The protective cardiac effects of Β-myrcene after global cerebral ıschemia/reperfusion in C57BL/J6 mouse.
To investigate the protective effect of β-myrcene (MYR) on oxidative and histological damage in mice heart tissue caused global cerebral ischemia/reperfusion (IR) in C57BL/J6 mice. Animals(n=40) were randomly divided into four groups: (1)control, (2)IR, (3)MYR and (4)MYR+IR. The control group was received 0.1% carboxymethyl cellulose as a vehicle following a medial incision without carotid occlusion. In the IR group, the bilateral carotid arteries were clipped for 15min, and treated with the vehicle intraperitoneally(ip) for 10 days. MYR (200mg/kg) was received dissolved in 0.1%CMC for 10 days. In the MYR+IR group, the IR model was applied exactly as in the IR group, and then they were treated with MYR 10 days. The cerebral IR caused oxidative damage (increase TBARS, decrease antioxidant parameters). Treatment of MYR was increased in GSH,GPx,CAT,SOD activity while TBARS level was decreased. In addition, degenerative changes in I/R group heart tissue were ameliorated by MYR administration. The administration of β-myrcene protects oxidative and histological damage in the heart tissue after global ischemia-reperfusion and may be useful safe alternative treatment for cardiac tissue after ischemic stroke.


[Three cases of malignant lymphoma that developed from the chest wall].
Chronic tuberculous pyothrax and the development of non-Hodgkin's lymphoma (NHL) on the chest wall are believed to be closely related. We encountered three patients with NHL involving the chest wall in whom the tumor may have had a different origin Patient 1: A 65-year-old man with a history of pulmonary tuberculosis and right-sided pyothrax at the age of 28 years was found to have a tumor on the right sided of the chest wall, and NHL was diagnosed. Patient 2: A 65-year old woman with a history of right-sided tuberculous pyothrax at the age of 2 years had a left-sided chest-wall tumor, and NHL was diagnosed. Patient 3: A 78-year-old man with a history of tuberclous pleuritis on the left side at the age of 77 years was found to have a left-sided chest-wall tumor, and NHL was diagnosed. In patients 1 and 2, the Epstein-Barr virus was found in tissue specimens by in situ hybridization. These findings suggest that chronic tuberculous pyothrax and the development of NHL on the chest wall were not closely related in these patients, and that the Epstein-Barr virus may play an important role in the development of NHL on the chest wall after tuberculous pyothrax.


Food safety impacts of antimicrobial use and their residues in aquaculture.
Residues of antimicrobials in food have received much attention in recent years because of growing food safety and public health concerns. Their presence in food of animal origin constitutes socioeconomic challenges in international trade in animal and animal products. The major public health significances of antimicrobial residues include the development of antimicrobial drug resistance, hypersensitivity reaction, carcinogenicity, mutagenicity, teratogenicity, bone marrow depression, and disruption of normal intestinal flora. Indiscriminate use of antimicrobials in aquaculture resulting in occurrence of residues in aquaculture products and associated harmful health effects in humans requires control measures to ensure consumer protection. This article focuses on factors contributing to the presence of antimicrobial residues in aquaculture products and their implications on consumers' safety. Regulatory actions aimed at prudent use of veterinary drugs in food-producing animals with emphasis on aquaculture for safe and wholesome food production are also reviewed. Prudent use of antibiotics in aquaculture under veterinary supervision is critical in ensuring safety of aquaculture products. Good animal husbandry practices as well as the use of alternatives to antibiotics such as vaccination, probiotics, phage therapy, and essential oils are recommended panaceas to reducing the use of antimicrobial residues in aquaculture and consequent food safety effects.


Photoluminescence properties of CdS and CdMnS quantum dots prepared by a reverse-micelle method.
We have investigated photoluminescence properties of CdS and CdMnS quantum dots (QDs) prepared by a reverse-micelle method. Before the surface modification, a broad luminescence band that originates from defects is dominant in CdS QDs. By the modification, the intensity of the band-edge luminescence is remarkably increased. The surface modification also causes drastic changes of decay profiles of the band-edge luminescence. The intensity of Mn2+ luminescence originating from the intra-3d shell transition of Mn2+ is also increased by the surface modification of CdMnS QDs. The decay time of the band-edge luminescence in surface-modified CdMnS QDs is faster than that in CdS QDs, which is due to the energy transfer from excitons to Mn2+.


Early radiographic manifestations of carcinoma of the esophagus.
The survival of patients with esophageal carcinoma is greatest if treatment is begun when the tumor is small and confined to the esophagus. To better define the early radiographic manifestations of this disease, we analyzed the clinical and pathological information and the radiographs from 9 patients with esophageal carcinomas 3.5 cm or less in diameter. All tumors involved one wall of the esophagus and most appeared as plaques or flat sessile polyps, occasionally with central ulceration. Air-contrast views of the distended esophagus demonstrated the tumors to best advantage and should facilitate early detection.


Comparison of DSM-IV and proposed ICD-11 formulations of PTSD among civilian survivors of war and war veterans.
The World Health Organization recently proposed a reformulation of posttraumatic stress disorder (PTSD) for the 11(th) edition of the International Classification of Diseases (ICD-11), employing only 6 symptoms. The aim of this study was to investigate the impact of this reformulation of PTSD as compared to criteria according to Diagnostic and Statistical Manual of Mental Disorders (4th ed., DSM-IV; American Psychiatric Association, 1994) on the prevalence of current PTSD as well as comorbid major depressive episode and anxiety disorders other than PTSD. Study 1 involved previously collected interviews with 560 Kosovar civilian war survivors; Study 2 employed a previously collected sample of 142 British war veterans. Results revealed no change in the diagnostic status under the criteria proposed for ICD-11 in 87.5% of civilian war survivors and 91.5% of war veterans. Participants who only met the newly proposed criteria showed lower rates of comorbid major depressive episode than participants who only met DSM-IV criteria (13.6% vs. 43.8% respectively). Rates of comorbid anxiety disorders did not significantly differ between participants who lost or gained a PTSD diagnosis under the proposed criteria.


Chemical constituents of diesel exhaust particles induce IL-4 production and histamine release by human basophils.
An epidemiologic relationship between airway allergic diseases and exposure to atmospheric pollutants has been demonstrated and suggested to be one factor in the increasing prevalence of asthma. Diesel exhaust particles (DEPs) have been shown to participate in the development of allergic airway inflammation, in which the targets include macrophages, B and T cells, epithelial cells, and mast cells. In addition to the adjuvant effect of DEPs on total and allergen-specific IgE production, DEPs also act to induce chemokines and cytokines and may play a key role in primary sensitization. DEPs have been shown to increase local IL-4-containing Kit(+) cells soon after in vivo nasal challenge. The aim of this study was to examine the effects of DEPs on human basophils, a key source of IL-4. Peripheral blood leukocytes from allergic and control subjects were cultured in the presence of organic extracts of DEP (DEPex) with or without allergen. The cultures were analyzed for IL-4-containing cells by using multiparameter flow cytometry, IL-4 secretion with ELISA, and histamine release. Basophils, when exposed in vitro to DEPex, expressed IL-4 and released histamine significantly (P <.01) more than with antigen activation. DEPex did not synergize with allergen in cytokine production and histamine release. DEPex-induced basophil IL-4 expression peaked at 2 hours and persisted through 20 hours, in contrast to allergen-induced IL-4, which was transient. The effect of DEPex on basophil cytokine expression and histamine release was dose dependent and occurred with cells from both allergic and nonallergic subjects. DEPex induced IL-4 expression and histamine release in highly enriched basophil populations, suggesting it acts directly on basophils. Other peripheral blood leukocytes, including T cells, did not contribute to this cytokine expression. Preincubation with N-acetylcysteine completely abrogated DEPex-driven basophil IL-4 expression. Basophils are a direct target for DEPex, inducing IL-4 expression and histamine release in an IgE-allergen independent fashion. N-acetylcysteine inhibition of DEPex-driven IL-4 expression provides evidence that generation of reactive oxygen species is required for the effects observed. The capability of DEPex to activate basophils in both allergic and nonallergic subjects suggests a potential role of this pollutant in the increasing prevalence of allergic diseases.


Activation of the mouse IL-2 gene by okadaic acid: synergy with interleukin-1.
Interleukin-1 (IL-1) has potent immunoregulatory and inflammatory functions. Its activity is mediated by an 80-kDa receptor on the cell surface and leads to activation of other genes. The underlying molecular events are largely unknown. We investigated the role of phosphatases in activation of the IL-2 gene in EL4 thymoma cells. We found that the protein phosphatase PP1 and PP2A inhibitor okadaic acid (OA) alone was able to significantly stimulate IL-2 production by the IL-1-responsive EL4 subline EL4 5D3 and also by the IL-1-nonresponsive EL4 subline EL4D6/76. In the IL-1-responsive cell line OA strongly synergized with phorbol myristate acetate (PMA) and IL-1. In the IL-1-nonresponsive cell line OA synergized with PMA but not with IL-1. Under suboptimal conditions of PMA/OA synergy an additional synergistic effect of IL-1 was shown. This was true for IL-2 and IL-6 production. Sphingomyelinase or sphingosine had no detectable effect. The kinetics of OA- and PMA-induced expression of IL-2 mRNA and IL-2 protein was different. PMA induced maximal expression between 6 and 12 h and was almost undetectable at 24 h. OA-induced expression was first obvious at 12 h and continued longer than 36 h. In both cases IL-1 caused no shift in kinetics, but potentiated the effects of the different tumor promoters. Utilizing IL-2 promoter-CAT constructs we showed in transfection experiments that the synergistic effect was also evident on the transcriptional level. We conclude from the data that phosphatases play an important role for IL-2 expression and that IL-1 can use additional pathways of activation that are different from events induced by PMA or OA.


Correlation between morphology of colonies formed by human thyroid tumor cells in collagen gel culture and invasive ability.
Two different types of colonies from human thyroid papillary carcinomas were observed in collagen gel culture. One was a branching type, with many three-dimensional outgrowths. The other was a spherical type, with no outgrowths. As viewed by electron microscopy, the tumor cells of spherical-type colonies had more microvilli on their surfaces than did cells in the branching-type colonies. Histochemically, the tumor cells of spherical-type colonies had stronger positive reactions than did tumor cells of branching-type colonies. This suggests that tumor cells of spherical-type colonies have a higher potential for dissemination and invasion than do tumor cells of branching-type colonies. In fact, cases with higher percentages of spherical-type colonies could show extracapsular invasion histopathologically. Our results indicate that collagen gel culture is a useful method for studying the heterogeneity of tumor cells as well as their invasive ability in vitro.


