A pooled testing strategy for identifying SARS-CoV-2 at low prevalence.
Suppressing infections of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) will probably require the rapid identification and isolation of individuals infected with the virus on an ongoing basis. Reverse-transcription polymerase chain reaction (RT-PCR) tests are accurate but costly, which makes the regular testing of every individual expensive. These costs are a challenge for all countries around the world, but particularly for low-to-middle-income countries. Cost reductions can be achieved by pooling (or combining) subsamples and testing them in groups1-7. A balance must be struck between increasing the group size and retaining test sensitivity, as sample dilution increases the likelihood of false-negative test results for individuals with a low viral load in the sampled region at the time of the test8. Similarly, minimizing the number of tests to reduce costs must be balanced against minimizing the time that testing takes, to reduce the spread of the infection. Here we propose an algorithm for pooling subsamples based on the geometry of a hypercube that, at low prevalence, accurately identifies individuals infected with SARS-CoV-2 in a small number of tests and few rounds of testing. We discuss the optimal group size and explain why, given the highly infectious nature of the disease, largely parallel searches are preferred. We report proof-of-concept experiments in which a positive subsample was detected even when diluted 100-fold with negative subsamples (compared with 30-48-fold dilutions described in previous studies9-11). We quantify the loss of sensitivity due to dilution and discuss how it may be mitigated by the frequent re-testing of groups, for example. With the use of these methods, the cost of mass testing could be reduced by a large factor. At low prevalence, the costs decrease in rough proportion to the prevalence. Field trials of our approach are under way in Rwanda and South Africa. The use of group testing on a massive scale to monitor infection rates closely and continually in a population, along with the rapid and effective isolation of people with SARS-CoV-2 infections, provides a promising pathway towards the long-term control of coronavirus disease 2019 (COVID-19).


Arabidopsis thaliana receptor-like protein AtRLP23 associates with the receptor-like kinase AtSOBIR1.
Plants employ a large number of receptors localizing to the cell surface to sense extracellular signals. Receptor-like proteins (RLPs) form an important group of such trans-membrane receptors, containing an extracellular domain which is involved in signal perception and a short cytoplasmic domain. In contrast to receptor-like kinases (RLKs), RLPs lack a cytoplasmic kinase domain. How intracellular signaling is triggered downstream of RLPs upon perception of an extracellular signal, is therefore still poorly understood. Recently, the RLK SOBIR1 (Suppressor Of BIR1-1) was identified as an essential regulatory RLK of various RLPs involved in plant immunity against fungal pathogens. (1) Given that SOBIR1 appears to be a crucial component of RLP-containing complexes, we aimed to identify additional proteins interacting with SOBIR1. Here, we report on the immunopurification of a functional Arabidopsis thaliana (At)SOBIR1-yellow fluorescent protein (YFP) fusion protein stably expressed in Arabidopsis, followed by mass-spectrometry to identify co-purifying proteins. Interestingly, and in line with various studies showing interaction between RLPs and SOBIR1, we discovered that AtSOBIR1 interacts with AtRLP23, an RLP of which the function is currently unknown.


Axial length measurement failure rates using optical biometry based on swept-source OCT in cataractous eyes.
Ocular dimensions measurement is extremely important in cataract procedures and refractive surgery. The use of optical techniques for axial measurements has been developed in recent years. The purpose was to summarize the outcomes reported when swept-source optical coherence tomography (SS-OCT) optical biometry failed during axial length measurement. A peer-reviewed literature search was carried out to identify publications reporting clinical outcomes for cataractous eyes measured with SS-OCT optical biometers available on the market. A comprehensive analysis of the available data was performed, focusing on parameters such as the sample of eyes evaluated, failure rates, and specifically, the cataract type when the measurement was not possible. 27 studies were included in this review. In general, SS-OCT biometers lead to only small failure rates when measuring axial length (but in some cases up to 38.49%). In the few cases where the measurement was not possible, the cataract type of the eyes was mainly mature white or grade ≥ IV. SS-OCT optical biometers show good outcomes when measuring axial length in eyes with advanced cataracts. We believe that the use of SS-OCT technology may be considered the gold standard for measuring axial length in any type of cataract.


Oxidative stress in Cohen diabetic rat model by high-sucrose, low-copper diet: inducing pancreatic damage and diabetes.
Increased oxidative stress contributes to the development and progression of both types of diabetes mellitus (DM) and its complications. In the Cohen diabetic (CD) rats, a known genetic model of nutritionally induced type 2 DM, a high-sucrose, low-copper diet (HSD) induces within 4 weeks DM in the sensitive (CDs) rats but not in the resistant (CDr) rats. To assess the possible involvement of oxidative stress in the induction of DM, we studied the effect of HSD on the tissue levels of antioxidants and the extent of oxidative injuries in these animals in comparison with the regular outbred strain of nondiabetic Sabra rats. The specific aims were to investigate, at the onset of HSD-induced DM, (1) the extent of oxidative injury, as reflected by levels of malondialdehyde and protein carbonyl groups; (2) the overall antioxidant capacities to cope with increased oxidative stress; and (3) the modification of oxidative damage biomarkers in various tissues of CDr, CDs, and Sabra rats. Female CDs, CDr, and Sabra rats were fed regular diet or HSD for 4 to 5 weeks; and several parameters of oxidative injuries and antioxidant levels were determined. Changes in the levels of nonenzymatic low-molecular weight antioxidants (LMWAs) were measured by cyclic voltammetry and oxygen radical absorbance capacity. The activities of the antioxidant enzymes superoxide dismutase and catalase were measured. Oxidative damage was evaluated by measuring lipid peroxidation and protein oxidation. (1) In all animals fed HSD, the levels of LMWAs were decreased in most organs, although not plasma. (2) A significant difference was consistently found in antioxidant enzymes' activities in the pancreas of HSD-fed CDs rats, but not in other tissues. (3) The activities of superoxide dismutase and catalase and the levels of malondialdehyde and protein carbonyl group increased, whereas the levels of LMWAs decreased, in the pancreas of HSD-fed CDs rats. In the CD rats that develop DM when fed HSD, the pancreas showed susceptibility to oxidative stress-induced injuries. Thus, enhanced oxidative stress seems to play a role in the pathogenesis of DM in this strain.


Expression of COX2 and p53 in Rat Esophageal Cancer Induced by Reflux of Duodenal Contents.
Aim. Reflux of duodenal contents can induce mucosal injury, stimulate cell proliferation, and promote tumorigenesis. We examined the expression of COX2 and p53 in rat esophageal lesions induced by duodenal content reflux. Methods. Thirty 8-week-old male Wistar rats were exposed to duodenal content esophageal reflux. All animals underwent an esophagoduodenal anastomosis (EDA) with total gastrectomy in order to produce chronic esophagitis. Ten rats were the sham. Control. They were sacrificed at the 40th week. Their esophagi were examined for HE, COX2, p53, and proliferating cell nuclear antigen (PCNA). Results. After 40 weeks of reflux, dysplasia, squamous cell carcinoma (SCC), and adenocarcinoma (ADC) were found. PCNA labeling index was higher in dysplastic and cancer tissue than that in normal. Overexpression of COX2 was shown in ADC and SCC. Wild-type p53 accumulation was found in ADC, and not in SCC. Conclusion. Reflux of duodenal contents into the esophagus led to ADC and SCC in rats. COX2 may play an important role in esophageal cancer by duodenal content reflux. Our present results suggest an association between wild-type p53 accumulation and COX2 expression in ADC, with no such relation seen in SCC.


Impact of urban agriculture on malaria vectors in Accra, Ghana.
To investigate the impact of urban agriculture on malaria transmission risk in urban Accra larval and adult stage mosquito surveys, were performed. Local transmission was implicated as Anopheles spp. were found breeding and infected Anopheles mosquitoes were found resting in houses in the study sites. The predominant Anopheles species was Anopheles gambiae s.s.. The relative proportion of molecular forms within a subset of specimens was 86% S-form and 14% M-form. Anopheles spp. and Culex quinquefasciatus outdoor biting rates were respectively three and four times higher in areas around agricultural sites (UA) than in areas far from agriculture (U). The annual Entomological Inoculation Rate (EIR), the number of infectious bites received per individual per year, was 19.2 and 6.6 in UA and U sites, respectively. Breeding sites were highly transitory in nature, which poses a challenge for larval control in this setting. The data also suggest that the epidemiological importance of urban agricultural areas may be the provision of resting sites for adults rather than an increased number of larval habitats. Host-seeking activity peaked between 2-3 am, indicating that insecticide-treated bednets should be an effective control method.


Catapol reduced the cognitive and mood dysfunctions in post-stroke depression mice via promoting PI3K-mediated adult neurogenesis.
Adult hippocampal neurogenesis provides a regenerative resource for neural tissue and enhances neural plasticity, which is beneficial for brain functional rehabilitation post stroke. Recently, an increasing number of metabolic drugs have been reported to attenuate behavioral symptoms in neurodegeneration or psychiatric disorders via promoting adult hippocampal neurogenesis. Bioeffects of catapol show its potential as an antidiabetic though it has been previously widely indicated to perform the neuroprotective functions. However, the systematic evidence to support the behavioral effects of catapol to PSD model and what is the role of adult neurogenesis in such effects remains unexplored. In current study, we created the PSD model by combining MCAO procedure and CORT feeding. The treatment of catapol strikingly reduced the depressive/anxiety behavior in PSD model. Moreover, treatment of catapol also improved the cognitive functions. Immunofluorescence indicates that catapol could promote adult hippocampal neurogenesis in PSD model, and TMZ treatment further confirmed the role of the hippocampal neurogenesis in catapol's therapeutic effects to PSD. Cultural neurons also indicates that PI3K is the key signal in regulating catapol mediated neurogenesis. By administrating the PI3K specific inhibitor, we found that PI3K is the key to mediate the behavioral effects of catapol to PSD. In conclusion, catapol could perform as the effective drug to treat PSD via the PI3K mediated adult hippocampal neurogenesis.


[The sexuality by Marañón].
It is noticeable that he always had an interest in sexuality Marañón. It must be noted that at the time this included a series of processes that now have become separated from it, as all human reproduction, both from a social standpoint as a scientist or political issues and problems in speaking so very active. But specifically, referring to the current concept of sexuality, much to Marañón investigated because, following the ideas of Freud, then in vogue, I wanted to know the importance that the hormones, newly discovered, had on the brain and the human personality. It is quite possible to believe that there is a brain chemistry that modulate the individual's character, against the prevailing idea among psychiatrists of his time. So his research with adrenaline on the behavior had a huge impact. Interested in the morphological evolution of sex and sexuality from birth to old age, remain valid provided knowledge about the process of sexual maturation and decline, menopause, or rather the climacteric, as rightly he called that period of time. He also made a deep study and systematization of the pathology adel origin and evolution of sex, in which he listed as intersex, both anatomically and functionally and psychic. Because he was always interested in the relationship of human behavior, the development of your body or endocrine constitution and personality. This is reflected in their psychobiographies as the paradigm "Bioassay of Henry IV of Castile and his time".


