Accelerated radiotherapy and concurrent chemotherapy for patients with contralateral central or mediastinal lung cancer relapse after pneumonectomy.
Treatment options are very limited for patients with lung cancer who experience contralateral central or mediastinal relapse following pneumonectomy. We present results of an accelerated salvage chemoradiotherapy regimen. Patients with localized contralateral central intrapulmonary or mediastinal relapse after pneumonectomy were offered combined chemoradiotherapy including concurrent weekly cisplatin (25 mg/m(2)) and accelerated radiotherapy [accelerated fractionated (AF), 60 Gy, 8×2 Gy per week] to reduce time for repopulation. Based on 4D-CT-planning, patients were irradiated using multifield intensity-modulated radiotherapy (IMRT) or helical tomotherapy. Between 10/2011 and 12/2012, seven patients were treated. Initial stages were IIB/IIIA/IIIB: 3/1/3; histopathological subtypes scc/adeno/large cell: 4/1/2. Tumour relapses were located in mediastinal nodal stations in five patients with endobronchial tumour in three patients. The remaining patients had contralateral central tumour relapses. All patients received 60 Gy (AF), six patients received concurrent chemotherapy. Median dose to the remaining contralateral lung, esophagus, and spinal cord was 6.8 (3.3-11.4), 8.0 (5.1-15.5), and 7.6 (2.8-31.2) Gy, respectively. With a median follow-up of 29 [17-32] months, no esophageal or pulmonary toxicity exceeding grade 2 [Common terminology criteria for adverse events (CTC-AE) v. 3] was observed. Median survival was 17.2 months, local in-field control at 12 months 80%. Only two local recurrences were observed, both in combination with out-field metastases. This intensified accelerated chemoradiotherapy schedule was safely applicable and offers a curative chance in these pretreated frail lung cancer patients.


[Surgical procedures to stabilize the upper cervical spine].
The options for surgical treatment of injuries to the upper cervical spine have increased considerably in recent years. A distinction can be made between two forms of surgical stabilization. Techniques of osteosynthesis serve to reconstruct the injured structure with the goal of maintaining mobility of the upper cervical spine. A spondylodesis, that can be performed at the atlantoaxial or occipitoatlantoaxial joint, aims to stabilize the upper cervical spine by fusion techniques. This article describes the surgical procedures for both treatment principles with regard to the indications, techniques, and complications.


The amino acid requirements of Corynebacterium diphtheriae PW 8 substrain CN 2000.
To determine the amino acid requirement and utilization pattern of Corynebacterium diphtheriae during growth and toxin production. Comparing across different batches of beef-based media, the growth and toxin yield were correlated significantly with nine of the amino acids. The amino acid utilization pattern during growth of C. diphtheriae further showed that only four of the nine amino acids, namely cystine, histidine, aspartate and methionine, were critical for growth of the vaccine strain. Further investigations using synthetic media with combinations of amino acid supplements demonstrated that among the four, cystine was the most growth limiting. Only certain amino acids are critical for growth and toxin production by C. diphtheriae, cystine being the single most important. Owing to the potential threat from Bovine Spongiform Encephalopathy (BSE), a need is recognized by vaccine manufacturers to substitute beef-based production media. An understanding of the specific amino acid requirements would help to develop and optimize alternative production media.


Cytochemical observations in preleukemic states and remission of akute leukemia.
In preleukemia and in remission of acute leukemia abnormal mononuclear cells ("string of bead" cells) have been observed and characterized with cytochemical methods. These cells may be resistant to cytostatic therapy and may be characterized as a source of a newly developing leukemic blast cells. Preleukemia and leukemic remissions seem to be identical states. Based on the morphological and cytochemical parallelity of cells in CFU-c-enriched fractions of the bone marrow and the so called string of bead cells we consider these cells to be closely related to the human commited stem cell.


S1P control of endothelial integrity.
Sphingosine 1-phosphate (S1P), a lipid mediator produced by sphingolipid metabolism, promotes endothelial cell spreading, vascular maturation/stabilization, and barrier function. S1P is present at high concentrations in the circulatory system, whereas in tissues its levels are low. This so-called vascular S1P gradient is essential for S1P to regulate much physiological and pathophysiological progress such as the modulation of vascular permeability. Cellular sources of S1P in blood has only recently begun to be identified. In this review, we summarize the current understanding of S1P in regulating vascular integrity. In particular, we discuss the recent discovery of the endothelium-protective functions of HDL-bound S1P which is chaperoned by apolipoprotein M.


Organization of a medications group for older patients with mental illness.
A medications group for older inpatients with mental illness improved their understanding of and compliance with medication regimens.


Antibodies against Rickettsiaceae in dogs of Setúbal, Portugal.
An indirect fluorescent antibody test was performed on sera collected from dogs housed in the municipal kennel of Setúbal to assess the prevalence of antibodies to Ehrlichia canis, the causative agent of canine ehrlichiosis and to Rickettsia conorii, agent of boutonneuse fever in humans. Two other members of the family Rickettsiaceae, Coxiella burnetii and Rickettsia typhi, were included in the serosurvey. Of the 104 dogs tested, 85.6% had antibodies to R. conorii, 50% to E. canis, 26.9% to R. typhi, and 4.8% to C. burnetii. These high seroprevalence rates of dogs with antibodies all year around against Rickettsiaceae suggest that physicians, public health officers and veterinarians should more frequently consider the diagnosis of these infections in Portugal.


Green Islands - nutrition not predation -an alternative hypothesis.
Mountain birch trees are said to survive as "green islands" around nests of red ants in Finnish Lapland because the ants kill larvae which would defoliate trees during outbreaks of the moth O. autumnata. An alternative hypothesis says that because the ants will concentrate soil nutrients (and possibly ameliorate soil moisture and temperature) in and around their nests, they provide a more favourable site for trees growing nearby. These trees are therefore less stressed and a poorer source of food for defoliators at times of outbreaks. Few if any young O. autumnata larvae survive on the trees which then survive in green islands around ant nests.


Pitfalls in diagnostic imaging of cystic pancreatic masses: a case of true cystic lesion mimicking a mucinous cystadenoma.
Imaging characterization is a frequent topic in diagnostic evaluation of patients with pancreatic cystic lesions. We present a patient with a true pancreatic cyst with internal septation in an adult female. The presence of the internal septum should be considered in the differential diagnosis, in fact in our case CT and MR imaging findings were incorrectly suggestive of mucinous cystadenoma. True pancreatic cyst may show septate architecture and thus for imaging characterization this feature should be considered in the differential diagnosis of cystic pancreatic masses.


Internal Consistency Analysis: a method for studying the accuracy of function assessment for health outcome and quality of life evaluation.
Social, mental and physical function are major components of health outcomes and health related life quality, but the accuracy of function measurement is difficult to study rigorously. Internal Consistency Analysis (ICA) uses multiple sources of evidence from a survey interview to study the accuracy of a classification. It was developed to study function classifications for a general health outcome measure, the Quality of Well-being (QWB) scale. ICA is described and evidence of its utility in improving the classifications needed for the QWB is presented.


The American Psychological Association's Hoffman report allegations of my association with the "CIA torture" program.
Until now, I have not responded to the undocumented and untrue portrayal of me in the Hoffman report, or the newspaper and email accounts of my alleged role in "torture." I have waited several years because I believed that the American Psychological Association leadership would completely disavow the Hoffman report and find a way to restore my reputation as well as that of the other former American Psychological Association presidents and the small number of its senior staff who were also falsely accused. Although this has not yet happened, I remain optimistic that it will. Here I present the facts as they relate to me.


Total Lesion Glycolysis on 18F-FDG PET/CT Is a Better Prognostic Factor Than Tumor Dose on 90Y PET/CT in Patients With Hepatocellular Carcinoma Treated With 90Y Transarterial Radioembolization.
This study aimed to evaluate the prognostic value of metabolic parameters on 18F-FDG PET/CT and tumor dose (TD) on posttreatment 90Y PET/CT in patients with hepatocellular carcinoma (HCC) who underwent 90Y transarterial radioembolization (TARE). Forty-seven HCC patients treated with 90Y TARE were retrospectively enrolled between January 2013 and October 2018. 18F-FDG PET/CT was performed before treatment. Maximum tumor SUV-to-mean normal liver SUV ratio (TLR), metabolic tumor volume (MTV), and total lesion glycolysis (TLG) were measured for each patient. Voxel dosimetry was performed on 90Y PET/CT images to measure TD. The prognostic significance of metabolic parameters on 18F-FDG PET/CT, TD on 90Y PET/CT, and clinical factors for overall survival (OS) was evaluated. In addition, TD on 90Y PET/CT was analyzed in relation to the administered dose of 90Y-labeled microspheres and metabolic parameters on 18F-FDG PET/CT. The median patient age was 57 years, and 37 patients (78.7%) were men. During the follow-up period, 25 patients (53.2%) died. In univariable analysis, Barcelona Clinic Liver Cancer stage C, Child-Pugh score, TD on 90Y PET/CT, TLR, MTV, and TLG were significant prognostic factors affecting OS (P < 0.05). In multivariable analysis, Barcelona Clinic Liver Cancer stage C and high TLG on 18F-FDG PET/CT were independent prognostic factors for OS (P < 0.05). The 1-year OS rates were 72.9% in patients with low TLG and 33.3% in patients with high TLG (P < 0.05). We also found that TD on 90Y PET/CT was not correlated with the administered dose of 90Y-labeled microspheres, but negatively correlated with TLG on pretreatment 18F-FDG PET/CT (P < 0.05). TLG, a parameter incorporating both the degree of 18F-FDG uptake and amount of metabolically active tumor volume on pretreatment 18F-FDG PET/CT, is a better prognostic factor than TD on 90Y PET/CT for predicting OS in HCC patients treated with 90Y TARE.


Frequency of uncomplicated angina pectoris in type A compared with type B persons (the Framingham Study).
The impact of type A behavior on coronary artery disease was examined in 570 men and 719 women based on 20 years of follow-up in the Framingham Study. A comparison of type A and B persons showed similar levels of systolic blood pressure, total and high density lipoprotein cholesterol and body mass index. Behavioral status also was unrelated to diabetes, cigarette smoking and alcohol intake. Despite similar cardiovascular risk profiles, type A behavior was associated with more than a 2-fold excess risk of angina pectoris, uncomplicated by other symptoms of coronary artery disease (p less than 0.05 for men and p less than 0.01 for women). Type A behavior, however, was not related to an increased risk of myocardial infarction and fatal coronary events. Among the victims of uncomplicated angina, the risk of subsequent coronary morbidity and mortality in both type A and type B men and women increased by more than 4-fold (p less than 0.001). Although the risk was reduced among type A persons, it was not statistically significant. It is concluded that uncomplicated angina pectoris occurs with greater frequency in type A persons than in those who are type B, without explanation by concomitant risk factors. In addition, the prognosis for myocardial infarction and coronary artery disease mortality in angina patients classified as type A is as serious as the prognosis for those who are type B.


