Etidronate disodium in the treatment of Paget's disease of bone.
Control of Paget's disease of bone has been possible through treatment with agents that decrease bone resorption; calcitonins, diphosphonates, and mithramycin. The pagetic lesion is not, however, cured. Etidronate disodium is one of the diphosphonates. The clinical improvement attained with this drug has to be set against adverse effects, of which pain is probably the most bothersome in practice. Clinical remission can last as long as 2 years after treatment is stopped.


Bridging implementation, knowledge, and ambition gaps to eliminate tuberculosis in the United States and globally.
We reflect on remarkable accomplishments in global tuberculosis (TB) control and identify persistent obstacles to the successful elimination of TB from the United States and globally. One hundred and twenty nine years after Koch's discovery of the etiologic agent of TB, this health scourge continues to account for 9.4 million cases and 1.7 million deaths annually worldwide. Implementation of the Directly Observed Treatment Short-course strategy from 1995 through 2009 has saved 6 million lives. TB control is increasingly being achieved in countries with high-income economies, yet TB continues to plague persons living in countries with low-income and lower-middle-income economies. To accelerate progress against the global effects of disease caused by TB and achieve its elimination, we must bridge 3 key gaps in implementation, knowledge, and ambition.


Transformation of patchouli alcohol to β-patchoulene by gastric juice: β-patchoulene is more effective in preventing ethanol-induced gastric injury.
Pogostemonis Herba is a functional food approved in Asian countries. Its major constituent, patchouli alcohol (PA), possesses a gastroprotective effect and is reported to transform into β-patchoulene (β-PAE) under acidic conditions. To investigate whether β-PAE, the metabolite of PA, has a protective effect on the gastrointestinal tract, the formation of β-PAE by gastric juice and the anti-ulcerogenic potential of β-PAE against ethanol-induced gastric injury were evaluated. The Results indicated that PA was converted to β-PAE by rat gastric juice. Additionally, β-PAE was significantly better than PA at reducing the area of gastric ulcer. The overproduction of malondialdehyde, tumour necrosis factor-α, interleukin (IL)-1β, IL-6, Fas, FasL and caspase-3 was markedly inhibited by β-PAE while the underproduction of superoxide dismutase, glutathione and catalase was significantly improved. β-PAE also regulated the NF-κB and ERK1/2 signalling pathways. Our findings suggest that β-PAE has potential therapeutic efficacy for antiulcer treatment.


Effects of positive behaviour support delivered by direct staff on challenging behaviours and quality of life of adults with intellectual disabilities: A multicentre cluster-controlled trial.
Effects of staff provided positive behaviour support (PBS) for individuals with intellectual disabilities are unclear. Using a multicentre non-randomised cluster controlled design, 26 teams of residential group homes, including 245 staff members of 167 individuals with intellectual disabilities, were allocated to a PBS or control group. Conducting multilevel analyses (n = 123) we examined individuals' changes in irritability, other challenging behaviours and quality of life. Compared to controls, irritability did not significantly decrease more in the intervention group, but lethargic behaviours did. Personal development and self-determination significantly increased. Irritability of individuals in the PBS group with higher levels of irritability or lower levels of intellectual disability significantly reduced more compared to controls. PBS was effective in reducing irritability of individuals with severe levels of irritability or intellectual disabilities. Moreover, PBS decreased lethargic behaviours and improved several domains of quality of life.


Sub-acute and long-term effects of ayahuasca on affect and cognitive thinking style and their association with ego dissolution.
Ayahuasca is a psychotropic plant tea from South America used for religious purposes by indigenous people of the Amazon. Increasing evidence indicates that ayahuasca may have therapeutic potential in the treatment of mental health disorders and can enhance mindfulness-related capacities. Most research so far has focused on acute and sub-acute effects of ayahuasca on mental health-related parameters and less on long-term effects. The present study aimed to assess sub-acute and long-term effects of ayahuasca on well-being and cognitive thinking style. The second objective was to assess whether sub-acute and long-term effects of ayahuasca depend on the degree of ego dissolution that was experienced after consumption of ayahuasca. Ayahuasca ceremony attendants (N = 57) in the Netherlands and Colombia were assessed before, the day after, and 4 weeks following the ritual. Relative to baseline, ratings of depression and stress significantly decreased after the ayahuasca ceremony and these changes persisted for 4 weeks. Likewise, convergent thinking improved post-ayahuasca ceremony up until the 4 weeks follow-up. Satisfaction with life and several aspects of mindfulness increased the day after the ceremony, but these changes failed to reach significance 4 weeks after. Changes in affect, satisfaction with life, and mindfulness were significantly correlated to the level of ego dissolution experienced during the ayahuasca ceremony and were unrelated to previous experience with ayahuasca. It is concluded that ayahuasca produces sub-acute and long-term improvements in affect and cognitive thinking style in non-pathological users. These data highlight the therapeutic potential of ayahuasca in the treatment of mental health disorders, such as depression.


Adjustments to diabetes medications in response to increases in hemoglobin a1c: an epidemiologic study.
The primary objective was to assess associations between increases in glycated hemoglobin (HbA1c) levels and medication adjustments among patients with diabetes. A secondary objective was to measure the effect of adjustments on subsequent HbA1c levels. A retrospective analysis of administrative data from a large health insurer in Hawaii of 7654 patients with diabetes mellitus type II, HbA1c levels greater than 7%, and who were taking oral diabetic medications. Patients were eligible if they had an HbA1c measurement in 2009, a prior measure 30 or more days previously, and at least 30 days of follow-up to identify medication adjustments. Patients were classified into 3 groups based on their extent of change in HbA1c levels. Patients were followed to determine the frequency of medication adjustments and to observe the possible benefit of making adjustments on subsequent HbA1c levels. Medication adjustments were the exception, occurring among less than a fourth of patients. Compared with patients without HbA1c increases, patients with <1% HbA1c increases made adjustments 20% more frequently, and patients with increased HbA1c levels of 1% or more made adjustments 60% more frequently. Patients with similar HbA1c increases were more likely to adjust their medications if they had higher baseline HbA1c levels. Medication adjustments were mostly for oral diabetes medications; insulin use was seldom initiated, and then primarily by patients with HbA1c levels of 9% or higher. Patients with medication adjustments averaged about 0.40% lower HbA1c levels when reassessed after 120 days or more. The results show limited responsiveness to increases in HbA1c levels and a low initiation rate of insulin use. Patients adjusting their medications, however, had clinically significant improvements in their HbA1c levels. Clinical inertia and patient concerns are discussed as factors possibly limiting the frequency of medication adjustments.


Theoretical perspectives and applications of group learning in PBL.
An essential part of problem-based learning (PBL) is group learning. Thus, an in depth understanding of the theoretical underpinnings of group learning in PBL allows educators to bridge theory and practice more effectively thus providing ideas and tools to enhance PBL practices and research. The theory-driven applications examined in this article establish grounds for future research in PBL. The purpose of this article is to describe and examine two theoretical perspectives of group learning in PBL and their potential applications to improve educational practice. They include: (1) social interdependence theory and the meaning of positive interdependence, (2) socio cognitive theory of networked expertise and the concept of knowledge creation in innovative knowledge communities (IKC). Potential applications include the following: development of instructional material to foster positive interdependency using concept maps; formal and structured use of peer feedback throughout PBL courses to promote individual and group accountability; creation and sharing of new knowledge about different topics within and across IKC; and use of rotating students with hybrid abilities across PBL groups to foster distributed cognition.


Ternary hybrid nanoparticle isomers: directing the nucleation of Ag on Pt-Fe(3)O(4) using a solid-state protecting group.
Colloidal hybrid nanoparticles are an important class of materials that incorporate multiple nanoparticles into a single system through solid-state interfaces, which can result in multifunctionality and the emergence of synergistic properties not found in the individual components. These hybrid structures are typically produced using seeded-growth methods, where preformed nanoparticles serve as seeds onto which additional domains are added through subsequent reactions. For hybrid nanoparticles that contain more than two domains, multiple configurations with distinct connectivities and functionalities are possible, and these can be considered as nanoparticle analogues of molecular isomers. However, accessing one isomer relative to others in the same hybrid nanoparticle system is challenging, particularly when the formation of a target isomer is disfavored relative to more stable or synthetically accessible configurations. Here, we show that an iron oxide shell installed onto the Pt domain of Pt-Fe3O4 hybrid nanoparticles serves as a solid-state protecting group that can direct the nucleation of a third domain to an otherwise disfavored site. Under traditional conditions, Ag nucleates exclusively onto the Pt domain of Pt-Fe3O4 heterodimers, resulting in the formation of the Ag-Pt-Fe3O4 heterotrimer isomer. When the Pt surface is covered with an iron oxide protecting group, the nucleation of Ag is redirected onto the Fe3O4 domain, producing the distinct and otherwise inaccessible Pt-Fe3O4-Ag isomer. Similar results are obtained for the Au-Pt-Fe3O4 system, where formation of the favored Au-Pt-Fe3O4 configuration is blocked by the iron oxide protecting group. The thickness of the iron oxide shell that protects the Pt domain can be systematically tuned by adjusting the ratio of oleic acid to iron pentacarbonyl during the synthesis of the Pt-Fe3O4 heterodimers, and this insight is important for controllably implementing the protecting group chemistry.


Optimizing radical yield from free chlorine with tailored UV light emitting diode emission spectra.
Novel UV sources, which do not contain mercury, provide the opportunity for enhancement of current oxidation technologies through spectral optimization, minimizing inefficiencies that currently limit conventional technology. Wastewater reuse is the primary full-scale application of UV advanced oxidation processes (AOPs) in practice but any background absorbance and the low molar absorption by conventional radical promoters (hydrogen peroxide) have historically limited their system efficiency, resulting in the underutilization of photons in a reactor. This bench-scale research evaluated use of longer wavelength UV light emitting diodes (265, 280, and 300 nm) matched with free chlorine to optimize the utilization of photons for advanced oxidation. Free chlorine possesses large absorption bands in the 280 to 300 nm range in basic pH waters which are common in carbon-based reuse and was used to experimentally verify quantum yields of hydroxyl radical generation across the UV LED peak emission wavelengths. pH- and wavelength-dependent fluence-based rate constants were experimentally derived using Nitrobenzene and Benzoic acid as probe compounds and evaluated to determine the contribution of the hydroxyl and chlorine radical. Reclaimed water taken from various advanced treatment steps was treated with this UV LED AOP to investigate how background absorbance affects radical generation and contaminant transformation kinetics. In addition, alternative performance metrics to evaluate hydroxyl radical production at different incident fluence rates and different rates of photon absorption at unique wavelengths across varying background UV absorbance levels were assessed.


