Circulating endothelial and endothelial progenitor cells in non-small-cell lung cancer.
New treatments have recently been introduced for treating non-small-cell lung cancer. Chemotherapeutic agents, such as pemetrexed, and targeted therapies, such as bevacizumab, erlotinib or gefitinib, have extended treatment options for selected histological subgroups. Antiangiogenic treatments, either associated with conventional chemotherapeutic drugs or given alone as maintenance therapy, constitute an active clinical research field. However, not all lung cancer patients benefit from antiangiogenic compounds. Moreover, tumour response assessment is often difficult when using these drugs, since targeted therapies generally do not cause rapid and measurable tumour shrinkage but, rather, long stabilisations and slight density changes on imaging tests. The finding of clinical or biological factors that might identify patients who will better benefit from these treatments, as well as identifying surrogate markers of tumour response and prognosis, is an issue of great interest. In that sense, different research lines have investigated the epidermal growth factor receptor (EGFR) and the vascular endothelial growth factor receptor (VEGFR) pathways. Circulating endothelial (CECs) and endothelial progenitor cells (CEPCs) are of prognostic value in different types of cancers, and relevant data are published about their potential usefulness as predictors of response to chemotherapy and antiangiogenic treatments. In this review, we discuss the data available on the role of CECs and CEPCs as prognostic factors and as surrogate markers of treatment response in non-small-cell lung cancer.


Human serum albumin inhibits prostacyclin production by endothelial cells: the relation of the inhibitory activity to sulfhydryl groups in albumin.
Human serum inhibited calcium ionophore-induced production of prostacyclin by cultured bovine aortic endothelial cells. The inhibitory fraction was purified from serum by anion-exchange and Blue-Sepharose affinity chromatography. The molecular weight of the purified substance was 67k dalton as determined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. It was identified as human serum albumin by N-terminal amino acid sequence analysis. Human serum albumin was separated to two forms by high-performance liquid chromatography: mercaptalbumin (SH type) and nonmercaptalbumin (SS type). Both types of albumin inhibited the conversion of arachidonic acid to prostaglandin H2 in a dose-dependent manner without affecting phospholipase A2 or prostacyclin synthetase. This inhibition was more potent in mercaptalbumin than in nonmercaptalbumin. These results suggest that the conversion between mercaptalbumin and nonmercaptalbumin may play an important role in the modulation of prostacyclin synthesis by endothelial cells.


Effect of ankle-foot orthosis alignment and foot-plate length on the gait of adults with poststroke hemiplegia.
To investigate the effect of ankle-foot orthosis (AFO) alignment and foot-plate length on sagittal plane knee kinematics and kinetics during gait in adults with poststroke hemiplegia. Repeated measures, quasi-experimental study. Motion analysis laboratory. Volunteer sample of adults with poststroke hemiplegia (n=16) and able-bodied adults (n=12) of similar age. Subjects with hemiplegia were measured walking with standardized footwear in 4 conditions: (1) no AFO (shoes only); (2) articulated AFO with 90 degrees plantar flexion stop and full-length foot-plate-conventionally aligned AFO (CAFO); (3) the same AFO realigned with the tibia vertical in the shoe-heel-height compensated AFO (HHCAFO); and (4) the same AFO (tibia vertical) with 3/4 length foot-plate-3/4 AFO. Gait of able-bodied control subjects was measured on a single occasion to provide a normal reference. Sagittal plane ankle and knee kinematics and kinetics. In adults with hemiplegia, walking speed was unaffected by the different conditions (P=.095). Compared with the no AFO condition, all AFOs decreased plantar flexion at initial contact and mid-swing (P<.001) and changed the peak knee moment in early stance from flexor to extensor (P<.000). Both AFOs with full-length foot-plates significantly increased the peak stance phase plantar flexor moment compared with no AFO and resulted in a peak knee extensor moment in early stance that was significantly greater than control subjects, whereas the AFO with three-quarter length foot-plate resulted in ankle dorsiflexion during stance and swing that was significantly less than control subjects. These findings suggest that when an articulated AFO is to be used, a full-length foot-plate in conjunction with a plantar flexion stop may be considered to improve early stance knee moments for people with poststroke hemiplegia.


[Use of anthrax as biological weapon].
We describe the epidemiology of anthrax and the several human disease aspect, by spores penetration through the skin or by inhalation or ingestion, and the action of exotoxin secreted by B. anthracis. We detail pulmonary anthrax that could derive from intentional release of endospore as biological weapon. Laboratory diagnosis of Cereus group with cultural, FDA and PCR methods are reported. Environment disinfection, vaccination, antibiotic prophylaxis, passive antibody administration and treatment of anthrax are reported.


Nonverbal synchrony in virtual reality.
How might nonverbal synchrony naturally evolve in a social virtual reality environment? And how can avatar embodiment affect how participants coordinate nonverbally with each other? In the following pre-registered between-subjects experiment, we tracked the movements of pairs of users during a collaborative or competitive task in immersive virtual reality. Each conversational partner controlled either a customized avatar body or an abstract cube that responded to their movements. We compared the movements of the actual user pairs between the two conditions, and to an artificial "pseudosynchrony" dataset composed of the movements of randomly combined participant pairs who did not actually interact. We found stronger positive and negative correlations between real pairs compared to pseudosynchronous pairs, providing evidence for naturally occurring nonverbal synchrony between pairs in virtual reality. We discuss this in the context of the relationships between avatar appearance, task success, social closeness and social presence.


Cutaneous Adnexal Carcinoma with Apocrine Differentiation: A Challenging Diagnosis and Personalized Treatment with mTOR Inhibitor in a Very Rare Disease.
Cutaneous adnexal carcinoma with apocrine differentiation is a rare neoplasm arising from cutaneous adnexa, especially of the head and neck and trunk region. Because of its rarity, the diagnosis is challenging and often impossible to distinguish from metastatic cutaneous adenocarcinoma of the breast. The standard of care remains surgery for resectable disease. To date, univocal guidelines for metastatic disease are lacking, particularly regarding systemic therapy. We report a clinical case of a patient diagnosed with cutaneous adnexal adenocarcinoma with apocrine differentiation of the left axilla with lymph node and bone metastasis. We started with carboplatin and paclitaxel chemotherapy regimen, with good response. After progression, we performed a next-generation sequencing analysis (by the Foundation One CDx test) to identify genomic alteration in cancer-related genes. We found PIK3CA and KRAS mutations. Due to this result, the patient started a second-line treatment with a personalized therapy including an mTOR inhibitor, everolimus, and, to date, he is still under treatment. To our knowledge, this is the first case of a patient responding both to chemotherapy and to a personalized treatment with an mTOR inhibitor. It is important to support the value of genomic screening in this rare neoplasm.


Carbon and oxygen isotopic analyses of calcite in calcite-dolomite mixtures: Optimization of selective acid extraction.
Carbon and oxygen isotopic compositions of individual minerals in calcite-dolomite mixtures could be measured using a selective acid extraction technique based on the different reaction rates of calcite and dolomite with phosphoric acid. However, poor accuracies of calcite are usually obtained when mixtures of low calcite content are analyzed, which may result in incorrect conclusions. To overcome this shortcoming, improvements are needed in accuracy and precision when using the technique with mixtures of low calcite content. Calcite and dolomite were analyzed under different reaction conditions using a GV Isoprime™ II isotope ratio mass spectrometer equipped with a dual inlet (DI) and an automatic sampler, to study the relationships between isotopic compositions and CO2 yield, and reaction time and temperature. Artificial mixtures with varied calcite:dolomite ratios were prepared, and their calcite isotopic compositions were determined with the aim of optimizing analytical conditions. The CO2 yields and isotopic compositions of calcite and dolomite were obtained on-line under different experimental conditions using DI-isotope ratio mass spectrometry (DI-IRMS). Based on the analysis results of artificial mixtures, the reaction conditions for analyzing isotopic composition of calcite in mixtures were optimized as follows. Samples should have grain sizes of 75-80 μm; and samples with calcite contents of >50%, 30-50% and < 30% should be reacted with acid for 10-15 min at 50°C, 6 min at 50°C and 45 min at 25°C, respectively. Optimized analytical conditions are suggested for the determination of the isotopic compositions of calcite in mixtures with improved accuracy by an automatic selective acid extraction technique.


The diversity of case management needs for the care of homeless persons.
Health care providers have been attempting to meet the special needs of homeless people on a national level since 1984. The need to implement strategies specific to serving the diversity of services required by homeless people has been apparent. To devise appropriate strategies, clinical information was drawn from the Health Resources and Services Administration-Health Care for the Homeless (HRSA-HCH) projects, which were created in 1987 primarily to fill such a need. In addition, data gathered by the HCH projects (1984-87) funded by the Robert Wood Johnson and Pew Memorial Trust were used. It is suggested that the past mode of providing health care for the homeless has been found to be inadequate when confronting the complex problems of the homeless person of today. In general, health care providers need to focus more on case management activities, which may include activities not necessarily associated with the provision of health care services (for example, finding and providing food, clothing, shelter, and assessing entitlement eligibility) to achieve the ultimate goal--stabilization--and when possible, reintegration of the homeless person back into society.


Dichotic listening and the cerebral organization of the phonetic and semantic components of language.
Two words were presented dichoticly and the subject was required to point to visually presented words that either rhymed with or were semantically related to those words. Task demands were varied in terms of the number and type of stimuli which the auditory and visual words actually matched. Performance was superior when either type of stimulus was presented to the Left Hemisphere via the Right Ear, resulting in the standard Right Ear Advantage (REA) for verbal material. The strength of the REA, however, depended both on the type of stimuli and the specific demands of the task. It was concluded that, since language has many components, dichotic listening can be used to investigate the relative contributions of the two cerebral hemispheres to those various components.


Interaction of regulatory T cells with antigen-presenting cells in health and disease.
Among antigen-presenting cells (APCs), dendritic cells as well as monocytes acquire immunostimulatory capacity only after appropriate maturation. Therefore, blockade of the maturation/activation results in a steady state or alternatively activated phenotype, which induces tolerance rather than immunity. Functional analyses revealed recently that steady-state dendritic cells and alternatively activated macrophages, respectively, actively induce regulatory T cells (Tregs) in the periphery of the body. Thus, production of Tregs does not rely exclusively on thymic development. Vice versa, Tregs respond to APCs by several means. Recent lines of evidence indicate that Tregs prevent terminal differentiation of subpopulations of APCs or lead to upregulation of surface expression of immunosuppressive molecules. Thus, Tregs foster an environment that further promotes their development. In conclusion, the mutual interaction of Tregs and APCs enables Tregs to sustain their immunosuppressive function(s), which in healthy individuals may be crucial for the maintenance of peripheral tolerance. Since macrophages bridge the innate and the acquired immune system, Tregs are able to gain influence on the innate immune system by interacting with macrophages beyond the mere interaction with effector T cells.