Serum uric acid, cholesterol, and psychological moods throughout stressful naval training.
Navy recruits, all 51 volunteers for a preliminary underwater demolition team (UDT) training program, were followed through 4 weeks of training; 27 men passed and 24 failed the training course. Serum uric acid and serum cholesterol levels, as well as psychological moods data were collected on all volunteers at the start of training and at the end of each of the four training weeks. Men who passed training were compared to those who failed. In addition, these same measures were carried out with a control group of 66 naval recruits. Pre-UDT trainees who passed the program demonstrated high levels of positive moods, early peaks in serum uric acid level, and stable serum cholesterol levels throughout training. These findings supported previous work with successful UDT trainees. Pre-UDT trainees who failed the program demonstrated intermediate levels of positive moods, a midtraining period peak in serum uric acid, and a significant rise in serum cholesterol during the final 2 weeks of the course. The serum cholesterol rise seen during a period shortly prior to failure substantiates previous findings. A comparison group showed low levels of positive moods, an initial peak in serum uric acid, and stable serum cholesterol levels. Two mood scales had siginificant correlations with serum uric acid for only men who passed training. A motivation scale, given at the start of training, correlated with serum uric acid levels for men who failed training.


Seven questions about stroke and epilepsy.
Seizures and stroke are both common neurologic conditions, but when they occur in close temporal proximity they produce much more concern than either does alone. The stroke specialist (and the family) fear that convulsions will worsen the stroke because of acute hypertension and airway compromise, and the epileptologist is concerned that these acute seizures are the harbingers of later epilepsy. Other less commonly recognized but important aspects of this relationship are that subclinical seizures worsen some forms of stroke, and some anticonvulsants may have more adverse effects on stroke patients than they do in other groups. In surveying the connections between these two conditions, I have attempted to address seven questions. For some questions, there are data to help provide an answer; for others, there is only opinion; and for a maddening few, newer research is making older suggestions less certain.


Role of G Protein-Coupled Receptors in the Regulation of Structural Plasticity and Cognitive Function.
Cognition and other higher brain functions are known to be intricately associated with the capacity of neural circuits to undergo structural reorganization. Structural remodelling of neural circuits, or structural plasticity, in the hippocampus plays a major role in learning and memory. Dynamic modifications of neuronal connectivity in the form of dendritic spine morphology alteration, as well as synapse formation and elimination, often result in the strengthening or weakening of specific neural circuits that determine synaptic plasticity. Changes in dendritic complexity and synapse number are mediated by cellular processes that are regulated by extracellular signals such as neurotransmitters and neurotrophic factors. As many neurotransmitters act on G protein-coupled receptors (GPCRs), it has become increasingly apparent that GPCRs can regulate structural plasticity through a myriad of G protein-dependent pathways and non-canonical signals. A thorough understanding of how GPCRs exert their regulatory influence on dendritic spine morphogenesis may provide new insights for treating cognitive impairment and decline in various age-related diseases. In this article, we review the evidence of GPCR-mediated regulation of structural plasticity, with a special emphasis on the involvement of common as well as distinct signalling pathways that are regulated by major neurotransmitters.


An integrative model of the impairments in insight in schizophrenia: emerging research on causal factors and treatments.
Poor insight, or unawareness of some major aspect of mental illness, is a major barrier to wellness when it interferes with persons seeking out treatment or forming their own understanding of the challenges they face. One barrier to addressing impaired insight is the absence of a comprehensive model of how poor insight develops. To explore this issue we review how poor insight is the result of multiple phenomena which interfere with the construction of narrative accounts of psychiatric challenges, rather than a single social or biological cause. Expert commentary: We propose an integrative model of poor insight in schizophrenia which involves the interaction of symptoms, deficits in neurocognition, social cognition, metacognition, and stigma. Emerging treatments for poor insight including therapies which focus on the development of metacognition are discussed.


A multiprofessional study of patients with myofascial pain-dysfunction syndrome. I.
A research team comprising a dentist, a psychiatrist and two physiotherapists examined 113 female patients consecutively referred because of myofascial pain-dysfunction (MPD) syndrome and, for comparison, 46 female patients who attended the dental clinic for a positively diagnosed dental problem. In both groups all subjects were Norwegians, nearly all in the age of reproduction and belonging to the upper social strata. Every second subject in the Comparison group had perceived some MPD-symptoms. The dentist's main findings in the MPD-patient group were high scores on the Anamnestic index and on the Dysfunction index, and moderate scores on the Occlusal index. The psychiatrist's main findings were high scores on restrained aggression and on anxiety, and tense control of emotions generally. The physiotherapists' findings were general muscular tension and inadequate respiratory function in an upright position.


COVID-19-free workplace: Measuring the level of antibodies against coronavirus as a basis for testing strategy in companies.
The Czech Republic is one of the countries most affected by the coronavirus pandemic - approximately 16% of the population had a positive PCR test, 2-3 times more people underwent infection without undergoing this examination. It is particularly useful for employers to know how many employees have already contracted the infection and for how many people are still at risk of the coronavirus infection. For this purpose, it is appropriate to examine IgG antibodies. However, the testing strategy is different at present - antigen testing is mandatory to look for infectious individuals, regardless of human immunity. The aim of the pilot study was to determine the number of immune individuals after infection at three clinics of GENNET s.r.o. At the same time, unvaccinated individuals who had not had COVID-19 or had undergone it more than three months ago were tested with antigen tests. The cohort included 297 subjects, of whom 182 were not vaccinated (61.3 %) and 115 subjects (38.7 %) were after the vaccination. Of the unvaccinated, 71 people had in the past a positive PCR test (39 %), another 18 people had positive IgG antibodies without infection (9.9 %) and 38 people (20.9 %) had negative IgG antibodies. So far, 55 persons (30.2 %) have not been examined. If we add people vaccinated and people with antibodies, then 74.3 % of employees of the GENNET Archa clinic, 68 % of employees from the GENNET Kostelní clinic and 58.1 % from the GENNET Liberec clinic were immune to infection. 153 individuals on average (60 of whom had antibodies) were tested for the antigen test in four rounds. The infection was detected in two people. Both belonged to the group without tested antibodies. No person with antibodies was tested positive for antigen. People who have antibodies after vaccination or infection are substantially less prone to infection and have a low risk of continuing to spread the virus. By examining antibodies, employers will gain a better overview of the situation in the workplace. Based on our study, we recommend including antibody testing into antiepidemic measures and limit antigen testing to seronegative individuals.


An enzyme linked immunoassay for anti-müllerian hormone: a new tool for the evaluation of testicular function in infants and children.
Anti-Müllerian hormone (AMH), also called Müllerian-inhibiting substance or factor was measured by an interspecific enzyme-linked immunoassay in the serum of 218 normal children and adults of both sexes and in 110 boys with various developmental disorders. AMH levels were high [81.67 ng/ml +/- 7.44(SEM)] in normal males under 2 yr of age, fell progressively in older boys and, decreased sharply at puberty. Serum AMH was not detectable in adults or in females at any age, with very rare exceptions. AMH serum concentrations were significantly decreased in infants with disorders of sex differentiation, particularly testicular dysgenesis, and increased in patients with delayed puberty. In contrast, levels were not significantly affected by either cryptorchidism or chorionic gonadotropin stimulation. AMH shows promise as a marker of testicular function in infancy.


Histone acetylation: influence on transcription, nucleosome mobility and positioning, and linker histone-dependent transcriptional repression.
We demonstrate using a dinucleosome template that acetylation of the core histones enhances transcription by RNA polymerase III. This effect is not dependent on an increased mobility of the core histone octamer with respect to DNA sequence. When linker histone is subsequently bound, we find both a reduction in nucleosome mobility and a repression of transcription. These effects of linker histone binding are independent of core histone acetylation, indicating that core histone acetylation does not prevent linker histone binding and the concomitant transcriptional repression. These studies are complemented by the use of a Xenopus egg extract competent both for chromatin assembly on replicating DNA and for RNA polymerase III transcription. Incorporation of acetylated histones and lack of linker histones together facilitate transcription by >10-fold in this system; however, they have little independent effect on transcription. Thus core histone acetylation significantly facilitates transcription, but this effect is inhibited by the assembly of linker histones into chromatin.


Self-guided Change: The most common form of long-term, maintained health behavior change.
Millions of people change risky, health-related behaviors and maintain those changes. However, they often take years to change, and their unhealthy behaviors may harm themselves and others and constitute a significant cost to society. A review-similar in nature to a scoping review-was done of the literature related to long-term health behavior change in six areas: alcohol, cocaine and heroin misuse, gambling, smoking, and overeating. Based on the limited research available, reasons for change and strategies for changing and for maintaining change were also reviewed. Fifty years of research clearly indicate that as people age, in the case of alcohol, heroin and cocaine misuse, smoking, and gambling, 80-90 percent moderate or stop their unhealthy behaviors. The one exception is overeating; only 20 percent maintain their weight loss. Most of these changes, when they occur, appear to be the result of self-guided change. More ways to accelerate self-guided, health-related behavior change need to be developed and disseminated.


Structural basis for specific RNA recognition by the alternative splicing factor RBM5.
The RNA-binding motif protein RBM5 belongs to a family of multi-domain RNA binding proteins that regulate alternative splicing of genes important for apoptosis and cell proliferation and have been implicated in cancer. RBM5 harbors structural modules for RNA recognition, such as RRM domains and a Zn finger, and protein-protein interactions such as an OCRE domain. Here, we characterize binding of the RBM5 RRM1-ZnF1-RRM2 domains to cis-regulatory RNA elements. A structure of the RRM1-ZnF1 region in complex with RNA shows how the tandem domains cooperate to sandwich target RNA and specifically recognize a GG dinucleotide in a non-canonical fashion. While the RRM1-ZnF1 domains act as a single structural module, RRM2 is connected by a flexible linker and tumbles independently. However, all three domains participate in RNA binding and adopt a closed architecture upon RNA binding. Our data highlight how cooperativity and conformational modularity of multiple RNA binding domains enable the recognition of distinct RNA motifs, thereby contributing to the regulation of alternative splicing. Remarkably, we observe surprising differences in coupling of the RNA binding domains between the closely related homologs RBM5 and RBM10.


