[Coding Causes of Death with IRIS Software. Impact in Navarre Mortality Statistic].
There are few studies that analyze changes in mortality statistics derived from the use of IRIS software, an automatic system for coding multiple causes of death and for the selection of the underlying cause of death, compared to manual coding. This study evaluated the impact of the use of IRIS in the Navarre mortality statistic. We proceeded to double coding 5,060 death certificates corresponding to residents in Navarra in 2014. We calculated coincidence between the two encodings for ICD10 chapters and for the list of causes of the Spanish National Statistics Institute (INE-102) and we estimated the change on mortality rates. IRIS automatically coded 90% of death certificates. The coincidence to 4 characters and in the same chapter of the CIE10 was 79.1% and 92.0%, respectively. Furthermore, coincidence with the short INE-102 list was 88.3%. Higher matches were found in death certificate of people under 65 years. In comparison with manual coding there was an increase in deaths from endocrine diseases (31%), mental disorders (19%) and disease of nervous system (9%), while a decrease of genitourinary system diseases was observed (21%). The coincidence at level of ICD10 chapters coding by IRIS in comparison to manual coding was 9 out of 10 deaths, similar to what is observed in other studies. The implementation of IRIS has led to increased of endocrine diseases, especially diabetes and hyperlipidaemia, and mental disorders, especially dementias.


Brodalumab for severe hidradenitis suppurativa: a case of clinico-radiologic improvement and literature review.
Hidradenitis suppurativa (HS) is a chronic autoinflammatory follicular disease, affecting body areas that are rich in apocrine glands. Moderate-to-severe HS may severely impair patients' quality of life also because the available therapies are often unsatisfactory. Several lines of evidence suggest that inflammatory cytokines such as tumor necrosis factor-α (TNF-α) and interleukin (IL)-17 play a pivotal role in the physiopathology of HS. TNF-α inhibitors have long been used with benefit in moderate-severe forms of HS. However, several monoclonal antibodies against IL-17 isoforms are currently being investigated for HS. We report the case of a 50-year-old man with long-standing HS and concomitant palmo-plantar psoriasis treated with brodalumab after failure of various TNF-α inhibitors. The HS lesions and the patient's quality of life improved steadily over time until week-136. Interestingly, the clinical benefit was confirmed by radiological improvement with MRI evaluation. Our case report demonstrates the long-term efficacy and safety of brodalumab in HS encouraging the use of drugs to inhibit the T helper-type 17 immune axis, especially in cases of HS refractory to therapy with TNF-α inhibitors.


[Tumors of the diaphragm, diagnosis and surgical treatment].
Primary tumors of the diaphragm are very rare, and we often have difficulties in preoperative diagnosis and accurate evaluation of invasion. We experienced 3 surgical cases of tumor of diaphragm:primary mucinous adenocarcinoma, metastatic gastrointestinal stromal tumor, and mesothelioma. Besides computed tomography (CT) and conventional magnetic resonance imaging(MRI), respiratory dynamic cine magnetic resonance imaging (cine MRI) was performed. Cine MRI was acquired using steady state free precession (SSFP) sequence, and about 80 consecutive images of the same slice were taken while a patient breathed deeply. In all cases, cine MRI showed lack of tumor movement along the diaphragm during respiration. During surgery, we found that tumor was originated from diaphragm and there was no adhesion to other organs. Securing a sufficient margin, we resected tumor including the diaphragm. Since the defect of diaphragm was from 4 to 5cm in short diameter, we could close the diaphragm by direct suture. Cine MRI could provide useful information concerning discrimination between diaphragmatic and para-diaphragmatic tumor.


[A critical evaluation of food programs in Argentina].
Argentina has an over 60-year history of food programs which have received few to no evaluations, even considering the highly important epidemiological and social changes that have occurred in the target population. In this article, nationwide State-run food programs with the objective of contributing to the food security of the families in greatest need are reviewed, the nutritional situation of the target population is reassessed, and arguments for analyzing current programs using a typology based in the components of food security are proposed. A general review of the conceptions, content and reach of food programs should be carried out, in order for these programs to cease to act as mere social assistance and instead be transformed in bearers of the right to better food and nutrition.


The relationship between maximal hip abductor strength and resultant loading at the knee during walking.
The peak external knee adduction moment (KAM) is implicated in progression of knee osteoarthritis (OA). Recently, hip abductor weakness has also been found in patients with knee OA; however, it remains unknown as to how or if this weakness is a consequence of OA, or a predisposing factor. If it is the latter, a direct relationship between hip strength and KAM magnitude would be expected. The purpose of this study was to evaluate the relationship between hip abductor strength and KAM magnitude during walking. In fourteen adults, maximal isometric hip abductor strength was measured, and the KAM was quantified during gait. Additionally, internal hip abductor moments, vertical and medial ground-reaction-forces (GRFs), and GRF to knee joint center lever-arms were quantified during gait. The relationship between hip strength and GRFs, lever-arms and KAM were assessed using correlation. Internal hip abductor moments were compared to maximum hip strength by paired samples t-test. Correlations between hip strength and the vertical GRF (r = -0.05, p = 0.87), medial GRF (r = -0.24, p = 0.41), lever arm (r = -0.01, p = 0.97), and KAM (r = -0.24, p = 0.41) were not statistically significant. Peak internal hip abductor moments during gait (1.1 ± 0.2 Nm/kg) were significantly lower than maximal hip abductor strength (1.8 ± 0.3 Nm/kg, p < 0.001). It is concluded that hip abductor strength is not related to KAM magnitude. It seems more likely that hip abductor weakness is a consequence of OA rather than a predisposing factor.


Chronic obstructive pulmonary disease (COPD) among opioid-dependent patients in agonist treatment. A diagnostic study.
To estimate the prevalence of chronic obstructive pulmonary disease (COPD) and related risk factors in people in opioid agonist treatment (OAT), to compare airflow limitation severity and age-specific COPD prevalence rates with those in the general population, and to assess the OAT patients' willingness to adopt life-style changes and to use therapeutic offers for COPD management. Cross-sectional study in a random sample of OAT patients. Out-patient centres for substance addiction medicine in Zurich, Switzerland. A total of 125 participants, recruited from November 2016 to April 2017 through invitation letters followed by phone or personal contact. Standardized questionnaires about drug use, smoking habits and medical history, completed during face-to-face interviews or from medical records. Spirometry without and-depending on the result-with bronchodilation. Almost one-third [30.3%; 95% confidence interval (CI) = 22.6-39.0%] of the 119 participants with valid spirometry tests were diagnosed with COPD. Among males aged 30-59 years, the age-adjusted prevalence of at least moderate airflow limitation (GOLD grade ≥ 2) was 2.4 (95% CI = 1.3-4.4) times as high as in the ever-smoking Swiss population in the same age group. Smoking tobacco (92.0%) and substance inhalation (cannabis = 97.6%, cocaine = 69.6%, heroin = 68.0%) were highly prevalent among all participants. The participants expressed considerable interest in life-style changes and use of therapeutic offers for COPD management, with smoking cessation being least (20.2% of tobacco smokers interested) and pharmacological treatment to alleviate COPD symptoms most popular. In Switzerland, COPD prevalence and multiple risk factors for COPD appear to be high among people in OAT compared with the general population. Individuals in OAT appear to develop COPD at a younger average age compared with the general population and are open to life-style changes and other COPD management approaches.


A nested case-control study of the risk of suicide attempts after discharge from psychiatric care: the role of co-morbid substance use disorder.
The literature suggests that the risk of suicide is high within the first weeks after discharge from psychiatric care, but practically no studies have estimated the risk of suicide attempt after discharge from psychiatric care. The aim of this study was to examine the risk level for suicide attempt after discharge from psychiatric care, and to control for effects from psychiatric diagnoses, number and length of previous admission. An analysis of the role of co-morbid substance use disorder in suicide attempts risk was completed. The study is a Danish register-based nested case-control study; 3037 cases were identified from Register for Suicide Attempts, and 60,295 individuals, matched by gender and age, were identified for comparison. Retrospective personal data on psychiatric care was obtained from the Danish Psychiatric Central Register. Risk of suicide attempts was estimated by the use of conditional logistic regression. We found a significant high peak in risk of suicide attempts in the first weeks after discharge from psychiatric care. The risk was lowered as time passed by. Suicide attempt risk was not equally distributed across various psychiatric diagnoses, and co-morbidity of substance abuse with mental illness raised risk in an additive way. We found only small gender differences in risk. In order to lower the risk of suicide attempts, we need to improve after-care when discharging from psychiatric care. A differentiation between the possibilities of after-care for different mental illnesses is needed.


Closely related members of the Medicago truncatula PHT1 phosphate transporter gene family encode phosphate transporters with distinct biochemical activities.
Phosphorus is one of the essential mineral nutrients required by all living cells. Plants assimilate phosphate (Pi) from the soil, and their root systems encounter tremendous variation in Pi concentration, both temporally and spatially. Genome sequence data indicate that plant genomes contain large numbers of genes predicted to encode Pi transporters, the functions of which are largely unexplored. Here we present a comparative analysis of four very closely related Pi transporters of the PHT1 family of Medicago truncatula. Based on their sequence similarity and locations in the genome, these four genes probably arose via recent gene duplication events, and they form a small subfamily within the PHT1 family. The four genes are expressed in roots with partially overlapping but distinct spatial expression patterns, responses to Pi and expression during arbuscular mycorrhizal symbiosis. The proteins are located in the plasma membrane. Three members of the subfamily, MtPT1, MtPT2, and MtPT3, show low affinities for Pi. MtPT5 shares 84% amino acid identity with MtPT1, MtPT2, and MtPT3 but shows a high affinity for Pi with an apparent Km in yeast of 13 microm. Sequence comparisons and protein modeling suggest that amino acid residues that differ substantially between MtPT5 and the other three transporters are clustered in two regions of the protein. The data provide the first clues as to amino acid residues that impact transport activity of plant Pi transporter proteins.


Severe cytokine release syndrome in a patient receiving PD-1-directed therapy.
Cytokine release syndrome (CRS) is a phenomenon of immune hyperactivation described in the setting of cellular and bispecific T-cell engaging immunotherapy. Checkpoint blockade using anti-programmed cell death 1 (anti-PD-1) inhibitors is an approach to antitumor immune system stimulation. A 29-year-old female with alveolar soft part sarcoma developed severe CRS after treatment with anti-PD-1 therapy. CRS was characterized by high fevers, encephalopathy, hypotension, hypoxia, hepatic dysfunction, and evidence of coagulopathy, and resolved after infusion of the interleukin-6 inhibitor tocilizumab and corticosteroids.