Thyroid Hemiagenesis from Childhood to Adulthood: Review of Literature and Personal Experience.
Thyroid hemiagenesis (TH) is a rare congenital abnormality of the thyroid gland, characterised by the absence of one lobe. The true prevalence of this congenital abnormality is not known because the absence of one thyroid lobe usually does not cause clinical symptoms by itself. Between 1970 and 2010, 329 cases of TH have been reported. It is interesting to note that most cases have an agenesis of the left lobe (80% of cases) followed by the isthmus (44-50% of cases). Although the female to male ratio was 1:1.4 in 24,032 unselected 11-to 14-yr-old schoolchildren from South-eastern Sicily, several other reports have documented a higher prevalence in women, which may indicate a possible gender association. Most cases of TH are diagnosed when patients present a lesion in the functioning lobe. The functioning lobe of the thyroid gland can be a site of pathological changes similar to a normally developed gland and may present a spectrum of diseases like multinodular goiter, colloid goiter, follicular adenoma, thyroiditis, hypothyroidism and hyperthyroidism. In three of our patients, TH was associated with Hashimoto thyroiditis (n = 1) and with subclinical hypothyroidism (n = 2). The frequency of thyroid abnormalities in patients with TH varies with age, due to the longer exposure of the hemi-agenetic gland to TSH overstimulation in older patients. This could explain the controversy about the benign character of this anomaly. Other extrathyroidal lesions, such as parathyroid adenoma or hyperplasia, cervical thymic cysts, ectopic sublingual thyroid gland and thyroglossal duct cyst have been reported with TH. Therefore, systematic follow-up of all identified cases is recommended.


[Influence of alcohol containing products on serum lipid spectrum].
The study was undertaken to examine of influence of alcohol containing products of household chemistry on serum lipid spectrum. The research has shown, that alcohol containing products of household chemistry at the patients with Toxic hepatitis in comparison with the persons using ethyl alcohol was revealed in lower relative contents of total phospholipids, Free fatty acids, cholesterol ethers, total lysophospholipids, sphyngomyelin and higher level of free cholesterol and phosphatidylcholine. The level of total lipids at the patients with Toxic hepatitis was in 3 times higher than normal.


Epidural extramedullary haemopoiesis in thalassaemia.
Intrathoracic extramedullary haematopoiesis is a rare condition. Involvement of the spinal epidural space with haematopoietic tissue is rather unusual. A 31-year-old-man with a known diagnosis of beta-thalassaemia was referred with focal back pain. Magnetic resonance imaging revealed diffuse bone-marrow changes, thoracic paraspinal masses and lobulated epidural masses, suggesting extramedullary haemopoiesis. The patient was treated with radiotherapy and blood transfusions. Follow-up MRI was performed for evaluation efficacy of the treatment.


Accuracy of implantation of a unicompartmental total knee arthroplasty with 2 different instrumentations: a case-controlled comparative study.
The accuracy of implantation is an accepted prognostic factor for the long-term survival of unicompartmental total knee arthroplasties (UKAs). We adapted the conventional instruments for tricompartmental total knee arthroplasty implantation, with intramedullary femoral and extramedullary tibial guiding rods, to a UKA implantation. A total of 52 patients in whom a UKA was implanted with this instrumentation were matched (using age, sex, body mass index, preoperative coronal mechanical femorotibial angle, and severity of preoperative degenerative changes according to Ahlback) with 52 patients operated with the alternative instruments. Accuracy of implant placement measured by radiography was improved significantly by the new instrumentation, but there was no difference in the survival rate or the clinical outcome after 5 years in both groups. No complication related to the new instrumentation occurred. Longer follow-up is required to determine the advantages and disadvantages of both techniques.


Chemotherapy enhances metastasis formation via VEGFR-1-expressing endothelial cells.
Recent studies suggest that chemotherapy, in addition to its cytotoxic effects on tumor cells, can induce a cascade of host events to support tumor growth and spread. Here, we used an experimental pulmonary metastasis model to investigate the role of this host response in metastasis formation. Mice were pretreated with chemotherapy and after clearance of the drugs from circulation, tumor cells were administered intravenously to study potential "protumorigenic" host effects of chemotherapy. Pretreatment with the commonly used chemotherapeutic agents cisplatin and paclitaxel significantly enhanced lung metastasis in this model. This corresponded to enhanced adhesion of tumor cells to an endothelial cell monolayer that had been pretreated with chemotherapy in vitro. Interestingly, chemotherapy exposure enhanced the expression of VEGF receptor 1 (VEGFR-1) on endothelial cells both in vitro and in vivo. Administration of antibodies targeting VEGFR-1 reversed the early retention of tumor cells in the lungs, thereby preventing the formation of chemotherapy-induced pulmonary metastases. The data indicate that chemotherapy-induced expression of VEGFR-1 on endothelial cells can create an environment favorable to tumor cell homing. Inhibition of VEGFR-1 function may therefore be used to counteract chemotherapy-induced retention of tumor cells within the metastatic niche, providing a novel level of tumor control in chemotherapy.


Nutrients with Antioxidant Properties and Their Effects on Lower-Limb Ulcers: A Systematic Review.
Chronic lower-limb ulcers (LLUs) are ulcers that fail to proceed through an orderly and timely process to produce anatomic and functional integrity. LLUs reduce the quality of life of affected individuals and are a public health problem. The treatment options include medications or surgery. Nutrition therapy is an important adjunct to improve the clinical picture and healing of LLUs. Considering that nutrients with antioxidant properties can improve the process of tissue healing, this systematic review aimed to evaluate the efficacy of antioxidant nutrient supplementation in the treatment of LLUs through randomized clinical trials. This systematic review was performed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-analyses and the Cochrane Handbook for Systematic Reviews of Interventions. The guiding question was-can antioxidant nutrients help in the treatment of chronic LLUs? In total, 1184 articles were found when searching for antioxidant nutrients associated with the most common causes of LLUs. Fourteen articles were included in this review after removing duplicates, studies with topical and/or venous use of antioxidants, and articles published in other languages, except English. Omega-3 fatty acids, magnesium, zinc, vitamins A, C, D, and resveratrol along with probiotics positively improved the ulcer healing. These effects were more significant when there was initially a deficiency of the respective supplemented nutrients. Therefore, correcting and maintaining an adequate nutritional status can improve ulcer healing and contribute to the clinical treatment of patients with LLUs.


Numerical Study on Spray Drying Process: Effect of Nonuniform Temperature Field and Interaction between Droplets on Evaporation Rates of Individual Droplets.
Spray drying process is widely used to produce particulate materials in the pharmaceutical industries, such as porous materials for direct compression, solid dispersion for improvement of drug dissolution properties, micro encapsulation to stabilize active compounds, taste masking, preparation of dry powder for inhalation. However, as many factors affect the physical properties of dried particles and the spray drying processes have complex behaviors in which heat and mass transfer occur simultaneously, the detailed mechanisms of dry particle generation have yet to be sufficiently elucidated. In this study, computational fluid dynamics was used to simulate water droplet evaporation in a spray dryer, and the evaporation kinetics of "individual droplets" in the droplet aggregate (group) were analyzed. The numerical simulation revealed that each droplet had different evaporation rates owing to the following two reasons. First, the driving force of evaporation, ΔT, changed every moment as the droplets traveled through different temperature fields in the drying tower. Second, it was calculated the driving force for droplet evaporation differed from the ideal system because the evaporation of other droplets changed the fluid characteristics around the droplets. The obtained results are important findings that lead to the understanding the spray drying process to design and manufacture the pharmaceutical products.


Can fractal dimensions objectivize gastropod shell morphometrics? A case study from Lake Lugu (SW China).
Morphometrics are fundamental for the analysis of size and shape in fossils, particularly because soft parts or DNA are rarely preserved and hard parts such as shells are commonly the only source of information. Geometric morphometrics, that is, landmark analysis, is well established for the description of shape but it exhibits a couple of shortcomings resulting from subjective choices during landmarking (number and position of landmarks) and from difficulties in resolving shape at the level of micro-sculpture.With the aid of high-resolution 3D scanning technology and analyses of fractal dimensions, we test whether such shortcomings of linear and landmark morphometrics can be overcome. As a model group, we selected a clade of modern viviparid gastropods from Lake Lugu, with shells that show a high degree of sculptural variation. Linear and landmark analyses were applied to the same shells in order to establish the fractal dimensions. The genetic diversity of the gastropod clade was assessed.The genetic results suggest that the gastropod clade represents a single species. The results of all morphometric methods applied are in line with the genetic results, which is that no specific morphotype could be delimited. Apart from this overall agreement, landmark and fractal dimension analyses do not correspond to each other but represent data sets with different information. Generally, the fractal dimension values quantify the roughness of the shell surface, the resolution of the 3D scans determining the level. In our approach, we captured the micro-sculpture but not the first-order sculptural elements, which explains that fractal dimension and landmark data are not in phase.We can show that analyzing fractal dimensions of gastropod shells opens a window to more detailed information that can be considered in evolutionary and ecological contexts. We propose that using low-resolution 3D scans may successfully substitute landmark analyses because it overcomes the subjective landmarking. Analyses of 3D scans with higher resolution than used in this study will provide surface roughness information at the mineralogical level. We suggest that fractal dimension analyses of a combination of differently resolved 3D models will significantly improve the quality of shell morphometrics.