1alpha-hydroxycholecalciferol has little effect on phytate phosphorus utilization in laying hen diets.
Previous research in our laboratory demonstrated marked increases in phytate P utilization when P-deficient corn-soybean meal diets were supplemented with 1a-hydroxycholecalciferol [1alpha-(OH) D3] and fed to chicks. Our objective was to determine if 1alpha-(OH) D3 would improve phytate P utilization when supplemented to vitamin D-adequate laying hen diets. The five experimental treatments were 1) P-deficient corn-soybean basal diet [17% CP, 3.8% Ca, and 0.10% nonphytate NPP)], 2) basal with 2.5 microg/kg 1alpha-(OH) D3, 3) basal with 5 microg/kg 1alpha-(OH) D3, 4) basal with 10 microg/kg 1alpha-(OH) D3, and 5) basal with 0.35% supplemental inorganic P (0.45% NPP, positive control). Diets were fed to six replicate groups of 12 HyLine W-98 White Leghorn laying hens from 44 to 52 wk of age. Hen-day egg production was significantly depressed by 47 wk of age for the basal diet treatment and by 47, 49, and 48 wk of age, respectively, for the 2.5, 5, and 10 microg/kg of 1alpha-(OH) D3 treatments compared to the positive control diet. Supplementation with 5 or 10 microg/kg 1alpha-(OH) D3 did improve (P < 0.05) egg production, but egg production for those treatments was much lower than that for the 0.45% NPP treatment. Our results indicate that 1alpha-(OH) D3 did not substantially improve P utilization in laying hens fed corn-soybean meal diets.


Enhanced CD8 T-cell anti-viral function and clinical disease in B7-H1-deficient mice requires CD4 T cells during encephalomyelitis.
Anti-viral CD8 T-cell activity is enhanced and prolonged by CD4 T-cell-mediated help, but negatively regulated by inhibitory B7-H1 interactions. During viral encephalomyelitis, the absence of CD4 T cells decreases CD8 T cell activity and impedes viral control in the central nervous system (CNS). By contrast, the absence of B7-H1 enhances CD8 T-cell function and accelerates viral control, but increases morbidity. However, the relative contribution of CD4 T cells to CD8 function in the CNS, in the absence of B7-H1, remains unclear. Wild-type (WT) and B7-H1-/- mice were infected with a gliatropic coronavirus and CD4 T cells depleted to specifically block T helper function in the CNS. Flow cytometry and gene expression analysis of purified T-cell populations from lymph nodes and the CNS was used to directly monitor ex vivo T-cell effector function. The biological affects of altered T-cell responses were evaluated by analysis of viral control and spinal-cord pathology. Increased anti-viral activity by CD8 T cells in the CNS of B7-H1-/- mice was lost upon depletion of CD4 T cells; however, despite concomitant loss of viral control, the clinical disease was less severe. CD4 depletion in B7-H1-/- mice also decreased inducible nitric oxide synthase expression by microglia and macrophages, consistent with decreased microglia/macrophage activation and reduced interferon (IFN)-γ. Enhanced production of IFN-γ, interleukin (IL)-10 and IL-21 mRNA was seen in CD4 T cells from infected B7-H1-/- compared with WT mice, suggesting that over-activated CD4 T cells primarily contribute to the increased pathology. The local requirement of CD4 T-cell help for CD8 T-cell function is not overcome if B7-H1 inhibitory signals are lost. Moreover, the increased effector activity by CD8 T cells in the CNS of B7-H1-/- mice is attributable not only to the absence of B7-H1 upregulation on major histocompatibility complex class I-presenting resident target cells, but also to enhanced local CD4 T-cell function. B7-H1-mediated restraint of CD4 T-cell activity is thus crucial to dampen both CD8 T-cell function and microglia/macrophage activation, thereby providing protection from T-cell-mediated bystander damage.


High-Resolution Mapping of Crossover Events in the Hexaploid Wheat Genome Suggests a Universal Recombination Mechanism.
During meiosis, crossovers (COs) create new allele associations by reciprocal exchange of DNA. In bread wheat (Triticum aestivum L.), COs are mostly limited to subtelomeric regions of chromosomes, resulting in a substantial loss of breeding efficiency in the proximal regions, though these regions carry ∼60-70% of the genes. Identifying sequence and/or chromosome features affecting recombination occurrence is thus relevant to improve and drive recombination. Using the recent release of a reference sequence of chromosome 3B and of the draft assemblies of the 20 other wheat chromosomes, we performed fine-scale mapping of COs and revealed that 82% of COs located in the distal ends of chromosome 3B representing 19% of the chromosome length. We used 774 SNPs to genotype 180 varieties representative of the Asian and European genetic pools and a segregating population of 1270 F6 lines. We observed a common location for ancestral COs (predicted through linkage disequilibrium) and the COs derived from the segregating population. We delineated 73 small intervals (<26 kb) on chromosome 3B that contained 252 COs. We observed a significant association of COs with genic features (73 and 54% in recombinant and nonrecombinant intervals, respectively) and with those expressed during meiosis (67% in recombinant intervals and 48% in nonrecombinant intervals). Moreover, while the recombinant intervals contained similar amounts of retrotransposons and DNA transposons (42 and 53%), nonrecombinant intervals had a higher level of retrotransposons (63%) and lower levels of DNA transposons (28%). Consistent with this, we observed a higher frequency of a DNA motif specific to the TIR-Mariner DNA transposon in recombinant intervals.


High performance teamwork training and systems redesign in outpatient oncology.
Oncology care is delivered largely in ambulatory settings by interdisciplinary teams. Treatments are often complex, extended in time, dispersed geographically and vulnerable to teamwork failures. To address this risk, we developed and piloted a team training initiative in the breast cancer programme at a comprehensive cancer centre. Based on clinic observations, interviews with key staff and analyses of incident reports, we developed interventions to address four high-risk areas: (1) miscommunication of chemotherapy order changes on the day of treatment; (2) missing orders on treatment days without concurrent physician appointments; (3) poor follow-up with team members about active patient issues; and (4) conflict between providers and staff. The project team developed protocols and agreements to address team members' roles, responsibilities and behaviours. Using a train-the-trainer model, 92% of breast cancer staff completed training. The incidence of missing orders for unlinked visits decreased from 30% to 2% (p<0.001). Patient satisfaction scores regarding coordination of care improved from 93 to 97 (p=0.026). Providers, infusion nurses and support staff reported improvement in efficiency (75%, 86%, 90%), quality (82%, 93%, 93%) and safety (92%, 92%, 90%) of care, and more respectful behaviour (92%, 79%, 83%) and improved relationships among team members (91%, 85%, 92%). Although most clinicians reported a decrease in non-communicated changes, there was insufficient statistical power to detect a difference. Team training improved communication, task coordination and perceptions of efficiency, quality, safety and interactions among team members as well as patient perception of care coordination.


Moral distress and moral courage in everyday nursing practice.
In this article the author examines the concepts of moral distress and moral courage within the context of nursing practice. Examples of challenging healthcare situations from the United Kingdom and Ireland are discussed in the light of the examination of these two concepts. The examples illuminate features of healthcare situations that need to be considered in relation to different organisational and cultural contexts. This requires an understanding of the complexity of clinical contexts and an appreciation of the fallibility and vulnerability of nurses and other practitioners. The goal of this article is to encourage healthcare organisations to create supportive structures and sensitive leadership that will enhance moral courage in the work setting.


The complexity of rural contexts experienced by community disability workers in three southern African countries.
An understanding of rural communities is fundamental to effective community-based rehabilitation work with persons with disabilities. By removing barriers to community participation, persons with disabilities are enabled to satisfy their fundamental human needs. However, insufficient attention has been paid to the challenges that rural community disability workers (CDWs) face in trying to realise these objectives. This qualitative interpretive study, involving in-depth interviews with 16 community disability workers in Botswana, Malawi and South Africa, revealed the complex ways in which poverty, inappropriately used power and negative attitudes of service providers and communities combine to create formidable barriers to the inclusion of persons with disabilities in families and rural communities. The paper highlights the importance of understanding and working with the concept of 'disability' from a social justice and development perspective. It stresses that by targeting attitudes, actions and relationships, community disability workers can bring about social change in the lives of persons with disabilities and the communities in which they live.


Emergency treatment options for pediatric traumatic brain injury.
Traumatic brain injury is a leading killer of children and is a major public health problem around the world. Using general principles of neurocritical care, various treatment strategies have been developed to attempt to restore homeostasis to the brain and allow brain healing, including mechanical factors, cerebrospinal fluid diversion, hyperventilation, hyperosmolar therapies, barbiturates and hypothermia. Careful application of these therapies, normally in a step-wise fashion as intracranial injuries evolve, is necessary in order to attain maximal neurological outcome for these children. It is hopeful that new therapies, such as early hypothermia or others currently in preclinical trials, will ultimately improve outcome and quality of life for children after traumatic brain injury.


Order Matters: The Benefits of Ordinal Fragility Curves for Damage and Loss Estimation.
Probabilistic loss assessments from natural hazards require the quantification of structural vulnerability. Building damage data can be used to estimate fragility curves to obtain realistic descriptions of the relationship between a hazard intensity measure and the probability of exceeding certain damage grades. Fragility curves based on the lognormal cumulative distribution function are popular because of their empirical performance as well as theoretical properties. When we are interested in estimating exceedance probabilities for multiple damage grades, these are usually derived per damage grade via separate probit regressions. However, they can also be obtained simultaneously through an ordinal model which treats the damage grades as ordered and related instead of nominal and distinct. When we use nominal models, a collapse fragility curve is constructed by treating data of "near-collapse" and "no damage" the same: as data of noncollapse. This leads to a loss of information. Using synthetic data as well as real-life data from the 2015 Nepal earthquake, we provide one of the first formal demonstrations of multiple advantages of the ordinal model over the nominal approach. We show that modeling the ordering of damage grades explicitly through an ordinal model leads to higher sensitivity to the data, parsimony and a lower risk of overfitting, noncrossing fragility curves, and lower associated uncertainty.