[Controlled release using temperature-responsive poly(N-isopropylacrylamide) gel].
Poly (N-isopropylacrylamide) (PNIPAAm) gels were found to undergo discontinuous swelling-deswelling changes in response to a limited alteration in external temperatures. By utilizing such as thermosensitive characteristic of the PNIPAAm gel, controlled drug release was studied extensively. Drug release profiles were well established in connection with the temperature dependence of swelling ratio for the gel. The thermal regulation of the swelling degree of the gel made it possible for us to design several ways for performing a unique drug release profile such as a "pulsatile" or "on-off" release of indomethacin. Attempts to develop a more excellent drug release system have being made through studies of molecular design and synthesis for PNIPAAm-based thermosensitive gels.


Clusters of transmembrane residues are critical for human prostacyclin receptor activation.
Relaxation of vascular smooth muscle and prevention of blood coagulation are mediated by ligand-induced activation of the human prostacyclin (hIP) receptor, a seven-transmembrane-domain G-protein-coupled receptor (GPCR). In this study, we elucidate the molecular requirements for receptor activation within the region of the ligand-binding pocket, identifying transmembrane residues affecting potency. Eleven of 30 mutated residues in the region of the ligand-binding domain exhibited defective activation (decreased potency). These critical residues localized to four distinct clusters (analysis via a rhodopsin-based human prostacyclin receptor homology model). Residues Y75(2.65) (TMII), F95(3.28) (TMIII), and R279(7.40) (TMVII) comprised the immediate binding-pocket cluster and were shown to be essential for proper receptor activation, compared to equivalent expression levels of the wild-type hIP (WT EC(50) = 1.2 +/- 0.1 nM; Y75(2.65)A EC(50) = 347.3 +/- 62.8 nM, p < 0.001; F95(3.28)A EC(50) = 8.0 +/- 0.6 nM, p < 0.001; R279(7.40)A EC(50) = 130 +/- 63.0 nM, p < 0.001). Residues S20(1.39) (TMI), F24(1.43) (TMI), and F72(2.62) (TMII) were localized to a cluster involving P17(1.36), a critical residue thought to facilitate transmembrane movement during changes in activation conformation. A third cluster formed around amino acid D60(2.50) (TMII), containing the highly conserved (100% of prostanoid receptors) D288(7.49)/P289(7.50) motif located in TMVII. Last, a large hydrophobic cluster composed of aromatic residues F146(4.52) (TMIV), F150(4.56) (TMIV), F184(5.40) (TMV), and Y188(5.44) (TMV) was observed away from the ligand-binding pocket, but still necessary for hIP activation. These results assist in delineating the potential molecular requirements for agonist-induced signaling through the transmembrane domain. Such observations may be generally applicable, as many of these clusters are highly conserved among the prostanoid receptors as well as other class A GPCRs.


EB1 and EB3 control CLIP dissociation from the ends of growing microtubules.
EBs and CLIPs are evolutionarily conserved proteins, which associate with the tips of growing microtubules, and regulate microtubule dynamics and their interactions with intracellular structures. In this study we investigated the functional relationship of CLIP-170 and CLIP-115 with the three EB family members, EB1, EB2(RP1), and EB3 in mammalian cells. We showed that both CLIPs bind to EB proteins directly. The C-terminal tyrosine residue of EB proteins is important for this interaction. When EB1 and EB3 or all three EBs were significantly depleted using RNA interference, CLIPs accumulated at the MT tips at a reduced level, because CLIP dissociation from the tips was accelerated. Normal CLIP localization was restored by expression of EB1 but not of EB2. An EB1 mutant lacking the C-terminal tail could also fully rescue CLIP dissociation kinetics, but could only partially restore CLIP accumulation at the tips, suggesting that the interaction of CLIPs with the EB tails contributes to CLIP localization. When EB1 was distributed evenly along the microtubules because of overexpression, it slowed down CLIP dissociation but did not abolish its preferential plus-end localization, indicating that CLIPs possess an intrinsic affinity for growing microtubule ends, which is enhanced by an interaction with the EBs.


Visual information affects adaptation to novel talkers: Ethnicity-specific and ethnicity-independent learning of L2-accented speech.
Prior work demonstrates that exposure to speakers of the same accent facilitates comprehension of a novel talker with the same accent (accent-specific learning). Moreover, exposure to speakers of multiple different accents enhances understanding of a talker with a novel accent (accent-independent learning). Although bottom-up acoustic information about accent constrains adaptation to novel talkers, the effect of top-down social information remains unclear. The current study examined effects of apparent ethnicity on adaptation to novel L2-accented ("non-native") talkers while keeping bottom-up information constant. Native English listeners transcribed sentences in noise for three Mandarin-accented English speakers and then a fourth (novel) Mandarin-accented English speaker. Transcription accuracy of the novel talker improves when: all speakers are presented with east Asian faces (ethnicity-specific learning); the exposure speakers are paired with different, non-east Asian ethnicities and the novel talker has an east Asian face (ethnicity-independent learning). However, accuracy does not improve when all speakers have White faces or when the exposure speakers have White faces and the test talker has an east Asian face. This study demonstrates that apparent ethnicity affects adaptation to novel L2-accented talkers, thus underscoring the importance of social expectations in perceptual learning and cross-talker generalization.


The role of religion in shaping sexual frequency and satisfaction: evidence from married and unmarried older adults.
This study assesses the role of religion in influencing sexual frequency and satisfaction among older married adults and sexual activity among older unmarried adults. The study proposes and tests several hypotheses about the relationship between religion and sex among these two groups of older Americans, using nationally representative data from the National Social Life, Health, and Aging Project. Results suggest that among married older adults, religion is largely unrelated with sexual frequency and satisfaction, although religious integration in daily life shares a weak, but positive, association with pleasure from sex. For unmarried adults, such religious integration exhibits a negative association with having had sex in the last year among women, but not among men.


Analysing the impact of nucleo-cytoplasmic shuttling of β-catenin and its antagonists APC, Axin and GSK3 on Wnt/β-catenin signalling.
The canonical Wnt signalling pathway plays a critical role in development and disease. The key player of the pathway is β-catenin. Its activity is mainly regulated by the destruction complex consisting of APC, Axin and GSK3. In the nucleus, the complex formation of β-catenin and TCF initiates target gene expression. Our study provides a comprehensive analysis of the role of nucleo-cytoplasmic shuttling of APC, Axin, and GSK3 and the inactivation of β-catenin by the destruction complex in Wnt/β-catenin signalling. We address the following questions: Can nucleo-cytoplasmic shuttling of APC, Axin and GSK3 increase the [β-catenin/TCF] concentration? And, how is the [β-catenin/TCF] concentration influenced by phosphorylation and subsequent degradation of nuclear β-catenin? Based on experimental findings, we develop a compartmental model and conduct several simulation experiments. Our analysis reveals the following key findings: 1) nucleo-cytoplasmic shuttling of β-catenin and its antagonists can yield a spatial separation between the said proteins, which results in a breakdown of β-catenin degradation, followed by an accumulation of β-catenin and hence leads to an increase of the [β-catenin/TCF] concentration. Our results strongly suggest that Wnt signalling can benefit from nucleo-cytoplasmic shuttling of APC, Axin and GSK3, although they are in general β-catenin antagonising proteins. 2) The total robustness of the [β-catenin/TCF] output is closely linked to its absolute concentration levels. We demonstrate that the compartmental separation of β-catenin and the destruction complex does not only lead to a maximization, but additionally to an increased robustness of [β-catenin/TCF] signalling against perturbations in the cellular environment. 3) A nuclear accumulation of the destruction complex renders the pathway robust against fluctuations in Wnt signalling and against changes in the compartmental distribution of β-catenin. 4) Elucidating the impact of destruction complex inhibition, we show that the [β-catenin/TCF] concentration is more effectively enhanced by inhibition of the kinase GSK3 rather than the binding of β-catenin to the destruction complex.


Current topics in artificial insemination of sheep.
There have been developments in several aspects of artificial insemination (AI) in recent years, some of which have been directly responsible for proliferation of AI in the sheep-breeding industries of several countries. The most notable advances have probably been associated with the development of intrauterine insemination by laparoscopy. There is potential for refinement of some of the related techniques, particularly in the area of control of ovulation and definition of appropriate times and optimum doses of spermatozoa for insemination. It is unlikely that laparoscopic AI will be developed sufficiently that it will become readily affordable, and therefore widely practised, by commercial producers. Unfortunately, there has been little progress in the past few years in improvement of the methods of cryopreservation of ram semen. There is considerable potential for AI to have a significant impact on the genetic improvement of sheep, though this has yet to be evaluated in practice. However, if the full potential of AI in sheep is to be realized, it will likely only happen when methods of freezing semen are improved sufficiently that cervical or even vaginal insemination can be widely used with frozen-thawed semen, or when practicable methods of deep cervical or intrauterine insemination through the cervix are developed.


Targeting truncated RXRα for cancer therapy.
Retinoid X receptor-alpha (RXRα), a unique member of the nuclear receptor superfamily, is a well-established drug target, representing one of the most important targets for pharmacologic interventions and therapeutic applications for cancer. However, how RXRα regulates cancer cell growth and how RXRα modulators suppress tumorigenesis are poorly understood. Altered expression and aberrant function of RXRα are implicated in the development of cancer. Previously, several studies had demonstrated the presence of N-terminally truncated RXRα (tRXRα) proteins resulted from limited proteolysis of RXRα in tumor cells. Recently, we discovered that overexpression of tRXRα can promote tumor growth by interacting with tumor necrosis factor-alpha-induced phosphoinositide 3-kinase and NF-κB signal transduction pathways. We also identified nonsteroidal anti-inflammatory drug Sulindac and analogs as effective inhibitors of tRXRα activities via a unique binding mechanism. This review discusses the emerging roles of tRXRα and modulators in the regulation of cancer cell survival and death as well as inflammation and our recent understanding of tRXRα regulation by targeting the alternate binding sites on its surface.


