Invariance of vestibulo-ocular reflex gain to head impulses in pitch at different initial eye-in-orbit elevations: implications for Alexander's law.
These findings are in line with previous data on the horizontal vestibulo-ocular reflex (VOR) from this laboratory and suggest that eye position signals do not modulate natural vestibular responses. Hence, the Alexander's law (AL) phenomenon cannot be interpreted simply as a consequence of vestibular or oculomotor nuclei activity modulation with desired gaze. AL states that the intensity of the spontaneous nystagmus of a patient with a unilateral vestibular lesion grows with increasing gaze in the direction of the fast phase. Some of the mechanisms proposed to account for the gaze effects assume a direct modification of the normal VOR by eye position signals. We tested the validity of these assumptions and investigated the effects of gaze direction on the normal vertical human VOR in the behaviorally relevant high frequency range. Head and eye movements were recorded with the search coil method during passive head impulses in pitch, while subjects were asked to hold gaze at various elevation angles in 8° steps within ± 16° from the straight ahead reference position. Upward and downward head rotations produced VOR gains of similar magnitude. Furthermore, the gain remained unaffected by eye-in-orbit position for both upward and downward head impulses.


Caspase-12 silencing attenuates inhibitory effects of cigarette smoke extract on NOD1 signaling and hBDs expression in human oral mucosal epithelial cells.
Cigarette smoke exposure is associated with increased risk of various diseases. Epithelial cells-mediated innate immune responses to infectious pathogens are compromised by cigarette smoke. Although many studies have established that cigarette smoke exposure affects the expression of Toll-liked receptor (TLR), it remains unknown whether the nucleotide-binding oligomerization domain-containing protein 1 (NOD1) expression is affected by cigarette smoke exposure. In the study, we investigated effects of cigarette smoke extract (CSE) on NOD1 signaling in an immortalized human oral mucosal epithelial (Leuk-1) cell line. We first found that CSE inhibited NOD1 expression in a dose-dependent manner. Moreover, CSE modulated the expression of other crucial molecules in NOD1 signaling and human β defensin (hBD) 1, 2 and 3. We found that RNA interference-induced Caspase-12 silencing increased NOD1 and phospho-NF-κB (p-NF-κB) expression and down-regulated RIP2 expression. The inhibitory effects of CSE on NOD1 signaling can be attenuated partially through Caspase-12 silencing. Intriguingly, Caspase-12 silencing abrogated inhibitory effects of CSE on hBD1, 3 expression and augmented induced effect of CSE on hBD2 expression. Caspase-12 could play a vital role in the inhibitory effects of cigarette smoke on NOD1 signaling and hBDs expression in oral mucosal epithelial cells.


Primary care redesign for person-centred care: delivering an international generalist revolution.
Person-centred primary care is a priority for patients, healthcare practitioners and health policy. Despite this, data suggest person-centred care is still not consistently achieved - and indeed, that in some areas, care may be worsening. Whole-person care is the expertise of the medical generalist - an area of clinical practice that has been neglected by health policy for some time. It is internationally recognised that there is a need to rebalance specialist and generalist primary care. Drawing on 15 years of scholarship within the science of medical generalism (the expertise of whole-person medical care), this discussion paper outlines a three-tiered approach to primary care redesign; describing changes needed at the level of the consultation, practice set up and strategic planning. The changing needs of patients living with complex chronic illness has already started a revolution in our understanding of healthcare systems. This paper outlines work to support that paradigm shift from disease-focused to person-focused primary healthcare.


The use of gamete intra-fallopian transfer with donor spermatozoa after failed donor insemination.
The objective of this study was to assess the efficacy of gamete intra-Fallopian transfer (GIFT) in couples who had failed to conceive by donor insemination. The study was designed as a retrospective analysis of couples who entered the GIFT programme after 12 failed cycles of donor insemination. It took place in a comprehensive reproductive clinic with large donor insemination and in-vitro fertilization/GIFT programmes. A total of 197 patients received a total of 350 treatments from 1985 until 1992. Couples entered the GIFT programme with the routine stimulation and monitoring. The only difference was that frozen spermatozoa were used for the insemination. The main outcome measure was pregnancy, defined as a positive beta-human chorionic gonadotrophin (> 30 IU/l) at 16 days after replacement of gametes. The overall pregnancy rate achieved was 31% per cycle. Life table analysis showed a cumulative pregnancy rate of 75.4 +/- 5.7% after four cycles and 96.0 +/- 2.7% after eight cycles. It was concluded that the use of GIFT with donor spermatozoa is a highly effective treatment and should be offered to all couples who fail to conceive with donor insemination.


Dual radiobiological interpretations of retrospective clinical data: the time factor.
Dual interpretations are different radiobiological mechanisms that explain theoretically the same observed results. Radiobiological interpretations of the time factor are most frequently based on changes in total dose that produce a given effect. If this dose is increased by different mechanisms (e.g. increasing overall time and decreasing dose per fraction) at the same time, proposals for altered fractionation schemes based on the choice of one or the other mechanism, in principle, can lead to erroneous predictions of outcome. This is especially the case when the analyses are based on retrospective clinical data, where the influence of patient selection is unknown. Examples of dual interpretations taken from the literature on head and neck, melanoma and prostate cancer are discussed.


Anti-laminin 332 mucous membrane pemphigoid in a young woman treated with rituximab.
Mucous membrane pemphigoid, formerly known as cicatricial pemphigoid, is a rare and difficult-to-treat bullous disorder that occurs most commonly in older adults. We describe a 32-year-old woman who was diagnosed with anti-laminin 332 mucous membrane pemphigoid through indirect immunofluorescence for laminin 332 following nonspecific histologic and direct immunofluorescence findings. At 16 weeks following completion of her first cycle of with rituximab 375mg/m2 weekly for four weeks, her mucosal erosions had resolved. Although not widely available, this case highlights the utility of anti-laminin 332 immunofluorescence for diagnostic confirmation of this entity and the efficacy of rituximab in obtaining disease control.


Synovial fluid eosinophilia in Lyme disease.
We describe three 14-year-old boys who developed synovial fluid eosinophilia associated with Lyme disease. One patient, with arthritis that began in 1975, had the first documented case of Lyme disease in New Jersey. Lyme disease should be considered when eosinophilia is noted on analysis of synovial fluid from patients with undiagnosed arthritis.


In vitro fertilization in inbred BALB/c mice II: effects of lactate, osmolarity and calcium on in vitro capacitation.
To elucidate requirements for in vitro sperm capacitation in inbred BALB/c mice, osmolarity, calcium and lactate were optimized using modified simplex optimization medium (mKSOM). Modified human tubal fluid (mHTF), a capacitation-supporting medium, was used as a control. In the first series of experiments, the effects of calcium and osmolarity were studied in the presence of lactate. Although preincubation with >or=5 mM CaCl2 improved fertilization after insemination significantly, it was still significantly lower than incubation with mHTF. To obtain fertilization at the equivalent levels to that of mHTF, isotonic osmolarity (305 mOsmol) was required. Trehalose, an osmotic reagent, could substitute for NaCl partially. In the second series of experiments, the effects of lactate were examined using a concentration of 5 mM calcium and isotonic osmolarity. Preincubation with <or=2.5 mM lactate increased fertilization significantly (>75%), as well as the percentages of B (capacitated) pattern sperm (>or=40%) in chlortetracycline (CTC) staining, as compared with incubation in mHTF (46% and 28%, respectively; p<0.05). In the third series of experiments, the effects of osmolarity and calcium in the absence of lactate were examined. An increase in osmolarity during sperm preincubation increased both fertilization and B-pattern sperm significantly in a dose-dependent manner. Trehalose, sucrose and choline chloride could substitute for NaCl. An increase in CaCl2 concentration during preincubation had no effect on fertilization, but this increase reduced the percentages of B-pattern sperm. In vitro capacitation of inbred BALB/c mice is sensitive to lactate and osmolarity, but that sensitivity for calcium varies depending on the presence or absence of lactate.


Anti-CD11a prevents deletion of self-reactive T cells in neonatal C57BR mice.
The process of thymic maturation permits development of T cells expressing receptors which recognize self-major histocompatibility complex (MHC) determinants, but deletes T cells recognizing self-MHC determinants with high affinity. This selection process is evolutionarily conserved, and presumably serves in part to prevent the release of autoreactive cells. However, the mechanisms involved in the selection process, and the molecules required are incompletely characterized. Lymphocyte function-associated antigen-1 (LFA-1) is an accessory molecule important in T-cell activation, is involved in thymocyte-epithelial cell binding, and contributes to the maturation of CD4-CD8- thymocytes to the CD4+CD8+ stage. In this report we have investigated whether LFA-1 also contributes to the thymic deletion of potentially self-reactive cells. Neonatal C57Br mice were injected with amounts of a monoclonal antibody to LFA-1 that saturated thymic binding sites, then splenocytes were examined for T cells expressing receptors normally deleted in the thymus. The results demonstrate that V beta 17a+ T cells, normally deleted in this strain, can be detected in the spleen following administration of anti-LFA-1, thus supporting the hypothesis that LFA-1 also contributes to negative selection. The potential significance of LFA-1 involvement in multiple thymic maturation events is discussed.


Governing street-based injecting drug users: a critique of heroin overdose prevention in Australia.
This article provides a critical analysis of existing approaches to the prevention of heroin overdose in Australia. It draws on almost 2 years of ethnographic research with street-based injecting drug users (IDUs), street-based sex workers and service providers in Melbourne, Australia's second largest city, and on recent anthropological and sociological work on governmentality. The substantive sections of the article argue: (1) that heroin overdose prevention in Australia contains implicit or explicit assumptions of rationality and personal autonomy, continues to emphasise individual behaviour change and inscribes a self-disciplined, self-aware, self-regulating subject; and (2) that the social, cultural and economic realities--the 'lived experience'--of street-based IDUs and sex workers may undermine or hinder the successful adoption of overdose prevention strategies. The paper concludes by arguing that the 'chaotic' practices of street-based IDUs and sex workers arise in response to particular 'risk environments', and that individually focused overdose prevention strategies, while an important first step, need to be complemented by measures addressing the macro- and micro-aspects of risk environments.


Defective killing of enterococci: a common property of antimicrobial agents acting on the cell wall.
We tested the ability of antimicrobial agents that act on the cell wall to kill enterococci and found defective killing (a minimal bactericidal concentration/minimal inhibitory concentration ratio of greater than or equal to 32) with both beta-lactams (penicillin G and cephalothin) and non-beta-lactams (vancomycin, cycloserine, and bacitracin). Our results indicate that the resistance of enterococci to antimicrobial killing spans the spectrum of agents known to inhibit cell wall synthesis and suggest that the mechanism responsible for enterococcal resistance to killing by these drugs may be a defective autolytic enzyme system.