Preparation and properties of an immobilized derivative of penicillinase.
Penicillinase (beta-lactamase I, EC 188.8.131.52) secreted by Bacillus cereus, strain 569/H, was covalently attached to aminoethyl cellulose via glutaraldehyde. The immobilized derivative shows increased thermostability and decreased susceptibility to conformational changes induced by certain substrates of penicillinase. The decline in the rate of hydrolysis of such substrates was consequently suppressed by immobilization. A marked increase in Km was observed with all substrates except for the unsubstituted 6-aminopenicillanic acid. The altered properties of the new derivative are attributed to the constraint imposed by immobilization on the conformational flexibility of the enzyme molecule. Thus, apart from obvious technological interest, immobilized penicillinase provides a useful model for the study of the role of flexibility in the function of an enzyme.


Mortality from diabetes mellitus and its impact on life expectancy at 60 years of age in Mexico.
To analyze the behavior of mortality from diabetes mellitus (DM) for both sexes in Mexico from 1998 to 2018, and its impact on life expectancy (LE) from 60 to 85 years of age in the three-year periods 1998-2000 and 2016-2018, compared with other causes of death, as well as to determine the loss of years of life expectancy associated with DM in each three-year period. The current study is observational and descriptive. Age-adjusted rates of mortality from DM were calculated for each sex from 1998 to 2018. Sex-specific life tables were constructed for 1998-2000 and 2016-2018, and both LE between 60 and 85 years, and years of life expectancy lost (YLELL) due to DM and selected causes between both ages were calculated. Between 1998 and 2018, the adjusted DM-resulting male mortality rate grew 55% in the population aged 60 and over, while the female mortality rate grew 20%. Between 1998-2000 and 2016-2018, male LE for 60-85 age group decreased 0.22 years, while female LE increased 0.24. In 2016-2018, DM was responsible for 1.30 YLEL among men of 60 to 85 years (19% of the total YLEL), and 1.24 YLEL for women (24% of the total), more than the other causes analyzed. The increase in mortality from DM has substantially contributed both to reduce LE of older adult men, and to slow the increase of LE among women aged 60 years and older so far this century. Thus, preventive policies should be implemented since early ages to reduce the high levels of overweight and obesity in the country and, therefore, the significant population ratio suffering from DM.


wERKing the Waves in Collective Cell Migration.
It remains unclear how intercellular force transmission is coupled with intracellular biochemical signaling to achieve collective cell migration. In this issue of Developmental Cell, Hino et al. demonstrate that intracellular ERK signaling propagates as waves across a tissue and couples with intercellular mechano-transduction to direct epithelial cell migration.


Venereal disease.
Equine venereal infections of concern in the United States include EHV-3, T. equigenitalis, P. aeruginosa, and K. pneumoniae. Stallions may also harbor EAV in the genital tract and transmit the virus to mares during coitus. With the exception of EHV-3, the stallion generally remains asymptomatic while transmitting infections to mares during breeding. Methods for diagnosis, treatment, and control of these infections are discussed.


Autotomography with metrizamide myelography: an aid to visualisation of the cranio-cervical junction and cerebellar tonsils.
A simple method for improved visualisation of the structures at the foramen magnum and upper cervical spine during supine metrizamide myelography by using autotomography is described. Ten patients have been examined by this technique and the relevant structures have been clearly outlined in every case. It is concluded that the significance of side-effects with this technique is not great when compared with the important information obtained.


A 45,X/69,XXY fetus.
Post-mortem examination of a 20-week fetus showed incompletely masculinised external genitalia, hypoplastic adrenal glands and minor physical stigmata suggestive of a chromosome abnormality. Gonad and skin were karyotyped and both were found to contain two cell lines, 45,X and 69,XXY. It appears this fetus is a true 45,X/69,XXY mosaic.


Competition for Active TGFβ Cytokine Allows for Selective Retention of Antigen-Specific Tissue- Resident Memory T Cells in the Epidermal Niche.
Following antigen-driven expansion in lymph node, transforming growth factor-β (TGFβ) is required for differentiation of skin-recruited CD8+ T cell effectors into epidermal resident memory T (Trm) cells and their epidermal persistence. We found that the source of TGFβ -supporting Trm cells was autocrine. In addition, antigen-specific Trm cells that encountered cognate antigen in the skin, and bystander Trm cells that did not, both displayed long-term persistence in the epidermis under steady-state conditions. However, when the active-TGFβ was limited or when new T cell clones were recruited into the epidermis, antigen-specific Trm cells were more efficiently retained than bystander Trm cells. Genetically enforced TGFβR signaling allowed bystander Trm cells to persist in the epidermis as efficiently as antigen-specific Trm cells in both contexts. Thus, competition between T cells for active TGFβ represents an unappreciated selective pressure that promotes the accumulation and persistence of antigen-specific Trm cells in the epidermal niche.


Research Note: Isolation, speciation, and anticoccidial sensitivity of Eimeria spp. recovered from wild turkey feces in the United States.
Between 2018 and 2020, over 100 wild turkey fecal samples were collected from the Eastern and Central thirds of the United States, where commercial turkey production is uncommon. We hypothesized that anticoccidial-sensitive Eimeria spp. would be present in wild turkey fecal samples. Samples containing Eimeria spp. oocysts were amplified in vivo. If propagation was successful, the samples were PCR-speciated and subjected to anticoccidial sensitivity testing (AST) for key members of both ionophore and chemical categories of anticoccidial drugs. The purpose of this study was to isolate Eimeria spp. relevant to commercial turkey production that possessed sensitivity to monensin, zoalene, and amprolium. Future research would evaluate the efficacy of wild turkey Eimeria spp. as vaccine candidates for reducing coccidiosis in commercial turkey flocks utilizing single oocyst-derived stocks obtained in the present study.


Experimental Studies and Modeling of the Degradation Process of Poly(Lactic-co-Glycolic Acid) Microspheres for Sustained Protein Release.
In this study, poly(lactic-co-glycolic acid) microspheres (PLGA MS)for controlled protein release by double emulsion-solvent evaporation were produced and characterized for their morphological and technological features. MS autocatalytic degradation was described by a mathematical model based on a Michaelis and Menten-like chemical balance. Here, for the first time MS degradation was correlated to the advancement of MS degradation front with respect to the degraded radius, derived from mass loss experiments. The model can satisfactorily describe the kinetics of advancement of the degradation front experimentally derived for all MS formulations, especially when produced at higher PLGA concentrations.


MR imaging of perineural metastasis along the vidian nerve.
The perineural space is a well recognized pathway of tumor spread of head and neck cancer. We report a case of perividian metastasis studied with magnetic resonance imaging.


Two decades of cardiac transplantation at the Montreal Heart Institute.
The first heart transplantation in Canada was performed in 1968 at the Montreal Heart Institute (Montreal, Quebec). After nine patients transplanted in the precyclosporine era, the program was stopped. With the advent of cyclosporine, the program was reactivated in 1983. To review the experience of the Montreal Heart Institute with heart transplantation between 1983 and 2005. Three hundred patients underwent heart transplantation and were followed at the transplant clinic. Patients were divided into two groups: group 1--first decade (1983 to 1993, n=145) and group 2--second decade (1994 to 2005, n=155). There were 125 men (86%) and 20 women (14%) with a mean age of 45+/-10 years in group 1 compared with 118 men (76%) and 37 women (24%) with a mean age of 48+/-12 years in group 2 (P=0.03 and P=0.02, respectively). Indications for transplantation included congestive heart failure and/or ischemic heart disease in the majority of patients of both groups, with 83% in group 1 and 73% in group 2, respectively. In group 1, 30 patients (21%) required preoperative pharmacological support and 13 patients (9%) were on mechanical support compared with 16 (10%) and 34 (22%) patients in group 2 (P<0.01). The mean age of donors was 27+/-10 years and 34+/-13 years in groups 1 and 2, respectively (P<0.01). Major causes of mortality for donors included a motor vehicle accident in 65 cases (45%) and brain hemorrhage in 43 cases (30%) in group 1 compared with 34 cases (22%) and 68 cases (44%) in group 2 donors (P<0.01). The one-, five- and 10-year actuarial survival rates were 86%, 77% and 71%, respectively, in group 1 compared with 84%, 80% and 68%, respectively, in group 2 (P=0.95). The one-, five- and 10-year freedom from rejection rates were 35%, 28% and 25%, respectively, in group 1 compared with 41%, 36% and 33%, respectively, in group 2 (P=0.13). The one-, five- and 10-year freedom from infection rates were 38%, 24% and 17%, respectively, in group 1 compared with 37%, 23% and 19%, respectively, in group 2 (P=0.72). The one- and five-year freedom from graft coronary artery disease rates were 93% and 67%, respectively, in group 1 compared with 88% and 81%, respectively, in group 2 (P<0.01). The one-, five- and 10-year cancer-free survival rates were 98%, 91% and 73%, respectively, in group 1 compared with 98%, 90% and 77%, respectively, in group 2 (P=0.76). Patients who underwent heart transplantation in the second decade of the investigators' experience were older and in worse preoperative clinical condition; the donors were also older. However, survival and event-free survival rates remained similar throughout both periods.


Partial purification and properties of thiamine pyrophosphokinase from pig brain.
Pig brain thiamine pyrophosphokinase (ATP: thiamine pyrophosphotransferase, EC 220.127.116.11) was purified 260-fold over extracts of brain acetone powder. A direct, radiometric assay was used to follow the purification. By isoelectric focusing, the purified enzyme appeared to have an isoionic point of approx. pH 4.2, but these preparations were still not homogeneous by disc-gel electrophoresis nor by analytical ultracentrifugation. The purified enzyme has a broad pH optimum extending from pH 8.3 to 9.3 in 0.028 M phosphate/glycylglycine buffers. For optimal enzymatic activity, the ratio of magnesium to ATP must be fixed at 0.6, which suggests that for this ATP-pyrophosphoryl transfer reaction, the enzymatically preferred reactant may be Mg(ATP)6-/2. A preliminary study of the kinetics of the reaction reveals that the enzyme may function via a partial "ping-pong" mechanism; on this basis, dissociation constants for ATPt and for thiamine were evaluated. Pyrithiamine, butylthiamine, ethylthiamine, and oxythiamine appeared to be competitive inhibitors with respect to thiamine as the variable substrate, and their inhibitor dissociation constants were calculated. The relatively poor affinity of oxythiamine to the enzyme emphasizes the 4-amino group in the pyrimidine ring as one of the specificity requirements for thiamine pyrophosphokinase. Preliminary values for the apparent equilibrium coefficient of the thiamine pyrophosphokinase-catalyzed reaction, in terms of total species, has been approximated at several initial concentrations of reactants: e.g. K'eq,app = (see article) 9.66 - 10(-3) M; and [Th]initial - 1 - 10(-6) and 2 - 10(-6) M, respectively, where TDP, Th, t and eq represent thiamine diphosphate, thiamine, total concentration and equilibrium concentration, respectively.


