Start small, dream big: Experiences of physical activity in public spaces in Colombia.
Multi-sectoral strategies to promote active recreation and physical activity in public spaces are crucial to building a "culture of health". However, studies on the sustainability and scalability of these strategies are limited. This paper identifies the factors related to the sustainability and scaling up of two community-based programs offering physical activity classes in public spaces in Colombia: Bogotá's Recreovía and Colombia's "Healthy Habits and Lifestyles Program-HEVS". Both programs have been sustained for more than 10years, and have benefited 1455 communities. We used a mixed-methods approach including semi-structured interviews, document review and an analysis of data regarding the programs' history, characteristics, funding, capacity building and challenges. Interviews were conducted between May-October 2015. Based on the sustainability frameworks of Shediac-Rizkallah and Bone and Scheirer, we developed categories to independently code each interview. All information was independently analyzed by four of the authors and cross-compared between programs. Findings showed that these programs underwent adaptation processes to address the challenges that threatened their continuation and growth. The primary strategies included flexibility/adaptability, investing in the working conditions and training of instructors, allocating public funds and requesting accountability, diversifying resources, having community support and champions at different levels and positions, and carrying out continuous advocacy to include physical activity in public policies. Recreovía and HEVS illustrate sustainability as an incremental, multi-level process at different levels. Lessons learned for similar initiatives include the importance of individual actions and small events, a willingness to start small while dreaming big, being flexible, and prioritizing the human factor.


Inside-out vs. standard vein graft to repair a sensory nerve in rats.
Nerve regeneration in a sensory nerve was obtained by the application of different techniques: inside-out vein graft (IOVG group) and standard vein graft (SVG group). These techniques provide a good microenvironment for axon regeneration in motor nerves, but their efficiency for regeneration of sensory nerves is controversial. The saphenous nervtce was sectioned and repaired by the inside-out and standard vein graft techniques in rats. After 4, 12, and 20 weeks the graft and the distal stump were observed under electron microscopy. In each studied period, the pattern, diameters, and thickness of the myelin sheaths of the regenerated axons were measured in the graft and distal stump. A comparative study about the regenerated nerve fibers by these two different techniques was performed. Regenerated nerve fibers were prominent in both vein grafts 4 weeks after the surgical procedures. On the other hand, in the distal stump, regenerated nerve fibers were observed only from 12 weeks. In both inside-out vein graft and standard vein graft statistical difference was not observed about the diameters and thickness of the myelinated fibers after 20 weeks. On the other hand, the inside-out group had greater regenerated axon number when compared to the standard group. There is a capillary invasion in both graft and distal stump, especially in the IOVG group. The regenerated axons follow these capillaries all the time like satellite microfascicles. After 20 weeks, the diameters of regenerated fibers repaired by the standard vein graft technique were closer to the normal fibers compared to the inside-out vein graft. On the other hand, the pattern of these regenerated axons was better in the IOVG group.


Endothelium-dependent hyperpolarization-related relaxations diminish with age in murine saphenous arteries of both sexes.
We investigated the effects of aging on the contributions of NO and endothelium-dependent hyperpolarization (EDH) to endothelium-dependent relaxation in saphenous arteries of male and female C57BL/6J mice aged 12, 34 and 64 weeks. Vasomotor responses of saphenous arteries were analysed by wire myography in the absence and presence of stimuli of the endothelium, inhibitors of NOS, and inhibitors and stimulants of small (KCa 2.3) and intermediate (KCa 3.1) conductance calcium-activated potassium channels. Arterial relaxing responses to sodium nitroprusside and to ACh in the absence of pharmacological inhibitors (indomethacin and L-NAME), were similar in all age groups and sexes, but those mediated by endothelium-derived NO were slightly but significantly increased in 64-week-old male mice. In the presence of inhibitors, 12-week-old animals showed pronounced ACh-induced relaxation, which was significantly reduced in 34- and 64-week-old mice of both sexes. The EDH-related component of ACh-induced relaxations was abolished by TRAM-34 (KCa 3.1 blocker) or UCL 1684 (KCa 2.3 blocker). Although the maximal relaxation induced by NS309 (KCa activator) was not affected by aging, the sensitivity for NS309 significantly decreased with aging. The presence of SKA-31 (KCa modulator) potentiated relaxations induced by ACh in arteries of 12-week-old but not older mice. In a small muscular artery of mice of either sex, total endothelium-dependent relaxation is not affected by age. However, possibly due to changes in KCa channel function, the contribution of EDH to endothelium-dependent relaxations decreased with age. The contribution of endothelium-derived NO increases in old male mice.