A signaling role for leptin in puberty onset in female rats?
The brain might initiate puberty in response to adequate leptin signaling from the periphery. We studied the link between whole body fat, plasma leptin levels, and puberty onset, in both controls and food-restricted female Wistar rats from age 22 to 42 days. Body fat correlated positively with the prevailing plasma leptin levels (r = 0.776) and with the time of puberty onset, i.e. vaginal opening (VO) (r = 0.691). Blood samples collected every other day at ZT 2, 6, and 12, showed a diurnal rhythm in leptin levels with a nadir at ZT 6. Furthermore, leptin levels increased over the pubertal period. Food restriction (FR) delayed the time of VO considerably (median VO at 38 vs 28 d), and body fat and plasma leptin levels were lower in the FR group (p <0.01), although the positive correlation between body fat and leptin levels remained. Only the absolute, but not the relative amount of body fat increased with age. These data support the notion that leptin could indeed serve as the link between nutritional status and the reproductive axis, and in this way participate in the timing of puberty.


Elastohydrodynamic autoregulation in soft overlapping channels.
Controlling fluid flow from an unsteady source is a challenging problem that is relevant in both living and man-made systems. Animals have evolved various autoregulatory mechanisms to maintain homeostasis in vital organs. This keeps the influx of nutrients essentially constant and independent of the perfusion pressure. Up to this point, the autoregulation processes have primarily been ascribed to active mechanisms that regulate vessel size, thereby adjusting the hydraulic conductance in response to, e.g., sensing of wall shear stress. We propose an alternative elastohydrodynamic mechanism based on contacting soft vessels. Inspired by Starling's resistor, we combine experiments and theory to study the flow of a viscous liquid through a self-intersecting soft conduit. In the overlapping region, the pressure difference between the two channel segments can cause one pipe segment to dilate while the other is compressed. If the tissue is sufficiently soft, this mode of fluid-structure interactions can lead to flow autoregulation. Our experimental observations compare well to a predictive model based on low-Reynolds-number fluid flow and linear elasticity. Implications for conduit arrangement and passive autoregulation in organs and limbs are discussed.


Immunological characteristics of PEP carboxylase from leaves of C3-, C4- and C3-C4 intermediate species of Alternanthera--comparison with selected C3- and C4- plants.
Immunological cross-reactivity of phosphoenolpyruvate carboxylase (PEPC) in leaf extracts of C3-, C4- and C3-C4 intermediate species of Alternanthera (along with a few other C3- and C4- plants) was studied using anti-PEPC antibodies raised against PEPC of Amaranthus hypochondriacus (belonging to the same family as that of Alternanthera, namely Amaranthaceae). Antibodies were also raised in rabbits against the purified PEPC from Zea mays (C4- monocot-Poaceae) as well as Alternanthera pungens (C4- dicot-Amaranthaceae). Monospecificity of PEPC-antiserum was confirmed by immunoprecipitation. Amount of PEPC protein in leaf extracts of A. hypochondriacus could be quantified by single radial immunodiffusion. Cros- reactivity of PEPC in leaf extracts from selected C3-, C4-, and C3-C4 intermediate species (including those of Alternanthera) was examined using Ouchterlony double diffusion and Western blots. Anti-PEPC antiserum raised against A. hypochondriacus enzyme showed high cross-reactivity with PEPC in leaf extracts of A. hypochondriacus or Amaranthus viridis or Alternanthera pungens (all C4 dicots), but limited cross-reactivity with that of Zea mays, Sorghum or Pennisetum (all C4 monocots). Interestingly, PEPC in leaf extracts of Alternanthera tenella, A. ficoides, Parthenium hysterophorus (C3-C4 intermediates) exhibited stronger cross-reactivity (with anti-serum raised against PEPC from Amaranthus hypochondriacus) than that of Pisum sativum, Commelina benghalensis, Altenanthera sessilis (C3 plants). Further studies on cross-reactivities of PEPC in leaf extracts of these plants with anti-PEPC antisera raised against PEPC from leaves of Zea mays or Alternanthera pungens confirmed two points--(i) PEPC of C3-C4 intermediate is distinct from C3 species and intermediate between those of C3- and C4-species; and (ii) PEPC of C4-dicots was closer to that of C3-species or C3-C4 intermediates (dicots) than to that of C4-monocots.


Analysis and stability of the constituents of St. John's wort oils prepared with different methods.
St. John's wort is a medicinal plant with a long history of use in traditional medicine all over Europe. Traditional preparations and in particular the infused oil from SJW flowers remains one of the most popular and curative topical remedy against ulcerations and burns. The presence of the characteristic polyprenylated acylphloroglucinol derivatives, namely hyperforin and analogs are instead related to the oil's therapeutic activity. Indeed, it is well known that hyperforin has a potent antibacterial activity. In this study we tried to rationalize the production system of the oily preparation in order to obtain the highest concentration and stability of phloroglucinols. Five different samples of SJW oils were evaluated by HPLC-DAD-MS analysis to verify the variability and stability of the constituents according to the following factors: different harvesting time, fresh or dried plant material, use of sunlight or heating systems during extraction. The stability of these oils during 1 year was also tested.


Characterisation of two snake toxin-targeting human monoclonal immunoglobulin G antibodies expressed in tobacco plants.
Current snakebite antivenoms are based on polyclonal animal-derived antibodies, which can neutralize snake venom toxins in envenomed victims, but which are also associated with adverse reactions. Therefore, several efforts within antivenom research aim to explore the utility of recombinant monoclonal antibodies, such as human immunoglobulin G (IgG) antibodies, which are routinely used in the clinic for other indications. In this study, the feasibility of using tobacco plants as bioreactors for expressing full-length human monoclonal IgG antibodies against snake toxins was investigated. We show that the plant-produced antibodies perform similarly to their mammalian cell-expressed equivalents in terms of in vitro antigen binding. Complete neutralization was achieved by both the plant and mammalian cell-produced anti-α-cobratoxin antibody. The feasibility of using plant-based expression systems may potentially make it easier for laboratories in resource-poor settings to work with human monoclonal IgG antibodies.


[Bioindicator role of plants in the evaluation of soil pollution in small northern towns].
The study has established that only purple willow and cedar out of 23 species of the plants being examined are the most sensitive representatives of northern phytocenosis to the pollutants (heavy metals). Minimization of the air levels of pollutants and urbanized environmental sanitation require the re-orientation town-planning measures to a new scheme of creating a green plantation system, the expansion of whose area should be made in accordance with selection of plants of various species, by proceeding from the major tasks of the planting of trees and gardens and by taking into account the natural and climatic conditions for formation of ambient air pollution in this area, from the pattern of the placing and operation of structural-and-planning constructions of a town, from the morphofunctional features of representatives of northern phytocenosis to the action of man-caused impurities and environmental toxic substances. At the same time, while forming the environmental infrastructure the most important function of green plantations in the towns should be not only recreational and decorative, but also hygienic and sanitary ones that are to clear the environment from hazardous substances, to absorb gases, and to adsorb dust, which will undoubtedly promote environmental sanitation and therefore health maintenance and promotion in urban dwellers.


On the influence of thymidine analogues on the activity of phage fd promoters in vitro.
RF I DNA of phage fd containing 5-bromo-deoxyuridine (br5Ud) or deoxyuridine (Ud) instead of deoxythymidine (Td) inthe codogenic strand was synthesized in vitro. The modified genomes could be cleaved by restriction endonuclease Hpa II. Although the recognition site of Hpa II is CCGG, the cleavage rate was significantly reduced with Ud-containing DNA. Both base substitutions altered the mobilities of several DNA fragments under the conditions of polyacrylamide gel electrophoresis. The fragments containing binding sites for RNA polymerase were assayed for the rates of stable complex formation. The substitution of Td for both, Ud and br5Ud, strongly influenced this parameter. Thus the methyl group of Td has to be regarded as one of the sites in DNA which determine the rate of stable RNA polymerase binding and thereby possibly mediate promoter activity in vitro (24,25,26). In most cases the rate of complex formation was decreased by Ud, but increased by br5Ud.


[Protection of the pulmonary toxic effects of normobaric oxygen by inducers of cytochrome P450-linked monooxygenases].
Inducers of cytochrome P450-linked mono-oxygenases increase the normobaric oxygen tolerance of the adult rat. Pulmonary inducers, as 3-methylcholanthrene and beta-naphthoflavone permit the rat survival and simultaneously a decrease of pulmonary edema. Phenobarbital, an hepatic inducer had lesser effects both on survival rate and on pulmonary and lymphoïd oxygen toxicity.


The rare PGM1 7-1 phenotype in a Polish family.
The phenotype PGM1 7-1 is described in eight members of a Polish family. Analysis of the findings confirmed the hereditary character of this phenotype, dependent on presence of the PGM71 gene in conjunction with the PGM11 gene in all the subjects examined.


Alternative pre-mRNA splicing of the sterol 27-hydroxylase gene (CYP 27) caused by a G to A mutation at the last nucleotide of exon 6 in a patient with cerebrotendinous xanthomatosis (CTX).
A recently identified G to A mutation at the last nucleotide of exon 6 of the sterol 27-hydroxylase gene (CYP 27) in a patient with cerebrotendinous xanthomatosis (CTX) was shown here to cause alternative pre-mRNA splicing of the gene. Northern blot analysis of the patient's RNA revealed a broadened band in the human CYP 27 mRNA region compared to that of the normal sample, indicating that there may exist differently spliced mRNA species in the patient. RT-PCR produced three fragments in the patient, one was full-length size and the other two were of smaller sizes. Sequence analysis confirmed that the nucleotide of the full-length size was identical to that of the normal full-length cDNA, except for the G to A mutation at codon 362, which corresponds to the last nucleotide of exon 6. One of the smaller size species lacked exon 6 and the other was absent from the 3' terminal 88 bp of exon 6 due to the use of an activated cryptic 5' splice site in exon 6. The correctly spliced mRNA harbouring the G to A mutation was responsible for the deficiency of the sterol 27-hydroxylase activity, as confirmed by transfection experiment. Transfection of constructed minigenes, with or without the mutation, showed that correctly spliced mRNA was observed in the normal minigene while the mutant minigene was differently spliced. This is the first report of a G to A substitution at the last nucleotide of an exon resulting in both normal and abnormal pre-mRNA splicings, including exon skipping and activating of a coding region cryptic 5' splice site. The results reveal a new molecular basis for the CTX and provide information on aberrant splicing of pre-mRNA in multi-exon genes.