Reactive Oxygen Species in HIV Infection.
Reactive oxygen species (ROS) are a family of oxygen molecules with an unpaired electron and play an important role in homeostasis and pathogenesis. The reactive molecules modify lipids, proteins and nucleic acids, and modulate a wide range of cellular functions. The importance of ROS in infection has been established through clinical and in vitro studies. Here we review the role of oxidative stress in HIV pathogenesis, the impact of ROS on immune responses in HIV patients, and ROS-mediated regulation of HIV infection. Future studies on the interplay between ROS and HIV infection may offer a new strategy for prevention and treatment.


Dermatology patients' and their doctors' representations about adherence.
The aim of our study was to identify representations about patient adherence among dermatologists (N=40) and their patients (N=153). A combined qualitative-quantitative methodology was applied. Dermatologists identified good doctor-patient relationship, information from the doctor, and background information as the most important determinants of adherence. In patients' rankings, information from the doctor and understandable communication received the highest scores. Multidimensional scaling arranged patients' results into four content groups which helped to reveal the structure of the representations. Our results may contribute to the evidence-based confirmation that transparency of views and expectations in doctor-patient communication is a basic determinant of successful adherence.


Hypoxia and carbon monoxide in the vasculature.
Hypoxia is sensed by all mammalian cells and elicits a variety of adaptive and pathophysiological responses at the molecular and cellular level. For the pulmonary vasculature, hypoxia causes increased vasoconstriction and vessel-wall remodeling. These responses are mediated by complex intracellular cascades leading to altered gene expression and cell-cell interaction. Hypoxia transiently increases the transcriptional rate of the heme oxygenase-1 (HO-1) gene, resulting in increased production of carbon monoxide (CO) and bilirubin. CO has vasodilatory and antiinflammatory properties in the vasculature, whereas bilirubin is an antioxidant. Both enzymatic products could thus modulate the hypoxic cellular response. Accumulating data suggest that CO inhibits the hypoxic induction of genes encoding vasoconstrictors and smooth muscle cell mitogens in the early hypoxic phase. During chronic hypoxia, low CO levels tilt the balance toward increased production of growth factors and vasoconstrictors that promote vessel-wall remodeling. Mice null in the HO-1 gene manifest decreased tolerance to hypoxia with right ventricular dilatation and infarction, whereas targeted lung overexpression of HO-1 prevents hypoxia-induced inflammatory responses and protects against the development of pulmonary hypertension. Such observations point to CO as a critical modulator of the body's adaptive responses to hypoxia.


Stapling of an endobronchial suction tube with the bronchus during robot-assisted right lower lobectomy: a case report.
Troubleshooting intraoperative complications requires careful management, and the safest technique should be chosen. We recently experienced a unique intraoperative bronchial complication during pulmonary lobectomy in robot-assisted thoracic surgery (RATS). There is no consensus on whether to continue RATS or convert to a more familiar technique, such as video-assisted thoracic surgery (VATS) or thoracotomy, for intraoperative complications that occur during RATS, and the decision should be determined individually. A 74-year-old woman with primary lung adenocarcinoma (clinical stage IA2) underwent robot-assisted right lower lobectomy under one-lung ventilation and CO2 insufflation. Intraoperatively, the anesthesiologist placed the endobronchial suction tube in the right bronchus with intention of maintaining the right lung collapse, which was simultaneously stapled with the right lower bronchus during the right lower lobe bronchial closure using a robotic stapler. During robot-assisted manipulation, we removed the staples involved with the suction tube, one by one, using robotic-arm forceps and sutured the partially opened stump. Subsequently, the bronchial stump was covered with a pedicled pericardial fat pad. The postoperative course was uneventful, and the patient developed no complications when followed up 8 months after discharge. Hence, we could rectify this intraoperative bronchial complication using a robot-assisted technique and avoid conversion to VATS or thoracotomy. The precise manipulation techniques in RATS contributed to facilitate the successful execution of surgical procedures, such as staple removal and re-suturing of the bronchial stump and may be a useful as a method for such troubleshooting such intraoperative complications.


The genotoxic effects of arachidonic acid in V79 cells are mediated by peroxidation products.
Chinese hamster lung fibroblasts (V79 cells) were exposed to 2, 20, 160, and 200 microM arachidonic acid (AA). At 20 microM, a stimulatory effect on cell growth was observed, while at 200 microM, an inhibitory effect was found. AA at 160 and 200 microM induced a 10- to 12-fold increase of 6-thioguanine-resistant mutants in V79 cells, whereas increased alkaline labile sites on DNA were consistently produced only with 200 microM treatment doses. The induction of alkaline labile lesions was partially inhibited in the presence of an antioxidant NDGA. [3H]AA metabolism in cells was examined by HPLC analysis following reductive transmethylation of the cell lipid extracts. Two fractions corresponding to [3H]AA-derived peroxidation products were identified by HPLC-radiochromatography and analyzed by mass spectrometry. Quantitative evaluation of the radioactivity associated with these peaks revealed an increase in [3H]AA peroxidation products when cells were exposed to increasing amounts of AA. The AA-dependent stimulation of lipid peroxidation product formation was partially inhibited when cells were treated in the presence of NDGA. The results provide evidence that substantially enlarged AA pools in cells may induce genotoxic effects mediated through increased endogenous lipid peroxidation products.


Primary Health-Care Staff Barriers to Immunization.
Missed opportunities for immunization (MOI) is considered as the most important preventable reason for underimmunization. Health-care workers stand beyond more than half the children's missed opportunities due to gaps in their knowledge, attitudes, and practices (KAP) regarding immunization. This study assessed immunization staff at primary health-care centers in Baghdad/Al-Karkh for KAP that may lead to MOI. KAP survey was conducted on field immunization service providers at primary health-care centers in Baghdad/Al-Karkh. Barriers are considered to present whenever scores found <80 in any of KAP. Data were collected using a self-administered structured questionnaire analyzed by SPSS 24. Among 217 respondent health professionals, 69 (31.8%) were physicians and 148 (68.2%) were nurses. The studied sample got mean scores for KAP of 84.7 ± 11.4, 71.1 ± 22.7, and 74.8 ± 20.3, respectively. Physicians had higher mean knowledge score compared to nurses (P < 0.05). Both physicians and nurses got mean scores below 80 for both attitudes and practices. Attitudes and practices in both physicians and nurses need to be improved to avoid MOI.


Effects of obesity on women's reproduction and complications during pregnancy.
Obesity is increasing rapidly among women all over the world, and more women in fertile ages become overweight and obese. Among all other problems, women who are obese have higher rates of amenorrhoea and infertility. Obese women have a higher risk of complications during pregnancy such as hypertensive diagnoses and gestational diabetes, and delivery complications such as higher rates of caesarean sections and prolonged time of delivery. The aim of this article is to review the consequences of being obese during the reproductive life of a woman.


Formulation, in vitro characterization and optimization of taste-masked orally disintegrating co-trimoxazole tablet by direct compression.
Orally disintegrating tablet (ODT) is a dosage form that overcomes the problem of swallowing which is prevalent in about 35% of the general population. Co-trimoxazole (CTX) is given for patients with HIV for the prophylaxis of opportunistic infection (OI), commonly for pneumocystis carinii pneumonia. It was reported that CTX was associated with a 25-46% reduction in mortality among individuals infected with HIV in sub-Saharan Africa. Esophageal candidiasis which usually comes along with HIV/AIDS is one of AIDS defining illness affecting up to 1 in 5 of people with AIDS. This opportunistic illness is manifested by painful or difficulty of swallowing. In this respect, CTX ODT offer the advantages of both liquid dosage forms in terms of easy swallowing thereby improve patient compliance and solid dosage forms in terms of dose uniformity, stability, lower production, and transportation costs. The objective of this study was to formulate, characterize and optimize CTX ODT which could overcome swallowing problem and improve patient compliance. Co-trimoxazole ODTs were prepared by direct compression technique using a semi synthetic super disintegrant (crospovidone) along with other excipients. Two taste masking techniques were employed, addition of sweetening agent, and solid dispersion by using a pH sensitive polymer, Eudragit E-100 at different ratios (1:1, 1:2 and 1:3). Taste masking was determined by comparing taste threshold value and in vitro drug release. Preliminary study was used to investigate the effect of crospovidone, compression force (CF) and Hydroxypropyl cellulose (HPC) on disintegration time, friability and wetting time (WT). Factorial design was used as it enables simultaneous evaluation of formulation variables and their interaction effect. From the preliminary study, the factors that were found significant were further optimized using central composite design. Design-Expert 22.214.171.124 software was employed to carry out the experimental design. The bitterness threshold concentration of Trimethoprim was found to be 150 μg/ml and the in vitro drug release of the three batches of drug to polymer ratio (F1:1, 1:2 and 1:3) was 2.80±0.05, 2.77±0.00 and 2.63±0.00 respectively. From the optimization study, the optimal concentration for the superdisintegrant was 8.60% w/w and a CF of 11.25 KN which gave a rapid disintegration and WT of 13.79 and 23.19 seconds respectively and a friability of 0.666%. In this study, co-trimoxazole ODT was formulated successfully. Central composite design was effectively used to model and optimize friability, DT and WT. The method was found effective for estimating the effect of independent variables on the dependent variables by using polynomial equation and surface plots. Optimization of the response variables was possible by using both numerical and graphical optimization and the predicted optimal conditions were confirmed experimentally and were found to be in good agreement within 5% of the predicted responses. The results of the study showed that CTX ODT had significantly rapid disintegration, less than 1% friability and enhanced dissolution profiles. The successful formulation of CTX ODT can solve difficulty of swallowing of conventional tablets for some group of patients which are unable to swallow solid oral dosage form.


Chitin-induced activation of immune signaling by the rice receptor CEBiP relies on a unique sandwich-type dimerization.
Perception of microbe-associated molecular patterns (MAMPs) through pattern recognition receptors (PRRs) triggers various defense responses in plants. This MAMP-triggered immunity plays a major role in the plant resistance against various pathogens. To clarify the molecular basis of the specific recognition of chitin oligosaccharides by the rice PRR, CEBiP (chitin-elicitor binding protein), as well as the formation and activation of the receptor complex, biochemical, NMR spectroscopic, and computational studies were performed. Deletion and domain-swapping experiments showed that the central lysine motif in the ectodomain of CEBiP is essential for the binding of chitin oligosaccharides. Epitope mapping by NMR spectroscopy indicated the preferential binding of longer-chain chitin oligosaccharides, such as heptamer-octamer, to CEBiP, and also the importance of N-acetyl groups for the binding. Molecular modeling/docking studies clarified the molecular interaction between CEBiP and chitin oligosaccharides and indicated the importance of Ile122 in the central lysine motif region for ligand binding, a notion supported by site-directed mutagenesis. Based on these results, it was indicated that two CEBiP molecules simultaneously bind to one chitin oligosaccharide from the opposite side, resulting in the dimerization of CEBiP. The model was further supported by the observations that the addition of (GlcNAc)8 induced dimerization of the ectodomain of CEBiP in vitro, and the dimerization and (GlcNAc)8-induced reactive oxygen generation were also inhibited by a unique oligosaccharide, (GlcNβ1,4GlcNAc)4, which is supposed to have N-acetyl groups only on one side of the molecule. Based on these observations, we proposed a hypothetical model for the ligand-induced activation of a receptor complex, involving both CEBiP and Oryza sativa chitin-elicitor receptor kinase-1.