Mortality in HIV infected individuals in Pune, India.
With the presence of HIV epidemic for more than two decades in India, rise in the number of HIV related deaths is expected. Data on mortality in HIV infected individuals from prospective studies are scanty in India. We report here data on mortality in a systematically followed cohort of HIV infected individuals at Pune, Maharashtra, India. A total of 457 HIV infected individuals were enrolled in a prospective study in Pune between September 2002 and November 2004. They were evaluated clinically and monitored for CD4 counts at every quarterly visit. Mortality data were collected from the records of hospital facilities provided by the study. If the death occurred outside such hospitals; relatives of the participants were requested to inform about the death. Median CD4 count in study participants was 218 cells/μl (95% CI: 107-373) at baseline. The median duration of follow up was 15 months (IQR: 12, 22). Mortality was higher in antiretroviral therapy (ART) naive patients compared to those who received treatment (16.59 vs. 7.25 per 100 person years). Participants above 35 yr of age, CD4 count less than or equal to 100 cells/μl at baseline, tuberculosis at any study time point and ART status were independently associated with high mortality [(RR=1.97; 95% CI: (1.23, 3.14), P=0.005, (RR=33.20, 95%CI (7.59, 145.29), P<0.001, (RR=2.38, 95% CI (1.38, 4.09), P= 0.002 and RR=5.60, 95% CI (3.18, 9.86), P<0.001, respectively]. Interpretation & conclusions : High mortality at advanced immunosuppression highlights the importance of early detection of HIV infection. Emphasis needs to be given at timely diagnosis and management of tuberculosis and ART initiation. It is important to create awareness about availability of free antiretroviral drugs in the government ART roll out programme.


Propofol is cardioprotective in a clinically relevant model of normothermic blood cardioplegic arrest and cardiopulmonary bypass.
The general anesthetic propofol has been shown to be cardioprotective. However, its benefits when used in cardioplegia during cardiac surgery have not been demonstrated. In this study, we investigated the effects of propofol on metabolic stress, cardiac function, and injury in a clinically relevant model of normothermic cardioplegic arrest and cardiopulmonary bypass. Twenty anesthetized pigs, randomized to propofol treatment (n = 8) and control (n = 12) groups, were surgically prepared for cardiopulmonary bypass (CPB) and cardioplegic arrest. Doses of warm blood cardioplegia were delivered at 15-min intervals during a 60-min aortic cross-clamped period. Propofol was continuously infused for the duration of CPB and was therefore present in blood cardioplegia. Myocardial biopsies were collected before, at the end of cardioplegic arrest, and 20 mins after the release of the aortic cross-clamp. Hemodynamic parameters were monitored and blood samples collected for cardiac troponin I measurements. Propofol infusion during CPB and before ischemia did not alter cardiac function or myocardial metabolism. Propofol treatment attenuated the changes in myocardial tissue levels of adenine nucleotides, lactate, and amino acids during ischemia and reduced cardiac troponin I release on reperfusion. Propofol treatment reduced measurable hemodynamic dysfunction after cardioplegic arrest when compared to untreated controls. In conclusion, propofol protects the heart from ischemia-reperfusion injury in a clinically relevant experimental model. Propofol may therefore be a useful adjunct to cardioplegic solutions as well as being an appropriate anesthetic for cardiac surgery.


Group cognitive behavioural therapy for stroke survivors with depression and their carers.
Depression in stroke survivors is common, leads to poorer outcomes and often not treated. A group cognitive behavioural therapy (CBT) program (Brainstorm) for stroke survivors with depression, and their carers has been running as part of usual care since 2007. To evaluate the implementation and acceptability of Brainstorm, a closed group intervention consisting of up to 10 sessions of education, activity planning, problem solving and thought challenging. Participating stroke survivors and their carers complete assessment measures at baseline, post-treatment and 1-month and 6-months follow-up. A mixed models for repeated measures data was conducted with depression and anxiety scores for stroke survivors (Beck Depression Inventory-II; Hospital Anxiety and Depression Scale) and the assessment of depression, anxiety and carer burden for carers. Acceptability was assessed by session attendance and written and open participant feedback upon completion of the program. Forty-eight community dwelling stroke survivors and 34 carers attended Brainstorm, with a median attendance of 88% of sessions. Follow-up assessments were completed by 77% (post-treatment), 46% (1-month) and 38% (6-month) of stroke survivors. Stroke survivors' depression scores decreased from baseline to post-treatment (p<.001); maintained at 1-month (p<.001) but not at 6-month (p=.056). Anxiety scores decreased between baseline and 1-month (p=.013). Carer burden, depression and anxiety scores at 1-month and 6-month follow-up, for carers, were all reduced when compared with baseline (p<.05). The Brainstorm group intervention for depression in stroke survivors appears to have been effectively implemented and is acceptable to stroke survivors and carers.