Spatial Assessment of Heterogeneous Tissue Natural Frequency Using Micro-Force Optical Coherence Elastography.
Analysis of corneal tissue natural frequency was recently proposed as a biomarker for corneal biomechanics and has been performed using high-resolution optical coherence tomography (OCT)-based elastography (OCE). However, it remains unknown whether natural frequency analysis can resolve local variations in tissue structure. We measured heterogeneous samples to evaluate the correspondence between natural frequency distributions and regional structural variations. Sub-micrometer sample oscillations were induced point-wise by microliter air pulses (60-85 Pa, 3 ms) and detected correspondingly at each point using a 1,300 nm spectral domain common path OCT system with 0.44 nm phase detection sensitivity. The resulting oscillation frequency features were analyzed via fast Fourier transform and natural frequency was characterized using a single degree of freedom (SDOF) model. Oscillation features at each measurement point showed a complex frequency response with multiple frequency components that corresponded with global structural features; while the variation of frequency magnitude at each location reflected the local sample features. Silicone blocks (255.1 ± 11.0 Hz and 249.0 ± 4.6 Hz) embedded in an agar base (355.6 ± 0.8 Hz and 361.3 ± 5.5 Hz) were clearly distinguishable by natural frequency. In a beef shank sample, central fat and connective tissues had lower natural frequencies (91.7 ± 58.2 Hz) than muscle tissue (left side: 252.6 ± 52.3 Hz; right side: 161.5 ± 35.8 Hz). As a first step, we have shown the possibility of natural frequency OCE methods to characterize global and local features of heterogeneous samples. This method can provide additional information on corneal properties, complementary to current clinical biomechanical assessments, and could become a useful tool for clinical detection of ocular disease and evaluation of medical or surgical treatment outcomes.


Fungal infections of the central nervous system: the clinical syndromes.
Fungal infections of the central nervous system (CNS) are being increasingly diagnosed both in immunocompromised and immunocompetent individuals. Sinocranial aspergillosis is more frequently described from countries with temperate climates, more often in otherwise immunocompetent individuals. The clinical syndromes with which fungal infections of the CNS can present are protean and can involve most part of the neuroaxis. Certain clinical syndromes are specific for certain fungal infections. The rhinocerebral form is the most common presenting syndrome with zygomycosis and skull-base syndromes are often the presenting clinical syndromes in patients with sinocranial aspergillosis. Subacute and chronic meningitis in patients with HIV infection is more likely to be due to cryptococcal infection. Early recognition of the clinical syndromes in an appropriate clinical setting is the first step towards achieving total cure in some of these infections.


Experimental test of the viscous anisotropy hypothesis for partially molten rocks.
Chemical differentiation of rocky planets occurs by melt segregation away from the region of melting. The mechanics of this process, however, are complex and incompletely understood. In partially molten rocks undergoing shear deformation, melt pockets between grains align coherently in the stress field; it has been hypothesized that this anisotropy in microstructure creates an anisotropy in the viscosity of the aggregate. With the inclusion of anisotropic viscosity, continuum, two-phase-flow models reproduce the emergence and angle of melt-enriched bands that form in laboratory experiments. In the same theoretical context, these models also predict sample-scale melt migration due to a gradient in shear stress. Under torsional deformation, melt is expected to segregate radially inward. Here we present torsional deformation experiments on partially molten rocks that test this prediction. Microstructural analyses of the distribution of melt and solid reveal a radial gradient in melt fraction, with more melt toward the center of the cylinder. The extent of this radial melt segregation grows with progressive strain, consistent with theory. The agreement between theoretical prediction and experimental observation provides a validation of this theory.


Non-Hodgkin's lymphoma with bone involvement: a single center experience with 18 patients.
Non-Hodgkin's lymphoma (NHL) of bone is a rare entity. The most common histological subtype is diffuse large B cell lymphoma (DLBCL). The major presenting symptoms are soft tissue swelling, bone pain and pathological fracture. Treatment options are chemotherapy, radiotherapy, surgery, or a combination of these modalities. We retrospectively analyzed the 18 patients (11 females, 7 males) with NHL of bone who were diagnosed and treated between 1995-2005. The median age was 56.5 years. The median duration of symptoms was 4.5 months. The bone pain was the first symptom in all patients. Tru-cut biopsy was performed for diagnosis in most of the cases. Diagnosis in five patients (27.8%) required open biopsy. DLBCL (77.8%) was the most common histological type among all patients. Other histological subtypes were anaplastic large cell lymphoma (11.1%), Burkitt-like lymphoma (5.6%) and marginal zone lymphoma (5.6%). According to Ann Arbor staging system, 44.4% of patients were Stage I, 11.1% were Stage II and 44.4% were Stage IV. Bone marrow involvement was determined in four patients (22.2%). All patients except one were treated with anthracycline-containing regimens and eight patients (44.4%) received rituximab combination with chemotherapy. Radiation therapy was performed as the first-line therapy in 9 (50%) patients. The median follow-up was 37 months (range, 2-124 months). Among the 17 patients who achieved complete remission, five (27.8%) relapsed. All patients were still alive. The five-year relapse-free survival was 73.5%. The treatment of bone lymphoma can be planned according to the stage and location of the disease. Although we had a relatively low number of patients, it could be concluded that whether or not radiation therapy is performed, rituximab in combination with systemic chemotherapy has been proven beneficial on survival.


Efficacy of two triple eradication regimens in children with Helicobacter pylori infection.
Triple therapy with bismuth subsalicylate, amoxicillin, metronidazole (BAM) or with omeprazole, amoxicillin, clarithromycin (OAC) has been commonly used for the eradication of Helicobacter pylori infection. We compared the efficacy of these triple therapies in children with H. pylori infection. We retrospectively analyzed results in 233 children with H. pylori infection and treated with OAC (n=141) or BAM (n=92). Overall eradication rates of triple therapy with OAC and BAM were 74% and 85%, respectively, which showed no statistical difference. Our study showed that the triple therapy with BAM was more effective for the first-line eradication of H. pylori infection in Korean children, but has no statistical difference with OAC regimen.


Low Predictive Value of FRAX Adjusted by Trabecular Bone Score for Osteoporotic Fractures in Korean Women: A Community-Based Cohort Study.
The value of the Fracture Risk Assessment Tool (FRAX) and the trabecular bone score (TBS) for assessing osteoporotic fracture risk has not been fully elucidated in Koreans. We conducted this study to clarify the predictive value of FRAX adjusted by TBS for osteoporotic fractures in Korean women. After screening 7,192 eligible subjects from the Ansung cohort, 1,165 women aged 45 to 76 years with available bone mineral density (BMD) and TBS data were enrolled in this study. We assessed their clinical risk factors for osteoporotic fractures and evaluated the predictive value of FRAX with or without BMD and TBS. During the mean follow-up period of 7.5 years, 99 (8.5%) women suffered major osteoporotic fractures (MOFs) and 28 (2.4%) experienced hip fractures. FRAX without BMD, BMD-adjusted FRAX, and TBS-adjusted FRAX were significantly associated with the risk of MOFs (hazard ratio [HR] per percent increase, 1.08; 95% confidence interval [CI], 1.03 to 1.14; HR, 1.09; 95% CI, 1.03 to 1.15; and HR, 1.07; 95% CI, 1.02 to 1.13, respectively). However, BMD-adjusted FRAX and TBS-adjusted FRAX did not predict MOFs better than FRAX without BMD based on the Harrell's C statistic. FRAX probabilities showed limited value for predicting hip fractures. The cut-off values of FRAX without BMD, FRAX with BMD, and FRAX with BMD adjusted by TBS for predicting MOFs were 7.2%, 5.0%, and 6.7%, respectively. FRAX with BMD and TBS adjustment did not show better predictive value for osteoporotic fractures in this study than FRAX without adjustment. Moreover, the cut-off values of FRAX probabilities for treatment might be lower in Korean women than in other countries.


Electrocardiographic and respiratory responses to viscerotropic and neurotropic strains of Newcastle disease virus measured by radio telemetry.
Two groups each of White Rock chickens from 6 to 23 weeks old were monitored by radio telemetry to determine their electrocardiogram and respiration response after they were infected with either a velogenic viscerotropic isolate of Newcastle disease virus (VVND) or the neurotropic GB strain of Newcastle disease virus (NGB). Significant changes were found in the heart rate, R wave amplitude, ST segment elevation, T wave amplitude, RS complex interval, ST segment duration T wave interval, TP segment duration, PR segment duration and TP interval of the birds infected with VVND, but no significant ECG changes were found in the birds infected with NGB. There were no significant changes in respiration rate in any birds.


Evaluation of the Target Inhalation Mode (TIM) breathing maneuver in simulated nebulizer therapy in patients with cystic fibrosis.
Adaptive Aerosol Delivery (AAD) systems provide efficient drug delivery and improved lung deposition over conventional nebulizers by combining real-time analyses of patient breathing patterns and precisely timed aerosol delivery. Delivery and deposition are further enhanced by breathing techniques involving slow, deep inhalations. This exploratory study assessed the acceptability of slow, deep inhalations in 20 patients with cystic fibrosis (CF) during up to eight simulated nebulizer treatments with the I-neb AAD System. The breathing maneuver, Target Inhalation Mode (TIM) breathing, involved the lengthening of the patient's inhalation time over successive breaths with guidance from auditory and tactile (vibratory) feedback from the device. At the end of the first treatment, most patients felt that the instructions were easy to understand (90%) and that the vibratory feedback was pleasant (65%). Half of the patients found the procedure to be comfortable. At the end of the final treatment, most patients felt that the breathing maneuver was easy to understand (90%) and use (80%), but that the duration of the breath was too long (100%). Logged data revealed that 90% of patients were able to comply with the breathing maneuver. The two patients unable to comply had a forced vital capacity of <1.75 L. The average treatment time decreased from 288.4 to 141.6 sec during the first and final treatments, respectively. This study provides preliminary evidence of the acceptability of the TIM breathing maneuver in patients with CF and their ability to perform repeated TIM breathing during simulated nebulizer therapy with the I-neb AAD System.