Solid-phase and microwave-assisted syntheses of 2,5-diketopiperazines: small molecules with great potential.
Diketopiperazines (DKPs) are a well-known class of heterocycles that have recently emerged as a promising biologically active scaffold. Solid-phase organic synthesis has become an important tool in the combinatorial exploration of these privileged structures, expediting the synthesis and, therefore, the discovery of active compounds. To date, certain DKPs have shown potent activities against a range of diseases and biological phenomena, including bacterial infections, various cancers, asthma, infertility, premature labor, and HIV. Recent applications of solid-phase DKP synthesis, with a particular focus on cyclative cleavage and microwave-assisted reactions, are highlighted herein.


Hematological Manifestations of SLE at Initial Presentation: Is It Underestimated?
SLE can present with hematological manifestations alone or along with features of other system involvement. With a low index of clinical suspicion or inadequate follow up the diagnosis may be delayed or missed at the time of presentation, in those with hematological abnormalities as the initial manifestation. An observational study was conducted among patients of SLE, in a tertiary referral centre of North Kerala, with the purpose of estimating the proportion of patients with hematological manifestations as the initial presentation of the disease and to study their nature. It was observed that 82% of the patients had hematological manifestations at presentation. It is the most common presenting manifestation of SLE in people of North Kerala. Autoimmune hypothyroidism was one of the common coexisting abnormalities in these patients, which is not included in the American College of Rheumatology (ACR) criteria for diagnosis. Arthritis was uncommon among those who presented with hematological manifestations. A significant number of patients do not satisfy the ACR criteria at the time of diagnosis but do so on follow up. The ACR criteria are weak to diagnose such patients and therefore need revision. We therefore propose an alternative to ACR criteria as "Kozhikode criteria for SLE".


Enteric glia promote functional recovery of CTM reflex after dorsal root transection.
Transected dorsal root axons of adult rats can be induced to regenerate through the normally non-permissive environment of the dorsal root entry zone (DREZ) into the spinal cord by implanting enteric glia (EG) into the DREZ. We have now examined whether the regenerating central axons make functional connections by studying the return of function of a behavioral response, the cutaneous trunci muscle (CTM) reflex. Implantation of EG into the spinal cord DREZ led to functional recovery of the CTM reflex in 82%, 72% and 70% of animals 1, 2 and 3 months, respectively, after injury. In contrast, the CTM reflex did not recover in animals implanted with 3T3 or C6 glioma cells or with vehicle only.


Effects of Fe-loaded biochar on the bioavailability of Arsenic and cadmium to lettuce growing in a mining contaminated soil.
Arsenic (As) and cadmium (Cd) are two prominent metal contaminants in mining soil, threatening food and environmental safety. The effects of Fe-loaded biochar on the accumulation and translocation of As and Cd in a soil-lettuce system were investigated to evaluate the efficiency of Fe-loaded biochar in reducing As and Cd bioavailability. Application of Fe-loaded biochar at a rate of 0.5-1.5% decreased the concentrations of porewater As and Cd by 4.2-53.0% and -0.6-21.7%, respectively. The results of sequential extraction showed that Fe-loaded biochar can promote the transfer of As and Cd in soils from the available fraction to a relatively stable fraction, thus reducing the mobility and availability of As and Cd. The concentrations of As and Cd in lettuce shoots in the Fe-loaded biochar treatment were significantly decreased by 11.4-26.0% and 4.4-12.9% compared with those in the untreated soil, respectively. Fe-loaded biochar applied at a rate of 0.5-1.0% had no obvious effect on plant biomass, and the lowest weight of lettuce shoots and roots was observed in the treatment with Fe-loaded biochar applied at a rate of 1.5%, in which they were reduced by 12.9% and 18.0%, respectively. Overall, Fe-loaded biochar as a soil amendment was effective in simultaneously reducing As and Cd bioavailability in As and Cd co-contaminated soils, and an application rate lower than 1.5% is recommended to avoid significant decreases in plant growth.


Financial Incentives and Physician Practice Participation in Medicare's Value-Based Reforms.
To evaluate whether greater experience and success with performance incentives among physician practices are related to increased participation in Medicare's voluntary value-based payment reforms. Publicly available data from Medicare's Physician Compare (n = 1,278; January 2012 to November 2013) and nationally representative physician practice data from the National Survey of Physician Organizations 3 (NSPO3; n = 907,538; 2013). We used regression analysis to examine practice-level relationships between prior exposure to performance incentives and participation in key Medicare value-based payment reforms: accountable care organization (ACO) programs, the Physician Quality Reporting System ("Physician Compare"), and the Meaningful Use of Health Information Technology program ("Meaningful Use"). Prior experience and success with financial incentives were measured as (1) the percentage of practices' revenue from financial incentives for quality or efficiency; and (2) practices' exposure to public reporting of quality measures. We linked physician participation data from Medicare's Physician Compare to the NSPO3 survey. There was wide variation in practices' exposure to performance incentives, with 64 percent exposed to financial incentives, 45 percent exposed to public reporting, and 2.2 percent of practice revenue coming from financial incentives. For each percentage-point increase in financial incentives, there was a 0.9 percentage-point increase in the probability of participating in ACOs (standard error [SE], 0.1, p < .001) and a 0.8 percentage-point increase in the probability of participating in Meaningful Use (SE, 0.1, p < .001), controlling for practice characteristics. Financial incentives were not associated with participation in Physician Compare. Among ACO participants, a 1 percentage-point increase in incentives was associated with a 0.7 percentage-point increase in the probability of being "very well" prepared to utilize cost and quality data (SE, 0.1, p < .001). Physicians organizations' prior experience and success with performance incentives were related to participation in Medicare ACO arrangements and participation in the meaningful use criteria but not to participation in Physician Compare. We conclude that Medicare must complement financial incentives with additional efforts to address the needs of practices with less experience with such incentives to promote value-based payment on a broader scale.


The CXCL12/CXCR4/CXCR7 ligand-receptor system regulates neuro-glio-vascular interactions and vessel growth during human brain development.
This study investigates glio-vascular interactions in human fetal brain at midgestation, specifically examining the expression and immunolocalization of the CXCL12/CXCR4/CXCR7 ligand-receptor axis and its possible role in the vascular patterning of the developing brain. At midgestation, the telencephalic vesicles are characterized by well developed radial glia cells (RGCs), the first differentiated astrocytes and a basic vascular network mainly built of radial vessels. RGCs have been recognized to contribute to cerebral cortex neuro-vascular architecture and have also been demonstrated to act as a significant source of neural cells (Rakic, Brain Res 33:471-476, 1971; Malatesta et al, Development 127:5253-5263, 2000). According to our hypothesis CXCL12, a potent migration and differentiation chemokine released by RGCs, may act as a linking factor coordinating neuroblast migration with vessel growth and patterning through the activation of different ligand/receptor axes. The obtained results support this hypothesis showing that together with CXCR4/CXCR7-reactive neuroblasts, which migrate in close association with CXCL12 RGCs, layer-specific subsets of CXCL12 RGCs and astrocytes specifically contact the microvessel wall. Moreover, the CXCL12/CXCR4/CXCR7 system appears to be directly involved in microvessel growth, its members being differentially expressed in angiogenically activated microvessels and vascular sprouts.


Paraneoplastic syndromes in primary liver-cell carcinoma: experience in Ibadan, Nigeria.
Primary liver cell carcinoma (PLC) is common in Africa. It represents the commonest malignancy in the Nigerian males. White reports of paraneoplastic syndrome associated with PLC abound from the Western World--a geographic area of low incidence of the tumour--there is a paucity of information from the African continent generally, and specifically from Nigeria. This prospective study analyses the relative incidences of recognized syndromes in fifty Nigerians with PLC. Alpha-foetoproteinemia (51%) and hypercholesterolaemia (33%) are common while hypoglycemia (9%) and hypercalcaemia (4%) are uncommon. No case of porphyria cutanea tarda was encountered. Our findings are compared with reported incidences in the literature. The pathogenetic mechanisms of these syndromes are briefly reviewed.


Perspective: sex, recombination, and the efficacy of selection--was Weismann right?
The idea that sex functions to provide variation for natural selection to act upon was first advocated by August Weismann and it has dominated much discussion on the evolution of sex and recombination since then. The goal of this paper is to further extend this hypothesis and to assess its place in a larger body of theory on the evolution of sex and recombination. A simple generic model is developed to show how fitness variation and covariation interact with selection for recombination and illustrate some important implications of the hypothesis: (1) the advantage of sex and recombination can accrue both to reproductively isolated populations and to modifiers segregating within populations, but the former will be much larger than the latter; (2) forces of degradation that are correlated across loci within an individual can reduce or reverse selection for increased recombination; and (3) crossing-over (which can occur at different places in different meioses) will create more variability than having multiple chromosomes and so will have more influence on the efficacy of selection. Several long-term selection experiments support Weismann's hypothesis, including those showing a greater response to selection in populations with higher rates of recombination and higher rates of recombination evolving as a correlated response to selection for some other character. Weismann's hypothesis is also consistent with the sporadic distribution of obligate asexuality, which indicates that clones have a higher rate of extinction than sexuals. Weismann's hypothesis is then discussed in light of other patterns in the distribution of sexuality versus asexuality. To account for variation in the frequency of obligate asexuality in different taxa, a simple model is developed in which this frequency is a function of three parameters: the rate of clonal origin, the initial fitness of clones when they arise, and the rate at which that fitness declines over time. Variation in all three parameters is likely to be important in explaining the distribution of obligate asexuality. Facultative asexuality also exists, and for this to be stable it seems there must be ecological differences between the sexual and asexual propagules as well as genetic differences. Finally, the timing of sex in cyclical parthenogens is most likely set to minimize the opportunity costs of sex. None of these patterns contradict Weismann's hypothesis, but they do show that many additional principles unrelated to the function of sex are required to fully explain its distribution. Weismann's hypothesis is also consistent with what we know about the mechanics and molecular genetics of recombination, in particular the tendency for chromatids to recombine with a homolog rather than a sister chromatid at meiosis, which is opposite to what they do during mitosis. However, molecular genetic studies have shown that cis-acting sites at which recombination is initiated are lost by gene conversion as a result, a factor that can be expected to affect many fine details in the evolution of recombination. In summary, although Weismann's hypothesis must be considered the leading candidate for the function of sex and recombination, nevertheless, many additional principles are needed to fully account for their evolution.