The influence of travel time to health facilities on stillbirths: A geospatial case-control analysis of facility-based data in Gombe, Nigeria.
Access to quality emergency obstetric and newborn care (EmONC); having a skilled attendant at birth (SBA); adequate antenatal care; and efficient referral systems are considered the most effective interventions in preventing stillbirths. We determined the influence of travel time from mother's area of residence to a tertiary health facility where women sought care on the likelihood of delivering a stillbirth. We carried out a prospective matched case-control study between 1st January 2019 and 31st December 2019 at the Federal Teaching Hospital Gombe (FTHG), Nigeria. All women who experienced a stillbirth after hospital admission during the study period were included as cases while controls were consecutive age-matched (ratio 1:1) women who experienced a live birth. We modelled travel time to health facilities. To determine how travel time to the nearest health facility and the FTHG were predictive of the likelihood of stillbirths, we fitted a conditional logistic regression model. A total of 318 women, including 159 who had stillborn babies (cases) and 159 age-matched women who had live births (controls) were included. We did not observe any significant difference in the mean travel time to the nearest government health facility for women who had experienced a stillbirth compared to those who had a live birth [9.3 mins (SD 7.3, 11.2) vs 6.9 mins (SD 5.1, 8.7) respectively, p = 0.077]. However, women who experienced a stillbirth had twice the mean travel time of women who had a live birth (26.3 vs 14.5 mins) when measured from their area of residence to the FTHG where deliveries occurred. Women who lived farther than 60 minutes were 12 times more likely of having a stillborn [OR = 12 (1.8, 24.3), p = 0.011] compared to those who lived within 15 minutes travel time to the FTHG. We have shown for the first time, the influence of travel time to a major tertiary referral health facility on the occurrence of stillbirths in an urban city in, northeast Nigeria.


A 3-year follow-up study of all-ceramic single and multiple crowns performed in a private practice: a prospective case series.
Zirconia-based prostheses are commonly used for aesthetic crown and fixed restorations, although follow-up data are limited, especially for implant-supported crowns. The aim of this study was to evaluate the three-year clinical results of the installation of 463 zirconia core crowns by a general dental private practice. This study followed 142 patients (69 men and 73 women; aged 28-82 years) who had received 248 single crowns (202 tooth-supported, 36 implant-supported) and 225 multiple units of up to six elements (81 tooth-supported, 144 implant-supported). Clinical events, including fracture and loss of retention, secondary caries, and marginal integrity, were recorded. The overall failure rate was computed for the fractured and lost prostheses. Aesthetic, functional, and biological properties were rated, and patient satisfaction was investigated. During the three-year follow-up period, four patients were lost from the study (18 crowns, 4% of the total crowns). Three of the zirconia prostheses suffered fractures in more than three units (11 crowns; one- vs. three-year follow-up, p<0.05, Wilcoxon signed-rank test), and the cumulative prosthesis survival rate was 98.2%. Twelve units lost retention and were re-cemented, and no secondary caries of the abutment teeth were reported. The aesthetic, functional, and biological properties were generally well-rated, and there were no differences between tooth- and implant-supported crowns. The lowest scores were given regarding the anatomical form of the crowns, as some minor chipping was reported. Relatively low scores were also given for the periodontal response and the adjacent mucosa. Overall, patient satisfaction was high. At the three-year follow-up, the zirconia-core crowns appeared to be an effective clinical solution as they had favorable aesthetic and functional properties. Only the marginal fit of the prostheses should be improved upon.