Institutionalizing children and adolescents in private psychiatric hospitals.
Admissions of children and adolescents to private psychiatric hospitals have been increasing more and more rapidly in recent years. However, the increasing use of inpatient treatment is not consistent with current theory and research about the mental health needs of children and adolescents; often inpatient treatment cannot be justified on the basis of the admitting diagnosis. Hospitalization has an array of negative effects and is less effective in terms of treatment outcome and cost when compared with community-based alternatives. High rates of admissions continue because of changes in the juvenile justice law, insurance practices, lack of legal protection for youths and children, inappropriate government policy, and the growth and practices of for-profit hospitals. Implications for social policy and social work practice are discussed.


Coffee Consumption and Risk of Hypertension in Adults: Systematic Review and Meta-Analysis.
The association between coffee intake and hypertension (HTN) risk is controversial. Therefore, this systematic review and meta-analysis aimed at summarizing the current evidence on the association of coffee with hypertension risk in observational studies. PubMed/Medline and Web of Science were searched for observational studies up to February 2023. Observational studies which assessed the risk of HTN in the highest category of coffee consumption in comparison with the lowest intake were included in the current meta-analysis (registration number: CRD42022371494). The pooled effect of coffee on HTN was evaluated using a random-effects model. Twenty-five studies i.e., thirteen cross-sectional studies and twelve cohorts were identified to be eligible. Combining 13 extracted effect sizes from cohort studies showed that higher coffee consumption was associated with 7% reduction in the risk of HTN (95% CI: 0.88, 0.97; I2: 22.3%), whereas combining 16 effect sizes from cross-sectional studies illustrated a greater reduction in HTN risk (RR = 0.79, 95% CI: 0.72, 0.87; I2 = 63.2%). These results varied by studies characteristics, such as the region of study, participants' sex, study quality, and sample size. An inverse association was found between coffee consumption and hypertension risk in both cross-sectional and cohort studies. However, this association was dependent on studies characteristics. Further studies considering such factors are required to confirm the results of this study.


PDT dose parameters impact tumoricidal durability and cell death pathways in a 3D ovarian cancer model.
The successful implementation of photodynamic therapy (PDT)-based regimens depends on an improved understanding of the dosimetric and biological factors that govern therapeutic variability. Here, the kinetics of tumor destruction and regrowth are characterized by systematically varying benzoporphyrin derivative (BPD)-light combinations to achieve fixed PDT doses (M × J cm(-2)). Three endpoints were used to evaluate treatment response: (1) Viability evaluated every 24 h for 5 days post-PDT; (2) Photobleaching assessed immediately post-PDT; and (3) Caspase-3 activation determined 24 h post-PDT. The specific BPD-light parameters used to construct a given PDT dose significantly impact not only acute cytotoxic efficacy, but also treatment durability. For each dose, PDT with 0.25 μM BPD produces the most significant and sustained reduction in normalized viability compared to 1 and 10 μM BPD. Percent photobleaching correlates with normalized viability for a range of PDT doses achieved within BPD concentrations. To produce a cytotoxic response with 10 μM BPD that is comparable to 0.25 and 1 μM BPD a reduction in irradiance from 150 to 0.5 mW cm(-2) is required. Activated caspase-3 does not correlate with normalized viability. The parameter-dependent durability of outcomes within fixed PDT doses provides opportunities for treatment customization and improved therapeutic planning.


Differentiated thyroid cancer and selenium supplements for protection of salivary glands from 131I treatment.
Dear Editor, I read with great interest the article by Son et al about the radioprotective effect of selenium (Se) supplementation for the salivary glands from 131I treatment in patients with differentiated thyroid cancer (DTC). In this study, 8 patients received 300μg of Se (as inorganic sodium selenite; selenase®) orally for 10 days, 3 days before to 6 days after 131I treatment. On the occasion of the use of Se among these patients, I want with this letter to remind the differences among the prescribed Se supplements in clinical practice, such as the possible health consequences of Brazil nut consumption as another choice for the preparation of DTC patients for radioactive iodine (RAI) therapy. Selenium is an essential element with many pleiotropic effects that can be found in foods and supplements in organic form (as selenomethionine, selenocysteine, γ-glutamyl-Se-methylselenocysteine) or/and in inorganic form (as sodium selenate and sodium selenite). Selenium in multivitamin/multimineral supplements or in a stand-alone supplement is often available in the forms of L-selenomethionine, Se-enriched yeast (grown in a high-Se medium), mustard seed-derived Se, or as sodium selenite or sodium selenate. Because these two (organic and inorganic) forms of Se are absorbed and metabolized differently, it is very important for the physicians, when prescribe a Se supplement, to know the contained form of Se. Inorganic forms of Se are easily absorbed through the intestine but poorly retained. Once they reach the blood, inorganic Se is quickly filtered out by the kidneys and excreted in the urine. So, the consumption of supplements with inorganic forms of Se does not offer the maximum health benefits of the element. Conversely, Se-containing amino acids, such as selenomethionine and selenocysteine, are introduced directly into proteins, including muscle proteins. These organic proteins-bound Se (selenoproteins) are better retained, utilized, and incorporated by the human body. About 90% of the received selenomethionine is actually absorbed in the intestinal tract, and about half of that remains in the body. The higher degree of absorption of selenomethionine against selenite was described in a recently published systematic review and meta-analysis by Wichman et al. In this review, a significant decrease in serum thyroid peroxidase antibodies (TPO-Ab) levels was found among patients receiving 200μg selenomethionine, but not among those receiving 200μg sodium selenite. In another investigation, 10 groups of Se-replete subjects were randomly assigned to receive a placebo or either 200 or 400 or 600μg/day Se as selenomethionine, sodium selenite, or high-selenium yeast (in which an estimated 75% of Se was in the form of selenomethionine) for 16 weeks. Selenium bioavailability, based on urinary excretion, was greatest for selenomethionine and lowest for selenite. However, supplementation with any of these forms only affected plasma Se levels and not glutathione peroxidase activity or selenoprotein P concentration, suggesting that study participants were selenium replete before they began taking Se supplements. Because the absorption of selenite was approximately two-thirds of the absorption of selenomethionine in this study, we can assume that the daily dose of 300μg of sodium selenite in the study of Son et al corresponded to 200μg of selenomethionine which is the most frequently used dose in intervention trials. However, in our opinion, the prescription of supplements with organic forms of Se must be preferred, when required. It is also worth mentioning that the prescribed Se supplements should not contain iodine considering that for a successful RAI therapy after thyroidectomy, DTC patients must, not only increase their thyroid-stimulating hormone (TSH) levels, but also deplete the whole body iodine pool through a low-iodine diet (low-quality evidence). One of the richest known food sources of bioavailable Se, in the organic form of selenomethionine, are the Brazil nuts. Brazil nuts grow on massive tropical trees, the Bertholletia excelsa of the Lecythidaceae family, some reaching heights over 45m. The average Se content of each Brazil nut in most elemental analyses varies ranging from 2.7 to 11μg Se/g, and the average weight of each nut varies between 3 and 4 g. Their consumption can increase the likelihood of Se toxicity, regardless of the quantity of the nuts consumed, and thus is not be a safe dietary choice. Moreover, Brazil nuts may be infected externally by aflatoxins or can trigger allergic reactions in sensitive people. However, raw Brazil nuts don't contain iodine and thus their consumption would not undermine the dietary efforts of DTC patient in the framework of the required low-iodine diet. The consumption of 2-3 unshelled and raw (unsalted) Brazil nuts daily could be another choice for the post-thyroidectomy period up to 10 days after RAI therapy among DTC patients who do not want to receive supplements as source of Se. We must emphasize that some patients having DTC and also Hashimoto's thyroiditis may had previously received Se supplements or Brazil nuts for a long period of time before DTC was diagnosed and thyroidectomy had followed. In conclusion, the prescription of supplements with organic forms of Se must be preferred against of supplements with inorganic forms of Se among DTC patients for the protection of their salivary glands from 131I treatment and Brazil nuts could be another choice.


Plasmonic Microcantilever with Remarkably Enhanced Photothermal Responses.
Plasmonic nanostructures exhibit abundant optoelectronic properties. We explore here the technological potentials of plasmonic nanostructures as active component to actuate microcantilever sensors. We find that the photothermal excitation of microcantilevers can be greatly enhanced by Au nanoparticle (NPs). A detailed investigation reveals that the enhancement is wavelength dependent and can be attributed to selective excitation of localized surface plasmon resonance (LSPR). The associated effects are discussed based on a thorough examination of the geometric aspects of Au NPs, microcantilever lengths, and incident optical power. Some technological advantages offered by this method are also discussed.


Escherichia coli DNA ligase B may mitigate damage from oxidative stress.
Escherichia coli encodes two DNA ligases, ligase A, which is essential under normal laboratory growth conditions, and ligase B, which is not. Here we report potential functions of ligase B. We found that across the entire Enterobacteriaceae family, ligase B is highly conserved in both amino acid identity and synteny with genes associated with oxidative stress. Deletion of ligB sensitized E. coli to specific DNA damaging agents and antibiotics resulted in a weak mutator phenotype, and decreased biofilm formation. Overexpression of ligB caused a dramatic extension of lag phase that eventually resumed normal growth. The ligase function of ligase B was not required to mediate the extended lag phase, as overexpression of a ligase-deficient ligB mutant also blocked growth. Overexpression of ligB during logarithmic growth caused an immediate block of cell growth and DNA replication, and death of about half of cells. These data support a potential role for ligase B in the base excision repair pathway or the mismatch repair pathway.