Theoretical study of solvent effects on the ground and low-lying excited free energy surfaces of a push-pull substituted azobenzene.
The ground and low-lying excited free energy surfaces of 4-amino-4'-cyano azobenzene, a molecule that has been proposed as building block for chiroptical switches, are studied in gas phase and a variety of solvents (benzene, chloroform, acetone, and water). Solvent effects on the absorption and emission spectra and on the cis-trans thermal and photo isomerizations are analyzed using two levels of calculation: TD-DFT and CASPT2/CASSCF. The solvent effects are introduced using a polarizable continuum model and a QM/MM method, which permits one to highlight the role played by specific interactions. We found that, in gas phase and in agreement with the results found for other azobenzenes, the thermal cis-trans isomerization follows a rotation-assisted inversion mechanism where the inversion angle must reach values close to 180° but where the rotation angle can take almost any value. On the contrary, in polar solvents the mechanism is controlled by the rotation of the CN═NC angle. The change in the mechanism is mainly related to a better solvation of the nitrogen atoms of the azo group in the rotational transition state. The photoisomerization follows a rotational pathway both in gas phase and in polar and nonpolar solvents. The solvent introduces only small modifications in the nπ* free energy surface (S1), but it has a larger effect on the ππ* surface (S2) that, in polar solvents, gets closer to S1. In fact, the S2 band of the absorption spectrum is red-shifted 0.27 eV for the trans isomer and 0.17 eV for the cis. In the emission spectrum the trend is similar: only S2 is appreciably affected by the solvent, but in this case a blue shift is found.


Tracing ancient evolutionary divergence in parasites.
For parasitic platyhelminths that generally lack a fossil record, there is little information on the pathways of morphological change during evolution. Polystomatid monogeneans are notable for their evolutionary diversification, having originated from ancestors on fish and radiated in parallel with tetrapod vertebrates over more than 425 million years (My). This study focuses on the genus Polystomoides that occurs almost worldwide on freshwater chelonian reptiles. Morphometric data show a major divergence in structural adaptations for attachment; this correlates with a dichotomy in micro-environmental conditions in habitats within the hosts. Species infecting the urinary tract have attachment organs with large hamuli and small suckers; species in the oro-nasal tract differ fundamentally, having small hamuli and large suckers. Zoogeographical and molecular evidence supports ancient separation of these site-specific clades: a new genus is proposed - Uropolystomoides - containing urinary tract species distinct from Polystomoides sensu stricto in oro-nasal sites. Aside from differences in attachment adaptations, body plans have probably changed little over perhaps 150 My. This case contrasts markedly with polystomatids in other vertebrate groups where major morphological changes have evolved over much shorter timescales; the chelonian parasites show highly stable morphology across their global distribution over a long period of evolution, exemplifying 'living fossils'.


Reply to Boucher, B.J. Comment on "Lopes et al. Adiposity Metabolic Consequences for Adolescent Bone Health. Nutrients 2022, 14, 3260".
We appreciate your careful reading and comments [...].


Refining tumor-associated aneuploidy through 'genomic recoding' of recurrent DNA copy number aberrations in 150 canine non-Hodgkin lymphomas.
Identification of the genomic regions most intimately associated with non-Hodgkin lymphoma (NHL) pathogenesis is confounded by the genetic heterogeneity of human populations. We hypothesize that the restricted genetic variation of purebred dogs, combined with the contrasting architecture of the human and canine karyotypes, will increase the penetrance of fundamental NHL-associated chromosomal aberrations in both species. We surveyed non-random aneuploidy in 150 canine NHL cases, revealing limited genomic instability compared to their human counterparts and no evidence for CDKN2A/B deletion in canine B-cell NHL. 'Genomic recoding' of canine NHL data into a 'virtual human' chromosome format showed remarkably few regions of copy number aberration (CNA) shared between both species, restricted to regions of dog chromosomes 13 and 31, and human chromosomes 8 and 21. Our data suggest that gene discovery in NHL may be enhanced through comparative studies exploiting the less complex association between CNAs and tumor pathogenesis in canine patients.


Mechanism of dnaB protein action. IV. General priming of DNA replication by dnaB protein and primase compared with RNA polymerase.
The general priming system of dnaB protein and primase (Arai, K., and Kornberg, A. (1979) Proc. Natl. Acad. Sci. U. S. A. 76, 4308-4312) when compared with priming by RNA polymerase shows a number of striking differences. The general priming system is initiated primarily at single-stranded region(S), being active only on single-stranded DNAs (phages and homopolymers) and inhibited by single-stranded DNA binding protein (SSB). Transcripts are only 10 to 60 residues long. By contrast, RNA priming by RNA polymerase is initiated at base-paired regions that are not destabilized by SSB (Geider, K., Beck, E., and Schaller, H. (1978) Proc. Natl. Acad. Sci. U. S. A. 76, 645-649) and transcripts on DNA not coated with SSB are generally longer. In general priming, ATP (or GTP) has three functions: (i) an allosteric effect on dnaB protein in which the nonhydrolyzed analogs adenosine-5'-O-(3'-thiotriphosphate) (or guanosine-5'-O-(3'-thiotriphosphate) can substitute, (ii) initiation of primer synthesis which can incorporate deoxy-, as well as ribonucleotides, and (iii) elongation of the primer, in which the beta, gamma-imido analog can replace ATP (or GTP). An allosteric effect of ATP on RNA polymerase has not been demonstrated, nor has the facile synthesis of hybrid transcripts of ribo- and deoxyribonucleotides.


Entrapment of a Swan Ganz catheter in an IVC filter requiring caval exploration. A case report.
The placement of Swan Ganz (SW) catheters and inferior vena cava (IVC) filters are common procedures performed in critically ill patients. Many reports describe the independent misplacement of SG catheters and IVC filters, and others have reported migration of IVC filters and entanglement of various intravascular devices in IVC filter. Our patient is a 70-year-old Caucasian woman who underwent an aortic valve replacement and coronary artery bypass grafting. The patient developed a deep venous thrombosis and an infrarenal IVC filter was placed without incident. A Swan Ganz catheter was placed later in the postoperative period and became entangled in the IVC filter. We advised operative removal after several unsuccessful percutaneous attempts to retrieve the catheter. IVC filters are indicated for prevention of fatal pulmonary emboli in patients with a contraindication to anticoagulants or with recurrent embolism despite adequate anticoagulant therapy. Complications of IVC filters include caval thrombosis, retroperitoneal hemorrhage and perforation of the IVC, hepatic veins, duodenum and aorta. We describe our evaluation and operative approach and make recommendations for prevention of entangling the SG into the IVC filter.


[Dynamics of methylation changes within functional groups of genes during breast cancer progression].
For the first time in a comparative perspective the epigenetic status of the benign proliferative processes, breast cancer, and metastases to regional lymph nodes was studied using DNA methylation microarray "GoldenGate Cancer Panel I" ("Illumina", USA). The functional groups of differentially methylated genes were identified in each set of samples. The genes that regulate cell proliferation and mobility were methylated in samples with benign proliferative processes. An aberrant methylation of the genes responsible for cell differentiation and proliferation, as well as protein phosphorylation and cell mobility was observed in the samples with malignant phenotype. Differential methylation of the genes that regulate cell adhesion, the formation of anatomical structures, angiogenesis, immune response, signal transduction, and protein phosphorylation was found in the samples with metastases to regional lymph nodes in comparison with the morphologically unaltered breast epithelium. The tissues from the benign proliferative processes and metastases to regional lymph nodes were generally characterized by a relatively lower level of epigenetic variability in comparison with the tissues of the primary tumor.


Investigations of gas-phase lithium-peptide adducts: Tandem. mass spectrometry and semiempirical studies.
Tandem mass spectrometry using a hybrid mass spectrometer of BEqQ geometry was used to investigate the gas-phase formation of the [An (+) Li - H)(+) ion from lithium-peptide adducts. High resolution mass measurements as well as precursor and product ion scans of five peptides indicate that one source of [An (+) Li - H) arises from [An (+) Li](+). Semiempirical calculations (MNOO) and metastable ion decomposition studies of the peptide Gly-Gly-Gly show that the lithium ion prefers to coordinate to the three internal carbonyls of the neutral molecule to give a species that is energetically more stable than the lithiated zwitterion by 305 kJ/mol. Theoretical and experimental evidence suggest that the monolithiated precursor ion population may be a distribution of structural isomers. (J Am Soc Mass Spectrom 1990, 1, 473-480).


Intensity and efficiency of transmission and the development of microfilaraemia and disease: their relationship in lymphatic filariasis.
Currently available methods for measuring the intensity of transmission in the lymphatic filariases are all to some extent unsatisfactory. Clinical methods for defining the presence of filarial disease are also less than perfect, and many infected persons remain free of symptoms and signs for very long periods. Incidence rates of microfilaraemia calculated from prevalence rate data are combined with 'entomological inoculation rates' obtained by direct observations of vector landing rates, infective larval rates and infective larval densities in field studies to determine efficiencies of transmission, and to relate transmission parameters to observed microfilarial and disease prevalence rates. Published studies from various endemic areas of the world which provide sufficient data have been analysed, using reversible catalytic models. In general, it seems that much less intense levels of transmission are needed in sub-Saharan Africa to produce given rates of microfilaraemia and disease than in Asia and Oceania, in the case of Wuchereria bancrofti infections; similarly, the genus Anopheles appears to produce infection and disease much more efficiently than the genera Culex and Aedes when transmitting W. bancrofti. The only example of Brugia malayi transmitted by Mansonia spp. analysed provided the highest level of transmission efficiency found. Tolerable levels of transmission analogous to those used in onchocerciasis cannot at present be defined for the lymphatic filariases; it seems that the intensity of transmission required to produce new cases of disease is probably below that required to produce new cases or episodes of readily detectable microfilaraemia.