Receptor binding and tyrosine kinase activation by insulin analogues with extreme affinities studied in human hepatoma HepG2 cells.
The insulin-receptor affinity of five human insulin analogues with one to four amino acid substitutions was measured with human hepatoma cells (HepG2). The binding affinities ranged from 0.05% for AspB25 insulin, 18% for AspB9, GluB27 insulin, 80% for AspB28 insulin, and 327% for AspB10 insulin to 687% for HisA8, HisB4, GluB10, HisB27 insulin relative to human insulin. Binding constants obtained by competition experiments at steady state with [125I]TyrA14-labeled insulin and unlabeled analogues and by kinetic studies with [125I]TyrA14-labeled analogues and insulin gave essentially the same values. The kinetic studies showed that differences in affinity between analogues were due to differences in both dissociation and association rate constants. The affinity for insulinlike growth factor I receptor was low, ranging from less than 0.005% for AspB25 insulin to 0.6% for HisA8, HisB4, GluB10, HisB27 insulin. The potencies of insulin analogues in activation of the tyrosine kinase of solubilized and partially purified insulin receptors from HepG2 cells, measured with the exogenous substrate poly(Glu80-Tyr20), ranked in the same order as the binding affinities, the actual values being somewhat elevated for the high-affinity analogues, however. We conclude that these human insulin analogues are active in insulin-receptor binding and tyrosine kinase stimulation but show wide variation in affinity.


Amyloid Deposition in the Upper Aerodigestive Tract, A Single Institute Experience.
Objectives: The purpose of this study is to evaluate clinical information, laboratory results, and pathologic findings of patients with amyloidosis involving larynx, oral cavity, and pharynx from our institute. Methods: A total of 39 specimens from 28 patients were retrieved from 2000 to 2020. Data collection included clinical presentation, radiographic, laboratory results, and pathologic findings. Results: A total of 12 patients had laryngeal amyloidosis and true vocal cord was the most common location. Protein electrophoresis detected monoclonal protein in 10% (1/10) of patients tested. Two patients had hematopoietic disorder (2/12, 17%) and another patient had a peptide profile consistent with amyloid transthyretin (ATTR) detected by mass spectrometry. Twelve patients showed amyloidosis in the oral cavity with 75% involving the tongue. Monoclonal protein was found in 89% of cases tested. Nine patients (9/12, 75%) had systematic involvement including 6 with hematopoietic malignancy and 3 with biopsy-confirmed systemic light chain amyloidosis. Compared to the laryngeal amyloidosis, amyloid deposition in oral cavity had a significant higher association with systematic disease (P < .01). Pharyngeal amyloidosis was seen in 7 patients. Three of 6 patients tested (3/6, 50%) were found to have biopsy-confirmed hematopoietic malignancy. Conclusions: Laryngeal amyloidosis is mostly a localized disease. Amyloidosis involving oral cavity is associated with significantly higher risk of systematic involvement which warrants a comprehensive laboratory, radiographic, and pathologic workup. There is limited data about pharynx amyloidosis. Oropharynx and hypopharynx amyloidosis appear to be more likely associated with underlying hematologic malignancy compared to nasopharynx involvement.


Antibiotic use in developing countries.
Antimicrobials have been used successfully for over 6 decades, but genes expressing resistance to them have emerged in strains of bacteria and have disseminated through the global ecosystem to reach infecting microorganisms, produce disease, and seriously interfere with therapy, allowing infections to progress and kill despite antibiotic administration. The upsurge in prevalence of such resistance genes in the bacterial population that colonize and infect humans involves two processes, emergence and dissemination, in both of which there have been contributions from the developing world, where resistance is common and increasing. The emergence of pneumococcal isolates noted in Papua New Guinea and later in South Africa that 1 decade later spread to most of the world and the intercontinental spread between the United States and Venezuela of a new gentamicin resistance gene carried on an epidemic plasmid are examples of the ability of bacteria to travel freely, without regard to borders. Complex societal issues such as the misuse of antibiotics by physicians, pharmacists, and the public; the suboptimal quality of the drugs (emergence); and conditions such as crowding, lack of hygiene, poor or nonexistent hospital infection control practices, or insufficient surveillance (dissemination) play a largely unmeasured role that requires study and solutions. In the meantime, we may intervene to delay the emergence of resistance and to limit its spread by promoting the judicious use of antibiotics both at the local level as well as from multinational organized cooperative efforts. Education and improvement of surveillance and socioeconomic conditions are integral parts of any solution strategy.