Shark mandible evolution reveals patterns of trophic and habitat-mediated diversification.
Environmental controls of species diversity represent a central research focus in evolutionary biology. In the marine realm, sharks are widely distributed, occupying mainly higher trophic levels and varied dietary preferences, mirrored by several morphological traits and behaviours. Recent comparative phylogenetic studies revealed that sharks present a fairly uneven diversification across habitats, from reefs to deep-water. We show preliminary evidence that morphological diversification (disparity) in the feeding system (mandibles) follows these patterns, and we tested hypotheses linking these patterns to morphological specialisation. We conducted a 3D geometric morphometric analysis and phylogenetic comparative methods on 145 specimens representing 90 extant shark species using computed tomography models. We explored how rates of morphological evolution in the jaw correlate with habitat, size, diet, trophic level, and taxonomic order. Our findings show a relationship between disparity and environment, with higher rates of morphological evolution in reef and deep-water habitats. Deep-water species display highly divergent morphologies compared to other sharks. Strikingly, evolutionary rates of jaw disparity are associated with diversification in deep water, but not in reefs. The environmental heterogeneity of the offshore water column exposes the importance of this parameter as a driver of diversification at least in the early part of clade history.


Financing dental care: trends in public and private expenditures for dental services.
This article examines the financing of dental care in the United States. The major issues addressed include the amount and sources of funds, the reasons for increased dental care expenditures, the comparison of dental care with other medical care expenditures, the policy implications of current trends, and some cautious predictions about the financing of dental care in the next 10 to 20 years. The supply of dental services is expected to increase substantially in the next 10 to 20 years with more dental school graduates, a new midlevel practitioner, and greater use of allied dental health personnel. Whether the supply of services will grow faster than the demand for care is unknown.


Acute stress further decreases the effect of ovariectomy on immobility behavior and hippocampal cell survival in rats.
Most studies relating experimental depression and neurogenesis use mainly male rodents subjected to models of chronic stress. The forced swimming test (FST) is a widely utilized model of acute stress, but its effects on the neurogenic process in the hippocampus using females in different endocrine conditions has not been explored. The aim of this study was to evaluate the cell proliferation and early-, short- and long-lasting effects of forced swimming (FS) on adult hippocampal neurogenesis in rats in two endocrine conditions: proestrous and ovariectomized. To determine cell proliferation we used the endogenous marker Ki67. Cell survival was established with the thymidine analog, BrdU (75mg/kg, 2/12, i.p.), which was administered before FS to proestrous and ovariectomized rats. FS increased immobility and corticosterone levels in OVX but not in rats in proestrus. In addition, FS did not affect cell proliferation but significantly decreased the number of BrdU-labeled cells at 2h only in OVX-rats, an effect that remained for 3 and 14 days after FS. Data are discussed taking into consideration the relationship between gonadal and adrenal hormones in adult hippocampal neurogenesis in adult females. Our data also support the use of FS as a model for studying neurogenesis.


Properties of visually guided saccadic behavior and bottom-up attention in marmoset, macaque, and human.
Saccades are stereotypic behaviors whose investigation improves our understanding of how primate brains implement precise motor control. Furthermore, saccades offer an important window into the cognitive and attentional state of the brain. Historically, saccade studies have largely relied on macaques. However, the cortical network giving rise to the saccadic command is difficult to study in macaques because relevant cortical areas lie in deep sulci and are difficult to access. Recently, a New World monkey. the marmoset, has garnered attention as an alternative to macaques because of advantages including its smooth cortical surface. However, adoption of the marmoset for oculomotor research has been limited due to a lack of in-depth descriptions of marmoset saccade kinematics and their ability to perform psychophysical tasks. Here, we directly compare free-viewing and visually guided behavior of marmoset, macaque, and human engaged in identical tasks under similar conditions. In the video free-viewing task, all species exhibited qualitatively similar saccade kinematics up to 25° in amplitude although with different parameters. Furthermore, the conventional bottom-up saliency model predicted gaze targets at similar rates for all species. We further verified their visually guided behavior by training them with step and gap saccade tasks. In the step paradigm, marmosets did not show shorter saccade reaction time for upward saccades whereas macaques and humans did. In the gap paradigm, all species showed similar gap effect and express saccades. Our results suggest that the marmoset can serve as a model for oculomotor, attentional, and cognitive research while we need to be aware of their difference from macaque or human.NEW & NOTEWORTHY We directly compared the results of a video free-viewing task and visually guided saccade tasks (step and gap) among three different species: marmoset, macaque, and human. We found that all species exhibit qualitatively similar saccadic kinematics and saliency-driven saccadic behavior albeit with different parameters. Our results suggest that the marmoset possesses similar neural mechanisms to macaque and human for saccadic control, and it is an appropriate model to study neural mechanisms for active vision and attention.


Malignant fibrous histiocytoma of the temporomandiblar joint. Report of a case.
A case of malignant fibrous histiocytoma of the temporomandibular joint in a 21-year-old Japanese female was presented. The patient died of the tumor with local aggressive growth but without any organ metastasis, despite the intensive treatment including radical operation of the tumor, irradiation, and chemotherapy. This case suggested that radical curative operation was the only method of the treatment for this tumor. The clinicopathological features of the tumor are discussed, making reference to the malignant fibrous histiocytoma.


Laemophloeus souzalimai, a new species of lined flat bark beetle (Coleoptera, Cucujoidea, Laemophloeidae) from Southeast Brazil.
Distinctive, remarkable specimens from Bauru, So Paulo state, Brazil are recognized as a new species of the genus Laemophloeus Dejean (sensu stricto), which is described and illustrated in this paper. Laemophloeus souzalimai sp. nov. is most similar to L. germaini Grouvelle and can be readily distinguished from all New World species of the genus by the dorsal color testaceous, without elytral maculae, antennal club of 6 antennomeres, genal processes anteriorly projected, male head with somewhat pedunculated eyes, and frons with a broad, V-shaped impressed line. Additionally, the preexisting key to Laemophloeus species with antennal club of 6 or more antennomeres is modified to include the new species, and new records for five Brazilian species of the genus are provided.


Racial attitudes in young children as a function of interracial contact in the public schools.
The relative effects of integrated and segregated schooling on racial attitudes were studied in a comparison of young children attending all-black, all-white, and integrated schools. Results of this photo-choice study suggest that segregated classes discourage realistic perceptions of the excluded race and promote a preference for whites among whites and blacks, whereas interracial schooling contributes to acceptance of blacks by all students and has especially profound and complex effects on black children.


Trace elements and stable sulfur isotopes in plants of acid mine drainage area: Implications for revegetation of degraded land.
The abundances of trace elements, a low pH of water and soil in areas impacted by the acid mine drainage (AMD) may cause an excessive uptake of potentially toxic elements and nutritional imbalances in plants. Metal-tolerant, native plants are used for revegetation of degraded mining areas. We established levels of selected trace elements and stable sulfur isotopes in the above-ground plant biomass collected in a mining area in south-central Poland. In 2016, 20 samples of the most common species were collected from sites with a different influence of acid mine drainage and analyzed for trace elements by the inductively coupled plasma mass spectrometry technique. On the basis of the results obtained in 2016, the most contaminated site was selected for a more detailed study, in which sulfur contents and stable sulfur isotope ratios were determined together with trace elements in 17 samples. The results confirmed that the plants native to the AMD area efficiently accumulated trace elements, especially As and rare earth elements. Mosses showed the highest content of trace elements, but exhibited the lowest concentrations of sulfur accompanied by the highest δ34S values. It has been shown for the first time that stable sulfur isotope composition of AMD plants in south-central Poland is significantly depleted in the 34S isotope showing an average δ34S value of -10.5‰ in comparison with positive δ34S values in local vegetation growing outside the AMD area and in local precipitation.


Endoscopic perichondrium-cartilage H type technique for repairing chronic kidney-shaped perforations with 3 years of follow-up.
The objective of this study was to evaluate graft outcomes and complications of endoscopic perichondrium-cartilage H type technique for repairing chronic kidney-shaped perforation with 3 years of follow-up. Adult patients with chronic kidney-shaped perforation underwent endoscopic perichondrium-cartilage H type technique. The graft outcomes and complications were evaluated at 36 months after surgery. The total of 51 ears were included in this study. The mean operation time was 31.5 ± 4.1 min. Residual perforation was seen in 2 patients, the graft success rate was 96.1 % (49/51) at postoperative 12 months. Granular myringitis was noted in 8.2 % (4/49) patients in 49 patients with graft success. The mean preoperative ABG was 23.6 ± 3.7 dB, while the mean postoperative ABG postoperatively 12 months was 12.9 ± 5.2 dB (P < 0.05), the functional success rate was 94.1 % (48/51). At postoperative 36 months, only 32 (62.7 %, 32/51) patients were followed up, while 19 (37.3 %, 19/51) patients lost followup. Of the 32 patients with followup of 36 months, the mean follow-up time was 38.2 ± 7.1 (37-46) months, re-perforation was seen in one. All 32 patients performed the postoperative CT examination at last followup, CT revealed the well pneumatization of mastoids and middle ear. Endoscopic cartilage-perichondrium H type technique is an alternative method for repairing chronic kidney-shaped perforations, with a highly successful, short operation time, minimally invasive procedure, and no cholesteatoma.


Lactobacillus gastricus BTM 7 prevents intestinal colonization by biofilm forming Cronobacter sakazakii in Caenorhabditis elegans model host.
The study reports protective role of potential probiotic cultures against infection by biofilm forming Cronobacter sakazakii in Caenorhabditis elegans model system. Among the fifteen indigenous potential probiotics, the cell free supernatant of Lactobacillus gastricus BTM7 possessed highest antimicrobial action and biofilm inhibition against C. sakazakii. The competitive exclusion assays revealed that preconditioning with probiotics resulted in increased mean life span of the nematode to 12-13 days as compared to 5-6 days when the pathogen was administered alone. Enhanced expression of the marker genes (pmk-1, daf-16 and skn-1) was observed during the administration of probiotic cultures. The highest expression of pmk-1 (2.5 folds) was observed with administration of L. gastricus BTM7. The principal component analysis on selected variables revealed that L. gastricus BTM7 has the potential to limit the infection of C. sakazakii in C. elegans and enhance the expression of key genes involved in extending life span of the worm.