Clinical utility of a regional precision medicine molecular tumor board and challenges to implementation.
Molecular tumor boards provide precision treatment recommendations based on cancer genomic profile. However, practical barriers limit their benefits. We studied the clinical utility of the precision medicine molecular tumor board (PMMTB) and described challenges with PMMTB implementation. An observational cohort study included patients reviewed by the PMMTB between September 2015 to December 2017. Patients who had consented to the registry study were included. The primary endpoint of this study was time on treatment (ToT) ratio. Clinical utility was established if the primary endpoint had least 15% of patients achieving a ToT ratio of ≥1.3. Overall, 278 patients were presented to the PMMTB and 113 cases were included in the final analysis. The PMMTB identified at least one nonstandard of care (SOC) clinically actionable mutation for 69.0% (78/113) of cases. In patients who received non-SOC treatment, 43.8% (7/16) achieved a ToT ratio of 1.3 or more (p < 0.001). Fifty-nine patients did not receive non-SOC recommendations. Reasons for not pursuing treatment included 35.6% having response to current treatment, 20.3% died prior to starting or considering PMMTB recommendations, 13.6% pursued other treatment options based on clinician discretion, another 10.2% pursued other treatment options because clinical trials recommended were not geographically accessible, 8.5% had rapid decline of performance status, 6.8% lacked of financial support for treatment, and 5.1% were excluded from clinical trials due to abnormal laboratory values. The regional PMMTB non-SOC recommendations benefitted a majority of patients and additional processes were implemented to assist with non-SOC treatment accessibility.


Losses tune differently than gains: how gains and losses shape attentional scope and influence goal pursuit.
Research on the asymmetric effect of negative versus positive affective states (induced by gains or losses) on scope of attention, both at a perceptual and a conceptual level, is abundant. However, little is known about the moderating effect of anticipating gains or losses versus actually experiencing them and about any downstream consequences of these effects on goal-directed behaviour. In two studies, we show that gains versus losses induce qualitatively different processes. In Experiment 1, we demonstrate that the anticipation of monetary gains results in a narrowing of attentional scope, while experiencing gains broadens the scope of attention. We find the reverse pattern concerning monetary losses - while anticipation of monetary losses results in broadening of attentional scope, the actual experience of losses results in narrowing of attentional scope. Additionally, Experiment 2 replicates these findings and shows how differential attentional tuning as a function of the anticipation versus experience of gains versus losses modulates priming-induced goal-directed behaviour.


Line spectroscopic reflectometry for rapid and large-area thickness measurement.
Thickness measurements in the range of 0.1-1 mm over large optically transparent layers are essential in various manufacturing applications. However, existing non-contact measurement methods, which typically measure a single point or a few points at a time, fall short in their suitability for inline area measurement. Here, we introduce line spectroscopic reflectometry (LSR), an approach that extends the point measurement of traditional SR to line measurement, enabling rapid thickness measurement over large areas. By combining line beam illumination and line spectroscopy, LSR can measure 2048 points simultaneously, thereby boosting the measurement speed by two thousand times. We detail the measurement principle and the optical design in the near-infrared regime, and demonstrate thickness measurements of single-layered and double-layered samples over a measurement line length of up to 68 mm. Furthermore, we showcase the inline area measurement capability of LSR through one-dimensional sample scanning, with measurement rates limited only by camera readout rates.


[Recent results of clinical studies of synergistic treatment in obstructive respiratory tract diseases].
Asthma is a chronic inflammatory disease of the bronchial tree, characterised by reversible obturation, bronchial mucosal inflammation and bronchial hyperresponsiveness. In the treatment of asthma, most important is avoidance of provoking allergens and regular anti-inflammatory treatment with inhaled glucocorticosteroids. For patients, very important is quick relief from asthma symptoms, this is why they prefer fast and long acting beta 2-agonists as a symptomatic treatment. Optimal control of asthma symptoms can be achieved with combination treatment consisting of inhaled glucocorticosteroid and beta 2-agonist. Budesonide is a corticosteroid that treats the underlying airway inflammation in asthma; formoterol is a fast and long-acting beta 2-agonist that prevents and reverses airway obstruction. Thus budesonide and formoterol have complementary effects, treating two different components of asthma. Clinical studies show that in the treatment of asthma Symbicort is more effective than double dose GCS, due to the budesonide/formoterol synergy. It is at least as effective, well tolerated and safe as its mono-products in corresponding doses given via separate inhalers. More convenient treatment represents an important benefit for patients with asthma. Symbicort is recommended for regular treatment and could also be used "as needed" due to the rapid onset of the bronchodilatory effect of formoterol.


Is conservative management a safe approach for patients with acute acalculous cholecystitis presenting with an acute abdomen?
Patients with acute acalculous cholecystitis (AAC) often present with acute abdominal symptoms. However, recent clinical studies have suggested that some patients with AAC and an acute abdomen, especially when caused by viruses or rheumatic disease, may not require cholecystectomy and that conservative treatment is adequate. Whether cholecystectomy is superior to conservative treatment for patients with AAC presenting with a severe acute abdomen is still uncertain. This was a case series study of AAC-related literature published between 1960 and 2022. In total, 171 cases (104 viral infection-associated AAC and 67 rheumatic disease-associated AAC) were included. The prognoses of patients receiving cholecystectomy or conservative treatment were compared. To account for confounding factors, etiological stratification and logistic regression were performed. The prognosis was similar for patients undergoing cholecystectomy and conservative treatment (P value .364), and virus infection-associated AAC had a better prognosis than rheumatic disease-associated AAC (P value .032). In patients with AAC caused by viruses or rheumatic disease, the acute abdomen can be adequately managed by conservative treatment of the underlying etiology and does not mandate surgical intervention.


Current concepts in periodontal bioengineering.
Repair of tooth supporting alveolar bone defects caused by periodontal and peri-implant tissue destruction is a major goal of reconstructive therapy. Oral and craniofacial tissue engineering has been achieved with limited success by the utilization of a variety of approaches such as cell-occlusive barrier membranes, bone substitutes and autogenous block grafting techniques. Signaling molecules such as growth factors have been used to restore lost tooth support because of damage by periodontal disease or trauma. This paper will review emerging periodontal therapies in the areas of materials science, growth factor biology and cell/gene therapy. Several different polymer delivery systems that aid in the targeting of proteins, genes and cells to periodontal and peri-implant defects will be highlighted. Results from preclinical and clinical trials will be reviewed using the topical application of bone morphogenetic proteins (BMP-2 and BMP-7) and platelet-derived growth factor-BB (PDGF) for periodontal and peri-implant regeneration. The paper concludes with recent research on the use of ex vivo and in vivo gene delivery strategies via gene therapy vectors encoding growth promoting and inhibiting molecules (PDGF, BMP, noggin and others) to regenerate periodontal structures including bone, periodontal ligament and cementum.


Prevention of apoptosis in CNTF-dependent neurons by a mutant ICE and by viral protein CrmA but not by proto-oncogene product Bcl-2.
The interleukin-1beta converting enzyme (ICE) gene family, (homologues of C. elegans cell death gene product Ced-3) plays an important role in controlling programmed cell death. Nerve growth factor (NGF) promotes survival of cultured embryonic chicken dorsal root ganglion neurons. Ciliary ganglion neurons depend exclusively on ciliary neurotrophic factor (CNTF) for survival. Complete depletion of NGF or CNTF from culture medium induces apoptosis in both types of neurons. We can prevent apoptosis, due either to NGF or CNTF withdrawal and in either type of neuron, by overexpression of a mutant inactive ICE and an ICE inhibitor, the product of cowpox virus gene crmA. Bcl-2 does not prevent apoptosis in CNTF-dependent ciliary neurons or DRG neurons as it does in NGF-dependent neurons. These results suggest that neuronal cell death is mediated through a common effector mechanism involving the Ice family of genes, whereas different suppression mechanisms are engaged depending upon the specific neurotrophic factors present.


Size determination of hyaluronan using a gas-phase electrophoretic mobility molecular analysis.
Hyaluronan (HA) is a linear non-sulfated polysaccharide mainly found in the extracellular matrix. The size of HA can vary from a few disaccharides up to at least 25,000 units, reaching molecular weights of 10 10(3) kDa. HA has many biological functions, and both its size and tissue concentration play an important role in many physiological and pathological processes. It is relatively easy to determine the HA concentration using enzyme-linked binding protein assays, but the molecular weight of HA has so far been shown to be a more challenging task to measure. Here, we present a method for size determination of HA using gas-phase electrophoretic mobility molecular analysis (GEMMA), which utilizes the electrophoretic mobility of molecules in air to estimate the molecular weight of the analyte. We show that this method gives reliable molecular weight estimations of HA in the range of 30-2400 kDa, which covers almost its whole biological range. The average measuring time for one GEMMA spectrum is between 5 and 10 min using only 6 pg of HA. In addition, the peak area in a GEMMA spectrum can be used to estimate the HA concentration in the sample. The high sensitivity and small sample volumes make GEMMA an excellent tool for both size determinations and estimation of concentration of samples with low HA concentration, as is the case for HA extracted from small tissue samples.


Dental public health in California: a mixed picture.
Californians face significant dental public health problems. To address these problems, state government, professional organizations, and philanthropic entities in some areas have joined forces. Major issues such as fluoridation, access to care, and the role of the Dental Board of California are examined in terms of the varying roles these critical segments play in affecting the oral health of Californians. This issue of the Journal is dedicated to an examination of public health dentistry in California. While often thought of as innovative and at the "cutting-edge," the state presents a mixed picture of publicly funded oral health programs. Public health concerns sometimes take a lower priority or are overlooked by state government in an era of cutbacks. California lags behind other states in many public goods crucial to the overall quality of life of its residents. This dichotomy is evident in dental public health as it is in education, general health, and air quality. This paper assesses selected dental public health programs, identifying those where innovations have occurred and other program areas where the state has inadequately addressed the dental public health needs of its population.