Prostate-specific antigen kallikrein and the heart.
Currently, there is growing interest regarding prostate-specific antigen (PSA) and the cardiovascular system. Increased PSA serum levels have been reported after prolonged cardiopulmonary resuscitation, cardiac surgery, extracorporeal cardiopulmonary bypass, acute myocardial infarction (AMI) and coronary artery stenting. The possible role of PSA in cardiac events has been questioned due to the finding of PSA decrease during AMI and by the correlation of variation in PSA levels with coronary lesions and occurrence of major adverse cardiac events. Complexed PSA forms and uncomplexed PSA forms are observed in the bloodstream but the increasing formation of irreversible bound PSA seems to be a crucial finding during AMI. Large studies need to be carried out to confirm these preliminary results and to elucidate unclear aspects. These findings present many potential directions for future research including the role of uncomplexed forms of PSA, the possible distribution of PSA in the heart, the relative expression levels in heart disease states, the mode of expression regulation and other potential specific substrates. The journey of PSA investigation could be longer than initially expected.


Effect of U.V. irradiation and of various chemical conditions on the oxidation of NADH by pheomelanins.
The oxidation reaction of NADH with synthetic and natural pheomelanins was studied under various physicochemical conditions in order to obtain information about the molecular steps involved in the electron transfer process. The comparison with the previous data on eumelanins suggests that the reaction pathways are the same and that the greater photosensitivity of pheomelanins, observed in other experiments, is manifested in the redox reactions with NADH as an increased formation of quinone groups and of superoxide anions.


The ketogenic diet.
The ketogenic diet is a low-carbohydrate, adequate-protein, and high-fat diet with a long history of use for the treatment of intractable seizures in children. This dietary therapy has been enjoying increasing popularity in recent years, despite the availability of increasing numbers of new antiepileptic drugs and surgical treatments. The authors review the history of the ketogenic diet, the traditional protocol in initiating it, possible mechanisms of its action, evidence for efficacy, and side effects. In addition, they highlight some of the areas of active research in this field as well as future directions and unanswered questions. The ketogenic diet is an efficacious and relatively safe treatment of intractable seizures. Despite its long history, however, much remains unknown about the diet, including its mechanisms of action, the optimal protocol, and the full range of its applicability. Investigations of the diet are providing new insight into the mechanisms behind seizures and epilepsy itself, as well as possible new therapies.


Risky sexual behavior among rural female adolescents in Malaysia: a limited role of protective factors.
This paper presents the findings of a cross-sectional survey on the risk and protective factors of premarital sexual behavior among rural female adolescents in Peninsular Malaysia. We investigated data on 770 female respondents aged 13-17 years in rural areas to identify predictive factors for premarital sexual intercourse. Data were analyzed using bivariate and multivariate regression. Specific socio-demographic factors, psychological and family domains, peer delinquency, and knowledge and attitudes about sexuality were considered in risky sexual behaviors in rural Malay girls. The effects of other covariates for premarital sexual intercourse were controlled by logistic regression model. Of the 770 rural female students, about 3.2% of respondents reported experience of sexual intercourse in the past three months. Out of those sexually active girls, 36% were 17 years old and 20% stated having sexual intercourse with more than one partner, and 72% did not use contraception during the most recent sexual intercourse. Midnight activities, peer-sexual disorder, self-evaluation, and attitude toward sexual health were significant predictors of sexual intercourse in rural girls in Malaysia. The finding highlights the impact of psychological factors and peer group influences on the challenges of premarital sexual behavior among rural girls and the notion of school-based sexual health education for adolescents. This study triggers other researchers take into account a comprehensive view of protective factors operating in adolescents' risky sexual behaviors in Asian culture seeing that family domain variables, unexpectedly, exerted no predicting influence on sexually active female teens in rural areas in Malaysia.


Venetoclax and Obinutuzumab in Patients with CLL and Coexisting Conditions.
The BCL2 inhibitor venetoclax has shown activity in patients with chronic lymphocytic leukemia (CLL), but its efficacy in combination with other agents in patients with CLL and coexisting conditions is not known. In this open-label, phase 3 trial, we investigated fixed-duration treatment with venetoclax and obinutuzumab in patients with previously untreated CLL and coexisting conditions. Patients with a score of greater than 6 on the Cumulative Illness Rating Scale (scores range from 0 to 56, with higher scores indicating more impaired function of organ systems) or a calculated creatinine clearance of less than 70 ml per minute were randomly assigned to receive venetoclax-obinutuzumab or chlorambucil-obinutuzumab. The primary end point was investigator-assessed progression-free survival. The safety of each regimen was also evaluated. In total, 432 patients (median age, 72 years; median Cumulative Illness Rating Scale score, 8; median creatinine clearance, 66.4 ml per minute) underwent randomization, with 216 assigned to each group. After a median follow-up of 28.1 months, 30 primary end-point events (disease progression or death) had occurred in the venetoclax-obinutuzumab group and 77 had occurred in the chlorambucil-obinutuzumab group (hazard ratio, 0.35; 95% confidence interval [CI], 0.23 to 0.53; P<0.001). The Kaplan-Meier estimate of the percentage of patients with progression-free survival at 24 months was significantly higher in the venetoclax-obinutuzumab group than in the chlorambucil-obinutuzumab group: 88.2% (95% CI, 83.7 to 92.6) as compared with 64.1% (95% CI, 57.4 to 70.8). This benefit was also observed in patients with TP53 deletion, mutation, or both and in patients with unmutated immunoglobulin heavy-chain genes. Grade 3 or 4 neutropenia occurred in 52.8% of patients in the venetoclax-obinutuzumab group and in 48.1% of patients in the chlorambucil-obinutuzumab group, and grade 3 or 4 infections occurred in 17.5% and 15.0%, respectively. All-cause mortality was 9.3% in the venetoclax-obinutuzumab group and 7.9% in the chlorambucil-obinutuzumab group. These differences were not significant. Among patients with untreated CLL and coexisting conditions, venetoclax-obinutuzumab was associated with longer progression-free survival than chlorambucil-obinutuzumab. (Funded by F. Hoffmann-La Roche and AbbVie; ClinicalTrials.gov number, NCT02242942.).


Relationship between alcohol intake, health and social status and cardiovascular risk factors in the Urban Paris-Ile-de-France Cohort: is the cardioprotective action of alcohol a myth?
Observational studies document the inverse relationship between cardiovascular disease (CVD) and moderate alcohol intake. However, the causal role for alcohol in cardioprotection remains uncertain as such protection may be caused by confounders and misclassification. The aim of our study was to evaluate potential confounders, which may contribute to putative cardioprotection by alcohol. We evaluated clinical and biological characteristics, including cardiovascular (CV) risk factors and health status, of 149,773 subjects undergoing examination at our Center for CVD Prevention (The Urban Paris-Ile-de-France Cohort). The subjects were divided into four groups according to alcohol consumption: never, low (<or=10 g/day), moderate (10-30 g/day) and high (>30 g/day); former drinkers were analyzed as a separate group. After adjustment for age, moderate male drinkers were more likely to display clinical and biological characteristics associated with lower CV risk, including low body mass index, heart rate, pulse pressure, fasting triglycerides, fasting glucose, stress and depression scores together with superior subjective health status, respiratory function, social status and physical activity. Moderate female drinkers equally displayed low waist circumference, blood pressure and fasting triglycerides and low-density lipoprotein-cholesterol. Alcohol intake was strongly associated with plasma high-density lipoprotein-cholesterol in both sexes. Multivariate analysis confirmed that moderate and low drinkers displayed better health status than did never drinkers. Importantly, few factors were causally related to alcohol intake. Moderate alcohol drinkers display a more favorable clinical and biological profile, consistent with lower CV risk as compared with nondrinkers and heavy drinkers. Therefore, moderate alcohol consumption may represent a marker of higher social level, superior health status and lower CV risk.


Evaluation of physiological and blood serum differences in heat-tolerant (Romosinuano) and heat-susceptible (Angus) Bos taurus cattle during controlled heat challenge.
A study was performed to evaluate differences in thermoregulatory ability of 2 Bos taurus breeds with known differences in heat tolerance. Nine Angus (AG; 304 +/- 7 kg of BW) and 9 Romosinuano (RO; 285 +/- 7.5 kg of BW) steers were transported to the Brody Environmental Center at the University of Missouri. Steers were housed for 18 d at thermoneutrality (TN; 21 degrees C) before initiation of heat stress (HS), which consisted of daily cyclic air temperature (26 degrees C, night; 36 degrees C, day) for 14 d. Rectal temperature and respiration rate were measured 6 times daily throughout the study. Sweat rates at shaved skin sites were recorded on specific days. Blood samples were taken once per week. Angus steers maintained rectal temperature 0.5 degrees C greater than RO at TN (P < 0.001). Likewise, respiration and sweat rates were greater (P < 0.001) in AG than RO at TN (P < 0.05). Rectal temperature increased during HS for both breeds with AG maintaining greater temperatures (P < 0.001). Both breeds increased respiration rate during HS, with AG steers exhibiting the greater rate (P < 0.001). Sweat rate increased more than 4-fold during HS (P < 0.001), followed by reduction after 7 d. Even after HS acclimation, AG exhibited the greater sweat rate (P < 0.001). Breed differences for serum leptin, creatinine, and cholesterol were found throughout the study with AG being greater than RO. Although there were no breed differences (P = 0.21) at TN, only AG steers exhibited a HS-induced increase (P < 0.05) in prolactin, creatinine, and cholesterol concentrations to suggest that an increase in rectal temperature is required for this effect. Use of rectal temperature along with endocrine markers, such as prolactin, may aid in the identification of B. taurus sensitivity to heat.


Association between angiotensin-converting enzyme gene polymorphism and coronary artery disease.
An insertion/deletion (I/D) polymorphism in the gene for angiotensin-converting enzyme (ACE) is associated with myocardial infarction and other cardiac pathology. There is evidence for a role of the renin-angiotensin system in cell growth and in the repair of damaged arterial walls, so the ACE gene is postulated to be a candidate gene affecting the important clinical problem of coronary artery disease (CAD). In view of the clinical importance of the ACE as a major marker of cardiovascular diseases, we investigated the I/D polymorphism of the ACE gene in Turkish CAD patients in comparison with control subjects to evaluate a possible association between CAD and the gene encoding ACE. Polymerase chain reaction, restriction fragment length polymorphism, and agarose gel electrophoresis techniques were used to determine the ACE genotype in 58 subjects. The frequencies of ACE D and ACE I allele among the patients with CAD were 62.26% and 37.73 % and in the control subjects were 49.3% and 50.76%, respectively. The greater frequency of deletion allele (D) was in the CAD group than in the control subjects was significant (P < 0.01).