Cocaine distribution in wild Erythroxylum species.
Cocaine distribution was studied in leaves of wild Erythroxylum species originating from Bolivia, Brazil, Ecuador, Paraguay, Peru, Mexico, USA, Venezuela and Mauritius. Among 51 species, 28 had never been phytochemically investigated before. Cocaine was efficiently and rapidly extracted with methanol, using focused microwaves at atmospheric pressure, and analysed without any further purification by capillary gas chromatography coupled to mass spectrometry. Cocaine was reported for the first time in 14 species. Erythroxylum laetevirens was the wild species with the highest cocaine content. Its qualitative chromatographic profile also revealed other characteristic tropane alkaloids. Finally, its cocaine content was compared to those of two cultivated coca plants as well as with a coca tea bag sample.


CYP3A5 and ABCB1 polymorphisms as predictors for sunitinib outcome in metastatic renal cell carcinoma.
In our exploratory studies, we associated single nucleotide polymorphisms (SNPs) in candidate genes with the efficacy and toxicities of sunitinib in metastatic renal cell carcinoma (mRCC). To see whether previously reported associations of SNPs with sunitinib-induced toxicities and efficacy in mRCC can be confirmed in a large cohort of patients. The mRCC patients treated with sunitinib and a DNA sample available were pooled from three exploratory studies conducted in the United States, Spain, and the Netherlands. A total of 22 SNPs and 6 haplotypes in 10 candidate genes related to the pharmacokinetics and pharmacodynamics of sunitinib were selected for association testing. SNPs and haplotypes were tested for associations with toxicity, dose reductions, progression-free survival (PFS), overall survival (OS), and best objective response. A total of 333 patients were included. We confirmed 2 of the 22 previously reported SNP associations. The presence of CYP3A5*1 was associated with dose reductions (odds ratio: 2.0; 95% confidence interval [CI], 1.0-4.0, p=0.039). The presence of CGT in the ABCB1 haplotype was associated with an increased PFS (hazard ratio: 1.9; 95% CI, 1.3-2.6; p<0.001) and remained significant after Bonferroni correction. These associations are consistent with prior observations. The confirmation of previously reported associations between polymorphisms in CYP3A5 and ABCB1 with sunitinib toxicity and efficacy, respectively, indicates that genotyping of these genetic variants will be useful for guiding sunitinib treatment. A prospective validation study is needed to confirm our findings on ABCB1 and CYP3A5 genetic polymorphisms. We confirmed that variants in genes involved in processing sunitinib through the body have an effect on sunitinib treatment outcome. These findings confirm the potential of testing for these genetic variants to improve individual patient care for patients with metastatic renal cell carcinoma treated with sunitinib.


A glassy carbon electrode modified with reduced graphene oxide and gold nanoparticles for electrochemical aptasensing of lipopolysaccharides from Escherichia coli bacteria.
An electrochemical aptasensor is described for the voltammetric determination of lipopolysaccharide (LPS) from Escherichia coli 055:B5. Aptamer chains were immobilized on the surface of a glassy carbon electrode (GCE) via reduced graphene oxide and gold nanoparticles (RGO/AuNPs). Fast Fourier transform infrared, X-ray diffraction and transmission electron microscopy were used to characterize the nanomaterials. Cyclic voltammetry, square wave voltammetry and electrochemical impedance spectroscopy were used to characterize the modified GCE. The results show that the modified electrode has a good selectivity for LPS over other biomolecules. The hexacyanoferrate redox system, typically operated at around 0.3 V (vs. Ag/AgCl) is used as an electrochemical probe. The detection limit is 30 fg·mL-1. To decrease the electrochemical potential for detection of LPS, Mg/carbon quantum dots were used as redox active media. They decrease the detection potentialto 0 V and the detection of limit (LOD) to 1 fg·mL-1. The electrode was successfully used to analyze serum of patients and healthy persons. Graphical abstractSchematic representation of the modification of reduced graphene oxide gold nanoparticles with aptamer chains to immobilize on the glassy carbon electrode surface for electrochemical detection of lipopolysaccharides.


Segmental intrarenal catheterization in renin-mediated hypertension.
Segmental renal vein blood was collected in 9 hypertensive patients who had a focal renal lesion on excretory urography and/or a high peripheral plasma renin activity. The main renal vein catheterization was normal in all patients. Segmental renal vein catheterization demonstrated a renin-producing lesion in 3 patients, all of whom were cured of the hypertension postoperatively. Segmental renal vein catheterization is safe and allows the recognition of increased renin production from focal lesions of the kidney that may not be demonstrated radiographically or by main vein catheterization.


Abdominoplasty for treatment of abdominal gun-shot wound sequalae - A case report.
Gun violence is a public health epidemic in the United States with 15,315 non-suicide related deaths reported in 2019 by the Gun Violence Archive. To date, abdominoplasty is primarily a cosmetic procedure, which involves low-lying incision, removal of excess skin, fat, and tissue, and strengthening of the abdominal wall musculature. There currently are limited reports in regard to abdominoplasty as a procedure for scar revision and abdominal deformity repair associated with gunshot related injuries. An African American female patient, 38 years of age, presented for correction of a wide healed surgical incision and incisional hernia in the midline abdomen. This resulted from a trauma laparotomy in treatment of multiple gunshot wounds. Patient presented post-operatively with no complications. She had successful reduction of her incisional hernia using an anatomic repair. Her wide hypertrophic abdominal scar was excised and primarily closed. In the cases of abdominal hernia and scarring secondary to trauma laparotomies performed for gunshot wounds, abdominoplasty is an option for revision and repair.


Governing in the Anthropocene: are there cyber-systemic antidotes to the malaise of modern governance?
The Anthropocene imposes new challenges for governments, demanding capabilities for dealing with complexity and uncertainty. In this paper we examine how effective governing of social-biophysical dynamics is constrained by current processes and systems of government. Framing choices and structural determinants combine to create governance deficits in multiple domains, particularly in relation to the governing of complex larger-scale social-biophysical systems. Attempts to build capability for governing 'wicked problems' are relevant to sustainability science and Anthropocene governance, but these have mostly failed to become institutionalised. Two cases studies are reported to elucidate how the systemic dynamics of governing operate and fail in relation to espoused purpose. In the UK attempts to enact 'joined-up' government' during the years of New Labour government reveal systemic flaws and consistent praxis failures. From Australia we report on water governance reforms with implications for a wide range of complex policy issues. We conclude that innovations are needed to build capacity for governing the unfolding surprises and inherent uncertainties of the Anthropocene. These include institutionalising, or structural incorporation, of cyber-systemic thinking/practices that can also enhance empowerment and creativity that underpins sustainability science.


Removal of toxin (tetrodotoxin) from puffer ovary by traditional fermentation.
The amounts of puffer toxin (tetrodotoxin, TTX) extracted from the fresh and the traditional Japanese salted and fermented "Nukazuke" and "Kasuzuke" ovaries of Takifugu stictonotus (T. stictonotus) were quantitatively analyzed in the voltage-dependent sodium current (I(Na)) recorded from mechanically dissociated single rat hippocampal CA1 neurons. The amount of TTX contained in "Nukazuke" and "Kasuzuke" ovaries decreased to 1/50-1/90 times of that of fresh ovary during a salted and successive fermented period over a few years. The final toxin concentration after fermentation was almost close to the TTX level extracted from T. Rubripes" fresh muscle that is normally eaten. It was concluded that the fermented "Nukazuke" and "Kasuzuke" ovaries of puffer fish T. Stictonotus are safe and harmless as food.


Seroprevalence of Hepatitis B Virus Among Pregnant Women in India: A Systematic Review and Meta-Analysis.
Hepatitis B virus (HBV) infection during pregnancy is associated with perinatal transmission contributing to the pool of HBV infection in the population. There is a wide variation in the reported data on the seroprevalence of HBV in pregnant patients from various parts of India. Hence, a systematic review and meta-analysis was conducted to determine the pooled seroprevalence of HBV and its associated demographic factors. A comprehensive literature search of Medline, Scopus, and Google Scholar was conducted from January 2000 to April 2022 for studies evaluating the prevalence of HBV in pregnant patients from India. A total of 44 studies with data on 272,595 patients were included in the meta-analysis. The pooled prevalence of hepatitis B surface antigen (HBsAg) in pregnant women was 1.6% [95% confidence interval (CI), 1.4-1.8]. Among patients with HBsAg positivity, the pooled prevalence of hepatitis B e antigen was 26.0% (95%CI 17.4-34.7). There was no significant difference in the odds of HBV seroprevalence based on the age (<25 years vs. > 25 years) [odds ratio (OR) 1.07, 95%CI 0.74-1.55], parity (primipara vs. multipara) (OR 1.09, 95%CI 0.70-1.70) or area of residence (urban vs. rural) (OR 0.88, 95%CI 0.56-1.39). However, the odds of HBV seroprevalence in those with no or primary education was higher than in those with secondary level education or higher (OR 2.29, 95%CI 1.24-4.23). Prior history of risk factors was present in 13.5-22.7% of patients indicating a vertical mode of acquisition. There is a low endemicity of HBV among pregnant women in India. Risk factors are seen in less than 25% of the cases, indicating vertical transmission as the predominant mode of acquisition, which can be reduced by improving vaccination coverage.


[Workplace health promotion among elderly employees in Germany. Results in the IAB establishment panel 2011].
The aim of the secondary analysis is the exploration of the prevalence and determinants of workplace health promotion among elderly employees. The Institute for Employment Research (IAB) establishment panel is an annual representative survey of employers. In 2011 a total of 13,378 establishments with at least 1 elderly employee (50 + years) participated in personal interviews. In 2011, 4 % of the establishments in Eastern and Western Germany included measures for workplace health promotion among employees aged 50 years and older, which were often associated with personnel measures among the elderly. The prevalence of workplace health promotion varies considerably among the sectors of industry and the Federal States and substantially increases with the size of the establishment. Establishments with a works council are disproportionally highly committed to workplace health promotion among the elderly employees. There is a large development potential for a better integration of workplace health promotion among elderly employees in personnel and enterprise strategies.