Intraprostatic spiral during waiting time for transurethral prostatectomy.
When benign prostatic hyperplasia results in voiding problems such as acute or chronic urinary retention, transurethral prostatectomy is often necessary. We have evaluated 24 patients, treated with an intraprostatic spiral, during waiting time for transurethral prostatectomy. The spiral treatment was a success in 21 patients. Three patients had a transurethral prostatectomy before scheduled time due to spiral failure, 2 with urinary retention, 1 with severe local discomfort. We conclude that spiral treatment of symptomatic benign prostatic hyperplasia while waiting for transurethral prostatectomy has a high success rate and is recommended as a favorable alternative to an indwelling urethral catheter.


Test particle limit for the pair structure of quenched-annealed fluid mixtures.
A density functional route to the pair structure of quenched-annealed fluid mixtures is presented. The bulk two-body partial pair correlation functions of the mixture are identified with the one-body density distributions in an external potential that models a fixed test particle. Quenched-annealed (replica) density functional theory is used to calculate the inhomogeneous one-body density distributions. A closed theory is obtained by using an exact sum rule that equates two different expressions for the cross pair correlation function between unlike species. Results for binary quenched-annealed hard sphere mixtures are found to agree well with computer simulation data, improving over results from the replica Ornstein-Zernike equations using the direct correlation functions, obtained as second functional derivatives of the quenched-annealed excess free energy functional, as input. The proposed framework allows for the independent determination of the blocked part of the fluid-fluid partial pair correlation function.


The influence of body weight on chosen physiological parameters in wrestling.
In this study, the authors attempted to determine whether the dynamics of blood lactate and glucose in wrestling depend on the weight class. Blood lactate and glucose curves during and after a wrestling match were determined. We also explained the dynamics of blood lactate and glucose in the context of recent glucose and lactate metabolism research. A sample of 60 youth wrestlers (15-20 years) were divided into three weight groups. Each athlete participated in one wrestling match. During the fight, the athletes' heart rate, glucose, and blood lactate were measured. The differences in body mass between the athletes did not affect the dynamics of lactate and glucose in wrestling competition (Fisher LSD test). We established that lactate and glucose dynamics are the same for all weight groups (Fisher LSD-Lactate 1 < 2 < 3 = 4 > 5, Fisher LSD-Glucose 1 = 2 < 3 < 4 < 5). Understanding lactate and glucose metabolism in wrestling is important for wrestling coaches because they need to evaluate a wrestler's anaerobic energy status.


[Effects of postoperative urine protein levels on predicting acute kidney injury in critically ill patients undergoing non-cardiac surgery].
Objective: To investigate the predictive value of postoperative urine protein level in critically ill patients undergoing non-cardiac surgery with acute kidney injury (AKI). Methods: A total of 661 critically ill patients undergoing non-cardiac surgery, who visited the Department of Critical Care Medicine of Peking University First Hospital from May 20, 2019 to November 24, 2020, were enrolled in this prospective study. The clinical data of the patient's age, gender, body mass index, laboratory examination, surgical status, etc. were collected. AKI diagnostic criteria of the 2012 KDIGO guidelines were used to diagnose the occurrence of AKI after surgery. The independent predictors of AKI were determined by multivariate logistic regression. Results: The age of this patient cohort was (69±15) years. The prevalence of AKI was 45.4% (300/661). Multivariate logistic regression showed that urine protein semi-quantitative ≥2+(OR=2.62, 95%CI: 1.05-6.56, P=0.039) was independent factor for postoperative AKI in critically ill patients undergoing non-cardiac surgery, other independent factors include higher age (OR=1.04, 95%CI: 1.02-1.06, P=0.001), higher body mass index (BMI) (OR=1.12, 95%CI: 1.04-1.21, P=0.004), lower plasma hemoglobin level (OR=0.98, 95%CI: 0.97-1.00, P=0.019), lower central venous pressure (OR=0.89, 95%CI: 0.83-0.97, P=0.005) and lower total hypotension time (OR=1.01, 95%CI: 1.00-1.01, P=0.041). Conclusions: Urine protein semi-quantitative ≥2+after surgery is an independent predictive factor for the occurrence of postoperative AKI in critically ill patients undergoing non-cardiac surgery. It is important to check urine routine immediately after surgery to detect and deal with high-risk patients.


Southwestern national park service employee risk, knowledge, and concern for triatomine exposure: A qualitative analysis using a novel knowledge, attitudes, and practices survey.
Chagas disease (CD), caused by the parasite Trypanosoma cruzi, is a neglected parasitic infection in the United States (US). In the Southwestern US, National Park Service (NPS) employees are a unique population with potential exposure to CD. This population lives in close contact with several species of sylvatic triatomine bugs, the vectors of T. cruzi, that may enter residential buildings at night. Despite the higher potential risk of CD transmission for southwestern NPS employees, the socio-cultural factors that impact autochthonous CD transmission in the US remain unknown. To address this gap, we investigated how NPS employee knowledge and attitudes impact their triatomine preventive behaviors. We distributed a 42-item online questionnaire to NPS employees at four national parks in Arizona and Texas. We detected high self-reported bite exposure in NPS housing, despite moderate- to high-frequency of prevention behaviors. Specific behaviors, such as often or always repairing window screens, were associated with a decreased risk of putative triatomine bug exposure. Additionally, NPS employees had low knowledge of CD. For those with greater knowledge of CD, it was not associated with increased frequency of prevention behavior. We found that increased CD anxiety was associated with increased personal agency to reduce the risk of CD. These results demonstrate the influence of knowledge and attitudes regarding CD on triatomine prevention behavior within a potential high-risk population in the US, and the importance of utilizing strategies beyond provision of education to influence behaviors.


Bayesian motion estimation accounts for a surprising bias in 3D vision.
Determining the approach of a moving object is a vital survival skill that depends on the brain combining information about lateral translation and motion-in-depth. Given the importance of sensing motion for obstacle avoidance, it is surprising that humans make errors, reporting an object will miss them when it is on a collision course with their head. Here we provide evidence that biases observed when participants estimate movement in depth result from the brain's use of a "prior" favoring slow velocity. We formulate a Bayesian model for computing 3D motion using independently estimated parameters for the shape of the visual system's slow velocity prior. We demonstrate the success of this model in accounting for human behavior in separate experiments that assess both sensitivity and bias in 3D motion estimation. Our results show that a surprising perceptual error in 3D motion perception reflects the importance of prior probabilities when estimating environmental properties.


Physiological, Biochemical, and Root Proteome Networks Revealed New Insights Into Salt Tolerance Mechanisms in Pongamia pinnata (L.) Pierre.
Cultivation of potential biofuel tree species such as Pongamia pinnata would rehabilitate saline marginal lands toward economic gains. We carried out a physiological, biochemical, and proteomic analysis to identify key regulatory responses which are associated with salt tolerance mechanisms at the shoot and root levels. Pongamia seedlings were grown at 300 and 500 mM NaCl (∼3% NaCl; sea saline equivalent) concentrations for 15 and 30 days, gas exchange measurements including leaf net photosynthetic rate (A sat ), stomatal conductance (g s ), and transpiration rate (E), and varying chlorophyll a fluorescence kinetics were recorded. The whole root proteome was quantified using the free-labeled nanoLC-MS/MS technique to investigate crucial proteins involved in signaling pathways associated with salt tolerance. Pongamia showed no visible salt-induced morphological symptoms. However, Pongamia showed about 50% decline in gas exchange parameters including A sat , E, and g s 15 and 30 days after salt treatment (DAS). The maximum potential quantum efficiency of photosystem (PS) II (Fv/Fm) was maintained at approximately 0.8 in salt-treated plants. The thermal component of PSII (DIo) was increased by 1.6-fold in the salt-treated plants. A total of 1,062 protein species were identified with 130 commonly abundant protein species. Our results also elucidate high abundance of protein species related to flavonoid biosynthesis, seed storage protein species, and carbohydrate metabolism under salt stress. Overall, these analyses suggest that Pongamia exhibited sustained leaf morphology by lowering net photosynthetic rates and emitting most of its light energy as heat. Our root proteomic results indicated that these protein species were most likely recruited from secondary and anaerobic metabolism, which could provide defense for roots against Na+ toxicity under salt stress conditions.


Clostridium difficile in retail meat products, USA, 2007.
To determine the presence of Clostridium difficile, we sampled cooked and uncooked meat products sold in Tucson, Arizona. Forty-two percent contained toxigenic C. difficile strains (either ribotype 078/toxinotype V [73%] or 027/toxinotype III [NAP1 or NAP1-related; 27%]). These findings indicate that food products may play a role in interspecies C. difficile transmission.


How threat perceptions relate to learning and conspiracy beliefs about COVID-19: Evidence from a panel study.
According to appraisal theory, individuals cope with perceived threats in different ways. If engaging in problem-focused coping, for example, they may seek information useful for eliminating the root cause of the threat. However, during crises such as the COVID-19 pandemic, people tend to navigate complex information environments marked by high levels of uncertainty. In such contexts, individuals may adopt maladaptive behaviours-for instance, avoiding information or switching to pseudo-epistemic coping-in which they engage with non-scientific explanations. As a consequence, they may learn less from their information environment and become susceptible to conspiracy theories. Against that background, we investigated how threat perceptions relate to learning, believing in conspiracy claims and conspiracy thinking in context of the COVID-19 pandemic. Drawing from two-wave panel data, we found that threat perceptions were associated with a decrease in knowledge and an increase in believing conspiracy claims. Taken together, our findings indicate that high levels of threat perceptions in uncertain information environments may impede societal learning and encourage conspiracy beliefs. Thus, although provoking general anxiety may support short-term political goals, including adherence to policy during crises, accumulated threat perceptions may adversely affect citizens' motivation to cooperate in the long term.


