'A synergy model of health': an integration of salutogenesis and the health assets model.
This article proposes to advance the connections between salutogenic theory and assets models for health improvement. There is a need to integrate their use in public health and health promotion so that their respective potentials can be fully developed. This requires their synergies to be made more explicit so that a more coherent approach can be taken to their utilization. A mechanism is therefore needed that helps to raise awareness of them and their value as a resource together. Bronfenbrenner's bioecological theory provides one framework that can support better integration of salutogenesis with the applied nature of assets-based models. This paper proposes a new 'synergy model for health' that integrates key concepts associated with salutogenic theory-generalized and specific resistance resources (GRRs/SRRs) and generalized and specific resistance deficits and the sense of coherence (SOC). In doing so, it highlights those GRRs and SRRs which are assets that, either individually or collectively, help to develop a stronger SOC. Higher levels of SOC can then support the transformations of potential resources into available assets (that people can understand, manage and make sense of), capable of producing positive health development. The proposed 'Synergy model of health' aims to contribute to a deeper theoretical understanding of health and development through the integration of the key elements of both salutogenesis and assets models. This can facilitate a better contextualization of the ideas into public health policy and practice by making the salutogenic theory more action-oriented and the assets model more theoretical.


Classification of breast masses using selected shape, edge-sharpness, and texture features with linear and kernel-based classifiers.
Breast masses due to benign disease and malignant tumors related to breast cancer differ in terms of shape, edge-sharpness, and texture characteristics. In this study, we evaluate a set of 22 features including 5 shape factors, 3 edge-sharpness measures, and 14 texture features computed from 111 regions in mammograms, with 46 regions related to malignant tumors and 65 to benign masses. Feature selection is performed by a genetic algorithm based on several criteria, such as alignment of the kernel with the target function, class separability, and normalized distance. Fisher's linear discriminant analysis, the support vector machine (SVM), and our strict two-surface proximal (S2SP) classifier, as well as their corresponding kernel-based nonlinear versions, are used in the classification task with the selected features. The nonlinear classification performance of kernel Fisher's discriminant analysis, SVM, and S2SP, with the Gaussian kernel, reached 0.95 in terms of the area under the receiver operating characteristics curve. The results indicate that improvement in classification accuracy may be gained by using selected combinations of shape, edge-sharpness, and texture features.


Localization of oestrogen receptor alpha, oestrogen receptor beta and androgen receptors in the rat reproductive organs.
There is now evidence that oestrogens and androgens can influence male and female reproductive systems. In order to accurately identify the sites of action of oestrogens and androgens, we have proceeded to the histological localization of the two oestrogen receptor (ER) subtypes, ERalpha and ERbeta, and the androgen receptor (AR) in the reproductive tissues of adult rats of both sexes. AR was detected by immunocytochemistry, while ERalpha and ERbeta were localized by both immunocytochemistry and in situ hybridization. In the pituitary gland of animals of both sexes, ERalpha was found in the majority of nuclei of secretory cells in the anterior pituitary. The intermediate and posterior lobes did not show any staining. ERbeta was not found to be expressed in any of the pituitary lobes. Using AR antibodies, nuclear staining was detected in about 50% of secretory cells of the anterior lobe, the intermediate and posterior lobes being completely unstained. In the testis, ERalpha was localized in nuclei of Leydig cells as well as in round spermatocytes and spermatids, while ERbeta could only be detected in Sertoli cell nuclei. AR immunoreactivity was found in nuclei of Sertoli, peritubular myoid and Leydig cells. In the prostate, ERbeta was observed in epithelial cells of tubulo-alveoli, while the stroma was unlabelled. ERalpha was not found to be expressed in any prostate cells. In the prostate, AR was detected in nuclei of epithelial, stromal and endothelial cells. In seminal vesicles, staining of ERalpha was found in nuclei of epithelial and stromal cells. Similar findings were observed using AR antibodies. While ERbeta mRNA could not be detected by in situ hybridization, weak staining for ERbeta was localized in epithelial cells of seminal vesicles. In the ovary, both ERalpha and ERbeta were found to be expressed. ERbeta mRNA was found in granulosa cells of growing follicles, while ERalpha was present in theca cells, interstitial gland cells and germinal epithelium. AR immunoreactivity was detected in granulosa cell nuclei in growing follicles and also in scattered interstitial cells. In the oviduct and uterus, ERalpha was observed in nuclei of epithelial cells as well as of stromal and muscle cells. Similarly, AR immunoreactivity was present in nuclei of epithelial cells, stromal and muscle cells in both the oviduct and uterus. ERbeta was not detected in the oviduct and uterus. The present findings indicate a cell-specific localization of ERalpha, ERbeta and AR in reproductive tissues in rats of both sexes. By establishing the precise sites of action of oestrogens and androgens they contribute to a better understanding of the respective role of these steroids in reproduction function.


Influence of age and endocrine factors on the volume of benign prostatic hyperplasia.
To determine whether endocrine factors influence the volume of benign prostatic hyperplasia (BPH), 23 hormonal factors were measured in the serum of 64 men ages 42 to 71 years with low volume prostatic cancer and these levels were correlated with the volume of benign hyperplastic tissue in their radical prostatectomy specimens. With age there was a significant increase in the volume of BPH. Also with age there was a significant decrease in the serum levels of free testosterone, androstenedione, dehydroepiandronsterone (DHA), dehydroepiandronsterone sulphate (DHA-S), delta 5-androstenediol, and 17-hydroxypregnenolone, and a significant increase in sex hormone-binding globulin (SHBG), LH, and FSH. When BPH volume and hormone levels were corrected for age, BPH volume correlated positively with free testosterone, estradiol, and estriol. These data indicate that with age patients with larger volumes of BPH have higher serum androgen and estrogen levels suggesting that serum androgen and estrogen levels may be factors in the persistent stimulation of BPH with age. If so, therapeutic attempts at lowering plasma testosterone levels, reducing estrogen levels, or blocking androgenic stimulation through other mechanisms may interfere with the progression of BPH with age. Conversely, the fact that androgen production declines gradually with age may explain the observation that only 20 to 30% of men who live to age 80 require surgical treatment for urinary obstruction from BPH.


Oxidative stress tolerance of a spore clone isolated from Shirakami kodama yeast depends on altered regulation of Msn2 leading to enhanced expression of ROS-degrading enzymes.
We analyzed the stress response in a spore clone from Shirakami kodama yeast, Saccharomyces cerevisiae, with an exceptional high tolerance to oxidative stress. The levels of reactive oxygen species (ROS) in this clone were very low, whereas the genes for superoxide dismutase (SOD2) and catalase (CTT1) were highly expressed and those enzymes also had high activities even under non-stress conditions. Both genes are regulated by general stress-responsive transcription factors Msn2 and Msn4, and Yap1, a transcription factor required for oxidative stress tolerance, and the removal of Msn2 or Yap1 caused a significant decrease in CTT1-expression. Under non-stress conditions, Msn2 was ~3.6-fold more abundant in the nucleus of the spore clone compared with a laboratory strain, whereas the nuclear abundance of Yap1 remained unchanged. Thus, a high tolerance to oxidative stress in this spore clone results from a high expression of ROS-degrading enzymes by the abundant accumulation of Msn2 in the nucleus. We found that oxidative stress caused by the presence of furfural did not impair fermentation by this strain, which could make it attractive for ethanol production from lignocellulosic biomass.


Generation of CD4+ blastoid T cells in recipients of BP/IFA-sensitized spleen cells.
While sensitization of Lewis rats with BP/IFA does not induce EAE, recipients given BP/IFA-sensitized cells after culture with BP do develop EAE. To clarify the pathophysiology responsible for this discrepancy, cell dynamics were studied in the recipients. The CD4+ T cells from BP/IFA-sensitized donors showed no proliferative response to BP and no change in cell size or surface molecule expression, even in the presence of BP in culture. On the other hand, the recipient cells proliferated vigorously, regardless of the presence or absence of BP. In this case, a large number of CD4+ blastoid T cells was generated only in the presence of BP in culture. Such cells showed marked upregulation of CD4, CD2, class I and II MHC, and IL2 receptor molecules, a finding we also observed in the case of BP-cultured cells from BP/CFA-sensitized rats with severe EAE. The proportion of CD4+ blastoid T cells generated after culture depended on the number of cells transferred and on the presence of BP in culture, and closely correlated with the severity of EAE in the recipients. These data suggest that BP/IFA-sensitization can also induce BP-reactive cells capable of becoming CD4+ blastoid T cells with marked upregulation of CD4, CD2, class I and II MHC, and IL2 receptor molecules directly related to potent encephalitogenicity, in vivo.


Apolygus lucorum effector Al6 promotes insect feeding performance on soybean plants: RNAi analysis and feeding behaviour study with electrical penetration graph.
The mirid bug Apolygus lucorum, a dominant mirid species in northern China, is a notorious polyphagous pest with more than 200 hosts, including several major crops such as cotton and soybean, resulting in massive economic loss. Studies of insect salivary effectors may provide a novel control strategy for A. lucorum. An A. lucorum effector, that is, Al6, that inhibits plant immunity by using glutathione peroxidase to repress reactive oxidase accumulation was previously identified. In this study, we further explored the molecular functions of Al6 associated with feeding behaviour and insect survival on soybean, a major host of A. lucorum, using RNA interference and electrical penetration graph (EPG) techniques. We initially observed the injury symptom of this mirid bug and characterized feeding behaviour on soybean leaves using EPG. Our results revealed that A. lucorum preferred to feed on young plant organs such as tender leaves, shoots and buds. This mirid bug used cell rupture as a feeding strategy to ingest cell contents from plant tissues. Subsequently, we silenced the Al6 gene using RNAi and investigated the feeding behaviour, honeydew excretion, body weight, and survival rates of A. lucorum on soybean after Al6 knockdown. Our results demonstrated that silencing of Al6 significantly reduced feeding duration, amount of honeydew secretion, body weight, and survival rates of A. lucorum. Thus, our findings provide a novel molecular target of plant-mediated RNAi for the control of A. lucorum.


