiovascular disease in Hajj pilgrims.
The changing pattern of hospital admissions during Hajj, the Muslims yearly pilgrimage attracting millions of pilgrims from all around the globe, has gradually seen infectious causes of hospital admission replaced by cardiovascular diseases as a leading cause of both intensive care unit admission and death. While this trend is partly associated with the high quality of medical services and awareness programs targeted at reducing the spread of infections, at the same time it underscores an urgent need to establish a pragmatic system to manage the challenge of cardiovascular morbidities and mortality during Hajj. A PubMed Central (PMC) literature search without date restrictions was performed for articles reporting on the medical experience during Hajj. There were 109 articles were returned using "Hajj" and "mortality" as search terms. After determining relevance to the current theme based on both direct and indirect reference to the pattern hospital admission during Hajj, 20 articles reporting on conducted studies were obtained. Data from these studies reporting on the pattern and outcome of hospitalization during Hajj were examined and helped in arriving at the conclusions presented in this review.


Eyewitness to history: Landmarks in the development of computerized electrocardiography.
The use of digital computers for ECG processing was pioneered in the early 1960s by two immigrants to the US, Hubert Pipberger, who initiated a collaborative VA project to collect an ECG-independent Frank lead data base, and Cesar Caceres at NIH who selected for his ECAN program standard 12-lead ECGs processed as single leads. Ray Bonner in the early 1970s placed his IBM 5880 program in a cart to print ECGs with interpretation, and computer-ECG programs were developed by Telemed, Marquette, HP-Philips and Mortara. The "Common Standards for quantitative Electrocardiography (CSE)" directed by Jos Willems evaluated nine ECG programs and eight cardiologists in clinically-defined categories. The total accuracy by a representative "average" cardiologist (75.5%) was 5.8% higher than that of the average program (69.7, p<0.001). Future comparisons of computer-based and expert reader performance are likely to show evolving results with continuing improvement of computer-ECG algorithms and changing expertise of ECG interpreters.


Inhibitory action of conventional food-grade natural antioxidants and of natural antioxidants of new development on the thermal-induced oxidation of cholesterol.
Cholesterol is a molecule with an unsaturated bond; therefore, like polyunsaturated fatty acids, it is prone to oxidation. Cholesterol oxidation products (COPs) are found in many common foods and have been shown to be atherogenic, cytotoxic, mutagenic and possibly carcinogenic. Therefore, efforts to prevent or to avoid COPs formation during manufacture and/or processing of foods are of high priority. The effect of natural antioxidants on COPs formation has not been extensively studied. We assayed the effect of some widely applied natural antioxidants, such as tocopherol homologs (alpha-T, gamma-T, and delta-T) and rosemary extract, and of some natural products of newly developed as antioxidants, such as the flavonoids quercetin, catechin, morin, and rutin, and also of an alkaloid-derived product, boldine, to inhibit cholesterol oxidation of soybean oil, added of cholesterol, induced in the Rancimat test conditions (150 degrees C and air bubbling). Formation of six different COPs at the induction period and at the 100 microS conductivity value was monitored by gas chromatography. Under the experimental conditions gamma-T, quercetin, and rosemary extract prove effective to inhibit both soybean oil oxidation and COP formation. alpha-T, catechin, and morin are less efficient to prevent COP formation. delta-T, rutin and boldine are devoid of protective action against COP formation. gamma-T, quercetin and rosemary extract may inhibit COP formation from the nucleus and from the lateral chain of the cholesterol molecule.


Validation of the ABCD-GENE score to identify high platelet reactivity in east Asian patients undergoing percutaneous coronary intervention.
High platelet reactivity (HPR) is associated with subsequent thrombotic events in patients undergoing percutaneous coronary intervention (PCI). Recently, the ABCD-GENE score was developed to identify patients at risk for HPR, incorporating both clinical and genetic factors. However, this score was derived and validated in mostly Caucasian subjects and it has not been validated in an East Asian population. Individual patient data from 4 prospective studies were pooled, in which platelet reactivity was measured using the VerifyNow assay on clopidogrel and genotyping of CYP2C19 was performed after PCI. Study populations included patients with general stable coronary artery disease, hemodialysis, age ≥75 and/or body weight <50 kg, and acute coronary syndrome. VerifyNow P2Y12 reactivity units >208 was defined as HPR. Of 184 patients, 111 (60%) had HPR on clopidogrel. In the receiver operating characteristics curve analyses, the ABCD-GENE score significantly predicted HPR on clopidogrel (AUC 0.78, best cut-off value 9, p < 0.001). Across the 4 studies and their combinations, the diagnostic ability and cut-off values of ABCD-GENE score for HPR on clopidogrel were consistent. The ABCD-GENE score had significant and moderate diagnostic ability for HPR on clopidogrel in Japanese patients undergoing PCI. The predictivity was consistent across a broad spectrum of patient populations, suggesting the applicability of this novel scoring system in clinical practice worldwide.


[A rare mode of revelation of Wegener's granulomatosis: myocarditis associated with a fibroblastic endocarditis].
We report, through this observation, a rare case of Wegener's disease revealed by myocarditis associated with fibroblastic endocarditis. The patient was initially admitted to hospital with global heart failure. The ECG showed atrial flutter rhythm disorder. Echocardiographic examination revealed non-dilated left ventricle with severe dysfunction and positive troponin dosage. Severe renal failure was discovered fortuitously and required hemodialysis. It was associated with an inflammatory anaemia confirmed by serum ferritin and myelogram. c-ANCA dosage was strongly positive, confirming the diagnosis. Chest CT scanning objectified right basal pneumonia. After starting appropriate treatment, including corticotherapy and immunosuppressive treatment, evolution was favorable with the normalization of left ventricular systolic function. Although obvious clinical cardiac events are rare, cardiac involvement in Wegener's disease is described, requiring rapid diagnostic orientation and rigorous knowledge of this serious disease.


Effect of inflammatory and noninflammatory stress on plasma ketone bodies and free fatty acids and on glucagon and insulin in peripheral and portal blood.
Inflammatory stress as characterized by infection with Streptococcus pneumoniae, administration of endotoxin, or the induction of a turpentine abscess is characterized by the inhibition of the ketosis assoicated with fasting and a decline in the level of free fatty acids in the plasma. Moreover, rats subjectd to these inflammatory stresses demonstrate a significant rise in peripheral and portal insulin and glucagon. Rats subjected to noninflammatory stresses, screen-restraint, or noninvasive femoral fracture did not demonstrate the inhibition of ketosis but did show a decrease in plasma free fatty acids. The noninflammatroy stresses did not show an abnormal elevation of plasma or portal insulin or glucagon.


[Study of the clinicopathology on verruciform xanthoma of the oral cavity].
Three cases of oral cavity mucosal verruciform xanthoma were studied to investigate the pathogenesis of verruciform xanthoma. Immunohistochemical staining with S-P and in situ hybridization using the probe to detect HPV mRNA and MMP-2, MMP-9 RNA. The foam cells were strongly positive for CD68 (KP1) and Vimentin. The cytokeratin, PCNA and S-100 showed negative in foam cells. ISH testing failed to detect HPV (types 6, 11, 16, 18) in any of the three cases of verruciform xanthoma. MMP-2, MMP-9 showed positive staining in epithelial cells and foam cells. Verruciform xanthoma is most likely not a human papillomavirus associated lesion and the foam cells like that, are most likely derived from monocyte-macrophage lineage.


Manual strangulation: experimental approach to the genesis of hyoid bone fractures.
Discovery of a fracture of the hyoid bone during forensic autopsy is a feature that raises suspicions of constriction of the neck. Studies have shown the influence of gender and build of the individual on the morphology of this bone. Our aims were to confirm these findings and to develop an experimental protocol for simulating manual strangulation in order to determine the force required to fracture the hyoid bone and the influence of anthropometric parameters on this force. A total of 77 intact hyoid bones were obtained, scanned, modeled, measured and embedded in resin. Using a hydraulic press, we applied force to the distal extremity of the greater horn. The relationships between the parameters of sex, weight and height of the subject, anteroposterior length of the hyoid, width between the greater horns, angle, fusion of the greater horns and force applied were analyzed. Our study confirmed sexual dimorphism, shown by greater length in males (>37.8 mm) than in females, and a larger angle in females (a shorter bone with a width>43.7 mm and an angle>31°01). The study confirmed the positive correlation between the length of the hyoid and the weight and height of the subject (p<0.05). Sixty-seven of the 77 hyoid bones fractured during the experiment (87% fracture rate). Of the fractures, 48% occurred at the junction between the body and the greater horns, 49% in the greater horns (mean distance from the distal extremity of the horn 17.33±4.37 mm), and 3% in the median part of the body. No significant association was found between gender and type of fracture, or between fusion or non-fusion of the horn (p>0.05). Fused bones were not more susceptible to fracture than non-fused bones. Fracture occurred at a mean force of 30.55 N (±18.189). Multiple linear regression showed a significant negative correlation between force required for fracture and age, weight and height of the subject, anteroposterior length and angle. The younger the individual, the slighter their build, the longer the bone and the smaller the angle, the greater the force required to fracture the hyoid bone.