[Long-term treatment of senile macular degeneration with Cosaldon A+E].
During the early phase of senile degeneration of the macula treatment with Cosaldon A+E offers real changes of improvement. In the later phases long-term Cosaldon therapy can bring about an appreciable improvement when other vasoactive substances are administered at intervals. The addition of the vitamins A and E improves the efficacy of Cosaldon. Results in 157 patients are supported by statistics.


Screening relatives in arrhythmogenic right ventricular cardiomyopathy: yield of imaging and electrical investigations.
Arrhythmogenic right ventricular cardiomyopathy (ARVC) is an inherited disease and presymptomatic screening of relatives is recommended. In 2010, the Task Force Criteria (TFC2010) introduced specific diagnostic imaging parameters. The aim of the study was to evaluate the diagnostic yield of family screening and the value of different diagnostic modalities. Family evaluation, including cardiac magnetic resonance (CMR), is routinely offered to ARVC relatives at our institution. We retrospectively registered baseline characteristics, symptomatology, and results of non-invasive examinations from 2010 to 2016 and assessed the findings according to TFC2010. A total of 286 relatives (150 females; age 12-76 years; 251 first-degree) were included. A total of 103 (36%) individuals reported cardiovascular symptoms. The non-invasive workup showed that 101 (35%) relatives had ≥1 positive parameter on signal-averaged electrocardiogram (ECG), 40 (14%) had abnormal findings on Holter monitoring, 36 (13%) fulfilled an ECG criterion, six (2%) fulfilled CMR criteria, and echocardiographic abnormalities was seen in one (0.3%) relative. In total, 21 (7% overall; 13% among gene-positive subgroup) relatives were diagnosed with ARVC and 78 (27% overall; 49% among gene-positive subgroup) with borderline ARVC based on the combined non-invasive evaluations. Family history and electrical investigations alone diagnosed 20 out of 21 (95%) ARVC cases and 73 out of 78 (94%) borderline cases. Consecutive evaluation of ARVC relatives diagnosed 7% with definite and 27% with borderline ARVC according to the TFC2010. Screening relatives for electrical abnormalities with 12 lead ECG, signal-averaged ECG, and Holter monitoring was more sensitive than imaging modalities.


Identification of Bacteroides fragilis by co-agglutination, using a specific monoclonal antibody.
A monoclonal antibody, mAbC3 (IgG(2b)), specific for the Bacteroides fragilis lipopolysaccharide (LPS) was produced and found to react with a common epitope in most strains within the species. mAbC3 was adsorbed to Staphylococcus aureus Cowan I strain and used in a co-agglutination assay for identification of B. fragilis. Almost 98% of the B. fragilis strains were positive in co-agglutination. Among the 283 non-B. fragilis only two strains showed false positive reaction. These results show that the mAbC3 has a high specificity and can be used for the rapid identification of the B. fragilis species.


Role of Osteogenic Coatings on Implant Surfaces in Promoting Bone-To-Implant Contact in Experimental Osteoporosis: A Systematic Review and Meta-Analysis.
The aim of this systematic review and meta-analysis was to evaluate the role of osteogenic coatings (placement of a thin film of organic and inorganic osteoinductive and osteoproliferative materials) on implant surfaces in augmenting bone-to-implant contact (BIC) in osteoporotic bone. To answer the focused question "Do osteogenic coatings on implant surfaces increase BIC in osteoporotic bone?" PubMed/MEDLINE, EMBASE, ISI Web of Knowledge, Scopus, and Google-Scholar databases were searched till June 2017 using different combinations of the following key words: bone-to-implant contact, coating, implant surface, osseointegration, and osteoporosis. Letters to the Editor, review articles, case-reports/case-series, and commentaries were excluded. Six animal studies were included, in which osteoporosis was induced by bilateral ovariectomy. In all studies, implant surface roughness was increased by various osteogenic surface coatings including alumina, hydroxyapatite, calcium phosphate, and zoledronic acid. Five studies showed that bone volume and BIC are significantly higher around implants with coated surfaces than noncoated implants. In 1 study, there was no difference in BIC around coated and noncoated implants. Although experimental studies have shown that osteogenic coatings are effective in enhancing BIC, their clinical relevance requires further investigations.