Crystalline Morphology and Polymorphic Phase Transitions in Electrospun Nylon 6 Nanofibers.
Uniform nylon 6 nanofibers with diameters around 200 nm were prepared by electrospinning. Polymorphic phase transitions and crystal orientation of nylon 6 in unconfined (i.e., as-electrospun) and a high T(g) (340 degrees C) polyimide confined nanofibers were studied. Similar to melt-spun nylon 6 fibers, electrospun nylon 6 nanofibers also exhibited predominant, meta-stable gamma crystalline form, and the gamma-crystal (chain) axes preferentially oriented parallel to the fiber axis. Upon annealing above 150 degrees C, gamma-form crystals gradually melted and recrystallized into the thermodynamically stable alpha-form crystals, which ultimately melted at 220 degrees C. Release of surface tension accompanied this melt-recrystallization process, as revealed by differential scanning calorimetry. For confined nanofibers, both the melt-recrystallization and surface tension release processes were substantially depressed; gamma-form crystals did not melt and recrystallize into alpha-form crystals until 210 degrees C, only 10 degrees C below the T(m) at 220 degrees C. After complete melting of nano-confined crystals at 240 degrees C and recrystallization at 100 degrees C, only alpha-form crystals oriented perpendicular to the nanofiber axis were obtained. In the polyimide-confined nanofibers, the Brill transition (from the monoclinic alpha-form to a high temperature monoclinic form) was observed at 180-190 degrees C, which was at least 20 degrees C higher than that in unconfined nylon 6 at approximately 160 degrees C. This, again, was attributed to the confinement effect.


The roles of effective communication and client engagement in delivering culturally sensitive care to immigrant parents of children with disabilities.
Delivering pediatric rehabilitation services to immigrant parents of children with disabilities requires the practice of culturally sensitive care. Few studies have examined the specific nature of culturally sensitive care in pediatric rehabilitation, especially the notions of effective communication and client engagement. Interviews were held with 42 therapists (10 social workers, 16 occupational therapists and 16 speech language pathologists) from two locations in Canada (Toronto and Quebec City). Data were analyzed using an inductive content analysis approach. Study themes included the importance and nature of effective communication and client engagement in service delivery involving immigrant parents. Participants discussed using four main types of strategies to engage immigrant parents, including understanding the family situation, building a collaborative relationship, tailoring practice to the client's situation and ensuring parents' understanding of therapy procedures. The findings illuminate the importance of effective, two-way communication in providing the mutual understanding needed by therapists to engage parents in the intervention process. The findings also richly describe the engagement strategies used by therapists. Clinical implications include recommendations for strategies for therapists to employ to engage this group of parents. Furthermore, the findings are applicable to service provision in general, as engaging families in a collaborative relationship through attention to their specific situation is a general principle of good quality, family-centered care. Implications for Rehabilitation Effective communication permeates the delivery of culturally sensitive care and provides mutual understanding, which is fundamental to client engagement. The findings illuminate the nature of "partnership" by indicating the role of collaborative therapist strategies in facilitating engagement. Four main strategies facilitate effective communication and client engagement, including understanding the family situation, building a collaborative relationship, tailoring practice to the client's situation and ensuring parents' understanding of therapy procedures. Engaging families in a collaborative relationship through attention to their specific situation is a general principle of good quality, family-centered care.


A phase I study of the oral combination of CI-994, a putative histone deacetylase inhibitor, and capecitabine.
This study was conducted to determine the toxicity profile, maximum tolerated dose (MTD) and pharmacokinetics of the putative histone deacetylase inhibitor CI-994 in combination with capecitabine. Fifty-four patients were treated according to three different dosing schemes in which the capecitabine dose was fixed and the CI-994 dose was escalated. Capecitabine was administered in twice daily divided doses, and CI-994 was given as a single daily dose. In schedule A, 26 patients were treated with capecitabine 1650 mg/m2/day and CI-994 for 2 weeks of a 3-week cycle. In schedule B, six patients received capecitabine 1650 mg/m2/day for two 3-week cycles and CI-994 for 5 of 6 weeks. In schedule C, 22 patients were treated with capecitabine 2000 mg/m2/day and CI-994 for 2 of 3 weeks. At the MTD, the principal dose-limiting toxicity was thrombocytopenia. The pharmacokinetics of CI-994 were unaltered by capecitabine, and there was no correlation between body surface area and major pharmacokinetic parameters. Platelet count nadir was best predicted by the observed maximal concentration (C(max)) of CI-994. The recommended phase II dose is 6 mg/m2 (or 10 mg) of CI-994 in combination with capecitabine 2000 mg/m2/day for 2 weeks of a 3-week cycle.


Evidence for fractal correlation properties in variations of peripheral arterial tone during REM sleep.
Previous studies utilizing detrended fluctuation analysis (DFA) of heart rate variability during sleep revealed a higher fractal exponent during rapid eye movement (REM) sleep than non-REM sleep. The aim of this study was to determine whether the same difference exists in the variations of peripheral arterial tone (PAT). Finger pulse wave measured by a novel plethysmographic technique was monitored during sleep in 12 chronic heart failure patients, 8 heavy snorers, and 12 healthy volunteers. For each subject, at least two 15-min time series were constructed from the interpulse intervals and from pulse wave amplitudes during REM and non-REM sleep. Fractal scaling exponents of both types of time series were significantly higher for REM than non-REM sleep in all groups. In each of the groups and in both sleep stages, the fractal scaling exponents based on pulse wave amplitude were significantly higher than those based on pulse rate variability. A repeat of the analysis for short-, intermediate-, and long-term intervals revealed that the fractal-like exponents were evident only in the short- and intermediate-term intervals. Because PAT is a surrogate of sympathetic activation, our results indicate that variations in sympathetic activation during REM sleep have a fractal-like behavior.


The Tripartite Model for Assessing Symptoms of Depression and Anxiety: Psychometric Properties of the Chinese Version of the Mood and Anxiety Symptoms Questionnaire in Patients With Essential Hypertension.
In patients with hypertension, psychosocial factors, such as depressive symptoms and anxiety, are associated with reduced quality of life and triple the risk of nonadherence with medical treatment regimens. Thus, screening tests are crucial to identify patients who may require further assessment and treatment. The objective of the current study was to test the psychometric properties of the Chinese version of the Mood and Anxiety Symptoms Questionnaire-Short Form (MASQ-SF-C) in patients with essential hypertension. The MASQ-SF-C, the Center for Epidemiologic Studies Depression Scale (CES-D), and the State-Trait Anxiety Inventory (STAI) were administered to a convenience sample of 869 hypertensive patients in 4 hospitals. A confirmatory factor analysis was used to test the tripartite model. We evaluate the internal consistency of the MASQ-SF-C and we used the Bland-Altman approach to evaluate convergent validity between the MASQ-SF-C t score and symptoms of (1) depressive symptoms and (2) anxiety. Cronbach's α coefficient for the total MASQ-SF-C was .95, and Cronbach's α coefficients for the 3 subscales were .83 for anhedonic depression (AD), .91 for anxiety arousal (AA), and .94 for general distress (GD), indicating adequate internal consistency reliability. The mean interitem correlation coefficients were as follows: MASQ-SF-C, 0.29; AD, 0.28; AA, 0.38; and GD, 0.40. The 1-month test-retest reliability for the MASQ-SF-C was 0.72. Confirmatory factor analyses indicated that the 3 first-order factors (GD, AD, and AA) fit the data well (nonnormed fit index = 0.953, comparative fit index = 0.936, incremental fit index = 0.936, root-mean-square error of approximation = 0.038). This study supported the reliability and validity of the MASQ-SF-C, indicating that it can be used for assessing depressive symptoms and anxiety concurrently in Chinese-speaking patients with hypertension.


An increase in superoxide generation of bronchoalveolar lavage fluids in the model of late asthmatic response in guinea pigs.
To clarify the possible role of superoxide anion of bronchoalveolar cells in the pathogenesis of late asthmatic response (LAR), I performed an allergen inhalation test using a guinea pig LAR model and estimated subsequent changes in activities of superoxide generation in bronchoalveolar lavage fluids (BALFs). Significant increases in superoxide generation of BALFs occurred not only immediately, but 6 hr after ovalbumin inhalation challenge in the LAR model, and the increased levels were prolonged 24 hr later. The present results suggest that significant increases in superoxide anion of the respiratory cells were involved in the antigen-induced late responsiveness of bronchial asthma.


The short vitamin D receptor is associated with increased risk for generalized aggressive periodontitis.
Generalized aggressive periodontitis (GAP) exhibits severe inflammation and alveolar bone loss. Vitamin D receptor (VDR) regulates both bone metabolism and inflammation-related genes, and its polymorphisms and haplotypes may affect the functional activity of the VDR protein in GAP. We analysed the genetic effect of VDR start codon, intron, and exon polymorphisms, and their haplotypes on the development of GAP. The VDR start codon 27823C > T (rs2228570, FokI), intron 8 60890G > A (rs154410, BsmI), and exon 9 61968T > C (rs731236, TaqI) polymorphisms were determined by using the polymerase chain reaction-restriction fragment length polymorphism analysis among 93 GAP patients and 143 healthy controls. The VDR start codon 27823*C/*C genotype was associated with an increased risk for GAP [odds ratio (OR) = 1.83, p = 0.028], but the intron 8 60880G > A and exon 9 61968T > C polymorphisms were not associated with GAP. The VDR haplotype homozygote ht1(C-G-T) carrying 27823*C allele was associated with a 1.8-fold increased risk of GAP (OR = 1.84, p = 0.030). These results demonstrate that the short VDR (27823*C/*C) protein may influence GAP susceptibility.


Asymptomatic hemorrhagic transformation after acute ischemic stroke: is it clinically innocuous?
Whether asymptomatic hemorrhagic transformation (HT) is clinically innocuous, that is, unassociated with clinically detectable neurologic deterioration, remains an open question. To explore this, we examined whether asymptomatic HT affects long-term poor outcome and risk of stroke recurrence. We consecutively and prospectively enrolled patients with acute ischemic stroke who were admitted to our hospital. Based on clinical and imaging data, patients were diagnosed as having asymptomatic HT, symptomatic HT, or not HT, and the 3 groups were compared in terms of basic clinical characteristics, poor outcome, and stroke recurrence. We constructed Kaplan-Meier survival curves and compared groups by means of log rank tests for significant difference. Of the 1789 patients enrolled, 143 (8.0%) presented with asymptomatic HT, 25 (1.4%) presented with symptomatic HT. These patients with were more likely to be female, to have experienced atrial fibrillation, and to have higher National Institute of Health Stroke Scale score on stroke than were patients without HT. After adjusting for other confounding factors, the risk of poor outcome was significantly higher among those with asymptomatic HT and symptomatic HT than among those without HT. Moreover, patients with asymptomatic HT and symptomatic HT showed a significantly lower cumulative 1-year survival rate than did those without HT (P < .001). The patients showed similar rates of cumulative stroke recurrence at 1 year (P = .673). Asymptomatic HT and symptomatic HT after acute ischemic stroke worsened long-term clinical outcomes, although it did not affect risk of stroke recurrence. These findings suggest that asymptomatic HT should not be considered clinically innocuous.