[Fucoxanthin induces prostate cancer PC-3 cell apoptosis by causing mitochondria dysfunction and oxidative stress].
To investigate the apoptosis- inducing effect of fucoxanthin in human prostate cancer PC-3 cells and the underlying mechanism. The viability and apoptosis of PC-3 cells treated with fucoxanthin were analyzed using commercial kits, and the mitochondrial membrane potential, mitochondrial morphology and mitochondrial superoxide were detected using fluorescence probe staining. The contents of ATP, H2O2, malondialdehyde (MDA), superoxide and the total antioxidant capacity of PC-3 cells were determined. The protein expressions of Bcl-2, Bax and cytochrome c were detected with Western blotting, and the activity of caspase-9 and caspase- 3/7 was detected using corresponding kits. Fucoxanthin significantly inhibited the viability of PC-3 cells in a time- and dose-dependent manner, and dose-dependently induced apoptosis of the cells (P < 0.05). Fucoxanthin-treated PC-3 cells showed significantly decreased mitochondrial membrane potential, mitochondrial fragmentation and increased superoxide level in the mitochondria (P < 0.05), and these effects of fucoxanthin were dose- dependent. Fucoxanthin dose-dependently decreased ATP level and the total antioxidant capacity of PC-3 cells, increased the contents of H2O2, MDA and superoxide (all P < 0.05), enhanced the protein expressions of Bax and cytochrome c in the cytoplasm, and lowered the protein expressions of Bcl-2 and cytochromes in the mitochondria (P < 0.05). Fucoxanthin induces apoptosis of PC-3 cells by triggering mitochondrial dysfunction to cause oxidative stress and by activating mitochondria-mediated apoptotic signaling pathways, suggesting its potential in prostate cancer treatment.


Combined immunoprophylaxis in the prevention of perinatal transmission of hepatitis B and hepatitis D virus infections in Saudi children.
The efficacy of the combined immunoprophylaxis approach (passive plus active immunization) was evaluated in babies born to 52 HBsAg-carrier Saudi mothers, of whom seven (13.5%) were HBeAg-positive and seven were anti-HDV-positive. Newborns were given 100 IU of hepatitis B immune globulin (HBIG) from the Hepuman Berna-Swiss Serum and Vaccine Institute, Berne, and hepatitis B vaccine (5 micrograms) within 12 hours of birth, and the vaccine was given again at 1 and 6 months of age (5 micrograms/injection). After 18 months of follow-up, all but one baby had protective levels of antibody to HBsAg and none of the babies born to anti-HDV-positive carrier mothers showed evidence of HDV infection. These results show that the combined immunoprophylaxis approach is quite successful in protecting against perinatal transmission of HBV and HDV in the Saudi population. Furthermore, early vaccination against HBV will also protect against HDV infection later in life.


Antibiotic DE-3936, a polyether antibiotic identical with lonomycin. Taxonomy, fermentation, isolation and characterization.
Antibiotic DE-3936 was isolated from the fermentation broth of a streptomycete No. 9735-1, which is identified as a strain of Streptomyces hygroscopicus. The antibiotic is a hydrophobic compound having the molecular formula of of C44H75O14Na and is active against Gram-positive bacteria, mycobacteria, mycoplasma and protozoa, especially coccidia. Its chemical and biological properties indicate that antibiotic DE-3936 belongs to the group of polyether antibiotics and is identical with lonomycin.


Microorganisms Profile and Antimicrobial Resistance Pattern in Outborn Neonates in Northern India: A Hospital-Based Observational Study.
Neonates born somewhere else (outborn) and treated in a referral centre have different microbiological profile. We report the microorganism's profile and antimicrobial resistance (AMR) in blood culture proven sepsis in outborn neonates. Culture positive neonatal sepsis from a neonatal unit of a referral institute catering to outborn neonates was studied over an 18 months duration. Data from the hospital information system were used to analyse the culture positivity rates, the spectrum of the microorganisms isolated and AMR pattern. Out of 5258 admitted neonates, 3687 blood samples were sent for suspect sepsis. The blood cultures were positive in 537 (14.6%) samples from 514 neonates. Gram-positive cocci (GPC) were the most common [240 (45%)] followed by gram-negative bacilli (GNB) [233 (43.4%)] and fungi [64 (11.9%)]. Coagulase negative staphylococcus (CONS) contributed to two-thirds of GPC followed by Klebsiella [93 (17.3%)] and Acinetobacter species [52 (9.7%)]. In 403 (75%) neonates, organisms grew in the samples sent at or within 24 h of admission. The case fatality rate was significantly higher in those with culture positive sepsis. The resistance to meropenem and imipenem was documented in 57.1% and 49.7%, respectively and 48% of the GNB was multidrug resistant. CONS followed by Klebsiella species were the most common organisms isolated. Three-fourths of the neonates had organisms grown at or within 24 h from admission. More than half of the GNB were multidrug resistant. The case fatality rate was significantly higher in those with culture positive sepsis.


Carotid artery stenting in a community setting: experience outside of a clinical trial.
Carotid artery angioplasty and stenting (CAS) currently represents a less invasive percutaneous alternative to conventional endarterectomy for the treatment of carotid occlusive disease. We report here the results and complication rates of CAS performed by a team of interventionalists at a non-clinical trial center utilizing a standardized CAS protocol. CAS was attempted in 51 arteries in 48 patients (mean age 71 +/- 9 years, range 53-90). Fifteen (29%) of 48 patients were symptomatic. Indications for CAS were previous ipsilateral endarterectomy (15/51, 29%), previous neck radiation therapy (1/51, 2%), or significant coronary artery disease (30/51, 59%). SMART((R)) stents were deployed via percutaneous femoral artery access, with anticoagulation (heparin, abciximab, aspirin, clopidogrel) and temporary transvenous cardiac pacemakers employed in all patients. Neuroprotection was not used. Neurological examination and duplex scans were performed in follow-up. CAS was successfully performed in 96% of cases (49 lesions/46 patients) with angiographic stenoses of 88 +/- 8%. Neurological complications included one (2%) minor stroke that occurred 12 hr after CAS. There were no periprocedural mortalities. Clinically significant bradycardia or asystole occurred in 11/49 (22%) procedures, necessitating short-term ventricular pacing. All stented vessels remained patent during 12.2 +/- 10.1 (range 1-37) months follow-up period. One asymptomatic restenosis (>70%) occurred at 3 months, which was successfully reangioplastied; we thus had 1-year angiographic restenosis rate of 2%. Patients selected for CAS may represent a subset of patients with carotid disease who have considerable comorbidities or unfavorable anatomy compared to those undergoing conventional endarterectomy. CAS may be performed safely outside of a clinical trial with results similar to those of published series from trial centers using a standardized protocol.


Multi-genic pattern found in rare type of hypopituitarism: a whole-exome sequencing study of Han Chinese with pituitary stalk interruption syndrome.
Pituitary stalk interruption syndrome (PSIS) is a rare type of hypopituitarism manifesting various degrees of pituitary hormone deficiency. Although mutations have been identified in some familial cases, the underpinning mechanisms of sporadic patients with PSIS who are in a vast majority remain elusive, necessitating a comprehensive study using systemic approaches. We postulate that other genetic mechanisms may be responsible for the sporadic PSIS. To test this hypothesis, we conducted a study in 24 patients with PSIS of Han Chinese with no family history using whole-exome sequencing (WES) and bioinformatic analysis. We identified a group of heterozygous mutations in 92% (22 of 24) of the patients, and these genes are mostly associated with Notch, Shh, Wnt signalling pathways. Importantly, 83% (20 of 24) of the patients had more than one mutation in those pathways suggesting synergy of compound mutations underpin the pathogenesis of sporadic PSIS.


A review of approaches for analysing obstructive sleep apnoea-related patterns in pulse oximetry data.
Overnight pulse oximetry allows the relatively non-invasive estimation of peripheral blood haemoglobin oxygen saturations (SpO2 ), and forms part of the typical polysomnogram (PSG) for investigation of obstructive sleep apnoea (OSA). While the raw SpO2 signal can provide detailed information about OSA-related pathophysiology, this information is typically summarized with simple statistics such as the oxygen desaturation index (ODI, number of desaturations per hour). As such, this study reviews the technical methods for quantifying OSA-related patterns in oximetry data. The technical methods described in literature can be broadly grouped into four categories: (i) Describing the detailed characteristics of desaturations events; (ii) Time series statistics; (iii) Analysis of power spectral distribution (i.e. frequency domain analysis); and (d) Non-linear analysis. These are described and illustrated with examples of oximetry traces. The utilization of these techniques is then described in two applications. First, the application of detailed oximetry analysis allows the accurate automated classification of PSG-defined OSA. Second, quantifications which better characterize the severity of desaturation events are better predictors of OSA-related epidemiological outcomes than standard clinical metrics. Finally, methodological considerations and further applications and opportunities are considered.


Reversal by hypotonic medium of the antiviral state induced by lymphoblastoid interferon in human HeLa cells.
The induction kinetics of the antiviral state in HeLa cells treated with human lymphoblastoid interferon (IFN) was studied. In cells treated with 4-200 U/ml IFN, the antiviral state was fully established in 7-9 h. Inhibition of virus multiplication was more rapid if the concentration of IFN was increased to 1,000 U/ml. This antiviral state gradually disappeared during the 48 h after IFN removal. Several compounds known to act on the cell membrane or on the cytoskeleton were tested for their influence on the establishment and reversal of the antiviral state. None of them were found to influence these two parameters to a significant extent. In contrast, placing HeLa cells in medium lacking NaCl partially reversed the blockade to virus multiplication induced by IFN treatment. Cells treated with IFN and later placed in hypotonic medium synthesized virus proteins after encephalomyocarditis virus infection, although at a reduced level compared to cells that had not been treated with IFN.


Myocardial effects of mitoxantrone and doxorubicin in the mouse and guinea pig.
Mitoxantrone (DHAQ) was compared to doxorubicin for myocardial effects in the mouse and the guinea pig. Histologically, DHAQ induced a high incidence of focal myocardial damage in mice, similar to that observed with doxorubicin. Functionally, like doxorubicin, DHAQ significantly reduced the rate of contraction and histamine responsiveness of guinea pig right atria in vitro. Additionally, long-term ip administration of either DHAQ or doxorubicin reduced the atrial response to histamine in vitro. These data suggest that DHAQ may have a spectrum of myocardial activity similar to that of doxorubicin.


Use of internet medical websites and NHS direct by neurology outpatients before consultation.
With increasing personal access to the internet, and the mass of medical information available in cyberspace, many patients may access information before an outpatient consultation. Since this information may shape individual health beliefs and expectations, yet is acknowledged to be of very variable quality, it may be important for practitioners to know about their patients' self-directed findings. Medical information may also be gained from the NHS Direct telephone helpline. This study measured the frequency of use of the internet and of NHS Direct by questioning consecutive new referrals attending general neurology outpatient clinics over a three-month period. A comparison was made between patients' searches and their final diagnosis. Patients' views on the use of the information received were sought.