[Long-term result of combination of transcatheter arterial chemoembolization and percutaneous ethanol injection for treatment of hepatocellular carcinoma].
Both transcatheter arterial chemoembolization (TACE) and percutaneous ethanol injection (PEI) are the most important and popular procedures of interventional treatment for hepatocellular carcinoma (HCC). Although the improvement of the short-term efficacy of the combination of TACE and PEI has been proved, the long-term efficacy is seldom reported so far. The purpose of this study was to evaluate the long-term efficacy of the combination of TACE and PEI for treatment of HCC. Six hundred and seventy-five patients with HCC from 2 cm to 15 cm in the greatest diameter (average 9.6 cm) were enrolled in this study. Among them, 179 were treated by a combination of TACE using the emulsion of lipiodol and anti-cancer drugs and PEI (TACE/PEI group) and 496 patients by TACE alone (TACE group). Ten patients in each group underwent resection after the final interventional treatment and the resected specimens were detected by histopathology method. The unresected patients had been followed up for 5-7 years and the 1-, 3-, 5 -, and 7-year survival rates were evaluated. The clinical data of the patients in two groups before intervention were comparable. Pathological data of two groups showed that remarkable differences were found in the mean necrosis rates (100.0+/-0.0% vs 91.5+/-7.1%, P< 0.05) and the complete necrosis rates of tumors (100% vs 20%, P = 0.0007), while there were no statistical significances in the extent of shrinkage of tumors after treatment between two groups. The results of follow-up showed that the 1-, 3-, 5-, and 7-year survival rates were 80.5%, 58.6%, 29.6%, 16.5% in TACE-PEI group, and 68.5%, 27.8%, 7.2%, 5.2% in TACE group, respectively. Significant differences were found between two groups (P< 0.01). The combination of TACE and PEI is a valuable remedy for HCC to prolong long-term survival rate.


Stromal decidualization of endometriosis in the rhesus macaque (Macaca mulatta): a case report.
During exploratory laparotomy, a 10-year-old female rhesus macaque was found to have a 6.0 x 9.5 x 2.0-cm multichambered, yellow, cystic mass cranial to the uterus, from which large amounts of opaque, white fluid were discharged into the abdominal cavity. The animal was euthanized, and the body was submitted for gross and histologic evaluation. Sections of the mass examined microscopically consisted of sheets of polygonal to round cells, with well defined cell borders and moderate amounts of eosinophilic cytoplasm. Scattered throughout these cells were few, variably sized glandular structures composed of columnar to cuboidal epithelium. Glandular epithelial cells were positive for keratin, and the sheets of polygonal cells were positive for vimentin and negative for keratin and CD 68. Gross and histologic appearance, immunohistochemical findings, and history of medroxyprogesterone acetate injections were compatible with a diagnosis of stromal decidualization of endometriosis. Subsequent biopsies of similar lesions in other rhesus macaques in the colony being treated with medroxyprogesterone acetate for endometriosis revealed comparable histologic findings.


Synergistic action of trimethoprim and sulfamethoxazole for Nocardia asteroides: efficacious therapy in five patients.
Eighteen isolates of Nocardia asteroides were tested for in vitro susceptibility to trimethoprim (TMP) and sulfamethoxazole (SMZ) alone and in various combinations using disc and paper strip diffusion tests. TMP-SMZ showed synergistic action for two-thirds of teh nocardia isolates tested. Five patients with Nocardia pneumonia were treated with TMP-SMZ and all were cured. Four of the patients' isolates were tested and all showed synergistic patterns of inhibition with the spaced disc and paper strip methods. The agar diffusion disc and synergy tests of TMP-SMZ appear to correlate with clinical usefulness when the Nocardia are susceptible with large zones of inhibition around the combination TMP-SMZ disc.


Hypercoordinate silicon complexes based on hydrazide ligands. A remarkably flexible molecular system.
Though only one row apart on the periodic table, silicon greatly differs from carbon in its ability to readily form five- and six-coordinate complexes, termed "hypercoordinate silicon compounds". The assorted chemistry of these compounds is varied in both structures and reactivity and has generated a flurry of innovative research endeavors in recent years. This Account summarizes the latest work done on a specific class of hypercoordinate silicon compounds, specifically those with two hydrazide-derived chelate rings. This family is especially interesting due to the ability to form multiple penta- and hexacoordinate complexes, the chemical reactivity of pentacoordinate complexes, and the observation of intermolecular ligand crossovers in hexacoordinate complexes. Pentacoordinate complexes in this family exhibit marked structural flexibility, as demonstrated by the construction of a complete hypothetical Berry-pseudorotation reaction coordinate generated from individual crystallographic molecular structures. Although hexacoordinate complexes generally crystallize as octahedra, with a decrease in the ligand donor strength the complexes can crystallize as bicapped tetrahedra. Hexacoordinate complexes bearing a halogen ligand undergo a solvent-driven equilibrium ionic dissociation, which is controlled by solvent, temperature, counterion, and chelate structure and has been directly demonstrated by conductivity measurements and temperature-dependent (29)Si NMR. Hexacoordinate silicon complexes can also undergo reversible neutral nonionic dissociation of the N-Si dative bond. Ionic pentacoordinate siliconium salts react readily via methyl halide elimination, initiated by their own counterion acting as a base. Pentacoordinate complexes can also undergo intramolecular aldol condensations of imines, which may find potential as a template for organic synthesis. In addition, these complexes are capable of performing an uncatalyzed intramolecular hydrosilylation of imine double bonds. Perhaps the most striking manifestations of flexibility are the facile and complete intermolecular ligand crossovers. Crossovers have been observed between different hexacoordinate complexes, and between complex molecules and their differently substituted precursors, and take place within minutes. Although the precise mechanisms of these transformations remain elusive, NMR and single-crystal X-ray diffraction measurements have shed light on these interesting phenomena. A profusion of crystallographic data and careful NMR experimentation has led to an improved understanding of penta- and hexacoordinate hydrazide-based silicon dichelates. The diverse chemical reactivity of these complexes demonstrates both the scope and complexity of silicon chemistry. Future exploration into the structures and chemistry of hypercoordinate silicon will continue to enhance our understanding and appreciation of this unique element.


Localization and quantitative analysis of antigen-antibody binding on 2D substrate using imaging NanoSIMS.
Iron containing-antigen bound specifically to antibody immobilized on a surface is analyzed by nanoscale secondary ion mass spectrometry (NanoSIMS). This technique is well adapted compared with X-ray photoelectron spectroscopy and energy dispersive spectroscopy, which do not allow the detection of iron. The obtained Fe(+) map gives a good representation of the antigen repartition on the surface. NanoSIMS analysis of competition experiments performed with albumin and iron-free antigen are in good accordance with results obtained by a classical fluorescence microscopy approach. These results underline the interest of imaging NanoSIMS as a label-free method, allowing the localization and quantitative analysis of antigen-antibody binding with better spatial resolution than imaging ellipsometry and SPR.


Highly Conductive and Sensitive Wearable Strain Sensors with Metal/Nanoparticle Double Layer for Noninterference Voice Detection.
Human voice recognition via skin-attachable devices has significant potential for gathering important physiological information from acoustic data without background noise interference. In this study, a highly sensitive and conductive wearable crack-based strain sensor was developed for voice-recognition systems. The sensor was fabricated using a double-layer structure of Ag nanoparticles (NPs) and Ag metal on a biocompatible polydimethylsiloxane substrate. The top metal layer acts as a conducting active layer, whereas the bottom Ag NP layer induces channel cracks in the upper layer, effectively hindering current flow. Subsequently, the double-layer film exhibits a low electrical resistance value (<5 × 10-5 Ω cm), ultrahigh sensitivity (gauge factor = 1870), and a fast response/recovery time (252/168 μs). A sound wave was detected at a high frequency of 15 kHz with a signal-to-noise ratio (SNR) over 40 dB. The sensor exhibited excellent anti-interference characteristics and effectively differentiated between different voice qualities (modal, pressed, and breathy), with a systematic analysis revealing successful detection of the laryngeal state and glottal source. This ultrasensitive wearable sensor has potential applications in various physiological signal measurement methods, personalized healthcare systems, and ubiquitous computing.


Using medical billing data to evaluate chronically ill children over time.
This study evaluates stability of chronic condition identification in children older than 4 years in a health plan billing data using Clinical Risk Groups. A total of 31,055 children were continuously enrolled for 4 years; 7.5% (2,334) identified with a chronic condition status in year 1, 2002, and another 15.4% (4,784) during subsequent years; 63.6% (19,759) were identified as "healthy" throughout. The most stable were those identified with a catastrophic health condition. The least stable were those with minor and moderate/dominant major chronic conditions. Overall, 73.1% (1,706) of the children with chronic conditions in year 1 improved in status, and 5.7% (133) progressed to more complex conditions.


A Modified Skip-Gram Algorithm for Extracting Drug-Drug Interactions from AERS Reports.
Drug-drug interactions (DDIs) are one of the indispensable factors leading to adverse event reactions. Considering the unique structure of AERS (Food and Drug Administration Adverse Event Reporting System (FDA AERS)) reports, we changed the scope of the window value in the original skip-gram algorithm, then propose a language concept representation model and extract features of drug name and reaction information from large-scale AERS reports. The validation of our scheme was tested and verified by comparing with vectors originated from the cooccurrence matrix in tenfold cross-validation. In the verification of description enrichment of the DrugBank DDI database, accuracy was calculated for measurement. The average area under the receiver operating characteristic curve of logistic regression classifiers based on the proposed language model is 6% higher than that of the cooccurrence matrix. At the same time, the average accuracy in five severe adverse event classes is 88%. These results indicate that our language model can be useful for extracting drug and reaction features from large-scale AERS reports.


Should timing be considered before abandoning convalescent plasma in covid-19? Results from the Turkish experience.
Results with convalescent plasma therapy in coronavirus disease 2019 (COVID-19) have been contradictory. Timing seems to be an important factor for COVID-19 convalescent plasma(CCP) to be effective. Aim of this study is to compare disease outcomes in hospitalized COVID-19 patients who were treated with CCP within first three or seven days of symptoms to patients with symptoms longer than seven days. A multicenter retrospective study was conducted to evaluate disease outcomes in hospitalized COVID-19 patients who received CCP in addition to standard of care (SOC) approach. Patients were subgrouped according to time of CCP administration; within three days of symptoms, seven days of symptoms and after seven days of symptoms. A control group was formed from age, gender and comorbidity matched hospitalized patients who received SOC treatments without CCP. Length of hospital stay, rates of anti-inflammatory treatment initiation, intensive care unit (ICU) admission and mortality was set as outcome measures. A total of 223 patients were enrolled in this study, 113 patients received CCP (38 within three days, 63 within seven days, 50 after seven days of symptom onset). Rate of anti-inflammatory treatment initiation was significantly lower (38.1 % vs 62.7 %, p = 0.002, relative risk, 0.60,73; 95 % confidence interval [CI], 0.42 to 0.85) and length of hospital stay was significantly shorter (median(IQR) 8(4) days vs 9.5(5.25) days, p = 0.0025) in patients who received CCP within seven days of symptom onset when compared to SOC group. CCP therapy may provide better outcomes when applied within seven days of symptoms.