Expansion of visual space during optokinetic afternystagmus (OKAN).
The mechanisms underlying visual perceptual stability are usually investigated using voluntary eye movements. In such studies, errors in perceptual stability during saccades and pursuit are commonly interpreted as mismatches between actual eye position and eye-position signals in the brain. The generality of this interpretation could in principle be tested by investigating spatial localization during reflexive eye movements whose kinematics are very similar to those of voluntary eye movements. Accordingly, in this study, we determined mislocalization of flashed visual targets during optokinetic afternystagmus (OKAN). These eye movements are quite unique in that they occur in complete darkness and are generated by subcortical control mechanisms. We found that during horizontal OKAN slow phases, subjects mislocalize targets away from the fovea in the horizontal direction. This corresponds to a perceived expansion of visual space and is unlike mislocalization found for any other voluntary or reflexive eye movement. Around the OKAN fast phases, we found a bias in the direction of the fast phase prior to its onset and opposite to the fast-phase direction thereafter. Such a biphasic modulation has also been reported in the temporal vicinity of saccades and during optokinetic nystagmus (OKN). A direct comparison, however, showed that the modulation during OKAN was much larger and occurred earlier relative to fast-phase onset than during OKN. A simple mismatch between the current eye position and the eye-position signal in the brain is unlikely to explain such disparate results across similar eye movements. Instead, these data support the view that mislocalization arises from errors in eye-centered position information.


Women's fear of crime: the role of fear for the well-being of significant others.
A number of explanations have been suggested in the literature for the finding that women consistently report higher levels of fear of crime than males. The "shadow" hypothesis argues that fear of crime among females reflects fear of sexual assault. The "intimate" hypothesis argues that women's fear of crime is the result of exposure to intimate violence. Females' fear of crime is expected to be explained by their fear of partners' violence. The main argument of this article is that women's fear of crime might be the result of traditional family gender roles. When asked, women might express fear not only for their own well-being but for that of their children. A survey of a representative sample of women in the third largest city of Israel was used to test this assumption. Women's fear of crime was found to be affected by fear of sexual assault and fear of violent partners. In addition, consistent with the argument of this study, women's fear of violent and sexual victimization of their children had a significant effect on their perception of fear. Future directions for research are suggested.


Multidisciplinary treatment of hepatocellular carcinoma in 2023: Italian practice Treatment Guidelines of the Italian Association for the Study of the Liver (AISF), Italian Association of Medical Oncology (AIOM), Italian Association of Hepato-Bilio-Pancreatic Surgery (AICEP), Italian Association of Hospital Gastroenterologists (AIGO), Italian Association of Radiology and Clinical Oncology (AIRO), Italian Society of Pathological Anatomy and Diagnostic Cytology (SIAPeC-IAP), Italian Society of Surgery (SIC), Italian Society of Gastroenterology (SIGE), Italian Society of Medical and Interventional Radiology (SIRM), Italian Organ Transplant Society (SITO), and Association of Patients with Hepatitis and Liver Disease (EpaC) - Part II - Non-surgical treatments.
Worldwide, hepatocellular carcinoma (HCC) is the third most common cause of cancer-related death. The remarkable improvements in treating HCC achieved in the last years have increased the complexity of its management. Following the need to have updated guidelines on the multidisciplinary treatment management of HCC, the Italian Scientific Societies involved in the management of this cancer have promoted the drafting of a new dedicated document. This document was drawn up according to the GRADE methodology needed to produce guidelines based on evidence. Here is presented the second part of guidelines, focused on the multidisciplinary tumor board of experts and non-surgical treatments of HCC.


Comparison of the 585 nm pulse dye laser and the short pulsed CO2 laser in the treatment of striae distensae in skin types IV and VI.
Striae distensae, or stretch marks, are a very common cosmetic problem. The successful management of stretch marks has long been a source of frustration and curiosity for both the clinician and the researcher. Recent studies suggest lasers may have a role in their management. As yet, no study has reported on the effects of either of these lasers in the treatment of stretch marks on persons with skin types 4 to 6. To assess the efficacy of short pulsed CO2 laser and pulsed dye laser for the treatment of stretch marks in skin types 4, 5, and 6. Four patients were initially enrolled in the study. All were female with abdominal stretch marks, present for a range of 8 to 19 years. The patients had skin types ranging from 4 to 6. The test area consisted of a stretch mark long enough to be divided into three contiguous 2 cm sections, labeled A, B, and C. Section A served as the short pulsed CO2 test site, section B served as a control, while section C served as the 585 nm pulsed dye site. Patients were seen for evaluation after 1 week, then every 4 weeks for a total of 20 weeks. Patients were evaluated subjectively by the investigators, and the patients' own self-evaluation was reported as well. Following the 585 nm pulse dye laser, at 20 week follow-up patients with type 4 skin showed no improvement, while type 6 skin showed hyperpigmentation. The short pulsed CO2 test site showed persistent erythema in type 4 skin and marked hyperpigmentation in type 6 skin. For patients with types 4, 5, and 6 skin, laser treatment of striae should be avoided or used with great caution.


Implementing the community health worker model within diabetes management: challenges and lessons learned from programs across the United States.
The purpose of this qualitative study was to examine methods of implementation of the community health worker (CHW) model within diabetes programs, as well as related challenges and lessons learned. Semi-structured interviews were conducted with program managers. Four databases (PubMed, CINAHL, ISI Web of Knowledge, PsycInfo), the CDC's 1998 directory of CHW programs, and Google Search Engine were used to identify CHW programs. Criteria for inclusion were: DM program; used CHW strategy; occurred in United States. Two independent reviewers performed content analyses to identify major themes and findings. Sixteen programs were assessed, all but 3 focused on minority populations. Most CHWs were recruited informally; 6 programs required CHWs to have diabetes. CHW roles and responsibilities varied across programs; educator was the most commonly identified role. Training also varied in terms of both content and intensity. All programs gave CHWs remuneration for their work. Common challenges included difficulties with CHW retention, intervention fidelity and issues related to sustainability. Cultural and gender issues also emerged. Examples of lessons learned included the need for community buy-in and the need to anticipate nondiabetes related issues. Lessons learned from these programs may be useful to others as they apply the CHW model to diabetes management within their own communities. Further research is needed to elucidate the specific features of this model necessary to positively impact health outcomes.


The Use of Hybrid Lumbar Puncture Simulation to Teach Entrustable Professional Activities During a Medical Student Neurology Clerkship.
This article was migrated. The article was marked as recommended. Background: In 2014, the Association of American Medical Colleges (AAMC) published a list of 13 Entrustable Professional Activities (EPAs) that medical school graduates should be able to perform upon starting residency. The University of Pittsburgh School of Medicine (UPSOM) has surveyed our neurology clerkship students in regard to EPAs since 2017; according to this data we have been deficient in addressing EPAs 4 (enter and discuss orders/prescriptions), 11 (obtain informed consent for tests and/or procedures), and 12 (perform general procedures of a physician). We therefore developed a hybrid simulation experience encompassing these three skills, centered around lumbar puncture (LP). Methods: We created a hybrid LP simulation for students on the neurology clerkship encompassing EPAs 4, 11, and 12. Students first obtained informed consent for LP from a Standardized Patient, then performed LP on a specialized manikin. They then entered orders on CSF into a simulated patient chart. Real-time feedback was provided for all three components. Students filled out surveys to assess their perceived confidence and skill with these activities both pre- and post-simulation. Results: The percentage of students who increased their confidence with LP from minimal or less to average or more was 58.24%, 38.47%, and 26.38% for LP, informed consent, and order entry, respectively. The percentage of students who improved from not being able to perform/needing significant supervision to being able to perform with minimal supervision/ independently was 25.27%, 47.25% and 28.58%, for LP, informed consent, and order entry, respectively. These differences were all statistically significant (p Conclusions/Significance: Hybrid LP simulation was effective in increasing medical student confidence and perceived skill with EPAs 4, 11, and 12.


An Artificial Neural Network Model for the Prediction of Perioperative Blood Transfusion in Adult Spinal Deformity Surgery.
Prediction of blood transfusion after adult spinal deformity (ASD) surgery can identify at-risk patients and potentially reduce its utilization and the complications associated with it. The use of artificial neural networks (ANNs) offers the potential for high predictive capability. A total of 1173 patients who underwent surgery for ASD were identified in the 2017-2019 NSQIP databases. The data were split into 70% training and 30% testing cohorts. Eighteen patient and operative variables were used. The outcome variable was receiving RBC transfusion intraoperatively or within 72 h after surgery. The model was assessed by its sensitivity, positive predictive value, F1-score, accuracy (ACC), and area under the curve (AUROC). Average patient age was 56 years and 63% were female. Pelvic fixation was performed in 21.3% of patients and three-column osteotomies in 19.5% of cases. The transfusion rate was 50.0% (586/1173 patients). The best model showed an overall ACC of 81% and 77% on the training and testing data, respectively. On the testing data, the sensitivity was 80%, the positive predictive value 76%, and the F1-score was 78%. The AUROC was 0.84. ANNs may allow the identification of at-risk patients, potentially decrease the risk of transfusion via strategic planning, and improve resource allocation.


[Study of radiation dose to the eye lens by multi-detector row computed tomography of the temporal bone].
The exposure of the eye lens caused by multi-detector row computed tomography (MDCT) of the temporal bone is a serious problem. Our aim was to evaluate the radiation dose to the eye lens by different scan baselines (orbitomeatal line; OML, acanthiomeatal line; AML) and examine the difference of the depiction of the temporal bone structures. Measurement of the exposure to the eye lens was performed by means of MDCT of the temporal bone with a radio-photoluminescence glass dosimeter using a rand phantom. Moreover, we studied only one volunteer (58-year-old male) who had no symptom and was not suspected of having any ear abnormalities with a two scan baseline. Visualization of the major anatomical structures of the temporal bone (the tympanic portion of the facial nerve canal, the body of the incus, stapes superstructures, vestibule etc.) was performed on the volunteer. The average absorbed dose was 6.42 mGy by the OML and 1.59 mGy by the AML, respectively. With regard to visualization of the temporal bone structures, all structures were of equal quality with the two scan baseline. With the AML line, the radiation dose to the eye lens was reduced to 75%. Therefore, the authors recommended an AML for use for MDCT of the temporal bone. In clinical practice, the optimization of scanning factor (kVp, mAs etc.) and the use of the radio-protection should be implemented for radiation dose reduction of the eye lens by MDCT of the temporal bone.