The expression and functionality of stromal caveolin 1 in human adenomyosis.
What is the expression pattern and functionality of caveolin 1 (CAV1) in the endometrium of patients with adenomyosis? The stromal CAV1 expression is down-regulated that leads to the release of a variety of molecules that either enhance the metastatic capacity of endometrial cells or contribute to adenomyosis-associated dysmenorrhea. Adenomyosis is characterized by invasion of endometrium into the uterine myometrium. CAV1 has been linked to tumor progression and clinical outcome in a variety of human malignancies; however, its role in adenomyosis development and adenomyosis-associated dysmenorrhea is still poorly recognized. We retrospectively analyzed the expression levels of CAV1 and RANTES protein using immunohistochemistry in 65 patients who were pathologically diagnosed with adenomyosis and 12 control women without related pathology, who were subjected to surgery between 2009 and 2010. Endometrial tissues from six additional normal females without related pathology were collected from 2011 to 2012; these tissues were subjected to subsequent primary cell culture experiments. The expression of CAV1 and RANTES was examined by immunohistochemistry in ectopic endometrium and paired eutopic endometrium of 65 adenomyosis patients and 12 control patients. Primary endometrial stromal cells (ESCs) and endometrial epithelial cells (EECs) were isolated from 6 additional control females without related pathology. The expression of CAV1 in ESCs was either (i) inhibited by siRNA transfection and methyl-β-cyclodextrin (MβCD) treatment or (ii) increased by pcDNA3.1/CAV1 transfection. The impact of each treatment on the proliferation, migration and invasion of both ESCs and EECs was evaluated by methylthiazolydiphenyl-tetrazolium assay, colony formation assay, Transwell migration and invasion assay. Furthermore, ESC treatment with MβCD and siCAV1 was assessed for the effect on the expression of a panel of inflammatory cytokines. The levels of two pain mediators, nitric oxide (NO) and prostaglandin E2 (PGE2), were assessed in CAV-1-depleted and control ESCs, whereas immunoblotting was performed to characterize signaling pathways downstream to loss of stromal CAV1 in endometrium. The correlation between dysmenorrhea severity and stromal CAV1 and RANTES expression was further examined using 'Pearson's' correlation analysis. Stromal CAV1 expression in ectopic endometrium of adenomyosis patients was significantly lower than that of paired eutopic endometrium or normal controls as analyzed by immunohistochemistry (P < 0.001). Although no significant difference was observed in the proliferation of CAV1-depleted ESCs when compared with control group, EECs cultured with conditioned media from CAV1-depleted ESCs demonstrated a significantly elevated proliferation rate when compared with those treated with control ESC-conditioned media. Moreover, both CAV1-depleted ESCs and EECs cultured with conditioned media from CAV1-depleted ESCs showed enhanced migration and invasion capacity when compared with control group (P < 0.05). In contrast, incubation with conditioned media of ESCs with enforced CAV1 expression led to decreased proliferation capacity of EECs. Furthermore, the expression of RANTES in ESCs treated with MβCD and siCAV1 was significantly increased. Stromal RANTES expression in the ectopic endometrium of adenomyosis patients was significantly higher than that of paired eutopic endometrium or normal controls as analyzed by immunohistochemistry (P = 0.0026). Stromal CAV1 expression in eutopic endometrium was significantly lower in women with more severe dysmenorrhea (P < 0.05) and was negatively correlated with dysmenorrhea severity in adenomyosis patients (r(2) = 0.1549; P = 0.012, 'Pearson's' χ(2) test), whereas stromal RANTES expression in eutopic endometrium was significantly higher in women with more severe dysmenorrhea (P < 0.05) and was positively correlated with dysmenorrhea severity in adenomyosis patients (r(2) = 0.1646; P = 0.0094, 'Pearson's' χ(2) test). Silencing of CAV1 in ESCs led to increased release of NO and PGE2 when compared with control and was associated with enhanced activity of ERK-FAK signaling pathway. This study assessed the functional role of stromal CAV1 and RANTES in a small number of human adenomyosis samples by immunohistochemistry and in primary human ESCs by functional studies. In future investigations, a larger sample size should be adopted and the functional role of stromal CAV1 should be further characterized in animal models. Loss of stromal CAV1 expression may play a critical role in the pathogenesis of adenomyosis and is correlated with adenomyosis-related dysmenorrhea. National Basic Research Program of China and Ph.D. Programs Foundation of Ministry of Education of China. None.


Is global measles eradication feasible?
Measles is one of most infectious diseases. Before the introduction of the measles vaccine, practically all children in the long run contracted measles. By the end of the 1980s most countries of the world had incorporated measles vaccine into their routine vaccination programs. Globally, some 800,000 deaths due to measles still occur every year, half of them in Africa. Eradication of measles would play an important role in improving child survival. The goal to eradicate measles from the Americas was set by the Pan American Sanitary Conference in 1994. Progress to date has been remarkable. Measles is no longer an endemic disease in the Americas and interruption of transmission has been documented in most countries. As of August 2005, 3 years have elapsed since the detection of the last indigenous case in Venezuela in September 2002. This experience shows that interruption of measles transmission can be achieved and sustained over a long period of time and that global eradication is feasible if appropriate strategy is implemented. Even in a new paradigm in which eradication is not followed by the discontinuation of vaccination, eradication of measles will be a good investment to avoid expensive epidemics and save the almost one million children that die every year to infection with the measles virus. It is not a dream to think that we will se a world free of measles by the year 2015.


Vertebral Aneurysmal Bone Cyst Mimicking Osteosarcoma: Case Report and Review of the Literature.
Aneurysmal bone cysts are benign osseous lesions containing blood-filled cavities separated by walls of connective tissue. They can be difficult to identify clinically due to similarities in presentation, imaging, and histology with other pathologies. Specifically, it is important to distinguish these benign lesions from malignant processes, as both surgical and medical management differ. We present the case of a 21-year-old patient who presented with impaired motor and sensory function in his lower extremities. Radiologic findings were concerning for an invasive neoplasm, and the intraoperative frozen section supported this conclusion. However, an additional histological investigation was confirmatory for a diagnosis of an aneurysmal bone cyst. The patient underwent corpectomy, laminectomy, and a posterior spinal fusion, and regained motor and sensory function shortly thereafter. This report details the importance of considering aneurysmal bone cysts in the differential of infiltrative bone lesions, despite their benign nature, as medical and surgical management can vary greatly.


[Xanthine oxidase in homogenized cow's milk and Oster's hypothesis: a review].
Oster has postulated that the enzyme xanthine oxidase in homogenized cow's milk is the cause of myocardial infarction and angina pectoris. This enzyme may be absorbed by ingestion, especially of the small particles of the fat globules, and then carried by lymph streams to the arterial vascular system, where it is deposited into the myocardium. Then it destroys the aldehydes liberated from the cell membrane-based plasmalogens. This results in the intimal damage to the cell membranes of the arterial intima and the myocardium and ultimately in the development of typical atherosclerotic lesions in the arteries. The presented review is a critical approach to this hypothesis. The following factors are discussed: - the influence of conditions prevailing in the intestine and the stomach on the activity of the xanthine oxidase in milk, - the possibility of this enzyme being absorbed in the intestine, - the formation of antibodies against absorbed xanthine oxidase and - the behaviour of xanthine oxidase administered intravenously. Compared with present knowledge, this theory gives little evidence only.


[Brazilian Protocol for Sexually Transmitted Infections 2020: Zika virus infection].
This article addresses vector, sexual and vertical transmission of Zika virus, a topic covered in the Clinical Protocol and Therapeutic Guidelines for Comprehensive Care for People with Sexually Transmitted Infections, published by the Brazilian Ministry of Health in 2020. Although in Brazil Zika virus is transmitted most predominantly by Aedes aegypti, the vertical and sexual transmission routes are of significant importance for reproductive health. Sexual transmission demands the use of specific prophylactic interventions, including the use of male or female condoms, especially among couples planning pregnancy. Vertical transmission is linked to severe structural abnormalities of the central nervous system and there is still no vaccine or known pharmacological resources that can prevent it. As the disease is predominantly asymptomatic, failure to comply with basic principles of care and guidelines related to the spread of infection transcends the severity of the symptoms of the disease.


Enhancing the alignment of the preclinical and clinical stroke recovery research pipeline: Consensus-based core recommendations from the Stroke Recovery and Rehabilitation Roundtable translational working group.
Stroke recovery research involves distinct biological and clinical targets compared to the study of acute stroke. Guidelines are proposed for the pre-clinical modeling of stroke recovery and for the alignment of pre-clinical studies to clinical trials in stroke recovery.


Further studies on the hypernoradrenergic state of treated hypertensives: effect of captopril.
We investigated the effect of captopril on plasma norepinephrine concentration and blood pressure in two groups of hypertensive patients. One group consisted of five severely hypertensive patients rendered hypernoradrenergic by administration of a minoxidil-propranolol-diuretic regimen. The other group was ten untreated mildly hypertensive patients. Two hours after 12.5mg of captopril, blood pressure was lowered (p less than .05) in four of the five hypernoradrenergic patients from 180 +/- 8/102 +/- 8 to 132 +/- 7/77 +/- 8 mmHg. Chronic administration of 100-150mg of captopril tid caused no further blood pressure reduction. Precaptopril plasma norepinephrine concentration was 925 +/- 206 and two hours after the 12.5mg dose was 807 +/- 80 pg/ml. Three months later having advanced the dose to 300-450 mg/day it was lower (p less than .05) at 752 pg/ml. The acute blood pressure response correlated (r = -0.72, p less than .001) with the precaptopril plasma norepinephrine. Precaptopril blood pressure in the mild hypertensive patients was 146 +/- 4/98 +/- 1, after a 25-100mg dose it was 137 +/- 6/91 +/- 2 (diastolic p less than .05) and at two months with the same captopril dose bid it was 141 +/- 8/88 +/- 4 mmHg (diastolic p less than .01). Corresponding initial PNE was 425 +/- 72, two hours after captopril 405 +/- 47 and 310 +/- 63 pg/ml (p less than .05) with chronic administration. Thus, captopril lowers blood pressure in both hypernoradrenergic and eunoradrenergic hypertensive patients without increasing plasma norepinephrine suggesting some unique dampening effect of this drug on the sympathetic nervous system. Also, addition of captopril to triple therapy lowered blood pressure in proportion to plasma norepinephrine levels suggesting importance to its action on this sympathetic nervous system effector.