[Coffee and health].
The coffee bean contains over 2000 chemical compounds, the health effects of which are known only to a limited extent. Previous coffee researchers and laymen focused solely on caffeine and its positive effect on mental alertness. Other ingredients in coffee, especially its polyphenols, also have an influence on our health. In Finland, coffee is the source of more than half of the so-called antioxidants that are thought to be important for health. Coffee drinkers have lower mortality and morbidity rates than non-drinkers in respect of many common chronic diseases.


[Effects of rotational grazing methods on soil aggregates and organic carbon characteristics in desert steppe.]
Reasonable rotation is of great significance to grassland management. We examined the distribution characteristics, stability, organic carbon content and contribution rate of 0-30 cm soil aggregates in the forbidding grazing, continuous grazing, and rotation in the two-paddock, four-paddock and six-paddock rotational districts in a desert steppe in Ningxia. The results showed that except for the forbidding grazing grassland that was dominated by mechanically stable large aggrega-tes, other water-stable aggregates were mainly composed of microaggregates. Increasing the rotational grazing zoning was conducive to maintain the content of water-stable aggregates in the surface soil and increase the content of large aggregates. The mechanical stability aggregate fractal dimension was the largest in continuous grazing, increased the fractal dimension of the rotation and shepherd partition to reduce the trend, but the fractal dimension of water-stable aggregates did not change. The average weight diameter (MWD) and geometric mean diameter (GMD) of the aggregates were the largest in the pastoral grassland and increased with the increases of the rotational grassland partition. MWD and GMD were negatively correlated with the microaggregate content. The organic carbon content in water-stable large aggregate was higher in the six-paddock rotational district and forbidding grazing, and the two-paddock rotational grazing and continuous grazing were lower. The contribution rate of micro-aggregates organic carbon to soil organic carbon content was higher in this region. In the 0-20 cm soil layer, the contribution rate of organic carbon in large aggregates increased with the increases of rotation. Considering the characteristics of soil aggregates and their organic carbon, the rotation of six-paddock was the most suitable method for rotational grazing in the desert steppe of the study area.


The synthetic [Tyr5,12,Lys7]-polyphemusin II peptide (T22) binds to the CD4 cell surface molecule.
The [Tyr5,12,Lys7]-polyphemusin II peptide (T22) inhibits HIV-1 replication in lymphocytes. The mechanism of T22 inhibition of HIV-1 replication may involve T22 competition with HIV-1 for attachment sites on the plasma membrane of targeted cells. Here we find that the T22 peptide binds to the CD4 molecule in affinity columns. We also find that antiserum to CD4 inhibits cell attachment to T22. Further CD4+ transfected cells attach to T22 while their parental cells which do not express CD4 do not attach to T22. These data demonstrate that T22 binds to the CD4 molecule and supports the hypothesis that T22 inhibits HIV-1 replication by binding to the cell surface CD4 molecule and inhibiting uptake of the virus.


Occult HIV infection: diagnosis and treatment of older patients.
The decrease in immune status that accompanies normal aging leaves individuals age 50 and older increasingly susceptible to the two main modes of HIV infection: sexual activity and blood transfusions. Although therapy for older HIV patients is essentially the same as for younger patients, knowledge of appropriate drug dosages and nutritional issues that influence the care of the older HIV patient is essential for physicians treating this population. Physicians need to recognize the clinical features of HIV-related dementia and opportunistic infections that distinguish it from other age-related illnesses such as Alzheimer's and Parkinson's disease. Known risk factors that affect older patients should influence physicians to routinely include HIV in their differential diagnoses.


Impact of the east Asian economic crisis on health and health care: Malaysia's response.
In the wake of the east Asian economic crisis, the health budget for the public sector in Malaysia was cut by 12%. The Ministry of Health responded swiftly with a series of broad-based and specific strategies. There was a careful examination of the operating expenditure and where possible measures were taken to minimise the effects of the budget constraints at the service interface. The MOH reprioritised the development of health projects. Important projects such as rural health projects and training facilities, and committed projects, were continued. In public health, population-based preventive and promotive activities were expected to experience some form of curtailment. There is a need to refocus priorities, maximise the utilisation of resources, and increase productivity at all levels and in all sectors, both public and private, in order to minimise the impact of the economic downturn on health.


Clinical findings and serum cardiac troponin I concentrations in horses after intragastric administration of sodium monensin.
Six adult horses were administered sodium monensin, 1.0-1.5 mg/kg, via gastric gavage. Anorexia and/or diarrhea occurred within 24 hr after monensin administration in all 6 horses. Cardiac disease and dysfunction were evaluated by both elevations in heart rate, echocardiography, and an increase in serum concentrations of cardiac troponin I (cTnI), occurred in 4 horses. The development and severity of cardiac disease was likely affected by the monensin dose, vehicle (water or corn oil) mixed with monensin, and/or whether the monensin was administered to fed or fasted horses. Initial increases in cTnI concentrations occurred between 24 and 72 hr after monensin administration. The 2 horses with the highest cTnI concentrations died or were euthanized within 5 days after monensin administration and had severe cardiac disease. One horse had increased cTnI concentrations from day 2 to day 16, but no apparent change in ventricular contractile function was evident on echocardiography. The fourth diseased horse did not return to cTnI reference intervals until day 27 after monensin administration, and the ventricular function was still abnormal just before euthanasia 9 months later. Cardiac troponin I measurements could be useful in managing farm outbreaks of accidental monensin feeding by the early identification of horses with cardiac disease.


Relationship of skin target site free drug concentration (C*) to the in vivo efficacy: an extensive evaluation of the predictive value of the C* concept using acyclovir as a model drug.
For the past few years, our laboratory has been involved in the development of a novel approach for predicting topical in vivo efficacy based on the estimation of skin target site free drug concentration (C*) from in vitro flux data. We have used acyclovir (ACV) as a model drug in the treatment of cutaneous herpes simplex virus type 1 infections in hairless mice. The goal of this study was to rigorously evaluate the applicability of this approach over the entire range of topical efficacy (i.e., from 0 to 100%). We employed a variety of ACV formulations differing in solvent compositions, enhancers, and excipients (and therefore in their efficacies) to achieve this goal. The C* values were estimated from the in vitro flux data obtained in an in vivo-in vitro experimental design that closely approximated the in vivo treatment protocol. For the in vivo antiviral efficacy studies, a finite dose of ACV formulation was applied twice a day, beginning the day after virus inoculation, for 4 days. The lesions were scored on the fifth day, and the efficacies were calculated as described earlier. Our results indicate that, for a variety of formulations over a wide range of efficacies, the predictions based on C* are in good agreement with the observed in vivo efficacies. These findings strongly demonstrate the predictive value of C* over the entire range of topical efficacy, thereby further strengthening its potential for future studies. The findings also indicate that although the excipients in a formulation may alter the rate and extent of available drug at the target site, in these cases, they do not seem to have any effect on the in vivo potency of the drug.


Determination of radio-frequency phase in harmonic frequency modulation spectroscopy.
We have devised two useful schemes to determine the rf phase of the modulation waveforms in harmonic FM spectroscopy, a novel technique that we reported recently for the removal of residual amplitude modulation. The first method is based on the study of the signal line shapes as a function of the relative rf phase of the two modulating signals. By comparing the experimental results with the theoretical ones, the rf phase can be accurately inferred. The second method requires an analysis of the laser FM sideband spectrum. Since the two harmonic rf waveforms are coherently generated and applied simultaneously to the modulator, the frequency-modulated sideband spectrum should show an interference pattern that reveals the rf phase relationship. With the rf phase information available, a suitable feedback control may then be easily incorporated into the spectroscopic detection system.


Contributions of exciton fine structure and hole trapping on the hole state filling effect in the transient absorption spectra of CdSe quantum dots.
The optoelectronic properties of quantum confined semiconductor nanocrystals depend critically on the band edge electron and hole levels and their exciton fine structures. Transient absorption (TA) spectroscopy has been widely used to probe the dynamics of photogenerated electrons, holes, and excitons in these materials through their state filling induced bleach of the band edge exciton transition. Such effects, in principle, reflect the band edge fine structures and are well understood for the conduction band electrons. However, the valence band hole state filling signals remain poorly understood due to the complexity of the valence band level structure and the presence of fast hole trapping in many materials. Herein, we report a study of the valence band hole state filling effect by comparing the TA spectra of CdSe quantum dots (QDs) with different degrees of hole trapping and by selective removal of the conduction band electrons to adsorbed methyl viologen molecules. We observe that in CdSe/CdS core/shell QDs with a high photoluminescence quantum yield of 81%, the valence band hole contributes to 22% ± 1% of the exciton bleach, while a negligible hole state filling signal is observed in CdSe core only QDs with a photoluminescence quantum yield of 17%. This hole state filling effect can be explained by a simplified valence band edge hole model that contains two sets of twofold degenerate hole levels that are responsible for the higher energy bright exciton and lower energy dark exciton states, respectively. Our result clarifies the TA spectral features of the valence band holes and provides insights into the nature of single hole states in CdSe-based QDs.


Visual Search for People Among People.
Humans can effectively search visual scenes by spatial location, visual feature, or whole object. Here, we showed that visual search can also benefit from fast appraisal of relations between individuals in human groups. Healthy adults searched for a facing (seemingly interacting) body dyad among nonfacing dyads or a nonfacing dyad among facing dyads. We varied the task parameters to emphasize processing of targets or distractors. Facing-dyad targets were more likely to recruit attention than nonfacing-dyad targets (Experiments 1, 2, and 4). Facing-dyad distractors were checked and rejected more efficiently than nonfacing-dyad distractors (Experiment 3). Moreover, search for an individual body was more difficult when it was embedded in a facing dyad than in a nonfacing dyad (Experiment 5). We propose that fast grouping of interacting bodies in one attentional unit is the mechanism that accounts for efficient processing of dyads within human groups and for the inefficient access to individual parts within a dyad.


