Carbon Nanotube Chemical Sensors.
Carbon nanotubes (CNTs) promise to advance a number of real-world technologies. Of these applications, they are particularly attractive for uses in chemical sensors for environmental and health monitoring. However, chemical sensors based on CNTs are often lacking in selectivity, and the elucidation of their sensing mechanisms remains challenging. This review is a comprehensive description of the parameters that give rise to the sensing capabilities of CNT-based sensors and the application of CNT-based devices in chemical sensing. This review begins with the discussion of the sensing mechanisms in CNT-based devices, the chemical methods of CNT functionalization, architectures of sensors, performance parameters, and theoretical models used to describe CNT sensors. It then discusses the expansive applications of CNT-based sensors to multiple areas including environmental monitoring, food and agriculture applications, biological sensors, and national security. The discussion of each analyte focuses on the strategies used to impart selectivity and the molecular interactions between the selector and the analyte. Finally, the review concludes with a brief outlook over future developments in the field of chemical sensors and their prospects for commercialization.


Insulin-like effect of zinc on adipocytes.
In view of the known effect of zinc on the crystalline nature of insulin, we have investigated whether zinc alters the biologic potency of this hormone. Using the rate of lipogenesis by rat epididymal adipocytes as an index of the biologic potency of insulin, we have shown that zinc exerts a potent stimulatory effect upon lipogenesis in vitro similar to, but quite independently of, insulin and that it has an additive effect with that of insulin when both are incubated together. This effect of zinc on adipocytes and the biologic potency of insulin, hitherto unreported, is of significance at the biologic, pharmacologic, and clinical level.


Globus pallidus interna deep brain stimulation improves chorea and functional status in a patient with chorea-acanthocytosis.
We report a 39-year-old woman with chorea-acanthocytosis (ChAc) who was referred with refractory hyperkinetic movement and truncal bending spasm. She was diagnosed with ChAc with clinical features and laboratory findings of acanthocytosis in peripheral blood smear, and genetic studies revealed novel mutations in the VPS13 gene. Because her symptoms did not respond well to medical treatment, she was in a totally dependent state. We decided to perform globus pallidus interna deep brain stimulation (GPi-DBS) for symptom control. After the operation her hyperkinetic movement, bradykinesia, and truncal bending motion were improved, the preoperative total score of the motor section on the Unified Huntington's Disease Rating Scale (UHDRS) was 44, the independence scale was 50, and functional capacity was 1. However, a year after GPi-DBS, the postoperative score on the motor section was 12, the independence scale was 80, functional capacity was 9, and she had become capable of independent daily life. Although there is currently no curative treatment for ChAc, GPi-DBS represents a promising option for symptomatic control.


The ArcB sensor kinase of Escherichia coli autophosphorylates by an intramolecular reaction.
The Arc two-component system, comprising the ArcB sensor kinase and the ArcA response regulator, modulates the expression of numerous genes in response to the respiratory conditions of growth. ArcB is a tripartite histidine kinase whose activity is regulated by the oxidation of two cytosol-located redox-active cysteine residues that participate in intermolecular disulfide bond formation. Here we show that ArcB autophosphorylates through an intramolecular reaction which diverges from the usually envisaged intermolecular autophosphorylation of homodimeric histidine kinases.


Emergency CT of blunt abdominal trauma: experience from a large urban hospital in Southern China.
Trauma is one of the leading causes of death for men and women under the age of 45 years old, and abdominal injuries contribute to a large number of these deaths. Prompt diagnosis is very important for treatment decision making and can be life-saving. CT has become an essential imaging modality in emergency medicine. In this pictorial review, we present our experience of CT in blunt abdominal trauma and describe CT findings of common injuries, including hemoperitoneum, solid viscera, hollow viscera, mesenteric and diaphragmatic injuries. Unenhanced CT is routinely used, tailored protocols should be reserved for patients with questionable or subtle findings at unenhanced CT, especially for bowel and mesenteric injuries. The decision can be made by radiologists based on initial findings or by referring clinicians based by clinical presentations or deterioration of patients' condition.


[Study of 30 years on the change in the frequency of esophageal squamous cell carcinoma, esophageal adenocarcinoma and adenocarcinoma of the esophagogastric union].
Esophageal cancer mortality is high and the incidence of this neoplasm is increasing. Our aim was to compare the frequency of esophageal adenocarcinoma cases (EA) and squamous cell carcinoma (SCC) cases in two study periods (1977-1988 vs. 1989-2006). Patients with esophageal cancer or adenocarcinoma of gastroesophageal junction (AGEJ) referred to the Nation al Institute of Medical Sciences and Nutrition "Salvador Zubirán" during 1989-2006 were included. The frequency of EA, SCC was compared with the previously reported series of our institute during 1977-1988. Risk factors for esophageal cancer and AGEJ were investigated. From 1989 to 2006 82 patients were studied, 23 with SCC, 29 with EA and 29 with AGEJ. There was a significant association between gastroesophageal reflux disease (GERD) and EA (OR = 9.5; CI 95% 1.9-48.5, P = 0.0025), and also between GERD and AGEJ (OR 5.6; CI 95% 1.07-28.8, P = 0.03). The association between Barrett's esophagus and EA (OR 14; CI 95% 1.65-119.2, P = 0.0035) and for GEJC (RM 13.6; IC 95% 1.6-116, P = 0.004) was significant. There was an increase in the frequency of AE from 11% (6/57) in the first period to 56% (29/52) in the second period (P < 0.001). The rela tion SCC/EA change from 7:1 in the first period to 0.8:1 in the second. There has been an increase in EA, being now the predominant hystologic type of esophageal cancer.


Two renal alpha 2-adrenergic receptor sites revealed by p-aminoclonidine binding.
[3H]p-aminoclonidine [3H]PAC, a specific alpha 2-adrenergic agonist, was used to characterize alpha 2-adrenoceptor binding in rat renal membranes. Rosenthal plots demonstrated two binding sites with Kds of approximately 1.7 and 14.2 nM and Bmaxs (maximum binding) of 47.3 and 218.8 fmol/mg protein for the high- and low-affinity sites, respectively. These characteristics were confirmed by estimate of Kd parameters based on association and dissociation experiments. Pseudo-Hill coefficients generated from drug inhibition experiments were all less than unity, suggesting differential binding at two alpha 2-adrenoceptor binding sites. Specific alpha 2-adrenergic agonists exhibited greater binding affinity to both sites than did nonspecific drugs, and all drugs displayed greater affinity for the high- than the low-affinity binding site. Both guanyl nucleotides and sodium chloride inhibited [3H]PAC binding more at the high-affinity than at the low-affinity site. Renal denervation resulted in significant upregulation of receptor density only at the high-affinity sites with no change in receptor affinity at either site, suggesting that a majority of the alpha 2-adrenoceptors in the kidney are postsynaptic. Thus all lines of evidence in this study indicate that two alpha 2-adrenoceptor binding sites exist in the rat kidney.


Cell cycle re-entry mechanisms after DNA damage checkpoints: giving it some gas to shut off the breaks!
In order to maintain genetic integrity, cells are equipped with cell cycle checkpoints that detect DNA damage, orchestrate repair, and if necessary, eliminate severely damaged cells by inducing apoptotic cell death. The mitotic machinery is now emerging as an important determinant of the cellular responses to DNA damage where it functions as both the downstream target and the upstream regulator of the G2/M checkpoint. Cell cycle kinases and the DNA damage checkpoint kinases appear to reciprocally control each other. Specifically, cell cycle kinases control the inactivation of DNA damage checkpoint signaling. Termination of a DNA damage response by mitotic kinases appears to be an evolutionary conserved mechanism that allows resumption of cell cycle progression. Here we review recent reports in which molecular mechanisms underlying checkpoint silencing at the G2/M transition are elucidated.


Optimal allocation of reproductive effort: manipulation of offspring number and size in the bank vole.
The number of offspring attaining reproductive age is an important measure of an individual's fitness. However, reproductive success is generally constrained by a trade-off between offspring number and quality. We conducted a factorial experiment in order to study the effects of an artificial enlargement of offspring number and size on the reproductive success of female bank voles (Clethrionomys glareolus). We also studied the effects of the manipulations on growth, survival and reproductive success of the offspring. Potentially confounding effects of varying maternal quality were avoided by cross-fostering. Our results showed that the number of offspring alive in the next breeding season was higher in offspring number manipulation groups, despite their smaller body size at weaning. Offspring size manipulation had no effect on offspring growth or survival. Further, the first litter size of female offspring did not differ between treatments. In conclusion, females may be able to increase the number of offspring reaching reproductive age by producing larger litters, whereas increasing offspring size benefits neither the mother nor the offspring.


Different effects of long-term exposures to SO2 and NO2 air pollutants on asthma severity in young adults.
Numerous studies demonstrated that exposure to ambient air pollutants contributes to severity and frequency of asthma exacerbations. However, whether common air pollutants, such as nitrogen dioxide (NO2) and sulfur dioxide (SO2), exert differential effects on asthma occurrence and severity is unclear. The aim of this investigation was to determine whether exposure to NO2 and/or SO2 may initiate different long-term effects on prevalence and severity of asthma in young adults. Medical records of 137,040 males, 17 years old, who underwent standard premilitary service health examinations during 1999-2008 were examined. Air-pollution data for NO2 and SO2 were linked to the place of residence of each subject. The influence of specific air pollutants on asthma prevalence and severity was evaluated using bivariate logistic regression, controlling for individuals' sociodemographic attributes. For both ambient air pollutants, there was a significant dose-response effect on severity of asthma at ambient concentrations below the current National Ambient Air Quality Standards. However, in residential areas with high levels of SO2 (13.3-592.7µg/m(3)) and high levels of NO2 (27.2-43.2µg/m(3)) the risk of asthma occurrence was significantly higher than that in residential areas with high levels of NO2 (27.2-43.2 µg/m(3)) and intermediate levels (6.7-13.3 µg/m(3)) of SO2 pollution. The effects of exposure to SO2 and NO2 air pollutants on the respiratory airways system appear to differ, with possible implications regarding medical management, even in cases of exposure to mixtures of these pollutants.