Screening and periodical medical examinations as important part of public health: problem of the legal implementation.
Introduction: Public health is an important concept, which is continually being globalized and integrated into today's society. It helps to improve and prolong the quality of life of people and prevent the spread of epidemics and serious incurable diseases. The components of public health include protection, prevention, and promotion. Prevention, the measures taken to prevent disease as opposed to treatment consist of screening and periodical medical examinations. There are two types of screening- universal screening and case finding (individual screening). Universal screening and periodical medical examination are identical concepts; the terms dispensary and individual screening (case finding) have similar meanings and can be used interchangeably. These concepts and their importance are analyzed in this research. The aim: A research on the legal regulation of periodic health examinations and screening as a two systems, which provides the implementation of prevention within the public health. Analysis of foreign experience such countries as: Great Britain, USA, Austria, Germany, Australia, France, Italy and others. Materials and methods: The research based on: Ukrainian legislation, European Union's Law Acts, decisions of the ECHR, EU's member-states law, WHO Acts and Recommendations, scientific articles. The research is also based on general scientific and special research methods (such as dialectical, comparative, analytic, synthetic). Review: In Europe (except Germany and Austria) is happening the transition from the system of mandatory periodical medical examination to new screening system. However, despite this, periodical medical examinations of Europeans held in connection with exist system health insurance (both voluntary and mandatory). Conclusions: Screening and periodical medical examinations are two of the most important aspects of public health as they help to diagnose diseases at an early stage, even before showing any symptoms. Screening and periodical medical examinations ensures the safety and health of the entire population as opposed to certain individuals and therefore be mandatory procedure in today's society.


Is the framing effect a framing affect?
Over the past 30 years, researchers have shown that human choices are highly sensitive to the ways in which alternatives are presented. For example, when individuals face a choice between a sure and a risky option, their willingness to take risks varies depending on whether the alternatives are framed in terms of gain or loss. The current major hypothesis that explains such a framing effect predicts that compared with an equivalent risky option, sure gains are emotionally attractive and sure losses are emotionally aversive. Using a behavioural paradigm, the main objective of the current study was to experimentally observe the extent to which the emotional attraction to sure gains and aversion to sure losses are at the core of framing susceptibility. First, our results showed that, as the literature suggests, the emotional attraction to sure gains and aversion to sure losses underpin the framing effect. Second, our results showed that methodological factors moderated the role of these emotional mechanisms in the framing effect. Implications and directions for future studies are discussed.


Neurospora crassa catalases, singlet oxygen and cell differentiation.
The morphogenetic transitions of the N. crassa asexual life cycle are responses to a hyperoxidant state in which probably singlet oxygen is generated. Induction of catalase activity and catalase oxidation by singlet oxygen are consequences of this recurrent hyperoxidant state. Here the biochemical properties and regulation of two large monofunctional catalases are reviewed, and a new catalase-peroxidase gene and activity is described. Catalase-3 is associated to growing and Catalase-1 to non-growing cells. Under stressful conditions one of these catalases is synthesized, depending on whether growth can be continued or a resistant cell has to be made. The catalase-peroxidase Catalase-2 was possibly derived from a bacterial enzyme. In contrast to the other catalases, Catalase-2 had catalase and peroxidase activity. Catalase-2 was expressed under conditions in which vacuolization of hyphae is observed. All three enzymes have a chlorin in its active site instead of ferroprotoheme IX and are resistant to molar concentrations of hydrogen peroxide. These and all other catalases tested so far are oxidized by singlet oxygen, probably at the heme moiety. The catalase activity is virtually unaffected by oxidation, but the enzymes are probably degraded more rapidly than the unmodified ones.


Phosphazene cations.
Cations derived from (NPCl2)3, hexachloro-cyclo-triphosphazene, the weakly basic precursor of phosphazene polymers, have been prepared using strongly electrophilic reagents based on carborane anions. N-protonated, N-methylated, and N-silylated adducts of (NPCl2)3 have been isolated and characterized by X-ray crystallographic and spectroscopic methods. The normally potent chloride-abstracting silyl reagents of the type R3Si(carborane) are unable to abstract chloride from (NPCl2)3, even though the coordinatively unsaturated N2P2Cl5+ cation is widely accepted as a reactive intermediate in the ring-opening polymerization of (NPCl2)3.


Rational design of a transition state analogue with picomolar affinity for Pseudomonas aeruginosa PvdQ, a siderophore biosynthetic enzyme.
The Pseudomonas aeruginosa enzyme PvdQ can process different substrates involved in quorum-sensing or in siderophore biosynthesis. Substrate selectivity was evaluated using steady-state kinetic constants for hydrolysis of N-acyl-homoserine lactones (HSLs) and p-nitrophenyl fatty acid esters. PvdQ prefers substrates with alkyl chains between 12 and 14 carbons long that do not bear a 3-oxo substitution and is revealed here to have a relatively high specificity constant for selected N-acyl-HSLs (kcat/KM = 10(5) to 10(6) M(-1) s(-1)). However, endogenous P. aeruginosa N-acyl-HSLs are ≥100-fold disfavored, supporting the conclusion that PvdQ was not primarily evolved to regulate endogenous quorum-sensing. PvdQ plays an essential biosynthetic role for the siderophore pyoverdine, on which P. aeruginosa depends for growth in iron-limited environments. A series of alkylboronate inhibitors was found to be reversible, competitive, and extremely potent (Ki ≥ 190 pM). A 1.8 Å X-ray structure shows that 1-tridecylboronic acid forms a monocovalent bond with the N-terminal β-chain Ser residue in the PvdQ heterodimer, mimicking a reaction transition state. This boronic acid inhibits growth of P. aeruginosa in iron-limited media, reproducing the phenotype of a genetic pvdQ disruption, although co-administration of an efflux pump inhibitor is required to maintain growth inhibition. These findings support the strategy of designing boron-based inhibitors of siderophore biosynthetic enzymes to control P. aeruginosa infections.


Transforming the curriculum through the intergenerational lens.
Our society is aging at a rapid rate and with this trend comes many of the social and economic demands that the profession of Social Work addresses. Akey dilemma of the profession is how to interest and educate undergraduate social work students in aging and gerontology so that the needs of elderly can be supported. Social Work students notoriously are primarily interested in working with children and adolescents. With the support of the John A. Hartford Foundation's Geriatric Enrichment in Social Work Education grant, the authors developed a Spiral Perspective to infuse intergenerational content into the curriculum of their department and to give students exposure to geriatric content throughout their educational experience.


Endothelial to mesenchymal transition in the cardiovascular system.
Endothelial to mesenchymal transition (EndMT) is a special type of epithelial to mesenchymal transition. It is a process that is characterized by the loss of features of endothelial cells and acquisition of specific markers of mesenchymal cells. A variety of stimuli, such as inflammation, growth factors, and hypoxia, regulate EndMT through various signaling pathways and intracellular transcription factors. It has been demonstrated that epigenetic modifications are also involved in this process. Recent studies have identified the essential role of EndMT in the cardiovascular system. EndMT contributes to steps in cardiovascular development, such as cardiac valve formation and septation, as well as the pathogenesis of various cardiovascular disorders, such as congenital heart disease, myocardial fibrosis, myocardial infarction and pulmonary arterial hypertension. Thus, comprehensive understanding of the underlying mechanisms of EndMT will provide novel therapeutic strategies to overcome congenital heart disease due to abnormal development and other cardiovascular diseases. This review will focus on summarizing the currently understood signaling pathways and epigenetic modifications involved in the regulation of EndMT and the role of EndMT in pathophysiological conditions of the cardiovascular system.


Roles of lysophosphatidic acid in cardiovascular physiology and disease.
The bioactive lipid mediator lysophosphatidic acid (LPA) exerts a range of effects on the cardiovasculature that suggest a role in a variety of critical cardiovascular functions and clinically important cardiovascular diseases. LPA is an activator of platelets from a majority of human donors identifying a possible role as a regulator of acute thrombosis and platelet function in atherogenesis and vascular injury responses. Of particular interest in this context, LPA is an effective phenotypic modulator of vascular smooth muscle cells promoting the de-differentiation, proliferation and migration of these cells that are required for the development of intimal hyperplasia. Exogenous administration of LPA results in acute and systemic changes in blood pressure in different animal species, suggesting a role for LPA in both normal blood pressure regulation and hypertension. Advances in our understanding of the molecular machinery responsible for the synthesis, actions and inactivation of LPA now promise to provide the tools required to define the role of LPA in cardiovascular physiology and disease. In this review we discuss aspects of LPA signaling in the cardiovasculature focusing on recent advances and attempting to highlight presently unresolved issues and promising avenues for further investigation.


Prevalence of overweight among Malaysian adults from rural communities.
Assessment of the nutritional status of 4054 households from rural communities in Peninsular Malaysia was undertaken from 1992 to 1995. Body mass index (BMI) and waist-to-hip ratio (WHR) were obtained from a self-selected sample of 1854 men and 2741 women aged >= 18 years. The BMI and WHR results are presented according to gender, age groups and type of community as defined by the main occupation, namely, fishing, rice farming, estate work, rubber and coconut small-holding. The mean BMI for men and women of all age groups are 22.5 kg/m2 and 23.8 kg/m2, respectively. The mean BMI for both genders increases with age between 18.0 and 49.9 years, after which the value declines. The prevalence of pre-obese (BMI >= 25.0-29.9 kg/m2) is 19.8% for men and 28.0% for women. The prevalence of obese men and women (>= 30.0 kg/m2) is 4.2% and 11.1%, respectively. The highest prevalence of pre-obese and obese men is found in the age groups of 30.0-49.9 years, while that for women is in the 40.0-49.9 years age group. The prevalence of pre-obesity and obesity is higher in women than in men for every age group. A similar result was indicated by WHR whereby a higher proportion of women (22.5%) than men (5%) for all ages was found to show central obesity. The prevalence of overweight adults is higher when compared with previous studies on subjects from almost similar rural communities. This study indicated that overweight is on the increase in rural communities, especially among female subjects.


[Ultrastructural relief of unaffected mucosa in recurrent oral ulcer patients. 2].
Electron microscopy was performed on clinically normal vestibular mucosa biopsies of two patients affected with recurrent oral ulcers. Apoptotic cells were absent from vestibular mucosa; this is in contrast with the pathogenetic theory proposed by Honma et al., 1985 (1). Only a few modifications in the keratinization process (intracytoplasmic desmosomes, electrondense granules in basal keratinocytes) and an unusually high number of dendritic cells were found; dendritic cells could be involved in local immunological iperreactivity, responsible for the ulcers of these subjects.