Increased Retinal Oxygen Metabolism Precedes Microvascular Alterations in Type 1 Diabetic Mice.
To investigate inner retinal oxygen metabolic rate (IRMRO2) during early stages of type 1 diabetes in a transgenic mouse model. In current study, we involved seven diabetic mice (Akita/+, TSP1-/-) and seven control mice (TSP1-/-), and applied visible-light optical coherence tomography (vis-OCT) to image functional parameters including retinal blood flow rate, oxygen saturation (sO2) and the IRMRO2 value longitudinally from 5 weeks of age to 13 weeks of age. After imaging at 13 weeks of age, we analyzed the imaging results, and examined histology of mouse retina. Between diabetic mice and the control group, we observed significant differences in venous sO2 from 9 weeks of age (P = 0.006), and significant increment in IRMRO2 from 11 weeks of age (P = 0.001) in diabetic mice compared with control group. We did not find significant differences in retinal blood flow rate as well as arterial sO2 during imaging between diabetic and control mice. Histologic examination of diabetic and control mice at 13 weeks of age also revealed no anatomical retinal alternations. In diabetic retinopathy, complications in retinal oxygen metabolism may occur before changes of retinal anatomical structure.


Periosteal osteoblastoma of the pelvis: a rare case.
Among the rare bone tumors, the osteoblastoma is a fascinating tumor. The rarity, the predisposition to occur in any bone and the diagnostic dilemma makes this infrequent tumor interesting. It is sporadically reported in the literature and what is rarer is its occurrence in the pelvis. The unusual location and inconclusive radiographic findings with diffused diagnostic evidences delays the management of benign osteoblastoma. We encountered a patient with benign osteoblastoma of the pubic ramus of right side. An excisional biopsy was performed. Peroperatively, the tumor appeared as oval, reddish brown, bony hard mass lying just over the cortex of the right pubic ramus and not breaching the cortex. Histopathological study revealed an osteoid rich lesion. Its presence in pubis must not be ignored and periosteal osteoblastoma should be considered as a differential diagnosis.


Epidermolysis Bullosa Acquisita (Brunsting-Perry Pemphigoid Variant) Localized to the Face and Diagnosed With Antigen Identification Using Skin Deficient in Type VII Collagen.
Brunsting-Perry pemphigoid is defined as an autoimmune vesiculobullous eruption typically localized on the head and neck region with minimal or no mucosal involvement. The disease tends to run a chronic and recurrent course with residual scarring. Histological features are characterized by subepidermal bullae and linear IgG deposits at the dermo-epidermal junction. We report a case of a 46-year-old lady who presented with typical features of Brunsting-Perry pemphigoid. Autoantibodies to type VII collagen were identified by using recessive dystrophic epidermolysis bullosa skin which lacks type VII collagen in an indirect immunofluorescence assay. As a result, we diagnosed our patient as having the Brunsting-Perry pemphigoid variant of epidermolysis bullosa acquisita (EBA). This finding led us to review the literature on target antigens in Brunsting-Perry pemphigoid. Only 11 out of the 58 cases reported to date had target antigens identified. Interestingly, type VII collagen was the second most common target antigen/autoantibody (4 cases) detected after BP180 (5 cases). However, 2 further cases of EBA localized to the face with typical features of Brunsting-Perry pemphigoid were found in the literature. Although the target antigens are heterogeneous in Brunsting-Perry pemphigoid, a significant number of cases represent a clinical presentation of localized EBA.


Localization of the ergtoxin-1 receptors on the voltage sensing domain of hERG K+ channel by AFM recognition imaging.
The inhibition of the human ether-à-go-go-related (hERG) K+ channels is the major cause of long QT syndromes inducing fatal cardiac arrhythmias. Ergtoxin 1 (ErgTx1) belongs to scorpion-toxins, which are K+ channel-blockers, and binds to hERG channel with 1:1 stoichiometry and high affinity (Kd approximately 10 nM). Nevertheless, patch-clamp recordings recently demonstrated that ErgTx1 does not establish complete blockade of hERG currents, even at high ErgTx1 concentrations. Such phenomenon is supposed to be consistent with highly dynamic conformational changes of the outer pore domain of hERG. In this study, simultaneous topography and recognition imaging (TREC) on hERG HEK 293 cells was used to visualize binding sites on the extracellular part of hERG channel (on S1-S2 region) for Anti-Kv11.1 (hERG-extracellular-antibody). The recognition maps of hERG channels contained recognition spots, haphazardly distributed and organized in clusters. Recognition images after the addition of ErgTx1 at high concentrations ( approximately 1 microM) revealed subsequent partial disappearance of clusters, indicating that ErgTx1 was bound to the S1-S2 region. These results were supported by AFM force spectroscopy data, showing for the first time that voltage sensing domain (S1-S4) of hERG K+ channel might be one of the multiple binding sites of ErgTx1.