[A lack of understanding of the rulings by disciplinary committees].
The fact that certain rulings of disciplinary committees evoked much criticism among colleagues is distressing in itself, but such criticism should be interpreted with due caution, as different explanations are conceivable. For instance, the published abstract of the committee ruling may have gaps with regard to facts and motivation. It is also possible that the committee has good grounds to accentuate the professional standards, which understandably may meet some resistance among the medical profession. Finally, it is theoretically possible that the disciplinary tribunal is not fully informed about relevant professional standards and current practice. It is precisely to minimize such possible communication breakdowns that disciplinary powers have largely been entrusted to persons from the medical profession.


The relationship between body mass index and blood pressure in patients undergoing chronic hemodialysis: A reverse epidemiology in Jakarta, Indonesia.
In the general population, obesity is positively correlated with hypertension. On the other hand, there was hypothesis of "reverse epidemiology" in the relationship between body mass index (BMI) and blood pressure (BP) of hemodialysis (HD) patients. This study aimed to investigate the "reverse epidemiology" of the relationship between the two variables in Jakarta, Indonesia. Cross-sectional study was conducted at Cipto Mangunkusumo Hospital, Koja District Hospital, and Cengkareng District Hospital in July 2018. Total sampling was performed with a total of 525 HD patients aged >18 years. All data were analyzed from the medical records. Of 525 patients, 27.4% were obese. The post hoc analyses showed that obese patients had significantly lower post-HD systolic BP (P = 0.006) and diastolic BP (P = 0.004) than the normal-weight patients. The Chi-square analyses showed that the overweight group [odds ratio (OR) = 0.53; 95% confidence interval (CI) 0.31-0.87; P = 0.011] and the obese group (OR = 0. 63; 95% CI 0.400.97; P= 0.038) had significant protective effect (OR <1) on the post-HD hypertension. Being obese was a strong predictor for reduced BP (coefficient β = -0.02; P = 0.031). BMI is inversely associated with BP in patients undergoing chronic HD.


Open, intraperitoneal, ventral hernia repair: lessons learned from laparoscopy.
Recent literature suggests that laparoscopic repair of ventral hernias may have very low recurrence rates. However, laparoscopy may not be feasible in certain situations. We describe an open technique that uses the tension-free retrofascial principles of laparoscopic repair without the need for subcutaneous flaps. Through an incision in the hernia, the peritoneum is entered and adhesions are taken down. A piece of DualMesh (W.L. Gore & Associates, Inc, Newark, Del) is trimmed to fit with a 5-cm circumferential overlap. A vertical incision is made in the mid portion of the mesh. The mesh is fixed in an intraperitoneal retrofascial position using GORE-TEX sutures (W.L. Gore & Associates, Inc). The sutures are brought through the abdominal wall using a laparoscopic suture passer and tied into place on one side of the mesh. That side is then tacked to the posterior fascia with a spiral tacking device. The other side is sutured into place in a similar fashion and then tacked to the fascia by passing the spiral tacking device through the incision in the mesh. The mesh incision is closed with a running GORE-TEX suture. The overlying tissues are closed in layers.


Video-Assisted Thoracoscopic Versus Robotic-Assisted Thoracoscopic Thymectomy: Systematic Review and Meta-analysis.
Minimally invasive thoracic surgical procedures, performed with or without the assistance of a robot, have gained popularity over the last decade. They have increasingly become the choice of intervention for a number of thoracic surgical operations. Minimally invasive surgery decreases postoperative pain, hospital stay and leads to a faster recovery in comparison with conventional open methods. Minimally invasive techniques to perform a thymectomy include video-assisted thoracoscopic surgery (VATS) or robotic-assisted thoracoscopic surgery (RATS). In this study, we aim to systematically review and interrogate the literature on minimally invasive thymectomy and draw a meta-analysis on the outcomes between the two approaches. An extensive electronic health database search was performed on all articles published from inception to May 2015 for studies describing outcomes in VATS and RATS thymectomy. A total of 350 patients were included in this study, for which 182 and 168 patients underwent RATS and VATS thymectomy, respectively. There were no recorded in-hospital deaths for either procedure. There was no statistical difference in conversion to open, length of hospital stay, or postoperative pneumonia. Operational times for RATS thymectomy were longer. The VATS and RATS thymectomy offer good and safe operative and perioperative outcomes. There is little difference between the two groups. However, there is poor evidence basis for the long-term outcomes in minimally invasive procedures for thymectomy. It is imperative that future studies evaluate oncological outcomes both short and long term as well as those related to safety.


[Therapeutic lymphapheresis in leukostasis-induced priapism].
Priapism occurred as a result of leukostasis due to an extreme rise in leukocyte count (503,000/microliter, 96% lymphocytes) in a 46-year-old man with chronic lymphatic leukaemia. In addition to surgical treatment, anticoagulant administration and cytostatic treatment several courses of lymphapheresis were performed using a cell separator. This latter procedure quickly reduced the number of lymphocytes and improved the patient's operability.


Modification of the methylation pattern in the vicinity of the chicken globin genes in avian erythroblastosis virus transformed cells.
Having previously found a reduced transcription of globin genes and an abortive processing of the already transcribed globin pre-mRNA in Avian Erythroblastosis Virus (AEV) transformed cells (1), we compared the genomic DNA of these cells with that of normal chicken erythroblasts, using 32-P-labelled cDNA probes specific for the beta, alpha A and alpha D globin sequences. Restriction endonuclease digestion, electrophoresis of digests in agarose gels, Southern blotting and hybridization were carried out. Our results show that the overall genome organization is not disturbed in the immediate neighbourhood of the adult globin genes; the observed restriction fragments are identical for both DNAs after EcoRI, HindIII, BamHI and XbaI digestion, using the beta, alpha A and alpha D globin cDNA probes. However, we observe specific modifications at some methylation sites in the beta, beta-like and alpha D regions: after HpaII or MspI digestion in the alpha D region and after HhaI digestion in the beta and beta-like region, heavier bands appear in the transformed cell DNA in addition to the ones observed in normal DNA. This implies that, at some specific sites, the transformed cell DNA is more methylated than the normal erythroblast DNA. The possible significance of this observation is discussed.


Who gives pertussis to infants? Source of infection for laboratory confirmed cases less than 12 months of age during an epidemic, Sydney, 2009.
An important approach to protecting infants against pertussis is to provide a booster vaccination to close contacts, however this strategy requires a good understanding of infection sources to be effective. The objective of this study was to identify the most important sources of transmission of pertussis infection to infants, regardless of hospitalisation status. Standardised interviews were conducted during routine follow-up calls with the parent or guardian of laboratory confirmed pertussis cases less than 12 months of age notified to 3 Sydney metropolitan public health units during a pertussis outbreak from January to May 2009. All contacts with a coughing illness or laboratory confirmed pertussis during the 3 weeks prior to onset of illness in the index case, were recorded. A source of infection could not be identified for 29 infants (31%) and a total of 86 known or suspected sources were identified for the other 66 infants. The most frequently identified sources were siblings (36%) and parents (24%), followed by other family members (21%), friends (13%), and settings outside the home such as medical centres (6%). Of 20 siblings aged 3 or 4 years, 16 (80%) were sources of infection, compared with 14 of the 44 (32%) other siblings less than 18 years of age. During this epidemic siblings were more important sources of infant infection than parents. Siblings aged 3 and 4 years of age were particularly important transmitters of pertussis infection to infants. Minimising pertussis infection in 3 and 4 year olds may be an important measure to prevent infant infection.


Attachment to fibronectin or vitronectin makes human neutrophil migration sensitive to alterations in cytosolic free calcium concentration.
Transient increases in cytosolic free calcium concentration, [Ca2+]i, appear to be required for the migration of human neutrophils on poly-D-lysine-coated glass in the presence of dilute serum (Marks, P. W., and F. R. Maxfield. 1990. J. Cell Biol. 110:43-52). In contrast, no requirement for [Ca2+]i transients exists when neutrophils migrate on albumin-coated glass in the absence of serum. To determine the mechanism that necessitates [Ca2+]i transients on poly-D-lysine in the presence of serum, migration was examined on substrates consisting of purified adhesive glycoproteins. In the absence of external Ca2+, a treatment which causes the cessation of [Ca2+]i transients, migration on fibronectin (fn) and vitronectin (vn) was significantly inhibited. Migration was also inhibited in Ca2(+)-buffered cells on these substrates, indicating that this effect was the result of an alteration of [Ca2+]i. In the absence of external Ca2+, the inhibition of migration on fn or vn was more pronounced when soluble fn or vn was added to cells migrating on these substrates. This effect of soluble adhesive glycoprotein was specific: in the absence of external Ca2+, soluble fn did not affect the migration of cells on vn, and soluble vn did not affect the migration on fn. No additional inhibition of migration was observed in Ca2(+)-buffered cells with the addition of soluble adhesive glycoprotein. These data indicate that [Ca2+]i transients are involved in continued migration of human neutrophils on fn or vn, proteins which are part of the extracellular matrix that neutrophils encounter in vivo.