Carotid intimal medial thickness in human immunodeficiency virus-infected women: effects of protease inhibitor use, cardiac risk factors, and the metabolic syndrome.
Little is known regarding carotid intimal medial thickness (IMT) in HIV-infected women and the risk factors for subclinical atherosclerosis in this population, including antiretroviral therapy and the metabolic syndrome. Our objective was to assess carotid IMT in relationship to HIV status and antiretroviral therapy in HIV-infected women in comparison with healthy age- and body mass index (BMI)-matched control subjects. The study took place at an academic medical center and included 97 HIV-infected women compared with 86 age- and BMI-matched healthy control subjects. We assessed carotid IMT, metabolic syndrome, and risk factors for increased IMT. Carotid IMT was not increased in HIV-infected women [0.62 mm (0.57-0.68); median (IQR)] compared with non-HIV-infected women [0.61 mm (0.55-0.68)] matched for age and BMI (P = 0.07) but was increased significantly among HIV patients receiving a protease inhibitor (PI) [0.65 (0.59-0.71) mm] vs. non-PI-treated patients [0.61 (0.57-0.66) mm] (P < 0.05) and vs. control subjects [0.61 (0.55-0.68) mm] (P < 0.05). The prevalence of metabolic syndrome was significantly increased among the HIV-infected women compared with control subjects and particularly in PI- vs. non-PI-treated HIV patients (45 vs. 19%, P = 0.001). Metabolic syndrome score correlated with IMT among non-HIV patients but not among the HIV group. Individual risk factors most strongly associated with IMT in multivariate regression modeling in the control group were age and waist-to-hip ratio, and among the HIV group age and waist circumference. These data demonstrate increased carotid IMT in HIV-infected women receiving PI therapy, which may be due to associated metabolic abnormalities related to PI therapy or more direct effects of this medication class on the vasculature. Additional studies of the mechanisms by which PI uses results in subclinical atherosclerosis are needed.


Mutation patterns identify adult patients with de novo acute myeloid leukemia aged 60 years or older who respond favorably to standard chemotherapy: an analysis of Alliance studies.
Thus far, only 5-15% of AML patients aged ≥60 years are cured with chemotherapy. Identification of patients who are less (more) likely to respond to standard chemotherapy might enable early risk stratification toward alternative treatment regimens. We used a next-generation sequencing panel of 80 cancer- and/or leukemia-associated genes to profile molecularly 423 older patients with de novo AML. Using variables identified in multivariable models and co-occurring mutations in NPM1-mutated AML, we classified the patients into good-, intermediate-, and poor-risk groups for complete remission (CR) attainment, disease-free (DFS), and overall survival (OS). Whereas 81% of good-risk patients (comprising NPM1-mutated patients harboring mutations in chromatin remodeling, cohesin complex, methylation-related, spliceosome, and/or RAS pathway genes, FLT3-TKD, and/or patients without FLT3-ITD) achieved a CR, only 32% of poor-risk patients (with U2AF1, WT1 mutations and/or complex karyotype) did. Intermediate-risk patients had a 50% CR rate. Similarly, using NPM1 co-mutation patterns and SF1 mutation status, we identified patients with favorable DFS and OS 3-year rates of 46% and 45%, respectively. Patients with adverse genetic features had DFS and OS rates of only 2% and 4%. We show that application of our proposed criteria may refine the 2017 European LeukemiaNet classification for older patients treated with chemotherapy.


Metabolism of daunomycin (NSC-82151) in vitro and the chemotherapeutic activity of isolated metabolites in vivo.
Daunomycin (D1) was quantitatively converted to a metabolite, D2 (> 98% conversion), by an aerobic, cell-free system containing nicotinamide adenine dinucleotide phosphate, reduced form (NADPH) and the 100,000 x g supernatant fluid of rat kidneys. Under lowered oxygen concentrations, cell homogenates plus NADPH converted D, quantitatively to an unknown metabolite, D(x), with D2 as a possible intermediate. The chromatographic properties of D(x) differed from those of D2 and the aglycones of D1 and D2 (D4 and D3 respectively). Sufficient quantities of D2 and D(x) were prepared using NADPH-supplemented cell-free preparations from the kidneys of rats to assay their chemotherapeutic activity in vivo. The metabolite D2 was as effective as daunomycin (D1) against P388 leukemic cells growing in mice, but only one sixth as active against L1210 leukemic cells growing in suspension culture. The metabolite D(x) was much less active than either D2 or D1 when assayed against L1210 cells growing in culture and was inactive against P388 cells growing in mice.


[Coronavirus infection in immunodeficient patients with hemoblastosis and deficient hemopoesis].
Coronavirus infection (CVI) was studied in 227 patients hospitalized in the clinic of the Research Institute of Hematology and Transfusiology in 1993-2003 with diagnosed acute and chronic leucosis, multiple myelogenic disease and aplastic anemia. Their blood sera and secretions of the nasal cavity were examined in the indirect hemagglutination (IHA) test with dried standard erythrocyte diagnostic preparations. CVI was shown to be activated in three year cycles in immunodeficient patients, which occurred, respectively, in 66.1, 56.9, 47.8 and 51.6% of cases in the above mentioned groups of patients. In 87% of cases CVI was associated with other respiratory pathogens, the following being prevailed: respiratory syncytial virus (37.9%), parainfluenza virus (32.2%) and Mycoplasma pneumoniae (36.8%). CVI was provoked by such factors as the course of the main disease and specific treatment, previous respiratory infections of other etiology with M. pneumoniae infection playing the leading role (60%). The most severe course of CVI was observed in patients with acute leucosis (in 75% of cases accompanied by lesions of lower respiratory tracts). The use of the highly sensitive IHA test made it possible to determine the potential for both serum and local antibodies production in the patients under observation.


Bacterial antigens induce collagenase and prostaglandin E2 synthesis in human gingival fibroblasts through a primary effect on circulating mononuclear cells.
Our previous work suggests that one mechanism through which connective tissue breakdown might occur in periodontal diseases is the production of metalloproteinases, including collagenase, by gingival fibroblasts. In this study we investigated whether highly purified preparations of lipopolysaccharide (LPS) and lipoteichoic acid (LTA) from a number of putative periodontal pathogens could induce monolayer cultures of human gingival fibroblasts to synthesize collagenase and prostaglandin E2. Using both biochemical assays and immunocytochemical techniques, we found that cells synthesized only very small amounts of collagenase in direct response to LPS or LTA (0.1 to 20.0 micrograms/ml). At the highest dose of both antigens, prostaglandin E2 production was increased. We then studied whether LPS and LTA could signal collagenase production by interacting primarily with a different cell type. Our results show that LPS and LTA were each able to stimulate cultures of human blood mononuclear cells (greater than 95% monocytes) to release collagenase-inducing cytokines. By indirect immunocytochemistry, we found that a large proportion of human gingival fibroblasts was activated to produce collagenase by supernatants from LPS- and LTA-stimulated mononuclear cells, whereas gingival fibroblasts cultured with supernatants from unstimulated mononuclear cells were not. Furthermore, in a population of activated fibroblasts we demonstrated, using a double-labeling technique, that some cells made collagenase and the specific tissue inhibitor of metalloproteinases (TIMP) simultaneously. As yet, the collagenase-inducing signals remain poorly characterized but the interleukins-1 and tumor necrosis factors seem likely candidates.


Unicoloniality in Reticulitermes urbis: a novel feature in a potentially invasive termite species.
Social insects are among the world's most successful species at invading of new habitats. A good example of this invasive ability is Reticulitermes (Rhinotermitidae), a prominent group of subterranean termites. As a result of human intervention, i.e. transportation and creation of urban heat islands, Reticulitermes have been able to invade and thrive in cities located in areas where the natural habitat is normally too cold for colonization. They commonly infest man-made structures where they can cause extensive damage.This study was designed to evaluate the invasiveness of Reticulitermes urbis that was probably introduced in France from the Balkans. Invasive potential was assessed on the basis of features typical to invasive social insects, i.e. unicoloniality, low intraspecific aggression, high level of polygyny and colony reproduction by budding. The opportunity to study establishment and spreading processes arose after extensive sampling of an imported Reticulitermes urbis population was performed over the entire city of Domène, France (Rhône-Alpes region).For the first time, genetic analysis showed that the termites belonged to a single 'genetic entity' forming a vast colony covering about seven hectares. The colony was structured as an extended family with separate reproductive centres. We speculate that termites were introduced in a single location from which they gradually budded throughout the old town. Based on the absence of aggression among different nests within the colony, we defined this 'genetic entity' as a supercolony.


Nanoparticle loading level and properties of experimental hybrid resin luting agents.
This study investigated the influence of nanoparticle loading level on properties of experimental hybrid resin luting agents. Silanated 2-μm barium borosilicate glass microparticles and 7-nm silica nanoparticles were used. Five materials were obtained by loading a photocurable Bis-GMA/TEGDMA co-monomer with a total mass fraction of 60% inorganic fillers. The mass fraction of nanoparticles was set at 0% (control), 1% (G1), 2.5% (G2.5), 5% (G5), or 10% (G10). The properties evaluated were flexural strength (σ) and modulus (E(f) ), Knoop hardness number (KHN), and film thickness (FT). Dispersion/interaction of the particles with the resin phase was assessed by scanning electron microscopy (SEM). Data were submitted to statistical analysis (5%). For σ, G1 > G2.5 = G5 = G10, and control > G10. For E(f) , G2.5 > control = G1 > G5 > G10. For KHN, G5 = G10 > control = G1 = G2.5. For FT, G10 = G5 > control = G1, and G10 > G2.5. Incorporation of nanoparticles was associated with observation of clusters in the SEM analysis. The clusters were more frequent for higher nanoparticle loadings. Modest incorporation of nanoparticles may improve the properties of resin luting materials. Nanofiller mass fractions above 2.5% should, however, be avoided because they may be detrimental to the properties of the resin luting agents.


Analysis of retinal nerve fibre layer changes in anisometropic amblyopia by Heidelberg retina tomograph.
To identify if anisometropic amblyopia is associated with changes in optic disk morphology. The study comprised a total of 80 eyes recruited from Shifa Foundation Community Health Centre and the Pakistan Institute of Medical Sciences, Islamabad between May and October 2012. Anisometropic amblyopia was the only cause of disability (visual acuity > or = 6/12) in amblyopic eyes whereas normal eyes had a best corrected visual acuity of 6/6 and no morbidities. Patients with other causes of amblyopia, co-morbid ocular diseases, and in whom a good-quality image could not be obtained were excluded. Mean retinal nerve fiber layer thickness was analysed using Heidelberg retina tomograph. Analysis of frequency distribution, probability and regression were run on the data collected during the study using SPSS version 15.0. The mean age of the patients was 23.85 +/- 5.85 years. The retinal nerve fibre layer thickness ranged between 0.09 mm and 0.35 mm (mean: 0.23 mm +/- 0.07) in amblyopic eyes, and between 0.18 mm and 0.36 mm (mean: 0.25 mm +/- 0.05) in normal eyes. The difference was not statistically significant (p = 0.087). No association was found between the retinal nerve fiber layer thickness or the age and refractive error of patients. The optic disk does not appear to be the site of morphological changes in amblyopia.