GNAS is not involved in gastrointestinal tumour formation in Peutz-Jeghers syndrome.
Peutz-Jeghers syndrome (PJS), caused by germ-line mutations in LKB1, is characterized by the development of hamartomatous polyps in the gastrointestinal (GI) tract. McCune Albright syndrome (MAS), caused by somatic activating mutations in GNAS, presents with cutaneous, skeletal, and endocrine manifestations. Recently, hamartomatous GI polyps with histological features similar to those in PJS were observed in MAS patients, suggesting a role for GNAS in the pathogenesis of PJS. This study reports the first somatic GNAS mutation analysis in GI tumours of PJS patients. No mutations were observed, suggesting that GNAS is not involved in the pathogenesis of GI tumours in PJS.


[Combined osteosynthesis in diaphyseal fractures of the long tubular bones].
An operative method of union and fixation of long tubular bones consisting in combination of the compressive-destruction and intramedullary osteosynthesis is described. The method is minimally traumatic and gives high degree of stabilization of fragment ends. Early functional load on the extremity facilitates the union of fractures.


Teachers' experiences of teaching in a blended learning environment.
This paper considers teachers' experiences of teaching undergraduate nursing students in a blended learning environment. The basic idea of the study programme was to support students to reflect on theory and practice, and provide with access to expert and professional knowledge in real-life problem-solving and decision making. Learning was organised to support learning in and about work: students worked full-time and this provided excellent opportunities for learning both in practice, online and face-to-face sessions. The aim of the study was to describe teachers' experiences of planning and implementing teaching and learning in a blended-learning-based adult nursing programme. The research method was qualitative, and the data were collected by three focus group interviews, each with four to six participants. The data were analysed using qualitative content analysis. The results show that the blended learning environment constructed by the combination of face-to-face learning and learning in practice with technology-mediated learning creates challenges that must be taken into consideration when planning and implementing blended teaching and learning. However, it provides good opportunities to enhance students' learning in and about work. This is because such programmes support student motivation through the presence of "real-life" and their relevance to the students' own places of work. Nevertheless, teachers require knowledge of different pedagogical approaches; they need professional development support in redesigning teaching and learning.


Supercooling and freezing processes in nanoconfined water by time-resolved optical Kerr effect spectroscopy.
Using heterodyne-detected optical Kerr effect (HD-OKE) measurements, we investigate the vibrational dynamics and the structural relaxation of water nanoconfined in Vycor porous silica samples (pore size ≃ 4 nm) at different levels of hydration and temperatures. At low levels of hydration corresponding to two complete superficial water layers, no freezing occurs and the water remains mobile at all the investigated temperatures with dynamic features similar, but not equal to, the bulk water. The fully hydrated sample shows the formation of ice at about 248 K. This process does not involve all the contained water; a part of it remains in a supercooled phase. The structural relaxation times measured from the decay of the time-dependent HD-OKE signal shows the temperature dependence largely affected by the hydration level; the low frequency (ν < 500 cm(-1)) vibrational spectra obtained by the Fourier transforms of the HD-OKE signal appear less affected by confinement.


Hepatotoxicity during TB treatment in people with HIV/AIDS related to NAT2 polymorphisms in Pernambuco, Northeast Brazil.
Hepatotoxicity during tuberculosis (TB) treatment is frequent and may be related to the Arylamine N-Acetyltransferase (NAT2) acetylator profile, in which allele frequencies differ according to the population. The aim of this study was to investigate functional polymorphisms in NAT2 associated with the development of hepatotoxicity after initiating treatment for TB in people living with HIV/AIDS (PLWHA) in Pernambuco, Northeast Brazil. This was a prospective cohort study that investigated seven single nucleotide polymorphisms located in the NAT2 coding region in 173 PLWHA undergoing TB treatment. Hepatotoxicity was defined as elevated aminotransferase levels and identified as being three times higher than it was before initiating TB treatment, with associated symptoms of hepatitis. A further 80 healthy subjects, without HIV infection or TB were used as a control group. All individuals were genotyped by direct sequencing. The NAT2*13A and NAT2*6B variant alleles were significantly associated with the development of hepatotoxicity during TB treatment in PLWHA (p<0.05). Individual comparisons between the wild type and each variant genotype revealed that PLWHA with signatures NAT2*13A/NAT2*13A (OR 4.4; CI95% 1.1-18.8; p 0.037) and NAT2*13A/NAT2*6B (OR 4.4; CI95% 1.5-12.7; p 0.005) significantly increased the risk of hepatotoxicity. This study suggests that NAT2*13A and NAT2*6B variant alleles are risk factors for developing hepatotoxicity, and PLWHA with genotypes NAT2*13A/NAT2*13A and NAT2*13A/NAT2*6B should be targeted for specific care to reduce the risk of hepatotoxicity during treatment for tuberculosis.


Amrinone relaxes potassium-induced contracture of failing right ventricular muscle of cats.
The effects of amrinone (5.3 X 10(-4) M) on isometric contraction and K+-induced contracture force of right ventricular muscle isolated from normal cats (n = 6) and cats in right ventricular failure (RVF, n = 6), 3-14 days after partial pulmonary artery ligation, were studied. Peak isometric contractile force (Po) and maximal rate of force development (dP/dt) of RVF muscles (1.38 +/- 0.21 g/mm2; means +/- SEM, and 11 +/- 1 g/s/mm2, respectively) were significantly lower than normal muscles (2.46 +/- 0.41 g/mm2, p less than 0.025, and 24 +/- 3 g/s/mm2, p less than 0.005, respectively). Duration of contraction (DC) was significantly longer in RVF muscles (442 +/- 32 ms) than in normal muscles (361 +/- 11 ms, p less than 0.025). Times to peak twitch force (TTP) and peak K+-induced contracture force (Pc) of RVF and normal muscles were not different. Amrinone increased Po and dP/dt significantly in normal muscles (+78 +/- 24%; means +/- SEM; p less than 0.01, and +53 +/- 17%, p less than 0.025, respectively), but not RVF muscles (+11 +/- 16% and +8 +/- 19%, respectively). TTP and DC of normal muscle were unchanged by amrinone, whereas TTP was unchanged while DC was shortened (-12 +/- 3%, p less than 0.025) in RVF muscle. Amrinone relaxed Pc similarly and significantly in normal (-28 +/- 7%, p less than 0.005) and RVF (-26 +/- 4%, p less than 0.025) muscles. These results suggest that part of amrinone's salutary action in the failing heart occurs through modification of myocardial relaxation.


Kinetics of anthocyanin condensation reaction in model wine solution under pulsed light treatment.
The effects of Pulsed Light (PL) technology on the anthocyanin condensation reaction in model wine solutions were investigated. Model wine solutions containing malvidin-3-O-glucoside, cyanidin-3-O-glucoside, and delphinidin-3-O-glucoside were separately prepared with the presence of (-)-epicatechin and acetaldehyde. The solutions were subjected to PL treatment with 2, 4, and 8 J/cm2 energy and stored in 10 °C. The loss of anthocyanin during the treatment and the aging period fitted the first-order reaction model (R2 > 98 %). Delphinidin-3-O-glucoside suffered the highest loss, only 46 % remaining after 60 s treatment; the malvidin-3-O-glucoside showed the lower loss, 72 % remaining after 60 s treatment. Furthermore, the PL treatment significantly influenced the kinetics of anthocyanin loss. The results from LC ESI TOF/Q-TOF MS/MS analysis revealed that in the PL treated samples, more peaks eluted in the chromatogram assigned to anthocyanin ethyl-linked (-)-epicatechin products, suggesting that PL treatment led to the formation of new isomers of anthocyanin ethyl-linked (-)-epicatechin. The color characteristics of the model solutions were affected by the PL treatment and the formation of ethyl-linked products. For example, the ΔE* value for samples treated with 8 J/cm2 increased by 42.52, 55.73, and 45.61 % for malvidin-3-O-glucoside, cyanidin-3-O-glucoside, and delphinidin-3-O-glucoside respectively after 110 days.


Risk assessment of formaldehyde for the general population in Japan.
Formaldehyde is used in the production of resins, molding compounds, photographic film, bactericide, and tissue preservative. The purpose of this study was to provide an up-to-date critical review of the information to the toxicological profile of formaldehyde, and to assess the risk of formaldehyde for the general population in Japan. Inhaled formaldehyde is an effective sensory irritant at a dosage of 0.5 ppm in mice. Following inhalation in laboratory animals, more than 6 ppm formaldehyde causes degenerative non-neoplastic effects in mice and monkeys and nasal tumors in rats. It is considered that formaldehyde induces genotoxic effects directly in vitro and secondarily in vivo. Sensory irritation of the eyes and respiratory tract in response to inhalation exposure to formaldehyde has been reported at 0.08 ppm and above in human study. Formaldehyde is carcinogenic at the site of contact as a consequence of epithelial cell regenerative proliferation resulting from cytotoxicity and mutation, based on studies in both animals and humans. Levels of formaldehyde in atmosphere detected in rural, suburban, and urban areas in Japan were 2.5-3.2 ppb from 1998 to 2003. The majority of the population is exposed to atmosphere concentrations of formaldehyde less than those associated with sensory irritation. The reference concentration of formaldehyde in atmosphere for the Japanese general population is recommended to be 0.01 ppm.