Implanted tumor growth is suppressed and survival is prolonged in sixty percent of food-restricted mice.
To examine the effect of food restriction on immune functions in the tumor-bearing state, mice were divided into a control group (fed 5.0 g diet/d; 71 kJ/d) and a 60% food-restricted group (fed 3.0 g diet/d; 43 kJ/d) at 8-wk of age, and 4 wk later, L1210 tumor cells were inoculated intradermally. In the food-restricted mice, tumor growth was significantly suppressed, and mean survival time after the tumor inoculation was prolonged (P < 0.05). The plasma concentrations of two antitumor cytokines, interferon-gamma (IFN-gamma) and tumor necrosis factor-alpha (TNF-alpha), were greater in the food-restricted group before tumor inoculation (P < 0. 05). Furthermore, the food-restricted mice had significantly higher plasma levels of IFN-gamma and TNF-alpha after tumor inoculation, although the treatment significantly increased these cytokine levels in both groups. Splenic natural killer cell cytotoxicity was also higher in the tumor-bearing food-restricted mice than in controls (P < 0.05). Food-restricted mice have strong antitumor immunity, and as a result, tumor growth is suppressed and survival time is prolonged in these mice.


Effect of dentin phosphoprotein on phosphate-induced apoptosis of odontoblast-like cells.
Dentin phosphoprotein, the major noncollagenous protein in dentin, has effects on differentiation of odontoblast-like cells. This study was designed to investigate the effect of the protein on apoptosis of the cells. The odontoblast-like cells were prepared from the pulp cells of rat incisors. Apoptosis was detected by measuring caspase-3 activity by using DEVD-AMC as a fluorescent substrate. The cells formed calcification nodules in the presence of 2-glycerophosphate and expressed dentin sialophosphoprotein. Apoptosis was not observed in the cells through the differentiation stages. Then, apoptosis was induced by raising inorganic phosphate concentration in the medium. Elevation of phosphate concentration to 5 mM reduced the number of viable cells and increased caspase-3 activity, indicating the induction of apoptosis. Addition of bovine dentin phosphoprotein in the medium suppressed phosphate-induced apoptosis. Phosvitin and poly(Asp) had similar antiapoptotic effects.


Signal transduction by the B-cell antigen receptor.
The antigen receptor of B lymphocytes (BCR) plays important roles in recognition of foreign antigens and self-components to allow the immune system to make appropriate antibody responses. The BCR is a complex between membrane immunoglobulin and the Ig-alpha and Ig-beta heterodimer. Site-directed mutagenesis experiments have shown that the mu heavy chain transmembrane domain plays a key role in the association of mIgM with Ig-alpha/Ig-beta. In the absence of complex formation, mIgM is retained in the endoplasmic reticulum, and this function is also specified by the mu chain transmembrane domain. The ability of various mutant mIgM molecules to associate with Ig-alpha/Ig-beta correlates well with their ability to induce signal transduction reactions such as protein tyrosine phosphorylation and phosphoinositide breakdown. Thus, the signaling ability of the BCR appears to reside in the Ig-alpha/Ig-beta heterodimer. The cytoplasmic domains of Ig-alpha and Ig-beta each contain an ITAM sequence, which is defined by its limited homology with subunits of the T-cell antigen receptor and of Fc receptors. Moreover, chimeric proteins containing these ITAMs and surrounding sequences from the cytoplasmic domains of Ig-alpha or Ig-beta exhibit signaling function characteristics of the intact BCR. The Ig-alpha and Ig-beta chimeras are each capable of inducing all of the BCR signaling events tested and thus represent redundant functions. Cross-linking these chimeras leads to their phosphorylation and to binding of the intracellular tyrosine kinases Lyn and Syk. The BCR expressed in the nonlymphoid AtT20 cells, which express the Src-family tyrosine kinase Fyn but not Syk, was not able to trigger vigorous signaling reactions. Introduction of the active form of Syk into these cells restored some signaling events. These results are consistent with a model in which the ITAMs act to initiate the BCR signaling reactions by binding and activating tyrosine kinases.


Inequality of access to surgical specialty health care: why children with government-funded insurance have less access than those with private insurance in Southern California.
More than 25 million children in the United States are dependent on federal and state medical insurance programs for their health care needs. In California, 3.25 million children depend on Medi-Cal for their health insurance. In Southern California alone, the figure is as high as 1.81 million. However, 9.30 million children nationally and 1.55 million in California have no health insurance. Various public policies that would increase enrollment in these programs are being discussed to address this problem. However, before their implementation, it is important to understand what impact such policies would have on the actual delivery of health care to this patient population. In California, 2 predominant health care delivery models exist for Medi-Cal: a fee-for-service (so-called regular or straight Medi-Cal) and a managed care plan. One third of the children in Medi-Cal in the state are enrolled in the fee-for-service plan with the remainder in the managed care plan, whereas in Southern California, this figure is slightly lower at 28% in the fee-for-service plan. The objective of this study was to determine the number of otolaryngologists in Southern California who would offer a new patient appointment for an evaluation for tonsillectomy for a child with commercial insurance versus government-funded (Medi-Cal) insurance through direct contact with the physician and to determine whether the surgeon would offer to perform the procedure or refer the patient to another institution and to identify the specific reason(s) for any disparity in access to health care. A written questionnaire was sent via regular mail to 303 otolaryngologists in the Southern California area in 2003. A total of 100 fully completed questionnaires were received. Ninety-seven surgeons would offer an office appointment to a child with commercial insurance as compared with only 27 for a child with Medi-Cal. Of those 27 surgeons, 8 would then refer the child to another physician to perform the surgery, and only 19 would actually offer to perform surgery, if indicated. Reasons provided for not offering an office appointment or surgery for the child with Medi-Cal include excessive paperwork and/or administrative burdens (96%), low monetary reimbursement for the surgery (92%), and low monetary reimbursement for the office visit (87%). There is a tremendous inequality of access to surgical specialty health care for children with government-funded insurance when compared with those with commercial insurance in Southern California. Physicians indicate that this disparity is related to excessive administrative burdens and low monetary reimbursement. The implications of our findings on public health care policies are discussed.


Effectiveness of low-Dye taping for the short-term treatment of plantar heel pain: a randomised trial.
Plantar heel pain is one of the most common musculoskeletal disorders of the foot and ankle. Treatment of the condition is usually conservative, however the effectiveness of many treatments frequently used in clinical practice, including supportive taping of the foot, has not been established. We performed a participant-blinded randomised trial to assess the effectiveness of low-Dye taping, a commonly used short-term treatment for plantar heel pain. Ninety-two participants with plantar heel pain (mean age 50 +/- 14 years; mean body mass index 30 +/- 6; and median self-reported duration of symptoms 10 months, range of 2 to 240 months) were recruited from the general public between February and June 2005. Participants were randomly allocated to (i) low-Dye taping and sham ultrasound or (ii) sham ultrasound alone. The duration of follow-up for each participant was one week. No participants were lost to follow-up. Outcome measures included 'first-step' pain (measured on a 100 mm Visual Analogue Scale) and the Foot Health Status Questionnaire domains of foot pain, foot function and general foot health. Participants treated with low-Dye taping reported a small improvement in 'first-step' pain after one week of treatment compared to those who did not receive taping. The estimate of effect on 'first-step' pain favoured the low-Dye tape (ANCOVA adjusted mean difference -12.3 mm; 95% CI -22.4 to -2.2; P = 0.017). There were no other statistically significant differences between groups. Thirteen participants in the taping group experienced an adverse event however most were mild to moderate and short-lived. When used for the short-term treatment of plantar heel pain, low-Dye taping provides a small improvement in 'first-step' pain compared with a sham intervention after a one-week period.


Concordance of common movement disorders among familial cases.
Multicase families are frequently utilized in studies of movement disorders (MDs). We report families with two or more MD cases seen at the Movement Disorder Clinic, Saskatoon (MDCS). In 30% of the MD probands, there was either a history or documentation of at least one secondary MD case in the family. Only those MD cases that were seen at the MDCS were considered in this study. A total of 56 probands and 77 secondary MD cases were seen at the MDCS between 1968 and 1996. In 24 (31.2%) of the secondary cases, the diagnosis was different from that in the proband. In 46 families (82%), only one secondary case was seen, and the diagnosis was concordant with the proband in 71.7%. In the remaining 10 families with two or more secondary cases, the diagnosis was concordant in 64.5% of cases. The largest subgroup was Parkinson's disease (PD)--40 probands and 53 secondary cases. of these secondary cases, 73.6% had PD. The concordance rate was 91% in essential tremor, but only 12.5% if the proband had essential tremor + parkinsonism. Considering that a large proportion of secondary cases have a diagnosis discordant with the proband, we recommend that, whenever possible, MD diagnosis in secondary cases be based on clinical assessment.


Human recombinant luteinizing hormone is as effective as, but safer than, urinary human chorionic gonadotropin in inducing final follicular maturation and ovulation in in vitro fertilization procedures: results of a multicenter double-blind study.
In a prospective, comparative, dose-finding study, the minimal effective dose of recombinant human LH (rhLH) required to induce final follicular maturation and early luteinization in patients undergoing in vitro fertilization and embryo transfer was determined. In addition, the efficacy and safety of rhLH were compared with urinary human CG (u-hCG). A total of 259 infertile women, aged 18-39 yr, were enrolled in the study. After pituitary desensitization using a GnRH agonist, rhFSH was administered for ovarian stimulation. Patients then received either rhLH or u-hCG to achieve final follicular maturation. The doses of rhLH administered were 5,000, 15,000, 30,000, or 15,000 + 10,000 IU (second injection administered 3 days after the first injection; 129 patients), and those of u-hCG were consistently 5,000 IU (121 patients). Ovum pick-up was performed 34--38 h after rhLH or u-hCG injection. After fertilization in vitro, up to three embryos were replaced in the uterine cavity. The numbers of oocytes retrieved after u-hCG or rhLH administration were not significantly different between the four different doses of rhLH, when compared with each corresponding u-hCG group, nor when compared with the pool of all u-hCG groups. Similarly, there were no statistically significant differences in: the number of oocytes retrieved per follicle with a diameter of over 10 mm on the day of u-hCG or rhLH administration; the number of patients with at least one oocyte retrieved; oocyte nuclear maturity; oocyte potential for fertilization; the number of embryos; the number of total, biochemical, and clinical pregnancies; and the embryo implantation rate. However, in many of these parameters, the lowest dose of rhLH seemed suboptimal when compared with the higher dose. In terms of safety, rhLH was well tolerated at a dose of up to 30,000 IU. Moderate ovarian hyperstimulation syndrome (OHSS) was reported in 12.4% of patients who received u-hCG and 12.0% of patients who received two injections of rhLH. No moderate or severe OHSS was reported in patients who received a single dose of rhLH up to 30,000 IU. The results show that a single dose of rhLH is effective in inducing final follicular maturation and early luteinization in in vitro fertilization and embryo transfer patients and is comparable with 5,000 IU u-hCG. A single dose of rhLH results in a highly significant reduction in OHSS compared with hCG. The dose of rhLH giving the highest efficacy to safety ratio was between 15,000 and 30,000 IU.