Sjögren's syndrome: the hidden disease.
Sjögren's syndrome is the most common autoimmune disorder among women. This chronic, progressive condition targets moisture-producing glands and seriously disrupts quality of life. With vague symptomatology, individuals frequently delay seeking medical attention and develop systemic organ involvement. Comprehension of clinical features will assist nurses and nurse practitioners in primary care settings to facilitate diagnosis and supportive therapy, thus reducing the burden of disease.


A split-body, randomized, blinded study to evaluate the efficacy of a topical spray composed of essential oils and essential fatty acids from plant extracts with antimicrobial properties.
Bacterial pyoderma is a frequent presentation in dogs. Despite the widespread availability of effective systemic and topical antimicrobial products, good clinical practice currently recommends avoidance of long-term use to mitigate the development of bacterial resistance. To evaluate the speed of resolution of clinical signs of bacterial pyoderma in dogs treated with a systemic antimicrobial agent with or without the use of an adjunctive spray with antimicrobial properties. Twelve dogs with superficial bacterial pyoderma. In this controlled and blinded study, all dogs were treated with oral cefalexin and a topical spray (PYOClean Spray) for 4 weeks. The spray was applied to one half of each dog's body, whereas a placebo spray was applied to the other half. Twelve dogs completed the study. Mean clinical scores were significantly reduced on spray-treated sites, for test product and placebo (respectively), by 47% and 34% at Week 1, 83% and 60% at Week 2, 95% and 82% at Week 3, and 100% and 96% at Week 4. Fifty percent of treated sites were considered clinically and cytologically cured at Week 2, 83% at Week 3, and 100% at Week 4 compared to 8%, 50% and 83% for the placebo sites, respectively. These results demonstrate that use of a topical spray which contains plant-derived essential oils and fatty acids, and compounds with antimicrobial properties (Manuka oil and N-acetyl cysteine) may help to speed resolution of pyoderma and may allow for shorter antimicrobial treatment time.


["Stunned myocardium" on echo cardiogram in myotonic dystrophy: a case report].
A 56-year-old woman with a 23 year-history of myotonic dystrophy was admitted to our hospital because of dysphagia and aspiration pneumonia. On admission, patient's ECG showed Ist degree of atrioventricular block and elongation of QRS (133 msec.). On the third hospital day, abnormal Q wave abruptly appeared in aVL associated with elevation of ST segment in V2 and V3, reverse T wave in I, II, III, aVF and V 2-6 leads on ECG. Echo cardiogram demonstrated asynergy at the apex and septal wall. Coronary angiography was normal. Left ventricular ejection fraction determined by left ventriculography decreased to 47.4%. Based on these findings, we thought "stunned myocardium" had developed. Biopsied myocardium from the apex, septum, and free wall showed non-specific findings including mild fibrosis and lymphocytic infiltration. Although overt myocardial disease is rare in myotonic dystrophy, myocardiac disease such as "stunned myocardium" not due to arrhythmia or coronary angiopathy may develop under severe infection, stress, and/or respiratory distress.


Identifying Ectopic Pregnancy in a Large Integrated Health Care Delivery System: Algorithm Validation.
Surveillance of ectopic pregnancy (EP) using electronic databases is important. To our knowledge, no published study has assessed the validity of EP case ascertainment using electronic health records. We aimed to assess the validity of an enhanced version of a previously validated algorithm, which used a combination of encounters with EP-related diagnostic/procedure codes and methotrexate injections. Medical records of 500 women aged 15-44 years with membership at Kaiser Permanente Southern and Northern California between 2009 and 2018 and a potential EP were randomly selected for chart review, and true cases were identified. The enhanced algorithm included diagnostic/procedure codes from the International Classification of Diseases, Tenth Revision, used telephone appointment visits, and excluded cases with only abdominal EP diagnosis codes. The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and overall performance (Youden index and F-score) of the algorithm were evaluated and compared to the validated algorithm. There were 334 true positive and 166 true negative EP cases with available records. True positive and true negative EP cases did not differ significantly according to maternal age, race/ethnicity, and smoking status. EP cases with only one encounter and non-tubal EPs were more likely to be misclassified. The sensitivity, specificity, PPV, and NPV of the enhanced algorithm for EP were 97.6%, 84.9%, 92.9%, and 94.6%, respectively. The Youden index and F-score were 82.5% and 95.2%, respectively. The sensitivity and NPV were lower for the previously published algorithm at 94.3% and 88.1%, respectively. The sensitivity of surgical procedure codes from electronic chart abstraction to correctly identify surgical management was 91.9%. The overall accuracy, defined as the percentage of EP cases with correct management (surgical, medical, and unclassified) identified by electronic chart abstraction, was 92.3%. The performance of the enhanced algorithm for EP case ascertainment in integrated health care databases is adequate to allow for use in future epidemiological studies. Use of this algorithm will likely result in better capture of true EP cases than the previously validated algorithm.


Child adoption in the Western Highlands Province of Papua New Guinea.
This study investigated the epidemiology of child adoption in the Western Highlands Province of Papua New Guinea. A prospective case-control study of 100 adopted and 100 control children matched by age and sex was done in 1995. The age at the time of adoption ranged from 7 days to 8 years with 64 being adopted in the neonatal period. 28 were adopted because the biological mother had died, 23 because the adoptive mothers had been unable to bear children and 16 because the biological mother was unmarried or 'too young'. Only 11 adopted children were not blood relatives of the adoptive mother; 10 children had been abandoned and 1 had been bought for cash. 97 adoptive mothers were married. The majority (61%) had no formal education and 95% were not in paid employment. Compared with the mothers of the control children fewer adoptive mothers had received any formal education and more of them smoked cigarettes, drank alcohol or chewed betelnut. Social characteristics of the adoptive fathers were similar to the fathers of the control children. Of the 66 living biological mothers for whom information was available, 39 (59%) were married, 16 (24%) single, 8 (12%) divorced and 3 (5%) widowed. For 21 (32%) of the biological mothers the adopted baby was their first. 19 adopted babies were breastfed, 8 exclusively, 6 with the addition of non-human milk and 5 with additional solid feeds. Two-thirds of the adopted children and only 5 controls were bottle-fed. There were no significant differences in nutritional status between the two groups and immunization status was similar. There was widespread ignorance about legal adoption procedures. Only 8 adoptive mothers had any knowledge of and only 2 had followed formal adoption procedures. In this group of adopted children it appeared that most were well cared for, as their nutritional status and immunization status were similar to non-adopted children. There have, however, been suggestions that adoption is a risk factor for child abuse in Papua New Guinea and adoption has recently been associated with severe malnutrition and mortality in a highlands hospital inpatient population. Information relating to formal adoption processes should be more widely disseminated throughout Papua New Guinean communities to protect the rights of adopted children and their adoptive parents.


The therapeutic potential of carbon monoxide.
Carbon monoxide (CO) is increasingly being accepted as a cytoprotective and homeostatic molecule with important signalling capabilities in physiological and pathophysiological situations. The endogenous production of CO occurs through the activity of constitutive (haem oxygenase 2) and inducible (haem oxygenase 1) haem oxygenases, enzymes that are responsible for the catabolism of haem. Through the generation of its products, which in addition to CO includes the bile pigments biliverdin, bilirubin and ferrous iron, the haem oxygenase 1 system also has an obligatory role in the regulation of the stress response and in cell adaptation to injury. This Review provides an overview of the physiology of CO, summarizes the effects of CO gas and CO-releasing molecules in preclinical animal models of cardiovascular disease, inflammatory disorders and organ transplantation, and discusses the development and therapeutic options for the exploitation of this simple gaseous molecule.


The patellar shift index: a reliable and valid measure for patellofemoral congruence following total knee arthroplasty with unresurfaced patella.
The aim of this study was to develop a new radiographic measure, the patellar shift index (PSI), for the precise estimation of patellar position relative to the trochlea after a total knee replacement with an unresurfaced patella. This study included radiographs of 51 patients suffering from anterior knee pain following total knee arthroplasty. Patellofemoral axial radiographs were analyzed to compare the reliability of the PSI to the classical measures of patellofemoral congruence, the lateral patellar tilt (LPT) and patellar displacement (PD). Intra-rater reliability of the PSI, LPT and PD was estimated using the intraclass correlation coefficient (ICC) and the inter-rater reliability using Krippendorff's alpha (Kα). Agreement proportion of was calculated for the PD. Face validity of the PSI was also tested. The PSI had excellent intra (mean ICC=0.91) and inter-rater (Kα=0.92) reliability, as did LPT (mean ICC=0.96; Kα=0.89). The calculation of PD caused a low level of agreement (47.1%) between evaluators in terms of which images could be measured. The exclusion of these radiographs resulted in a high PD intra (ICC=0.96) and inter-rater (Kα=0.97) reliability. The PSI appears to be a reliable and valid measure for patellofemoral congruence in a replaced knee joint with an unresurfaced patella. The superiority of the PSI is the result of its consideration of the geometry and size of the replaced knee joint and independence from radiographic magnification.


The unilateral stapes gusher.
A stapes gusher is an alarming situation occurring during stapes surgery for mixed hearing loss. It is characterized by the sudden profuse flow of cerebrospinal fluid in the middle ear and external ear canal after opening the vestibule of the inner ear. An adult patient with unilateral stapes gusher is described; he was operated on both ears with a good hearing result on both sides. The stapes on the side with the cerebrospinal fluid leak was malformed, especially in the posterior crus--a finding which may suggest the possibility of a stapes gusher. The small-hole stapedotomy is a safe technique when dealing with a profuse cerebrospinal fluid leak, and it enables the closure of the leak with additional tamponade of the oval niche and the achievement of a good hearing result.


Magnetic resonance and single-photon emission tomography findings in a pair of twins discordant for Alzheimer's disease.
The value of functional and morphological neuroimaging in the early diagnosis of Alzheimer's disease (AD) is still debated. Described here are cerebral perfusion and linear measures of medial temporal lobe atrophy in 2 monozygotic twins discordant for AD who were investigated with technetium 99m-hexamethylpropy-leneamineoxime single-photon emission tomography (SPET) and magnetic resonance (MR) imaging. Both showed pathological cortical perfusion findings on SPET, while medical temporal lobe atrophy was present only in the affected twin. MR measures of medial temporal lobe atrophy have greater agreement with clinical data than do SPET measures of cerebral perfusion. Evaluation of atrophy may be useful in the early diagnosis of AD.