Identifying the true number of specimens of the extinct blue antelope (Hippotragus leucophaeus).
Native to southern Africa, the blue antelope (Hippotragus leucophaeus) is the only large African mammal species known to have become extinct in historical times. However, it was poorly documented prior to its extinction ~ 1800 AD, and many of the small number of museum specimens attributed to it are taxonomically contentious. This places limitations on our understanding of its morphology, ecology, and the mechanisms responsible for its demise. We retrieved genetic information from ten of the sixteen putative blue antelope museum specimens using both shotgun sequencing and mitochondrial genome target capture in an attempt to resolve the uncertainty surrounding the identification of these specimens. We found that only four of the ten investigated specimens, and not a single skull, represent the blue antelope. This indicates that the true number of historical museum specimens of the blue antelope is even smaller than previously thought, and therefore hardly any reference material is available for morphometric, comparative and genetic studies. Our study highlights how genetics can be used to identify rare species in natural history collections where other methods may fail or when records are scarce. Additionally, we present an improved mitochondrial reference genome for the blue antelope as well as one complete and two partial mitochondrial genomes. A first analysis of these mitochondrial genomes indicates low levels of maternal genetic diversity in the 'museum population', possibly confirming previous results that blue antelope population size was already low at the time of the European colonization of South Africa.


Toward a conceptualization of race in epidemiologic research.
This paper is a review of the prevailing conceptual basis of the use of race in health research. The author explores the current definitions of race in health research, and describes some of the history of race fabrication. In the examination of the association between race and disease the author describes black/white differences in age-adjusted mortality, infant mortality rates and birthweight. The analysis of race and disease is frustrated by incomplete theoretical constructs. Race, as used in health research, tends to be a unidimensional construct and the complex interplay between race and other social status variables is simplified. These problems are illustrated, and the author suggests a multidimensional construct of race.


Osteotomy assisted maxillary posterior impaction with miniplate anchorage.
This case report presents orthodontic treatment with miniplate anchorage accelerated by osteotomy-assisted maxillary posterior impaction in a severe open bite case. A 14-year-old girl with a severe anterior open bite was treated by intrusion of the maxillary posterior teeth. A segmental osteotomy was applied, and the miniplates were fixed to the zygomatic buttress area. The intrusive force was applied with nickel-titanium closed coil springs using a force of 250 g between the miniplates and the upper first and second molar buccal tubes. The intrusion was completed 2.5 months after osteotomy. The treatment was continued with the fixed orthodontic appliances and completed after 12 months. At the end of treatment, optimal occlusion and the correction of the anterior open bite were achieved. The maxillary molars were impacted 4.0 mm, and the mandibular plane showed a counterclockwise autorotation of 3.0 degrees . The results showed that osteotomy-facilitated orthodontic treatment clearly reduced the treatment time and had no adverse effects. In conclusion, this one-stage osteotomy technique can be an effective option to help molar intrusion in severe open bite cases.


Oxycodone intoxication in an infant: accidental or intentional exposure?
A case is presented of a 10 month old male who went into cardiac arrest at a local store. The infant subsequently expired and was autopsied at the Office of the Chief Medical Examiner, State of Maryland. The only remarkable finding was the detection of oxycodone in the postmortem specimens; the blood and liver oxycodone concentrations were 0.6 mg/L and 1.6 mg/kg, respectively. Oxycodone was identified and quantitated by gas chromatography-nitrogen-phosphorus detection and confirmed by full scan electron ionization gas chromatography-mass spectrometry. The medical examiner ruled that the cause of death was oxycodone intoxication, and the manner of death was homicide. The key toxicologic question in this case was whether or not it was reasonable for the infant to be exposed to oxycodone exclusively through breast milk or through an alternate source. It was concluded that, at best, there were serious concerns about the likelihood of drug exposure through consumption of breast milk.


Romk1 Knockout Mice Do Not Produce Bartter Phenotype but Exhibit Impaired K Excretion.
Romk knock-out mice show a similar phenotype to Bartter syndrome of salt wasting and dehydration due to reduced Na-K-2Cl-cotransporter activity. At least three ROMK isoforms have been identified in the kidney; however, unique functions of any of the isoforms in nephron segments are still poorly understood. We have generated a mouse deficient only in Romk1 by selective deletion of the Romk1-specific first exon using an ES cell Cre-LoxP strategy and examined the renal phenotypes, ion transporter expression, ROMK channel activity, and localization under normal and high K intake. Unlike Romk(-/-) mice, there was no Bartter phenotype with reduced NKCC2 activity and increased NCC expression in Romk1(-/-) mice. The small conductance K channel (SK) activity showed no difference of channel properties or gating in the collecting tubule between Romk1(+/+) and Romk1(-/-) mice. High K intake increased SK channel number per patch and increased the ROMK channel intensity in the apical membrane of the collecting tubule in Romk1(+/+), but such regulation by high K intake was diminished with significant hyperkalemia in Romk1(-/-) mice. We conclude that 1) animal knockouts of ROMK1 do not produce Bartter phenotype. 2) There is no functional linking of ROMK1 and NKCC2 in the TAL. 3) ROMK1 is critical in response to high K intake-stimulated K(+) secretion in the collecting tubule.


Cardiac influence of the β3-adrenoceptor in the goldfish (Carassius auratus): a protective role under hypoxia?
The goldfish (Carassius auratus) exhibits a remarkable capacity to survive and remain active under prolonged and severe hypoxia, making it a good model for studying cardiac function when oxygen availability is a limiting factor. Under hypoxia, the goldfish heart increases its performance, representing a putative component of hypoxia tolerance; however, the underlying mechanisms have not yet been elucidated. Here, we aimed to investigate the role of β3-adrenoreceptors (ARs) in the mechanisms that modulate goldfish heart performance along with the impact of oxygen levels. By western blotting analysis, we found that the goldfish heart expresses β3-ARs, and this expression increases under hypoxia. The effects of β3-AR stimulation were analysed by using an ex vivo working heart preparation. Under normoxia, the β3-AR-selective agonist BRL37344 (10-12 to 10-7 mol l-1) elicited a concentration-dependent increase of contractility that was abolished by a specific β3-AR antagonist (SR59230A; 10-8 mol l-1), but not by α/β1/β2-AR inhibitors (phentolamine, nadolol and ICI118,551; 10-7 mol l-1). Under acute hypoxia, BRL37344 did not affect goldfish heart performance. However, SR59230A, but not phentolamine, nadolol or ICI118,551, abolished the time-dependent enhancement of contractility that characterizes the hypoxic goldfish heart. Under both normoxia and hypoxia, adenylate cyclase and cAMP were found to be involved in the β3-AR-dependent downstream transduction pathway. In summary, we show the presence of functional β3-ARs in the goldfish heart, whose activation modulates basal performance and contributes to a hypoxia-dependent increase of contractility.


Effect of influenza B virus on nutrient transport in cultured epithelial cells.
The possibility that influenza virus could induce changes in membrane permeability to nutrients ordinarily concentrated within the cell was examined. Madin-Darby canine kidney cells were infected with egg-grown influenza B virus at 37 degrees C and pH 7.4 (a condition in which influenza virus enters cells by endocytosis). Control cells were mock-infected with allantoic fluid from chick embryos. Transport of phosphate, 2-deoxyglucose, and alpha-aminoisobutyric acid was measured at various intervals, 0 to 10 hours after infection. Uptake of alpha-aminoisobutyric acid and phosphate by infected cells was inhibited at 2 hours as compared with controls, whereas at 6 to 10 hours, the uptake of all nutrients was higher in infected cells. Infected cells preloaded with phosphate or 2-deoxyglucose did not demonstrate increased release of these nutrients. Thus, the virally induced inhibition of uptake early in infection is not a consequence of loss of membrane integrity. Transport studies were also performed in cells with prebound virus exposed to pH 5.0 for 60 seconds at 37 degrees C and then incubated at pH 7.4, at 37 degrees C. Under these conditions, influenza A viruses are known to enter the cell membrane by fusing directly with it and to initiate cell to cell fusion as well. We demonstrated that influenza B virus also caused cell fusion under these conditions. In contradistinction to studies described above at pH 7.4, fused, infected cells demonstrated both marked release and diminished uptake of nutrients as compared with controls. We conclude that influenza B virus does have an effect on host cell membrane permeability; the type of effect seen is markedly influenced by factors known to determine mode of virus entry into the cell.


An Analysis of Anatomy Education Before and During Covid-19: May-August 2020.
Coronavirus disease 2019 (Covid-19) created unparalleled challenges to anatomy education. Gross anatomy education has been particularly impacted given the traditional in-person format of didactic instruction and/or laboratory component(s). To assess the changes in gross anatomy lecture and laboratory instruction, assessment, and teaching resources utilized as a result of Covid-19, a survey was distributed to gross anatomy educators through professional associations and listservs. Of the 67 survey responses received for the May-August 2020 academic period, 84% were from United States (US) institutions, while 16% were internationally based. Respondents indicated that in-person lecture decreased during Covid-19 (before: 76%, during: 8%, P < 0.001) and use of cadaver materials declined (before: 76 ± 33%, during: 34 ± 43%, P < 0.001). The use of cadaver materials in laboratories decreased during Covid-19 across academic programs, stand-alone and integrated anatomy courses, and private and public institutions (P ≤ 0.004). Before Covid-19, cadaveric materials used in laboratories were greater among professional health programs relative to medical and undergraduate programs (P ≤ 0.03) and among stand-alone relative to integrated anatomy courses (P ≤ 0.03). Furthermore, computer-based assessment increased (P < 0.001) and assessment materials changed from cadaveric material to images (P < 0.03) during Covid-19, even though assessment structure was not different (P > 0.05). The use of digital teaching resources increased during Covid-19 (P < 0.001), with reports of increased use of in-house created content, BlueLink, and Complete Anatomy software (P < 0.05). While primarily representing US institutions, this study provided evidence of how anatomy educators adapted their courses, largely through virtual mediums, and modified laboratory protocols during the initial emergence of the Covid-19 pandemic.