Biotinylation: a simple method for labelling complement component C8 with preservation of functional activity.
Biotinylation of human C8 with the water-soluble biotin derivative biotinylamidohexanoic acid, N-hydroxysulfosuccinimide ester is an excellent method for labelling this terminal complement component with preservation of its functional activity. The biotinylated product can be detected both in native form and also following its incorporation into the terminal complement complexes. Detection assays include Western blotting, crossed immunoblotting, ELISA, and immunocytochemistry. Biotinylation is an attractive alternative method for labelling C8 and may be used for detecting and quantifying C8 and C5b-9 complexes in their soluble and membrane-bound forms.


Dermanyssus gallinae and chicken egg production: impact, management, and a predicted compatibility matrix for integrated approaches.
The poultry red mite, Dermanyssus gallinae, is a worldwide threat to egg production and animal and human welfare. This mite is also a potential vector for several significant diseases. EU regulation that forbids the use of conventional cages for egg-laying hens may favour the growth of D. gallinae, a species known to thrive in more complex housing systems. Current control measures emphasize the use of chemical acaricides, which may have limited efficacy on D. gallinae considering its temporary blood-feeding behaviour. In integrated pest management (IPM), two or more compatible measures targeting physical, environmental, and/or biological aspects could be judiciously combined to enhance the effectiveness against D. gallinae infestation. To inform current and future IPM for D. gallinae, a compatibility matrix is proposed to guide the selection of control measures for field application.


Imaging of perianal Crohn's disease.
Perianal fistulas and abscesses are common complications of Crohn's disease, affecting up to 50% of patients during their disease course. Accurate diagnosis and classification of perianal disease is crucial before and during treatment to plan an adequate approach for each patient and to avoid irreversible functional consequences. Although examination under anaesthesia has been considered the gold standard for diagnosis and classification of Crohn's disease perianal fistulas, taken alone it does not have perfect accuracy, stressing the need for concomitant or alternative, non-invasive, methods of evaluation. In this context, imaging modalities assessed for diagnosis, classification and monitoring of Crohn's disease perianal fistulas include pelvic magnetic resonance imaging, anorectal endoscopic ultrasonography, transcutaneous perianal ultrasound, fistulography and computed tomography. In particular, magnetic resonance imaging and endoscopic ultrasonography findings have shown the best accuracy, and the ability to influence therapeutic management of these patients. For transcutaneous perianal ultrasound too, good preliminary data have been reported. This paper reviews the available data on imaging methods for the management of perianal Crohn's disease.


Microplastic contamination of fish gills and the assessment of both quality assurance and quality control during laboratory analyses.
Microplastic pollution has received substantial international attention in terrestrial and marine environments and in the atmosphere. In this study, we assessed microplastic pollution and analyzed the accumulation of microplastics in the gills of fish caught in the Zhoushan fishing ground from September 2017 to March 2018. The average abundance of microplastics was 0.49 ± 0.54 particles/gill and frequently found chemical polymers was polyethylene terephthalate. We also conducted experiments on microplastic pollution in the water and the working solutions used during the analytical process and found that the source of microplastic contamination was the solutions used. Moreover, we evaluated and scored experimental quality control and quality assurance adapted from the 'Total Accumulated Score' method. Valuable steps are recommended in order to produce reliable results and improve the quality of results in microplastic analyses.


Lack of association between rs597668 polymorphism near EXOC3L2 and late-onset Alzheimer's disease in Han Chinese.
Recently, an international genome-wide association study (GWAS) additionally found rs597668 near EXOC3L2/BLOC1S3/MARK4 was a new genome-wide significance locus associated with late-onset Alzheimer's disease (LOAD) in Caucasians. Follow-up replication studies were conducted almost exclusively in Caucasians, and the effects of the risk locus in other populations are as yet unknown. This study investigated the GWAS-associated locus near EXOC3L2 in 1205 unrelated Northern Han Chinese subjects comprising 598 LOAD patients and 607 healthy controls matched for gender and age. The results showed no significant differences in the genotypic or allelic distributions of rs597668 polymorphism between LOAD cases and healthy controls (genotype: P=0.653; allele: P=0.603), even after stratification for apolipoprotein E (APOE) ɛ4 status and statistical adjustment for age, gender and APOE ɛ4 status. This study suggests that the rs597668 polymorphism near EXOC3L2 may not play a major role in the susceptibility to LOAD in the Northern Han Chinese population.


Elevated renal afferent nerve activity in a rat model of endothelin B receptor deficiency.
Renal nerves have been an attractive target for interventions aimed at lowering blood pressure; however, the specific roles of renal afferent (sensory) versus efferent sympathetic nerves in mediating hypertension are poorly characterized. A number of studies have suggested that a sympathoexcitatory signal conveyed by renal afferents elicits increases in blood pressure, whereas other studies identified sympathoinhibitory afferent pathways. These sympathoinhibitory pathways have been identified as protective against salt-sensitive increases in blood pressure through endothelin B (ETB) receptor activation. We hypothesized that ETB-deficient (ETB-def) rats, which are devoid of functional ETB receptors except in adrenergic tissues, lack appropriate sympathoinhibition and have lower renal afferent nerve activity following a high-salt diet compared with transgenic controls. We found that isolated renal pelvises from high salt-fed ETB-def animals lack a response to a physiological stimulus, prostaglandin E2, compared with transgenic controls but respond equally to a noxious stimulus, capsaicin. Surprisingly, we observed elevated renal afferent nerve activity in intact ETB-def rats compared with transgenic controls under both normal- and high-salt diets. ETB-def rats have been previously shown to have heightened global sympathetic tone, and we also observed higher total renal sympathetic nerve activity in ETB-def rats compared with transgenic controls under both normal- and high-salt diets. These data indicate that ETB receptors are integral mediators of the sympathoinhibitory renal afferent reflex (renorenal reflex), and, in a genetic rat model of ETB deficiency, the preponderance of sympathoexcitatory renal afferent nerve activity prevails and may contribute to hypertension.NEW & NOTEWORTHY Here, we found that endothelin B receptors are an important contributor to renal afferent nerve responsiveness to a high-salt diet. Rats lacking endothelin B receptors have increased afferent nerve activity that is not responsive to a high-salt diet.


Two dual-specific (anti-IgG and anti-dsDNA) monoclonal autoantibodies derived from the NZB/NZW F1 recognize an epitope in the hinge region.
The anti-IgG properties of two dual-specific (anti-dsDNA and anti-IgG) monoclonal NZB/NZW F1-derived autoantibodies, BV 17-45 and BV 16-13, were studied to resolve the location and possible commonality of the IgG epitope. To determine if BV 17-45 and BV 16-13 recognized the same IgG epitope, the relative temperature sensitivity of the conformational IgG epitopes were evaluated using the conformational sensitive immunoassay. Comparison of the temperature sensitivity of the conformational immunoglobulin epitopes over a temperature range of 25-100 degrees C suggested that the epitope recognized by BV 17-45 was the same as the IgG epitope recognized by BV 16-13. Further studies with papain- and pepsin-generated F(ab')2, Fab, and Fc fragments of BV 17-45 and BV 16-13 revealed that the dual-specific autoantibodies BV 17-45 and BV 16-13 both bound an epitope in the hinge region of the IgG molecule. The potential correlation between these studies and the pathogenic nature of dual-specific autoantibodies is discussed.


Sociodemographic, neighborhood, psychosocial, and substance use correlates of cocaine use among Black adults: Findings from a pooled analysis of national data.
Cocaine use (CU) is serious a public health issue affecting U.S. adults, including Blacks. Cocaine-related overdose deaths have also trended upwards among this population. However, there remains a lack of research on correlates of CU among a nationally representative sample of Black adults. The current study examines the prevalence and correlates of past-year CU among Black adults aged 18 and older (N = 9,821). Data from the National Survey on Drug Use and Health (2015-2016) were used and a weighted logistic regression model was estimated. Findings showed 2.4% of Black adults reported past-year CU-significantly higher than rates of CU among other assessed racial groups. Opioid use/misuse, encounters with drug dealers, easier access to cocaine, unemployment, and being 35 or older were associated with increased odds of CU. Greater risk perception of CU and religiosity were associated decreased odds of CU. Results identified several correlates associated with past-year CU among Black adults. Findings suggest addressing CU among this population will likely require the development of multilevel prevention and intervention strategies and an increased focus on opioid use/misuse as opioids have been recently implicated in cocaine-related overdose deaths.