Current Use of Pelvic Organ Prolapse Quantification by AUGS and ICS Members.
: To determine the current use of the pelvic organ prolapse quantification (POP-Q) by members of the American Urogynecologic Society (AUGS) and the International Continence Society (ICS). : Surgically active members of AUGS and ICS completed a Web-based questionnaire about their use of the POP-Q and included queries regarding respondent's clinical training, surgical experience, and practice setting. Users of POP-Q described their POP-Q use including patient's position, tools used to measure or assist with exposure, use of strain, and bladder volume. Strengths and weaknesses of the POP-Q system were also assessed. : The 308 respondents had a median of 8 years (range, 0-35 years) of independent performance of POP surgery. Most were from the United States (70%), in a shared practice (64%), with at least 2 years of fellowship training (61%), and had trainees participating in patient care (81%). Of the respondents, 76% reported using the POP-Q; however, the technique of POP-Q varied. Of the 24% not using the POP-Q, two-thirds reported past POP-Q use. For these individuals, prolapse description was done using Baden-Walker (57%), descriptive words (38%), or other grades (7%). More than 50% of nonusers reported that the POP-Q is "too time-consuming" or that their "colleagues do not use it." : Although most surveyed members of AUGS and ICS are using the POP-Q, we detected variability in the day-to-day practice of POP-Q use. To further advance the communication benefits of the POP-Q, a revision that provides evidence-based guidance may be a worthwhile refinement.


A clinical comparison of pain perception to the Wand and a traditional syringe.
This study compared the pain response of a group of 40 volunteers to the Wand with the response to syringe injections. Of 240 total injections given, 120 were with the Wand system, and 120 were with the traditional aspirating syringe. Three injections were evaluated: injections to the middle superior alveolar (MSA) of the maxillary right first premolar and the maxillary left first premolar; palatal injections of the maxillary right first premolar and the maxillary left first premolar; and inferior alveolar nerve injection (IAN) of both the right and the left sides. Each volunteer received 6 injections, 3 on one side with the Wand and 3 on the opposite side with the syringe (control). All injections were given by the primary investigator without the use of a topical anesthetic. Pain perception levels were recorded with a 4-point visual analog scale: no pain, mild pain, moderate pain, and severe pain. The results were evaluated statistically by using an unpaired t test. The results showed injections with the syringe were statistically more painful than injections with the Wand in 4 of 18 evaluations: MSA of the maxillary left first premolar, female volunteers responses to MSA of the maxillary left first premolar, IAN left side injections, and male responses to IAN left injections (P =.01, P =.05, P =.05 and P =.05, respectively). The Wand generally seemed to provide less painful injections; however, the mean ratings of pain were mostly mild pain for both injections. Therefore, the clinical significance of the results should be interpreted with caution. The operator technique and tactile skill in syringe injections and site of injection (right or left) could be important factors that were not evaluated in this study.


Radon exposure: a major cause of lung cancer in nonsmokers.
Exposure to radon can impact human health. This is a nonsystematic review of articles written in English, Spanish, French, or Portuguese published in the last decade (2013-2023), using databases such as PubMed, Google Scholar, EMBASE, and SciELO. Search terms selected were radon, human health, respiratory diseases, children, and adults. After analyzing the titles and abstracts, the researchers initially identified 47 studies, which were subsequently reduced to 40 after excluding reviews, dissertations, theses, and case-control studies. The studies have shown that enclosed environments such as residences and workplaces have higher levels of radon than those outdoors. Moreover, radon is one of the leading causes of lung cancer, especially in nonsmokers. An association between exposure to radon and development of other lung diseases, such as asthma and COPD, was also observed. It is crucial to increase public awareness and implement governmental control measures to reduce radon exposure. It is essential to quantify radon levels in all types of buildings and train professionals to conduct such measurements according to proven efficacy standards. Health care professionals should also be informed about this threat and receive adequate training to deal with the effects of radon on human health.


[Diabetes and pancreas transplantation].
Kidney disease is a severe and frequent complication in diabetes. In the terminal phase, treatment requires dialysis and, if possible, kidney transplantation. Provided that there are no contraindications, simultaneous kidney/pancreas transplantation is currently considered the treatment of choice in patients with type 1 diabetes mellitus and terminal kidney disease. Pancreas transplantation is a complex process initially associated with a greater morbidity than kidney transplant alone. At present, however, patient and graft survival is good thereby leading to total normalization of metabolic control and allowing the patient to carry out a normal life without the need to administer insulin and with the consequent benefits in quality of life and the evolution of the complications of the disease. The results of pancreas transplant alone are somewhat worse than those with combined kidney/pancreas transplantation. They are, however, sufficiently satisfactory to be considered a good therapeutic option in patients who have previously received a kidney. Nonetheless, the transplantation of the pancreas alone in diabetic patients without renal insufficiency or previous kidney transplant is another question. Although this type of transplantation would be ideal, it currently remains restricted to patients with a labile diabetes who require repeated hospital admission due to metabolic decompensation and/or severe hypoglycemic episodes accompanied by loss of consciousness.


Centriole foci persist in starfish oocytes despite Polo-like kinase 1 inactivation or loss of microtubule nucleation activity.
Centrioles must be eliminated or inactivated from the oocyte to ensure that only the two functional centrioles contributed by the sperm are present in the zygote. Such removal can occur during oogenesis, as in Drosophila, where departure of Polo kinase from centrosomes leads to loss of microtubule nucleating activity and centriole removal. In other species, oocyte-derived centrioles are removed around the time of fertilization through incompletely understood mechanisms. Here, we use confocal imaging of live starfish oocytes and zygotes expressing markers of microtubule nucleating activity and centrioles to investigate this question. We first assay the role of Polo-like kinase 1 (Plk1) in centriole elimination. We find that although Plk1 localizes around oocyte-derived centrioles, kinase impairment with BI-2536 does not protect centrioles from removal in the bat star Patiria miniata. Moreover, we uncover that all four oocyte-derived centrioles lose microtubule nucleating activity when retained experimentally in the zygote of the radiate star Asterias forbesi. Interestingly, two such centrioles nevertheless retain the centriolar markers mEGFP::PACT and pmPoc1::mEGFP. Together, these findings indicate that centrioles can persist when Plk1 activity is impaired, as well as when microtubule nucleating activity is lacking, uncovering further diversity in the mechanisms governing centriole removal.


Conservation of the sizes of 53 introns and over 100 intronic sequences for the binding of common transcription factors in the human and mouse genes for type II procollagen (COL2A1).
Over 11,000 bp of previously undefined sequences of the human COL2A1 gene were defined. The results made it possible to compare the intron structures of a highly complex gene from man and mouse. Surprisingly, the sizes of the 53 introns of the two genes were highly conserved with a mean difference of 13%. After alignment of the sequences, 69% of the intron sequences were identical. The introns contained consensus sequences for the binding of over 100 different transcription factors that were conserved in the introns of the two genes. The first intron of the gene contained 80 conserved consensus sequences and the remaining 52 introns of the gene contained 106 conserved sequences for the binding of transcription factors. The 5'-end of intron 2 in both genes had a potential for forming a stem loop in RNA transcripts.


Pretest Video Education Versus Genetic Counseling for Patients With Prostate Cancer: ProGen, A Multisite Randomized Controlled Trial.
Germline genetic testing (GT) is recommended for men with prostate cancer (PC), but testing through traditional models is limited. The ProGen study examined a novel model aimed at providing access to GT while promoting education and informed consent. Men with potentially lethal PC (metastatic, localized with a Gleason score of ≥8, persistent prostate-specific antigen after local therapy), diagnosis age ≤55 years, previous malignancy, and family history suggestive of a pathogenic variant (PV) and/or at oncologist's discretion were randomly assigned 3:1 to video education (VE) or in-person genetic counseling (GC). Participants had 67 genes analyzed (Ambry), with results disclosed via telephone by a genetic counselor. Outcomes included GT consent, GT completion, PV prevalence, and survey measures of satisfaction, psychological impact, genetics knowledge, and family communication. Two-sided Fisher's exact tests were used for between-arm comparisons. Over a 2-year period, 662 participants at three sites were randomly assigned and pretest VE (n = 498) or GC (n = 164) was completed by 604 participants (VE, 93.1%; GC, 88.8%), of whom 596 participants (VE, 98.9%; GC, 97.9%) consented to GT and 591 participants completed GT (VE, 99.3%; GC, 98.6%). These differences were not statistically significant although subtle differences in satisfaction and psychological impact were. Notably, 84 PVs were identified in 78 participants (13.2%), with BRCA1/2 PV comprising 32% of participants with a positive result (BRCA2 n = 21, BRCA1 n = 4). Both VE and traditional GC yielded high GT uptake without significant differences in outcome measures of completion, GT uptake, genetics knowledge, and family communication. The increased demand for GT with limited genetics resources supports consideration of pretest VE for patients with PC.


Stagnation and transonic effects in thermal blooming.
The effects of slewed high-energy beams on an absorbing medium are considered near regions where the relative air velocity is (a) zero and (b) transonic. Limiting effects on the density changes are buoyancy and sound speed changes, respectively. In both cases, the immediate environs of the singular point are greater contributors to phase changes in the beam than are the singularities themselves. Detailed hydrodynamic calculations are carried out for the stagnation region and the steady near-sonic region and compared (in the case of the stagnation region) with a perturbation calculation. Moment methods are used to estimate stagnation-region effects on the subsequent development of the beam.


Cognitive-behavioral therapy as an adjunct to serotonin reuptake inhibitors in obsessive-compulsive disorder: an open trial.
We report the results of an open trial of cognitive-behavioral therapy (CBT) using exposure and ritual prevention as an adjunct to serotonin reuptake inhibitors (SRIs) in obsessive-compulsive disorder (OCD). We hypothesized that exposure and ritual prevention would significantly reduce OCD symptoms in patients who remained symptomatic despite an adequate trial of an SRI and enable patients to discontinue their medication. OCD patients taking an adequate dose of an SRI > or = 12 weeks who remained symptomatic (i.e., a Yale-Brown Obsessive Compulsive Scale [Y-BOCS] score > or = 16) were eligible. While taking a stable dose of an SRI, patients received 17 sessions of exposure and ritual prevention. For the intent-to-treat group, the paired t test was used to compare scores on the Y-BOCS, the National Institute of Mental Health (NIMH) Global OCD scale, the Clinical Global Impressions scale, and the Hamilton Rating Scale for Depression before and after exposure and ritual prevention. Six of 7 eligible patients entered the study, and 5 completed it. All 6 improved on all OCD measures. The mean +/- SD Y-BOCS score was 23.8 +/- 2.6 prior to exposure and ritual prevention and 12.2 +/- 4.3 after it (p < .001). The mean percentage decrease on the Y-BOCS was 49% (range, 26%-61%). Patients were rated by the therapist and rated themselves as much (N = 4) or very much (N = 2) improved. Blood drug levels did not change in most patients during exposure and ritual prevention; thus, the improvement was attributed to this type of therapy. No patients discontinued their medication. This open trial suggests that CBT using exposure and ritual prevention can lead to a significant reduction in OCD symptoms in patients who remain symptomatic despite an adequate trial of an SRI.