Anaerobic and aerobic relative contribution to total energy release during supramaximal effort in patients with left ventricular dysfunction.
Energetic metabolism during effort is impaired in patients with left ventricular dysfunction (Dysf), but data have been lacking up to now on the relative anaerobic vs. aerobic contribution to total energy release during supramaximal effort. Recently, the maximal accumulated oxygen deficit (MAOD) has been shown to be measurable in Dysf patients, making it possible to evaluate the anaerobic/aerobic interaction under conditions of maximal stress of both anaerobic and aerobic metabolic pathways in this population. Nineteen Dysf patients and 17 normal patients (N) underwent one ramp cardiopulmonary, three moderate-intensity constant-power, and three supramaximal constant-power (1- to 2-min, 2- to 3-min, and 3- to 4-min duration) exercise tests. MAOD was the difference between accumulated O(2) demand (accO(2)dem; estimated from the moderate-intensity O(2) uptake/watt relationship) and uptake during supramaximal tests. Percent anaerobic (%Anaer) and aerobic (%Aer) energetic release were [(MAOD/accO(2)dem).100] and 100 - %Anaer, respectively. MAOD did not vary between 1-2, 2-3, and 3-4 min supramaximal tests, whereas accO(2)dem increased significantly with and was linearly related to test duration in both Dysf and N. Consequently, %Anaer and %Aer decreased and increased, respectively, with increasing test duration but did not differ between Dysf and N in 1-2 min, 2-3 min, and 3-4 min tests. Our study demonstrates a similar relative anaerobic vs. aerobic contribution to total energy release during supramaximal effort in Dysf and N. This finding indicates that energetic metabolism during supramaximal exercise is exercise tolerance independent and that relative anaerobic vs. aerobic contribution in this effort domain remains the same within the physiology- or pathology-induced limits to individual peak exercise performance.


Solid-phase iodothyronine-5'-deiodinase (5'-D) assays applied in production of monoclonal antibodies against 5'-D.
Characterization of iodothyronine-deiodinating enzymes has been difficult due to loss of enzyme activity during purification. To obtain a new tool for studying these enzymes we investigated the possibility of developing monoclonal antibodies (MAbs) against iodothyronine-5'-deiodinase (5'-D). Two specific and sensitive solid-phase microassays were developed for screening hybridoma supernatants for the presence of antibodies inhibiting rat kidney 5'-D and antibodies binding to but not inhibiting the enzyme. BALB/c mice were immunized with a 3-((3-cholamidopropyl)-dimethylammonio)-1-propanesulphonate (CHAPS)-solubilized 5'-D-rich membrane preparation from rat kidney cortical tissue. Spleen cells were fused with NSI-Ag 4/l mouse myeloma cells by means of polyethylene glycol. Two hybridoma cell lines (AF5 and BE8) secreting MAbs specifically binding to without inhibiting 5'-D were produced. The AF5 antibody was of the IgG2a subclass and the BE8 antibody of the IgG2b subclass. Binding of one of the antibodies to the enzyme inhibited binding of the other in both an enzyme-linked immunosorbent assay (ELISA) and a specific enzyme-binding assay. CHAPS-solubilized kidney microsomal fraction was chromatographed on a Sepharose 6B column. Elution profiles of 5'-D activity and MAb-binding antigens, as measured by ELISA with both AF5 and BE8, were identical. Monoclonal antibodies should be valuable probes in the further elucidation of the nature of the iodothyronine-deiodinating activity in various tissues.


Indiscernible Benefit of Double-Unit Umbilical Cord Blood Transplantation in Children: A Single-Center Experience From Hong Kong.
Double-unit umbilical cord blood (DU-UCB) may extend the use of UCB transplantation and improve clinical outcomes. Data in the literature show that single-unit dominance happened in a vast majority of recipients, and the mechanism is unknown. We examined the clinical relevance and engraftment kinetics of DU-UCB transplant in 65 consecutive children who underwent unrelated single-unit (n = 25) and double-unit (n = 40) UCB transplantation for various hematological malignancies (n = 45) and nonmalignant disorders (n = 20). Our result showed no discernible benefit to children receiving double-unit transplant over those receiving single-unit transplant when the total nucleated cell (TNC) doses are ≥2.5 × 10(7)/kg, in terms of the hastening of the engraftment of neutrophils and platelets, reduction of nonengraftment, disease recurrence, early mortality, and graft-versus-host disease, despite significantly higher numbers of TNCs in double units. Further analyses demonstrated that the phenomena were not associated with underlying disease, duration of UCB storage, postthaw viability, HLA disparity, ABO incompatibility, gender, or doses of TNCs, CD34(+) cells, CD3(+) cells, or colony-forming units. Engrafting units in DU-UCB transplants were notably associated with higher CD34(+) cell dose. Chimerism studies demonstrated that single-unit dominance started before neutrophil engraftment in DU-UCB transplants. Data from the study suggested no advantage of infusing double-unit UCB, if an adequately dosed single-unit UCB is available. Successful prediction of the dominant graft would optimize algorithms of UCB selection and maximize the long-term engraftment of chosen units.


Magnetic Shielding Studies of C2 and C2 H2 Support Higher than Triple Bond Multiplicity in C2.
The carbon-carbon bonds in the ground states of C2 and C2 H2 , at their equilibrium geometries, are compared by analysing the changes in the off-nucleus magnetic shielding tensor within the space surrounding each of these molecules. A wide range of quantum-chemical approaches, including full-valence CASSCF-GIAO, CCSD(T)-GIAO and CCSDT-GIAO, all with the cc-pVQZ basis set, as well as HF-GIAO and MP2-GIAO, with the cc-pVQZ, cc-pV5Z and cc-pV6Z basis sets, show that the surroundings of the carbon-carbon bond in C2 are more shielded than those of the carbon-carbon bond in C2 H2 . The additional shielding of the carbon-carbon bond in C2 is found to be due to a larger paramagnetic contribution to the component of the shielding tensor which is perpendicular to the molecular axis. The analysis of the off-nucleus shielding data indicates that the carbon-carbon bond in C2 is "bulkier" and, therefore, of a higher multiplicity, but weaker than the corresponding bond in C2 H2 . According to the results of the shielding calculations, the carbon nuclei in C2 should be much more shielded than those in C2 H2 , with 13 C isotropic magnetic shieldings in the ranges of around 224-227 ppm and around 123-125 ppm for C2 and C2 H2 , respectively.


On the performance of the M-C (M = Fe, Ru, Os) unit toward methane activation.
Gas-phase reactions of [MC]+ (M = Os and Ru) with methane at ambient temperature have been studied by using quadrupole-ion trap (Q-IT) mass spectrometry combined with quantum chemical calculations. Theoretical calculations reveal the influence of electronic signatures and that it is the energy gap of the associated frontier molecular orbitals that dominates the ability of the cluster in the initial H3C-H bond breaking. By extension, a theoretical consideration upon changing the ligand from carbide to carbyne and eventually to carbene reveals that the reactivities of the M-complex (M = Os, Ru and Fe) are determined by the energy gap of the involved orbitals. In addition, a few factors like the dipole moment, spin density and charge distributions influence the orbital energy gap to different extents. Thus, altering the local structure of the active center to modulate the orbital distribution may be a possible means of regulation of the activity.


Therapeutic effect of topical ozonated oil on the epithelial healing of palatal wound sites: a planimetrical and cytological study.
To evaluate the effect of ozonated oil on palatal wounds. Eighteen patients were randomized and allocated to either the ozone group (n = 8) or control (n = 10) group. Free gingival graft surgery was performed, and post-harvested palatal wounds were treated with either 2 mL ozonated oil or control oil daily for 1 week. A planimetrical analysis analyzed the digital image for the wound sizes and shape factor at baseline, at 24 h, and days 5, 7, 14, 21, and 28, postoperatively. A cytological analysis used the keratinization and superficial cell indices at baseline, 24 h, and days 3, 7, 14, and 21 and the second and third months, postoperatively. Planimetrical results showed a significant (P ≤ 0.05) improvement in wound size on days 5, 7, 14, 21, and 28, postoperatively, in the ozone group compared to the control group. Cytological results showed a significant (P ≤ 0.001) improvement in epithelial healing on days 7, 14, and 21, and the second and third months, postoperatively, after the application of ozonated oil compared to control oil. Our results showed significant improvement in wound size and epithelial healing after topical ozonated oil application compared to control oil on palatal wounds.


[Emotional and personality characteristics of patients with dystonia].
To examine emotional characteristics, especially personality profile, of patients with dystonia. Three hundred patients with dystonia were enrolled in the study. Control groups consisted of 50 healthy individuals and 62 patients with hemifacial spasm (GFS). HADS, Beck depression inventory and Spielberger-Khanin anxiety scale were used. The 16 Personality Factors Questionnaire (16PF) was used to study personality profile. Higher levels of anxiety and depression in patients with dystonia compared to the control groups were identified. The level of anxiety and depression was not correlated with disease severity. Personality profile study confirmed the high level of anxiety in patients with dystonia and additionally showed increased emotional instability and poor emotional control. Intellectual personality characteristics of patients with dystonia had no differences compared to the control groups. An analysis of socio-psychological characteristics of personality in patients with dystonia and GFS showed restricted interpersonal and social communications since the motor defect noticeable to others leads to severe social exclusion and the desire for self-isolation.