Radiation risk estimation models.
Cancer risk models and their relationship to ionizing radiation are discussed. There are many model assumptions and risk factors that have a large quantitative impact on the cancer risk estimates. Other health end points such as mental retardation may be an even more serious risk than cancer for those with in utero exposures.


Marjolin's ulcer: a rare entity with a call for early diagnosis.
Marjolin's ulcer (MU) is an umbrella term covering squamous cell carcinoma (SCC), basal cell carcinoma and malignant melanoma that develop in chronic wounds, sinuses or scars. Cutaneous (non-MU) SCC is related to excessive sun-exposure, with Fitzpatrick skin types I and II being more susceptible. Radiation, genetic disorders (eg, Xeroderma pigmentosum) and immunosuppression, are other important risk factors often involved in the development of cutaneous malignancies and may also be involved in the development of MU. MU, first described by Jean-Nicholas Marjolin in 1828, is more aggressive than non-MU SCC, with a higher potential for early metastasis. A high index of suspicion and early histological diagnosis in chronic wounds and unstable scars with recent changes in characteristics offer the best prognosis with treatment. We present a case alongside a literature review contrasting the characteristics of MU and non-MU SCC, and suggest a management plan for early MU identification and prevention.


Sympathetic overactivity in hypertension and cardiovascular disease.
From the first description of its anatomy by T. Willis to the novel therapeutic manipulations, it is unanimously recognized that the sympathetic nervous system (SNS) holds a crucial role in cardiovascular homeostasis. The introduction of sophisticated techniques, as microneurography and regional norepinephrine spillover provided the evidence for the role of sympathetic overactivity in various cardiovascular disease entities. Sympathetic activation is common in patients with essential hypertension and contributes to initiation, maintenance and progression of the disease and it contributes to the manifestation of its major complications. A considerable body of evidence relates SNS overactivity with high sodium intake in experimental animals and humans and the underlying mechanisms have nowadays been elucidated. SNS activity is more pronounced in patients with resistant hypertension and there are several conditions that lead to this phenomenon, as older age, kidney disease, obesity and metabolic syndrome, mental stress and sleep apnea. SNS overactivity holds also a key physiopathological role in heart failure, acute coronary syndromes and arrhythmias. Moreover, inhibition of sympathetic overactivity by various means, including central SNS suppressing drugs, peripheral alpha- and beta- adrenergic receptor blockers, or novel approaches as renal sympathetic denervation have been used successfully in the treatment of all these disorders.


First Extensive Analysis of 18F-Labeled Fluorodeoxyglucose Positron Emission Tomography-Computed Tomography in a Large Cohort of Patients With HIV-Associated Hodgkin Lymphoma: Baseline Total Metabolic Tumor Volume Affects Prognosis.
18F-labeled fluorodeoxyglucose positron emission tomography with computed tomography (18F-FDG PET-CT) data in HIV-associated Hodgkin lymphoma (HIV-HL) are scarcely reported. In addition to the description of the characteristics of both baseline and interim 18F-FDG PET-CT examinations (PET1 and iPET, respectively), the aim of this study was to assess the prognostic value of PET1 and previously identified clinical parameters in this population. PET1 of 109 patients with HIV-HL, treated with doxorubicin, bleomycin, vinblastine, and dacarbazine chemotherapy regimen since 2007, and 104 iPET were centrally reviewed. All the patients were enrolled in an ongoing prospective single-center cohort of HIV-associated lymphoma. Most patients had a disseminated disease according to the Ann Arbor classification (30% stage III and 43% stage IV), with especially bone marrow and liver as extranodal localizations. After a median follow-up of 6.7 years, 12 patients relapsed (11%) and 13 died (12%). Five-year progression-free survival (PFS) was 75.1%, and 5-year overall survival was 86.1%. Median total metabolic tumor volume (TMTV) was 121.4 cm3. The optimal TMTV cutoff identified for prognostic analysis was 527 cm3, with a 2-year PFS of 71% in the 20 patients with TMTV > 527 cm3, compared with 91% in the 89 patients with TMTV ≤ 527 cm3 (P = .004). On multivariate analysis, a high TMTV was the only parameter independently associated with PFS. In this large series of HIV-HL patients with a homogeneous management, high TMTV on PET1 examination was associated with a poor prognosis.


[Medical treatment of arteriosclerosis obliterans (ASO)].
The medical treatment of ASO should be approached in three ways. The first should be to minimize the risk factors of "atherosclerosis", the second should be the treatment of leg ischemia, and the third should be the management of other ischemic organs. Among the risk factors involved, cigarette smoking, diabetes mellitus and hyperlipidemia are frequently evident. Smoking must be given up and the other diseases should be controlled by diet, exercise and drug therapy respectively. In order to relieve symptoms such as cold sensation and intermittent claudication, drug therapy such as antiplatelet therapy and vasodilatory drugs are useful in the treatment of some patients with ASO. Daily physical exercises are also effective in extending the walking distance in patients with intermittent claudication. This exercise is even more effective when it is combined with drug therapy. The prevention of vascular events such as myocardial infarction and stroke and the prevention of vascular death are very important in patients with ASO. It can therefore be concluded that antiplatelet therapy is not only effective in relieving symptoms, but also in reducing the incidence of vascular events and death.


Immunostimulatory role of tryptic digest of Abrus agglutinin.
Many bioactive peptides are in therapeutic use as immunomodulators at present. The origin of these bioactive peptides is diverse. Such bioactive peptides are reported to be present in enzymatic digest of food and milk proteins. In our previous work we have reported that Abrus agglutinin retains its bioactivity even after heat denaturation but loses its haemagglutination properties. This leads to the supposition that immunostimulatory regions in the protein might be responsible for its in vivo and in vitro stimulatory properties. Thus the bioactivity of tryptic digest of Abrus agglutinin (TDA) was checked in vitro to ascertain the presence of some bioactive region in the protein, which will lead to the discovery of certain immunostimulatory peptides which might be of use in nonspecific immunotherapy. In this study it is observed that TDA stimulates macrophage increasing the phagocytic and bactericidal activity as well as hydrogen peroxide production. TDA also proliferates splenocytes leading to Th1 response and NK cell activation.


Inhibition of Semaphorin 4D/Plexin-B1 signaling inhibits the subchondral bone loss in early-stage osteoarthritis of the temporomandibular joint.
The aim of this study was to demonstrate the biological function of Semaphorin 4D (Sema4D)/Plexin-B1 in the bone formation features of osteoblasts in early-stage temporomandibular joint (TMJ) osteoarthritis. Sema4D/Plexin-B1, expressed by osteoclasts/osteoblasts, plays a balancing role in bone formation and resorption. However, previous studies have mainly focused on bone resorption by osteoclasts in early-stage osteoarthritis. This study used our reported experimental unilateral anterior crossbite (UAC) mouse model to explore subchondral bone changes, which were assessed by micro-CT analysis. The changes in osteoblasts were investigated after the inhibition of Sema4D by BMA-12 injection with the detection of bone formation-related markers. A Transwell migration assay was performed to reveal the specific impact of Sema4D on osteoblasts in vitro. The data demonstrated that subchondral bone loss in early-stage TMJ osteoarthritis was accompanied by the upregulated expression of Sema4D in cartilage and subchondral bone and Plexin-B1 in subchondral bone. Reducing Sema4D levels could inhibit subchondral bone loss and cartilage degeneration in early-stage TMJ osteoarthritis. In vitro, the results revealed that Sema4D could reduce the expression of osteocalcin and alkaline phosphatase and increase the migrating capability of Plexin-B1-positive osteoblasts. Our results revealed that elevated Sema4D expression in early-stage TMJ osteoarthritis might decrease the bone formation activity of osteoblasts in the subchondral bone by binding to Plexin-B1 expressed by osteoblasts. Inhibiting Sema4D/Plexin-B1 signaling in early-stage osteoarthritis represents a promising strategy for new therapeutic approaches to osteoarthritis.


International cooperation in neonatal screening: technical training course for newborn and infant screening.
We report the outline and results of our experience with a group training course of neonatal screening for health care professionals in developing countries. Sapporo City Institute of Public Health (SCIPH) has been offered a training course on neonatal screening once a year since 1991 under the Technical Training Program of the Japan International Cooperation Agency (JICA). The aims of this training course are to enhance the participants' technical knowledge and skills, and also to deepen their understanding of the principle of neonatal screening as well as the relevant diseases. Lectures and laboratory practice on phenylketonuria (PKU), congenital hypothyroidism (CH), congenital adrenal hyperplasia (CAH) and neuroblastoma are included in the 3-month program. After the completion of the training, participants are expected to play a major role in establishing and expanding neonatal screening system in each of their countries. We have received a total of 67 participants from 25 countries until March 1998: 58 pediatricians; 2 gynecologists; 6 biochemists; 1 administrative officer. After they returned to their countries, 11 engaged in neonatal screening and started PKU and CH screening in their institute, city or province in Argentina, Brazil, Mexico, Peru and Thailand. We believe that these results fulfilled our objectives. Also, for follow-up, SCIPH has been giving information and consultation to the participants on requests. This international cooperation network could also benefit our present network of the International Society Screening in the future.


A woman with dyspnea and recurrent pneumothorax: when dyspnea is not asthma.
Lymphangioleiomyomatosis (LAM) is a rare disease characterized by cystic lung lesions, lymphatic abnormalities, and angiomyolipomas. It can take a significant amount of time to diagnose LAM due to the vague symptoms of fatigue, progressive dyspnea, pneumothorax, and pleural effusion. We present a case of a 29-year-old woman with recurrent spontaneous pneumothorax and progressive dyspnea who was initially misdiagnosed with asthma and was later found to have LAM. As with all rare diagnoses, there needs to be a suspicion of the disease in order for a further workup to be initiated. In patients with a compatible High-resolution CT scan of the chest, a high vascular endothelial growth factor-D (VEGF-D) value is diagnostic for LAM, and no other confirmatory test is needed.


SARS-CoV-2 Placental Infection in an Unvaccinated Mother Resulting in Fetal Demise.
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in pregnancy may have devastating complications including fetal demise. Here, we describe a case of SARS-CoV-2 infection in a second-trimester pregnancy. The placenta demonstrated the presence of SARS-CoV-2 viral RNA along with intervillositis and perivillous fibrin deposition. SARS-CoV-2 directly infects the trophoblastic cells of the placenta through the angiotensin-converting enzyme 2 receptor. This case report details the clinical history of a SARS-CoV-2-infected pregnancy with fetal demise. In addition, we show the images of the placental pathology and SARS-CoV-2 RNA in situ studies.