An investigation into the number and nature of the urgent care consultations managed and referred by community pharmacists in South-East England.
Community pharmacies are recognised as an under-utilised, accessible resource that could support the urgent care agenda. This study aimed to provide a snapshot of the number and nature of urgent care requests presented to a sample of community pharmacies in three counties in southern England, to determine how requests are managed, whether management is appropriate, as assessed by a group of experts, and whether customers receiving the care are satisfied with pharmacists' interventions. A representative sample of pharmacists across the region was invited to keep a log-book documenting all urgent care requests over a two-week period. Data were analysed to estimate frequency and type of requests and to compare consultations in core and non-core hours. Log-book entries were scrutinised blind by an expert panel to determine appropriateness of pharmacist's responses. Customers receiving pharmacists' interventions were surveyed to assess satisfaction. Seventeen pharmacies kept log-books detailing 432 urgent care consultations, equating to 13 consultations per pharmacy per week. Of these, 70% (n = 302) were dealt with by the pharmacist in-house with 30% (n = 130) resulting in referrals. Locum pharmacists were significantly more likely to refer to other NHS services than regular pharmacists. Over half the requests were for symptom management, skin problems presenting most commonly (38% of all symptoms presented). Forty-seven percent of consultations were considered to have 'averted the need for other NHS services'. Pharmacists' referral (but not assessment of urgency) was deemed appropriate by the expert panel in 90% of consultations. Ninety-five percent of customers surveyed were satisfied with the service and would use the pharmacy again. Extrapolating findings across the study population (approximately 4.4 million) suggests that community pharmacists manage over 11 500 urgent care consultations per week, with 8050 managed independently. These prevent approximately 5400 other NHS encounters, while also meeting customer expectations and expert panel endorsement.


Adipose tissue fibrosis: the unwanted houseguest invited by obesity.
The prevalence of obesity is increasing exponentially across the globe. The lack of effective treatment options for long-term weight loss has magnified the enormity of this problem. Studies continue to demonstrate that adipose tissue holds a biological memory, one of the most important determinant of long-term weight maintenance. This phenomenon is consistent with the metabolically dynamic role of adipose tissue: it adapts and expands to store for excess energy and serves as an endocrine organ capable of synthesizing a number of biologically active molecules that regulate metabolic homeostasis. An important component of the plasticity of adipose tissue is the extracellular matrix, essential for structural support, mechanical stability, cell signaling and function. Chronic obesity upends a delicate balance of extracellular matrix synthesis and degradation, and the ECM accumulates in such a way that prevents the plasticity and function of the diverse cell types in adipose tissue. A series of maladaptive responses among the cells in adipose tissue leads to inflammation and fibrosis, major mechanisms that explain the link between obesity and insulin resistance, risk of type 2 diabetes, cardiovascular disease, and nonalcoholic fatty liver disease. Adipose tissue fibrosis persists after weight loss and further enhances adipose tissue dysfunction if weight is regained. Here, we highlight the current knowledge of the cellular events governing adipose tissue ECM remodeling during the development of obesity. Our goal is to delineate the relationship more clearly between adipose tissue ECM and metabolic disease, an important step toward better defining the pathophysiology of dysfunctional adipose tissue.


Guided subwavelength slow-light mode supported by a plasmonic waveguide system.
We introduce a plasmonic waveguide system, which supports a subwavelength broadband slow-light guided mode with a tunable slowdown factor at a given wavelength. The system consists of a metal-dielectric-metal (MDM) waveguide side-coupled to a periodic array of MDM stub resonators. The slowdown factor at a given wavelength can be tuned by adjusting the geometrical parameters of the system. In addition, there is a trade-off between the slowdown factor and the propagation length of the supported optical mode. Finally, we show that light can be coupled efficiently from a conventional MDM waveguide to the plasmonic waveguide system.


Pericentromeric recombination suppression and the 'large X effect' in plants.
X chromosome was reported to be a major contributor to isolation between closely related species-the 'large X' effect (LXE). The causes of LXE are not clear, but the leading theory is that it is caused by recessive species incompatibilities exposed in the phenotype due to the hemizygosity of X-linked genes in the heterogametic sex. However, the LXE was also reported in species with relatively recently evolved sex chromosomes where Y chromosome is not completely degenerate and X-linked genes are not hemizygous, such as the plant Silene latifolia. Recent genome sequencing and detailed genetic mapping in this species revealed a massive (> 330 Mb) non- or rarely-recombining pericentromeric region on the X chromosome (Xpr) that comprises ~ 90% of the chromosome and over 13% of the entire genome. If any of the Xpr genes are involved in species incompatibilities, this would oppose interspecific gene flow for other genes tightly linked in the Xpr. Here we test the hypothesis that the previously reported LXE in S. latifolia is caused by the lack of recombination on most of the X chromosome. Based on genome-wide analysis of DNA polymorphism and gene expression in S. latifolia and its close cross-compatible relative S. dioica, we report that the rarely-recombining regions represent a significant barrier for interspecific gene flow. We found little evidence for any additional factors contributing to the LXE, suggesting that extensive pericentromeric recombination suppression on the X-chromosome is the major if not the only cause of the LXE in S. latifolia and S. dioica.


Point of care strategy for rapid diagnosis of novel A/H1N1 influenza virus.
Within months of the emergence of the novel A/H1N1 pandemic influenza virus (nA/H1N1v), systematic screening for the surveillance of the pandemic was abandoned in France and in some other countries. At the end of June 2009, we implemented, for the public hospitals of Marseille, a Point Of Care (POC) strategy for rapid diagnosis of the novel A/H1N1 influenza virus, in order to maintain local surveillance and to evaluate locally the kinetics of the pandemic. Two POC laboratories, located in strategic places, were organized to receive and test samples 24 h/24. POC strategy consisted of receiving and processing naso-pharyngeal specimens in preparation for the rapid influenza diagnostic test (RIDT) and real-time RT-PCR assay (rtRT-PCR). This strategy had the theoretical capacity of processing up to 36 samples per 24 h. When the flow of samples was too high, the rtRT-PCR test was abandoned in the POC laboratories and transferred to the core virology laboratory. Confirmatory diagnosis was performed in the core virology laboratory twice a day using two distinct rtRT-PCR techniques that detect either influenza A virus or nA/N1N1v. Over a period of three months, 1974 samples were received in the POC laboratories, of which 111 were positive for nA/H1N1v. Specificity and sensitivity of RIDT were 100%, and 57.7% respectively. Positive results obtained using RIDT were transmitted to clinical practitioners in less than 2 hours. POC processed rtRT-PCR results were available within 7 hours, and rtRT-PCR confirmation within 24 hours. The POC strategy is of benefit, in all cases (with or without rtRT-PCR assay), because it provides continuous reception/processing of samples and reduction of the time to provide consolidated results to the clinical practitioners. We believe that implementation of the POC strategy for the largest number of suspect cases may improve the quality of patient care and our knowledge of the epidemiology of the pandemic.


[Seventeen cases of lung transplantations for lymphangioleiomyomatosis].
The number of lung transplantation has tended to increase as a treatment for patients with pulmonary lymphangioleiomyomatosis (LAM) in Japan. However, we have little evidence about the correlation between preoperative medical parameters and intraoperative complications. A retrospective study was performed in 17 patients with LAM undergoing the lung transplantations between 2006 and 2011. Major intraoperative complications were as follows: hypotension, pulmonary hypertension, hypoxemia and blood loss of more than 1,000 ml. According to the medical records, no patients was diagnosed pulmonary hypertension before surgery and no preoperative parameters predicted intraoperative pulmonary hypertension. Therefore, according to the medical records it seemed difficult to predict the risk of the intraoperative pulmonary hypertension and hypotension. Intraoperative hypoxemia and the requirements of percutaneous cardiopulmonary support (PCPS) are not associated with preoperative PaO2 and %FEV1.0. Pleurodesis and the use of PCPS were significantly correlated with an increased risk of intraoperative massive bleeding. The four year survival rate was 87.8%. %FEV1.0, PaO2/FI(O) and %DL(CO) after surgery improved when compared to those before surgery. Although the intraoperative complications such as hypotension, pulmonary hypertension, hypoxemia and/or massive bleeding frequently occurred in patients with LAM during the lung transplantations, it was difficult to predict them except the massive bleeding of more than 1,000 ml before surgery. However, lung transplantation is a valuable therapy for patients with end-stage LAM.


Multivariate Analysis of COVID-19 for Countries with Limited and Scarce Data: Examples from Nepal.
This paper aims to understand the dynamics of the spread of COVID-19 for Nepal. It is carried out with the help of multivariate statistics techniques. Direct relationships among variables are obvious, as they are easily seen and measured. But, hidden variables and their interrelationships also have a significant effect on the spread of a pandemic. Multinomial logistic regression, odds ratio, linear mixed-effect models, and principal component analysis are used here to analyze these hidden variables and their interrelationships. Also, such studies are very important for countries with limited and scarce data. These countries do not have a backbone of good-quality official records. Understanding the spread of a disease in a developing country also helps in management and eradication of that disease. The multivariate daily data of new cases, deaths, recovered, total cases, total deaths, total recovered, and total infected (isolated) are used here. The daily incidence of new cases is also modeled here using nonlinear regression. Two best nonlinear models are discussed here. ARIMA models are used for analyzing and forecasting the progression of the variables for two months into the future. The impact of government restriction in the form of strict lockdown 1, partially relaxed lockdown 1, completely relaxed lockdown 1, and strict lockdown 2 is minutely analyzed. These controls were exercised to curtail the spread of the pandemic. The role of these controls in curbing the spread of the pandemic is also studied here. The results obtained from this study can be applied to other countries of South Asia and Africa.