The role of the hospitalists in the workforce to address the shortages of intensivists in hospitals here in Thailand.
The problem of a shortage of intensivists in Thailand is increasing annually. As stated in The Thai Society of Critical Care Medicine Database, 2013, the number of qualified intensivists currently is 163, working in 76 provinces in Thailand. This disproportion in the ratio of intensivists has affected patient outcomes. In an attempt to solve this problem, there has been an increased number of hospitalists working in place of the intensivists. Medical specialties are not available in many hospitals of Thailand. Thus, the hospitalists, who care for Intensive Care Unit (ICU) patients, are not trained to care for the acutely ill, hospitalized patients. Their competencies vary depending on their experience and training. In other countries, there has been evidence that properly trained hospitalists can work effectively in the ICU. This awareness of the importance of intensivists in Thailand is one of the stifling factors; the improvement of the hospitalists, determining the hospitalists' workforce and increasing the number of the intensivists to match future demands are needed.


[COCHLEAR IMPLANTATION IN ELDERLY INDIVIDUALS: INSIGHTS BASED ON A RETROSPECTIVE EVALUATION].
In old age, the typical decline in temporal processing, auditory memory, speed of information processing, and ability to filter out irrelevant competing auditory input lead to deterioration in speech perception. This thereby broadens the target population for cochlear implantation among elderly individuals with severe-to-profound hearing loss. These features also raise concern regarding cochlear implant (CI) fitting and outcomes. To establish expectations from CI in older individuals. This is a retrospective case review of 20 individuals with severe or severe-to-profound hearing loss, aged 60 or older (mean, 66.6 ± 5.25; range, 60-81 at the time of CI. Evaluation included speech-perception tests and the Glasgow Benefit Inventory (GBI) for testing quality of life. Between pre- and post-implantation, mean group values improved from 18.6% to 55.5%, from 37.2% to 84.5%, and from 11.2% to 60.5%, respectively, on the above speech-perception tests. No major postoperative complications were observed. The device was used consistently by all but one patient. GBI revealed improvement on all subscales. After implantation speech perception improved, there were no major post-CI complications, and post-implantation vertigo was less significant than expected in this age group. These results diminish concerns regarding CI in elderly individuals.


A neurobiological theory of automaticity in perceptual categorization.
A biologically detailed computational model is described of how categorization judgments become automatic in tasks that depend on procedural learning. The model assumes 2 neural pathways from sensory association cortex to the premotor area that mediates response selection. A longer and slower path projects to the premotor area via the striatum, globus pallidus, and thalamus. A faster, purely cortical path projects directly to the premotor area. The model assumes that the subcortical path has greater neural plasticity because of a dopamine-mediated learning signal from the substantia nigra. In contrast, the cortical-cortical path learns more slowly via (dopamine independent) Hebbian learning. Because of its greater plasticity, early performance is dominated by the subcortical path, but the development of automaticity is characterized by a transfer of control to the faster cortical-cortical projection. The model, called SPEED (Subcortical Pathways Enable Expertise Development), includes differential equations that describe activation in the relevant brain areas and difference equations that describe the 2- and 3-factor learning. A variety of simulations are described, showing that the model accounts for some classic single-cell recording and behavioral results.


Effect of 2-alkynoic acids on in vitro growth of bacterial and mammalian cells.
3-Decynoyl-N-acetylcystamine is known to inhibit the in vitro growth of Escherichia coli but not of yeasts or mammalian cells. Neither the free acid nor the 2 positional isomer is active (L. R. Kass, J. Biol. Chem. 243:3223-3228, 1968). Other studies have shown that 2-hexadecynoic acid is fungitoxic whereas most of the shorter chain isomers are inactive (H. Gershon and L. Shanks, Can J. Microbiol. 24:591-597, 1978). Since these studies suggested that positional or chain length isomers of the acetylenic acids may selectively inhibit the growth of microorganisms, the effect of the alkynoic acids on the in vitro growth of gram-positive and gram-negative bacteria was evaluated. 2-Hexadecynoic acid was found to be the most active species. This acid was bacteriostatic for all gram-positive bacteria tested. The acid was readily taken up by the treated cells and incorporated into the phospholipid fraction. When added to the culture medium, 2-hexadecynoic acid inhibited the growth of HeLa cells, but when mixed with an equivalent amount of palmitic acid, growth inhibition was not observed.


The senescent cataract patient: a management philosophy.
Senescent cataracts are a frequently encountered anomaly in optometric practice. Optometric management of these patients is an ongoing process only beginning with the physical diagnosis and encompassing necessary patient education, counseling, and advocacy.


Evolutionary forces shaping the Golgi glycosylation machinery: why cell surface glycans are universal to living cells.
Despite more than 3 billion years since the origin of life on earth, the powerful forces of biological evolution seem to have failed to generate any living cell that is devoid of a dense and complex array of cell surface glycans. Thus, cell surface glycans seem to be as essential for life as having a DNA genetic code, diverse RNAs, structural/functional proteins, lipid-based membranes, and metabolites that mediate energy flux and signaling. The likely reasons for this apparently universal law of biology are considered here, and include the fact that glycans have the greatest potential for generating diversity, and thus evading recognition by pathogens. This may also explain why in striking contrast to the genetic code, glycans show widely divergent patterns between taxa. On the other hand, glycans have also been coopted for myriad intrinsic functions, which can vary in their importance for organismal survival. In keeping with these considerations, a significant percentage of the genes in the typical genome are dedicated to the generation and/or turnover of glycans. Among eukaryotes, the Golgi is the subcellular organelle that serves to generate much of the diversity of cell surface glycans, carrying out various glycan modifications of glycoconjugates that transit through the Golgi, en route to the cell surface or extracellular destinations. Here I present an overview of general considerations regarding the selective forces shaping evolution of the Golgi glycosylation machinery, and then briefly discuss the common types of variations seen in each major class of glycans, finally focusing on sialic acids as an extreme example of evolutionary glycan diversity generated by the Golgi. Future studies need to address both the phylogenetic diversity the Golgi and the molecular mechanisms for its rapid responses to intrinsic and environmental stimuli.


Iris mattress suture: a technique for sectoral iris defect repair.
Achieving a cosmetic and functional outcome from iris defect repair is a surgical challenge. We describe an adaptation of techniques to address a case of 2.5 clock hours of sectoral iris tissue defect. Our method combines Siepser's modified closed-chamber sliding knot technique with the placement of a double-armed iris mattress suture to approximate iris tissue to the scleral wall and thereby create a pseudo-iris root. This technique reduces glare and achieves a cosmetic outcome for the patient.


Rapid quantitative method for Salmonella detection in polluted waters.
A procedure has been developed for the enumeration of salmonellae in polluted waters using several modifications of existing techniques. Confirmation of salmonellae is achieved within 48 hr. This procedure includes selective enrichment in m-Tetrathionate Broth (22 +/- 1 hr), plating on Brilliant Green Sulfa Agar (20 +/- 1 hr), and confirmation by flagellar (H) agglutination of the growth in a mannosecontaining medium (6 +/- 1 hr). An incubation temperature of 41.5 C was used throughout this procedure. Dilution to extinction techniques (most probable number) were employed to enumerate salmonellae. Large sample volumes were concentrated through the use of membrane filters. This technique proved to be rapid and reliable for the enumeration of salmonellae in water, waste water, and waste-water sludges.


The Drought-Mediated Soybean GmNAC085 Functions as a Positive Regulator of Plant Response to Salinity.
Abiotic stress factors, such as drought and salinity, are known to negatively affect plant growth and development. To cope with these adverse conditions, plants have utilized certain defense mechanisms involved in various aspects, including morphological, biochemical and molecular alterations. Particularly, a great deal of evidence for the biological importance of the plant-specific NAM, ATAF1/2, CUC2 (NAC) transcription factors (TFs) in plant adaptation to abiotic stress conditions has been reported. A previous in planta study conducted by our research group demonstrated that soybean (Glycine max) GmNAC085 mediated drought resistance in transgenic Arabidopsis plants. In this study, further characterization of GmNAC085 function in association with salt stress was performed. The findings revealed that under this condition, transgenic soybean plants overexpressing GmNAC085 displayed better germination rates than wild-type plants. In addition, biochemical and transcriptional analyses showed that the transgenic plants acquired a better defense system against salinity-induced oxidative stress, with higher activities of antioxidant enzymes responsible for scavenging hydrogen peroxide or superoxide radicals. Higher transcript levels of several key stress-responsive genes involved in the proline biosynthetic pathway, sodium ion transporter and accumulation of dehydrins were also observed, indicating better osmoprotection and more efficient ion regulation capacity in the transgenic lines. Taken together, these findings and our previous report indicate that GmNAC085 may play a role as a positive regulator in plant adaptation to drought and salinity conditions.


Lithium dendrite-free plating/stripping: a new synergistic lithium ion solvation structure effect for reliable lithium-sulfur full batteries.
A new synergistic lithium ion solvation structure effect tailored by mixed organic/inorganic lithium salts is introduced to mitigate the growth of lithium-dendrites. A uniform lithium plating, lower polarization and higher coulombic efficiency are confirmed by lithium plating/stripping. The effect of different solvation structures was analyzed by Raman spectroscopy and simulations. Then, a reliable lithium-sulfur full battery with high performance over hundreds of cycles was configured.


Evaluation of behavioural effects of a selective NMDA NR1A/2B receptor antagonist in the unilateral 6-OHDA lesion rat model.
The degeneration of the dopaminergic nigrostriatal pathway in Parkinson's disease (PD) is associated with altered transmission at striatal NMDA receptors containing NR2B subunits. We investigated a potential novel therapeutic compound, 4-trifluoromethoxy-N-(2-trifluoromethyl-benzyl)-benzamidine (BZAD-01), a selective NMDA NR1A/2B receptor antagonist for PD and compared it with levodopa, the standard treatment for PD. This study also evaluated whether combining levodopa and BZAD-01 gave better improvements of parkinsonian symptoms. Parkinsonism was induced by microinjection of the toxin, 6-hydroxydopamine (6-OHDA) into the medial forebrain bundle (MFB) of 40 Sprague-Dawley rats. Parkinsonism and the efficacy of drugs were assessed using a battery of behavioural tests including balance beam, apomorphine-induced rotation, body axis bias or "curling", head position bias and disengage sensorimotor latency test. Immunohistochemistry was performed on post-mortem tissue to estimate the loss of dopaminergic neurons. The main effects were that BZAD-01 co-administration prevented chronic levodopa-induced potentiation of apomorphine rotation. However levodopa-treated rats were slower than either controls or BZAD-01-treated rats in the locomotor test. The improvement in the apomorphine rotation test suggests that BZAD-01 may be a useful adjunct to levodopa monotherapy.