Subcellular Localization of Asparaginase and Asparagine Aminotransferase in Pisum sativum Leaves.
Protoplasts isolated from young and mature pea leaves (Pisum sativum L.) were broken and their contents fractionated by differential centrifugation or on sucrose-density gradients. Asparaginase was found only in the cytosol of young leaves. Asparagine aminotransferase was found in both young and mature leaves and was localized exclusively in the peroxisome. This corroborates the observation that asparagine transamination is catalyzed by the serine:glyoxylate aminotransferase.


β-Mannosidosis in German Shepherd Dogs.
A neurological disease was investigated in 3 German Shepherd pups from the same litter that failed to grow normally, appeared stiff, were reluctant to move, and were deaf. They developed intermittent seizures and ataxia and had proprioceptive defects. Histopathology showed severe vacuolation of neurons, astrocytes in nervous tissue, renal tubular epithelial cells, and macrophages in nervous tissue, spleen, and liver. Vacuoles appeared empty with no storage material stained by periodic acid-Schiff (PAS) or Sudan black stains, leading to a diagnosis of a lysosomal storage disease and in particular an oligosaccharidosis. Biochemical and genomic studies showed that this was β-mannosidosis, not previously diagnosed in dogs. A c.560T>A transition in exon 4 of the MANBA gene was found, which segregated in these and other family members in a manner consistent with it being the causative mutation of an autosomal recessive disease. This mutation led to substitution of isoleucine to asparagine at position 187 of the 885 amino acid enzyme, a change expected to have functional significance.


Structural differences of oxidized iron-sulfur and nickel-iron cofactors in O2-tolerant and O2-sensitive hydrogenases studied by X-ray absorption spectroscopy.
The class of [NiFe]-hydrogenases comprises oxygen-sensitive periplasmic (PH) and oxygen-tolerant membrane-bound (MBH) enzymes. For three PHs and four MBHs from six bacterial species, structural features of the nickel-iron active site of hydrogen turnover and of the iron-sulfur clusters functioning in electron transfer were determined using X-ray absorption spectroscopy (XAS). Fe-XAS indicated surplus oxidized iron and a lower number of ~2.7 Å Fe-Fe distances plus additional shorter and longer distances in the oxidized MBHs compared to the oxidized PHs. This supported a double-oxidized and modified proximal FeS cluster in all MBHs with an apparent trimer-plus-monomer arrangement of its four iron atoms, in agreement with crystal data showing a [4Fe3S] cluster instead of a [4Fe4S] cubane as in the PHs. Ni-XAS indicated coordination of the nickel by the thiol group sulfurs of four conserved cysteines and at least one iron-oxygen bond in both MBH and PH proteins. Structural differences of the oxidized inactive [NiFe] cofactor of MBHs in the Ni-B state compared to PHs in the Ni-A state included a ~0.05 Å longer Ni-O bond, a two times larger spread of the Ni-S bond lengths, and a ~0.1 Å shorter Ni-Fe distance. The modified proximal [4Fe3S] cluster, weaker binding of the Ni-Fe bridging oxygen species, and an altered localization of reduced oxygen species at the active site may each contribute to O2 tolerance.


Investigation of the Neuropathic Pain Caused by Syringomyelia Associated with Chiari I Malformation.
Retrospective cohort study. To investigate the correlation between the syrinx morphology and neuropathic pain caused by syringomyelia associated with Chiari I malformation. Neuropathic pain caused by syringomyelia is refractory and markedly impairs the patient. We examined 24 patients with neuropathic pain caused by syringomyelia associated with Chiari I malformation. We statistically analyzed the illness duration and age at surgery between patients with and without neuropathic pain. Additionally, we classified the morphology of the syringes into deviated (D), enlarged (E), central (C), and bulkhead (B) types using T2-weighted axial imaging. Moreover, we investigated the correlation between syrinx morphology and neuropathic pain. A Mann-Whitney U-test was performed to compare between the presence or absence of neuropathic pain and the presence or absence of type D syringes. The median age at surgery was 27.5 years, and the median illness duration was 24 months. Among the 24 patients, 11 had preoperative neuropathic pain, one of which was free of neuropathic pain during the final follow-up period. Among patients with neuropathic pain, the syringes' preoperative morphology was type D in nine patients and types E and C in one patient each. No patient exhibited type B morphology. Among patients without neuropathic pain, the preoperative morphology of the syringes was type D in three patients, type E in seven patients, and types C and B in two patients each. For types D and E, a correlation between neuropathic pain and syrinx morphology was observed. Moreover, type D was associated with significant neuropathic pain in both preoperative and postoperative states. This study showed a correlation between the morphological features of the syringes and the occurrence of neuropathic pain in patients with syringomyelia associated with Chiari I malformation.


Receptor-mediated stimulatory effect of IL-1 beta on hyaluronic acid and proteoglycan biosynthesis by cultured rat ovarian cells: role for heterologous cell-cell interactions.
An increasing body of information supports the possibility that intraovarian interleukin (IL)-1 may play an intermediary role in gonadotropin-triggered ovulation. To further evaluate this hypothesis, we have examined the effect of IL-1 beta on ovarian proteoglycan/glycosaminoglycan economy, an established corollary of the preovulatory cascade. Rat ovarian cells were metabolically labeled with [35S]sulfate and [3H]glucosamine for 48h in the absence or presence of IL-1 beta, with or without an IL-1 receptor antagonist (IL-1ra). At the conclusion of this treatment period, total 35S and 3H incorporation into cell-associated and extracellular proteoglycan/glycosaminoglycan species was determined. Treatment of whole ovarian dispersates with IL-1 beta (10 ng/ml) produced substantial increments in the accumulation of extracellular macromolecular material [11.5-, 2.9- and 2.6-fold for hyaluronic acid (HA), heparan sulfate (HS) and dermatan sulfate (DS) proteoglycans, respectively]. In contrast, only modest increments (< or = 1.7-fold) were noted for IL-1 beta-treated granulosa cells (GC), theca-interstitial cells (TC), or 4:1 co-cultures (GC/TC) thereof. Treatment of whole ovarian dispersates with IL-1 beta also resulted in significant (P < 0.001) increments in the cell-associated accumulation of both HA (6.0-fold increase) and DS proteoglycans (3.4-fold increase). However, the cell-associated accumulation of HS proteoglycan was not significantly affected by IL-1 beta regardless of the cellular preparation under study. The concurrent provision of IL-1ra (5 micrograms/ml) all but neutralized the IL-1 beta effect on HA biosynthesis thereby suggesting mediation by specific ovarian IL-1 receptor(s). Taken together, these observations suggest that treatment of ovarian cells with IL-1 beta results in an overall increase in macromolecular biosynthesis as well as in redistribution favoring extracellular HA and DS (but not HS) proteoglycans. Moreover, since whole ovarian dispersates proved more responsive to IL-1 than isolated cellular components thereof, the present observations suggest an obligatory requirement for heterologous cell-cell interaction without which optimal HA or proteoglycan biosynthesis may not be realized. These observations along with the demonstration of IL-1-mediated amplification of gonadotropin-triggered ovulation provide strong indirect support for the view that IL-1 may be the centerpiece of an intraovarian regulatory loop concerned with the promotion of key periovulatory events.


Clinical evaluation of a low junction of the cystic duct.
The point of the junction of the cystic duct with the common hepatic duct was studied by means of various preoperative and intraoperative cholangiographic procedures and by gross intraoperative examinations in 468 surgical patients with biliary diseases. The cystic duct entered the hepatic duct at a very low position and was consequently long in 39 patients. The clinical significance of this abnormally low junction of the cystic duct was studied in comparison with 358 patients with gallstones with a normal cystic duct-hepatic duct junction. In the low-junction group with a short common bile duct several complications, including gallstone pancreatitis (7 patients), the Mirizzi syndrome (7), confluence stones (2), gallbladder cancer (3), and congenital dilation of the cystic duct (1), were demonstrated preoperatively. The anomalous junction of the cystic duct with the common bile duct may cause stagnation of bile and/or reflux of pancreatic juice into the bile duct, producing a choledochopancreatic ductal junction and posing difficulties at surgery.


Urine protein-to-creatinine ratio: a point of care for the diagnosis of preeclampsia.
The aim of this study was to determine the correlation between the urine protein-creatinine ratio (UPCR) and the 24-hour urine protein excretion test (UPET), and to identify the optimal threshold values of UPCR for the diagnosis of preeclampsia and its severe form. This prospective cohort study included 81 hypertensive pregnant patients who had a 24-h UPET and a UPCR tests. Two groups were created using a UPCR cut-off of 23.2 mg/mmol (40 negative UPCR, 41 positive UPCR). Forty-nine patients of were diagnosed with preeclampsia, and 23 of them had a severe disease. There was a significant correlation between UPCR and 24-h UPET. A cut-off UPCR value of 23.2 mg/mmol had an area under the curve (AUC) of 0.27, sensitivity of 89%, specificity 88%, positive predictive value 90%, a positive likelihood ratio (+LR) of 7.41 and a negative likelihood ratio (-LR) of 0.13 for the diagnosis of preeclampsia. UPCR value of 325 mg/mmol had an AUC of 0.841, and a sensitivity of 83%, specificity 81%, positive predictive value 81%, +LR of 4.4 and -LR of 0.2 for the diagnosis of severe preeclampsia. The UPCR test is highly correlated with the 24-h UPET. We propose a novel and sensitive cut-off for the diagnosis of preeclampsia by UPCR test. The UPCR test can be used for the identification of hypertensive patients with preeclampsia and severe disease.


Antimicrobial Resistance: Is the World UNprepared?
Long Blurb: On September 21st 2016 the United Nations General Assembly convenes in New York, United States to tackle a looming and seemingly inevitable global challenge with the potential to threaten the health and wellbeing of all people: antimicrobial resistance. In an Editorial, the PLOS Medicine Editors reflect on the challenge of coordinating the response to antimicrobial resistance in order to ensure the viability of current antimicrobials and the development of new therapies against resistant pathogens. Short Blurb: In this month's Editorial, the PLOS Medicine Editors reflect on the upcoming United Nations General Assembly meeting which convenes to discuss the global challenge of antimicrobial resistance.