Health technology assessment and health care in the European Union.
The papers on the 16 European countries presented in this issue show their great diversity of health systems. Health technology assessment (HTA) has been institutionalized in a number of members of the European Union and has a growing impact on health policy. A remaining challenge is to see HTA visible and useful at the European level, which requires more active coordination of national and regional activities. A network of HTA programs and researchers has been established. The HTA-Europe Steering Committee has suggested a number of actions by the European Commission to promote further coordination. The most important conclusion of the HTA-Europe report is that a permanent coordinating structure is needed at the European level.


Lesson of the month 1: Beware the atypical presentation: eosinophilic granulomatosis with polyangiitis presenting as acute coronary syndrome.
We describe the case of a 45-year-old woman presenting with troponin positive cardiac-sounding chest pain. An initial emergency angiogram demonstrated two vessel coronary disease, including a distal right coronary artery occlusion. No percutaneous coronary intervention was performed and the patient was treated medically. At re-presentation with further pain a few days later, coronary angiography demonstrated no significant coronary lesions. After consideration of other multisystem symptoms and raised eosinophil count, the patient was diagnosed with eosinophilic granulomatosis with polyangiitis (formerly known as Churg-Strauss syndrome) presenting with coronary arteritis. This case should remind physicians to be vigilant and to consider non-atherosclerotic causes of acute coronary syndrome presentation, which should not always result in a stent.


Imaging through scattering media using speckle pattern classification based support vector regression.
Imaging through scattering media is a common practice in many applications of biomedical imaging. Object image would deteriorate into unrecognizable speckle pattern when scattering media is presented. Many methods have been investigated to reconstruct the object image when only speckle pattern is available. In this paper, we demonstrate a method of single-shot imaging through scattering media. This method is based on classification and support vector regression of the measured speckle pattern. We prove the possibility of speckle pattern classification and related formulas are presented. The specified and limited imaging capability without speckle pattern classification is demonstrated. Our proposed approach, that is, speckle pattern classification based support vector regression method, makes up the deficiency. Experimental results show that, with our approach, speckle patterns could be utilized for classification when object images are unavailable, and object images can be reconstructed with high fidelity. The proposed approach for imaging through scattering media is expected to be applicable to various sensing schemes.


[Prevention of ostial obstruction after microendoscopic endonasal dacryocystorhinostomy].
Ostial dilatator was created to prevent recurrence and improve efficacy of microendoscopic endonasal dacryocystorhinostomy. Proposed technique was for the first time used in 52 patients. Postoperative results were analyzed: recovery was achieved in 78% of cases, improvement - in 22%. In a control group (51 patients) we used conventional technique, recovery was achieved in 67% of patients and improvement in 28%, in 5% recurrence occurred. The use of ostial dilatator resulted in microendoscopic endonasal dacryocystorhinostomy efficacy improvement.


The Function of the Short Lateral Collateral Ligaments of the Canine Tarsus: A Cadaveric Study.
Information on the clinical behavior and treatment of cases with an isolated rupture of the short collateral ligaments of the canine tarsus is sparse and contradictory in the veterinary literature. Our objective was to evaluate the function of the short lateral collateral ligaments (SLCLs) of the tarsocrural joint in 90° flexion. Eight canine cadaveric limbs were tested for internal/external rotation and valgus/varus before and after transection of one or both SLCLs. In one group, the fibulocalcaneal ligament was transected first, followed by the fibulotalar. In the second group, the order of ligament transection was reversed. Angular changes between two k-wires were measured and compared. External rotation increased significantly after transection of one or both SLCLs (P = .009 and P < .0005), as did varus (P = .021 and P = .001). Lateral subluxation was only possible when both SLCLs were cut. Unlike the long lateral collateral ligament, which stabilizes against deviation toward medial, both SLCLs are major stabilizers against subluxation toward lateral. This important difference must be considered in clinical patients with isolated rupture of the SLCLs.


Dual burden households and intra-household nutritional inequality in Indonesia.
Overweight is an increasing problem in many developing countries, coexisting with underweight and contributing to a dual burden of malnutrition, sometimes in the same households. We analyze the phenomenon of dual burden households in Indonesia, using 15-year panel data. Currently, 16 percent of Indonesian households are classified as dual burden. In these households, children are often underweight, whereas adults are overweight. The nutrition transition seems to have differential impacts on the body mass index of different age cohorts. Dual burden households are a transitory phenomenon. This phenomenon started in the richer segments, but now the prevalence of dual burden households is highest in the poorest population groups. Most households that move out of the dual burden category end up as overweight. We also develop a continuous Theil index of intra-household nutritional inequality. While the overall prevalence of dual burden households has hardly changed over the last 10 years, the Theil index increased steadily. This underlines that the dual burden classification has limitations in terms of capturing nutritional dynamics. Socioeconomic determinants of dual burden and nutritional inequality are analyzed with regression models.


The topography of lactose synthesis.
1. At short incubation times, and under suitable osmotic conditions, the lactose synthesized by Golgi-derived vesicles of rat mammary gland is 85-90% particulate. Evidence is presented for its occlusion within the lumen of the vesicles. 2. Ovalbumin is used as a bulky active-site inhibitor to show that the active site of lactose synthase lies on the inner face of the Golgi membrane. 3. Phlorrhizin and phloretin inhibit lactose synthesis by such vesicles, indicating the presence of a glucose-transport system. 4. The relationship of this topography to the synthesis of N-acetylneuraminyl-lactose and to the secretion of milk sugars is discussed.


Displaced amacrine and ganglion cells in the newt retina.
The inner nuclear layer and ganglion cell layer of the newt retina contain taurine- and GABA-accumulating cells which are located immediately adjacent to the inner plexiform layer. Transport studies with horseradish peroxidase (HRP) indicate the presence of displaced ganglion cells within the inner nuclear layer of the retina. These are more numerous at the periphery of the retina and constitute about 2.5% of the retinal ganglion cells. Autoradiography, combined with HRP-transport studies, indicate that the taurine-accumulating cells in the ganglion cell layer of the newt retina are not 'true' ganglion cells, but may be displaced amacrine cells. Counts of axons in the optic nerve compared with cell bodies in the ganglion cell layer, demonstrate that only 50-60% of the cells in the ganglion cell layer of the newt retina are truly ganglion cells.


Physically-enhanced ghost encoding.
In this Letter, we propose a physically enhanced ghost encoding scheme that is realized by exploring optical channel characteristics, i.e., physically and dynamically generated scaling factors. It is found that scaling factors can be physically and dynamically generated to serve as security keys in a ghost encoding scheme, dramatically enlarging the key space and enhancing the security of optical ghost encoding schemes. To the best of our knowledge, this is the first time that dynamic scaling factors have been controlled in the optical path to realize physically enhanced ghost encoding. In addition to the illumination patterns used in optical ghost encoding schemes, the proposed method applies a variable beam attenuator and an amplitude-only spatial light modulator (SLM) to physically generate dynamic scaling factors as keys. Nonlinear variation of scaling factors is achieved in different free-space wave-propagation environments in the proposed method. A series of optical experiments are conducted to verify the feasibility and effectiveness of the proposed physically enhanced ghost encoding scheme. The proposed method could open up new research perspectives in optical ghost encoding.


The Gly571Arg mutation, associated with the autonomic and sensory disorder congenital insensitivity to pain with anhidrosis, causes the inactivation of the NTRK1/nerve growth factor receptor.
Point mutations affecting the NTRK1/TRKA gene, encoding one of the receptors for the nerve growth factor (NGF), have been detected in congenital insensitivity to pain with anhidrosis (CIPA), a human hereditary sensory neuropathy characterized by absence of reaction to noxious stimuli and anhidrosis. To define the defect of NTRK1 in CIPA patients, we have introduced one of the previously reported mutations (Gly571Arg) into both the NTRK1 and the TRK-T3 oncogene cDNAs. The expression of the mutated constructs into COS1 cells revealed that the introduced mutation, while not affecting its correct membrane localization, rendered the NTRK1 protein unable to undergo activation upon stimulation with NGF. Similarly, the mutation abolished the constitutive activation of the TRK-T3 oncogene. Transfection into NIH3T3 and PC12 cells showed the loss of transforming and differentiating activity by the mutated constructs. Our results demonstrate clearly that the CIPA mutations cause the inactivation of the NTRK1 receptor, thus exerting a loss of function effect, and provide an experimental approach to distinguish functional mutations from genetic polymorphisms.


Neuromyelitis Optica Spectrum Disorder and Other Non-Multiple Sclerosis Central Nervous System Inflammatory Diseases.
This article reviews the clinical features, diagnostic approach, treatment, and prognosis of central nervous system inflammatory diseases that mimic multiple sclerosis (MS), including those defined by recently discovered autoantibody biomarkers. The discovery of autoantibody biomarkers of inflammatory demyelinating diseases of the central nervous system (aquaporin-4 IgG and myelin oligodendrocyte glycoprotein IgG) and the recognition that, despite some overlap, their clinical phenotypes are distinct from MS have revolutionized this field of neurology. These autoantibody biomarkers assist in diagnosis and have improved our understanding of the underlying disease pathogenesis. This has allowed targeted treatments to be translated into clinical trials, three of which are now under way in aquaporin-4 IgG-seropositive neuromyelitis optica (NMO) spectrum disorder. Knowledge of the clinical attributes, MRI findings, CSF parameters, and accompanying autoantibody biomarkers can help neurologists distinguish MS from its inflammatory mimics. These antibody biomarkers provide critical diagnostic and prognostic information and guide treatment decisions. Better recognition of the clinical, radiologic, and laboratory features of other inflammatory MS mimics that lack autoantibody biomarkers has allowed us to diagnose these disorders faster and initiate disease-specific treatments more expeditiously.