[Physiological and reparative regeneration of the mitochondria].
The ultrastructure of mitochondria of hepatocytes in normal and pathological conditions was studied. It was shown that the process of regeneration of the ultrastructure of swollen mitochondria with a lucent matrix up to the normal state was completed in hepatocytes of the rat and chick embryos within one day. It was established that one of the ways of intraorganoid regeneration of mitochondria in hepatocytes of chick embryos and of mice after injections of CCl4 twice a week for 5 months was clasmatosis of the destroyed mitochondria fragments and their removal through the partially disintegrated exterior membrane of mitochondria followed by the membrane restoration. The process of mitochondrial regeneration after clasmatosis of its fragments was shown to require two days in the chick embryo hepatocytes.


Brief guided imagery and body scanning interventions reduce food cravings.
Elaborated Intrusion (EI) Theory proposes that cravings occur when involuntary thoughts about food are elaborated; a key part of elaboration is affectively-charged imagery. Craving can be weakened by working memory tasks that block imagery. EI Theory predicts that cravings should also be reduced by preventing involuntary thoughts being elaborated in the first place. Research has found that imagery techniques such as body scanning and guided imagery can reduce the occurrence of food thoughts. This study tested the prediction that these techniques also reduce craving. We asked participants to abstain from food overnight, and then to carry out 10 min of body scanning, guided imagery, or a control mind wandering task. They rated their craving at 10 points during the task on a single item measure, and before and after the task using the Craving Experience Questionnaire. While craving rose during the task for the mind wandering group, neither the guided imagery nor body scanning group showed an increase. These effects were not detected by the CEQ, suggesting that they are only present during the competing task. As they require no devices or materials and are unobtrusive, brief guided imagery strategies might form useful components of weight loss programmes that attempt to address cravings.


Scavenger receptor class B type I expression and elemental analysis in cerebellum and parietal cortex regions of the Alzheimer's disease brain.
Metal ions play an important role in health and disease by influencing cellular biochemical pathways. The increased concentrations of some metal ions may have cytotoxic effects through their ability to oxidatively modify biomolecules, which may cause oxidative stress-induced brain cell death leading to neurodegenerative disorders observed in Alzheimer's disease (AD). We therefore performed elemental analysis of human brain tissues by a sophisticated method of inductively coupled plasma mass spectrometry (ICP-MS) in two regions of the AD brain, the parietal cortex and cerebellum, and compared them with the age-matched control. Our analysis shows the differential distribution of some metal ions in the two regions of the brain. Most importantly, Si, Sn, Al and Mn showed significantly higher levels in the parietal cortex of the AD brain compared to the control. The other metal ions showing moderate increases in the parietal cortex were Na, Te, Cr, Fe and B. Since these metal ions can modify lipoproteins in the brain and modified lipoproteins are taken up by scavenger receptors class B type I (SR-BI), we also determined the presence of SR-BI in the parietal cortex and cerebellum regions of the control and AD brains using a sensitive method, the reverse transcriptase-polymerase chain reaction. Our results suggest that SR-BI are present in the parietal cortex as well as in the cerebellum of the control and AD brains, suggesting that the presence of SR-BI may be involved in the uptake of oxidatively modified lipoproteins and beta-amyloid (Abeta) protein complexed with apoE, suggesting implications in the progression of late onset AD and other neurodegenerative disorders characterized by the deposition of insoluble aggregates observed in the AD brain.


Alcohol satiety, hypertension and the renin-angiotensin system.
Evidence is presented which supports the hypothesis that the renin-angiotensin (r-a) system regulates alcohol intake. Documented findings suggest that an elevated level of r-a activity represents a satiety signal which stops alcohol intake. The fact that alcohol itself is known to stimulate r-a activity suggests that its intake may in some sense be self-regulating and that levels of r-a activity below those which signal satiety may even be rewarding. The role of the r-a system in hypertension is also considered. The ability of alcohol to elevate r-a activity may be seen as a contributing factor to alcohol-induced hypertension because angiotensin is a potent pressor agent. Furthermore, the notion that lower levels of angiotensin may be rewarding permits the hypothesis that essential hypertension may, in part, be the result of a self-induced increase in endogenous angiotensin. This would explain the otherwise puzzling utility of the angiotensin converting enzyme inhibitors in the treatment of essential hypertension.


Clinical and molecular epidemiology of extended-spectrum β-lactamase-producing Escherichia coli and Klebsiella pneumoniae in a long-term study from Japan.
The detection rates of extended-spectrum β-lactamase (ESBL)-producing bacteria in Japan are very low (∼5%) compared with those obtained worldwide. Further, the current trend of these bacteria in Japan is not known, and few studies with longitudinal observations have been reported. To obtain epidemiologic data on ESBL-producing bacteria, their genotypic features, and their antibiotic resistance patterns in Japan, we analyzed bacterial isolates from hospitalized patients at our institution over the 7-year period from 2003 to 2009. Of 2,304 isolates, 202 (8.8%) were found to be ESBL producers, including Escherichia coli, Klebsiella pneumonia, and Proteus mirabilis. The detection rates of the ESBL-producing isolates gradually increased and reached 17.1% and 10.5% for the E. coli and K. pneumoniae strains, respectively, in 2009. Genotyping analysis showed that ∼90% of the ESBL-producing isolates carried the CTX-M genotype, in which the CTX-M-9 group was predominant, although the CTX-M-2 group is considered to be the main genotype in Japan; further, many of the strains produced multiple β-lactamases. The detection rates of ESBL-producing bacteria may tend to be high within a limited region in Japan. A countrywide survey is required to understand the trend for ESBL-producing bacteria at the national level. In addition, our findings suggest that the genotypes of the detected ESBL producers are similar to those exhibiting a successful nosocomial spread worldwide.


Osteoid osteomata of the distal phalanx.
Osteoid osteomata are rarely found in the distal phalanges of the hand. The 23 cases in the English language literature are discussed and two additional cases are described. The usual presenting features are chronic pain, nail enlargement and increase in size of the terminal part of the digit. Diagnosis is difficult but surgical excision is effective for treating the patients' pain.


Short-chain fatty acids and colon cancer cells: the vitamin D receptor--butyrate connection.
Butyrate and its prodrug tributyrin, as well as 1,25-dihydroxyvitamin D3 (1,25-(OH)2D3), have important physiological effects on proliferation and differentiation in a variety of malignant cells. The aim of this study was to elucidate the role of the vitamin D receptor (VDR) in butyrate-induced cell differentiation and cell cycle arrest in Caco-2 cells, a human colon cancer cell line. Cell differentiation was evaluated by analyzing the activity of alkaline phosphatase (AP). Protein of VDR, cyclins, cyclin-dependent kinases (cdks) and of cdk inhibitors was quantified by Western blot analysis, VDR-mRNA by PCR. Pre- and postconfluent cells were assessed for VDR binding activity. Cell cycle was analyzed by flow cytometry. Tributyrin significantly increased VDR-mRNA level (250% vs. control) and VDR binding activity. Butyrate also enhanced VDR protein content in the nucleus in a time- and dose-dependent manner and more potently than other short-chain fatty acids of a related structure. Both butyrate (640% vs. control) and 1,25-(OH)2D3 (350% vs. control) significantly stimulated differentiation, whereas combined treatment with butyrate and 1,25-(OH)2D3 resulted in a synergistic amplification of AP activity (1400% vs. control). In the presence of the VDR antagonist ZK 191732, butyrate-induced differentiation was completely abolished (150% vs. control). While butyrate alone increased p21Waf1/Cip1 expression and down-regulated cdk 6 and cyclin A, and combined exposure with 1,25-(OH)2D3 resulted in a synergistic enhancement of butyrate-induced changes, expressions did not change from control level after treatment with butyrate and ZK 191732. G1 cell cycle arrest induced by butyrate was also abolished after combined treatment with butyrate and ZK 191732. In conclusion, differentiation and cell cycle arrest of Caco-2 cells induced by butyrate are mediated by up-regulation of VDR, followed by a stimulation of the negative cell cycle regulator p21Waf1/Cip1 and by a down-regulation of cdk 6 and cyclin A, both involved in cell cycle progression.


[Obstructive disorders of urine transport of the upper urinary tract--benign and malignant retroperitoneal fibrosis].
Our experience in diagnosis, treatment and follow-up course of patients suffering from benign and malignant retroperitoneal fibrosis are reported. Especially in idiopathic fibrosis the initial placement of percutaneous nephrostomy and long-term immunosuppression is the treatment of choice. In the follow-up ultrasonography and computerized tomography are valuable methods.