Association between Natural Resources for Outdoor Activities and Physical Inactivity: Results from the Contiguous United States.
Protected areas including national/state parks and recreational waters are excellent natural resources that promote physical activity and interaction with Nature, which can relieve stress and reduce disease risk. Despite their importance, however, their contribution to human health has not been properly quantified. This paper seeks to evaluate quantitatively how national/state parks and recreational waters are associated with human health and well-being, taking into account of the spatial dependence of environmental variables for the contiguous U.S., at the county level. First, we describe available natural resources for outdoor activities (ANROA), using national databases that include features from the Protected Areas Database, NAVSTREETS, and ATTAINSGEO 305(b) Waters. We then use spatial regression techniques to explore the association of ANROA and socioeconomic status factors on physical inactivity rates. Finally, we use variance analysis to analyze ANROA's influence on income-related health inequality. We found a significantly negative association between ANROA and the rate of physical inactivity: ANROA and the spatial effect explained 69%, nationwide, of the variation in physical inactivity. Physical inactivity rate showed a strong spatial dependence-influenced not only by its own in-county ANROA, but also by that of its neighbors ANROA. Furthermore, community groups at the same income level and with the highest ANROA, always had the lowest physical inactivity rate. This finding may help to guide future land use planning and community development that will benefit human health and well-being.


Longitudinal cognitive and functional changes in primary progressive aphasia.
The variants of primary progressive aphasia (PPA) are predominantly diagnosed on the basis of specific profiles of language impairments. Deficits in other cognitive domains and their evolution over time are less well documented. This study examined the cognitive profiles of the PPA variants over time and determined the contribution of cognition on functional capacity. Longitudinal performance on the Addenbrooke's Cognitive Examination-III (ACE-III) total and cognitive subdomains were investigated in 147 PPA individuals (41 logopenic [lv-PPA], 44 non-fluent [nfv-PPA], and 62 semantic variants [sv-PPA]). The relative contribution of ACE-III subdomain scores to overall functional capacity over time was identified using mixed and hierarchical regression modelling. The annual rate of global ACE-III decline was twice that in lv-PPA than in nfv-PPA and sv-PPA, despite lv-PPA performing intermediate to the other variants at baseline assessment. Notably, attention and visuospatial subdomains declined faster in lv-PPA than in nfv-PPA and sv-PPA; and memory impairment was more severe in lv-PPA than in nfv-PPA at all time points. Functional decline was comparable across PPA variants; however, the contribution of cognition on functional capacity varied across variants and over time. The cognitive profiles of the PPA variants are distinct at baseline and over time. Crucially, cognitive decline in lv-PPA was more widespread and pervasive than in nfv-PPA and sv-PPA. Our findings also demonstrate the complex interplay between cognition and functional capacity. This study underscores the importance of routinely assessing cognition and functional capacity in PPA to improve diagnostic accuracy and provide targeted support services.


Acceptability of the distribution of DMPA-SC by community health workers among acceptors in the rural province of Lualaba in the Democratic Republic of the Congo: a pilot study.
The objective of this research is to assess the acceptability of the provision of subcutaneously administered depo medroxyprogesterone acetate (DMPA-SC) by nonclinically trained community health workers (CHWs) among acceptors in the rural province of Lualaba in the Democratic Republic of the Congo (DRC). In 2017, 34 CHWs received training in provision of DMPA-SC. Among other methods, DMPA-SC by CHWs was offered during household visits and at community outreach events. The initial survey included questions on acceptors' demographic characteristics, contraceptive use history and experience with provision of DMPA-SC by a CHW. The follow-up included questions about side effects experienced and continuation of DMPA-SC by a CHW. Seventy-four percent of initial acceptors of DMPA-SC (N=252) were first-time contraception users. Almost all (96.0%) felt very comfortable with a CHW performing the injection rather than a physician or nurse, and 97.6% perceived that the CHW was very comfortable performing the injection. A total of 239 women were interviewed at follow-up. Most expressed satisfaction with the method despite some side effects experienced. Almost all acceptors (97.9%) were satisfied with the information provided by CHWs, and 93.8% were satisfied with the overall service. Most (96.4%) would choose to continue receiving DMPA-SC by a CHW rather than in a health clinic, and 95.2% would recommend DMPA-SC by a CHW to a friend. Overall, administration of DMPA-SC by CHWs is acceptable to users in Lualaba. DMPA-SC can be safely provided within the community after proper training. This study validates the use of CHWs (without clinical training) to provide DMPA-SC in a rural sub-Saharan African setting. It also represents an important step in obtaining official MOH authorization for the scale-up of this mechanism of distribution to other underserved regions in the DRC.