Intestinal Epithelial Cells-Derived Hypoxia-Inducible Factor-1α Is Essential for the Homeostasis of Intestinal Intraepithelial Lymphocytes.
Hif-1α is a master regulator which involved in the transcriptional regulation of anti-inflammatory or cellular responding to hypoxia. Previous work shows that the absence of Hif-1α results in the destruction of intestinal epithelial cell (IEC) and abnormalities of intestinal barrier function. However, we know very little about other functions of Hif-1α on intestinal intraepithelial lymphocyte (IEL). Therefore, we generated a transgenic mouse (Hif1-α ΔIEC mice), which was knocked out Hif1-α specifically in IECs, to study the effect of Hif1-α on IEL. IELs were isolated from the small intestine and colon of mice, respectively, and examined by flow cytometry and quantitative real-time PCR. All the cytokines expression was detected by quantitative real-time PCR. The NSAID enteropathy was induced by gavaged with 5 mg/kg indomethacin and the experimental colitis was induced by administration of 2.5% DSS. We found that the number of IELs is increased in Hif1-α ΔIEC mice. It is showed that knockout of Hif1-α in IECs led to significant changes in IEL phenotype, including a marked decline in the CD8αα+ and TCRγδ+ population. The reduction of CD8αα+ IELs is accompanied by increased apoptosis, decreased proliferation and weakened migration in Hif1-α ΔIEC mice. Moreover, absence of intestinal epithelial Hif1-α markedly changed the population of IELs in NSAID-induced small intestinal injury and increased susceptibility to dextran sulfate sodium-induced colitis. In summary, our results first time demonstrate that IEC-derived Hif1-α is essential for maintaining IELs homeostasis and intestinal microbiota.


Phosphorylation-specific prolyl isomerase Pin1 as a new diagnostic and therapeutic target for cancer.
Proline directed phosphorylation is a key regulatory mechanism controlling the function of fundamental proteins involved in cell proliferation and oncogenic transformation. Recently, the identification of the phosphorylation dependent prolyl isomerase Pin1 has uncovered a distinct regulatory mechanism controlling protein function. Specifically, Pin1 controls the conversion of peptidyl proline bond conversion from cis to trans, only when the preceding serine or threonine is phosphorylated. The intrinsic inter-conversion of such bonds is rather slow and is further inhibited by phosphorylation. As a consequence catalysis by Pin1 is required to overcome this restriction. Importantly, structural evidence has now demonstrated that Pin1-catalyzed prolyl isomerization can have significant effects on the global structure of substrate proteins. Furthermore, Pin1 overexpression is found in several types of cancer where it functions to not only promote tumorigenesis induced by oncogenes such as Ras and Neu, but also to regulate molecules that facilitate persistent proliferative capacity. Consequently, Pin1-mediated phosphorylation-dependent isomerization represents a unique regulatory mechanism in cell signaling whose deregulation during tumorigenesis adds to the pro-proliferative capacity of tumor cells and therefore Pin1 represents a novel tumor marker and potential therapeutic target.


Color Doppler ultrasonography in the evaluation of compensatory arteries in patients with moyamoya disease: combined with cerebral angiography.
To evaluate the hemodynamics of maxillary artery (MA), superficial temporal artery (STA) and ophthalmic artery (OA), and evaluate the hemodynamics prediction capability of these arteries formed compensatory arteries into intracranial using Doppler ultrasonography. The evaluation of MA, STA, and OA with transcranial doppler ultrasonography and with cerebral angiography was made in 106 MMD patients (total of 212 hemispheres of the brain), 58 male and 48 female, aged 39.3±12.0 years old. Doppler ultrasonography measured the following blood flow parameters: peak systolic velocity (PSV), end-diastolic velocity (EDV), and resistance index (RI). DSA evaluate whether MA, STA, OA formed compensatory arteries into intracranial. Based on the compensation situation, the patients were divided into two groups: compensatory group and non-compensatory group. The differences of patient's hemodynamic parameters between compensatory and non-compensatory groups were performed using independent two-sample t-tests with equal or non-equal variance as appropriate. Categorical variables were summarized using frequency and percentage and compared using Chi-square tests. We evaluated the prediction ability of each hemodynamic parameters for each artery (combining left and right side) using Receiver Operating Curve. All the analyses were performed using SAS 9.4 (Cary, NC). Comparing the hemodynamic parameters between the compensatory group and non-compensatory group, all hemodynamic parameters of MA, STA and OA have statistically significant differences between the two groups. Depending on the ROC Curve, EDV (AUC=0.6933±0.0463) for MA, RI (AUC=0.8910±0.0569) for STA, EDV (AUC=0.7863± 0.0330) for OA are better predictors of compensatory growth. Color duplex ultrasonography is a reliable, noninvasive and economic tool to assess hemodynamic changes of MA, STA and OA, and has prediction capability of these arteries formed compensatory arteries into intracranial.


Transforming growth factor beta 1-induced changes in cell migration, proliferation, and angiogenesis in the chicken chorioallantoic membrane.
Application of TGF beta 1 (10-100 ng) to the chicken chorioallantoic membrane (CAM) for 72 h resulted in a dose-dependent, gross angiogenic response. The vascular effects induced by TGF beta 1 were qualitatively different than those induced by maximal doses of basic FGF (bFGF) (500 ng). While TGF beta 1 induced the formation of large blood vessels by 72 h, bFGF induced primarily small blood vessels. Histologic analysis revealed that TGF beta 1 stimulated pleiotropic cellular responses in the CAM. Increases in fibroblast and epithelial cell density in the area of TGF beta 1 delivery were observed as early as 4 h after TGF beta 1 treatment. By 8 h, these cell types also demonstrated altered morphology and marked inhibition of proliferation as evidenced by 3H-thymidine labeling. Thus, the TGF beta 1-stimulated accumulation of these cell types was the result of cellular chemotaxis from peripheral areas into the area of TGF beta 1 delivery. Microscopic angiogenesis in the form of capillary sprouts and increased endothelial cell density first became evident at 16 h. By 24 h, capillary cords appeared within the mesenchyme of the CAM, extending towards the point of TGF beta 1 delivery. 3H-thymidine labeling revealed that the growth of these capillary cords was due to endothelial cell proliferation. Finally, perivascular mononuclear inflammation did not become evident until 48 h of treatment, and its presence correlated spatially and temporally with the gross and histological remodelling of newly formed capillary cords into larger blood vessels. In summary, these data suggest that, in the chicken CAM, TGF beta 1 initiates a sequence of cellular responses that results in growth inhibition, cellular accumulation through migration, and microvascular angiogenesis.


Neuropeptide SP activates the WNT signal transduction pathway and enhances the proliferation of bone marrow stromal stem cells.
Substance P (SP) mediates multiple activities in various cell types, such as proliferation, anti-apoptotic response, and inflammation. We have investigated the effects of SP, NK1 antagonist and DKK1 on proliferation of bone marrow stromal stem cells (BMSCs), as well as the underlying mechanism. Isolated BMSCs were exposed to SP (10(-8) M) (group A), SP + NK1 antagonist (1 µM) (group B), SP + DKK1 (0.2 µg/mL) (group C), or the same amount of PBS (group D). Expression of gene and protein of Wnt/β-catenin signalling was detected using quantitative PCR and western blotting. SP (10(-8) M) significantly enhanced the proliferation of BMSCs and the number of viable cells was reduced by treatment with NK1 antagonist (1 µM) or DKK1 (0.2 µg/mL). SP also significantly increased the expression of C-myc mRNA, Lef1, β-catenin protein and C-myc protein, but decreased the expression of Tcf7 and p-β-catenin protein compared to group D. These roles of SP were inhibited by the NK1 antagonist and DKK1. Expression of CyclinD1 and β-catenin mRNAs, however, was not significantly influenced by SP, NK1 antagonist and DKK1. These findings suggest that SP enhances BMSC proliferation via regulation of the Wnt/β-catenin signalling pathway.


17β-Hydroxysteroid Dehydrogenase Type 1 Inhibition: A Potential Treatment Option for Non-Small Cell Lung Cancer.
In the face of the clinical challenge posed by non-small cell lung cancer (NSCLC), the present need for new therapeutic approaches is genuine. Up to now, no proof existed that 17β-hydroxysteroid dehydrogenase type 1 (17β-HSD1) is a viable target for treating this disease. Synthesis of a rationally designed library of 2,5-disubstituted furan derivatives followed by biological screening led to the discovery of 17β-HSD1 inhibitor 1, capable of fully inhibiting human NSCLC Calu-1 cell proliferation. Its pharmacological profile renders it eligible for further in vivo studies. The very high selectivity of 1 over 17β-HSD2 was investigated, revealing a rational approach for the design of selective inhibitors. 17β-HSD1 and 1 hold promise in fighting NSCLC.


Low plasma levels of docosahexaenoic acid are associated with an increased relapse vulnerability in substance abusers.
Low levels of some polyunsaturated fatty acids (PUFAs) could influence behaviors leading to the abuse of substances through their actions on serotonergic and dopaminergic mechanisms. Because substance abusers tend to have poor dietary habits, the possibility that a deficient intake of n-3 PUFAs, available from dietary sources only, and subsequent low n-3 plasma levels would predict their relapse rates was explored. Thirty-five patients admitted to substance abuse clinics were enrolled and followed for one year. Dietary questionnaires and blood samples were collected at baseline and on a quarterly basis, and relapse rates monitored on a monthly basis. Six patients dropped out shortly after study entry, 11 relapsed in the course of the study and dropped out, 7 relapsed but completed the study, and 11 did not relapse and completed the study. Non-relapsers were found to have significantly higher levels of docosahexaenoic acid (DHA) calculated as microg/ml and % TFA, when compared to relapsers (p = .031 and p = .010, respectively) and to relapsers and non-completers combined (p = .014 and p = .009, respectively). These pilot data suggest, but do not prove, the existence of a relationship between low levels of DHA and relapse vulnerability in some individuals who abuse substances. The study of the efficacy of n-3 supplements or of dietary modifications on relapse appears warranted.


Aplasia cutis congenita. A follow-up evaluation after 25 years.
Aplasia cutis congenita is a rare disease with less than 300 cases reported in the literature. A patient with extensive involvement of the skin was observed for 25 years. During adolescence, a reactive depression related to the residual cicatricial alopecia on the left side of the scalp developed. The psychiatric distress disappeared after corrective surgery was performed. It is recommended that patients with this disorder be regularly observed to select cases appropriate for early plastic surgery.