Placement of a multiorificed catheter in the inferior portion of the right atrium; percentage of gas retrieved and success rate of resuscitation after venous air embolism in prone dogs positioned with the abdomen hanging freely.
Based on reports of fatal venous air embolism (VAE) occurring during lumbar laminectomy and spinal fusion in prone patients positioned with the abdomen hanging freely, it has been recommended that monitoring for VAE should be used for such cases, and that a multiorificed central venous catheter should be inserted for aspiration of VAE. A previous study from this laboratory reported that, in prone dogs positioned with the abdomen hanging freely, a multiorificed catheter located in the superior portion of the right atrium did not increase the success rate of resuscitation after VAE given via the femoral vein. The present study was designed to examine aspiration of VAE when prone dogs positioned with the abdomen hanging freely were given a fatal VAE via a femoral vein and a multiorificed catheter was located in the inferior portion of the right atrium. Fourteen dogs were anesthetized with isoflurane and nitrous oxide in oxygen and positioned with the abdomen ventral and hanging freely, the head fixed in a stereotaxic frame, the upper extremities resting on a surface approximately 10 cm below the level of the stereotaxic frame and the lower extremities on a surface below the level of the upper extremities (to assure that VAE entering the inferior vena cava would ascend toward the heart). In the control group (n = 7) a catheter was placed in the inferior portion of the right atrium but was not used to aspirate VAE. In a second group (n = 7) a modified Arrow prototype multiorificed catheter was inserted in the inferior portion of the right atrium.(ABSTRACT TRUNCATED AT 250 WORDS)


Comparison of traditional field retting and Phlebia radiata Cel 26 retting of hemp fibres for fibre-reinforced composites.
Classical field retting and controlled fungal retting of hemp using Phlebia radiata Cel 26 (a mutant with low cellulose degrading ability) were compared with pure pectinase treatment with regard to mechanical properties of the produced fibre/epoxy composites. For field retting a classification of the microbial evolution (by gene sequencing) and enzyme profiles were conducted. By phylogenetic frequency mapping, different types of fungi, many belonging to the Ascomycota phylum were found on the fibres during the first 2 weeks of field retting, and thereafter, different types of bacteria, notably Proteobacteria, also proliferated on the field retted fibres. Extracts from field retted fibres exhibited high glucanase activities, while extracts from P. radiata Cel 26 retted fibres showed high polygalacturonase and laccase activities. As a result, fungal retting gave a significantly higher glucan content in the fibres than field retting (77 vs. 67%) and caused a higher removal of pectin as indicated by lower galacturonan content of fibres (1.6%) after fibres were retted for 20 days with P. radiata Cel 26 compared to a galacturonan content of 3.6% for field retted fibres. Effective fibre stiffness increased slightly after retting with P. radiata Cel 26 from 65 to 67 GPa, while it decreased after field retting to 52 GPa. Effective fibre strength could not be determined similarly due to variations in fibre fracture strain and fibre-matrix adhesion. A maximum composite strength with 50 vol% fibres of 307 MPa was obtained using P. radiata Cel 26 compared to 248 MPa with field retting.


Treatment of intracerebral arteriovenous malformations with isobutyl 2-cyanoacrylate: initial clinical experience.
From November 1976 to September 1979, 46 patients with intracranial arteriovenous malformations or fistulas participated in a clinical study using isobutyl 2-cyanoacrylate (IBCA), with tantalum, for palliative or preoperative occlusion of the blood supply to the abnormalities. Although failure to obtain satisfactory position of a functioning microcatheter precluded deposition of IBCA 10 times, a total of 51 of a possible 62 feeding vessels were occluded with the tantalum-impregnated glue. The technique, results, and complications are discussed in light of the clinical follow-up, which varied from 12 to 48 months.


Catheter related atrial thrombus caused by Abiotrophia defectiva: A case series and review of literature.
Catheter related atrial thrombus (CRAT) is a devastating complication associated with tunneled hemodialysis catheter. Abiotrophia defectiva is a rare fastidious pathogen implicated predominantly in culture negative infective endocarditis. Here we report three cases of CRAT in maintenance hemodialysis patients with variable clinical presentation caused by Abiotrophia defectiva. Video assisted thoracoscopic retrieval of atrial thrombus is a novel technique which is scarcely reported in medical literature for surgical management of large atrial thrombus. Our cases were managed by timely administration of antibiotics and anticoagulants followed by surgical retrieval of atrial thrombus with removal of tunneled dialysis catheter. This case series illustrates the importance of prompt diagnosis, appropriate anticoagulation with antibiotics, and mini-invasive surgical removal of atrial thrombus for the management of CRAT.


Uptake of Technology for Neurorehabilitation in Clinical Practice: A Scoping Review.
Technology-based interventions offer many opportunities to enhance neurorehabilitation with associated research activity gathering pace. Despite this fact, translation for use in clinical practice has lagged research innovation. An overview of the current "state of play" regarding the extent of clinical uptake and factors that might influence use of technologies is required. This scoping review explored the uptake of technologies as neurorehabilitation interventions in clinical practice and factors that are reported to influence their uptake. This systematic scoping review was conducted with narrative synthesis and evidence mapping. Studies of any design reporting uptake or implementation of technology (wearable devices, virtual reality, robotics, exergaming) for movement neurorehabilitation after stroke and other neurological conditions were sought via a formal search strategy in MEDLINE (Ovid), CINAHL, AMED, and Embase. Full-text screening and data extraction were completed independently by 2 reviewers. Of 609 studies returned, 25 studies were included after title, abstract, and full-text screening. Studies investigated a range of technologies at various stages of development. Only 4 of the included studies explored the sustained use of technology in practice. The following 5 themes representing experiences of technology use emerged: perceived usefulness, technology design, social interaction, integration with services, and suggested improvements to enhance uptake. Reporting of uptake and use of neurorehabilitation technologies in clinical practice is limited. The synthesis provided comprehensive knowledge of barriers to and facilitators of uptake to be considered in future protocols, including a steep learning curve required to engage with technology, a need for a supportive organizational culture, and a need for user involvement in both design and development. This scoping review has provided indicators from current evidence of important factors to consider in the planning of research into and clinical implementation of technologies for neurorehabilitation. It serves to support an evidence-based, user-centered platform for improved research on and translation of technologies in neurorehabilitation clinical practice.


A classification of manipulative hand movements.
The nature of manual manipulation of objects is discussed. It is argued that a functional distinction should be made between palmar grips which immobilise an object in the hand, and digital patterns which permit manipulation. Such a distinction is separate from any anatomically defined power and precision configurations. Manipulative hand movements may be grouped into three classes, based on differences between sequenced patterns of movement and synergies, the latter being further subdivided into simple and reciprocal patterns. Within each of the three classes, a number of individual movement patterns are described. These differ mainly in the number of digits involved and the way in which the thumb is employed. The classification is concerned with movements of the digits directed at manipulating an object within the hand. It is not concerned with movements of the hand as a whole, using the wrist or more proximal joints, while holding an immobilised object.


Splenectomy versus spleen-preserving surgery for splenic echinococcosis.
The spleen is the third most common location of hydatid disease after liver and lung. The aim of this study was to analyse the long-term outcome of surgical treatment of patients with splenic echinococcosis comparing splenectomy with spleen-preserving surgery. During a period of 25 years (1976-2001), 19 (5.4%) patients with splenic echinococcosis were treated in our department out of 349 patients with abdominal hydatid disease. In 16 patients the spleen was the only organ involved, while in 3 patients the liver was also affected. Eleven patients had splenectomy and in the other 8 the spleen was preserved: enucleation (n = 4), partial cystectomy and omentoplasty (n = 2) and cystojejunal Roux-en-Y anastomosis (n = 2). One (6%) patient died in the early postoperative period and 5 (29%) patients had postoperative complications. There was no significant difference between the splenectomy and spleen-preserving groups concerning median hospital stay and postoperative complication rate. The median follow-up in 15 patients was 52 (range 6-300) months. Two patients (13%) developed recurrence of the disease requiring re-operation at 2 and 3 years, respectively. Recurrence occurred in 1 (12%) patient in the splenectomy group and in 1 (14%) out of 7 patients in the spleen-preserving group. In the present series it was possible to preserve the spleen in 8 (42%) of 19 patients, without significant increase of recurrent echinococcosis.


Quality measures and quality improvements in colonoscopy.
Approximately 14 million colonoscopies are performed annually in the United States making this the most common gastrointestinal endoscopic procedure. Although the demand for colonoscopy remains strong, improvements in fecal DNA technology and computed tomography colonography now compete with colonoscopy as viable colon cancer screening alternatives. Increasing costs of providing healthcare have renewed the focus on the value of medical services. For colonoscopy to remain the dominant colon cancer screening strategy, it is imperative that we continue to measure and improve the quality of colonoscopy. The purpose of this article is to discuss quality measures and quality improvement in colonoscopy. We describe recent advances in five prominent quality measures: cecal intubation rate, adherence to recommended screening and surveillance interval, adenoma detection rate, quality of bowel preparation, and colonoscopy withdrawal time. Quality measures should be used by endoscopists to document and compare their performance with recommended benchmarks. Quality-improvement programmes can then be developed and targeted towards areas of deficiency.


The past and future in understanding the health risks of and responses to climate variability and change.
Climate change and health was established as a formal field of endeavor in the early 1990s, with the number of publications increasing since the mid-2000s. The key findings in assessment reports from the Intergovernmental Panel on Climate Change in 1995, 2001, 2007, and 2014 indicate the progress in understanding the magnitude and pattern of the health risks of a changing climate. The assessments maintained a similar structure, focusing on assessing the state of knowledge of individual climate-sensitive health outcomes, with confidence in the key findings tending to increase over time with greater understanding. The knowledge base is smaller than for other key sectors (e.g., agriculture) because of limited research investment in climate change and health. Vulnerability, adaptation, and capacity assessments can inform prioritization of the significant research gaps in understanding and managing the health risks of a changing climate; filling these research gaps would provide policy- and decision-makers with insights to increase short- and longer-term resilience in health and other sectors. Research needs include to understand how climate and development pathways could interact to alter health risks over time, better understand upstream drivers of climate-sensitive health outcomes, project aggregate health impacts to understand the breadth and depth of challenges that may need to be managed at geographic scales of interest, and project the time of emergence of changes in the geographic range and intensity of transmission of infectious diseases and other climate conditions. Engagement with other sectors is needed to ensure that their mitigation and adaptation activities also promote and protect health and take the health sector's needs into account. Making progress in these areas is critical for protecting the health of future populations.


[Evolution of the origin of strain of Shancigu (Rhizoma Pleionis)].
Shancigu (Rhizome Pleionis) was first recorded in the Ben cao shiyi (Supplements to Chinese Materia Medica). The source of the strain of this medicinal was unclear because of its too simple description in the medical books in the Tang and Song dynasties. Its original plant could be Cremastra appendiculata (D.Don) Makino, Tulipa edulis (Miq.) Baker and so on. The original plant of Shanciguwas Tulipaedulis since the Ming dynasty to the Republican period. The name of "Guangcigu" began to appear in the Republican period because of the changes of its processing method. The original plants evolved into Cremastra appendiculata, Pleione bulbocodioides (Franch.) Rolfe and Pleione yunnanensis Rolfe, with Tulipa edulisas the original plant of Guangcigu (Bulbus of Tulipasedulis). It is found that only the Tulipaedulis is the unequivocal origin with the longest medicinal history through sorting out of the original plants of Shancigu. Hence, it is suggested that Tulipa edulis should be recovered as the original strain of Shancigu.