Valyl-tRNA synthetase from Escherichia coli MALDI-MS identification of the binding sites for L-valine or for noncognate amino acids upon qualitative comparative labeling with reactive amino-acid analogs.
Bromomethyl ketone derivatives of L-valine (VBMK), L-isoleucine (IBMK), L-norleucine (NleBMK) and L-phenylalanine (FBMK) were synthesized. These reagents were used for qualitative comparative labeling of Escherichia coli valyl-tRNA synthetase (ValRS), an enzyme with Val/Ile editing activity, in order to identify the binding sites for L-valine or noncognate amino acids. Labeling of E. coli ValRS with the substrate analog valyl-bromomethyl ketone (VBMK) resulted in a complete loss of valine-dependent isotopic [32P]PPi-ATP exchange activity. L-Valine protected the enzyme against inactivation. Noncognate amino acids analogs isoleucyl-, norleucyl- and phenylalanyl-bromomethyl ketones (IBMK, NleBMK and FBMK) were also capable of abolishing the activity of ValRS, FBMK being less efficient in inactivating the synthetase. Matrix-assisted laser desorption-ionization mass spectrometry designated cysteines 424 and 829 as the target residues of the substrate analog VBMK on E. coli ValRS, whereas, altogether, IBMK, NleBMK and FBMK labeled His266, Cys275, His282, His433 and Cys829, of which Cys275, His282 and His433 were labeled in common by all three noncognate amino-acid-derived bromomethyl ketones. With the exception of Cys829, which was most likely unspecifically labeled, the amino-acid residues labeled by the reagents derived from noncognate amino acids were distributed between two fragments 259-291 and 419-434 in the primary structure of E. coli ValRS. In fragment 419-434, Cys424 was specifically labeled by the substrate analog VBMK, while His433 was labeled in common by all the used bromomethyl ketone derivatives of noncognate amino acids, suggesting that the synthetic site where aminoacyl adenylate formation takes place on E. coli ValRS is built up of two subsites. One subsite containing Cys424 might represent the catalytic locus of the active center where specific L-valine activation takes place. The second subsite containing His433 might represent the binding site for noncognate amino acids. The fact that Cys275 and His282, fragment 259-291, were labeled by IBMK, NleBMK and FBMK, but not by the substrate analog VBMK, suggests that these residues might be located at or near the editing site of E. coli ValRS. Comparison of fragment 259-291 with all the available ValRS amino-acid sequences revealed that His282 is strictly conserved, with the exception of its replacement by a glycine in a subgroup corresponding to the archaebacteria. Because a nucleophile is needed in the editing site to achieve hydrolysis of an undesired product at the level of the carbonyl group thereof, it is proposed that the conserved His282 of E. coli ValRS is involved in editing.


Polysaccharide-producing bacteria isolated from paper machine slime deposits.
Development of novel enzymatic methods for slime deposit control in paper mills requires knowledge of polysaccharide-producing organisms and the polysaccharide structures present in deposits. In this work, 27 polysaccharide-producing bacteria were isolated from slime samples collected from different parts of a paper machine. Most of the isolates produced polysaccharides in liquid culture and nine of them were selected for production of polysaccharides for characterisation. The selected isolates belonged to seven different genera: Bacillus, Brevundimonas, Cytophaga, Enterobacter, Klebsiella, Paenibacillus and Starkeya. Using ribotyping, partial 16S rDNA sequencing, physiological tests and fatty acid analysis, four of the nine isolates: Bacillus cereus, Brevundimonas vesicularis, K. pneumoniae and P. stellifer were identified to the species level. Production of polysaccharides by the selected isolates varied between 0.07 and 1.20 g L(-1), the highest amount being produced by B. vesicularis. The polysaccharides were heteropolysaccharides with varying proportions of galactose, glucose mannose, rhamnose fucose and uronic acids.


Continuous photochemical generation of catalytically active [CpRu]+ complexes from CpRu(η6-C6H6)PF6.
Inter- and intramolecular ene-yne coupling reactions catalyzed by a species generated in situ via photolysis of CpRu(η(6)-C(6)H(6))PF(6)--an inexpensive, readily available, and shelf-stable complex--have been demonstrated under conditions of continuous flow. Importantly, the catalyst can be recovered quantitatively at the end of the reaction. Various functional groups are tolerated by the reaction, which affords skipped diene products in high yields.


Clinical management of the baby with hypoxic ischaemic encephalopathy.
The results of randomized clinical trials indicate that the optimal management for infants with hypoxic ischaemic encephalopathy is therapeutic hypothermia combined with high quality standard neonatal intensive care. In addition to therapeutic hypothermia clinical management of the infant with hypoxic ischaemic encephalopathy should include the management of multiorgan dysfunction, obtaining and documenting detailed clinical information and performing appropriate investigations and assessment to confirm the diagnosis and to help direct care, and providing counseling and support to the family. This article is a summary of the in hospital clinical management of infants with hypoxic ischaemic encephalopathy.


Arrhythmia Surgery for Adults with Congenital Heart Disease.
Patients with repaired or unrepaired congenital heart anomalies are at increased risk for arrhythmia development throughout their lives, often paralleling the need for reoperations for hemodynamic residua. The ability to incorporate arrhythmia surgery into reoperations can result in improvement in functional class and decreased need for antiarrhythmic medications. Every reoperation for congenital heart disease can be viewed as an opportunity to assess the electrical and arrhythmia substrates and to intervene to improve the arrhythmias and the hemodynamic condition of the patient. The authors review and summarize the operative techniques for arrhythmia surgery that are based on the arrhythmia mechanisms.


A new ultra-high pressure liquid chromatography method for the determination of antioxidant flavonol aglycones in six Lysimachia species.
UPLC-DAD method was developed and validated for the quantitative determination of free flavonol aglycones (kaempferol, quercetin and myricetin) after acidic hydrolysis in six Lysimachia species. Quantitative analyses showed that the amounts of various flavonol aglycones were significantly different in Lysimachia vulgaris, Lysimachia nummularia, Lysimachia punctata, Lysimachia christinae, Lysimachia ciliata and Lysimachia clethroides. The L. clethroides sample was found to be the richest in kaempferol (25.77 ± 1.29 μg/mg extract) and quercetin (97.67 ± 4.61 μg/mg extract), while the L. nummularia sample contained the highest amount of myricetin (20.79 ± 1.00 μg/mg extract). The antioxidant capacity of hydrolysed extracts was evaluated using in vitro DPPH(•) (2,2-diphenyl-1-picrylhydrazyl) and ABTS(•+) [2,2'-azino-bis-(3-ethylbenzothiazoline-6-sulphonic acid)] decolourisation tests. The observed radical scavenging capacities of the extracts showed a relationship with the measured flavonol aglycone content and composition. The acidic treatment resulted in an increased free radical scavenging activity compared to the untreated methanol extract.


A negative adaptive response is expressed in peripheral blood lymphocytes that are exposed to mitomycin C and cycloheximide.
Mitomycin C (MMC) and cycloheximide (CHX) are known for their apoptotic and antitumor activity. CHX is also known for its property to inhibit protein synthesis and to reduce cytotoxicity of various antitumor drugs, i.e. inducing an adaptive survival response (ASR). The purpose of this study was to evaluate the effect of ASR induced by CHX in cells exposed to clastogenic doses of MMC. In all experiments we used human peripheral blood lymphocytes of 10 healthy male non-smokers, 25-35 years of age. Three groups were established. One control group of PBS-treated group. Two distinctive experimental groups were based on the induction or non-induction of ASR by CHX, i.e. one with MMC alone and a second one with CHX and MMC. The effect of ASR was induced by CHX at a dose of 10 mug/ml. MMC was used in 3 dose levels: 0.05 muM, 0.15 muM and 0.6 muM. To evaluate ASR induced by CHX in cells exposed to MMC we used the cytokinesis-blocked micronucleus test (CBMN) in vitro. CHX at a dose of 10 mg/ml induced an ASR in human peripheral blood lymphocytes of healthy subjects exposed to increasing doses of MMC. CHX induced statistically highly significant difference (p < 0.001) in the nuclear division index (NDI) compared to cells exposed to MMC alone. Genotoxicity of MMC measured by the percentage of micronuclei in binuclear (BN) cells was not elevated in the presence of CHX. Also, the increase in the NDI was correlated with the decrease in nuclear fragmentation (NF). The observed differences in NF and the NDI between the two groups showed that ASR to MMC induced by CHX could be a consequence of inhibition of apoptosis. We argue that adaptation (pro-life processes) can overwhelm its positive aspects (antimutagenic and anticarcinogenic) by increasing the population of cells with chromosome aberrations (chromosome instability) by apoptotic inhibition. CHX disturbs the apoptotic signal. Understanding that ASR can act as a pro-survival process leading to inhibition of apoptosis shall enhance in the future our knowledge of anticarcinogenesis, thus utilizing new paths for better treatment of cancer.


Gene expression profiling of the tumor microenvironment during breast cancer progression.
The importance of the tumor microenvironment in breast cancer has been increasingly recognized. Critical molecular changes in the tumor stroma accompanying cancer progression, however, remain largely unknown. We conducted a comparative analysis of global gene expression changes in the stromal and epithelial compartments during breast cancer progression from normal to preinvasive to invasive ductal carcinoma. We combined laser capture microdissection and gene expression microarrays to analyze 14 patient-matched normal epithelium, normal stroma, tumor epithelium and tumor-associated stroma specimens. Differential gene expression and gene ontology analyses were performed. Tumor-associated stroma undergoes extensive gene expression changes during cancer progression, to a similar extent as that seen in the malignant epithelium. Highly upregulated genes in the tumor-associated stroma include constituents of the extracellular matrix and matrix metalloproteases, and cell-cycle-related genes. Decreased expression of cytoplasmic ribosomal proteins and increased expression of mitochondrial ribosomal proteins were observed in both the tumor epithelium and the stroma. The transition from preinvasive to invasive growth was accompanied by increased expression of several matrix metalloproteases (MMP2, MMP11 and MMP14). Furthermore, as observed in malignant epithelium, a gene expression signature of histological tumor grade also exists in the stroma, with high-grade tumors associated with increased expression of genes involved in immune response. Our results suggest that the tumor microenvironment participates in tumorigenesis even before tumor cells invade into stroma, and that it may play important roles in the transition from preinvasive to invasive growth. The immune cells in the tumor stroma may be exploited by the malignant epithelial cells in high-grade tumors for aggressive invasive growth.


Velamentous cord insertion in monochorionic twin gestation. An added risk factor.
To study the effects of umbilical cord insertion combinations on outcomes in monochorionic (MC) twin placentas. Sixty consecutive MC placentas were analyzed by cord insertion patterns with regard to growth discordance, placental parenchymal sharing, types and patterns of intertwin vascular anastomoses, perinatal mortality and frequency of fetofetal transfusion. Cord insertions were classified as central/eccentric (CEN) or velamentous/marginal (VEL). Forty-five percent of the twins had VEL insertions. The CEN/VEL combination was found in 53% of pairs. The CEN/VEL group had the highest rates of growth discordance > 20%, unequal placental parenchymal sharing, uncompensated anastomoses and perinatal demise. VEL cord insertion and the CEN/VEL combination are indicators of high-risk subgroups within MC twins. VEL cord insertions can be diagnosed by ultrasound, identifying these high-risk groups.