Protein kinase Czeta represses the interleukin-6 promoter and impairs tumorigenesis in vivo.
Gene alterations in tumor cells that confer the ability to grow under nutrient- and mitogen-deficient conditions constitute a competitive advantage that leads to more-aggressive forms of cancer. The atypical protein kinase C (PKC) isoform, PKCzeta, has been shown to interact with the signaling adapter p62, which is important for Ras-induced lung carcinogenesis. Here we show that PKCzeta-deficient mice display increased Ras-induced lung carcinogenesis, suggesting a new role for this kinase as a tumor suppressor in vivo. We also show that Ras-transformed PKCzeta-deficient lungs and embryo fibroblasts produced more interleukin-6 (IL-6), which we demonstrate here plays an essential role in the ability of Ras-transformed cells to grow under nutrient-deprived conditions in vitro and in a mouse xenograft system in vivo. We also show that PKCzeta represses histone acetylation at the C/EBPbeta element in the IL-6 promoter. Therefore, PKCzeta, by controlling the production of IL-6, is a critical signaling molecule in tumorigenesis.


Glucosylation of taxifolin with cultured plant cells.
Cultured plant cells of Eucalyptus perriniana glucosylated taxifolin to its 3'- and 7-O-beta-D-glucosides and 3',7-O-beta-D-diglucoside. On the other hand, taxifolin was converted into 3'- and 7-O-beta-D-glucosides by cultured cells of Nicotiana tabacum and Catharanthus roseus.


Preparation, compatibility and barrier properties of attapulgite/poly (lactic acid)/thermoplastic starch composites.
In this study, AT (attapulgite)/PLA/TPS biocomposites and films were prepared by melt blending technique using PLA and TPS as matrix, polyethylene glycol (PEG) as plasticizing modifier of PLA and AT clay as additive. The effect of AT content on the performance of AT/PLA/TPS composites was investigated. The results showed that, as the AT concentration increased, the fracture surface of the composite showed a bicontinuous phase structure when the AT content was 3 wt%. The rheological properties showed that the addition of AT resulted in more significant deformation of the minor phase, which reduced the phase size and led to lower complex viscosity, and more processability from the industrial perspective. The mechanical properties showed that the addition of AT nanoparticles could simultaneously improve the tensile strength and elongation at break of the composites, reaching a maximum at 3 wt% load. The water vapor barrier performance results showed that AT significantly improved the WVP of the film, and the moisture resistance performance was increased by 254 % compared with the PLA/TPS composite film within 5 h. In conclusion, the obtained AT/PLA/TPS biocomposites showed potential in packaging engineering and injection molding products, especially when renewability and full biodegradability of the material are required.


The low temperature magnetic circular dichroism spectra of iron-sulphur proteins. II. Two-iron ferredoxins.
Variable temperature magnetic circular dichroism (MCD) spectra of a number of two-iron ferredoxins have been measured. The spectra of fully oxidised spinach and Spirulina maxima ferredoxin are independent of temperature between room temperature and 18 K, showing that no contribution to the room temperature MCD spectrum arises from the small population of low-lying excited states originating from the exchange coupling. However, the low temperature MCD spectra of the half-reduced proteins spinach and Spirulina maxima ferredoxin and adrenodoxin are all reasonably intense and temperature dependent. An interpretation of the spectrum of the charge-transfer region is suggested by starting with the assignments previously obtained from rubredoxin.


Understanding the optimal learning environment in palliative care.
The learning experiences of student nurses undertaking clinical placement are reported widely, however little is known about the learning experiences of health professionals undertaking continuing professional development (CPD) in a clinical setting, especially in palliative care. The aim of this study, which was conducted as part of the national evaluation of a professional development program involving clinical attachments with palliative care services (The Program of Experience in the Palliative Approach [PEPA]), was to explore factors influencing the learning experiences of participants over time. Thirteen semi-structured, one-to-one telephone interviews were conducted with five participants throughout their PEPA experience. The analysis was informed by the traditions of adult, social and psychological learning theories and relevant literature. The participants' learning was enhanced by engaging interactively with host site staff and patients, and by the validation of their personal and professional life experiences together with the reciprocation of their knowledge with host site staff. Self-directed learning strategies maximised the participants' learning outcomes. Inclusion in team activities aided the participants to feel accepted within the host site. Personal interactions with host site staff and patients shaped this social/cultural environment of the host site. Optimal learning was promoted when participants were actively engaged, felt accepted and supported by, and experienced positive interpersonal interactions with, the host site staff.


Intracavernosal prostaglandin E1 self vs office injection therapy in patients with erectile dysfunction.
We have investigated the reliability of intracavernosal prostaglandin E1 (PGE1) office vs self-injection therapy in patients with erectile dysfunction (ED). A total of 298 male patients with ED were enrolled in this study. In all patients, intracavernosal titration of the PGE1 dose was performed. A total of 106 patients were enrolled in the self-injection program, and 192 patients were enrolled in the office injection program. There were significant differences between number of injections and amount of PGE1 per month, total number of injections, and total amount of PGE1 on office and self-injection programs (P < 0.05 for each). There was a significant increase in the dropout rate in the office injection group compared with the self-injection group (P < 0.05). There was an increase in penile fibrosis in the self-injection program compared with the office program (P < 0.05). A self-injection program is reliable. Office injection program can be reserved for a subset of ED patients with special preferences.


The effects of immediate-release morphine on cognitive functioning in patients receiving chronic opioid therapy in palliative care.
Morphine and other potent opioids are frequently used in palliative care and pain management. When sustained-release (SR) opioids do not provide adequate background analgesia, additional immediate-release (IR) opioid (e.g. short-acting morphine) may be required to alleviate breakthrough or episodic pain. Despite the frequent use of IR morphine on top of SR opioids, little is known about the effects of such treatment on patients' everyday cognitive functioning. This study therefore used a double-blind, placebo-controlled, cross-over design to assess cognitive functioning in 14 patients receiving palliative care. All patients were taking SR opioid preparations and required <or=2 doses of IR morphine/day. Performance on cognitive measures (as well as subjective measures of pain and mood) after a dose of IR morphine was compared with placebo. Patients experienced significantly more pain-reduction following IR morphine (P=0.03), while other measures of subjective drug effects (e.g. sedation) were largely unaffected. Patients displayed anterograde memory impairment after IR morphine relative to placebo (P=0.003). Intriguingly, patients also had significant 'retrograde' memory impairment: delayed recall of verbal information presented before IR morphine also declined (P=0.024). In addition, IR morphine reduced performance on a complex tracking task (Reitan's trails B; P=0.03) whilst enhancing it on a simpler tracking task (Reitan's trails A; P=0.03). In conclusion, this study suggests that IR morphine, when taken on top of a SR opioid, produces transient anterograde and retrograde memory impairments and a decrement in two-target tracking. These impairments may impact negatively on patients' everyday functioning.


How to find and how to read articles in neonatology.
Staying abreast of the neonatal literature is an important task. Being aware of new information and knowing how to evaluate its reliability remain essential to be able to provide the most appropriate, evidence-based, therapy to our patients. This article discusses methods for being informed of, and critically reviewing, published research in order to fulfill these tasks without being overwhelmed by the number or complexity of publications.


Rothia dentocariosa endocarditis and aortic root abscess.
We report a case of endocarditis and associated paravalvular abscess due to Rothia dentocariosa which did not respond to antibiotic therapy. Nine case reports describing endocarditis caused by this organism, formerly thought to be non-pathogenic, have been recorded in the literature. The isolates were extremely sensitive to penicillin, and eight patients responded to this agent which, in most cases, was used in combination with an aminoglycoside. Surgery is recommended for an associated abscess, as the outcome in the two recorded cases has been fatal.


Antigen-specific human B-cell responses: modulation by immunoregulatory T-cell subsets.
In vitro T-cell requirements for and modulation of human B-cell responses were studied in individuals immunized in vivo to the protein antigen keyhole limpet hemocyanin or tetanus toxoid. T cells were required for antibody synthesis in both antigen-driven and pokeweed mitogen (PWM)-driven cultures. T cells were separated into T4+ and T8+ subpopulations using monoclonal antibodies, and their modulation of antibody synthesis was studied. T4+ cells functioned as helper cells in both antigen-driven and PWM-driven cultures in a dose-dependent manner. Whereas T8+ cells suppress both total and specific immunoglobulin secretion in PWM-stimulated cultures, in antigen-stimulated cultures T8+ cells do not suppress unless activated by another cell population present in peripheral blood mononuclear cells (PBMNC). This cellular requirement was further investigated by prestimulation of cells prior to addition to optimally stimulated antigen-driven cultures of PBMNC or B cells, monocytes, and helper T cells. No suppression of these optimally stimulated cultures was seen when T8+ cells were precultured with antigen or PWM. However, after 3-5 days preculture of total T cells with PWM or antigen and then selection of T4+ cells, these cells were able to induce fresh autologous T8+ cells to suppress optimally stimulated antigen-driven cultures. Addition of a precultured mixture of T8+ cells with 20% T4+ cells also resulted in antigen-induced suppression. These data indicate that T8+ cells can suppress antigen-driven cultures but require the presence of preactivated T4+ cells for induction of this suppression of antigen-specific T-cell-dependent human B-cell responses.


A comparative study of methylene blue adsorption and removal mechanisms by calcium carbonate from different sources.
Efficient removal of organic dye pollution from contaminated water is a concern in the absorbent applications. In this study, a green biogenic calcium carbonate (BCC) absorbent was fabricated using Bacillus licheniformis for the removal of methylene blue (MB) from water. This was found to have superior adsorption capacity compared with abiotic calcium carbonate (ACC) and operate within a broad pH range from 3 to 9. MB adsorption on BCC was physical and exothermic. The hydrophobic features, rough nanoporous microstructure, and organic-inorganic mesoporous structure of the BCC may all be responsible for its favorable adsorption mass transfer. The adsorption energy of BCC had a more negative value than that of ACC, indicating a stronger MB interaction with BCC with a lower energy barrier. Hydrogen bonding and electrostatic attraction were involved in the adsorption process. Overall, the findings established a theoretical foundation for the application of BCC in remediation of MB-contaminated water.