[Suppurative complications in acute pancreatitis].
The authors examining suppurative complications caused by acute necrotizing pancreatitis point out how such complications can arise early at the same time of acute pancreatitis with large spread in peripancreatic tissues and spaces and with worse prognosis or have a late appearance with a trend to localize and circumscribe. Four cases of pancreatic abscess, three of which largely diffused brought to death in spite of surgery, are reported.


Medicare and Medicaid programs; condition of participation: immunization standard for long term care facilities. Final rule.
The goal of this final rule is to increase immunization rates in Medicare and Medicaid participating long term care (LTC) facilities by requiring LTC facilities to offer each resident immunization against influenza annually, as well as lifetime immunization against pneumococcal disease. LTC facilities will be required to ensure that before offering the immunization, each resident or the resident's legal representative receives education regarding the benefits and potential side effects of immunization. The facilities will be required to offer immunization against influenza annually and immunization against pneumococcal disease once, unless medically contraindicated or the resident or the resident's legal representative refuses immunization. Increasing the use of Medicare-funded preventive services is a goal of both CMS and the Centers for Disease Control and Prevention (CDC). This final rule is intended to increase the number of elderly receiving influenza and pneumococcal immunization and decrease the morbidity and mortality rate from influenza and pneumococcal diseases.


Development of a highly specialized cDNA array for the study and diagnosis of epithelial ovarian cancer.
Ovarian cancer is a major cause of cancer death in women. Unfortunately, the molecular pathways underlying ovarian cancer progression are poorly understood, making the development of novel diagnostic and therapeutic strategies difficult. On the basis of our previous observations obtained from serial analysis of gene expression, we have constructed a specialized cDNA array for the study of ovarian cancer. Small, specialized arrays have several practical advantages and can reveal information that is lost in the "noise" generated by irrelevant genes present in larger arrays. The array, which we named Ovachip, contains 516 cDNAs chosen from our serial analysis of gene expression and cDNA array studies for their relevance to ovarian cancer. The gene expression patterns revealed with the Ovachip are highly reproducible and extremely consistent among the different ovarian specimens tested. This array was extremely sensitive at differentiating ovarian cancer from colon cancer based on expression profiles. The Ovachip revealed clusters of coordinately expressed genes in ovarian cancer. One such cluster, the IGF2 cluster, is particularly striking and includes the insulin-like growth factor II, the cisplatin resistance-associated protein, the checkpoint suppressor 1, the cyclin-dependent kinase 6, and a protein tyrosine phosphatase receptor. We also identified a cluster of down-regulated genes that included the cyclin-dependent kinase 7 and cyclin H. Thus, the Ovachip allowed us to identify previously unidentified clusters of differentially expressed genes that may provide new paradigms for molecular pathways important in ovarian malignancies. Because of the relevance of the arrayed genes, the Ovachip may become a powerful tool for investigators in the field of ovarian cancer and may facilitate progress in understanding the etiology of this disease and in its clinical management.


NIH SenNet Consortium to map senescent cells throughout the human lifespan to understand physiological health.
Cells respond to many stressors by senescing, acquiring stable growth arrest, morphologic and metabolic changes, and a proinflammatory senescence-associated secretory phenotype. The heterogeneity of senescent cells (SnCs) and senescence-associated secretory phenotype are vast, yet ill characterized. SnCs have diverse roles in health and disease and are therapeutically targetable, making characterization of SnCs and their detection a priority. The Cellular Senescence Network (SenNet), a National Institutes of Health Common Fund initiative, was established to address this need. The goal of SenNet is to map SnCs across the human lifespan to advance diagnostic and therapeutic approaches to improve human health. State-of-the-art methods will be applied to identify, define and map SnCs in 18 human tissues. A common coordinate framework will integrate data to create four-dimensional SnC atlases. Other key SenNet deliverables include innovative tools and technologies to detect SnCs, new SnC biomarkers and extensive public multi-omics datasets. This Perspective lays out the impetus, goals, approaches and products of SenNet.


Immunocytochemical markers of activation in cardiac transplant rejection.
Immunocytochemical analysis of endomyocardial biopsies from cardiac transplant patients has defined changes in expression of antigens, expressed on both the myocardium and endothelium which are characteristic of rejection. Biopsies taken from normal donor heart (prior to transplantation) have been compared with biopsies showing histological signs of rejection. There is induction of MHC class I antigen on the normally negative myocardial plasma membrane and induction of the adhesion molecule ICAM-1 on the intercalating discs. Capillary endothelial cells, which constitutively express Class II DR antigen and ICAM-1 in normal heart show increased of endothelial antigens Pal-E and FVIII-RA during rejection. These results demonstrate perturbation of the endothelial system during rejection and possibly indicate damage to the capillary endothelial cells.


Determination and Pharmacokinetic Study of Three Diterpenes in Rat Plasma by UHPLC-ESI-MS/MS after Oral Administration of Rosmarinus officinalis L. Extract.
Rosmarinus officinalis L. is commonly used as a spice and flavoring agent. Diterpenes are the main active compounds of R. officinalis. An Ultra High Performance Liquid Chromatography-Tandem Mass Spectrometry (UHPLC-ESI-MS/MS) method was developed for the determination of carnosol, rosmanol, and carnosic acid isolated from R. officinalis in rat plasma, and applied to a pharmacokinetic study after oral administration of R. officinalis extract. Sample preparation involved a liquid-liquid extraction of the analytes with ethyl acetate. Butylparaben was employed as an internal standard (I.S.). Chromatographic separation was carried out on a C18 column (ACQUITY UPLC® HSS T3, 1.8 μm, 2.1 mm × 100 mm) with a gradient system consisting of the mobile phase solution A (0.1% formic acid in water) and solution B (acetonitrile) at the flow rate of 0.3 mL/min. The quantification was obtained using multiple reaction monitoring (MRM) mode with electrospray ionization (ESI). The UHPLC-MS/MS assay was validated for linearity, accuracy, precision, extraction recovery, matrix effect and stability. This study described a simple, sensitive and validated UHPLC-MS/MS method for the simultaneous determination of three diterpene compounds in rat plasma after oral administration of R. officinalis extract, and investigated on their pharmacokinetic studies as well.


Hepatitis C virus infection and risk of osteoporosis: A meta-analysis.
Hepatitis C virus (HCV) infection is one of the most common infections worldwide. Several epidemiologic studies have suggested that patients with HCV infection might be at an increased risk of osteoporosis. However, the data on this relationship remains inconclusive. This meta-analysis was conducted with the aim to summarize all available evidence. A literature search was performed using MEDLINE and EMBASE databases from inception to June 2016. Studies that reported relative risks, odd ratios (OR), or hazard ratios comparing the risk of osteoporosis among HCV-infected patients versus those without HCV infection were included. Pooled OR and 95% confidence interval (CI) were calculated using a random-effect, generic inverse variance method. Four studies met our eligibility criteria and were included in the analysis. We found a higher risk of osteoporosis among patients with chronic HCV with OR of 1.65 (95% CI: 0.98-2.77). Sensitivity analysis including only studies with higher quality yielded a higher OR, and the result was statistically significant (OR: 2.47; 95% CI: 1.03-5.93). Our study demonstrated a higher risk of osteoporosis among HCV-infected patients. Further studies are required to clarify how this risk should be addressed in clinical practice.


Association Between Coronary Artery Disease and MicroRNA: Literature Review and Clinical Perspective.
Until recently, circulating micro-RNAs (miRNAs) have attracted major interest as novel biomarkers for the early diagnosis of coronary artery disease (CAD). This review article summarizes the available evidence on the correlation of micro-RNAs with both the clinical and subclinical coronary artery disease and highlights the necessity for exploring miRNAs as a potential diagnostic and prognostic biomarker of early CAD in an adult population. A systematic literature analysis and retrieval online systems Public/Publisher MEDLINE/ Excerpta Medica Database /Medical Literature Analysis and Retrieval System Online,(PUBMED/EMBASE/MEDLINE) search were conducted for relevant information. Search was limited to the articles published in English language and conducted on humans, January 2000 onwards. We excluded studies of heart surgery, coronary artery bypass grafting (CABG), angioplasty and heart transplant. Eighteen studies met the inclusion criteria. Seven out of 18 studies were multivariate, i.e. adjusted for age, gender, body mass index (BMI), smoking, hypertension, diabetes, and blood lipid profiles, while the remaining twelve studies were univariate analysis. Different sources of miRNAs were used, i.e. plasma/serum, microparticles, whole blood, platelets, blood mononuclear intimal and endothelial progenitor cells were investigated. Fourteen out of 18 studies showed up-regulation of different miRNA in CAD patients and in vulnerable plaque disease. Four out of 18 studies showed both the up-regulation and down-regulation of miRNA in the population, while only three studies showed down-regulation of miRNA. Various sources and types of miRNA were used in each study. This review gives an extensive overview of up-regulation and down-regulation of miRNA in CAD and non-CAD patients. The pattern of miRNA regulation with respect to CAD/non-CAD study subjects varies across individual studies and different parameters, which could be the possible reason for this aberrancy. We suggest further trials be conducted in future for highlighting the role of miRNA in CAD, which may improve both the diagnostic and therapeutic approaches to stratifying CAD burden in the general population.


Fluid challenge and balloon occlusion testing in patients with atrial septal defects.
Careful, stepwise assessment is required in all patients with atrial septal defect (ASD) to exclude pulmonary vascular or left ventricular (LV) disease. Fluid challenge and balloon occlusion may unmask LV disease and post-capillary pulmonary hypertension, but their role in the evaluation of patients with 'operable' ASDs is not well established. We conducted a prospective study in three Italian specialist centres between 2018 and 2020. Patients selected for percutaneous ASD closure underwent assessment at baseline and after fluid challenge, balloon occlusion and both. Fifty patients (46 (38.2, 57.8) years, 72% female) were included. All had a shunt fraction >1.5, pulmonary vascular resistance (PVR) <5 Wood Units (WU) and pulmonary arterial wedge pressure (PAWP) <15 mm Hg. Individuals with a PVR ≥2 WU at baseline (higher PVR group) were older, more symptomatic, with a higher baseline systemic vascular resistance (SVR) than the lower PVR group (all p<0.0001). Individuals with a higher PVR experienced smaller increases in pulmonary blood flow following fluid challenge (0.3 (0.1, 0.5) vs 2.0 (1.5, 2.8) L/min, p<0.0001). Balloon occlusion led to a more marked fall in SVR (p<0.0001) and a larger increase in systemic blood flow (p=0.024) in the higher PVR group. No difference was observed in PAWP following fluid challenge and/or balloon occlusion between groups; four (8%) patients reached a PAWP ≥18 mm Hg following the addition of fluid challenge to balloon occlusion testing. In adults with ASD without overt LV disease, even small rises in PVR may have significant implications on cardiovascular haemodynamics. Fluid challenge may provide additional information to balloon occlusion in this setting.