Targeting of the Hedgehog signal transduction pathway suppresses survival of malignant pleural mesothelioma cells in vitro.
The present study sought to determine whether the Hedgehog (Hh) pathway is active and regulates the cell growth of cultured malignant pleural mesothelioma (MPM) cells and to evaluate the efficacy of pathway blockade using smoothened (SMO) antagonists (SMO inhibitor GDC-0449 or the antifungal drug itraconazole [ITRA]) or Gli inhibitors (GANT61 or the antileukemia drug arsenic trioxide [ATO]) in suppressing MPM viability. Selective knockdown of SMO to inhibit Hh signaling was achieved by small interfering RNA in 3 representative MPM cells. The growth inhibitory effect of GDC-0449, ITRA, GANT61, and ATO was evaluated in 8 MPM lines, with cell viability quantified using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Cell death was determined by annexinV/propidium iodide staining and flow cytometry. SMO small interfering RNA mediated a two- to more than fivefold reduction of SMO and Gli1 gene expression as determined by real-time quantitative reverse-transcriptase polymerase chain reaction, indicating significant Hh pathway blockade. This was associated with significantly reduced cell viability (34% ± 7% to 61% ± 14% of nontarget small interfering RNA controls; P = .0024 to P = .043). Treating MPM cells with Hh inhibitors resulted in a 1.5- to 4-fold reduction of Gli1 expression. These 4 Hh antagonists strongly suppressed MPM cell viability. More importantly, ITRA, ATO, GANT61 induced significant apoptosis in the representative MPM cells. Hh signaling is active in MPM and regulates cell viability. ATO and ITRA were as effective as the prototypic SMO inhibitor GDC-0449 and the Gli inhibitor GANT61 in suppressing Hh signaling in MPM cells. Pharmaceutical agents Food and Drug Administration-approved for other indications but recently found to have anti-Hh activity, such as ATO or ITRA, could be repurposed to treat MPM.


Discrete cosine transform domain restoration of defocused images.
In discrete-cosine-transform-based (DCT-based) compressions such as JPEG it is a common practice to use the same quantization matrix for both encoding and decoding. However, this need not be the case, and the flexibility of designing different matrices for encoding and decoding allows us to perform image restoration in the DCT domain. This is especially useful when we have severe limitations on the computational power, for instance, with in-camera image manipulation for programmable digital cameras. We provide an algorithm that compensates partially for a defocus error in image acquisition, and experimental results show that the restored image is closer to the in-focus image than is the defocused image.


Expression of a recombinant full-length LRP1B receptor in human non-small cell lung cancer cells confirms the postulated growth-suppressing function of this large LDL receptor family member.
Low-density lipoprotein (LDL) receptor-related protein 1B (LRP1B), a member of the LDL receptor family, is frequently inactivated in multiple malignancies including lung cancer. LRP1B is therefore considered as a putative tumor suppressor. Due to its large size (4599 amino acids), until now only minireceptors or receptor fragments have been successfully cloned. To assess the effect of LRP1B on the proliferation of non-small cell lung cancer cells, we constructed and expressed a transfection vector containing the 13.800 bp full-length murine Lrp1b cDNA using a PCR-based cloning strategy. Expression of LRP1B was analyzed by quantitative RT-PCR (qRT-PCR) using primers specific for human LRP1B or mouse Lrp1b. Effective expression of the full length receptor was demonstrated by the appearance of a single 600 kDa band on Western Blots of HEK 293 cells. Overexpression of Lrp1b in non-small cell lung cancer cells with low or absent endogenous LRP1B expression significantly reduced cellular proliferation compared to empty vector-transfected control cells. Conversely, in Calu-1 cells, which express higher endogenous levels of the receptor, siRNA-mediated LRP1B knockdown significantly enhanced cellular proliferation. Taken together, these findings demonstrate that, consistent with the postulated tumor suppressor function, overexpression of full-length Lrp1b leads to impaired cellular proliferation, while LRP1B knockdown has the opposite effect. The recombinant Lrp1b construct represents a valuable tool to unravel the largely unknown physiological role of LRP1B and its potential functions in cancer pathogenesis.


Impact of Spironolactone on Longitudinal Changes in Health-Related Quality of Life in the Treatment of Preserved Cardiac Function Heart Failure With an Aldosterone Antagonist Trial.
Heart failure (HF) with preserved ejection fraction patients have equally impaired health-related quality of life (HRQL) compared with those with HF with reduced ejection fraction, but limited studies have evaluated the impact of therapies on changes in HRQL. Patients ≥50 years of age, with symptomatic HF and left ventricular ejection fraction ≥45%, were enrolled in Treatment of Preserved Cardiac Function Heart Failure With an Aldosterone Antagonist (TOPCAT) and randomized to spironolactone or placebo. Patients completed the Kansas City Cardiomyopathy Questionnaire (KCCQ), which was the primary HRQL instrument, and EQ5D visual analog scale at baseline, 4 months, 12 months, and annually thereafter. McMaster Overall Treatment Evaluation was assessed at 4 and 12 months to assess global change scores. Change scores (+SD) were calculated to determine between-group differences, and multivariable repeated-measures models were created to identify other factors associated with change scores. Paired KCCQ data were available for 91.7% of 3445 TOPCAT patients. By 4 months, the mean change in KCCQ was 7.7±16 and mean change in EQ5D visual analog scale was 4.7±16. Adjusted mean changes in KCCQ for the spironolactone group were significantly better than those for the placebo group at 4-month (1.54 better; P=0.002), 12-month (1.35 better; P=0.02), and 36-month (1.86 better; P=0.02) visits. No between-group differences in EQ5D visual analog scale change scores or McMaster Overall Treatment Evaluation were noted. Older age, obesity, current smoking, New York Heart Association class III/IV, and comorbid illnesses were associated with declines in KCCQ scores. Use of spironolactone was an independent predictor of improved KCCQ scores. In symptomatic HF with preserved ejection fraction patients, use of spironolactone was associated with an improvement in HF-specific HRQL. Several modifiable risk factors were associated with HRQL deterioration. URL: http://www.clinicaltrials.gov. Unique identifier: NCT00094302.


Fatigue is associated with excess mortality in the general population: results from the EPIC-Norfolk study.
Significant fatigue is a frequent reason for seeking medical advice in the general population. Patients, however, commonly feel their complaint is ignored. This situation may be because clinicians perceive fatigue to be benign, unrelated to traditional biomedical outcomes such as premature mortality. The present study aimed to investigate whether an association between significant fatigue and mortality actually exists, and, if so, to identify potential mechanisms of this association. A population-based cohort of 18,101 men and women aged 40-79 years who completed a measure of fatigue (Short Form 36 vitality domain, SF36-VT) in addition to providing information on possible confounding factors (age, sex, body mass index, marital status, smoking, education level, alcohol consumption, social class, depression, bodily pain, diabetes, use of β blockers, physical activity and diet) and mechanisms (haemoglobin, C-reactive protein and thyroid function) were followed up prospectively for up to 20 years. Mortality from all causes, cancer and cardiovascular disease was ascertained using death certification linkage with the UK Office of National Statistics. During 300,322 person years of follow-up (mean 16.6 years), 4397 deaths occurred. After adjusting for confounders, the hazard ratio (HR) for all-cause mortality was 1.40 (95 % confidence interval [CI] 1.25-1.56) for those reporting the highest fatigue (bottom SF36-VT quartile) compared with those reporting the lowest fatigue (top SF36-VT quartile). This significant association was specifically observed for those deaths related to cardiovascular disease (HR 1.45, 95 % CI 1.18-1.78) but not cancer (HR 1.09, 95 % CI 0.90-1.32). Of the considered mechanisms, thyroid function was most notable for attenuating this association. The risk of all-cause mortality, however, remained significant even after considering all putative confounders and mechanisms (HR 1.26, 95 % CI 1.10-1.45). High levels of fatigue are associated with excess mortality in the general population. This commonly dismissed symptom demands greater evaluation and should not automatically be considered benign.


Endosomal compartment of toad bladder epithelium.
Apical exocytosis and increased permeability are induced by antidiuretic hormone (ADH). After this, endocytosis is also induced by ADH and is associated with the decline in ADH-induced water permeability at the apical surface of the toad urinary bladder (9, 19, 20). During this process, horseradish peroxidase (HRP), a fluid phase marker, is taken up from the mucosal solution into endocytic tubules and multivesicular bodies. We now report that we can introduce from the apical (mucosal) side, a viral transmembrane protein (the G-protein of VSV) and that this protein can be retrieved as an integral membrane protein in endocytic membranes. This was demonstrated by immunoisolation of endosomal vesicles loaded with HRP using a monoclonal antibody against the cytoplasmic domain of the G-protein.


Glycosaminoglycans co-administration enhance insulin-like growth factor-I neuroprotective and neuroregenerative activity in traumatic and genetic models of motor neuron disease: a review.
In this report it is shown how glycosaminoglycans and insulin-like growth factor-I (IGF-I) promote muscle reinnervation and prevent motor neuron death in experimental models of motor neuron disease. Such effect appears to be mediated by insulin-like growth factor-1. The glycosaminoglycan moiety of proteoglycans is a constituent of the basal lamina active on nerve regeneration by means of the interaction with laminin and with several growth factors. We have previously shown that supplementation by means of subcutaneous injections of glycosaminoglycans affects neuronal degeneration and regeneration. In this study we report that following neonatal lesion of the rat sciatic nerve, glycosaminoglycan treatment promoted extensor digitorum longus muscle reinnervation with consequent improvement of muscle morphology. In saline-treated rats, reinnervation was only partial and there was a marked muscle fibre atrophy, whereas, glycosaminoglycan treatment of lesioned rats increased IGF-I mRNA and protein in the reinnervated muscle, and IGF-I and insulin-like growth factor binding protein-3 plasma levels. Similarly, treatment of lesioned rats with IGF-I promoted muscle reinnervation, and prevented muscle fibre atrophy, higher levels of IGF-I in the reinnervated muscle, of IGF-I, and insulin-like growth factor binding proteins in plasma. In the wobbler mouse IGF-I and glycosaminoglycans alone promote only a partial motor neuron survival and the preservation of forelimb function decays after 3 weeks of treatment. However when glycosaminoglycans and insulin-like growth factor are administered together the motor neuron disease in the wobbler mouse is halted and there is no more loss of motor neurons.