A shell matrix protein of Pinctada mazatlanica produces nacre platelets in vitro.
Nacre is the main component of the pearl oyster shells and it is synthesized by specialized soluble and insoluble shell matrix proteins. Insoluble proteins from the decalcification of the shell are the less studied proteins due to the technical problems to isolate them from the organic matrix. In this study, an insoluble shell matrix protein from Pinctada mazatlanica, pearlin (Pmaz-pearlin), was successfully cloned from the mantle tissue, and the native protein isolated from the shell was functionally characterized. The full coding sequence of Pmaz-pearlin mRNA consists of 423 base pairs, which encode to a 16.3 kDa pearlin. Analysis of the deduced amino acid sequence revealed that Pmaz-pearlin contained four acidic regions, an NG repeat domain, and Cys conserved residues, the latter potentially forms four disulfide bridges which might stabilize the protein structure. The isolated protein from the shell is a glycoprotein of ~ 16.74 kDa which can produce aragonite and calcite crystals in vitro. Our results show that Pmaz-pearlin is a well-conserved protein involved in nacre layer growth, which produces calcite crystals in the presence of CaCl2, aragonite crystal polymorphs with a hexagonal structure in the presence of MgCl2, and needle-like crystal structure polymorphs in the presence of CaCO3 The identity of the crystals was confirmed using RAMAN analyses.


The Effect of Metformin on Prognosis in Patients With Locally Advanced Gastric Cancer Associated With Type 2 Diabetes Mellitus.
This study examined the effect of metformin use on the prognosis of gastric cancer patients. The study population comprised 2187 patients who underwent curative gastrectomy for the treatment of gastric cancer. They were divided into 3 groups: metformin (n=103), non-metformin (n=139), and non-diabetes mellitus (DM) (n=1945) according to their history of type 2 DM and metformin use. Survival, disease recurrence, and the pathologic stage were analyzed. Overall survival was better in the metformin group than in the non-DM group (P=0.005). Metformin use was an independent prognostic factor of overall survival, cancer recurrence, and peritoneal recurrence. An effect of metformin use was especially notable in patients with T4 or N0 disease. Metformin improves the survival of patients with gastric cancer and type 2 DM.


A study of patients with Nelson's syndrome.
The prevalence of Nelson's syndrome has varied greatly, at least in part because of the variability of the diagnostic criteria employed by different authors. We define Nelson's syndrome as the presence of an enlarging pituitary tumour associated with elevated fasting plasma ACTH levels and hyperpigmentation in patients with Cushing's disease after bilateral adrenalectomy. We have compared patients with Cushing's disease who developed Nelson's syndrome after bilateral adrenalectomy with those who did not. Our objective was to find differences between the two groups which might predict the development of Nelson's syndrome. We have reviewed the records of 30 patients with Cushing's disease after adrenalectomy, and divided them into two groups; I: 14 who developed Nelson's syndrome and II, 16 who did not. The two groups of patients were compared in their clinical, laboratory and imaging data as well as in the therapeutic procedures that preceded the adrenalectomy. The comparison between the two groups of patients demonstrated a highly significant difference in relation to the development of cutaneous hyperpigmentation (100% in group I and 19% in group II) and neuro-ophthalmological symptoms (21% in group I and 0% in group II) after adrenalectomy. There were no significant differences in laboratory data before adrenalectomy. After adrenalectomy, plasma ACTH levels increased significantly in the patients of both groups, but to much higher levels in those who developed Nelson's syndrome. Plasma ACTH concentrations above 154 pmol/l occurred only in the subjects with Nelson's syndrome. Before adrenalectomy, a pituitary tumour was more frequent in the patients who developed Nelson's syndrome (55% vs. 33% at transsphenoidal pituitary exploration). Pituitary surgery and irradiation were undertaken before adrenalectomy in approximately equal numbers of patients in each group. The prevalence of Nelson's syndrome was 47% in our series of 30 patients with Cushing's disease after bilateral adrenalectomy. No clinical or laboratory data before adrenalectomy predicted the development of the syndrome. The value of prophylactic pituitary irradiation could not be evaluated from our clinical material. However, after adrenalectomy, the presence of hyperpigmentation and ACTH levels above 154 pmol/l had positive predictive value for the development of Nelson's syndrome. In this situation magnetic resonance imaging (MRI) of the pituitary is mandatory and, if no tumour is detected, MRI should be repeated at intervals.


An analytical study on the awareness, attitude and practice during the COVID-19 pandemic in Riyadh, Saudi Arabia.
Coronavirus disease (COVID-19) is an infectious disease caused by a new variable of the Coronaviridae family. COVID-19 spreads primarily by contacting the virus either from a COVID-19-infected individual through coughing or sneezing or from COVID-19-contaminated surfaces. On March 12, 2020, the World Health Organization (WHO) announced COVID-19 as a pandemic. The government of Saudi Arabia was among the first countries in the world to take quick and serious precautions. The Ministry of Health (MOH) has made the public aware of the virus transmission patterns and the importance of quarantine and curfew. Despite strict measures taken, the awareness of people towards infectious viruses remains the most important factor in limiting the widespread of diseases. A cross-sectional survey of 1767 participants, was conducted to explore the awareness, attitude and practice of COVID-19 in relation to socioeconomic data among residents in the city of Riyadh. Of all the participants, 58% showed a moderate level of awareness, 95% presented a high attitude and 81% presented an adequate practice regarding COVID-19. Significant positive correlation between awareness-attitude (r = 0.132, p-value < 0.001) and attitude-practice (r = 0.149, p-value < 0.001) were found. The gender of the participants was the only common characteristic significantly associated with both awareness and practice. This study revealed that males showed a slight increase (60%) in the level of awareness compared to female participants (57%), however, when it comes to the practice towards COVID-19, females showed slightly better practice (82%) than males (80%). The World health organization (WHO) and the Ministry of Health (MOH) were the main sources of information. Despite the moderate public awareness, their attitude and practice were better. Therefore, public awareness must be improved to be prepared for epidemic and pandemic situations. A comprehensive public health education program is important to increase awareness and to reach sufficient knowledge.


Evaluation of the level of awareness of the role of folic acid in the prevention of neural tube defects amongst women of reproductive age in a tertiary health institution.
Neural tube defects are major cause of infant mortality and disability. Their occurrence has been linked to folate deficiency during pregnancy. Periconceptional use of folate has been shown to significantly reduce their incidence. Awareness of this relationship is key to adopting appropriate measures to prevent them. This study was carried out to assess the level of this awareness among reproductive-age female employees in a tertiary hospital. Questionnaires designed to assess respondents' knowledge about neural tube defects and folic acid were completed by women of child-bearing age working in various departments of the University of Port Harcourt Teaching Hospital. Data were collated and analysed by a third party who had no knowledge of the respondents. 94.4% of the respondents had some knowledge about folic acid. 29.6% knew something about neural tube defects. 24.1% were aware that folate has a beneficial role in their prevention. 70.4% said they would not take it daily if they were not pregnant. The level of awareness about the role of folate in prevention of neural tube defects among respondents in this study is low; and thus there is poor response to suggestions regarding its periconceptional use. There is need to enhance this awareness to ensure that populations at risk benefit from research on the subject.


Myocarditis and idiopathic dilated cardiomyopathy.
Idiopathic dilated cardiomyopathy (IDC) accounts for 25% of cases of heart failure in the United States. Understanding the relationship between an inciting event or agent and the development of IDC has progressed only recently. Once IDC has developed, treatment is palliative and little can be done to alter the natural course of the disease. Active myocarditis, a suspected precursor of IDC, is myocardial inflammation and injury without ischemia. The disease ranges from a self-limited flulike illness to one of serious consequence with arrhythmias, heart failure, or death. Many agents have been associated with myocarditis, and the clinical manifestations depend on an interplay between the inciting agent and the host response. The development of a murine model and the expanded use of endomyocardial biopsy using the Dallas criteria have increased our understanding of myocarditis and its sequelae. Therapy consists of managing symptoms using conventional medical regimens for heart failure. Immunosuppressive therapy should be reserved for patients with biopsy-proven disease who have failed conventional therapy. Continued deterioration warrants ventricular assistance and consideration of cardiac transplantation.


Mechanism, pathophysiology, diagnosis, and management of renal transplant rejection.
In recent years, there has been a steady progress in basic research (immunogenetics and cellular immunology) that helped us in understanding the mechanisms underlying allograft rejection. Several laboratory tests were developed, and the results were shown to correlate with clinical rejection. However, most of these studies have not found a place in clinical practice because of their nonspecificity, lack of sensitivity, time lag, added expense, and inconvenience. The commonly employed diagnostic tests (i.e., renal transplant ultrasound and 131I hippuran scintigram) are helpful in differentiating rejection from other causes of graft malfunction. The specific renal parenchymal disease, such as acute or chronic rejection or de novo or recurrent glomerular disease, contributing to graft malfunction can only be diagnosed by renal histopathologic study. Because hyperacute and accelerated acute rejections are irreversible and necessitate graft nephrectomy, measures should be taken to prevent this problem. High-dose corticosteroids still remain the mainstay of therapy for acute cellular rejection. In the case of steroid-resistant rejections, treatment with ALG or OKT3 appears promising. As there is no effective therapy for chronic allograft rejection, usual measures of delaying the progression of chronic renal failure should be employed, and patients should be advised to return to maintenance dialysis before they develop uremic symptoms. If current experiments demonstrating selective immunosuppression with monoclonal antibodies are found successful in human trials, one can expect further improvement in the outcome of renal transplantation.


Long-term zinc deprivation accelerates rat vascular smooth muscle cell proliferation involving the down-regulation of JNK1/2 expression in MAPK signaling.
The accelerated proliferation of vascular smooth muscle cells (VSMCs) is a contributor for atherosclerosis by thickening the vascular wall. Since zinc modulation of VSMC proliferation has not been clarified, this study investigated whether zinc affects VSMC proliferation. Both a rat aorta origin vascular smooth muscle cell line (A7r5 VSMCs) and primary VSMCs which were collected from rat aorta (pVSMCs) were cultured with zinc (0-50 μM Zn) for short- (≤12 d) and long-term (28 d) periods under normal non-calcifying (0 or 1 mM P) or calcifying (>2 mM P) P conditions. Mouse vascular endothelial cells (MS I cells) were also cultured (under 0-50 μM Zn and 10 mM P for 20 d) to compare with VSMC cultures. While during short-term culture of VSMCs, zinc deprivation decreased cell proliferation in a zinc-concentration manner both under non-calcifying and calcifying conditions in A7r5 and pVSMCs (P < 0.05), during long-term cultures (28 d), A7r5 VSMC proliferation was inversely related to medium zinc concentration under normal physiological P conditions (regression coefficient r(2) = -0.563, P = 0.012). The anti-cell proliferative effect of zinc supplementation (>50 μM) was VSMC-specific. Long-term (35 d), low zinc treatment down-regulated JNK expression and activation, while not affecting ERK1/2 MAPK signaling in A7r5 VSMCs. The results showed that chronic zinc deprivation accelerated VSMC proliferation, perhaps due to down-regulation of MAPK-JNK signaling, and that the anti-cell proliferative role of zinc is VSMC-specific. The findings suggested that zinc may have anti-VSMC proliferative properties in atherosclerosis.