Limbic seizures, kindling, and psychosis: a link between neurobiology and clinical psychiatry.
This interplay between basic neurobiology and clinical psychiatry helps shape clinical thinking about behavioral disorders. At a basic science level, the potential exists for elucidating the functional anatomy and physiology of CNS regions involved in kindling. These studies should aid in understanding the basic mechanisms involved in this process, thus clarifying the processes involved in the associated behavioral changes. At a clinical level, improved techniques of CNS imaging such as provided by positron emission tomography should allow better elucidation of the functional anatomy related to specific psychiatric symptoms. By combining basic science and clinical research with careful clinical diagnosis and observation, we eventually should be able to understand many aspects of human psychopathology. Such understanding will lead to improved therapeutic strategies.


Melanocytic naevi and basal cell carcinoma: is there an association?
Melanoma and basal cell carcinoma (BCC) affect similar body sites and share a complex relationship with sun exposure. To establish the existence and magnitude of association between melanocytic naevi, the strongest predictors of melanoma, and BCC to give possible insights into shared pathways of solar ultraviolet tumourigenesis. In a community-based longitudinal Australian study, detailed information was collected about sun sensitivity, and dermatologists assessed skin colour and counted naevi on the forearms (1986) and back (1992). The BCC frequency and sites were prospectively monitored until 2007. Multivariate logistic regression was used to assess the association of naevi on the forearms or on the back with the development of BCC, adjusting for other risk factors. Of 1621 study participants in 1992, 1339 (average age 49) had complete follow-up and 401 (30%) of these had 1202 histologically confirmed BCCs until 2007. After adjustment for age, gender, skin colour, naevi on the back and sun exposure, overall BCC risk increased significantly in those with forearm naevi (odds ratio: 1.5; 95% confidence intervals: 1.1-1.9). Risk of BCC specifically on the back was doubled in those with many (11 or more) forearm naevi compared with no forearm naevi (odds ratio: 2.4; 95% confidence interval: 1.1-4.8). Naevi on the back were not associated with subsequent basal cell carcinoma. High naevus prevalence on the arms is associated with future BCC development.


Medical therapies to extend survival in hepatocellular carcinoma.
Hepatocellular carcinoma (HCC) is a serious malignancy with 21,000 new cases estimated for 2008. Several common diseases are associated with an increased risk of the development of HCC, including viral hepatitis, cirrhosis, and other chronic liver diseases. Most patients present with advanced disease, and therefore have only limited therapeutic options. However, advancements in screening and surveillance have allowed more patients to be identified and diagnosed with earlier-stage disease, increasing their therapeutic options. Several treatment modalities exist for early- and intermediate-stage disease, including ablative techniques and embolization methods. Additionally, advances in targeted therapy have resulted in the approval of the oral multitargeted tyrosine kinase inhibitor sorafenib, resulting in improved length of survival. In this roundtable discussion, the current epidemic of HCC is addressed, including factors contributing to an increased rate of occurrence. Additionally, the optimal screening and diagnosis of HCC patients is discussed, and the appropriate treatment modalities for each stage of HCC are presented.


Molecular and serologic detection of Ehrlichia spp. in endangered Brazilian wild captive felids.
Ehrlichiosis, an emergent tick-borne disease that affects both humans and animals, may represent a threat to the survival and preservation of wild felids in Brazil. There are few studies of ehrlichiosis in wild felids in Brazil, but Ehrlichia spp. are present in domestic cats. Antibodies to Ehrlichia canis have been reported in a puma (Puma concolor). In this study we assessed the presence of these hemoparasites in the blood of Brazilian wild captive felids. Of the 72 animals tested, 5 (7%) were seropositive for the E. canis antigen, and 11 (15%) were positive for E. canis DNA sequences. We also performed sequence alignment to establish the identity of the parasite species infecting these animals using 16S rRNA and omp-1 genes. Sequences based on 16S rRNA were similar to those found in dogs and cats from Thailand, Brazil, China, and Taiwan and with E. canis obtained from a single individual (human) in Venezuela. Ehrlichia sp. sequence from sampled felines based on omp-1 gene was similar to the p28 and p30 multigene family of E. canis. To our knowledge, this is the first study of molecular detection of Ehrlichia sp. in Brazilian wild feline species.


Experimental validation on dual-frequency outperforms single-frequency SSVEP with large numbers of targets within a given frequency range.
Multi-frequency steady-state visual evoked potential (SSVEP) aims to increase the number of targets in SSVEP-based brain-computer interfaces. However, the effectiveness of multi-frequency SSVEP when there is a large number of targets compared to traditional single-frequency SSVEP has not been demonstrated to date. It is also unclear the degree to which multi-frequency SSVEP outperforms single-frequency SSVEP as the number of targets increases. This study directly compares single-frequency and dual-frequency SSVEPs for different numbers of targets within a fixed (5 Hz) frequency range. Our results demonstrate that dual-frequency SSVEP maintains its performance at a high level of accuracy in the range while single-frequency SSVEP performance falls as the number of targets becomes very high within the given frequency range. In this particular study, dual-frequency SSVEP has a clear advantage when there are more than 120 targets in a 5 Hz frequency range.


Viruses infecting common bean (Phaseolus vulgaris L.) in Tanzania: A review on molecular characterization, detection and disease management options.
Common bean (Phaseolus vulgaris L.) is a major legume crop, serving as a main source of dietary protein and calories and generating income for many Tanzanians. It is produced in nearly all agro-ecological zones of Tanzania. However, the average yields are low (<1000 kg/ha), which is attributed to many factors including virus diseases. The most important viruses of common bean in Tanzania are Bean common mosaic virus (BCMV) and Bean common mosaic necrosis virus (BCMNV) but other viruses have also been reported. There has never been a review of common bean virus diseases in the country, and the lack of collated information makes their management difficult. Therefore, this review focuses on (1) occurrence of different viruses of common bean in Tanzania, (2) molecular characterization of these viruses, (3) detection tools for common bean viruses in Tanzania and (4) available options for managing virus diseases in the country. Literature and nucleotide sequence database searches revealed that common bean diseases are inadequately studied and that their causal viruses have not been adequately characterized at the molecular level in Tanzania. Increased awareness on common bean virus diseases in Tanzania is expected to result into informed development of strategies for management of the same and thus increased production, which in turn has implication on nutrition and income.


The complementary role of the Kinect virtual reality game training in a patient with metachromatic leukodystrophy.
Metachromatic leukodystrophy (MLD) is a lysosomal storage disease characterized by demyelination of the peripheral and central nerves. Patients with MLD can present with gait disturbances, progressive spastic quadriparesis, diffuse muscle atrophy, and areflexia attributable to central or peripheral nerve involvements. The rehabilitation of patients with MLD generally focuses on gait disturbances, balance impairments, and muscle weaknesses. Here, we present a case of MLD in which virtual reality (VR) training was used as an adjunctive therapy. We also discuss the complementary role of VR therapy, which was successfully integrated with a conventional rehabilitation program for a young patient with MLD who had impaired balance and gait. After completion of the integrated rehabilitation program, the patient demonstrated improvements in functional independency, mobility, walking speed, and balance. His total Functional Independence Measure score increased from 97 to 109, 6-minute walk test increased from 342 to 396 m, 10-minute walk test decreased from 11 to 7 seconds, and Berg Balance Scale score increased from 38 to 42 points. Moreover, 6 weeks after completion of the therapy, these improvements were sustained for the most part. Adding VR to a conventional rehabilitation program is an emerging trend in neurologic rehabilitation. Our patient with MLD demonstrated considerable improvements with a high level of enjoyment and satisfaction.


Apprehensions and Optimism among Dental Professionals during the COVID-19 Pandemic-A Nationwide Cross-Sectional Evaluation.
Globally, the pandemic of the coronavirus disease, which started in Wuhan, China, has become a major issue for public health. The COVID-19 epidemic notably causes health professionals to experience significantly more emotional stress than the general populace. The present study proposes to investigate the fear aspect in dentists in the initiation of clinical practice during these times. An online cross-sectional study was conducted among dental practitioners based on a pre-validated questionnaire. The data were expressed as frequency and percentage analyzed using the chi-square test using SPSS version 25. The data was obtained from 271 participants, where clinical practice after the first wave was mostly by freelancers (p-value = 0.01); most of whom were married (p-value = 0.065); 19.1% attached to institutes did not have changes in earnings; 28.1% of private practitioners had less than 10% reduction in cases. A total of 62% of private practitioners are concerned about the vaccine's preventative effects (p-value = 0.026), and 57% of private practitioners worry about being sued for the delay in treatment (p-value = 0.036). Only 33.1% of employees in institutions worry that becoming sick could endanger their family. As dentists continue to work their way through this pandemic, these pressures only occasionally have an impact on them. According to the researchers, this is the first study that has captured the anxiety and apprehensions that dental practitioners experienced during the height of the COVID-19 outbreak in India in April 2021. The study's findings demonstrate that the study population was generally upbeat and confident that they could quickly overcome their fear.


Seasonal variation in stable carbon and nitrogen isotope values of bats reflect environmental baselines.
The stable carbon and nitrogen isotope composition of animal tissues is commonly used to trace wildlife diets and analyze food chains. Changes in an animal's isotopic values over time are generally assumed to indicate diet shifts or, less frequently, physiological changes. Although plant isotopic values are known to correlate with climatic seasonality, only a few studies restricted to aquatic environments have investigated whether temporal isotopic variation in consumers may also reflect environmental baselines through trophic propagation. We modeled the monthly variation in carbon and nitrogen isotope values in whole blood of four insectivorous bat species occupying different foraging niches in southern Spain. We found a common pattern of isotopic variation independent of feeding habits, with an overall change as large as or larger than one trophic step. Physiological changes related to reproduction or to fat deposition prior to hibernation had no effect on isotopic variation, but juvenile bats had higher δ13C and δ15N values than adults. Aridity was the factor that best explained isotopic variation: bat blood became enriched in both 13C and 15N after hotter and/or drier periods. Our study is the first to show that consumers in terrestrial ecosystems reflect seasonal environmental dynamics in their isotope values. We highlight the danger of misinterpreting stable isotope data when not accounting for seasonal isotopic baselines in food web studies. Understanding how environmental seasonality is integrated in animals' isotope values will be crucial for developing reliable methods to use stable isotopes as dietary tracers.