Relative perceptions of prevalence, impact and importance of photosensitisation in Australian livestock: A survey of veterinarians, livestock traders and livestock producers.
To investigate the relative differences in the perceptions and awareness of outbreaks of photosensitisation in Australian livestock stakeholders, including veterinarians, livestock traders and producers. A questionnaire was developed and circulated to livestock veterinarians, producers and traders in Australia via email addresses obtained from public access sources. The questionnaire was designed to evaluate participants' awareness and perception of health, welfare, and production issues associated with outbreaks of photosensitisation and towards the incidence and importance of photosensitisation in livestock. One hundred and twenty-eight online responses were received in total. Nearly half of the respondents (49.0%) indicated they would encounter 1-3 outbreaks annually. The majority of veterinarian and livestock producers stated that outbreaks of photosensitisation were common and economically important, with cattle and sheep being equally considered as susceptible species to this condition, and secondary (hepatogeneous) photosensitisation is the most common type. This survey confirms the anecdotal evidence that photosensitisation in livestock in Australia is commonly encountered by veterinarians and livestock producers. However, there is no industry-wide common acceptance of the issue, broader opinions should be canvassed when considering impacts on stakeholders regarding photosensitisation outbreaks in livestock in Australia or abroad in the future.


Swing-phase pelvis perturbation improves dynamic lateral balance during walking in individuals with spinal cord injury.
The purpose of this study was to determine whether the control of lateral balance can be improved by applying repeated lateral perturbation force to the pelvis during swing versus stance phase walking in individuals with spinal cord injury (SCI). Fourteen individuals with incomplete SCI were recruited in this study. Each participant visited the lab once and was tested in two experimental sessions that consisted of (1) treadmill walking with bilateral perturbation force applied to the pelvis in the lateral direction during either swing or stance phase of each leg and (2) overground walking pre- and post-treadmill walking. Applying the swing-phase perturbation during walking induced a greater increase in the muscle activation of hip abductors and ankle plantar flexors and a greater improvement in lateral balance control after the removal of perturbation force, in comparison to the results of the stance-phase perturbation condition (P ≤ 0.03). Participants also exhibited a greater reduction in overground step width and a greater improvement in overground walking speed after a session of treadmill walking practice with the swing-phase perturbation, compared with the result of the stance-phase perturbation (P = 0.01). These findings suggest that applying perturbation force to the pelvis during the swing phase of gait while walking may enhance muscle activities of hip abductors and improve lateral balance control in individuals with SCI. A walking practice with the swing-phase pelvis perturbation can be used as a rehabilitation approach to improve the control of lateral balance during walking in people with SCI.


The use of the internal pudendal artery perforator flap after abdominoperineal reconstruction: A single center study.
Abdominoperineal resection (APR) is still a valuable option in the presence of cancer recurrences or salvage surgery. Primary perineal closure after conventional APR curries a high rate of wound complications. A multidisciplinary approach with perineal soft tissue reconstruction surgical time improves the immediate and long-term prognosis of these patients. The aim of the study is to report our experience with the use of the internal pudendal artery perforator flap in perineal region reconstruction after APR. We performed 11 perineal region reconstructions after conventional APR between September 2016 and December 2020. In 8 cases the reconstruction was performed on previously irradiated tissues while in 2 cases the radiotherapy was carried out on the perineal tissues solely for adjuvant therapy. A rotation perforating flap was harvested in 8 cases, an advance island flap in 2 cases, and a propeller type in one case. All 11 flaps survived with no immediate postoperative major complications. Only one case showed dehiscence of the donor site wound healed with conservative treatment. Average hospitalization time was 11 days internal pudendal artery perforator flap represents a valid and reliable reconstructive solution after APR showing low complication rates and minimal donor site morbidity even in patients with previous radiotherapy.


Pancreatic adenocarcinoma: A simple CT score for predicting margin-positive resection in patients with resectable disease.
Negative-margin status is a prognostic indicator for long-term survival following curative intent resection for pancreatic adenocarcinoma. Patients at increased risk for positive-margin resections may benefit from neoadjuvant chemotherapy prior to resection. We retrospectively analyzed preoperative computed-tomography (CT) scans in 108 consecutive patients that underwent curative intent resection for a resectable pancreatic ductal adenocarcinoma from 2009 to 2016 in two academic hospitals. Two radiologists independently staged the tumor, including tumor location, size, and tumor-to-superior mesenteric/portal vein (SMV/PV) contact. Uni and multivariate analysis were performed to identify independent predictors of an R1 resection. Twenty-nine patients had an R1 resection (26.9%). Tumor size, location, and presence of tumor-to-SMV/PV contact were significantly associated with an R1 resection. In multivariate analysis, the independent parameters associated with resection status were: tumor size (R2=9.7), and tumor location (neck R2=6.6; pancreaticoduodenal interface R2=4.4; uncinate process R2=4.1), but not tumor-to-SMV/PV contact (R2=0.1, p=0.7). A simple CT score was built based on tumor size and location. Patients with an R0 resectability score ≥3, i.e. patients with tumor size ≥30mm (except when tumor location is at the pancreatico-duodenal interface) or patients with tumor size ≥20mm AND tumor located in the uncinate process or neck, were at high-risk of an R1 resection (AUC, 0.82; sensitivity, 79%; specificity, 76%). This score also showed good diagnostic performances for predicting an R1 resection involving the medial resection margin only (AUC, 0.85). A simple score based on tumor location and size can accurately predict patients at high-risk of an R1 resection.


Effects of alcohol-free beer on lipid profile and parameters of oxidative stress and inflammation in elderly women.
We assessed the influence of alcohol-free beer on factors implicated in atherosclerosis, such as lipid profile, oxidative stress parameters, and proinflammatory cytokines, in postmenopausal women, a population particularly at risk for atherosclerotic disease. The study was carried out in 29 nuns, 58 to 73 y old, who live in a convent with a disciplined, regular, and homogeneous lifestyle. The nuns maintained their habits and diet routine, but their meals were supplemented with 500 mL/d of alcohol-free beer (0.0%) divided into two doses over a 45-d period. Lipid profile, inflammatory markers such as C-reactive protein, interleukins 1 and 6, and tumor necrosis factor-alpha, and parameters of oxidative metabolism were determined before and after the study period. There were no differences in the levels of C-reactive protein and proinflammatory cytokines after diet supplementation. The antibody titers to oxidized low-density lipoprotein were significant lower (P < 0.05), and thiobarbituric acid-reactive substances (-18%, P < 0.001) and plasma carbonyl group content (-21%, P < 0.001) were decreased when compared with initial values. Increases in alpha-tocopherol levels (+9%, P < 0.05) and erythrocytic glutathione levels (+29%, P < 0.001) were also noted. With respect to lipid profile, only subjects with cholesterol levels higher than 240 mg/dL showed lower levels after supplementation. Consumption of non-alcoholic beer produces a decrease in oxidative stress that can have a beneficial impact on cardiovascular risk; however, the circulating concentrations of inflammatory mediators involved in its pathophysiology remained unchanged.


Beyond the surface: accounting for confounders in understanding the link between collectivism and COVID-19 pandemic in the United States.
According to the parasite-stress theory, collectivism serves as a trait of ingroup assortative sociality, providing defense against infectious diseases. This study investigated the association between cultural collectivism and COVID-19 severity at the state (Study 1: N = 51), county (Study 2: N = 3,133), and daily (Study 3: N = 52,806) levels from the beginning of 2020 to the end of 2022. State-level collectivism was assessed using two distinct measures: the U.S. collectivism index, focusing on social interconnectedness and interdependence, and the subjective-culture individualism-collectivism index (reversed), capturing attitudes and beliefs related to religion, abortion, and same-sex marriage. By employing random-intercept multilevel models, the results demonstrated significant and negative effects of state-level collectivism, as measured by the U.S collectivism index, on COVID-19 cases per million, COVID-19 deaths per million, and composite COVID-19 severity index, after controlling for confounding factors, such as socioeconomic development, ecological threats, disease protective behaviors, cultural norms, and political influences. A mini meta-analysis (Study 4: N = 9) confirmed the significance of these effects across studies. These findings supported the proactive role of collectivism in defending against the novel coronavirus in the United States, aligning with the parasite-stress theory of sociality. However, the subjective-culture individualism-collectivism index (reversed) did not exhibit a significant relationship with COVID-19 severity when confounding factors were considered. The high correlation between the subjective-culture individualism-collectivism index (reversed) and the controlled variables suggested shared variance that could diminish its impact on COVID-19 outcomes. Accordingly, the present findings underscore the significance of accounting for confounding factors when examining the association between collectivism and COVID-19 severity at population level. By considering relevant confounding factors, researchers could gain a comprehensive understanding of the complex interplay between cultural collectivism and its influence on COVID-19 severity. Overall, this research contributes to our understanding of how cultural collectivism shapes the COVID-19 pandemic in the United States, emphasizing the importance of adjusting for confounding effects in population level studies.