Regulation of fatty acid degradation in Escherichia coli: isolation and characterization of strains bearing insertion and temperature-sensitive mutations in gene fadR.
Transposon Tn10 was used to mutagenize the fadR gene in Escherichia coli. Mutants bearing fadR:Tn10 insertion mutations were found to (i) utilize the noninducing fatty acid decanoate as sole carbon source, (ii) beta-oxidize fatty acids at constitutive rates, and (iii) contain constitutive levels of the five key beta-oxidative enzymes. These characteristics were identical to those observed in spontaneous fadR mutants. The constitutive phenotype presented by the fadR:Tn10 mutants was shown to be genetically linked to the associated transposon-encoded drug resistance. These results suggest that the fadR gene product exerts negative control over the fatty acid degradative regulon. The fadR gene of E. coli has been mapped through the use of transposon-mediated fadR insertion mutations. The fadR locus is at 25.5 min on the revised map and cotransduces with purB, hemA, and trp. Three-factor conjugational and transductional crosses indicate that the order of loci in this region of the chromosome is purB-fadR-hemA-trp. Spontaneous fadR mutants were found to map at the same location. Strains that exhibit alterations in the control of the fad regulon in response to changes in temperature were also isolated and characterized. These fadR(Ts) mutants were constitutive for the fad enzymes at elevated temperatures and inducible for these activities at low temperatures. The fadR(Ts) mutations also map at the fadR locus. These results strongly suggest that the fadR gene product is a repressor protein.


A global country-level analysis of the relationship between obesity and COVID-19 cases and mortality.
To assess the association of country-level obesity prevalence with COVID-19 case and mortality rates, to evaluate the impact of obesity prevalence on worldwide variation. Data on COVID-19 prevalence and mortality, country-specific governmental actions, socioeconomic, demographic, and healthcare capacity factors were extracted from publicly available sources. Multivariable negative binomial regression was used to assess the independent association of obesity with COVID-19 case and mortality rates. Across 168 countries for which data were available, higher obesity prevalence was associated with increased COVID-19 mortality and prevalence rates. For every 1% increase in obesity prevalence, the mortality rate was increased by 8.3% (incidence rate ratio [IRR] 1.083, 95% confidence interval [CI] 1.048-1.119; P < 0.001) and the case rate was higher by 6.6% (IRR 1.066, 95% CI 1.035-1.099; P < 0.001). Additionally, higher median population age, greater female ratio, higher Human Development Index (HDI), lower population density, and lower hospital bed availability were all significantly associated with higher COVID-19 mortality rate. In addition, stricter governmental actions, higher HDI and lower mean annual temperature were significantly associated with higher COVID-19 case rate. These findings demonstrate that obesity prevalence is a significant and potentially modifiable risk factor of increased COVID-19 national caseload and mortality. Future research to study whether weight loss improves COVID-19 outcomes is urgently required.


Identification and Fine Mapping of a Stably Expressed QTL for Cold Tolerance at the Booting Stage Using an Interconnected Breeding Population in Rice.
Cold stress is one of the major abiotic stresses that impede rice production. A interconnected breeding (IB) population consisted of 497 advanced lines developed using HHZ as the recurrent parent and eight diverse elite indica lines as the donors were used to identify stably expressed QTLs for CT at the booting stage. A total of 41,754 high-quality SNPs were obtained through re-sequencing of the IB population. Phenotyping was conducted under field conditions in two years and three locations. Association analysis identified six QTLs for CT on the chromosomes 3, 4 and 12. QTL qCT-3-2 that showed stable CT across years and locations was fine-mapped to an approximately 192.9 kb region. Our results suggested that GWAS applied to an IB population allows better integration of gene discovery and breeding. QTLs can be mapped in high resolution and quickly utilized in breeding.


Evaluation of through-and-through corneal sutures.
Sutures placed at the level of Descemet's membrane were compared with sutures placed through and through the full corneal thickness in 42 rabbit corneas using cataract and corneal wounds. The rabbits were killed, and sutures were removed at various postoperative periods up to four weeks. Evaluation of the wounds demonstrated that although the through-and-through technique provided good wound closure in the immediate postoperative period, the technique produced more damage to Descemet's membrane and to the endothelial cells, both at the time of suturing and at the time of suture removal, and tended to produce greater retrocorneal membrane formation. In addition, the through-and-through suturing technique was technically more difficult. In this study performed in rabbits, the one advantage of the through-and-through suture, ie, immediate posterior wound closure, was outweighed by its many disadvantages.


New approaches and procedures for cancer treatment: Current perspectives.
Cancer is a global health problem responsible for one in six deaths worldwide. Treating cancer has been a highly complex process. Conventional treatment approaches, such as surgery, chemotherapy, and radiotherapy, have been in use, while significant advances are being made in recent times, including stem cell therapy, targeted therapy, ablation therapy, nanoparticles, natural antioxidants, radionics, chemodynamic therapy, sonodynamic therapy, and ferroptosis-based therapy. Current methods in oncology focus on the development of safe and efficient cancer nanomedicines. Stem cell therapy has brought promising efficacy in regenerating and repairing diseased or damaged tissues by targeting both primary and metastatic cancer foci, and nanoparticles brought new diagnostic and therapeutic options. Targeted therapy possessed breakthrough potential inhibiting the growth and spread of specific cancer cells, causing less damage to healthy cells. Ablation therapy has emerged as a minimally invasive procedure that burns or freezes cancers without the need for open surgery. Natural antioxidants demonstrated potential tracking down free radicals and neutralizing their harmful effects thereby treating or preventing cancer. Several new technologies are currently under research in clinical trials, and some of them have already been approved. This review presented an update on recent advances and breakthroughs in cancer therapies.


Renal angiotensin II receptor regulation and renin-angiotensin system inhibition in one-kidney, one clip hypertensive rats.
To characterize glomerular and preglomerular vascular angiotensin II receptors during the acute phase of nonrenin-dependent one-kidney, one clip hypertension in rats, using the angiotensin II antagonists losartan and PD 123319, and to investigate their regulation after renin-angiotensin system blockade with either an angiotensin converting enzyme inhibitor, captopril, or an angiotensin II receptor antagonist, TCV-116. One-kidney, one clip hypertension was produced in male Sprague-Dawley rats by placing a silver clip (internal diameter 0.2 mm) on the left renal artery and removing the contralateral kidney. After 1, 2 or 4 weeks, the rats were killed, and their glomerular and preglomerular vascular membranes were purified. Competitive binding studies were performed using specific angiotensin II antagonists. Similarly, one-kidney, one clip hypertension was allowed to develop for 2 weeks before treatment with captopril or TCV-116 for 2 weeks. Competitive binding studies showed that only the angiotensin II type 1 (AT1) receptor was detected on both glomeruli and preglomerular vessels of all groups. The vascular AT1 receptor density was significantly higher in the 1 and 2 week one-kidney, one clip groups, but the glomerular receptor density was not different in these rats compared with age-matched uninephrectomized controls. The glomerular receptor density was significantly higher in captopril-treated rats and significantly lower in TCV-116-treated rats compared with untreated and control rats, but no significant changes were detected in any groups in vascular AT1 receptor density. Angiotensin II receptors on preglomerular vessels and glomeruli are differentially regulated during the early phase of hypertension and after renin-angiotensin system blockade. Vascular angiotensin II receptors are upregulated in the early phase of hypertension whereas glomerular angiotensin II receptors are not However, after renin-angiotensin system blockade, glomerular but not vascular angiotensin II receptors were differentially regulated according to the type of blockade.


The epithelium of the vesicular gland of the African giant rat (Cricetomys gambianus, Waterhouse): histology and ultrastructure.
The epithelium of the vesicular gland of the African giant rat was studied by the light and electron microscopes. The gland is compound tubuloalveolar, lined by a columnar epithelium, the apical surface of which is covered by a few short microvilli. The epithelial cells are the principal and basal cells. The principal cells have an abundance of rough surfaced endoplasmic reticulum (rER), which are often arranged in whorls. Basal cells are few, being wedged between adjacent principal cells in the basal region. They are fairly electron lucent and contain fewer organelles. Intraepithelial lymphocytes, which also occur mostly in the basal region are also present in the epithelium. The presence of these latter cells is noteworthy in that they are not a known feature of the epithelium of the vesicular gland of other species.


Reclassification of Desulfobacterium anilini as Desulfatiglans anilini comb. nov. within Desulfatiglans gen. nov., and description of a 4-chlorophenol-degrading sulfate-reducing bacterium, Desulfatiglans parachlorophenolica sp. nov.
A strictly anaerobic, mesophilic, sulfate-reducing bacterial strain (DS(T)), isolated from river sediment contaminated with volatile organic compounds, was characterized phenotypically and phylogenetically. Cells were Gram-reaction-negative, non-motile short rods. For growth, optimum NaCl concentration was 0.9 g l(-1), optimum temperature was 30 °C and optimum pH was 7.2. Strain DS(T) utilized phenol, benzoate, 4-hydroxybenzoate, 4-methylphenol, 4-chlorophenol, acetate, butyrate and pyruvate as electron donors for sulfate reduction. Electron donors were completely oxidized. Strain DS(T) did not utilize sulfite, thiosulfate or nitrate as electron acceptors. The genomic DNA G+C content of strain DS(T) was 58.9 mol%. Major cellular fatty acids were iso-C14 : 0, anteiso-C15 : 0 and C18 : 1ω7c. Phylogenetic analyses based on the 16S rRNA gene indicated its closest relatives were strains of Desulfobacterium anilini (about 98-99 % sequence similarity) but the DNA-DNA hybridization value with Desulfobacterium anilini Ani1(T) was around 40 %. Although strain DS(T) and its relatives shared most phenotypic and chemotaxonomic characteristics, the utilization of 4-chlorophenol, the range of electron acceptors and the optimum growth conditions differed. Strain DS(T) is closely related to strains of Desulfobacterium anilini, but constitutes a different species within the genus. Based on phylogeny, phenotypic characteristics and chemotaxonomic characteristics, strain DS(T) and Desulfobacterium anilini were clearly different from strains of other species of the genus Desulfobacterium. We thus propose the reclassification of Desulfobacterium anilini within a new genus, Desulfatiglans gen. nov., as Desulfatiglans anilini comb. nov. We also propose Desulfatiglans parachlorophenolica sp. nov. to accommodate strain DS(T). The type strain is DS(T) ( = JCM 19179(T) = DSM 27197(T)).


Margination propensity of vascular-targeted spheres from blood flow in a microfluidic model of human microvessels.
Many variants of vascular-targeted carriers (VTCs) have been investigated for therapeutic intervention in several human diseases. However, in order to optimize the functionality of VTC in vivo, carriers' physical properties, such as size and shape, are important considerations for a VTC design that evades the reticuloendothelial system (RES) and successfully interacts with the targeted vessel wall. Nonetheless, little evidence has been presented on the role of size in VTC's interactions with the vascular wall, particularly in the microcirculation. Thus, in this work, we explore how particle size, along with hemodynamics (blood shear rate and vessel size) and hemorheology (blood hematocrit) affect the capacity for spheres to marginate (localize and adhere) to inflamed endothelium in a microfluidic model of human microvessels. Microspheres, particularly the 2 μm spheres, were found to show disproportionately higher margination than nanospheres in all hemodynamic conditions evaluated due to the poor ability of the latter to localize to the wall region from midstream. This work represents the first evidence that nanospheres may not exhibit "near wall excess" in microvessels, e.g., arterioles and venules, and therefore may not be suitable for imaging and drug delivery applications in cancer and other diseases affecting microvessels.