Trypanosoma cruzi in a low- to moderate-risk blood donor population: seroprevalence and possible congenital transmission.
Several recent studies documented the seroprevalence of Trypanosoma cruzi in blood donors at high risk for infection, but little information is available regarding donors with lower levels of risk. Thus, the present study was designed to measure the seroprevalence of T. cruzi in a donor population with a low to moderate risk for infection. During a 10-month period, donations from all allogeneic blood donors in the American Red Cross Southwest Region were tested for T. cruzi antibodies by enzyme immunoassay, and results were confirmed by radioimmunoprecipitation. Confirmed-seropositive donors were counseled and lookback investigations were initiated for those who were repeat donors. A total of 100,089 donations were tested: 150 were repeatably reactive, and 3 (0.003%) were confirmed as positive for T. cruziantibodies. All three seropositive donors were from the Waco, TX, area, where the estimated seroprevalence rate was 1 in 7700. Two of these three donors reported no risk factors; both were born in the United States and had not traveled to an endemic area. Both had extensive familial histories of cardiac disease and complications. Blood donors seropositive for T. cruzi are present in populations with low to moderate risk, albeit at lower rates. The presence of seropositive blood donors without the usual identifiable risk factors argues against the use of a geographic screening question and also suggests that other routes of transmission, including the congenital route, should be considered in efforts to increase blood safety.


Continuous intraoperative EEG monitoring during carotid surgery.
Continuous intraoperative EEG monitoring and stump pressure measurements were studied during 85 carotid revascularizations performed in 40 symptomatic cerebrovascular patients and in 32 asymptomatic subjects with a cervical bruit. The decision to place a temporary shunt was made on the basis of intraoperative EEG abnormalities regardless of stump pressure values. 11 patients with contralateral carotid lesions showed marked EEG alterations, at the moment of clamping, which returned to normal after the placement of an indwelling shunt. Stump pressure values showed a wide variation and a poor correlation with intraoperative EEG changes. In the early postoperative period there were no deaths; no new neurological deficits were detected. In the follow-up there was only 1 asymptomatic carotid rethrombosis, not revealed by the EEG, which was suspected by Doppler sonography and confirmed by angiography. The authors conclude that EEG gives valuable information about cerebral functions during carotid revascularization and can reduce the intraoperative complications of the procedure. Stump pressure measurement cannot be used alone as a safe indicator of cerebral ischemia during carotid cross-clamping.


Evidence of the key role of metal-molecule bonding in metal-molecule-metal transport experiments.
The transport properties of two oligothiophene derivatives, that differ only by the chemical group coupling to gold, are compared. It is shown that the role of the coupling group in the transport properties can be decoupled from that of the conjugated body of the molecules and that Se is a better electronic coupling group than S. These results are accounted for semiquantitatively within the frame of the scattering theory of transport, using results from ultraviolet photoemission spectroscopy experiments as inputs for the position in energy of the molecular orbitals with respect to the Fermi level of the electrodes.


Hydra viridis: transfer of metabolites between Hydra and symbiotic algae.
"Back transfer" of metabolites from food to endosymbiotic algae in the digestive cells of Hydra viridis was demonstrated. Brine shrimp nauplii labeled with tritiated precursors of protein and nucleic acids (DNA and RNA) were fed to light and dark grown hydras. The fate of the label after a single feeding with radioactive material in hydra and algal fractions was followed by scintillation counting and autoradiographic techniques. Labeled thymidine was incorporated into DNA in both light- and dark-grown hydras. Although the symbiosis persists indefinitely in hydras in darkness (7-10 days) the number of algae per cell is reduced. Tritiated orotic acid and tritiated uridine, RNA precursors, were incorporated into peptides and proteins, and to a lesser extent into simple sugars, oligosaccharides, and oligonucleotides in hydra and algal fractions. Thus the metabolites of the brine shrimp food are available to both partners. A decrease over time in label introduced as 3H-orotic acid and 3H-uridine and incorporated into hydra RNA is compensated for by an increase in label in the algae, implying competition for constant quantities of metabolites from the single feeding. Although food availability, light, number of algae per cell, and other factors influence the quantity and rate of nutrient transfer between the partners, in both light and dark grown hydras the amount of "back transfer" of metabolites to the symbiotic algae is impressive.


Pharmacology of the sphincter of Oddi.
The sphincter of Oddi is the smooth muscle connection between the bile duct and the duodenum. Its physiological function is associated with a regular motility characterized by phasic contractions superimposed on the sphincter of Oddi baseline pressure. Recently introduced ERCP-manometry permits further studies of sphincter of Oddi pharmacology. A number of drugs have so far been studied. Sedatives of the diazepam type had no effect on the sphincter, while butylscopolaminium bromide, a typical neurotropic agent, brings about cessation of the sphincter motility for 3-8 minutes. Hymecromon lowered the sphincter baseline pressure from 9.8 to 7.8 mmHg. A 1.2 mg sublingual dose of nitroglycerin, a typical musculotropic agent, caused significant relaxation of the sphincter, and decreased baseline pressure from 8.9 mmHg to 2.9 mmHg; Sphincter motility was not affected. Morphine-like analgetics, in particular pentazocine, elevated sphincter baseline pressure, but buprenorphine and tramadol did not. Pharmacological doses of gastrointestinal hormones also affect the sphincter; CCK octapeptide, glucagon and secretin are able to decrease sphincter of Oddi baseline pressure, and CCK octapeptide abolishes sphincter motility. Sphincter of Oddi pharmacology is of clinical interest. The administration of sphincter-relaxing agents, in particular nitroglycerin and butylscopolaminium bromide, enables the endoscopist to extract small common bile duct stones without previous papillotomy. Analgetics that induce sphincter contraction and thus hinder the flow of bile and pancreatic juice, may be helpful for the treatment of pain in patients with pancreatico-biliary disease. Investigations into the effect of CCK on the healthy and diseased sphincter permit us to identify patients with sphincter dysfunction using a special CCK-provocation test.


Increased large VLDL particles confer elevated cholesteryl ester transfer in diabetes.
Plasma cholesteryl ester transfer (CET), reflecting transfer of cholesteryl esters from high density lipoproteins (HDL) towards apolipoprotein B-containing lipoproteins, may promote atherosclerosis development, and is elevated in Type 2 diabetes mellitus (T2DM). We determined the extent to which the relationship of plasma CET with very low density lipoprotein (VLDL) and low density lipoprotein (LDL) subfractions is modified in T2DM. Plasma CET, cholesteryl ester transfer protein (CETP) mass, as well as VLDL and LDL subfractions (nuclear magnetic resonance spectroscopy) were determined in 62 patients with T2DM and 53 nondiabetic subjects. Plasma CET and CETP mass were increased in T2DM, coinciding higher triglycerides and large VLDL particles (all P < 0·02). Plasma CET was positively related to the VLDL and the LDL particle concentration in age-, sex- and diabetes status-adjusted analysis (both P < 0·001). Multivariable linear regression analysis demonstrated an independent positive interaction between the presence of T2DM and the VLDL concentration on plasma CET (β = 0·238, P = 0·033). The relationship of plasma CET with the VLDL concentration was also positively modified by plasma glucose (β = 0·211, P = 0·004) and glycated haemoglobin (β = 0·190, P = 0·012). Of the individual VLDL subfractions, a positive interaction of diabetes status with large VLDL on plasma CET was observed (β = 0·280, P = 0·003). Neither the relationship of the LDL particle concentration nor of CETP mass with plasma CET was modified by the presence of T2DM (P > 0·15). Abnormalities in the concentration and composition of large VLDL particles are likely to contribute to elevated plasma CET in T2DM.


Anti-IgM treatment of C57BL/6-1pr/1pr mice: depletion of B cells reduces 1pr gene-induced lymphoproliferation and mononuclear cell vasculitis.
In order to study the role of B cells in autoimmune abnormalities observed in C57BL/6 mice bearing the autosomal mutant gene 1pr (lymphoproliferation), we treated mice from birth continuously with rabbit anti-IgM antiserum. Anti-IgM treatment resulted in the complete suppression of B cell development, documented by the absence of surface Ig-positive cells, the lack of lipopolysacchride-induced mitogenic responses, and the lack of autoantibody production. Although, anti-IgM-treated C57BL/6-1pr/1pr mice developed 1pr gene-associated lymphoproliferation due to the accumulation of Thy-1+, CD4-, CD8-, B220+ T lymphocytes in spleen and lymph nodes, the size of their spleen and lymph nodes was considerably smaller than that of normal rabbit serum-treated C57BL/6-1pr/1pr mice. Systemic vascular lesions associated with mononuclear cell infiltration were a little affected by anti-IgM treatment. This indicates that the development of mononuclear cell vasculitis in mice bearing the 1pr gene may be associated with the 1pr gene-induced lymphoproliferation and is independent of B cells and autoantibody production.


Identification of nine new HLA class I alleles in volunteers from the Singapore stem cell donor registries.
Based on unusual probe hybridization patterns, two human leukocyte antigen (HLA)-A, five HLA-B, and two HLA-C alleles (A*240208, A*3211Q; B*1822, B*3938Q, B*4606, B*4607N, B*5139; Cw*0321, Cw*0734) were identified in individuals from the Singapore Bone Marrow Donor Program and Singapore Cord Blood Bank. Eight of the nine alleles encode amino acid substitutions altering the antigen-binding region including three alleles with changes altering a cysteine at codon 164 (A*3211Q, B*3938Q, B*4607N). This substitution either eliminates a key disulfide bond or results in a stop codon, both likely affecting the expression of the HLA molecules. Only one allele (A*240208) carries a synonymous substitution.