Cost Effective Printing of Laboratory Reports: Biochemist's and Physician's debate and Institutions Dilemma.
Laboratory investigations account for significant percentage of healthcare expenses. Every hospital and laboratory especially in the government sector wants to cut down the expenses on reports and offer inferior printouts of reports. The debate of printing attractive reports (clientele aspiration) Vs costs cutting (managerial issues) continues. It becomes the moral responsibility of doctors to guide the management into implementing an effective and economical option of report transcription. Cutting cost is always good but it should be achieved in an effective way keeping in mind the expectation of all the stake holders and ensuring that quality is not significantly compromised. The data regarding economics of printing available on the Internet may be market driven and not a true reflection of printing cost. The present study was undertaken to generate data on the economics of printing reports on various platforms to enable managers to make informed decision on choice of optimal printing option. To provide practical data on economics of printing reports using various printing options available in the country. Four printing devices (laser printer, inkjet printer, dotmatrix printer and thermal printer) were connected to the laboratory information system and the reports printed from them were critically evaluated for the following parameters - cost of stationary, printing cost, time of printing and clientele satisfaction. The cost of printing a single report on laser printer, inkjet printer, dotmatrix printer and thermal printers was Rs 0.75, Rs 0.65, Rs 0.20 and Rs 0.93 respectively. The time taken to print 30 reports were 162 sec, 193 sec, 210 and 60 sec respectively. Clientele satisfaction scores were best with Laser and Inkjet printed reports. The most economical mode of printing is Dot Matrix printer using DOS output for printing. However, when the workload of a laboratory is high, then the use of laser printer is not prohibitively expensive option and can be resorted to. Use of thermal printer was found to be unsatisfactory.


Association Between Systolic and Diastolic Blood Pressure Variability and the Risk of End-Stage Renal Disease.
Recent data suggest that visit-to-visit variability of blood pressure (BP) is associated with cardiovascular events. We evaluated the role of BP variability as a determinant of end-stage renal disease (ESRD). Using nationally representative data from the Korean National Health Insurance System, 8 199 089 subjects had been enrolled during 2009 to 2010 who were free of ESRD and underwent ≥3 health examinations during 2005 to 2010 were followed to the end of 2017. BP variability was measured using the coefficient of variation, SD, and variability independent of the mean. The primary outcome was the development of ESRD, defined as a combination of the relevant disease code and the initiation of renal replacement therapy. The χ2 test, t test, and log-rank test were used in the statistical analysis. There were 16 567 cases of ESRD during a median follow-up of 7.89±0.88 years. The highest quartile of systolic or diastolic BP showed a higher incident rate of ESRD compared with the other 3 quartiles. It was augmented in patients with the highest quartile of both systolic and diastolic BP variabilities. Among patients with the highest quartile of systolic and diastolic BP variabilities, the uncontrolled hypertension group (>140/90 mm Hg) taking antihypertensive medication showed the highest incidence rate of ESRD. These results were consistent when modeling variability of BP using coefficient of variation, SD, and variability independent of the mean and in various sensitivity analyses. Systolic and diastolic BP variabilities were independently associated with an increased incidence of ESRD, and it was augmented when both variabilities were present together.


Porous carbons derived from hydrothermally treated biogas digestate.
Porous carbons from digestate-derived hydrochar were produced, characterized and their performance to reclaim phosphate from water was evaluated as a preliminary approach to demonstrate their practical application. In a first step, the digestate was converted into hydrochars through hydrothermal carbonization by using two different pH conditions: 8.3 (native conditions) and 3.0 (addition of H2SO4). The resulting hydrochars did not present significant differences. Consecutively, the hydrochars were activated with KOH to produce activated carbons with enhanced textural properties. The resulting porous carbons presented marked differences: the AC native presented a lower ash content (20.3 wt%) and a higher surface area (SBET = 1106 m2/g) when compared with the AC-H2SO4 (ash content = 43.7 wt% SBET = 503 m2/g). Phosphorus, as phosphate, is a resource present in significative amount in wastewater, causing serious problems of eutrophication. Therefore, the performance of the porous carbons samples to recover phosphate - P(PO43-) - from water was evaluated through exploitation assays that included kinetic studies. The lumped model presented a good fitting to the kinetic data and the obtained uptake capacities were the same for both carbons, 12 mg P(PO43-)/g carbon. Despite the poorer textural properties of AC-H2SO4, this carbon was richer in Ca, Al, Fe, K, and Mg cations which promoted the formation of mineral complexes with phosphate anions. The results obtained in this work are promising for the future development of P(PO43-) enriched carbons that can be used thereafter as biofertilizers in soil amendment applications.


ECG-Based Multiclass Arrhythmia Classification Using Beat-Level Fusion Network.
Cardiovascular disease (CVD) is one of the most severe diseases threatening human life. Electrocardiogram (ECG) is an effective way to detect CVD. In recent years, many methods have been proposed to detect arrhythmia using 12-lead ECG. In particular, deep learning methods have been proven to be effective and have been widely used. The attention mechanism has attracted extensive attention in many fields in a series of deep learning methods. Off-the-shelf solutions based on deep learning and attention mechanism for ECG classification mostly give weights to time points. None of the existing methods were considered using the attention mechanism dealing with ECG signals at the level of heartbeats. In this paper, we propose a beat-level fusion net (BLF-Net) for multiclass arrhythmia classification by assigning weights at the heartbeat level, according to the contribution of the heartbeat to diagnostic results. This algorithm consists of three steps: (1) segmenting the long ECG signal into short beats; (2) using a neural network to extract features from heartbeats; and (3) assigning weights to features extracted from heartbeats using an attention mechanism. We test our algorithm on the PTB-XL database and have superiority over state-of-the-art performance on six classification tasks. Besides, the principle of this architecture is clarified by visualizing the weight of the attention mechanism. The proposed BLF-Net is shown to be useful and automatically provides an effective network structure for arrhythmia classification, which is capable of aiding cardiologists in arrhythmia diagnosis.


Comparison of 1-Repetition-Maximum Performance Across 3 Weightlifting Overhead Pressing Exercises and Sport Groups.
To (1) compare the 1-repetition-maximum (1RM) performance between the push press, push jerk, and split jerk and (2) explore these differences between weightlifters, CrossFit athletes, and a mixed group of athletes. Forty-six resistance-trained males (age 28.8 [6.4] y; height 180.0 [6.0] cm; body mass 84.1 [10.2] kg; weightlifting training experience 3.64 [3.14] y) participated in this study. The 1RM performance of the push press, push jerk, and split jerk was assessed during the same session in a sequential order (ie, combined 1RM assessment method). Thirty-six participants were retested to determine between-sessions reliability of the 1RM values. Intraclass correlation coefficients (ICCs) and associated 95% confidence intervals (CIs) showed a high between-sessions reliability for the push press (ICC = .98; 95% CI, .95-.99), push jerk (ICC = .99; 95% CI, .98-1.00), and split jerk (ICC = .99; 95% CI, .98-1.00). There was a significant main effect of exercise (η2 = .101) and exercise × group interaction (η2 = .012) on 1RM performance (P < .001), whereas the main effect of group did not reach statistical significance (P = .175). This study provides evidence that the weightlifting overhead press derivatives affect 1RM performance. In addition, the interaction of exercise and sport group was caused by the higher differences in 1RM performance between exercises for weightlifters compared with CrossFit and a mixed group of athletes. Therefore, strength and conditioning professionals should be aware that the differences in 1RM performance between weightlifting overhead-press derivatives may be affected by sport group.


Localization of prolactin in chromophobe pituitary adenomas: study of human necropsy material by immunoperoxidase technique.
In order to identify prolactin-producing tumours in human pituitary glands, 45 chromophobe adenomas, obtained from unselected necropsies, have been studied by various staining procedures including the immunoperoxidase technique for the demonstration of prolactin. The presence of immunoreactive prolactin was revealed in the cytoplasm of the tumour cells in six cases (13%), indicating that the occurrence of prolactin-producing adenomas is not rare. No correlations were established between tumours and clinical history. Two adenomas were detected in female and four in male patients. The age of the patients at necropsy ranged from 28 to 75 years. Three adenomas were associated with disseminated carcinoma, two with fatal liver disease, and one with diabetes mellitus, atherosclerosis, and pyelonephritis. Manifest endocrine symptoms were not disclosed, and endocrine investigations, including measurements of blood prolactin levels, were not undertaken. Thus, direct evidence is lacking as to whether or not these tumours were actively secreting prolactin. In the non-tumorous parts of the anterior lobes the number of prolactin cells was decreased in two cases, suggesting that prolactin released from the adenoma cells suppressed prolactin production in the non-tumorous pituitary. However, the number of prolactin cells of the non-tumorous adenohypophysis seemed to be unchanged in two and increased in another two cases. The present findings conclusively proved the existence of the prolactin-producing adenomas as a distinct entity. These tumours do not stain with acid or basic dyes, they are PAS or thionin negative, and do not contain immunoreactive growth hormone. Thus, by conventional staining procedures they are indistinguishable from other chromophobe adenoma types. Herlant's erythrosin and Brookes' carmoisine methods, claimed spedifically to stain prolactin cells, failed to provide reliable results, hence their use cannot be recommended in tumour identification. Immunoperoxidase staining of prolactin is the only technique which conclusively reveals the presence of immunoreactive prolactin in the cytoplasm of the tumour cells and permits diagnosis. It is proposed that this technique be introduced in pituitary morphological studies. Its application may lead to a better understanding of problems related to prolactin-producing tumours and their secretory activity.


[Apropos of the studies of Lewis, Nusslein-Volhard and Wieschaus, 1995 Nobel prize winners, on the genetic mechanisms of embryonic development of drosophila. A model for human cancer progression].
EB Lewis, C Nusslein-Volhard and E Wieschaus were the winners of the Nobel prize in 1995 for the discovery of genes controling the embryonic development in drosophila. Drosophila development is dependent on sequential activities of three types of genes: the maternal genes, the segmentation genes, and the homeotic genes which are responsible for the segment identity and finally for the building of the body. Mutations of these genes are spectacular because they affect the body structure formed from individual segments. Therefore, the molecular processes regulating the development of inferior organisms such as yeast or more complex as the vertebrates were elucidated by these three researchers. These early biological mechanisms regulate the cell life through interactions with neighbouring cells. We speculate that any alteration of these processes might be implicated in cancer. Understanding of these molecular mechanisms which control cell interactions in cancer constitutes a basis for definition of new prognostic markers and putatively novel therapeutic approaches.