IgA Complexes Induce Neutrophil Extracellular Trap Formation More Potently Than IgG Complexes.
Neutrophil extracellular trap (NET) formation is a powerful instrument to fight pathogens, but may induce collateral damage in the affected tissues. Besides pathogen-derived factors, immune complexes are potent inducers of NET formation. Neutrophils express IgA and IgG specific Fc receptors (FcRs) and therefore respond to complexed IgA and IgG. Especially in the context of autoimmune diseases, IgA and IgG immune complexes have been shown to trigger NET formation, a process that putatively contributes to disease severity. However, it is of question if both antibody classes stimulate neutrophils to the same extent. In this study, we compared the capability of IgA and IgG complexes formed by heat aggregation to induce NET formation. While stimulation of neutrophils with IgA complexes robustly induced NET formation, complexed IgG only marginally increased the amount of NETs compared to the unstimulated control. Mixing IgA with IgG before heat aggregation did not increase the effect of complexed IgA on neutrophils. By contrast, the presence of IgG complexes seemed to disturb neutrophil stimulation by IgA complexes. The capacity of complexed IgG to induce NET formation could not be increased by the addition of autologous serum or the removal of terminal sialic acid in the Fc glycan. Together, our data show that IgA is a much more potent inducer of NET formation than IgG. IgA may thus be the main driving force in (auto)immune complex-mediated NET formation.


Emergence of a novel pathogenic recombinant virus from Bartha vaccine and variant pseudorabies virus in China.
Pseudorabies virus (PRV), the causative agent of Aujeszky's disease, has resulted in substantial economic losses in the swine industry worldwide. Previous reports have shown that the PRV variant is responsible for the Pseudorabies outbreaks in Bartha-K61-vaccinated farms in China. However, there is limited information about the evolution of recombination of the PRV variant. Here, we isolated two PRV variants from a Bartha-K61-vaccinated swine farm, named them the JSY7 and JYS13 strains, analysed their complete genomic sequences and evaluated pathogenicity. As results, the JSY7 and JSY13 strains showed different cytopathic effects and plaque sizes. The JSY7 and JSY13 strains had the same Aspartate insertions in the gE protein as other PRV variants. The JSY7 and JSY13 strains were clustered into the same clade based on a genomic phylogenetic analysis. However, the JSY7 strain was relatively close to recent PRV isolates in China, while the JSY13 strain was more closely related to earlier PRV isolates. Interestingly, the gC gene phylogenetic tree showed that the JSY7 strain belonged to genotype II lineage 3, while the JSY13 strain belonged to genotype I and is the same branch with the Bartha strain. Furthermore, the PRV variants were relatively distant from the Bartha strain in the phylogenetic analysis of the gB, gC and gD genes. Importantly, a recombination analysis showed that the JSY13 strain might be a natural recombinant between the minor parental genotype I Bartha strain and the major parental genotype II JSY7 strain. Finally, we also found that the JSY13 strain showed a moderate virulence compared to the JSY7 strain in mice. Taken together, our data provide direct evidence for genomic recombination of PRV in nature, which may play an important role in the evolution and virulence of PRV. This discovery suggests that live PRV vaccine can act as genetic donors for genomic recombination.


Robot-Assisted Latissimus Dorsi Flap Harvest for Partial Breast Reconstruction: Comparison With Endoscopic and Conventional Approaches.
Latissimus dorsi muscle flaps are widely utilized in breast reconstruction. Several methods have been introduced. The aim was to compare the outcomes of robot-assisted breast reconstruction with a latissimus dorsi muscle flap following partial mastectomy with the outcomes of conventional and endoscopic-assisted techniques. In this prospective single-institution study, Korean females diagnosed with breast cancer who underwent partial mastectomy and breast reconstruction with a latissimus dorsi flap from March 2020 to December 2021 were included. The outcomes of surgery and patient satisfaction utilizing the conventional, endoscopic-assisted, and robot-assisted techniques were compared. In total, 57 patients were included in this study, among whom 20 underwent conventional reconstruction, and 17 and 20 patients underwent endoscopic and robotic surgery, respectively. There was no statistically significant difference between the 3 methods in postoperative opioid analgesic dosage (P = .459), hospitalization period (P = .225), or the average total amount of donor site drainage during hospitalization (P = .175). With regard to patient satisfaction after surgery, especially regarding the donor site scar, the conventional method showed a significantly lower score than the other 2 techniques. Robot-assisted breast reconstruction with a latissimus dorsi muscle flap after partial mastectomy showed higher patient satisfaction than that for the conventional open method. Because robotic surgery is more convenient than the endoscopic technique, it is potentially a good alternative to conventional open or endoscopic surgery.


Evaluation of specific immunoglobulin G avidity enzyme linked immunosorbent assay (IgG avidity ELISA) in diagnosis of early and chronic Schistosomiasis mansoni.
This work was performed to study variations of Schistosoma specific immunoglobulins between early and chronic schistosomiasis mansoni in both children and adults. A modified enzyme linked immunosorbent assay (ELISA), based on dissociation of antigen antibody complexes with 8 mol/L urea (8 M urea) solution, was used to measure levels of low avidity immunoglobulin G antibodies (IgG Abs) against Schistosoma mansoni soluble egg antigen (SEA). The study included eighty (80) patients with active mansonian schistosomiasis. They were classified according to age, history, clinical symptomatology and examination and direct parasitological methods of diagnosis into early and chronically infected children and adults. Sera of all patients were subjected to: ELISA measuring Schistosoma specific IgM and IgG., immunoglobulin G (IgG) avidity ELISA and indirect haemagglutination test (IHA). Schistosoma specific IgG avidity ELISA detected higher levels of both urea IgG inhibition percentage and low avidity IgG Abs in early cases of schistosomiasis than chronic ones in both children and adults. Levels of urea IgG inhibition percentage were higher in children than adults. Schistosoma specific IgM/IgG ratio was more than one (> 1) in early cases in both children and adults and less than one (< 1) in chronic cases in children and 70% of adults. IHA titres were statistically higher in chronic cases than early ones in children only. So, it can be concluded that IgG avidity ELISA is a valuable method that helps to differentiate early from chronic schistosomiasis mansoni infection in both children and adults.


[Three cases of multiple liver metastases of carcinoid tumor responding to hepatic arterial infusion chemotherapy using degradable starch microspheres].
We describe three patients with multiple liver metastases of carcinoid tumor who received hepatic arterial infusion chemotherapy using degradable starch microspheres (DSM). A partial response was obtained in all cases, and no side effects were observed. We believe that this chemotherapy was an effective treatment for unresectable liver metastases of carcinoid tumor.


Clinical investigation of the Nucleus Slim Modiolar Electrode.
The Nucleus CI532 cochlear implant incorporates a new precurved electrode array, i.e., the Slim Modiolar electrode (SME), which is designed to bring electrode contacts close to the medial wall of the cochlea while avoiding trauma due to scalar dislocation or contact with the lateral wall during insertion. The primary aim of this prospective study was to determine the final position of the electrode array in clinical cases as evaluated using flat-panel volume computed tomography. Forty-five adult candidates for unilateral cochlear implantation were recruited from 8 centers. Eleven surgeons attended a temporal bone workshop and received further training with a transparent plastic cochlear model just prior to the first surgery. Feedback on the surgical approach and use of the SME was collected via a questionnaire for each case. Computed tomography of the temporal bone was performed postoperatively using flat-panel digital volume tomography or cone beam systems. The primary measure was the final scalar position of the SME (completely in scala tympani or not). Secondly, medial-lateral position and insertion depth were evaluated. Forty-four subjects received a CI532. The SME was located completely in scala tympani for all subjects. Pure round window (44% of the cases), extended round window (22%), and inferior and/or anterior cochleostomy (34%) approaches were successful across surgeons and cases. The SME was generally positioned close to the modiolus. Overinsertion of the array past the first marker tended to push the basal contacts towards the lateral wall and served only to increase the insertion depth of the first electrode contact without increasing the insertion depth of the most apical electrode. Complications were limited to tip fold-overs encountered in 2 subjects; both were attributed to surgical error, with both reimplanted successfully. The new Nucleus CI532 cochlear implant with SME achieved the design goal of producing little or no trauma as indicated by consistent scala tympani placement. Surgeons should be carefully trained to use the new deployment method such that tip fold-overs and over insertion may be avoided.


The role of delta and theta oscillations during ego-motion in healthy adult volunteers.
The successful cortical processing of multisensory input typically requires the integration of data represented in different reference systems to perform many fundamental tasks, such as bipedal locomotion. Animal studies have provided insights into the integration processes performed by the neocortex and have identified region specific tuning curves for different reference frames during ego-motion. Yet, there remains almost no data on this topic in humans.In this study, an experiment originally performed in animal research with the aim to identify brain regions modulated by the position of the head and eyes relative to a translational ego-motion was adapted for humans. Subjects sitting on a motion platform were accelerated along a translational pathway with either eyes and head aligned or a 20° yaw-plane offset relative to the motion direction while EEG was recorded.Using a distributed source localization approach, it was found that activity in area PFm, a part of Brodmann area 40, was modulated by the congruency of translational motion direction, eye, and head position. In addition, an asymmetry between the hemispheres in the opercular-insular region was observed during the cortical processing of the vestibular input. A frequency specific analysis revealed that low-frequency oscillations in the delta- and theta-band are modulated by vestibular stimulation. Source-localization estimated that the observed low-frequency oscillations are generated by vestibular core-regions, such as the parieto-opercular region and frontal areas like the mid-orbital gyrus and the medial frontal gyrus.


Undocumented Latina immigrants in Orange County, California: a comparative analysis.
"This article examines a unique data set randomly collected from Latinas (including 160 undocumented immigrants) and non-Hispanic white women in Orange County, California, including undocumented and documented Latina immigrants, Latina citizens, and non-Hispanic white women. Our survey suggests that undocumented Latinas are younger than documented Latinas, and immigrant Latinas are generally younger than U.S.-citizen Latinas and Anglo women. Undocumented and documented Latinas work in menial service sector jobs, often in domestic services. Most do not have job-related benefits such as medical insurance.... Despite their immigration status, undocumented Latina immigrants often viewed themselves as part of a community in the United States, which significantly influenced their intentions to stay in the United States. Contrary to much of the recent public policy debate over immigration, we did not find that social services influenced Latina immigrants' intentions to stay in the United States."