Measurement of oxidant and antioxidant levels in liver tissue obtained from patients with liver transplantation: A case-control study.
This study aimed to compare oxidant and antioxidant substance accumulation in the liver tissues of patients with chronic liver disease (recipients) who underwent liver transplantation (LT) with living liver donors (LLDs) who underwent living donor hepatectomy (LDH). This prospective study included 160 recipients (LT group) and 40 LLDs (LLD group). During surgery, a piece of liver tissue measuring a minimum of 10 × 10 mm was obtained from the edge of the right lobe of the liver of recipients and LLDs, incubated for 10 min in saline to remove blood, and stored at -70 °C until biochemical analysis was performed. Catalase (CAT), glutathione peroxidase (GSH-Px), superoxide dismutase (SOD), myeloperoxidase (MPO), prolidase, reduced glutathione (GSH), malondialdehyde (MDA), total oxidant status (TOS), total antioxidant status (TAS), oxidative stress index (OSI), total thiol, native thiol, and disulfide levels were measured in stored liver tissues. There was a statistically significant difference between LT and LLD groups in terms of age (p < 0.001), body mass index (p = 0.019), GSH-Px (p < 0.001), SOD (p = 0.001), MPO (p < 0.001), prolidase (p < 0.001), GSH (p < 0.001), and MDA (p = 0.003) values in favor of the LT group. Furthermore, there was a statistically significant difference between LT and LLD groups in terms of CAT (p < 0.001), TAS (p < 0.001), TOS (p < 0.001), OSI (p < 0.001), total thiol (p < 0.001), native thiol (p < 0.001), and disulfide (p < 0.001) values in favor of the LLD group. There were no differences between the groups in terms of sex. This study demonstrated that it is possible to assess the extent of oxidative stress in liver tissues by measuring the levels of antioxidant enzymes, oxidants, or the end-products of oxidative stress. With the use of optimum and minimally invasive methods, quantifying these molecules will potentially help evaluate the extent of liver disease and prognostication of liver cirrhosis.


Novel treatment of ovarian cancer cell lines with Imatinib mesylate combined with Paclitaxel and Carboplatin leads to receptor-mediated antiproliferative effects.
Imatinib is a small molecule inhibiting the tyrosine kinases bcr-abl, c-kit, PDGFR-alpha and PDGFR-beta. Investigations were performed to screen ovarian cancer cell lines and tumor samples for target receptor expression. Effects of Imatinib on cell proliferation and apoptosis induction were measured with and without additional cytotoxic agents. Expression patterns of abl, c-kit, PDGFR-alpha and PDGFR-beta (Imatinib targets) were studied in 5 cell lines and 111 tissue arrays by PCR and immunohistochemistry. Proliferation assays were performed with single agent Imatinib or combined with Paclitaxel and Carboplatin. Apoptosis was measured by DNA fragmentation. All cell lines expressed abl and PDGFR-beta. C-kit was only expressed in 2/5 cell lines and PDGFR-alpha in 4/5. Imatinib reduced cell growth and lead to pro-apoptotic changes. Combination of Carboplatin, Paclitaxel and Imatinib showed synergistic activity. Our results suggest that Imatinib may be useful for the specific treatment of ovarian cancer as an add-on to conventional chemotherapy.


Textual inference for eligibility criteria resolution in clinical trials.
Clinical trials are essential for determining whether new interventions are effective. In order to determine the eligibility of patients to enroll into these trials, clinical trial coordinators often perform a manual review of clinical notes in the electronic health record of patients. This is a very time-consuming and exhausting task. Efforts in this process can be expedited if these coordinators are directed toward specific parts of the text that are relevant for eligibility determination. In this study, we describe the creation of a dataset that can be used to evaluate automated methods capable of identifying sentences in a note that are relevant for screening a patient's eligibility in clinical trials. Using this dataset, we also present results for four simple methods in natural language processing that can be used to automate this task. We found that this is a challenging task (maximum F-score=26.25), but it is a promising direction for further research.


Thiazole derivative based topical nanoemulgel for inhibition of bacterial virulence in surface infections.
Antimicrobial resistance emerged as a global challenge owing to limited therapeutic options to control infections. Pseudomonas aeruginosa, an MDR pathogen already developed resistance against many conventional antibiotics. An "anti-virulence strategy" that targets bacterial virulence rather than growth proves effective against drug-resistant pathogens. Here, we used a structure-based drug design approach to identify lead molecules using the LasR receptor protein of P. aeruginosa as a target responsible for virulence production in this bacterium. From the identified hits, we developed lead-based nanoformulation and investigated its effectiveness for treating the P. aeruginosa associated surface-infection in-vivo. First, TC-based nanoemulsions were fabricated by high-pressure homogenization and evaluated for various in vitro parameters. The optimized nanoemulsions were thereby utilized to prepare NEG. The nanoemulsion (F3) exhibited low droplet size (51.04±1.88 nm), PDI (0.065±1.14), and negative zeta potential (-33.65±0.82 mV). In animals, topical application of NEG-3 demonstrated significant improvement on skin permeability (459±10.17 µg), drug influx (18.99±0.76 μg/cm2 hr), and repressed the CFU of P. aeruginosa induced-surface infection (P≤ 0.001). The histology of rat skin demonstrated a significant effect for groups treated with TC-based NEGs as compared with a negative control group, whereas no significant effect was seen on rat liver indicating low systemic exposure to the drug. Also, NEG3 showed no significant changes under different stability conditions after 3 months. TC-based NEGs open up the possibility of a more effective way to combat serious surface infections caused by P. aeruginosa.


MTHFR and MTRR Genetic Polymorphism of Methotrexate Therapy Outcomes in Early Rheumatoid Arthritis.
Methotrexate (MTX) is used as an anchor drug for the treatment of rheumatoid arthritis (RA) and there may be differences in drug action between genotypes. The purpose of this study was to investigate the relationship between clinical efficacy response and disease activity of MTX monotherapy with methylenetetrahydrofolate reductase (MTHFR) and methionine synthase reductase (MTRR) polymorphisms. In the study, a population of 32 patients in East China with early RA fulfilling the diagnostic standards of the American College of Rheumatology (ACR) were enrolled, all of them received MTX monotherapy. Genotyping of patients MTHFR C677T and A1298C, MTRR A66G using tetra-primer ARMS-PCR method and sanger sequencing to verify its accuracy. The distribution of three polymorphic genotypes that were studied is in accordance with the Hardy-Weinberg genetic equilibrium. The patient pathology variables smoke (OR = 0.088, P = 0.037), drink alcohol (OR = 0.039, P = 0.016) and males (OR = 0.088, P = 0.037) were significantly associated with non-response to MTX. Genotype, allele distribution and genetic statistical models were not found to be related to MTX treatment response and disease activity in both the response groups and non-response groups. Our findings suggest that the MTHFR C677T, MTHFR A1298C and MTRR A66G polymorphisms may not predict MTX clinical treatment response and disease activity in patients with early RA. The study revealed that smoke, alcohol, and males were possible influential factors for MTX non-response.


Turn on fluorescence sensing of vapor phase electron donating amines via tetraphenylporphyrin or metallophenylporphrin doped polyfluorene.
A sensitive, selective, reversible, and easy performance way of detecting electron donating volatile amines such as abused drug methamphetamine (MAPA) has been developed.


The relationship of serum IgA concentration to human immunodeficiency virus (HIV) infection: a cross-sectional study of HIV-seropositive individuals detected by screening in the United States Air Force.
Serum immunoglobulins were measured in 107 patients with human immunodeficiency virus seropositivity. Each patient was categorized by the Walter Reed staging classification and serum concentrations of immunoglobulins were compared with patient staging. Serum IgM concentrations were normal in all but nine patients. Serum IgG concentrations were elevated in 74 of 107 patients, with no significant differences noted between different stages of disease severity. Serum IgA concentrations were elevated in 38 of 107 patients, with a significant relationship noted between increasing staging category and increasing serum IgA concentration (p = 0.0001). Serum IgA concentrations in patients with human immunodeficiency virus seropositivity may be a useful marker of immunologic progression of disease.


MGAT: Multi-view Graph Attention Networks.
Multi-view graph embedding is aimed at learning low-dimensional representations of nodes that capture various relationships in a multi-view network, where each view represents a type of relationship among nodes. Multitudes of existing graph embedding approaches concentrate on single-view networks, that can only characterize one simple type of proximity relationships among objects. However, most of the real-world complex systems possess multiple types of relationships among entities. In this paper, a novel approach of graph embedding for multi-view networks is proposed, named Multi-view Graph Attention Networks (MGAT). We explore an attention-based architecture for learning node representations from each single view, the network parameters of which are constrained by a novel regularization term. In order to collaboratively integrate multiple types of relationships in different views, a view-focused attention method is explored to aggregate the view-wise node representations. We evaluate the proposed algorithm on several real-world datasets, and it demonstrates that the proposed approach outperforms existing state-of-the-art baselines.