The organization and connections of anterior and posterior parietal cortex in titi monkeys: do New World monkeys have an area 2?
We used multiunit electrophysiological recording techniques to examine the topographic organization of somatosensory area 3b and cortex posterior to area 3b, including area 1 and the presumptive area 5, in the New World titi monkey, Callicebus moloch. We also examined the ipsilateral and contralateral connections of these fields, as well as those in a region of cortex that appeared to be similar to both area 7b and the anterior intraparietal area (7b/AIP) described in macaque monkeys. All data were combined with architectonic analysis to generate comprehensive reconstructions. These studies led to several observations. First, area 1 in titi monkeys is not as precisely organized in terms of topographic order and receptive field size as is area 1 in macaque monkeys and a few New World monkeys. Second, cortex caudal to area 1 in titi monkeys is dominated by the representation of the hand and forelimb, and contains neurons that are often responsive to visual stimulation as well as somatic stimulation. This organization is more like area 5 described in macaque monkeys than like area 2. Third, ipsilateral and contralateral cortical connections become more broadly distributed away from area 3b towards the posterior parietal cortex. Specifically, area 3b has a relatively restricted pattern of connectivity with adjacent somatosensory fields 3a, 1, S2 and PV; area 1 has more broadly distributed connections than area 3b; and the presumptive areas 5 and 7b/AIP have highly diverse connections, including connections with motor and premotor cortex, extrastriate visual areas, auditory areas and somatosensory areas of the lateral sulcus. Fourth, the hand representation of the presumptive area 5 has dense callosal connections. Our results, together with previous studies in other primates, suggest that anterior parietal cortex has expanded in some primate lineages, perhaps in relation to manual abilities, and that the region of cortex we term area 5 is involved in integrating somatic inputs with the motor system and across hemispheres. Such connections could form the substrate for intentional reaching, grasping and intermanual transfer of information necessary for bilateral coordination of the hands.


Potentiation of cerebellar Purkinje cells facilitates whisker reflex adaptation through increased simple spike activity.
Cerebellar plasticity underlies motor learning. However, how the cerebellum operates to enable learned changes in motor output is largely unknown. We developed a sensory-driven adaptation protocol for reflexive whisker protraction and recorded Purkinje cell activity from crus 1 and 2 of awake mice. Before training, simple spikes of individual Purkinje cells correlated during reflexive protraction with the whisker position without lead or lag. After training, simple spikes and whisker protractions were both enhanced with the spiking activity now leading behavioral responses. Neuronal and behavioral changes did not occur in two cell-specific mouse models with impaired long-term potentiation at their parallel fiber to Purkinje cell synapses. Consistent with cerebellar plasticity rules, increased simple spike activity was prominent in cells with low complex spike response probability. Thus, potentiation at parallel fiber to Purkinje cell synapses may contribute to reflex adaptation and enable expression of cerebellar learning through increases in simple spike activity.


Vaccinia necrosum after smallpox vaccination for herpes labialis.
We have described a patient with vaccinia necrosum after smallpox vaccination for persistent herpes labialis. The patient eventually recovered after surgical resection of the lesion and multiple courses of vaccinia immune globulin and methisazone. This report emphasizes the needless risks of vaccinating patients with herpetic infections.


Induction of acalculous cholecystitis and pneumonitis in dogs following inhalation of constituents of cigarette smoke condensate.
In previous studies in this laboratory it was demonstrated that 1) constituents of the water-soluble phase of cigarette smoke condensate can activate Hageman-factor-dependent pathways of coagulation, fibrinolysis, and kinin generation; and 2) that in vivo activation of Hageman-factor-dependent pathways by intravenous injection of plant polyphenols in dogs and AFrican Green monkeys can induce acute acalculous cholecystitis and alveolitis. The purpose of this communication is to report that inhalation of the water-soluble, nondialyzable constituents of cigarette smoke condensate, or "tar," can activate Hageman-factor-dependent pathways in the dog and induce acute acalculous cholecystitis, pneumonitis, and the formation of thrombi in branches of pulmonary vessels.


Early adoption of injectable naltrexone for alcohol-use disorders: findings in the private-treatment sector.
The U.S. substance-abuse treatment system has been slow to adopt medications for the treatment of alcohol-use disorders (AUDs). The objectives of this study are to (a) determine how the inherent characteristics of injectable naltrexone (i.e., relative advantage, complexity, trialability, observability, compatibility) shape organizational-level decisions to adopt the medication and (b) identify key predictors of adoption and barriers that impede adoption. This study uses data from a nationally representative sample of 345 privately funded U.S. substance-abuse treatment programs to examine adoption (current use) of injectable naltrexone. Sixteen percent of private treatment programs are early adopters of injectable naltrexone. Multivariate logistic regression models reveal that organizational size and percentage of patients paying with private insurance are significant predictors of adoption. The most salient predictor of adoption is innovation compatibility, measured by program use of other AUD pharmacotherapies. Barriers to adoption include cost, lack of access to prescribing physicians, and lack of knowledge about the medication. Injectable naltrexone, however, is addressing the patient compliance barrier, demonstrated by 70% of patients receiving at least 2 months of medication. The adoption of AUD pharmacotherapies remains low, with only half of the sampled programs prescribing any AUD pharmacotherapies. Patterns of early adoption of injectable naltrexone are, however, promising. Results highlight innovation compatibility and relative advantage as explanations of organizational decisions to adopt injectable naltrexone. Future research will move beyond issues of adoption and provide a more detailed examination of the implementation process.


B3(Fv)-PE38KDEL, a single-chain immunotoxin that causes complete regression of a human carcinoma in mice.
The genes encoding the heavy- and light-chain Fv regions of the monoclonal murine antibody B3, which recognizes a carbohydrate antigen on the surface of many human carcinomas, were cloned by PCR techniques and used to generate single-chain immunotoxins containing Pseudomonas exotoxin (PE). The light and heavy chains were connected by a flexible linker to form a single-chain antigen-binding protein, B3(Fv), which was in turn fused to truncated forms of PE lacking the cell-binding domain. The single-chain Fv and two different B3(Fv) immunotoxins, B3(Fv)-PE40 and B3(Fv)-PE38KDEL, were expressed in Escherichia coli and the single-chain immunotoxins were purified to near homogeneity. Both recombinant immunotoxins were shown to be cytotoxic specifically to carcinoma cell lines that express the B3 antigen on their surface; B3(Fv)-PE38KDEL was significantly more active. Furthermore, intravenous administration of B3(Fv)-PE38KDEL caused complete regression of human epidermoid carcinomas growing subcutaneously in immunodeficient mice.


Effect of baseline glomerular filtration rate on survival in patients undergoing partial or radical nephrectomy for renal cortical tumors.
To evaluate the effect of baseline renal function and comorbidity index on survival in patients with renal tumors. We retrieved demographic, clinicopathologic, body mass index (BMI), and comorbidity data (assessed by Charlson-Romano index and hypertension) for 1479 patients who underwent partial or radical nephrectomy between January 4, 1995, and June 9, 2005, for localized renal tumors. We used the abbreviated Modified Diet and Renal Disease equation to estimate glomerular filtration rate (eGFR) using the last preoperative serum creatinine measurement. Body mass index and eGFR time trends were analyzed with linear regression. The effect of BMI, comorbidity, and baseline eGFR on disease-free and overall survival was studied using Cox regression controlling for pathologic stage, nodal status, and metastasis. Over a 10-year interval, median BMI increased from 27 (interquartile range [IQR], 24-31) to 28 (IQR, 25-31; P=.004), and median baseline eGFR decreased from 70 (IQR, 58-80) to 63 mL/min per 1.73 m(2) (IQR, 57-78; P<.001). Multivariate regression demonstrated an association between year of surgery and baseline eGFR (P<.001) even after adjusting for age, sex, comorbidity, BMI, and tumor size. We repeated the analysis for patients aged 18 to 70 years, and this association persisted (P<.001). Baseline eGFR, BMI, and comorbidity were not associated with disease-free survival after controlling for stage. However, moderately reduced baseline eGFR (45-60 mL/min per 1.73 m(2)) and severely reduced eGFR (<45 mL/min per 1.73 m(2)) were significantly associated with overall survival (hazard ratio, 1.5; P<.003; and hazard ratio, 2.8; P<.001; respectively). Baseline eGFR has declined over the past decade. Nephron-sparing techniques should be considered for patients with severely diminished baseline eGFR.


Brachytherapy for Patients With Prostate Cancer: American Society of Clinical Oncology/Cancer Care Ontario Joint Guideline Update.
Purpose To jointly update the Cancer Care Ontario guideline on brachytherapy for patients with prostate cancer to account for new evidence. Methods An Update Panel conducted a targeted systematic literature review and identified more recent randomized controlled trials comparing dose-escalated external beam radiation therapy (EBRT) with brachytherapy in men with prostate cancer. Results Five randomized controlled trials provided the evidence for this update. Recommendations For patients with low-risk prostate cancer who require or choose active treatment, low-dose rate brachytherapy (LDR) alone, EBRT alone, and/or radical prostatectomy (RP) should be offered to eligible patients. For patients with intermediate-risk prostate cancer choosing EBRT with or without androgen-deprivation therapy, brachytherapy boost (LDR or high-dose rate [HDR]) should be offered to eligible patients. For low-intermediate risk prostate cancer (Gleason 7, prostate-specific antigen < 10 ng/mL or Gleason 6, prostate-specific antigen, 10 to 20 ng/mL), LDR brachytherapy alone may be offered as monotherapy. For patients with high-risk prostate cancer receiving EBRT and androgen-deprivation therapy, brachytherapy boost (LDR or HDR) should be offered to eligible patients. Iodine-125 and palladium-103 are each reasonable isotope options for patients receiving LDR brachytherapy; no recommendation can be made for or against using cesium-131 or HDR monotherapy. Patients should be encouraged to participate in clinical trials to test novel or targeted approaches to this disease. Additional information is available at www.asco.org/Brachytherapy-guideline and www.asco.org/guidelineswiki .