Seeing Blue As Red: A Hypnotic Suggestion Can Alter Visual Awareness of Colors.
Some highly hypnotizable individuals have reported changes in objects' color with suggestions given in normal waking state. However, it is not clear whether this occurs only in their imagination. The authors show that, although subjects could imagine colors, a posthypnotic suggestion was necessary for seeing altered colors, even for a hypnotic virtuoso. She reported posthypnotic color alterations also selectively in response to specific target shapes in briefly presented object arrays. Surprisingly, another highly hypnotizable person showed a very different pattern of results. The control participants could not simulate virtuosos' results by applying cognitive strategies. The results imply that hypnosis can alter the functioning of automatic visual processes but only in some of the most hypnotizable individuals.


Intercellular communication and tissue growth. II. Tissue regeneration.
Intercellular communication was examined in regenerating rat liver and urodele skin, two tissues of fast but normal growth. In both, cellular communication is in general as good as in their respective normal intact state. This stands in striking contrast to the lack of cellular communication in tissues with cancerous growth. Upon wounding of the urodele skin, the normally permeable junctional membranes of cells near the wound border seal themselves off, thereby insulating the interiors of the communicated cell systems from the exterior. When the cells of two opposing borders make mechanical contact in the course of wound closure, communication between them ensues within 30 min. Within this period all cell movement also ceases ("contact inhibition"). The possible implications of these findings in the control of tissue growth are discussed.


Intraoperative pulmonary artery stenting: an alternative technique for the management of pulmonary artery stenosis.
Pulmonary artery reconstruction remains a challenging clinical problem. We sought to evaluate the use of intraoperative stenting in conjunction with open heart surgical repairs. We retrospectively analyzed data from 22 patients between 1998 and 2003 who underwent intraoperative pulmonary artery stenting. The mean age was 9.3 years (range, 9 months to 24 years). The left pulmonary artery was stented in 8 patients, the right in 13, the main in 1, and bilateral in 1. Available echocardiograms in 20 patients revealed a mean preoperative diameter of 7.6 mm (range, 3 to 16.5 mm) and a mean peak gradient of 45.4 mm Hg (range, 20 to 120 mm Hg). Augmentation patch angioplasty of the contralateral pulmonary artery was performed in 11 patients. Thirteen patients had pulmonary valve replacement and 11 had conduit replacement or augmentation. Three patients underwent tricuspid valve repair, 6 had Fontan, and 4 underwent a modified Maze procedure. Follow-up echocardiograms demonstrated a decrease in mean peak gradient to 4.3 mm Hg (range, 0 to 15 mm Hg), a change in mean peak gradient of 41.1 mm Hg (93% reduction). After stenting the mean pulmonary artery diameter increased to 10.9 mm (range, 6 to 17.9 mm). There was no perioperative mortality. At a mean follow-up of 22.8 months (range, 6 to 57 months), there were no surgical or percutaneous reinterventions. Intraoperative pulmonary artery stenting is a safe and effective technique that can be used as an alternative to patch angioplasty. Close follow-up is needed to examine the long-term outcome of this procedure, with special attention to the growth and development of the stented vessel.


Obstacles to effective model deployment in healthcare.
Despite an exponential increase in publications on clinical prediction models over recent years, the number of models deployed in clinical practice remains fairly limited. In this paper, we identify common obstacles that impede effective deployment of prediction models in healthcare, and investigate their underlying causes. We observe a key underlying cause behind most obstacles - the improper development and evaluation of prediction models. Inherent heterogeneities in clinical data complicate the development and evaluation of clinical prediction models. Many of these heterogeneities in clinical data are unreported because they are deemed to be irrelevant, or due to privacy concerns. We provide real-life examples where failure to handle heterogeneities in clinical data, or sources of biases, led to the development of erroneous models. The purpose of this paper is to familiarize modeling practitioners with common sources of biases and heterogeneities in clinical data, both of which have to be dealt with to ensure proper development and evaluation of clinical prediction models. Proper model development and evaluation, together with complete and thorough reporting, are important prerequisites for a prediction model to be effectively deployed in healthcare.


In vivo imaging of ocular blood flow using high-speed ultrasound.
Clinical ophthalmic ultrasound is currently performed with mechanically scanned, single-element probes, but these are unable to provide useful information about blood flow with Doppler techniques. Linear arrays are well-suited for the detection of blood flow, but commercial systems generally exceed FDA ophthalmic safety limits. A high-speed plane-wave ultrasound approach with an 18-MHz linear array was utilized to characterize blood flow in the orbit and choroid. Acoustic intensity was measured and the plane-wave mode was within FDA limits. Data were acquired for up to 2 sec and up to 20,000 frames/s with sets of steered plane-wave transmissions that spanned 2*θ degrees where 0 degrees was normal to the array. Lateral resolution was characterized using compounding from 1 to 50 transmissions and -6-dB lateral beamwidths ranged from 320 to 180 μm, respectively. Compounded high-frame-rate data were post-processed using a singular value decomposition spatiotemporal filter and then flow was estimated at each pixel using standard Doppler processing methods. A 1-cm diameter rotating scattering phantom and a 2-mm diameter tube with a flow of blood-mimicking fluid were utilized to validate the flow-estimation algorithms. In vivo data were obtained from the posterior pole of the human eye which revealed regions of flow in the choroid and major orbital vessels supplying the eye.


Humanized Mouse Models for Evaluation of PSC Immunogenicity.
New human pluripotent stem cell (hPSC)-derived therapies are advancing to clinical trials at an increasingly rapid pace. In addition to ensuring that the therapies function properly, there is a critical need to investigate the human immune response to these cell products. A robust allogeneic (or autologous) immune response could swiftly eliminate an otherwise promising cell therapy, even in immunosuppressed patients. In coming years, researchers in the regenerative medicine field will need to utilize a number of in vitro and in vivo assays and models to evaluate and better understand hPSC immunogenicity. Humanized mouse models-mice engrafted with functional human immune cell types-are an important research tool for investigating the mechanisms of the adaptive immune response to hPSC therapies. This article provides an overview of humanized mouse models relevant to the study of hPSC immunogenicity and explores central considerations for investigators seeking to utilize these powerful models in their research. © 2020 Wiley Periodicals LLC.


T lymphocyte ontogeny in adenosine deaminase-deficient severe combined immune deficiency after treatment with polyethylene glycol-modified adenosine deaminase.
Adenosine deaminase (ADA) deficiency causes severe combined immune deficiency (SCID) by interfering with the metabolism of deoxyadenosine, which is toxic to T lymphocytes at all stages of differentiation. Enzyme replacement with polyethylene glycol-modified ADA (PEG-ADA) has been previously shown to correct deoxyadenosine metabolism and improve mitogen-induced T lymphocyte proliferation. We studied the biochemical and immunologic effects of PEG-ADA in two infants with ADA-deficient SCID. While in a catabolic state, higher doses of PEG-ADA than previously described were required to normalize deoxyadenosine metabolism. After biochemical improvement, the patients recovered immune function in a pattern similar to that observed in normal thymic ontogeny and in patients with immunological reconstitution after bone marrow transplantation. Immune reconstitution was marked by the sequential appearance in the peripheral blood of phenotypic T lymphocytes corresponding to successive stages of thymic differentiation. Functional reconstitution was marked by the successive appearance of mitogen responses dependent on exogenous in vitro IL-2, mitogen responses not requiring exogenous IL-2, antigen-specific responses dependent on exogenous IL-2, and finally, antigen-specific responses not requiring exogenous IL-2. Natural killer function was tested in one patient and normalized with PEG-ADA therapy. Optimal PEG-ADA therapy appears to normalize thymic differentiation in ADA-deficient SCID, resulting in normal antigen-specific immune function.


The relationship between linoleic acid level in serum, adipose tissue and myocardium in humans.
A cross-sectional study of 80 consecutive cases at necropsy was undertaken to determine the relationship between linoleic acid in the serum, adipose tissue and myocardium of humans. The sample consisted of 55 males and 25 females aged 7 to 92 years who had died from cardiac and non-cardiac causes in the Southern Region of Tasmania, Australia. Fatty acids were extracted from samples of serum, adipose tissue and myocardium and separated using capillary gas liquid chromatography. Means and standard deviations were calculated for each of the main fatty acids in the three tissues studied. In serum and adipose tissue, there were significantly higher levels of linoleic acid (p<0.001 and p<0.001 in serum and adipose tissue, respectively) and total n-6 fatty acids (p< 0.002 and p< 0.001 in serum and adipose tissue, respectively) and significantly lower levels of oleic acid in females than in males (p< 0.001 and p<0.05 in serum and adipose tissue, respectively). In serum and adipose tissue, the ratio of total n-6 to total n-3 fatty acids was significantly higher in females than males (p<0.02 and p<0.001 in serum and adipose tissue, respectively). In myocardium, there were significantly higher levels of oleic acid (p<0.05) and linoleic acid (p<0.001) and significantly lower levels of arachidonic acid (p<0.001) and docosapentaenoic acid (p<0.02) in females than males. Total n-3 fatty acids in myocardium were significantly lower in females (p<0.001) resulting in a significantly higher ratio of total n-6 to total n-3 fatty acids in females (p<0.001). Highly significant Pearson correlations were found between levels of linoleic acid in adipose tissue and myocardium (p<0.0001), between adipose tissue and serum (p<0.001 ) and between serum and myocardium (p<0.001). The proportion of total polyunsaturated fatty acids (PUFA) in the myocardium was inversely related to the proportion of monounsaturated fatty acids (p<0.001) and inversely related to the proportion of saturated fatty acids (p<0.001). There was a significant positive correlation between the ratio of linoleic acid to linolenic acid in all three tissues. This study showed that there was a very strong relationship between the level of linoleic acid in adipose tissue and myocardial tissue, which suggests that dietary linoleic acid influences the level of myocar 1000 dial linoleic acid. These findings support the hypothesis that dietary linoleic acid has a direct influence on myocardial membrane linoleic acid levels.