Iron deficiency can upregulate expression of transferrin receptor at both the mRNA and protein level.
Expression of the transferrin receptor (TfR) is controlled essentially by post-transcriptional regulation, which is mediated by the interaction between iron regulatory proteins (IRPs) and iron-responsive elements (IREs) located in the 3'-untranslated region (UTR) of TfR mRNA. We examined whether additional controls of expression might occur by investigating the regulation of TfR in the absence of its' IREs by cloning 3'-UTR truncated TfR cDNA (TfRDeltaIRE) into pcDNA3.1(+) and stably expressing it in CHO-TRVb (Chinese Hamster Ovary, TfR variant cells, clone b) cells which have no endogenous TfR. Both the surface and the total cell TfR protein levels increased significantly after treating the stably transfected cells with the iron chelator desferrioxamine (DFO) compared with the control cells. In contrast, expression of the transferrin receptor 2 (TfR2), which was also cloned in the same vector and stably expressed in the TRVb-CHO cells, was not regulated by iron chelation. In addition, TfR2 fused to the 3'-UTR of TfR (TfR2-IRE) was cloned into the same vector and stably expressed in the CHO-TRVb cells. A comparison showed that expression of full-length TfR and TfR2-IRE increased by fivefold and twofold, respectively, after addition of DFO. Further experiments showed that TRVb-CHO cells, which were stably transfected with TfRDeltaIRE and exposed to either normal medium or DFO, resulted in similar levels of TfR mRNA, but the TfR protein biosynthetic rate increased with iron chelation. In summary, expression of TfR in cells placed in an iron-deficient milieu can increase by a mechanism which is independent of the IREs of TfR.


Anaerobic digestion of food waste - Challenges and opportunities.
The disposal of large amounts of food waste has caused significant environmental pollution and financial costs globally. Compared with traditional disposal methods (i.e., landfilling, incineration, and composting), anaerobic digestion (AD) is a promising technology for food waste management, but has not yet been fully applied due to a few technical and social challenges. This paper summarizes the quantity, composition, and methane potential of various types of food waste. Recent research on different strategies to enhance AD of food waste, including co-digestion, addition of micronutrients, control of foaming, and process design, is discussed. It is envisaged that AD of food waste could be combined with an existing AD facility or be integrated with the production of value-added products to reduce costs and increase revenue. Further understanding of the fundamental biological and physicochemical processes in AD is required to improve the technology.


Immobilization of paraoxonase onto chitosan and its characterization.
Paraoxonase was covalently immobilized onto a glutaraldehyde containing amino group functionalized chitosan surface by chemical immobilization at pH 8.0. The amount of covalently bound hPON1 was found to be 32 mg/10 chitosan beads. The properties of immobilized enzyme were investigated and compared to those of free enzyme. The effects of various parameters such as pH, temperature, heat, and storage stability on immobilized enzyme were investigated. Kinetic parameters of the immobilized enzyme were also evaluated. Thermal and storage stability experiments were carried out. It was observed that the immobilized enzyme had longer storage stability and retained 50 % of its initial activity during 26 days.


RNAi: antiviral therapy against dengue virus.
Dengue virus infection has become a global threat affecting around 100 countries in the world. Currently, there is no licensed antiviral agent available against dengue. Thus, there is a strong need to develop therapeutic strategies that can tackle this life threatening disease. RNA interference is an important and effective gene silencing process which degrades targeted RNA by a sequence specific process. Several studies have been conducted during the last decade to evaluate the efficiency of siRNA in inhibiting dengue virus replication. This review summarizes siRNAs as a therapeutic approach against dengue virus serotypes and concludes that siRNAs against virus and host genes can be next generation treatment of dengue virus infection.


Posttreatment imaging in head and neck cancer.
Posttreatment imaging is done when a recurrent tumour is suspected, to confirm the presence of such a lesion and to determine its extent. The extent of a recurrent cancer is important information for determining the possibility of salvage therapy. Imaging may also be used to monitor tumour response and to try to detect recurrent or persistent disease before it becomes clinically evident, possibly with a better chance for successful salvage. This article reviews the expected imaging findings after treatment of head and neck squamous cell cancer, and how to differentiate these from persistent or recurrent cancer. The relative value of anatomical and biological imaging modalities, including newer techniques such as diffusion-weighted magnetic resonance imaging, is addressed. The imaging findings in treatment-induced complications, such as tissue necrosis, sometimes difficult to differentiate from cancer, are explained.


Plantain starch granules morphology, crystallinity, structure transition, and size evolution upon acid hydrolysis.
Plantain native starch was hydrolysed with sulphuric acid for twenty days. Hydrolysis kinetics was described by a logistic function, with a zero-order rate during the first seven days, followed by a slower kinetics dynamics at longer times. X-ray diffraction results revealed a that gradual increase in crystallinity occurred during the first seven days, followed by a decrease to values similar to those found in the native starch. Differential scanning calorimetry analysis suggested a sharp structure transition by the seventh day probably due to a molecular rearrangement of the starch blocklets and inhomogeneous erosion of the amorphous regions and semi crystalline lamellae. Scanning electron micrographs showed that starch granules morphology was continually degraded from an initial oval-like shape to irregular shapes due to aggregation effects. Granule size distribution broadened as hydrolysis time proceeded probably due to fragmentation and agglomeration phenomena of the hydrolysed starch granules.


[Sonographic representation of fibroses (a contribution to the problem of tissue differentiation) (author's transl)].
Twelve patients with radiogenic fibroses were submitted to a sonographic examination by means of a grey-scale compound-scanner. As these skin fibroses are well suited for inspection and palpation, they are qualified to serve as a model with regard to the problem of sonographic tissue differentiation. Fibroses of medium and high degree are determined by characteristic properties in the B picture, whereas fibroses of low degree cannot be recorded by this technique.


Identifying Otosclerosis with Aural Acoustical Tests of Absorbance, Group Delay, Acoustic Reflex Threshold, and Otoacoustic Emissions.
Otosclerosis is a progressive middle-ear disease that affects conductive transmission through the middle ear. Ear-canal acoustic tests may be useful in the diagnosis of conductive disorders. This study addressed the degree to which results from a battery of ear-canal tests, which include wideband reflectance, acoustic stapedius muscle reflex threshold (ASRT), and transient evoked otoacoustic emissions (TEOAEs), were effective in quantifying a risk of otosclerosis and in evaluating middle-ear function in ears after surgical intervention for otosclerosis. To evaluate the ability of the test battery to classify ears as normal or otosclerotic, measure the accuracy of reflectance in classifying ears as normal or otosclerotic, and evaluate the similarity of responses in normal ears compared with ears after surgical intervention for otosclerosis. A quasi-experimental cross-sectional study incorporating case control was used. Three groups were studied: one diagnosed with otosclerosis before corrective surgery, a group that received corrective surgery for otosclerosis, and a control group. The test groups included 23 ears (13 right and 10 left) with normal hearing from 16 participants (4 male and 12 female), 12 ears (7 right and 5 left) diagnosed with otosclerosis from 9 participants (3 male and 6 female), and 13 ears (4 right and 9 left) after surgical intervention from 10 participants (2 male and 8 female). Participants received audiometric evaluations and clinical immittance testing. Experimental tests performed included ASRT tests with wideband reference signal (0.25-8 kHz), reflectance tests (0.25-8 kHz), which were parameterized by absorbance and group delay at ambient pressure and at swept tympanometric pressures, and TEOAE tests using chirp stimuli (1-8 kHz). ASRTs were measured in ipsilateral and contralateral conditions using tonal and broadband noise activators. Experimental ASRT tests were based on the difference in wideband-absorbed sound power before and after presenting the activator. Diagnostic accuracy to classify ears as otosclerotic or normal was quantified by the area under the receiver operating characteristic curve (AUC) for univariate and multivariate reflectance tests. The multivariate predictor used a small number of input reflectance variables, each having a large AUC, in a principal components analysis to create independent variables and followed by a logistic regression procedure to classify the test ears. Relative to the results in normal ears, diagnosed otosclerosis ears more frequently showed absent TEOAEs and ASRTs, reduced ambient absorbance at 4 kHz, and a different pattern of tympanometric absorbance and group delay (absorbance increased at 2.8 kHz at the positive-pressure tail and decreased at 0.7-1 kHz at the peak pressure, whereas group delay decreased at positive and negative-pressure tails from 0.35-0.7 kHz, and at 2.8-4 kHz at positive-pressure tail). Using a multivariate predictor with three reflectance variables, tympanometric reflectance (AUC = 0.95) was more accurate than ambient reflectance (AUC = 0.88) in classifying ears as normal or otosclerotic. Reflectance provides a middle-ear test that is sensitive to classifying ears as otosclerotic or normal, which may be useful in clinical applications.