The genetic organization of the capsular polysaccharide biosynthesis region of Actinobacillus pleuropneumoniae serotype 15.
Nucleotide sequence determination and analysis of the cps gene involved in the capsular polysaccharide biosynthesis of Actinobacillus pleuropneumoniae serotype 15 revealed the presence of three open reading frames, designated as cps15ABC genes. At the protein level, Cps15A and Cps15B showed considerably high homology to CpsA (67.0 to 68.7%) and CpsB (31.7 to 36.8%), respectively, of A. pleuropneumoniae serotypes 1, 4 and 12, revealing the common genetic organization of the cps among serotypes 1, 4, 12 and 15. However, Cps15C showed no homology to any proteins of A. pleuropneumoniae serotypes, indicating that cps15C may be specific to serotype 15. This study will provide the basic molecular knowledge necessary for the development of diagnostics and a vaccine for A. pleuropneumoniae serotype 15.


Gender differences in social and developmental factors affecting Puerto Rican adolescents during the early stage.
Adolescence is associated with risky behaviors related with social and developmental factors. Objectives were to describe social and developmental factors affecting Puerto Rican early adolescent by gender and type of school at study entry. Cross-sectional study design. The study group was composed by 168 seventh grade adolescents from private and public schools. Descriptive and non-parametric comparisons were performed. Significance differences among proportions for gender by type of school were found in the following variables: self-esteem and HIV/AIDS attitudes in public school and peer pressure and sensation seeking in private school. Our study revealed that public school adolescents are characterized by males with higher self-esteem and less attitude for HIV/AIDS, while in private school the males has more peer pressure and seeking sensation than females. Future studies could analyze factors related with changes in developmental factors, this step is important to evaluate the effectiveness of ASUMA interventions.


A Review of Second- and Third-line Infertility Treatments and Supporting Evidence in Women with Polycystic Ovary Syndrome.
In clomiphene-citrate-resistant anovulatory women with polycystic ovary syndrome (PCOS) and no other infertility factors, either metformin combined with clomiphene citrate or gonadotrophins could be used as a second-line pharmacological therapy, although gonadotrophins are more effective. Gonadotrophins could also be used as a second-line pharmacological therapy in anovulatory women with PCOS and clomiphene-citrate-failure. Laparoscopic ovarian surgery can also be used as a second-line therapy for ovulation induction in anovulatory women with clomiphene-citrate-resistant PCOS and no other infertility factors. The usefulness of letrozole as a second-line pharmacological treatment for ovulation induction in clomiphene-citrate-resistant women with PCOS requires further research. In terms of improving fertility, both pharmacological anti-obesity agents and bariatric surgery should be considered an experimental therapy in anovulatory women with PCOS and no other infertility factors. Where first- or second-line ovulation induction therapies have failed, in vitro fertilization (IVF)/ intracytoplasmic sperm injection (ICSI) could be offered as a third-line therapy in women with PCOS in the absence of an absolute indication for IVF/ICSI. For women with PCOS undergoing IVF/ICSI treatment, the gonadotropin-releasing hormone (GnRH) antagonist protocol is preferred and an elective frozen embryo transfer strategy could be considered. In assisted conception units with sufficient expertise, in-vitro maturation (IVM) of oocytes could be offered to women with PCOS.


Binary homogeneous nucleation in water-succinic acid and water-glutaric acid systems.
Binary homogeneous nucleation of water-succinic acid and water-glutaric acid systems have been investigated. The numerical approach was based on the classical nucleation theory. Usually, nucleation is discussed in terms of kinetics, but the thermodynamics involved is undoubtedly equally important. In this paper we studied the above mentioned binary systems giving a quantitative insight into the nucleation process and a detailed consideration of the thermodynamics involved. Both diacids in study are in solid state at room temperature. They behave in environment according to their liquid state properties because of the absence of crystalline lattice energies, and therefore their subcooled liquid state thermodynamics have to be considered. The lack of consistent thermodynamic data for pure organic components and their aqueous solutions represent a high source of uncertainty. However, the present simulations indicate that in atmospheric conditions these binary systems will not form new particles.


Mechanism of persistent ischemic mitral regurgitation after annuloplasty: importance of augmented posterior mitral leaflet tethering.
We hypothesized that surgical annuloplasty for ischemic mitral regurgitation (MR) that displaces the posterior annulus anteriorly can potentially augment posterior leaflet (PML) tethering, leading to persistent MR. Relationships between leaflet configurations and persistent ischemic MR after the annuloplasty were investigated. In 31 patients with surgical annuloplasty for ischemic MR and 20 controls, posterior and apical displacement of the leaflet coaptation, the anterior leaflet (AML) and PML tethering angles relative to the line connecting annuli, coaptation length (CL), and the MR grade were quantified before and early after surgery in echocardiographic left ventricular long-axis views. Six of the 31 patients showed persistent MR despite annuloplasty. Compared with patients without persistent MR, those with MR showed no improvement in the left ventricular ejection fraction and systolic volume, similar reduction in the annular area, significant increase in posterior displacement of the coaptation (P<0.01), no improvement in AML tethering, greater worsening in PML tethering (P<0.01), and no increase in the CL. All tethering variables were significantly correlated with both preoperative and postoperative MR in univariate analysis, and reduced CL was the primary independent determinant of both preoperative and postoperative MR. Although increased AML tethering was the primary determinant of the preoperative CL (r2=0.46, P<0.0001), increased PML tethering was the primary determinant afterward (r2=0.60, P<0.0001). Although tethering of both leaflets is the major determinant of ischemic MR before surgical annuloplasty, both leaflets tethering but with predominant and augmented PML tethering is related to persistent ischemic MR after the annnuloplasty.


Muscle in Variable Gravity: "I Do Not Know Where I Am, But I Know What to Do".
Purpose: Fascicle and sarcomere lengths are important predictors of muscle mechanical performance. However, their regulation during stretch-shortening cycle (SSC) activities in usual and challenging conditions is poorly understood. In this study, we aimed to investigate muscle fascicle and sarcomere behavior during drop jumps (a common SSC activity) in conditions of variable gravity. Methods: Fifteen volunteers performed repeated drop jumps in 1 g, hypo-gravity (0 to 1 g), and hyper-gravity (1 to 2 g) during a parabolic flight. Gastrocnemius medialis (GM) electromyographic activity and fascicle length (Lf) were measured at drop-off, ground contact (GC), minimum ankle joint angle (MAJ), and push-off. GM sarcomere number was estimated by dividing Lf, measured by ultrasound at rest, by published data on GM sarcomere length, and measured in vivo at the same joint angle. Changes in sarcomere length were estimated by dividing GM Lf in each jump phase by sarcomere number calculated individually. The sarcomere force-generating capacity in each jump phase was estimated from the sarcomere length-tension relationship previously reported in the literature. Results: The results showed that, regardless of the gravity level, GM sarcomeres operated in the ascending portion of their length-tension relationship in all the jump phases. Interestingly, although in hypo-gravity and hyper-gravity during the braking phase (GC-MAJ) GM fascicles and sarcomeres experienced a stretch (as opposed to the quasi-isometric behavior in 1 g), at MAJ they reached similar lengths as in 1 g, allowing sarcomeres to develop about the 70% of their maximum force. Conclusion: The observed fascicle behavior during drop jumping seems useful for anchoring the tendon, enabling storage of elastic energy and its release in the subsequent push-off phase for effectively re-bouncing in all gravity levels, suggesting that an innate neuromuscular wisdom enables to perform SSC movements also in challenging conditions.


Adjuvant tamoxifen and exemestane in women with postmenopausal early breast cancer (TEAM): 10-year follow-up of a multicentre, open-label, randomised, phase 3 trial.
After 5 years of median follow-up, the Tamoxifen Exemestane Adjuvant Multinational (TEAM) trial reported no difference in disease-free survival between exemestane monotherapy and a sequential scheme of tamoxifen followed by exemestane in postmenopausal patients with early-stage, hormone receptor-positive breast cancer. As recurrence risk in hormone receptor-positive breast cancer remains linear beyond 5 years after diagnosis, we analysed long-term follow-up outcomes of this trial. The TEAM trial, a multicentre, open-label, randomised, controlled, phase 3 trial, included postmenopausal patients with early-stage hormone receptor-positive breast cancer from nine countries. Patients were randomly allocated (1:1) by a computer-generated random permuted block method (block sizes 4-8) to either 5 years of oral exemestane monotherapy (25 mg once a day) or a sequential scheme of oral tamoxifen (20 mg once a day) followed by exemestane for a total duration of 5 years. After the publication of the IES trial, the protocol was amended (Dec 13, 2004). Patients assigned to tamoxifen were switched after 2·5-3·0 years to exemestane therapy for a total duration of 5·0 years of treatment. Randomisation was done centrally in each country. Long-term follow-up data for disease recurrence and survival was collected in six participating countries and analysed by intention to treat. The primary endpoint was disease-free survival at 10 years of follow-up. The trial is registered with ClinicalTrials.gov, numbers NCT00279448 and NCT00032136; with Netherlands Trial Register, number NTR 267; and the Ethics Commission Trial, number 27/2001. 6120 patients of the original 9776 patients in the TEAM trial were included in the current intention-to-treat analysis. Median follow-up was 9·8 years (IQR 8·0-10·3). During follow-up, 921 (30%) of 3075 patients in the exemestane group and 929 (31%) of 3045 patients in the sequential group had a disease-free survival event. Disease-free survival at 10 years was 67% (95% CI 65-69) for the exemestane group and 67% (65-69) for the sequential group (hazard ratio 0·96, 0·88-1·05; p=0·39). The long-term findings of the TEAM trial confirm that both exemestane alone and sequential treatment with tamoxifen followed by exemestane are reasonable options as adjuvant endocrine therapy in postmenopausal patients with hormone receptor-positive early breast cancer. These results suggest that the opportunity to individualise adjuvant endocrine strategy accordingly, based on patient preferences, comorbidities, and tolerability might be possible. Pfizer, Dutch Cancer Foundation.