Protective effect of ambroxol on pulmonary function after cardiopulmonary bypass.
To evaluate whether ambroxol administered orally during the perioperative period has a protective effect against postoperative pulmonary dysfunction in on-pump coronary artery bypass surgery. Fifty younger patients without known pulmonary disease were randomly assigned into 2 groups. In ambroxol group (n = 25), patients were given ambroxol for a week before and after the elective coronary artery bypass grafting. In control group (n = 25), placebo was given. Groups were compared with respect to pulmonary function tests (PFTs), lecithin/sphingomyelin (L/S) ratio in the bronchoalveolar lavage fluid, arterial blood gases, and incidence of perioperative morbidity. PFTs were performed before medication and repeated on the postoperative seventh day. Bronchoalveolar lavage fluid was obtained just before cardiopulmonary bypass and within the first postoperative hour. Room air arterial blood gases were checked before and 2 days after the operation. Postoperative lecithin/sphingomyelins were significantly lower than the preoperative values in both groups, but differences between the groups in either preoperative or postoperative measurements were not significant. Although preoperative PaO2 in both groups was similar, it was significantly lower in control group on postoperative second day (62.4 +/- 7.1 vs. 55.2 +/- 6.4 mm Hg, P < 0.05). In either groups, postoperative forced vital capacity and forced expiratory volume in 1 second were significantly lower than preoperative values with a more prominent decrease in control group. Perioperative morbidity was similar. In on-pump coronary artery bypass grafting, ambroxol improves postoperative PFTs and PaO2 levels without any significant clinical implication, and it exerts these effects possibly in ways other than surfactant modulation.


Chemotherapy-sparing treatment of haemophagocytic lymphohistiocytosis with intravenous immunoglobulins and corticosteroids.
Haemophagocytic lymphohistiocytosis (HLH) can be a rapidly fatal disease. Current treatment in adults is extrapolated from the HLH-2004 protocol that specifies a regimen of etoposide, dexamethasone and cyclosporine. However, HLH presents as a spectrum of disease severity. A therapeutic challenge arises for milder cases where the harms of potent chemotherapy such as etoposide may outweigh its benefit. We present a case of an adult with HLH who developed significant pancytopenia but was otherwise not critically ill and who responded to treatment with a chemotherapy-sparing approach consisting of intravenous immunoglobulins and corticosteroids alone. The case illustrates that tailored therapy may allow effective treatment of the disorder while minimising therapy-related toxicities.


CT-guided stereotactic biopsy of brain tumors: pathologic considerations.
Astrocytic tumors, the most common of the primary intracerebral neoplasms, are a heterogeneous group in terms of clinical behavior and pathologic appearance. Current histopathologic classification emphasizes this aspect; however, its application to tissue specimens removed by means of CT-guided stereotactic brain biopsy requires special considerations. Pertinent aspects of pathology relevant to assessment by CT scan stereotactic needle biopsy are discussed, together with a presentation of early results on the use of this diagnostic technique.


Clients and brothel managers in Kramat Tunggak, Jakarta, Indonesia: interweaving qualitative with quantitative studies for planning STD/AIDS prevention programs.
Clients and brothel managers are often the most powerful decision-makers regarding condom use in brothels, but since publicly promoting condom use is still "culturally" difficult in Indonesia, the most feasible way of reaching clients is through the female commercial sex workers (FCSWs) and their managers. The existence of quasi-official brothel complexes in many major Indonesian cities, however, does make the government a key player in promoting condom use within these complexes. Interweaving qualitative with quantitative studies, this paper, which is part of a larger study, reveals the FCSWs' client/managers-related determinants of condom use. Policies that will promote condom use in brothel complexes are critical to the prevention of the spread of HIV throughout this community, as well as from it to the greater community.


A review of retraction pockets: past, present and future management.
Retraction pockets can lead to hearing loss and cholesteatoma. Distinguishing stable from progressive disease is challenging to any otologist. The management of retraction pockets is a contentious issue with present treatment options often plagued with recurrence. The purpose of this article is to summarize recent developments in the aetiology of retraction pockets of the pars tensa, its diagnostic and management problems and to define possible future therapeutic options.


Tumor-Infiltrating CD8 T Cells Predict Clinical Breast Cancer Outcomes in Young Women.
Young women with breast cancer have disproportionately poor clinical outcomes compared to their older counterparts. The underlying biological differences behind this age-dependent disparity are still unknown and warrant investigation. Recently, the tumor immune landscape has received much attention for its prognostic value and therapeutic targets. The differential tumor immune landscape between age groups in breast cancer has not yet been characterized, and may contribute to the age-related differences in clinical outcomes. Computational deconvolution was used to quantify abundance of immune cell types from bulk transcriptome profiles of breast cancer patients from two independent datasets. No significant differences in immune cell composition that were consistent in the two cohorts were found between the young and old age groups. Regardless of absence of significant differences, the higher tumor infiltration of several immune cell types, such as CD8+ T and CD4+ T cells, was associated with better clinical outcomes in the young but not in the old age group. Mutational signatures analysis showed signatures previously not found in breast cancer to be associated with tumor-infiltrating lymphocyte (TIL) levels in the young age group, whereas in the old group, all significant signatures were those previously found in breast cancer. Pathway analysis revealed different gene sets associated with TIL levels for each age group from the two cohorts. Overall, our results show trends towards better clinical outcomes for high TIL levels, especially CD8+ T cells, but only in the young age group. Furthermore, our work suggests that the underlying biological differences may involve multiple levels of tumor physiology.


Genetic epidemiology of BRCA1.
Since the identification of the BRCA1 gene 10 years ago much has been learned about the role of the BRCA1 protein in cancer development. In particular, genetic and epidemiological approaches have informed about the spectrum of mutations that occur in the gene and the prevalence, penetrance, and phenotype associated with these mutations in various populations. Furthermore, advances have been made in understanding the environmental and genetic modifiers of cancer risk associated with BRCA1 mutations. In this review the current knowledge of the genetic epidemiology of BRCA1 is presented and the issues that still need to be addressed in this field are outlined.


Assessment of pulmonary microvascular permeability in acutely prepared sheep.
We hypothesized that the apparent difference in base-line lymph-to-plasma protein concentration ratios (L/P) between acutely and chronically prepared sheep is due to an underlying difference in pulmonary microvascular permeability. Therefore, we sought to determine the pulmonary microvascular osmotic reflection coefficient for acutely prepared sheep, in a manner similar to that used by Parker et al. (Circ. Res. 49: 1164-1172, 1981) in chronically prepared animals. In 20 acutely prepared sheep, we evaluated pulmonary lymph flow (QL) and L/P as left atrial pressure was progressively elevated. As a result of the elevated hydrostatic pressure, QL increased by 28 to 773% above base-line flows, accompanied by substantial dilution of lymphatic protein. At high QL, L/P approached a minimal value, (L/P)min, of 0.39. The osmotic reflection coefficient (sigma d), calculated as sigma d = 1 - (L/P)min, was 0.61, substantially lower than the value of 0.74 found by Parker et al. in chronically prepared sheep. We conclude that the higher base-line L/P found in acutely prepared sheep is due to higher pulmonary microvascular permeability, possibly the result of the more immediate surgical trauma.


Lectins in histochemistry. A survey.
The most pertinent works using lectin histochemistry at both light and electron microscopy were reviewed. The results and their eventual interpretation are summarized. The importance of lectins as a histochemical tool is mainly based upon the two following features: they possess a narrow specificity for various carbohydrate residues and they can be linked to different labels (fluorochrome, peroxidase, ferritin, colloidal gold) or be included in immunocytochemical techniques in order to be visualized at conventional, u.v. and electron microscopes. These have the advantage to preserve the cellular and tissular integrity. Various tissues and organs were investigated first as a descriptive manner and then under cell differentiation and ontogenetic points of view. Tissues from laboratory rodents and human were especially studied. Few works regarding other vertebrates have been published. However comparative studies could probably cast some lights regarding functions and phylogenetic evaluation. Finally, lectin histochemistry in pathology seems of great promise as indicated by the growing number of publications.


Effects of successive judo matches on fatigue and muscle damage markers.
This study aimed to investigate the acute effects of simulated judo matches on fatigue and muscle damage markers. Twenty male judo athletes participated in this study. The athletes performed three 5-minute judo matches separated by 15 minutes of passive rest between each match. The following measurements were performed before and after each match: shoulder external/internal rotation isokinetic torque and countermovement jump (CMJ). Blood samples were taken before the first match and after the third match for serum creatine kinase (CK) and lactate dehydrogenase (LDH) analysis. T-tests for dependent samples and analysis of variance for repeated measures were used to compare the variables over the time; the level of significance was set at 0.05. An overall effect of the successive matches on shoulder internal (PTIN) and external (PTEX) rotation peak torque and CMJ performance was observed. PTIN and PTEX showed significant decreases in postmatch 2 and postmatch 3 when compared with the baseline (p < 0.01). Also, CMJ height declined in postmatch 2 and postmatch 3 (p < 0.01) when compared with the baseline. Serum CK and LDH activity increased significantly after the third match (p < 0.01). It was concluded that 3 successive judo matches induced a decline of peak torque and muscle power in the upper and lower limbs, respectively, and also provoked an increase of muscle damage markers. These findings may provide important knowledge for coaches and physical trainers to improve judo-specific strength training in both the upper and lower limbs.


Drug resistance patterns in Mycobacterium leprae isolates from relapsed leprosy patients attending The Leprosy Mission (TLM) Hospitals in India.
Implementation of multidrug therapy (MDT) in leprosy control programmes has significantly reduced the global prevalence of the disease in the last two decades. After many years of use of MDT, it is expected that drug resistance in Mycobacterium leprae may emerge. This is a major concern, especially during the stage of elimination. In the present study, slit-skin smears were collected from 140 leprosy relapse cases from different Leprosy Mission hospitals across India. DNA extracted from 111 (79%) of these samples was analysed for the genes associated with drug resistance in M. leprae. More than 90% of the patients relapsed as multibacillary (MB) cases. In our study, four (3.6%) of the DNA samples analysed showed mutations associated with rifampicin resistance. We also observed that mutations associated with resistance to dapsone and ofloxacin were observed in 9 (8.1%) of the DNA samples each; two samples had both dapsone and ofloxacin resistance. Further surveillance and appropriate interventions are needed to ensure the continued success of chemotherapy for leprosy.


Physical and sexual assault histories among psychiatric outpatients.
Using a semistructured interview, the author obtained complete histories of experiences of being physically or sexually assaulted from 31 psychiatric outpatients. The majority (68%) of outpatients had experienced major physical and/or sexual assaults, and most assaults had not been revealed to the patients' prior therapists. Circumstances associated with the assaults, a comparison of outpatient and inpatient assault histories, and the relevance of the findings to clinical practice are discussed.