Fixed film phosphorus removal--flexible enough?
While biological phosphorus removal (BPR) has been practised for 30 years, up to recently it has been restricted mainly to activated sludge processes, with the corresponding need for large basin volumes. Yet, research with biofilm reactors showed that the principle of alternate anaerobic and aerated conditions was applicable to fixed bacteria by changing the conditions in time rather than in space. Attached growth enhanced biological phosphorus removal (EBPR) systems are attractive because of their compactness and capability to retain high biomass levels. However, the phosphorus extraction depends on backwashes to enhance the phosphorus-rich attached biomass, and correct control of unsteady effluent quality created by frequently modified process conditions. Accordingly, EBPR remains a challenging task in terms of combining nitrogen and phosphorus removal using attached growth systems. Nevertheless, a combination of activated sludge and biofilm carriers, in the integrated fixed-film activated sludge system, provides treatment opportunities not readily available using suspended growth systems. Current practice is only at the beginning of exploiting the full potential of this combination, but the first full-scale results show that compact tankage and low nutrient results based on biological principles are possible.


Array-based comparative genomic hybridization facilitates identification of breakpoints of a novel der(1)t(1;18)(p36.3;q23)dn in a child presenting with mental retardation.
Monosomy of distal 1p36 represents the most common terminal deletion in humans and results in one of the most frequently diagnosed mental retardation syndromes. This deletion is considered a contiguous gene deletion syndrome, and has been shown to vary in deletion sizes that contribute to the spectrum of phenotypic anomalies seen in patients with monosomy 1p36. We report on an 8-year-old female with characteristics of the monosomy 1p36 syndrome who demonstrated a novel der(1)t(1;18)(p36.3;q23). Initial G-banded karyotype analysis revealed a deleted chromosome 1, with a breakpoint within 1p36.3. Subsequent FISH and array-based comparative genomic hybridization not only confirmed and partially characterized the deletion of chromosome 1p36.3, but also uncovered distal trisomy for 18q23. In this patient, the duplicated 18q23 is translocated onto the deleted 1p36.3 region, suggesting telomere capture. Molecular characterization of this novel der(1)t(1;18)(p36.3;q23), guided by our clinical array-comparative genomic hybridization, demonstrated a 3.2 Mb terminal deletion of chromosome 1p36.3 and a 200 kb duplication of 18q23 onto the deleted 1p36.3, presumably stabilizing the deleted chromosome 1. DNA sequence analysis around the breakpoints demonstrated no homology, and therefore this telomere capture of distal 18q is apparently the result of a non-homologous recombination. Partial trisomy for 18q23 has not been previously reported. The importance of mapping the breakpoints of all balanced and unbalanced translocations found in the clinical laboratory, when phenotypic abnormalities are found, is discussed.


The deca-GX3 proteins Yae1-Lto1 function as adaptors recruiting the ABC protein Rli1 for iron-sulfur cluster insertion.
Cytosolic and nuclear iron-sulfur (Fe-S) proteins are involved in many essential pathways including translation and DNA maintenance. Their maturation requires the cytosolic Fe-S protein assembly (CIA) machinery. To identify new CIA proteins we employed systematic protein interaction approaches and discovered the essential proteins Yae1 and Lto1 as binding partners of the CIA targeting complex. Depletion of Yae1 or Lto1 results in defective Fe-S maturation of the ribosome-associated ABC protein Rli1, but surprisingly no other tested targets. Yae1 and Lto1 facilitate Fe-S cluster assembly on Rli1 in a chain of binding events. Lto1 uses its conserved C-terminal tryptophan for binding the CIA targeting complex, the deca-GX3 motifs in both Yae1 and Lto1 facilitate their complex formation, and Yae1 recruits Rli1. Human YAE1D1 and the cancer-related ORAOV1 can replace their yeast counterparts demonstrating evolutionary conservation. Collectively, the Yae1-Lto1 complex functions as a target-specific adaptor that recruits apo-Rli1 to the generic CIA machinery.


General, Auxiliary-Enabled Photoinduced Pd-Catalyzed Remote Desaturation of Aliphatic Alcohols.
A general, efficient, and site-selective visible light-induced Pd-catalyzed remote desaturation of aliphatic alcohols into valuable allylic, homoallylic, and bis-homoallylic alcohols has been developed. This transformation operates via a hybrid Pd-radical mechanism, which synergistically combines the favorable features of radical approaches, such as a facile remote C-H HAT step, with that of transition-metal-catalyzed chemistry (selective β-hydrogen elimination step). This allows achieving superior degrees of regioselectivity and yields in the desaturation of alcohols compared to those obtained by the state-of-the-art desaturation methods. The HAT at unactivated C(sp3)-H sites is enabled by the easily installable/removable Si-auxiliaries. Formation of the key hybrid alkyl Pd-radical intermediates is efficiently induced by visible light from alkyl iodides and Pd(0) complexes. Notably, this method requires no exogenous photosensitizers or external oxidants.


Risk-taking, peer-influence and child maltreatment: a neurocognitive investigation.
Maltreatment is associated with increased risk of a range of psychiatric disorders, many of which are characterized by altered risk-taking propensity. Currently, little is known about the neural correlates of risk-taking in children exposed to maltreatment, nor whether their risk-taking is atypically modulated by peer influence. Seventy-five 10- to 14-year-old children [maltreated (MT) group: N = 41; non-maltreated Group (NMT): N = 34] performed a Balloon Analogue Risk Task (BART), under three different peer influence conditions: while alone, while being observed by a peer and while being encouraged by a peer to take risks. The MT group engaged in less risk-taking irrespective of peer influence. There was no differential effect of peer influence on risk-taking behaviour across groups. At the neural level, the right anterior insula (rAI) exhibited altered risk sensitivity across conditions in the MT group. Across groups and conditions, rAI risk sensitivity was negatively associated with risk-taking and within the MT group greater rAI risk sensitivity was related to more anxiety symptoms. These findings suggest that children with a history of maltreatment show reduced risk-taking but typical responses to peer influence. Abnormal rAI functioning contributes to the pattern of reduced risk-taking and may predispose children exposed to maltreatment to develop future psychopathology.


Visualization of intrinsically disordered regions of proteins by high-speed atomic force microscopy.
Intrinsically disordered (ID) regions of proteins are recognized to be involved in biological processes such as transcription, translation, and cellular signal transduction. Despite the important roles of ID regions, effective methods to observe these thin and flexible structures directly were not available. Herein, we use high-speed atomic force microscopy (AFM) to observe the heterodimeric FACT (facilitates chromatin transcription) protein, which is predicted to have large ID regions in each subunit. Successive AFM images of FACT on a mica surface, captured at rates of 5-17 frames per second, clearly reveal two distinct tail-like segments that protrude from the main body of FACT and fluctuate in position. Using deletion mutants of FACT, we identify these tail segments as the two major ID regions predicted from the amino acid sequences. Their mechanical properties estimated from the AFM images suggest that they have more relaxed structures than random coils. These observations demonstrate that this state-of-the-art microscopy method can be used to characterize unstructured protein segments that are difficult to visualize with other experimental techniques.


Manipulation of the lighting schedule can modify the pharmacological effects of theophylline in chick embryos.
The effect of the lighting schedule on the pharmacological action of theophylline was studied in chick embryos. Fertile eggs of White Leghorns were incubated and investigated, on two occasions, under constant light conditions or under constant dark conditions. A single injection of theophylline 2.14, 4.29, 8.57 and 17.14 mg/egg into the air sac of fertile eggs was carried out on the 16th day of incubation. Electrocardiograms (ECGs) were recorded 0 to 60 min after drug injection. After drug injection, heart rate increased under constant light conditions, but decreased under dark conditions. In addition, arrhythmia was produced by theophylline, 17.14 mg/egg, under constant dark conditions. These results indicate that the manipulation of the lighting schedule may have a marked influence on the pharmacological effects of theophylline in chick embryos.


In silico investigation of FOXM1 binding and novel inhibitors in epithelial ovarian cancer.
Using TCGA database, we had demonstrated that aberrantly activated Forkhead box M1 (FOXM1) correlates to worse overall survival in a subgroup of platinum resistant patients. Application of thiostrepton, a natural thiazole antibiotics that inhibits FOXM1 transcription activity in the clinic is hampered by difficulties in synthesis, degradation potential, and solubility. In this study, we aim to identify potential FOXM1 small molecule inhibitors to develop a new class of therapeutic agents to address the challenges in treating chemotherapy resistant EOC. We used in silico screening of compounds against a solved structure of FOXM1 and subsequently to derive a list of possible compounds that could inhibit FOXM1. Three compounds were tested for in vitro cytotoxicity and FOXM1 expression level was confirmed by RT-PCR and Western blot in EOC cell lines. The FOXM1 structure obtained from 3G73 represented the DNA binding region of FOXM1 and possessed the winged helix fold representative of the Forkhead family of enzymes with two wings in direct contact with DNA. For ease of representation, we described both wings as a dimer and a single wing as a monomer. From this structure, we hypothesized two main models of how thiostrepton binding to FOXM1 could possibly curtail its transcriptional activity. In the first model thiostrepton could bind either of the wings or both wings and prevent association to DNA. In the second model thiostrepton bind the FOXM1/DNA complex and weaken association of FOXM1 to DNA. Subsequently, small molecular inhibitors could also use either of the models to inhibit transcription. To account for both models, the NCI diversity set was screened against the FOXM1 dimer:DNA complex (39 hits), dimer (11 hits) and monomer (14 hits). Those hits were further classified by chemical structure, biological function and chemical similarities to known molecules that target FOXM1. In cellular cytotoxicity assays, N-phenylphenanthren-9-amine (related to hit #225) successfully showed cytotoxicity to all three cell lines with IC50 around 1μM, and downregulate FOXM1 and transcription of its downstream molecules such as CCNB1. By a combination of in silico screening coupled to cellular cytotoxicity studies, we have taken the first step towards identifying potential inhibitors of FOXM1 that can replace thiostrepton.