Complications of self-circumcision: a case report and proposal.
Male circumcision is a common surgical technique that has been performed worldwide for thousands of years for medical, social, cultural, and religious reasons. It is usually conducted in childhood in a clinical setting, but the practice of adult self-circumcision has led to a market for nonmedically approved self-circumcision devices that can be purchased via the Internet. The aims of this report are to report the case of a 30-year-old white man who suffered complications after trying to perform a self-circumcision with a nonmedically approved device purchased via the Internet, and to propose that urologists should take the lead in investigating the problem of male self-circumcision. This case report documents the presentation and treatment of an attempted self-circumcision. The attempted self-circumcision was carried out without local anaesthetic and resulted in an incision in the foreskin. The patient presented with uncontrollable local bleeding 2 days after carrying out the procedure. Although questioned as to why he had attempted self-circumcision, the patient was reluctant and/or unable to explain his reasons. Daily local wound care and topical antibiotics resulted in complete wound healing after 2 months, and a clinical clamp circumcision was conducted to treat the remaining severe phimosis. Data on the prevalence and outcomes associated with the use of self-circumcision devices are few. The clinicians who treat the complications are best placed to collect data on self-circumcision and should publish case studies. Eventually there may be sufficient understanding of the sector of the population at risk from this practice to educate those likely to attempt self-circumcision, and enough evidence of harm for controls to be placed on the sale of these nonmedically approved devices via the Internet.


Restriction endonucleases in identification of a genome type of adenovirus 19 associated with keratoconjunctivitis.
Adenovirus type 19 (Ad19) was first associated with disease in 1973 when several outbreaks of keratoconjunctivitis were reported from Europe and North America. We have examined Ad19 isolates by deoxyribonucleic acid restriction with BamHI, BglI, and SmaI restriction endonucleases. All keratoconjunctivitis-associated Ad19 isolates were identical but different from the Ad19 prototype. The total number of resolved restriction fragments of the Ad19 prototype genome was 31, only 17 of which migrated as the restriction fragments of keratoconjunctivitis-associated genomes. We conclude that two different genome types of Ad19 exist, one of which has been responsible for the recent outbreaks of keratoconjunctivitis.


Beta-Glucans Supplementation Associates with Reduction in P-Cresyl Sulfate Levels and Improved Endothelial Vascular Reactivity in Healthy Individuals.
Oat and barley beta-glucans are prebiotic fibers known for their cholesterol-lowering activity, but their action on the human gut microbiota metabolism is still under research. Although the induction of short-chain fatty acids (SCFA) following their ingestion has previously been reported, no study has investigated their effects on proteolytic uremic toxins p-cresyl sulfate (pCS) and indoxyl sulfate (IS) levels, while others have failed to demonstrate an effect on the endothelial function measured through flow-mediated dilation (FMD). The aim of our study was to evaluate whether a nutritional intervention with a functional pasta enriched with beta-glucans could promote a saccharolytic shift on the gut microbial metabolism and improve FMD. We carried out a pilot study on 26 healthy volunteers who underwent a 2-month dietary treatment including a daily administration of Granoro "Cuore Mio" pasta enriched with barley beta-glucans (3g/100g). Blood and urine routine parameters, serum pCS/IS and FMD were evaluated before and after the dietary treatment. The nutritional treatment significantly reduced LDL and total cholesterol, as expected. Moreover, following beta-glucans supplementation we observed a reduction of serum pCS levels and an increase of FMD, while IS serum levels remained unchanged. We demonstrated that a beta-glucans dietary intervention in healthy volunteers correlates with a saccharolytic shift on the gut microbiota metabolism, as suggested by the decrease of pCS and the increase of SCFA, and associates with an improved endothelial reactivity. Our pilot study suggests, in addition to cholesterol, novel pCS-lowering properties of beta-glucans, worthy to be confirmed in large-scale trials and particularly in contexts where the reduction of the microbial-derived uremic toxin pCS is of critical importance, such as in chronic kidney disease.


Dose selection for biological enzyme replacement therapy indicated for inborn errors of metabolism.
This paper summarizes key features of the dose-finding strategies used in the development of 11 approved new molecular entities that are first-in-class enzyme replacement therapy (ERT), with a goal to gain insight into the dose exploration approaches to inform efficient dose-finding in future development of biological products for Inborn Errors of Metabolism (IEM). Dose exploration should preferably begin in in vitro studies, followed by testing multiple doses in an appropriate animal disease model, when available, which can provide important information for dose assessment in humans. Performing adequate dose-finding in early phase clinical studies in a well-defined study population, including pediatric subjects, is generally critical to inform dose selection for pivotal trials; alternatively, additional dose exploration can be incorporated as part of a pivotal trial. Two important considerations for successful dose selection include (1) identifying appropriate disease-specific endpoints, including pharmacodynamic (PD) end points and intermediate clinical end points or clinical end points, and (2) designing a study with adequate treatment durations for evaluating these end points. Appropriately selected PD biomarkers is useful for dose selection, and early development of these biomarkers can facilitate the overall clinical development program. Optimization of ERT doses, as well as evaluations of patient intrinsic factors and/or immune tolerance strategies may be necessary to overcome antibody responses or increase efficacy in IEM.


Thermally activated delayed fluorescence (TADF) and enhancing photoluminescence quantum yields of [Cu(I)(diimine)(diphosphine)](+) complexes-photophysical, structural, and computational studies.
The complexes [Cu(I)(POP)(dmbpy)][BF4] (1) and [Cu(I)(POP)(tmbpy)][BF4] (2) (dmbpy = 4,4'-dimethyl-2,2'-bipyridyl; tmbpy = 4,4',6,6'-tetramethyl-2,2'-bipyridyl; POP = bis[2-(diphenylphosphino)-phenyl]ether) have been studied in a wide temperature range by steady-state and time-resolved emission spectroscopy in fluid solution, frozen solution, and as solid powders. Emission quantum yields of up to 74% were observed for 2 in a rigid matrix (powder), substantially higher than for 1 of around 9% under the same conditions. Importantly, it was found that the emission of 2 at ambient temperature represents a thermally activated delayed fluorescence (TADF) which renders the compound to be a good candidate for singlet harvesting in OLEDs. The role of steric constraints within the complexes, in particular their influences on the emission quantum yields, were investigated by hybrid-DFT calculations for the excited triplet state of 1 and 2 while manipulating the torsion angle between the bipyridyl and POP ligands. Both complexes showed similar flexibility within a ±10° range of the torsion angle; however, 2 appeared limited to this range, whereas 1 could be further twisted with little energy demand. It is concluded that a restricted flexibility leads to a reduction of nonradiative deactivation and thus an increase of emission quantum yield.


Measuring quality of life in low-income, Spanish-speaking Puerto Ricans with type 2 diabetes residing in the mainland U.S.
This study assessed the psychometric properties of the Audit of Diabetes-Dependent Quality of Life (ADDQoL) modified for low-income, low-education, Spanish-speaking Puerto Ricans with type 2 diabetes residing in the northeastern United States. Cross-sectional data from 226 patients were analyzed. Scale modifications included simplification of instructions, question wording and response format, and oral administration. Reliability was assessed with Cronbach's alpha coefficient and internal structure by exploratory factor analysis. Criterion validity was assessed using correlation analysis and linear and logistic regression models assessing the association of the ADDQoL with standardized physical health status, mental health status, depression, and comorbidity indices. Two ADDQoL items were dropped. The modified scale had excellent internal consistency and supported the original scale factor structure. Criterion validity results supported the validity of this measure. The modified ADDQoL showed psychometric properties that support its use in low-income, Spanish-speaking Puerto Ricans with type 2 diabetes who reside in mainland U.S.


Cohorting to isolate asymptomatic spreaders: An agent-based simulation study on the Mumbai Suburban Railway.
The Mumbai Suburban Railways, locals, are a key transit infrastructure of the city and is crucial for resuming normal economic activity. Due to high density during transit, the potential risk of disease transmission is high, and the government has taken a wait and see approach to resume normal operations. To reduce disease transmission, policymakers can enforce reduced crowding and mandate wearing of masks. Cohorting - forming groups of travelers that always travel together, is an additional policy to reduce disease transmission on locals without severe restrictions. Cohorting allows us to: (i) form traveler bubbles, thereby decreasing the number of distinct interactions over time; (ii) potentially quarantine an entire cohort if a single case is detected, making contact tracing more efficient, and (iii) target cohorts for testing and early detection of symptomatic as well as asymptomatic cases. Studying impact of cohorts using compartmental models is challenging because of the ensuing representational complexity. Agent-based models provide a natural way to represent cohorts along with the representation of the cohort members with the larger social network. This paper describes a novel multi-scale agent-based model to study the impact of cohorting strategies on COVID-19 dynamics in Mumbai. We achieve this by modeling the Mumbai urban region using a detailed agent-based model comprising of 12.4 million agents. Individual cohorts and their inter-cohort interactions as they travel on locals are modeled using local mean field approximations. The resulting multi-scale model in conjunction with a detailed disease transmission and intervention simulator is used to assess various cohorting strategies. The results provide a quantitative trade-off between cohort size and its impact on disease dynamics and well being. The results show that cohorts can provide significant benefit in terms of reduced transmission without significantly impacting ridership and or economic & social activity.