Second-hand smoke exposure and mitigation strategies among home visitation workers.
Protection of workers from second-hand smoke (SHS) in occupational settings is an important policy priority, yet little attention has been given to SHS protection for home visitation health workers, who number almost 2 million in the USA. Self-reported SHS exposure, SHS mitigation strategies and suggestions for further SHS exposure reduction approaches were obtained from home visitation health workers in Massachusetts. A cross-sectional survey was conducted among Massachusetts Early Intervention workers (N=316) at their state-wide conference in April 2010. Eighty-three per cent of respondents reported at least 1 hour per month of SHS exposure, and 16% reported at least 11 hours per month. Nevertheless, only 22% of workers counselled clients on maintaining a smoke-free home. Fewer than 30% of workers had ever voiced concerns to their employing agency, and just 12% had raised their concerns directly with clients. Only 14% stated that their agency had rules designed to protect workers from SHS. SHS exposure occurs frequently among home visitation health workers. The data point to a substantial population who are not protected from SHS exposure by formal policies.


Infrared Astronomy After IRAS.
The 250,000 sources in the recently issued Infrared Astronomy Satellite (IRAS) all-sky infrared catalog are a challenge to astronomy. Many of these sources will be studied with existing and planned ground-based and airborne telescopes, but many others can no longer even be detected now that IRAS has ceased to operate. As anticipated by advisory panels of the National Academy of Sciences for a decade, study of the IRAS sources will require the Space Infrared Telescope Facility (SIRTF), a cooled, pointed telescope in space. This instrument may be the key to our understanding of cosmic birth-the formation of planets, stars, galaxies, active galactic nuclei, and quasars. Compared with IRAS and existing telescopes, SIRTF's power derives from a thousandfold gain in sensitivity over five octaves of the spectrum.


The Use of Artificial Intelligence in Assessing Affective States in Livestock.
In order to promote the welfare of farm animals, there is a need to be able to recognize, register and monitor their affective states. Numerous studies show that just like humans, non-human animals are able to feel pain, fear and joy amongst other emotions, too. While behaviorally testing individual animals to identify positive or negative states is a time and labor consuming task to complete, artificial intelligence and machine learning open up a whole new field of science to automatize emotion recognition in production animals. By using sensors and monitoring indirect measures of changes in affective states, self-learning computational mechanisms will allow an effective categorization of emotions and consequently can help farmers to respond accordingly. Not only will this possibility be an efficient method to improve animal welfare, but early detection of stress and fear can also improve productivity and reduce the need for veterinary assistance on the farm. Whereas affective computing in human research has received increasing attention, the knowledge gained on human emotions is yet to be applied to non-human animals. Therefore, a multidisciplinary approach should be taken to combine fields such as affective computing, bioengineering and applied ethology in order to address the current theoretical and practical obstacles that are yet to be overcome.


[Melatonin in dermatology. Experimental and clinical aspects].
Melatonin (N-acetyl-5-methoxytryptamine) is a hormone with multiple functions in humans, produced by the pineal gland and stimulated by beta-adrenergic receptors. Serum melatonin levels exhibit a circadian rhythm with low levels during the day, rise in the evening and maximum levels at night between 2 and 4 a.m. Melatonin participates in the regulation of several physiological processes such as seasonal biological rhythm, daily sleep induction, aging and modulation of immunobiological defence reactions. Furthermore, melatonin has a highly lipophilic molecular structure facilitating penetration of cell membranes and serving as an extra- and intracellular free radical scavenger. Melatonin seems to quench mainly hydroxyl radicals, the most damaging of all free radicals. Melatonin may play a role in the etiology and treatment of several dermatoses e.g. atopic eczema, psoriasis and malignant melanoma. The influence of melatonin on hair growth is another aspect. Topical application of melatonin inhibits the development of UV-erythema. Penetration through skin after topical application and oral bioavailability auxit further investigations on the pharmacokinetic and pharmacodynamic actions of melatonin.


Chirality-dependent reactivity of individual single-walled carbon nanotubes.
Electronic characteristics of a single-walled carbon nanotube (SWCNT) strongly depend on minor variations in its atomic arrangement, specifically chirality. Therefore, precise control over nanotube chirality is highly desired for their application. Theoretically, SWCNTs with different structures have different chemical reactivities, which can be further used for their chirality selection. Here, an approach is developed to examine the relationship between the chirality of SWCNTs and their intrinsic chemical reactivity. By oxidizing individual, high-quality, suspended SWCNTs and using the nanobeam electron diffraction technique, it is shown that the reactivity of SWCNTs to O2 is intricately related to their diameters, metallicity, and chiral angles. In particular, even minor differences in chiral angles lead to big differences in their reactivity, which concords with first-principles calculations. Based on the experimental observations, a chirality-dependent reactivity sequence is constructed for SWCNTs. These findings shed light on effective chiral separation of SWCNTs for their practical application in many fields.


Sellar lesion: not always a pituitary adenoma.
Inflammatory lesions of the hypophysis account for 0.5% of all symptomatic diseases of the pituitary, which include lymphocytic hypophysitis, granulomatous hypophysitis with or without specific etiology and pituitary abscess. Sellar tuberculoma is a rare type of granulomatous hypophysitis. We document a case of a postmenopausal lady who presented with galactorrhea, headache and blurring of vision. Based on preliminary investigations, a clinical diagnosis of pituitary adenoma was made and the pituitary gland was surgically excised. Histopathological examination showed caseating granulomas, along with normal areas of preserved pituitary gland and a final diagnosis of tuberculous hypophysitis was made. This case is being documented due to the extremely rare involvement of the pituitary gland by granulomatous lesions such as tuberculosis and to emphasize the role of intraoperative consultation to obviate the need for radical surgery in such lesions.


Familial Schwannomatosis: A Diagnostic Challenge.
Schwannomatosis is a disease characterized by the development of multiple benign tumours originating from Schwann cells. Schwannomatosis is a member of the family of diseases known as Neurofibromatosis (NF). Patients with Schwannomatosis develop multiple Schwannomas on cranial, spinal and peripheral nerves. We report a rare case of a 60-year-old female who presented with a painful swelling on the ulnar aspect of her distal forearm. She underwent an excisional biopsy for it; which was suggestive of a Schwannoma. Following ulnar swelling surgery, she developed acute low back pain, which was burning in nature with radiation along both lower limbs without any neurovascular deficit. She was treated conservatively, failing which an MRI was performed which suggested abnormal lesions in the intradural extra medullary compartment of the spinal canal. She had multiple swellings over the entire body with a positive family history of similar swellings in her sister and nephew. The painful lumbar swellings were excised which on histopathological examination revealed to be Schwannomas. No neurological deficit was observed postoperatively. There were no neurocutaneous markers, axillary freckling, visual or auditory disturbances seen in the patient or her relatives. Any patient with multiple painful progressive swellings in the body without the characteristic features of NF-1 and NF-2 should raise the suspicion of Schwannomatosis.


Engineering of aligned skeletal muscle by micropatterning.
Tissue engineered skeletal muscle has tremendous potential for the treatment of muscular injury or muscular dysfunction. However, in vitro methods to generate skeletal muscle with physiologically aligned myofiber structure remains limited. To develop a robust in vitro model that resembles the physiologically aligned structure of muscle fibers, we fabricated micropatterned polymer membranes of poly(dimethylsiloxane) (PDMS) with parallel microgrooves, and then examined the effect of micropatterning on myoblast cellular organization and the cell fusion process. In comparison to the myoblasts on non-patterned PDMS films, myoblasts on micropatterned PDMS films had well-organized F-actin assembly in close proximity to the direction of microgrooves, along with enhanced levels of myotube formation at early time points. The increase of cell cycle regulator p21(WAF/Cip1) and the organized interactions of N-cadherin in myoblasts on micropatterned surfaces may contribute to the enhanced formation of myotubes. Similar results of cellular alignment was observed when myoblasts were cultured on microfluidically patterned poly(2-hydroxyethyl methacrylate) (pHEMA) microgrooves, and the micropatterns were found to detach from the Petri dish over time. To apply this technology for generating aligned tissue-like muscle constructs, we developed a methodology to transfer the aligned myotubes to biodegradable collagen gels. Histological analysis revealed the persistence of aligned cellular organization in the collagen gels. Together, these results demonstrate that micropatterned PDMS or pHEMA can promote cell alignment and fusion along the direction of the microgrooves, and this platform can be utilized to transfer aligned myotubes on biodegradable hydrogels. This study highlights the importance of spatial cues in creating aligned skeletal muscle for tissue engineering and muscular regeneration applications.


Assessment of the performance regarding confirmatory diagnosis and initiation of antiretroviral therapy under a modified national HIV testing algorithm and pay-for-performance program in Taiwan.
A pay-for-performance plan for rapid antiretroviral therapy (ART) commencement was initiated in 2018, while a modified testing algorithm offers immunochromatographic test (ICT) to replace Western blot (WB), and simultaneous testing with ICT and Nucleic Acid Amplification Test (NAAT) for HIV-positive sera was adopted in 2019 in Taiwan. Serum specimens collected from 1117 suspected or confirmed HIV infection cases in 2016-2019 were reassessed the performance of WB, ICT, and NAAT. We reviewed the medical records of 10,732 individuals diagnosed with HIV in 2015-2021 to determine the time from screening to confirmatory diagnosis, followed by ART commencement. All 860 WB-positives were also positive by ICT and NAAT. The positive detection percentages were 37.0% by ICT and 51.4% by NAAT for 257 WB-indeterminate and -negative sera. The sensitivity for WB and ICT was 93.8% and 95.5%, respectively. In the people living with HIV (PLHIV) cohort, the median time from initial positive to confirmatory diagnosis decreased from 5 to 6 days before 2019 to 1 day in 2021. The median time from initial positive to ART initiation decreased from 37 days in 2015, 14 days in 2018, to 6 days in 2021. Compared to 2015-2017, the time to ART initiation was 91.48 days lower in 2018 (P < 0.001) and 100.66 days lower in 2019-2021 (P < 0.001) by the adjusted linear regression model. A significant decrease in the time to ART initiation was observed after initiation of the pay-for-performance program and optimized testing algorithm in Taiwan.