Prognostic and predictive value of tumor-infiltrating lymphocytes in breast cancer: a systematic review and meta-analysis.
Breast cancer is the most common invasive cancer to affect women in the world. Studies showed tumor-infiltrating lymphocytes can exhibit both beneficial and harmful effects on the biology and clinical outcome of breast cancer, the conclusion still remains incomplete. Here, we conducted a meta-analysis to evaluate the relationship between tumor-infiltrating lymphocytes and breast cancer. A comprehensive search strategy was used to search relevant literatures in PubMed and the ISI Web of Science. The correlation among TILs and breast cancer clinicopathological features and prognosis was analyzed by using Review Manager 5.3 and Stata 12.0. Seventeen eligible studies consisting of 12,968 participants were included. We found that higher value of tumor-infiltrating lymphocytes had no relationship with breast cancer clinicopathological variables. Interestingly, it was correlated with response to neoadjuvant chemotherapy in majority (pooled RR 2.43, 95% CI 1.99-2.97). Moreover, higher value of total tumor-infiltrating lymphocytes (both intraepithelial and stromal) was associated with better prognosis (pooled HR 0.88, 95% CI 0.83-0.94), whereas some subtypes predicted a worse prognosis. This meta-analysis indicated that high value of total TILs is not associated with breast cancer clinicopathological features, but can predict a favorable outcome for neoadjuvant chemotherapy in majority except for hormone receptor (-) subtype. And higher total TILs (both intraepithelial TILs and stromal TILs) may be the potential better prognostic indicators, while some subtypes like PD-1(+) TILs and Foxp3(+) TILs show a worse prognosis.


EGFR trans-activation mediates pleiotrophin-induced activation of Akt and Erk in cultured osteoblasts.
Pleiotrophin (Ptn) plays an important role in bone growth through regulating osteoblasts' functions. The underlying signaling mechanisms are not fully understood. In the current study, we found that Ptn induced heparin-binding epidermal growth factor (HB-EGF) release to trans-activate EGF-receptor (EGFR) in both primary osteoblasts and osteoblast-like MC3T3-E1 cells. Meanwhile, Ptn activated Akt and Erk signalings in cultured osteoblasts. The EGFR inhibitor AG1478 as well as the monoclonal antibody against HB-EGF (anti-HB-EGF) significantly inhibited Ptn-induced EGFR activation and Akt and Erk phosphorylations in MC3T3-E1 cells and primary osteoblasts. Further, EGFR siRNA depletion or dominant negative mutation suppressed also Akt and Erk activation in MC3T3-E1 cells. Finally, we observed that Ptn increased alkaline phosphatase (ALP) activity and inhibited dexamethasone (Dex)-induced cell death in both MC3T3-E1 cells and primary osteoblasts, such effects were alleviated by AG1478 or anti-HB-EGF. Together, these results suggest that Ptn-induced Akt/Erk activation and some of its pleiotropic functions are mediated by EGFR trans-activation in cultured osteoblasts.


A rational route to hybrid aptamer-molecularly imprinted magnetic nanoprobe for recognition of protein biomarkers in human serum.
Although antibody has played a great role in highly specific recognition of protein biomarkers, it faces poor stability, reproducibility, high-cost and time-consuming preparation, etc. Here, aptamer and molecularly imprinted polymers (MIPs), both as promising substitutes of antibody, were integrated onto magnetic nanoparticles by Au-S bonds and SiO2 as imprinted layer for preparing a new nanoprobe. Highly specific and sensitive recognition of different protein biomarkers, such as insulin for diabetes and alpha-fetoprotein (AFP) for hepatic carcinoma, were achieved respectively by the system of combining hybrid aptamer-molecularly imprinted magnetic nanoprobe and mass spectrometry. With the double affinities offered by aptamer-MIPs, insulin can be detected at 0.5 ng mL-1 in human serum dilution, the equlibrium dissociation constant between nanoprobe and insulin is measured as 23.61 ± 2.27 μM. Likewise, AFP can be sufficiently detected in human saliva dilution from 1000 ng mL-1 to 20 ng mL-1, and two patients with hepatic carcinoma are discriminated from healthy person due to the abnormally high expression of AFP in serum.


Gastric schwannoma after Nissen fundoplication. A rare complication?
Surgical repair of an hiatal hernia results in changes in the local anatomy of the cardia and fundus that may be difficult to interpret by radiological examination. Endoscopy can clarify the radiological changes resulting from surgery, such as pseudodiverticula and pseudotumors, and, when conducted as part of the routine follow-up program, may reveal uncommon complications.


Lowering of plasma free tryptophan in normal and portacaval shunt dogs.
The purpose of this study was to develop a method which would produce immediate and sustained lowering of plasma free tryptophan. Glucose, insulin, and mixtures of the two in different concentrations were infused into dogs over a period of 6 hr. Blood was sampled during the course of the infusion for assay of plasma free and total tryptophan, free fatty acids, glucose, and insulin. The infusate found to produce the most significant and sustained reduction in plasma free tryptophan in normal dogs was a mixture of 25% glucose and insulin. The lowering ranged from 26 to 47% during the course of the infusion. When the same infusion mixture was administered to dogs with established portacaval shunts, and elevated plasma free tryptophan concentrations (3.3 +/- 0.3 micrograms/ml compared to normal dogs which had 1.9 +/- 0.1 micrograms/ml), there was a 35% reduction to normal levels (2.0-2.2 micrograms/ml). A glucose-insulin mixture has, therefore, been found which, upon infusion into dogs, significantly lowers plasma free tryptophan levels. The effect of such an infusion on the plasma levels of free tryptophan, and the clinical course of patients with hepatic encephalopathy remains to be determined.


Growth hormone effects on creatine uptake by muscle in the hypophysectomized rat.
Specific radioactive enzyme assays were developed to measure the effect of growth hormone on kidney transamidinase and liver methyltransferase in the hypophysectomized rat. In contrast to minimal changes (20%) in liver methyltransferase, kidney transamidinase was decreased threefold in the hypophysectomized rat. Enzyme activities were equal to normal values in those rats receiving growth hormone for three days. The formation of creatine from radioactive precursors and the uptake of 14C-creatine in muscle was examined under these conditions. After injection of 14C-arginine in the hypophysectomized rat, the 14C-creatine content of muscle was greatly decreased compared to sham operated controls and the 14C-creatine content was normal after growth hormone administration. After injection of 14C-guanidoacetate and of 14-creatine, the 14C-creatine content of muscle was decreased in the hypophysectomized rat, but was equal to sham control values in rats receiving growth hormone. These studies indicate that the uptake of newly synthesized creatine by muscle is impaired in the hypophysectomized rat and that growth hormone can have a role in controlling the rate of creatine uptake by muscle in addition to its effect on kidney transamidinase and to other factors involved in creatine metabolism.


Statistical pattern detection in univariate time series of intensive care on-line monitoring data.
To determine how different mathematical time series approaches can be implemented for the detection of qualitative patterns in physiologic monitoring data, and which of these approaches could be suitable as a basis for future bedside time series analysis. Off-line time series analysis. Surgical intensive care unit of a teaching hospital. 19 patients requiring hemodynamic monitoring with a pulmonary artery catheter. None. Hemodynamic data were acquired in 1-min intervals from a clinical information system and exported into statistical software for further analysis. Altogether, 134 time series for heart rate, mean arterial pressure, and mean pulmonary artery pressure were visually classified by a senior intensivist into five patterns: no change, outlier, temporary level change, permanent level change, and trend. The same series were analyzed with low-order autoregressive (AR) models and with phase space (PS) models. The resulting classifications from both models were compared to the initial classification. Outliers and level changes were detected in most instances with both methods. Trend detection could only be done indirectly. Both methods were more sensitive to pattern changes than they were clinically relevant. Especially with outlier detection, 95% confidence intervals were too close. AR models require direct user interaction, whereas PS models offer opportunities for fully automated time series analysis in this context. Statistical patterns in univariate intensive care time series can reliably be detected with AR models and with PS models. For most bedside problems both methods are too sensitive. AR models are highly interactive, and both methods require that users have an explicit knowledge of statistics. While AR models and PS models can be extremely useful in the scientific off-line analysis, routine bedside clinical use cannot yet be recommended.


The use of cyclohexanone as a "derivatizing" reagent for the GC-MS detection of amphetamines and ephedrines in seizures and the urine.
A GC-MS method has been developed for the detection of amphetamine, methamphetamine, and the ephedrines, in seizures and the urine, based on on-GC condensation (derivatization) with cyclohexanone. The method is simple: the dried seizure material or the urine extract was mixed with cyclohexanone and injected into the GC-MS. The method was found to be superior to the methods based on acyl and trimethylsilyl (TMS) derivatization. Unlike for the acyl and TMS derivatives, the molecular and fragment ions of the cyclohexanone condensation products (cyclohexanone derivatives) were of substantial abundance, a useful property in unambiguous compound characterization. Furthermore, the high stability of the "derivatizing" reagent, cyclohexanone, compared with acyl and TMS derivatizing reagents, is a useful property in method development. The present method has proved selective and, tentatively, sensitive enough in the following areas (where methods based on acyl and TMS derivatization, as tested in this laboratory, have failed): (a) detection of amphetamine as a metabolite of methamphetamine; (b) detection of norpseudoephedrine as a metabolite of pseudoephedrine; (c) detection of amphetamine as an impurity of methamphetamine; (d) detection of cathine (norephedrine) as a constituent of Khat leaves; and (e) differentiation of Khat use from phenylpropanolamine use.


You are a medical photographer and your brief is wide.
A reflection on past product advertisements which were created for earlier versions of this journal and were specifically targeted at the Medical Photographer.