Ontogeny of adipokine expression in neonatal pig adipose tissue.
This study examined ontogeny of development for a range of adipokines in neonatal adipose tissue. Pigs (Sus scrofa) were selected across six litters for sampling subcutaneous (SQ) and perirenal (PR) adipose tissues at d1, d4, d7 or d21 of age and total RNA extraction. Reverse transcription and real-time PCR were used to quantify mRNA abundance for: leptin, adiponectin, interleukin 1beta (IL-1beta), IL-6, IL-8, IL-10, IL-15, tumor necrosis factor alpha (TNFalpha), haptoglobin, vascular endothelial growth factor (VEGF), macrophage migration inhibitory factor (MIF), monocyte chemoattractant protein 1 (MCP1) and cyclophilin. Leptin, adiponectin and IL-15 expression increased from d1 to d 21 of age in both SQ and PR. Haptoglobin, VEGF, MIF and IL-8 expression decreased between d1 and d4 of age in SQ. TNFalpha expression was unchanged from d1-7 and then increased at d21. IL-1beta, IL-6 and IL-10 expression were unchanged with age in SQ; whereas IL-1beta and IL-6 mRNA abundance in the PR increased with age. Analysis of the mRNA abundance for these adipokines within adipose tissue from d1 to d21 of age demonstrated that neonatal development of adipokine expression varies among the different adipokines and the internal and external sites of adipose tissue deposition (PR versus SQ).


Current methods of mutation detection.
Mutation detection is important in all areas of biology. Detection of unknown mutations can involve sequencing of kilobases of DNA, often in many patients. This has lead to the development of methods to screen DNA for mutations as well as methods to detect previously described mutations. This review discusses current methods used for such purposes with special emphasis on genetic diseases of humans. However, savings can be made by similar means in other areas of biology where repetitive or extensive sequencing for comparative purposes needs to be done. This review covers the methods used for detection of unknown mutations, namely the ribonuclease, denaturing gradient-gel electrophoresis, carbodiimide, chemical cleavage, single-strand conformation polymorphism, heteroduplex and sequencing methods. Once mutations have been defined they can be searched for repeatedly by methods referred to as diagnostic methods. Such methods include allele-specific oligonucleotide hybridization, allele-specific amplification, ligation, primer extension and the artificial introduction of restriction sites. We can now choose from a range of excellent methods, but the choice will usually depend on the background of the laboratory and/or the application in hand. Screening methods are evolving to more satisfactory forms, and the diagnostic methods can be automated to screen whole populations inexpensively.


GAPDH/Siah1 cascade is involved in traumatic spinal cord injury and could be attenuated by sivelestat sodium.
The glyceraldehyde-3-phosphate dehydrogenase (GAPDH)/Siah1 signaling pathway has been recognized as a sensor of nitric oxide (NO). It is associated with a variety of injurious conditions, suggesting its therapeutic potential for spinal cord injury (SCI). Sivelestat sodium (SIV), a neutrophil elastase (NE) inhibitor initially used to treat acute lung injury, has been known to protect against compression-induced and ischemic SCI. However, little is known about the relationship between the GAPDH/Siah1 cascade and SIV. Thus, we aimed to assess the role of GAPDH/Siah1 cascade in traumatic SCI and its possible link with SIV. Rats were assigned to four groups: sham group, SCI group, 5-mg/kg SIV group, and 10-mg/kg SIV. The traumatic SCI was induced by dropping a 10-g impactor from a height of 25mm on the dorsal surface of T9 and T10. SIV was injected intraperitoneally immediately after surgery. Our results showed that the nuclear translocation of GAPDH was induced together with the nuclear translocation of Siah1 and the formation of the GAPDH/Siah1 complex in the spinal cord after traumatic SCI. However, the activation of the GAPDH/Siah1 cascade was attenuated by treatment with SIV. We also found that SIV suppressed apoptosis, NE and inducible nitric oxide synthase (iNOS) protein expressions, the number of NE and iNOS immunostained cells, the production of interleukin (IL)-1β and tumor necrosis factor-alpha (TNF-α), and the activation of nuclear factor kappa light-chain enhancer of activated B cells (NF-κB) signaling in the spinal cord. The behavioral tests showed that SIV promoted functional recovery after traumatic SCI as reflected in the sustained increase in the Basso-Beattie-Bresnahan (BBB) scores throughout the observation period. In conclusion, our results reveal GAPDH/Siah1 as a novel signaling pathway during the progression of SCI, which can be blocked by SIV.


Antagonist resistant contractions of the porcine pulmonary artery by cysteinyl-leukotrienes.
The contractile response to cysteinyl-leukotrienes was studied in isolated porcine pulmonary arterial rings. In endothelium-denuded preparations, the concentration-response curves for leukotriene C(4) and leukotriene D(4) were identical, whereas leukotriene E(4) did not contract these tissues. The response to leukotriene C(4) was not blocked by either CysLT(1)/CysLT(2) receptor antagonism or by pre-treatment with leukotriene E(4). In preparations with an intact endothelium, leukotriene C(4) was somewhat more potent than leukotriene D(4) and the concentration-response curves were only slightly depressed in the presence of either ICI 204,219 (4-(5-cyclopentyloxycarbonylamino-1-methylindol-3-ylmethy l)-3-methoxy -N-o-tolylsulfonylbenzamide, 1 microM) or BAY u9773 (6(R)-(4'-carboxyphenylthio)-5(S)-hydroxy-7(E),9(E), 11(Z)14(Z)-eicosatetrenoic acid, 3 microM). Indomethacin (1.7 microM) significantly reduced the response to leukotriene C(4) whereas the response to leukotriene D(4) was unchanged. These findings suggest that a CysLT receptor subtype resistant to current antagonists mediated the major part of the contractions to leukotriene C(4) and leukotriene D(4) in intact preparations, and was the sole receptor associated with contractions of endothelium-denuded preparations.


Microfluidic Encapsulation of Phase-Change Materials for High Thermal Performance.
Microencapsulation of phase-change materials (PCMs) can prevent leakage of PCMs and enhance heat transfer with an increased surface area to volume ratio and thus benefit their pragmatic applications. However, the available methods have difficulties in microencapsulating PCMs with a tunable size, structure, and composition at will, thereby failing to accurately and flexibly tailor the thermal properties of microencapsulated PCMs (MEPCMs). Here, the microfluidic encapsulation of PCMs was presented for precisely fabricating MEPCMs with tunable thermal properties. The versatile fabrication of both organic and inorganic MEPCMs was demonstrated with high monodispersity, energy storage capacity, encapsulation efficiency, thermal stability, reliability, and heat charging and discharging rates. Notably, the inorganic MEPCMs exhibit an energy storage capacity of 269.3 J/g and a charging rate of 294.7 J/(g min), surpassing previously reported values. Owing to their high thermal performance, MEPCMs have been used for anticounterfeit applications. Droplet-based microfluidic fabrication opens up a new avenue for versatile fabrication of MEPCMs with well-tailored thermal properties, thus benefitting their applications.


[A case of a diagnostic error in Meckel's diverticulum with a right-sided torsive ovarian tumor].
The author described a case of a woman with Meckel's diverticulum, appendectomized, who was admitted to the gynecological ward after rejection of acute surgical abdomen with diagnosis ovarian tumour. Meckel's diverticulum with chronic serous-purulent peritonitis was established after laparotomy. Inferences are made in respect to this not quite rare intraoperative finding of Meckel's diverticulum and to the necessity of searching and its respective removal during laparotomy on other occasion.


Skin fibroblasts of children with idiopathic short stature show an increased mitogenic response to IGF-I and secrete more IGFBP-3.
To study differences in cellular parameters of GH and IGF-I responsiveness in skin fibroblasts of 14 children with idiopathic short stature (ISS) treated with recombinant human GH and 13 children with normal height. Secondly, to investigate whether these cellular parameters can predict the growth response to GH treatment in children with ISS. The mitogenic responsiveness to GH and IGF-I was investigated by 3H-Thymidine incorporation. Insulin-like growth factor binding protein-3 (IGFBP-3) levels in the media were measured by radioimmunoassay (RIA). No significant mitogenic responses were observed to various doses of GH (1000, 5000 or 50.000 ng/ml) in children with ISS or controls. ISS fibroblasts showed an increased mitogenic response to IGF-I (10 ng/ml) compared to controls (mean +/- SD 5.9 +/- 2.4- vs. 4.2 +/- 1.5-fold stimulation, P < 0.05), and GH enhanced this effect in both groups. IGFBP-3 secretion was increased in ISS fibroblasts when compared to controls under all conditions examined (basal, 200 and 5000 ng/ml GH, 10 ng/ml IGF-I for 24 and 48 h). High IGFBP-3 levels were related to low mitogenic responses to IGF-I or to GH + IGF-I in children with ISS (r = -0.7, P < 0.05), but not in controls. Within the ISS group, an enhanced mitogenic response to IGF-I in vitro was related to more extreme short stature before GH treatment (r = -0.70, P < 0.05) and to a relatively impaired response to high dose GH treatment in vivo (r = -0.52, P < 0.05). The demonstration of high IGFBP-3 levels and enhanced mitogenic response to IGF-I shows that ISS fibroblasts have different cellular characteristics compared to controls of normal height. It is hypothesized that in ISS an alteration of the signal transduction pathway between the GH receptor and IGFBP-3 synthesis results in a local imbalance with high IGFBP-3 levels and lower IGF-I availability for the IGF-I receptor. This may be reflected by an increased IGF-I responsiveness in vitro which is associated with an impaired capacity to grow in vivo.


Cisplatinum ototoxicity in children, long-term follow up.
To assess the long-term ototoxicity effect of platinum chemotherapy in a series of pediatric patients. A prospective cohort study. Patients who received platinum chemotherapy were identified through review of the pharmacy records from 2000 to 2005. Audiograms pre- and post-treatment with cisplatin were noted. The patients were brought back long after treatment for a repeat audiogram and a questionnaire to assess the impact of ototoxicity on their quality of life. Forty-nine patients received platinum chemotherapy. Patients' exclusion: two had no pre-chemo audiograms, one had retinoblastoma with congenital hearing loss, three were lost to follow up, five deceased, and seven refused participation. The total number of patients included was 31 with long-term follow up total of 21 patients. The follow up period ranged from 1.5 to 6.6 years (median of 3.4 years). Fourty-two percent (13/31) of the patients suffered from otoxicity (3 mild, 3 moderate, 7 severe-profound). Thirty-three (7/21) of audiograms worsened on long-term follow up. Questionnaire revealed 70% subjective hearing loss with 40% requiring hearing aids. Ototoxicity after platinum chemotherapy can present or worsen years after completion of therapy. Therefore, we recommend long-term follow up.