[Prognostic factors in patients with primary non-Hodgkin's lymphoma of the tonsil].
To investigate the prognostic value of the size of primary tumor (T staging) and international prognostic index (IPI) for patients with non-Hodgkin's lymphoma (NHL) of the tonsil, and to recommend the treatment strategy for early stage patients. 306 patients with untreated NHL of the tonsil were reviewed. According to Ann Arbor staging classification, 35 patients had stage I, 178 stage II, 49 stage III and 44 stage IV disease. According to 1997' AJCC staging system, 29 patients had T1, 142 T2, 117 T3 and 18 T4 disease. Twelve stage I patients were given radiotherapy alone and 23 stage II patients were given combined modality therapy (CMT). For patients with stage II lesion, 57 were given radiotherapy alone, 2 chemotherapy alone and 119 CMT. Chemotherapy was the main treatment in patients with stage III or IV lesions. The 5-year cancer specific survival (CSS) was 74% for patients with T(1), 59% for T(2), 56% for T(3) and 26% for T(4), respectively (P = 0.000). The 5-year CSS was 70% for patients with 0 risk factor, 49% for 1 risk factor, 25% for 2 or 3 risk factor, respectively (P = 0.000). CMT significantly improved disease free survival (DFS) from 46% (radiotherapy alone) to 60% (CMT) for stage II patients (P = 0.046). Multivariate analysis showed that performance status, Ann Arbor staging, T staging, B symptom, and IPI were independent prognostic factors. The T staging of the primary tumor and IPI are the important prognostic factors of patients with NHL of the tonsil. Combined modality therapy significantly improves the disease free survival of stage II patients.


Molecular typing of methicillin-resistant Staphylococcus aureus by polymerase chain reaction: distribution of the typed strains in hospitals.
Three methods for molecular typing of methicillin-resistant Staphylococcus aureus using polymerase chain reaction (PCR) were compared. The method which amplified the variable number of tandem repeat of dru sequences grouped the isolates into six types. Whereas, the method examining restriction fragment length polymorphism of coagulase gene and the method using arbitrarily primed-PCR showed poor diversity in typing. We investigated the distribution of dru types in two hospitals. Obvious concentration of a type in one ward was not recognized in our hospital. In the other hospital, a rare type was detected from the inpatients in the pediatrics ward. It suggested that the infection was an epidemic. We also found that some patients were infected with more than two strains. Even if two isolates show the same type, it does not necessarily mean that they originated from one clone. However, this method brings meaningful information on nosocomial infection, more easily than other genotyping.


Changes in risk factors for preterm birth in Western Australia 1984-2006.
To characterise changing risk factors of preterm birth in Western Australia between 1984 and 2006. Population-based study. Western Australia. All non-Aboriginal women giving birth to live singleton infants between 1984 and 2006. Multinomial, multivariable regression models were used to assess antecedent profiles by preterm status and labour onset types (spontaneous, medically indicated, prelabour rupture of membranes [PROM]). Population attributable fraction (PAF) estimates characterized the contribution of individual antecedents as well as the overall contribution of two antecedent groups: pre-existing medical conditions (including previous obstetric history) and pregnancy complications. Antecedent relationships with preterm birth, stratified by labour onset type. Marked increases in maternal age and primiparous births were observed. A four-fold increase in the rates of pre-existing medical complications over time was observed. Rates of pregnancy complications remained stable. Multinomial regression showed differences in antecedent profiles across labour onset types. PAF estimates indicated that 50% of medically indicated preterm deliveries could be eliminated after removing six antecedents from the population; estimates for PROM and spontaneous preterm reduction were between 10 and 20%. Variables pertaining to previous and current obstetric complications (previous preterm birth, previous caesarean section, pre-eclampsia and antepartum haemorrhage) were the most influential predictors of preterm birth and adverse labour onset (PROM and medically indicated). Preterm antecedent profiles have changed markedly over the 23 years studied. Some changes may be attributable to true change, others to advances in surveillance and detection. Still others may signify change in clinical practice.


Chronic low back pain and its association with lumbar vertebrae and intervertebral disc changes in adults. A case control study.
This study was done to determine the association between chronic low back pain and vertebral fractures, intervertebral disc space (IDS) narrowing, vertebral osteophytes and spondylolisthesis among adults. This case control study was done in Sri Lanka. Cases were patients with low back pain and controls were without low back pain. Postero-anterior and lateral radiographs of lumbar sacral spine of both groups were studied. To detect vertebral fractures in fourth and fifth lumbar vertebrae, anterior and posterior heights of vertebrae were measured using a Vernier caliper and antero-posterior ratio (A/P) was calculated. Having an A/P ratio value of < 0.89 was considered as a vertebral fracture. Presence of disc space narrowing, vertebral osteophytes and spondylolisthesis was assessed by two radiologists working independently. Bivariate and logistic regression analysis was done to find associations. There were 140 cases and 140 controls. Mean (SD) age for cases was 51.6 (17) years. Mean (SD) age for controls was 50 (15) years. Females made up 62% of cases and controls. Fifth lumbar vertebral fracture (odds ratio [OR] = 10.2; P = 0.001), fourth lumbar vertebral fracture (OR = 2.5; P = 0.017) and IDS narrowing (OR = 4.15, P = 0.009) had a significant association with low back pain and vertebral osteophytes and spondylolisthesis did not have a significant association with low back pain. Only vertebral fractures and IDS narrowing had a significant association with chronic low back pain.


Structural Contributions to Autocatalysis and Asymmetric Amplification in the Soai Reaction.
Diisopropylzinc alkylation of pyrimidine aldehydes-the Soai reaction, with its astonishing attribute of amplifying asymmetric autocatalysis-occupies a unique position in organic chemistry and stands as an eminent challenge for mechanistic elucidation. A new paradigm of "mixed catalyst-substrate" experiments with pyrimidine and pyridine systems allows a disconnection of catalysis from autocatalysis, providing insights into the role played by reactant and alkoxide structure. The alkynyl substituent favorably tunes catalyst solubility, aggregation, and conformation while modulating substrate reactivity and selectivity. The alkyl groups and the heteroaromatic core play further complementary roles in catalyst aggregation and substrate binding. In the study of these structure-activity relationships, novel pyridine substrates demonstrating amplifying autocatalysis were identified. Comparison of three autocatalytic systems representing a continuum of nitrogen Lewis basicity strength suggests how the strength of N-Zn binding events is a predominant contributor toward the rate of autocatalytic progression.


A mitochondrial genome assembly of the opal chimaera, Chimaera opalescens Luchetti, Iglésias et Sellos 2011, using PacBio HiFi long reads.
Chondrichthyans (sharks, rays and chimeras) are a fascinating and highly vulnerable group of early branching gnathostomes. However, they remain comparatively poorly sampled from the point of view of molecular resources, with deep water taxa being particularly data deficient. The development of long-read sequencing technologies enables the analysis of phylogenetic relationships through a precise and reliable assembly of complete mtDNA genomes. The sequencing and characterization of the complete mitogenome of the opal chimera Chimera opalescens Luchetti, Iglésias et Sellos 2011, using the long-read technique PacBio HiFi is presented. The entire mitogenome was 23,411 bp long and shows the same overall content, i.e. 13 protein-coding genes, 22 transfer RNA and 2 ribosomal RNA genes, as all other examined Chondrichthyan mitogenomes. Phylogenetic reconstructions using all available Chondrichthyan mitogenomes, including 11 Holocephali (chimeras and ratfishes), places C. opalescens within the Chimaeridae family. Furthermore, the results reinforce previous findings, showing the genus Chimera as paraphyletic and thus highlighting the need to expand molecular approaches in this group of cartilaginous fishes.


Laser photocoagulation combined with subtenon injection of triamcinolone acetonide for diabetic cystoid macular edema.
To compare the effects of laser photocoagulation combined with subtenon injection of triamcinolone acetonide with photocoagulation alone, for diabetic cystoid macular edema. This retrospective comparative study analyzed data for 34 eyes with cystoid macular edema treated with photocoagulation alone (n=17) or combined with triamcinolone (n=17). All patients were followed for 6 months after the procedure. Laser photocoagulation included focal photocoagulation focused on microaneurysms and light grid photocoagulation spread over the edematous retina. Subtenon injection of triamcinolone (20 mg/0.5 cc) was performed in the superior-temporal conjunctiva. In the photocoagulation only group, the pretreatment mean visual acuity (VA) measured by the logarithm of the minimum angle of resolution (LogMAR) was 1.06+/-0.49. The number of laser spots was 34+/-10. The 6 -month post- treatment mean LogMAR was 1.13+/-0.60. In the photocoagulation combined with triamcinolone group, the pretreatment mean LogMAR was 1.31+/-0.49. The number of laser spots was 42+/-14. The 6 -month post- treatment mean LogMAR was 1.26+/-0.49. In the photocoagulation only group, 7 eyes had stable vision (improved, stable or loss of <2 lines) and 8 eyes had vision loss (loss>or=2 lines). In the photocoagulation combined with triamcinolone group, 15 eyes had stable vision and 2 eyes had vision loss. Fewer eyes had vision loss in the photocoagulation combined with triamcinolone group. (chi-square test, p=0.024). This study, with a follow-up of 6 months, suggests that subtenon injection of triamcinolone combined with macular photocoagulation provides a better chance of stabilizing vision loss in patients with diabetic cystoid macular edema than photocoagulation alone.


Cloning, expression, and sequencing of squalene-hopene cyclase, a key enzyme in triterpenoid metabolism.
The pentacyclic hopanoids, a class of eubacterial lipids, are synthesized by squalene-hopene cyclase and side chain-elongating enzymes. With the aid of DNA probes based on the amino-terminal sequence of purified squalene-hopene cyclase from Bacillus acidocaldarius, clones of Escherichia coli that express this enzyme in the cytoplasmic membrane were isolated. According to the DNA sequence, the cyclase contained 627 amino acids with a molecular mass of 69,473 Da. A high percentage of the amino acids were basic. No significant similarity to existing sequenced proteins was found.


Galactolipid Synthesis in Vicia faba Leaves: III. Site(s) of Galactosyl Transferase Activity.
Leaves of Vicia faba were fed (14)CO(2) in light for periods of up to 6 hours. At intervals, leaf samples were homogenized and separated into fractions which contained "broken" and "intact" chloroplasts, and three other high speed centrifugal fractions containing other cell membranes and chloroplast envelopes. Analyses of the radioactive labeling of galactose from the galactolipids in these fractions and in purified chloroplast envelopes indicated that the major site of galactosyl transferase enzyme activity was in the chloroplast envelope. The data suggest that in time much of the radioactive galactolipid was transferred from the envelope to the thylakoid-containing fractions. The major site of galactolipid synthesis appears to be in the envelope but there is some evidence of another site in the thylakoids.