LPS-stimulated cytokine production in type I cells is modulated by the renin-angiotensin system.
The alveolar epithelium serves as a barrier to the entry of potential respiratory pathogens. Alveolar Type II (TII) cells have immunomodulatory functions, but whether Type I (TI) cells, which comprise approximately 95% of the alveolar epithelium, also play a role in immunity is unknown. Because the renin-angiotensin system (RAS) is emerging as an important mediator of inflammation, and angiotensin-converting enzyme 2 (ACE2), an element of the RAS, has been implicated in lung injury, we hypothesize that TI cells can produce cytokines in response to LPS stimulation, and that this inflammation can be modulated by the RAS. Alveolar TI cells were isolated from adult Sprague-Dawley rat lungs that had been injured with an intratracheal instillation of LPS. PCR was performed to determine whether TI cells expressed transcripts for TNF-α, IL-6, or IL-1β at baseline and after lung injury. Immunocytochemical and protein analysis detected angiotensin II (Ang II) and ACE2, as well as angiotensin Type 1 receptor (AT1R) and Type 2 receptor (AT2R), in TI cells. To separate cell-specific responses, primary TI cells were isolated, cultured, and exposed to LPS, Ang II, or specific inhibitors of AT1R or AT2R. Cytokine production was assayed by ELISA. LPS stimulated the production of all cytokines, whereas ACE2 and losartan, an AT1R inhibitor, blocked elements of the LPS-induced cytokine response. Primary TI cells produce cytokines when treated with LPS, contain important components of the RAS, and can modulate LPS-induced cytokine production via the RAS, suggesting a role for TI cells in the innate immune response of the lung.


Tuning size and sensing properties in colloidal gold nanostars.
Gold nanostars are multibranched nanoparticles with sharp tips, which display extremely interesting plasmonic properties but require optimization. We present a systematic investigation of the influence of different parameters on the size, morphology, and monodispersity of Au nanostars obtained via seeded growth in concentrated solutions of poly(vinylpyrrolidone) in N,N-dimethylformamide. Controlled prereduction of Au(3+) to Au(+) was found to influence monodispersity (narrower plasmon bands), while the [HAuCl(4)]/[seed] molar ratio significantly affects the morphology and tip plasmon resonance frequency. We also varied the size of the seeds (2-30 nm) and found a clear influence on the final nanostar dimensions as well as on the number of spikes, while synthesis temperature notably affects the morphology of the particles, with more rounded morphologies formed above 60 °C. This rounding effect allowed us to confirm the importance of sharp tips on the optical enhancing behavior of these nanoparticles in surface-enhanced raman scattering (SERS). Additionally, the sensitivity toward changes in the local refractive index was found to increase for larger nanostars, though lower figure of merit (FOM) values were obtained because of the larger polydispersity.


Resistance vessel structure: effects of treatment.
The purpose of this article is to review the evidence that the resistance vasculature is altered in hypertension, the role that it may play in the pathogenesis of the disease, and the effect of antihypertensive treatment on the abnormalities. In some models of hypertension, functional changes (i.e., increased vascular smooth muscle sensitivity) have been found, but in human essential hypertension, it appears that structural changes in the resistance vasculature predominate. The structural changes result in an increased media:lumen ratio of the resistance vessels, but it is not clear if these changes are also associated with an increased synthesis of vascular wall material, or whether they can alone be due to a remodeling of the vascular wall (i.e., redistribution of existing material). In both essential hypertension and in the spontaneously hypertensive rat, vascular smooth muscle volume appears to be normal, but is increased in renal hypertensive rats, suggesting that hypertrophy may be a response to imposed increases in load. Although there seems to be a close correlation between altered media:lumen ration and blood pressure in all forms of hypertension investigated, it is generally found to be difficult to obtain full regression of vascular structure. The reason for this remains obscure.


Risk of tuberculin conversion according to occupation among health care workers at a New York City hospital.
Concern about the risk to health care workers of occupationally acquired tuberculosis has resulted in extensive and frequently revised guidelines from the Centers for Disease Control and Prevention (CDC). Most recent studies, however, have determined that community, rather than occupational, exposure is the more significant risk for tuberculin conversion. To assess the relative contribution of community versus occupational risk, we reviewed the health records of 1,303 persons employed from 1991 to 1994 at St. Clare's Hospital in New York City, a hospital with a high tuberculosis case-rate. Demographic information included age, gender, postal zone of residence, country of birth, and BCG vaccination status, while occupations were placed into one of five groups. In multivariate analysis, occupation was significantly associated with risk of tuberculin conversion, while postal zone of residence was not. The group that included housekeeping, laundry, and security personnel and the physician-nurse group had the highest conversion rates. After implementation of CDC guidelines, there was a significant improvement in the employee tuberculin conversion rate. At our hospital, occupation was strongly associated with risk of tuberculin conversion.


Ductal carcinoma in situ of the breast with close or focally involved margins following breast-conserving surgery: treatment with reexcision or radiotherapy with increased dosage.
Following breast-conserving surgery for DCIS, reexcision before radiotherapy is recommended when margins are close or involved. We investigated whether an additional radiation dose could replace reexcision. We selected 208 women with DCIS of the breast treated with breast-conserving surgery between 1992 and 2002 who had either close margins (< 2 mm) (89 pts) or focally (< 1 mm) or minimally (1-15 mm) involved margins (119 pts). Sixty-one patients (29%) underwent reexcision before irradiation and 147 patients (71%) received breast irradiation with boost, without reexcision. Median follow-up was 89 months. Median age was 53 years with 7 patients less than 41. Involved margins were less frequent in the non reexcision group than in the reexcised group (50% vs. 74%, p = 0.0019). All other clinical and histological features were comparable. Median whole-breast radiation dose was 50 Gy. Median total doses to the tumour bed were 67 Gy (range, 45-77) and 60 Gy (range, 46-74), respectively (p < 0.0001). Of the 61 reexcised patients, 56% had residual DCIS and 6% had invasive cancer. Six underwent a mastectomy for persistent margin involvement. Seven-year locoregional failure rates were 9.3% without, and 9.6% with reexcision (ns). No differences were observed when adjusting for margin status. In carefully selected patients with close (< 2 mm) or focally/minimally involved margins, reexcision may be avoided and satisfactory local control achieved by increasing the radiation dose to the tumour bed to at least 66 Gy. These results only apply to patients older than 40 and would need confirmation in independent series.


Endothelial cells recruit macrophages and contribute to a fibrotic milieu in bleomycin lung injury.
Systemic sclerosis (SSc) is a systemic autoimmune disease that causes inflammation, vasculopathy, and fibrosis of the skin and internal organs. One of the most severe complications of SSc involves the development of pulmonary fibrosis. Endothelial cell injury precedes the development of fibrosis, and is believed to be an initiating event. Therefore, we aimed to characterize the role of endothelial cells in the progression of pulmonary fibrosis, using a well-established bleomycin (BLM) model of pulmonary fibrosis. Endothelial cells were isolated by cell sorting, and the analysis of gene expression was performed with quantitative RT-PCR. Endothelial injury was induced between the first and second week, as shown by the elevated expression of the vascular injury markers matrix metallopeptidase-12 and von Willebrand factor. After injury, endothelial activation was indicated by the up-regulation of selectins, CCL chemokines, and inflammatory mediators, including complement anaphylatoxin receptors (C3aR and C5aR), oncostatin M, and leukemia inhibitory factor. The endothelial cell overexpression of fibrotic mediators, including connective tissue growth factor, plasminogen activator inhibitor-1, osteopontin, fibronectin, and fibroblast specific protein-1, was observed in the second and fourth weeks. This study suggests that endothelial cells actively contribute to the disease process via multiple mechanisms, including the recruitment of inflammatory cells and the establishment of a profibrotic environment during the development of BLM-induced pulmonary fibrosis.


Verification of the biological weapons convention: what is needed?
The lack of transparency and verification of the Biological Weapons Convention (BWC) is one factor behind the current weakening of the ban on biological weapons. Despite recent setbacks, governments need to fill the verification gap so that violations of the BWC can be detected and deterred. Continued talks on a strong verification mechanism for the BWC should aim for an open verification regime and one that is flexible enough to adapt to new technical and political circumstances. Effective monitoring of compliance with the BWC will require concerted effort by governments and civil society.


ADDING VFA TO DXA IDENTIFIES FRACTURE RISK IN A WAY NOT DUPLICATED BY OTHER MEASURES.
Published studies have demonstrated that adding vertebral fracture assessment (VFA) to dual-energy X-ray absorptiometry (DXA) identifies more patients with increased fracture risk than DXA alone. But who needs VFA? This study attempts to determine if some test other than VFA could duplicate the additional information obtained by performing VFA on all first-time patients. This study looked at the Fracture Risk Assessment Tool (FRAX), height loss, age, documented back pain, and nonvertebral fragility fractures. VFA was performed on 1,259 (all) DXA patients at their first visit from March 2010 through September 2013. All DXA and VFA results were read by the same International Society for Clinical Densitometry-certified clinician. By DXA alone, 44% were osteoporosis. Adding VFA increased clinical osteoporosis by 36% of the original total patients. Eighty-three "normal bone mineral density" patients were changed to clinical osteoporosis. FRAX identified 53% of the patients with diagnosis changes. Historical height loss was not reliable. Increasing age correlated only weakly with clinical osteoporosis. These are modest numbers from a nonacademic referral practice and may not be typical of other populations. Thirty-six percent of our patients were misclassified by DXA alone, with fragility fractures already taken into account for T-scores of -1.5 and lower. FRAX, height loss, age, back pain, and fragility fractures all failed to identify many of the patients identified by VFA. Seeing the lateral spine images obtained by VFA influenced patients and families. VFA on all first-time patients should be reconsidered. BMD = bone mineral density DXA = dual-energy X-ray absorptiometry FRAX = Fracture Risk Assessment Tool HL = height loss ISCD = International Society for Clinical Densitometry VF = vertebral fracture VFA = vertebral fracture assessment.