[Reality of treatment of osteoporotic fractures in German trauma departments. A contribution for outcome research].
The implementation of clinical pathways has a proven positive effect on the diagnostic workup and initiation of therapy in osteoporotic fracture patients. Unlike in most countries, fracture care in Germany is provided by so-called trauma surgeons. Therefore, it is essential to focus on the trauma surgeon for correct diagnostic workup and therapy initiation after a fragility fracture. A questionnaire was mailed to 409 departments of traumatology inquiring about the existence of a standardized clinical pathway for diagnosis and treatment of patients with fragility fractures. One of the central issues of the survey was whether those pathways comply with national guidelines. Only institutions that stated that they followed a clinical pathway were analyzed. 80% of institutions took part in our survey, 35% of which reported following a defined clinical pathway. Diagnostic workup is in concordance with the national guidelines in 30%, and therapy is guideline-based in 51%, with 12% basing both diagnostic workup and therapy on the guidelines. Thus, the vast majority of German traumatology departments do not follow national guidelines regarding osteoporosis diagnostics and therapy in patients with fragility fractures, leading to a great opportunity to improve fragility fracture care by means of both education and interdisciplinary cooperation.


Single-chain surfactant monolayer on carbon paste electrode and its application for the studies on the direct electron transfer of hemoglobin.
A variety of single-chain surfactants with different charge properties and tail lengths can spontaneously adsorb on the hydrophobic surface of carbon paste electrode and form stable monolayers on the electrode surface. Hemoglobin (Hb) was successfully immobilized on these surfactant monolayers to form stable protein-surfactant composite films regardless of the charge and the tail length of surfactants. The resulting surface-confined Hb exhibited well-defined direct electron-transfer behaviors in all positively, neutrally and negatively charged surfactant films, suggesting the important role of hydrophobic interactions in the adsorption of Hb on surfactant films. When the density of surfactant monolayers was controlled to be the same, Hb was found to possess a better direct electron-transfer behavior on monolayers of cationic surfactants with a longer tail length. This, in combination with the tunneling effect in the direct electron transfer of Hb on surfactant films, demonstrated that the adsorption of Hb on surfactant monolayers may be mainly achieved by the partial intercalation of Hb in the loose structures of surfactant films through hydrophobic interactions between the alkane chains of surfactants and the hydrophobic regions of Hb. The native conformation of Hb adsorbed on these surfactant films was proved to be unchanged, reflected by the unaltered ultraviolet-visible (UV-vis) and reflection-absorption infrared (RAIR) spectra, and by the catalytic activity toward hydrogen peroxide (H(2)O(2)) and nitric oxide (NO) in comparison with the free Hb molecules.


General pharmacological profile of the novel muscarinic receptor agonist SNI-2011, a drug for xerostomia in Sjögren's syndrome. 3rd communication: effects on respiratory and cardiovascular systems.
A novel muscarinic receptor agonist, SNI-2011 ((+/-)-cis-2-methylspiro[1,3-oxathiolane- 5,3'-quinuclidine]monohydrochloride hemihydrate, cevimeline, CAS 153504-70-2), is a candidate therapeutic drug for xerostomia in Sjögren's syndrome. The general pharmacological properties of this drug on the respiratory and cardiovascular systems were investigated in guinea pigs and dogs. SNI-2011 reduced the contractile force and beating rate of isolated right guinea pig atrium at 1 x 10(-6) mol/l or higher and 3 x 10(-6) mol/l or higher, respectively. SNI-2011 reduced the contractile force of isolated left atrium induced by electric stimulation at 1 x 10(-6) mol/l or higher. In anesthetized dogs, SNI-2011 caused a transient decrease in blood pressure, tachycardia and an increase in femoral arterial blood flow at 0.01 mg/kg i.v. or higher. At 1 mg/kg it caused continuous bradycardia, a decrease in femoral arterial blood flow and an increase in respiration rate in addition to the changes observed immediately after injection. A transient negative T-wave was observed as the only change in the ECG immediately after injection at 1 mg/kg. However, when SNI-2011 was injected intraduodenally, a decrease in femoral arterial blood flow, bradycardia and a tendency to increase respiration rate were observed at doses of 1 to 3 mg/kg. All these events in dogs were antagonized by atropine. These results suggest that oral administration of SNI-2011, that is the clinical administration route, can distinctly reduce the muscarinic effects on the respiratory and cardiovascular systems compared to intravenous administration.


Endocannabinoids affect the reproductive functions in teleosts and amphibians.
Following the discovery in the brain of the bonyfish Fugu rubripes of two genes encoding for type 1 cannabinoid receptors (CB1A and CB1B), investigations on the phylogeny of these receptors have indicated that the cannabinergic system is highly conserved. Among the multiple functions modulated by cannabinoids/endocannabinoids through the CB1 receptors one of the more investigated is the mammalian reproduction. Therefore, since studies performed in animal models other than mammals might provide further insight into the biology of these signalling molecules, the major aim of the present paper was to review the comparative data pointing toward the endocannabinoid involvement in the reproductive control of non-mammalian vertebrates, namely bonyfish and amphibians. The expression and distribution of CB1 receptors were investigated in the CNS and gonads of two teleosts, Pelvicachromis pulcher and Carassius auratus as well as in the anuran amphibians Xenopus laevis and Rana esculenta. In general the large diffusion of neurons targeted by cannabinoids in both fish and amphibian forebrain indicate endocannabinoids as pivotal local messengers in several neural circuits involved in either sensory integrative activities, like the olfactory processes (in amphibians) and food response (in bonyfish), or neuroendocrine machinery (in both). By using immunohistochemistry for CB1 and GnRH-I, the codistribution of the two signalling molecules was found in the fish basal telencephalon and preoptic area, which are key centers for gonadotropic regulation in all vertebrates. A similar topographical codistribution was observed also in the septum of the telencephalon in Rana esculenta and Xenopus laevis. Interestingly, the double standard immunofluorescence on the same brain section, aided with a laser confocal microscope, showed that in anurans a subset of GnRH-I neurons exhibited also the CB1 immunostaining. The fact that CB1-LI-IR was found indeed in the FSH gonadotrophs of the Xenopus pituitary gland and CB1 receptors together with the fatty acid amide hydrolase, the degradative enzyme of the endocannabinoid anandamide, were demonstrated in both bonyfish and frog gonads, strongly suggests that endocannabinoids are involved in central and peripheral gonadotropic functions of teleosts and amphibians.


Association between atherogenic index of plasma and subclinical renal damage over a 12-year follow-up: Hanzhong adolescent hypertension study.
A high atherogenic index of plasma (AIP) is associated with increased cardiovascular risk and higher serum uric acid levels, but whether AIP is a strong risk factor for developing subclinical renal damage (SRD) is unknown. This study aimed to explore the effect of AIP variations on the prevalence of SRD in a 12-year follow-up study. (1) The cross-sectional study enrolled 2485 participants from the Hanzhong cohort in 2017; (2) A total of 202 participants were included in the small longitudinal cohort from 2005 to 2017. Longitudinal analysis was used to determine whether an elevated AIP predicts the development of SRD. In the cross-sectional analysis, the AIP level was correlated with the estimated glomerular filtration rate (eGFR) and urinary albumin-to-creatine ratio (uACR) (P < 0.05). The age-adjusted odds ratio (OR) for prevalent SRD in men in the high AIP group was 1.924 (1.355-2.732) (P < 0.001), while in women, the OR was 1.616 (1.049-2.490) (P = 0.030) in the high AIP group. In the longitudinal analysis, significantly higher uACR levels were found in participants with normal AIP at baseline and elevated AIP in 2013 (P < 0.05). The adjusted OR for prevalent SRD in the incident AIP group was 4.741 (1.668-13.472) (P = 0.003) compared with the control group. Our study indicates that elevated AIP increased the risk of developing SRD and was associated with uACR and eGFR. As a simple marker of CVD risk, AIP may emerge as a novel and reliable indicator of SRD.


Loss of XIAP sensitizes colon cancer cells to PPARgamma independent antitumor effects of troglitazone and 15-PGJ2.
We investigated whether the anticancer effect of a combination of XIAP down-regulation and PPAR gamma activation on colon cancer is PPARgamma receptor dependent. HCT116-XIAP(+/+) cells and HCT116-XIAP(-/-) cells were treated with troglitazone or 15-deoxy-Delta(12,14)-prostaglandin J2 (15-PGJ2) with or without prior exposure to PPARgamma inhibitor GW9662. Cell proliferation and apoptosis was evaluated. Athymic mice carrying HCT116-XIAP(-/-) cells-derived tumors were treated with troglitazone in the presence or absence of GW9662. Inhibition of cell proliferation and induction of apoptosis by troglitazone and 15-PGJ2 were more prominent in HCT116-XIAP(-/-) cells. PPARgamma ligand-induced growth inhibition, apoptosis, caspase and PARP cleavage could not be blocked by GW9662. Troglitazone significantly retarded growth of xenograft tumors and this effect was not blocked by GW9662. Marked apoptosis and an up-regulation of E-cadherin were observed in xenograft tumor tissues, and GW9662 did not affect these effects. Thus, a combination of XIAP down-regulation and PPARgamma ligands exert a significant anticancer effect in colon cancer via a PPARgamma independent pathway.


Psychometric properties and construct validity of the Muscle Appearance Satisfaction Scale among Hungarian men.
Limited studies have evaluated the psychometric properties of the Muscle Appearance Satisfaction Scale (MASS), a measure of muscle dysmorphia, in different cultures and languages. The aims were to examine the psychometric properties of the Hungarian version of the MASS (MASS-HU), and to investigate its relationship with self-esteem and exercise-related variables. Two independent samples of male weight lifters (ns=289 and 43), and a sample of undergraduates (n=240) completed the MASS, Eating Disorder Inventory, and Rosenberg Self-esteem Scale. Exploratory factor analysis supported the original five-factor structure of the MASS only in the weight lifter sample. The MASS-HU had excellent scale score reliability and good test-retest reliability. The construct validity of the MASS-HU was tested with multivariate regression analyses which indicated an inverse relationship between self-esteem and muscle dysmorphia. The 18-item MASS-HU was found to be a useful measure for the assessment of muscle dysmorphia among male weight lifters.