Pharyngoesophageal reconstruction with the anterolateral thigh flap: a clinical and functional outcomes study.
Functional outcomes and morbidities of pharyngoesophageal reconstruction have not been satisfactory. The purpose of the present study was to evaluate such outcomes following pharyngoesophageal reconstruction with the anterolateral thigh flap. Reconstruction of pharyngoesophageal defects was performed in 41 consecutive patients with the anterolateral thigh flap. There were 31 circumferential and 10 near-circumferential defects. In the initial nine patients, a portion of the flap was externalized for monitoring by deepithelializing a strip of skin at the distal anastomosis. This technique resulted in a 33-percent fistula rate and was thus modified for the subsequent 32 patients, in whom a true end-to-end, spatulated anastomosis was performed. Total flap loss occurred in one patient, and one patient had partial flap necrosis due to ischemic bowel and sepsis. The mean hospital stay was 6.7 +/- 1.9 days. With the modified technique, fistulas occurred in two out of 25 patients (8 percent) and two out of seven patients (29 percent) with circumferential and near-circumferential defects, respectively, for an overall fistula rate of 13 percent. Strictures occurred in three out of 25 (12 percent) of patients with circumferential defects only. Fluent speech was achieved in all 13 patients who had successful tracheoesophageal prosthesis placement. Among the 34 patients available for diet assessment, two patients (6 percent) required partial tube feeding owing to extensive tongue resection; all other patients tolerated a regular (88 percent) or pureed (6 percent) diet. The anterolateral thigh flap offers comparable complication rates, superior speech and swallowing functions, minimal donor-site morbidity, a quick recovery, and a short hospital stay.


Relationship between breast- and bottle-feeding and non-nutritive sucking habits.
The objective of the present study was to assess the persistence of non-nutritive sucking habits and its relationship with breastfeeding, as well as to establish the influence of sociodemographic factors on these habits among children aged 3 to 5 years. A case-control study was conducted with 1107 children from public and private daycare centres in Natal, Brazil: 450 in the case group (312 pacifier suckers and 138 thumb suckers) and 657 in the control group (habit-free). Data regarding sociodemographic conditions and duration of breastfeeding were obtained using a structured questionnaire. Breastfeeding for a duration of > 6 months (adjusted odds ratio = 0.311; 95% confidence interval = 0.226 to 0.428) was an independent protective factor against persistent pacifier sucking. The use of pacifiers was more frequent among 3-year-old children and among those from a higher income family and a higher level of schooling of parents. The relation between duration of breastfeeding and thumb sucking was not statistically significant (P = 0.087). There was an association between the thumb sucking habit with sex (female), low level of schooling of father and the child being born as the last male child in the birth order. No relation was found between breastfeeding and habit frequency (day/night and night) (P = 0.301). An association with habit frequency was found with the age of 3 years, female, the family income group that ranged between US $176 and US $875, and those attending private institutions. Breastfeeding for a duration of > 6 months was a protective factor against the persistence of pacifier sucking, but the subjectivity of the mother-child relationship must be investigated further.


Developmental appearance, species and tissue specificity of mouse 23-kDa, a retinal calcium-binding protein (recoverin).
A 23-kDa, soluble, calcium-binding photoreceptor-specific protein (23-kDa) has been shown to be identical to recoverin and the cancer-associated retinopathy protein. Recoverin has been reported to activate guanylate cyclase to increase the amount of cyclic GMP and thereby reopen cation channels within the photoreceptor cells. In this study, the 23-kDa protein was purified from bovine retinas and monospecific antibodies against it were generated in rabbits. Western analysis demonstrated 23-kDa in retinas from human, monkey, bovine, dog, rabbit, rat, mouse, frog, chameleon and iguana although it was not detected in chicken or fly retinas. No immunoreactivity was observed in any non-retinal tissues except the pineal gland. The 23-kDa protein was detected, by Western analysis, at postnatal day 5 in the mouse retina and it increased in amount in parallel with the differentiation of the photoreceptor cells in normal mice and it also decreased in parallel with their degeneration in the rd mouse. Immunocytochemical analysis of the adult mouse retina showed that 23-kDa is restricted primarily to the inner segments of the photoreceptor cells and, unlike arrestin, its localization did not shift in response to light/dark changes.


[DNA analysis and gene diagnosis of cystic fibrosis].
Cystic fibrosis (CF) is the most common autosomal recessive disorder in the Caucasian population, affecting approximately 1 in 2,000 newborns but the actual estimate varies with the geographic location. The incidence of CF in non-Caucasian populations is low. Intensive efforts using genetic linkage information ultimately led to the cloning of the CF gene prior to the identification of the gene product or its function. The gene encodes what is believed to be a transmembrane protein, which has been named the cystic fibrosis transmembrane conductance regulator (CFTR). The CFTR contains two nucleotide-binding folds (NBF) which show homology to numerous transport proteins with the greatest homology to the P-glycoproteins that are encoded by the multiple drug-resistance loci. A three- base deletion resulting in the loss of phenylalanine residue (delta F508) in the tenth exon of the CFTR gene is the mutation occurring on the majority of CF chromosomes. The overall frequency of delta F508 in the present mutant CF gene pool is about 70%, but the study populations are not equally represented: there is marked variation in the population of delta F508 among different geographic populations. Recently, numerous additional, less common mutations have been found. Some mutations occur on 2-5% of the CF chromosomes. Many of these are rare 'private' mutations, occurring in individual families of all racial and ethnic backgrounds. By contrast over 80% of Western European CF mutations have been identified. The highly heterogeneous nature of the remaining CF mutations provides important insights into the structure and function of the protein, but further improvements are needed in DNA-based genetic screening for CF carrier status.


Dermal perfusion of common donor sites free flaps in chronic smokers and nonsmokers.
The smoking behavior of the patient influences the indication of plastic surgeon in his reconstruction procedure on the assumption that smoking may increase the complication risks. In the present study, we evaluate the particular aspect of topographic differences in dermal perfusion in chronic smokers and nonsmokers. The perfusion parameter of 8 common donor sites for free flap transplantation were investigated in 152 smoking and nonsmoking subjects (n = 152; women: n = 78, 51%; men: n = 74, 49%; smokers: n = 38, 25%; nonsmokers: n = 114, 75%) using the O2C device (LAE Medizintechnik Giessen GmbH, Gießen, Germany). Oxygen saturation (%), relative hemoglobin concentration (AU [arbitrary unit]), Velocity (AU) and Flow (AU) were monitored noninvasively and compared. All monitored regions did not show any significant differences in parameters oxygen saturation (smokers = 40%, nonsmokers = 44.5%), relative hemoglobin concentration (smokers = 60 AU, nonsmokers = 60 AU), flow (smokers = 19.5 AU, nonsmokers = 16.5 AU) and velocity (smokers = 10 AU, nonsmokers = 10 AU) between chronic smoking and nonsmoking subjects (P < .05). Also, a distinction between smokers and nonsmokers as a function of gender (women: n = 78, 51%; men: n = 74, 49%) showed no significant differences in all 4 parameters. Varied statements regarding surgical complications in chronic and acute smokers were described in the literature. This raises the question of how far restricting the indication of reconstruction procedure for smoking patients due to higher complications is justified. In our study, there is no significant drop of dermal perfusion parameters after chronic tobacco consumption. Nonetheless, the unfavorable effects of smoking in general to human body and health remain undoubted.


Synthesis, structure, and bonding of stable complexes of pentavalent uranyl.
Stable complexes of pentavalent uranyl [UO(2)(salan-(t)Bu(2))(py)K](n) (3), [UO(2)(salan-(t)Bu(2))(py)K(18C6)] (4), and [UO(2)(salophen-(t)Bu(2))(thf)]K(thf)(2)}(n) (8) have been synthesized from the reaction of the complex {[UO(2)py(5)][KI(2)py(2)]}(n) (1) with the bulky amine-phenolate ligand potassium salt K(2)(salan-(t)Bu(2)) or the Schiff base ligand potassium salt K(2)(salophen-(t)Bu(2)) in pyridine. They were characterized by NMR, IR, elemental analysis, single crystal X-ray diffraction, UV-vis spectroscopy, cyclic voltammetry, low-temperature EPR, and variable-temperature magnetic susceptibility. X-ray diffraction shows that 3 and 8 are polymeric and 4 is monomeric. Crystals of the monomeric complex [U(V)O(2)(salan-(t)Bu(2))(py)][Cp*(2)Co], 6, were also isolated from the reduction of [U(VI)O(2)(salan-(t)Bu(2))(py)], 5, with Cp*(2)Co. Addition of crown ether to 1 afforded the highly soluble pyridine stable species [UO(2)py(5)]I.py (2). The measured redox potentials E(1/2) (U(VI)/U(V)) are significantly different for 2 (-0.91 and -0.46 V) in comparison with 3, 4, 5, 7 and 9 (in the range -1.65 to -1.82 V). Temperature-dependent magnetic susceptibility data are reported for 4 and 7 and give mu(eff) of 2.20 and 2.23 mu(B) at 300 K respectively, which is compared with a mu(eff) of 2.6(1) mu(B) (300 K) for 2. Complexes 1 and 2 are EPR silent (4 K) while a rhombic EPR signal (g(x) = 1.98; g(y) = 1.25; g(z) = 0.74 (at 4 K) was measured for 4. The magnetic and the EPR data can be qualitatively analyzed with a simple crystal field model where the f electron has a nonbonding character. However, the temperature dependence of the magnetic susceptibility data suggests that one or more excited states are relatively low-lying. DFT studies show unambiguously the presence of a significant covalent contribution to the metal-ligand interaction in these complexes leading to a significant lowering of the pi(u)*. The presence of a back-bonding interaction is likely to play a role in the observed solution stability of the [UO(2)(salan-(t)Bu(2))(py)K] and [UO(2)(salophen-(t)Bu(2))(py)K] complexes with respect to disproportionation and hydrolysis.


An assessment of microbial coronal leakage of temporary filling materials in endodontically treated teeth.
This in vitro study evaluated the microbial leakage of Cavit, IRM, and Dyract when used as temporary filling materials after root canal treatment. The degree of coronal leakage was assessed by using a microbiological marker consisting of Streptococcus faecalis and Candida albicans. For each of the two organisms, a set of 15 maxillary premolars were prepared chemomechanically and obturated with thermoplasticized gutta-percha. A 3.5-mm thick layer of one of the three temporary filling materials was inserted in the access cavities of the teeth from each group (each group was compromised of five teeth). The control teeth (four positive and four negative) lacked any filling material over the gutta-percha, whereas the orifice and the apical foramen of the negative control were completely sealed with nail polish. Each tooth was placed in a well of a 24-well tissue culture plate and embedded in trypticase soy broth and 0.5% Bactoagar. An organism suspension was inoculated in the access cavity, and microbial penetration was detected as an increase in turbidity of the broth. At the end of 30 days, the results showed that all positive control teeth leaked within 1 week, whereas those that served as negative control remained uncontaminated throughout the test period. With both organisms, IRM started to leak after 10 days, whereas Cavit and Dyract leaked after 2 weeks.