Activity and stability of yeast alcohol dehydrogenase (YADH) entrapped in aerosol OT reverse micelles.
The activity and stability of yeast alcohol dehydrogenase (YADH) entrapped in aerosol OT reverse micellar droplets have been investigated spectrophotometrically. Various physical parameters, e.g., water pool size, w(0), pH, and temperature, were optimized for YADH in water/AOT/isooctane reverse micelles. It was found that the enzyme exhibits maximum activity at w(0) = 28 and pH 8.1. It was more active in reverse micelles than in aqueous buffers at a particular temperature and was denatured at about 307 degrees C in both the systems. At a particular temperature YADH entrapped in reverse micelles was less stable than when it was dissolved in aqueous buffer.


Gender differences in the association between depressive symptoms and carotid atherosclerosis among middle-aged and older Koreans: the Namwon study.
We investigated the association of depressive symptoms with carotid intima-media thickness (IMT) and plaques in the general Korean population. A total of 7,554 Korean males and females aged 45-74 yr who were free from cardiovascular diseases were included in the analyses. Depressive symptoms were assessed by the Center for Epidemiologic Studies Depression Scale (CES-D). Subjects with a score of ≥16 were classified as having clinically significant depressive symptoms. Carotid ultrasonography was used to measure mean carotid IMT (C-IMT) and to determine the presence of plaques. A significant association between depressive symptoms and C-IMT was observed only in females. After adjustment for established cardiovascular risk factors, females with depressive symptoms had significantly greater C-IMT than females without depressive symptoms (mean difference 0.011±0.004 mm; 95% confidence interval, 0.003-0.019 mm). Compared with controls, the fully adjusted risk of females with depressive symptoms for abnormal C-IMT (≥1.0 mm) was significant (odds ratio, 1.63; 95% confidence interval, 1.16-2.30). No significant association between depressive symptoms and carotid plaques was observed in either gender. This study shows a significant association between depressive symptoms and C-IMT in middle-aged and older females.


A large-scale analysis of racial disparities in police stops across the United States.
We assessed racial disparities in policing in the United States by compiling and analysing a dataset detailing nearly 100 million traffic stops conducted across the country. We found that black drivers were less likely to be stopped after sunset, when a 'veil of darkness' masks one's race, suggesting bias in stop decisions. Furthermore, by examining the rate at which stopped drivers were searched and the likelihood that searches turned up contraband, we found evidence that the bar for searching black and Hispanic drivers was lower than that for searching white drivers. Finally, we found that legalization of recreational marijuana reduced the number of searches of white, black and Hispanic drivers-but the bar for searching black and Hispanic drivers was still lower than that for white drivers post-legalization. Our results indicate that police stops and search decisions suffer from persistent racial bias and point to the value of policy interventions to mitigate these disparities.


Design of a bio-inspired pneumatic artificial muscle with self-contained sensing.
Pneumatic artificial muscles (PAMs) are one of the most famous linear actuators in bio-inspired robotics. They can generate relatively high linear force considering their form factors and weights. Furthermore, PAMs are inexpensive compared with traditional electromagnetic actuators (e.g. DC motors) and also inherently light and compliant. In robotics applications, however, they typically require external sensing mechanisms due to their nonlinear behaviors, which may make the entire mechanical system bulky and complicated, limiting their use in simple systems. This study presents the design and fabrication of a low-cost McKibben-type PAM with a self-contained displacement and force sensing capability that does not require any external sensing elements. The proposed PAM can detect axial contraction force and displacement at the same time. In this study, the design of a traditional McKibben muscle was modified to include an inductive coil surrounding the muscle fibers. Then, a thin, soft silicone layer was coated outside of the muscle to protect and hold the sensing coil on the actuator. This novel design measures coil inductance change to determine the contraction force and the displacement. The process can be applied to a variety of existing McKibben actuator designs without significantly changing the rigidity of the actuator while minimizing the device's footprint.


A cost comparison of long-acting insulin analogs vs NPH insulin-based treatment in patients with type 2 diabetes using routinely collected primary care data from the UK.
The aim of this analysis was to investigate total healthcare costs, HbA1c, and weight changes over a 36-month period in patients with type 2 diabetes initiated on NPH or long-acting insulin analogs. Electronic patient data from 479 general practices in the UK (THIN database) were examined for new users of glargine (n = 794), detemir (n = 252), or NPH insulin (n = 430). Annualized healthcare costs and clinical outcomes in years 1, 2, and 3 following insulin initiation were quantified and compared with baseline, using ANOVA and linear regression models. A significant difference (p < 0.05) in total healthcare costs increases at year 1 vs baseline was observed between glargine and detemir, detemir and NPH, but not between glargine and NPH (increase: +£486, +£635, and +£420 for glargine, detemir, and NPH users, respectively). However, increases by year 3 were not significantly different between the insulins. A propensity score analysis comparing analog and NPH insulin showed that, following insulin initiation, increases in costs were higher with insulin analogs at year one (+£220), but this difference decreased over time in each year following insulin initiation (+£168 and +£146, respectively, for years 2 and 3). HbA1c reductions were not significantly different between the groups at all time points. Differences in weight gain between glargine and NPH were statistically significant at year 1 (0.87 kg vs 1.11 kg) and year 3 (1.15 kg vs 1.57 kg), but other estimates of between-group differences in weight gain were non-significant. Following insulin initiation, the difference in healthcare costs of long-acting analogs compared to NPH insulin was transient. By year 3, the cost differences were not significantly different between the two cohorts, driven by an observed reduction in the cost of self-monitoring of blood glucose (SMBG) in the analog group and an increase in the cost of bolus insulin in the NPH group.


Temporary inactivation of the anterior part of the bed nucleus of the stria terminalis blocks alarm pheromone-induced defensive behavior in rats.
Rats emit an alarm pheromone in threatening situations. Exposure of rats to this alarm pheromone induces defensive behaviors, such as head out behavior, and increases c-Fos expression in brain areas involved in the mediation of defensive behaviors. One of these brain areas is the anterior bed nucleus of the stria terminalis (aBNST). The goal of the present study was to investigate if pharmacological inactivation of the aBNST by local microinjections of the GABAA receptor-agonist muscimol modulates alarm pheromone-induced defensive behaviors. We first established the behavioral paradigm of alarm pheromone-induced defensive behaviors in Sprague-Dawley rats in our laboratory. In a second experiment, we inactivated the aBNST, then exposed rats to one of four different odors (neck odor, female urine, alarm pheromone, fox urine) and tested the effects of the aBNST inactivation on the behavior in response to these odors. Our data show that temporary inactivation of the aBNST blocked head out behavior in response to the alarm pheromone. This indicates that the aBNST plays an important role in the mediation of the alarm pheromone-induced defensive behavior in rats.


Cardiac tamponade due to pneumopericardium.
Pneumopericardium is rare in acute asthma and cardiac tamponade has not been reported. The case is reported of a 20 year old asthmatic patient in whom assisted ventilation and high airway pressures resulted in tension pneumopericardium with clinical signs of cardiac tamponade that were relieved by pericardial aspiration.


Agriculture-related severe craniofacial injuries in rural children and adolescents.
The severe craniofacial injuries connected with agricultural work in rural children and adolescents were analysed. The analysis took into account the causes for injuries, their types and treatment. The studied group were hospitalized and constituted 18.6% of the patients of the specialized surgery department. The most severe injuries of the face and the bone structure occurred during operating or assisting in operating farming equipment, wood processing, as a result of the fall from a height, or were injuries inflicted by an animal. Causes of injuries sustained by rural children are analogous to factors causing injuries in adult agricultural workers. The practice of employing children to perform agricultural work should be prohibited because severe injuries of the facial skeleton and soft tissues may lead to disorders in children's physical and mental development.


Elevated homocysteine levels: What inborn errors of metabolism might we be missing?
Elevated total plasma homocysteine (hyperhomocysteinemia) is a marker of cardiovascular, thrombotic, and neuropsychological disease. It has multiple causes, including the common nutritional vitamin B12 or folate deficiency. However, some rare but treatable, inborn errors of metabolism (IEM) characterized by hyperhomocysteinemia can be missed due to variable presentations and the lack of awareness. The aim of this study is to identify undiagnosed IEM in adults with significantly elevated homocysteine using key existing clinical data points, then IEM specific treatment can be offered to improve outcome. We conducted a retrospective study with data mining and chart review of patients with plasma total homocysteine >30 μmol/L over a two-year period. We offer biochemical and genetic testing to patients with significant hyperhomocysteinemia without a clear explanation to diagnose IEM. We identified 22 subjects with significant hyperhomocysteinemia but no clear explanation. Subsequently, we offered genetic testing to seven patients and diagnosed one patient with classic homocystinuria due to cystathionine beta-synthase deficiency. With treatment, she lowered her plasma homocysteine and improved her health. This study stresses the importance of a thorough investigation of hyperhomocysteinemia in adults to identify rare but treatable IEM. We propose a metabolic evaluation algorithm for elevated homocysteine levels.


Regulating China's health code system to prepare for future pandemics.
This study investigates the challenges that China's health code system presents to individuals' lives and social development, using normative analysis and a case study. It looks for effective strategies to reform and regulate this system to prepare for future pandemics. Health code apps and mini programs have been widely deployed as effective tools for COVID-19 containment in China. However, their widespread and improper use has created risks due to the lack of both a systematic design and a basic supervision mechanism. The health code system risks infringing on individual privacy during data collection and storage. During the pandemic, the right to liberty and the right to treatment of Chinese citizens who lacked an appropriate health code were severely compromised. In some instances, the health code system was used as a stability maintenance tool by the authorities through arbitrary health code conversions. This article argues that China's health code systems should be reformed and regulated in preparation for future pandemics and that a new act regulating its management and use should be launched at the national level. Data collection, retention, and processing should be limited to the minimum amount of data needed to achieve the objective of protecting public health. The health code conversion power wielded by the authorities should be defined and regulated, the rules and procedures of code conversion should be transparent, arbitrary health code conversion behaviors should be prevented and punished, and persons whose rights have been violated by wrongful code conversion should have access to legal remedies.