Amino-terminal pro-brain natriuretic peptide in normal and hypertensive pregnancy.
To investigate serum levels of amino-terminal pro-brain natriuretic peptide (Nt pro-BNP) as an index of left-ventricular function in normal pregnancy and pregnancies complicated by hypertension and also to investigate levels in both primigravid and multigravid women. Women with hypertension in pregnancy (at least two readings of systolic blood pressure > 140 mm Hg and diastolic blood pressure > 90 mm Hg) (n = 24) and normotensive women (n = 42) were included in the study. Serum Nt pro-BNP was measured using an enzyme-linked immunosorbent assay technique. The median serum Nt pro-BNP level in pregnancies complicated by hypertension was 420 fmol/L, which was significantly greater than that measured in samples obtained from normotensive women in pregnancy (340 fmol/L) (p = 0.03). There was a nonsignificant trend toward increased levels in proteinuric as compared to nonproteinuric hypertension in pregnancy. Multigravida had higher Nt pro-BNP levels (n = 26; median Nt pro-BNP = 358 fmol/L) than primigravida (n = 16; median Nt pro-BNP = 278 fmol/L) (p = 0.01) in association with normal pregnancy. Multigravida also demonstrated a dramatic rise in serum Nt pro-BNP levels in association with hypertension in pregnancy (n = 13; median Nt pro-BNP = 572 fmol/L) as compared to normal pregnancy (n = 26; median Nt pro-BNP = 358 fmol/L) (p = 0.009). Serum Nt pro-BNP is elevated in women with hypertensive disorders of pregnancy, indicating elevated left-ventricular filling pressures. Measured serum levels in both normal and hypertensive pregnancy are higher in multigravida than in primigravida.


Histological and histochemical studies on the fundic mucosa of the camel's stomach (Camelus dromedarius).
The one-humped camel, like our domestic ruminants, has a capacious compartmentalized stomach and is a ruminating animal. In our studies wer followed the currently predominant opinion that the camel stomach consists of three compartments (Vallenas, cummings, Munnel 1971). The third one of it is considered as the tubular portion following the second compartment or reticulum and extends till to the pylorus. The Tunica mucosa in the terminal dilated part (distal one-fifth) of this third compartment bears at its greater curvature very thick folds enclosing flat furrows which divide the mucosa into nearly regular areas (gastric areas). This portion of the third compartment contains the proper gastric glands (fundic glands) which differ somewhat from those in the advanced ruminants, especially in the arrangement of the parietal cells and the behaviour of the chief cells which can store mucosubstance during fastening or diminishing of the food in the camel.


Infection of CD8+ T lymphocytes with HIV. Requirement for interaction with infected CD4+ cells and induction of infectious virus from chronically infected CD8+ cells.
In this study, we have investigated the basic requirements for HIV-1 infection of CD8+ lymphocytes in vitro. Unfractionated PBL obtained from healthy HIV-1 seronegative donors were activated with PHA and infected in vitro with HIV-1LAV. Based on immunofluorescent labeling, the vast majority of cells (85 to 97%) surviving peak virus replication belonged to the CD8+ subset and only a small percentage (0.5 to 1.5%) were CD4+. Amplification of HIV-1 proviral sequences by polymerase chain reaction performed on the sorted surviving CD8+ cells demonstrated that CD8+ cells harbored HIV-1 proviral DNA. In addition, stimulation of these HIV-1-infected, CD8(+)-sorted cells either with PHA or anti-CD2 mAb resulted in induction of virus replication, as measured by reverse transcriptase activity. Electron microscopic analysis of CD8+ cells chronically infected with HIV-1 and stimulated with PHA showed typical virions budding from, and associated with, the surface of cells immunolabeled with gold beads directed toward the CD8 molecule. Infection of CD8+ cells with HIV-1 occurred only when CD4+ cells were present in the PHA-activated lymphocyte population exposed to HIV-1 at the beginning of the culture or when sorted CD8+CD4- lymphocytes were cocultured with autologous sorted CD8-CD4+ cells that had been previously infected with HIV-1. Coculture of these cells with PHA-blasts and incubation of their supernatants with a CD4+ cell line showed that these chronically infected CD8+ cells could spread HIV-1 infection to uninfected CD4+ cells after stimulation with PHA or anti-CD2 mAb. Therefore, these results suggest that the minimal requirement for in vitro infection of CD3+CD8+CD4- lymphocytes is the presence of infected CD4+ cells and that infected CD8+ T lymphocytes can further spread the infection to CD4+ cells.


CNS axonal degeneration and transport deficits at the optic nerve head precede structural and functional loss of retinal ganglion cells in a mouse model of glaucoma.
Glaucoma is a leading neurodegenerative disease affecting over 70 million individuals worldwide. Early pathological events of axonal degeneration and retinopathy in response to elevated intraocular pressure (IOP) are limited and not well-defined due to the lack of appropriate animal models that faithfully replicate all the phenotypes of primary open angle glaucoma (POAG), the most common form of glaucoma. Glucocorticoid (GC)-induced ocular hypertension (OHT) and its associated iatrogenic open-angle glaucoma share many features with POAG. Here, we characterized a novel mouse model of GC-induced OHT for glaucomatous neurodegeneration and further explored early pathological events of axonal degeneration in response to elevated IOP. C57BL/6 J mice were periocularly injected with either vehicle or the potent GC, dexamethasone 21-acetate (Dex) once a week for 10 weeks. Glaucoma phenotypes including IOP, outflow facility, structural and functional loss of retinal ganglion cells (RGCs), optic nerve (ON) degeneration, gliosis, and anterograde axonal transport deficits were examined at various stages of OHT. Prolonged treatment with Dex leads to glaucoma in mice similar to POAG patients including IOP elevation due to reduced outflow facility and dysfunction of trabecular meshwork, progressive ON degeneration and structural and functional loss of RGCs. Lowering of IOP rescued Dex-induced ON degeneration and RGC loss, suggesting that glaucomatous neurodegeneration is IOP dependent. Also, Dex-induced neurodegeneration was associated with activation of astrocytes, axonal transport deficits, ON demyelination, mitochondrial accumulation and immune cell infiltration in the optic nerve head (ONH) region. Our studies further show that ON degeneration precedes structural and functional loss of RGCs in Dex-treated mice. Axonal damage and transport deficits initiate at the ONH and progress toward the distal end of ON and target regions in the brain (i.e. superior colliculus). Most of anterograde transport was preserved during initial stages of axonal degeneration (30% loss) and complete transport deficits were only observed at the ONH during later stages of severe axonal degeneration (50% loss). These findings indicate that ON degeneration and transport deficits at the ONH precede RGC structural and functional loss and provide a new potential therapeutic window for rescuing neuronal loss and restoring health of damaged axons in glaucoma.


Protanopic observers show nearly normal color constancy with natural reflectance spectra.
The ability of color-deficient observers to discriminate between illuminant changes and surface-reflectance changes in a scene was tested with natural and Munsell reflectance spectra. To avoid the confounding effects of spatial structure, stimuli were simulations of Mondrian-like colored patterns, presented on a computer-controlled color monitor. Protanopes performed less well than normal trichromats, regardless of the type of reflectance spectra, but they were least disadvantaged with patterns comprising reflectance spectra drawn from urban and rural scenes, more characteristic of the natural environment.


Occult papillary carcinoma of the thyroid presenting as a cervical cyst.
A cystic neck mass representing metastatic papillary thyroid cancer to a cervical lymph node may be the presenting symptom in patients with an occult papillary cancer of the thyroid. This cystic change can cause diagnostic problems and not infrequently delay identification of the primary thyroid tumor. This study investigates the frequency, treatment, and pathologic features of this entity. All clinical charts and microscopic slides of 136 consecutive patients who underwent thyroid operation for papillary carcinoma (PC) from 1990 to 1995 were reviewed. Hematoxylin-and-eosin and immunohistochemical stains (IMHS) for thyroglobulin also were reviewed. Eight patients (5.8%) presented with a cystic neck mass and no palpable thyroid lesion. In all 8 patients, the diagnosis was made by an excision of the cystic neck mass. In 3 patients, the cyst demonstrated classical features of PC, such as papillae and psammoma bodies. In the remaining 5 (62%), only focal papillae or nuclear features of papillary carcinoma were present. A careful review of the histology and IMHS were necessary to arrive at the correct diagnosis in these 5 patients. Occult papillary cancer of the thyroid presenting as a cystic neck mass is not uncommon and must be considered in the differential diagnosis. Excision and careful review of the histology and IMHS is necessary to prevent delay of the proper diagnosis. Although the thyroid tumor was less than 1 cm and sometimes only microscopic, the extensive nodal metastasis has led us to favor near total or total thyroidectomy and modified neck dissection in this entity.


Application to rat lung of the extended Rorschach-Hazlewood model of spin-lattice relaxation.
The spin-lattice relaxation time T1 was measured in excised degassed (airless) rat lungs over the frequency range 6.7 to 80.5 MHz. The observed frequency dependence was fitted successfully to the water-biopolymer cross-relaxation theory proposed by H. E. Rorschach and C. F. Hazlewood (RH) [J. Magn. Reson. 70, 79 (1986)]. The rotating frame spin-lattice relaxation time T1(rho) was also measured in rat lung fragments over the frequency range 0.56 to 5.6 kHz, and the observed frequency dependence was explained with an extension of the RH model. The agreement between the theory and the experimental data in both cases is good.


Assessment of chitosan antimicrobial effect on wine microbes.
Chitosan is an active highly charged polysaccharide that has initially been developed in oenology to eliminate the spoilage yeast B. bruxellensis. However, different forms of chitosan exist, some complying with EU regulation for their use in wines, others not. Moreover, with the trend in oenology of limiting SO2, more and more questions arise as to the impact of chitosan on other microorganisms of the grape and wine environment. We investigated the antimicrobial efficiency of chitosan on a large oenological microbial collection, englobing technological as well as spoilage microorganisms. Results show that most species are affected at least transiently. Furthermore, a high variability prevails within most species and sensitive, intermediate and tolerant strains can be observed. This study also highlights different efficiencies depending on the wine parameters or the winemaking stage, giving important indications on which winemaking issues can be solved using chitosan. Chitosan treatment does not seem to be appropriate to limit the musts microbial pressure and Saccharomyces cerevisiae cannot be stopped during alcoholic fermentation, especially in sweet wines. Likewise, acetic acid bacteria are poorly impacted by chitosan. After alcoholic fermentation, chitosan can efficiently limit non-Saccharomyces yeast and lactic acid bacteria but special care should be given as to whether malolactic fermentation is wanted or not. Indeed, O. oeni can be severely impacted by chitosan, even months after treatment. Finally, this study highlights the crucial importance of the chitosan type used in its efficiency towards microbial stabilization. While a high molecular weight chitosan has limited antimicrobial properties, a chitosan with a much lower one, complying with EU and OIV regulation and specifications for its use in wine is much more efficient.