Anti-CD20 antibody promotes cancer escape via enrichment of tumor-evoked regulatory B cells expressing low levels of CD20 and CD137L.
The possible therapeutic benefits of B-cell depletion in combating tumoral immune escape have been debated. In support of this concept, metastasis of highly aggressive 4T1 breast cancer cells in mice can be abrogated by inactivation of tumor-evoked regulatory B cells (tBreg). Here, we report the unexpected finding that B-cell depletion by CD20 antibody will greatly enhance cancer progression and metastasis. Both murine and human tBregs express low levels of CD20 and, as such, anti-CD20 mostly enriches for these cells. In the 4T1 model of murine breast cancer, this effect of enriching for tBregs suggests that B-cell depletion by anti-CD20 may not be beneficial at all in some cancers. In contrast, we show that in vivo-targeted stimulation of B cells with CXCL13-coupled CpG oligonucleotides (CpG-ODN) can block cancer metastasis by inhibiting CD20(Low) tBregs. Mechanistic investigations suggested that CpG-ODN upregulates low surface levels of 4-1BBL on tBregs to elicit granzyme B-expressing cytolytic CD8(+) T cells, offering some explanative power for the effect. These findings underscore the immunotherapeutic importance of tBreg inactivation as a strategy to enhance cancer therapy by targeting both the regulatory and activating arms of the immune system in vivo.


Rat-derived amniotic epithelial cells differentiate into mature hepatocytes in vivo with no evidence of cell fusion.
Amniotic epithelial cells (AEC) derived from human placenta represent a useful and noncontroversial source for liver-based regenerative medicine. Previous studies suggested that human- and rat-derived AEC differentiate into hepatocyte-like cells upon transplantation. In the retrorsine (RS) model of liver repopulation, clusters of donor-derived cells engrafted in the recipient liver and, importantly, showed characteristics of mature hepatocytes. The aim of the current study was to investigate the possible involvement of cell fusion in the emergence of hepatocyte clusters displaying a donor-specific phenotype. To this end, 4-week-old GFP(+)/DPP-IV(-) rats were treated with RS and then transplanted with undifferentiated AEC isolated from the placenta of DPP-IV(+) pregnant rats at 16-19 days of gestational age. Results indicated that clusters of donor-derived cells were dipeptidyl peptidase type IV (DPP-IV) positive, but did not express the green fluorescent protein (GFP), suggesting that rat amniotic epithelial cells (rAEC) did not fuse within the host parenchyma, as no colocalization of the two tags was observed. Moreover, rAEC-derived clusters expressed markers of mature hepatocytes (eg, albumin, cytochrome P450), but were negative for the expression of biliary/progenitor markers (eg, epithelial cell adhesion molecule [EpCAM]) and did not express the marker of preneoplastic hepatic nodules glutathione S-transferase P (GST-P). These results extend our previous findings on the potential of AEC to differentiate into mature hepatocytes and suggest that this process can occur in the absence of cell fusion with host-derived cells. These studies support the hypothesis that amnion-derived epithelial cells can be an effective cell source for the correction of liver disease.


Outcomes of pathologically localized high-grade prostate cancer treated with radical prostatectomy.
Adjuvant radiation therapy (ART) is recommended without consideration of radical prostatectomy Gleason score (RP GS) for cases with adverse features. We compared the outcomes of pathologically localized high-grade (GS 8-10) prostate cancer (PC) with those of pT3 GS 7 PC.A total of 1585 men who underwent RP between 1995 and 2015 comprised the cohort, which was divided into group 1 (RP GS 7(3 + 4) and pT3; n = 760), group 2 (RP GS 7(4 + 3) and pT3; n = 565), and group 3 (RP GS 8-10 and pT2; n = 260). Biochemical recurrence (BCR), all-cause mortality (ACM), and PC-specific mortality (PCSM) risk were compared among groups using Cox regression and competing risk analysis.At a median follow-up of 58 months (interquartile range: 37-85), 721 men experienced BCR and 84 died (22 due to PC). BCR-free survival rates were lower in group 3 than in group 1 (P < .001); nevertheless, no difference was observed between groups 2 and 3 (P = .638). Furthermore, no difference in ACM was noted among groups. PCSM rates were higher in group 3 than in groups 1 and 2 (P = .001 and P = .005, respectively). This association persisted in multivariate models after adjustment for clinicopathological variables.Patients with RP GS 8-10 and pT2 PC had higher BCR and PCSM rates than those with RP GS 7 and pT3 PC. Localized high-grade PC should be considered in decision-making for ART.


[Metabolic side effects of antiretroviral therapy].
Antiretroviral therapy for HIV-I-infections is accompanied with the occurrence of several metabolic side effects. An often encountered complication of antiretroviral therapy is the adipose redistribution syndrome characterised by an altered distribution of body fat, and linked with protease inhibitor (PI) and nucleoside-reverse-transcriptase inhibitors (NRTIs). Some NRTIs have lactate acidosis as a side effect in rare cases (0.1%), which is accompanied by a high mortality. The far less serious side effect hyperlactaemia is more frequently observed; this is a symptomatic elevation of the lactate level without acidosis. Insulin resistance is not only ascribed to therapy-induced lipoatrophy and visceral fat accumulation, it is also directly related to the use of some PIs and NRTIs. PIs and abacavir and to a lesser extend didanosine result in a high risk of cardiovascular disease. Moreover, the prevalence of traditional cardiovascular risk factors in HIV-infected subjects is higher than that in HIV-seronegative subjects. Clinically relevant interactions exist between PIs and statins. Pravastatin seems to be accompanied with the lowest chance of interaction and is therefore recommended as cholesterol-lowering therapy. The metabolic side effects are outweighed by the favourable effect of the antiretroviral agents. Counteraction of these side effects may therefore not be at the expense of the antiretroviral therapy.


Application of the occupational health services model in Thai primary care units.
This study explored the elements of the occupational health services model in Thai primary care units. Seven focus groups with nurses and public health professionals working in primary care units, employees, employers, and occupational health service-related authorities were conducted. Content analysis of the focus groups revealed 15 practical elements in five domains: system inputs, throughputs, services, outputs, and feedback. Examples of existing elements in the five domains were occupational health staff competencies (inputs), collaborative network building (throughputs), on-site occupational health services (services), number of activities performed as on-site occupational health services (outputs), and evaluation (feedback) of occupational health services delivery. The findings have implications for further development of the occupational health services model in Thai primary care units, such as training the staff of primary care units to become competent in delivering effective occupational health services.


Insulin-like growth factor I receptors in retinal rod outer segments.
We have previously reported that the GDP-bound alpha-subunit of the GTP-binding protein transducin, present in outer segments of retinal rod cells (ROS), serves as a high affinity in vitro substrate (Km = 1 microM) for the insulin receptor kinase. The present study demonstrates that transducin also serves as in vitro substrate for an endogenous IGF-I receptor kinase isolated from ROS membranes. The presence of insulin-like growth factor I (IGF-I) receptors in ROS is evident from the high affinity and specific binding of 125I-IGF-I to ROS membranes (Kd = 3 nM) which contain 110 fmol of IGF-I binding sites/mg of membrane protein. Furthermore, cross-linking of 125I-IGF-I labels the 135-kDa alpha-subunit of this receptor. 125I-Insulin binding capacity to ROS membranes is less than 5% that of IGF-I. The IGF-I-stimulated tyrosine kinase activity in solubilized and partially purified receptors from ROS autophosphorylates its own 95-kDa beta-subunits as well as other substrates like transducin. Insulin, which is 200-fold less potent than IGF-I in competing for 125I-IGF-I binding, is only 5-fold less potent than IGF-I in stimulating the receptor kinase activity. This suggests that insulin is much more potent than IGF-I in coupling ligand binding with kinase activation. The previously reported presence of IGF-I in the vitreous, together with our present studies, strongly suggest that the IGF-I receptor kinase, through phosphorylation of endogenous proteins like transducin, could play a role in mediating transmembrane signal transduction in ROS.


Prognosis of malignant mammary tumor in 53 cats.
Medical records of fifty-three cats diagnosed as malignant mammary tumor from 1982 to 1993 were reviewed. The mean age of the cats at diagnosis was 11.1 years, and Japanese domestic and Siamese breeds were predominant. Survival rates after 1 and 2 years of diagnosis were 31.8% and 17.7%, respectively, suggesting poor prognosis of this malignancy. The survival time was significantly associated with tumor size or WHO clinical stage, but not with breed, age, or gender. Twenty-nine cats with pulmonary metastasis died within 5 months following metastatic detection. Postoperative prognosis was significantly related to the tumor size at surgery, but not with type of surgery and adjuvant chemotherapy using cyclophosphamide and/or vincristine.


Performance linked to residence time distribution by a novel wool-based bioreactor for tertiary sewage treatment.
Laboratory-scale experiments were carried out using up-flow 7 L Submerged Aerated Filter reactors packed with wool fibre or commercial plastic pall rings, Kaldnes, (70% by volume) support media for the tertiary treatment of sewage. The performance of the wool bioreactor was more consistent than that with Kaldnes medium, for both TOC removal (93%) and SS removal (90%). Both plastic and wool-packed bioreactors achieved complete nitrification at the load of about 0.4 kgCOD/m(3)/day. The sludge yield of the wool bioreactor was almost half that of the bioreactor with Kaldnes suggesting that wool could retain residual organics and particulates. The wool however was degraded and it was concluded that wool would have to be considered as additional sacrificial adsorption capacity rather than an alternative medium. The performance was linked to the residence time distribution studies and these changes in the wool structure. Biomass growth increased the retention of the tracer in the wool reactor by, it was suggested, exposing a greater surface area. Results from the plastic media on the other hand showed increased mixing possibly by increasing the mobility of the plastic. Aeration increased the mixing in both reactors, and patterns were in all cases predominantly well-mixed.


Nitric oxide-mediated regulation of transepithelial sodium and chloride transport in murine nasal epithelium.
Transepithelial ion transport is regulated by a variety of cellular factors. In light of recent evidence that nitric oxide (NO) production is decreased in cystic fibrosis airways, we examined the role of NO in regulating sodium and chloride transport in murine nasal epithelium. Acute intervention with the inducible NO synthase (iNOS)-selective inhibitor S-methylisothiourea resulted in an increase of amiloride-sensitive sodium absorption observed as a hyperpolarization of nasal transepithelial potential difference. Inhibition of iNOS expression with dexamethasone also hyperpolarized transepithelial potential difference, but only a portion of this increase proved to be amiloride sensitive. Chloride secretion was significantly inhibited in C57BL/6J mice by the addition of both S-methylisothiourea and dexamethasone. Mice lacking iNOS expression [NOS2(-/-)] also had a decreased chloride-secretory response compared with control mice. These data suggest that constitutive NO production likely plays some role in the downregulation of sodium absorption and leads to an increase in transepithelial chloride secretion.