Osteosarcoma in New Zealand: an outcome study comparing survival rates between 1981-1987 and 1994-1999.
To review the data and outcome of patients with osteosarcoma in New Zealand from 1994 to 1999 and to compare this to data retrieved from a similar study from 1981 to 1987. Data from 1994-1999 was obtained from the New Zealand Cancer Registry; raw data was also retrieved from the 1981-1987 study. There were 96 cases in the 1981-1987 cohort and 84 cases in the 1994-1999 cohort. Overall, 5-year survival from osteosarcoma improved from 32.3% to 44.0% between the cohorts. When the cohorts were compared, there was a trend toward improved outcome in most subgroups The outcome in patients with osteosarcoma in New Zealand has improved over the study period and is similar to that seen in the overseas literature.


Acquired immunodeficiency syndrome and its ocular complications.
Human immunodeficiency virus infection is the first major pandemic of the 20th century. At present, almost 10 million people are known to be infected with this virus, and it is estimated that by the year 2000, approximately 40 million people will be infected. Transmission of this deadly infection is predominantly by sexual contact. Individuals infected with this virus pass through several predictable stages with progressive decrease in circulating CD4+ T cells. During the advanced stage, these patients develop various opportunistic infections or malignancies, or both. It is this advanced stage that was first recognized as AIDS, which has a 100% mortality rate. The opportunistic organisms that can involve the eye in patients with AIDS include cytomegalovirus, herpes zoster, Toxoplasma gondii, Mycobacterium tuberculosis, Cryptococcus neoformans, Mycobacterium avium-intracellulare, Pneumocystis carinii, Histoplasma capsulatum, Candida, and others. Intraocular lesions from these agents often represent disseminated infections. Visual morbidity occurs secondary to retinitis due to cytomegalovirus, herpes zoster, or Toxoplasma gondii. Anti-viral agents such as ganciclovir or foscarnet are effective against cytomegalovirus infection. The role of the ophthalmologist in the diagnosis and management of AIDS is becoming increasingly important. Not only does the eye reflect systemic disease, but ocular involvement may often precede systemic manifestations. In the AIDS patient, the ophthalmologist thus has an opportunity to make not only a slight-saving, but also life-saving diagnosis of disseminated opportunistic infections.


PROS1 genotype phenotype relationships in a large cohort of adults with suspicion of inherited quantitative protein S deficiency.
Inherited protein S deficiency (PSD) is an established risk factor for venous thromboembolism (VTE). However, data are conflicting concerning risk of VTE associated with decreased free PS level (FPS) and information on PROS1 genotype-phenotype relationship is sparse. In a retrospective cohort of 579 patients with inherited type I/III deficiency suspicion, PROS1 genotyping was performed and the effect of genotype on FPS and on VTE risk was investigated. We found 116 (including 65 novel) detrimental mutations (DM) in 222 (type I/III in 194, type II in 28), PS Heerlen in 74, possibly non DM in 38 and no mutation in 245 subjects. Among DMs, type I/IIIDMs only were found in subjects with FPS< 30 %. Prevalence of type I/III DM decreased with increasing FPS level. Risk of VT associated with FPS level and genotype was studied in the 467 subjects with personal or family history of thrombosis. Only type I/IIIDM carriers presented with an increased risk of VTE [1.41 (95 %CI (1.05-1.89)] compared to subjects with no mutation. Among the group of type I/IIIDM heterozygotes and subjects with no mutation, the optimal FPS cut-off point for identifying subjects at increased VTE risk was searched for. We found that only subjects with FPS< 30 % and type I/IIIDM presented with an increased risk [1.48 (95 %CI 1.08-2.04)]. Our findings confirm the value of a cut-off FPS level for identifying subjects at increased VTE risk far below the lower limit of the normal range and suggest a place for PROS1 genotyping in PSD diagnosis strategy.


Molecular Mapping of Fusarium Head Blight Resistance in the Spring Wheat Line ND2710.
ND2710 is a hard red spring wheat line with a very high level of resistance to Fusarium head blight (FHB). It was selected from the progeny of a cross between ND2603 (an advanced breeding line derived from the Sumai 3/Wheaton cross) and Grandin (a spring wheat cultivar). The FHB resistance of ND2710 is presumably derived from Sumai 3 because the other parents (Grandin and Wheaton) are very susceptible to FHB. To identify and map the quantitative trait loci (QTL) for FHB resistance in ND2710, we developed a mapping population consisting of 233 recombinant inbred lines (RILs) from the cross between ND2710 and the spring wheat cultivar Bobwhite. These RILs along with their parents and checks were evaluated for reactions to FHB in three greenhouse experiments and one field experiment during 2013 to 2014. The population was also genotyped with the wheat 90K iSelect single-nucleotide polymorphism (SNP) assay, and a genetic linkage map was developed with 1,373 non-cosegregating SNP markers, which were distributed on all 21 wheat chromosomes spanning 914.98 centimorgans of genetic distance. Genetic analyses using both phenotypic and genotypic data identified one major QTL (Qfhb.ndwp-3B) on the short arm of chromosome 3B, and three minor QTL (Qfhb.ndwp-6B, Qfhb.ndwp-2A, and Qfhb.ndwp-6A) on 6B, 2A, and 6A, respectively. The major QTL on 3B was detected in all experiments and explained 5 to 20% of the phenotypic variation, while the three minor QTL on 6B, 2A, and 6A explained 5 to 12% phenotypic variation in at least two experiments, except for Qfhb.ndwp-2A, which was only detected in the field experiment. Qfhb.ndwp-3B and Qfhb.ndwp-6B were mapped to the genomic regions containing Fhb1 and Fhb2, respectively, confirming that they originated from Sumai 3. The additive effect of the major and minor QTL may contribute to the high level of FHB resistance in ND2710. The SNP markers closely linked to the FHB resistance QTL will be useful for marker-assisted selection of FHB resistance in wheat breeding programs.


H5N1 influenza viruses in Lao People's Democratic Republic.
A prospective surveillance program for influenza viruses was established in Lao People's Democratic Republic (PDR) in July of 2005. We report isolation of H5N1 virus genetically distinct from H5N1 circulating in 2004, which indicates reintroduction of H5N1 into Lao PDR after its disappearance (i.e., no virologic or serologic evidence) for 2 years.


Identification and mapping of an immunogenic region of Mycoplasma hyopneumoniae p65 surface lipoprotein expressed in Escherichia coli from a cloned genomic fragment.
A previously characterized lipid-modified amphiphilic surface protein of Mycoplasma hyopneumoniae, p65, has been defined by its reaction with a surface-binding monoclonal antibody (MAb) and by its exclusive partitioning into the detergent phase during Triton X-114 phase fractionation (K. S. Wise and M. F. Kim, J. Bacteriol. 169:5546-5555, 1987). In the current study, polyclonal mouse antibody (PAb) to gel-purified p65 was used to identify recombinant phage plaques expressing p65-related epitopes. Several characteristic partial tryptic fragments of p65 were recognized by both PAb and p65 and MAb to p65, but the PAb population specifically eluted from recombinant phage plaques bound only epitopes restricted to the largest of these fragments. Graded carboxypeptidase-Y digestion of intact M. hyopneumoniae generated C terminally truncated peptides that were recognized by PAb to p65 and MAb to p65, indicating that the C terminus and much of the adjoining region of p65 were present and accessible on the external face of the membrane. However, antibody eluted from recombinant phage plaques bound only to the largest truncated polypeptide, suggesting that a recombinant product corresponding to the C-terminal region of p65 was expressed in Escherichia coli. A 19-kilodalton recombinant protein (p19), which was recognized by PAb to p65 but not by MAb to p65, was detected in recombinant phage lysates. Serum antibodies from swine taken after, but not before, experimentally induced M. hyopneumoniae pneumonia preferentially recognized the native, amphiphilic p65 lipoprotein and also bound specifically to the p19 recombinant product. This confirmed that the p65 lipoprotein is a major immunogen of M. hyopneumoniae recognized during disease and identified its C-terminal region as an immunogenic domain.


Acute bacterial rhinosinusitis causes hyperresponsiveness to histamine challenge in mice.
To develop a physiologic test of nasal responsiveness in mice and to evaluate whether mice with acute bacterial sinusitis develop nasal hyperresponsiveness. Several experimental studies will be described. The first was a titration pilot study. The second was a randomized, placebo-controlled study. The remainder were before-and-after trials. SPECIES: BALB/c or C57BL/6 mice. For these experiments, we exposed mice to histamine intranasally, then counted the number of sneezes and nose rubs as the primary outcome measure of nasal responsiveness. First, we constructed a dose-response curve. Second, we treated the mice with desloratadine, a histamine 1 receptor antagonist, prior to histamine exposure. Third, we challenged, with intranasal histamine, mice made allergic using 2 techniques. Fourth, we infected mice with Streptococcus pneumoniae to determine whether acute sinusitis causes nasal hyperresponsiveness to histamine exposure. Nasal histamine challenge led to a reproducible, dose-dependent increase in sneezing and nose rubs. The response to histamine exposure was blocked by desloratadine (P < or = .05). Allergic mice had a significant increase in responsiveness (P < or = .05) over baseline after exposure to antigen. Mice with acute sinusitis had a sustained increase in responsiveness, although less severe than after allergy, compared with baseline values that lasted 12 days after infection (P < or = .05). Nasal challenge with histamine is a physiologic test of nasal responsiveness. The hyperresponsiveness of allergic mice to histamine exposure parallels the response to nonspecific stimuli during the human allergic reaction. In addition, we showed that acute bacterial sinusitis causes nasal hyperresponsiveness in mice.


Technical Delivery Parameters of 2000 Proton Treatment Courses.
To summarize the technical delivery parameters of proton plans delivered at the Mayo Clinic in Rochester, Minnesota. The database of treated patient proton plans was queried to extract field parameters such as gantry angle, patient support angle, minimum and maximum water-equivalent depth (WED) treated, number of layers, field size, patient orientation, and monitor units. The plans were analyzed in aggregate, by disease site, and by fractionation. There were 2963 proton plans for 2023 distinct treatment sites delivered between June 2015 and September 2018. The mean number of fields per plan was 2.8. The mean number of energy layers per field was 51.9. The mean monitor unit per field was 117.4. The median maximum field dimension was 12.4 cm; 95% of the fields had a maximum dimension < 28.7 cm, and the maximum field dimension was 39.8 cm. The median maximum field WED was 16.4 cm; 95% of the fields reached a maximum WED of ≤ 26.4 cm, and the maximum field WED was 32.4 cm. A large variety of disease sites were treated using the maximum field size (40 cm) and WED (32.4 cm) capabilities of our half-gantry system.