Quality of life in dementia: a systematically conducted narrative review of dementia-specific measurement scales.
Ascertaining the quality of life (QoL) in people with dementia is important for evaluating service outcomes and cost-effectiveness. This paper identifies QoL measures for people with dementia and assesses their properties. A systematic narrative review identified articles using dementia QoL measures. Electronic databases searched were AMED, CINAHL, EMBASE, Index to Theses, IBSS, MEDLINE, PsycINFO, Sociological Abstracts, and Web of Science. All available years and languages (if with an English language abstract) were included. Searches yielded 6806 citations; 3043 were multiple duplicates (759 being true duplicates). Abstracts were read; 182 full papers were selected/obtained, of which 126 were included as relevant. Few measures were based on rigorous conceptual frameworks. Some referenced Lawton's model (Dementia Quality of Life [DQOL] and Quality of Life in Alzheimer's Disease [QOL-AD]), though these tapped part of this only; others claimed relationship to a health-related QoL concept (e.g. DEMQOL), though had less social relevance; others were based on limited domains (e.g. activity, affect) or clinical opinions (Quality of Life in Late-Stage Dementia [QUALID]). Many measures were based on proxy assessments or observations of people with dementia's QoL, rather than their own ratings. The Bath Assessment of Subjective Quality of Life in Dementia (BASQID) was developed involving people with dementia and caregivers, but excluded some of their main themes. All measures were tested on selective samples only (ranging from community to hospital clinics, or subsamples/waves of existing population surveys), in a few sites. Their general applicability remains unknown, and predictive validity remains largely untested. The lack of consensus on measuring QoL in dementia suggests a need for a broader, more rigorously tested QoL measure.


Elevated Expression of CCN3 in Articular Cartilage Induces Osteoarthritis in Hip Joints Irrespective of Age and Weight Bearing.
Osteoarthritis (OA) occurs not only in the knee but also in peripheral joints throughout the whole body. Previously, we have shown that the expression of cellular communication network factor 3 (CCN3), a matricellular protein, increases with age in knee articular cartilage, and the misexpression of CCN3 in cartilage induces senescence-associated secretory phenotype (SASP) factors, indicating that CCN3 promotes cartilage senescence. Here, we investigated the correlation between CCN3 expression and OA degenerative changes, principally in human femoral head cartilage. Human femoral heads obtained from patients who received total hip arthroplasty were categorized into OA and femoral neck fracture (normal) groups without significant age differences. Gene expression analysis of RNA obtained from femoral head cartilage revealed that CCN3 and MMP-13 expression in the non-weight-bearing part was significantly higher in the OA group than in the normal group, whereas the weight-bearing OA parts and normal cartilage showed no significant differences in the expression of these genes. The expression of COL10A1, however, was significantly higher in weight-bearing OA parts compared with normal weight-bearing parts, and was also higher in weight-bearing parts compared with non-weight-bearing parts in the OA group. In contrast, OA primary chondrocytes from weight-bearing parts showed higher expression of CCN3, p16, ADAMTS4, and IL-1β than chondrocytes from the corresponding normal group, and higher ADAMTS4 and IL-1β in the non-weight-bearing part compared with the corresponding normal group. Acan expression was significantly lower in the non-weight-bearing group in OA primary chondrocytes than in the corresponding normal chondrocytes. The expression level of CCN3 did not show significant differences between the weight-bearing part and non-weight-bearing part in both OA and normal primary chondrocytes. Immunohistochemical analysis showed accumulated CCN3 and aggrecan neoepitope staining in both the weight-bearing part and non-weight-bearing part in the OA group compared with the normal group. The CCN3 expression level in cartilage had a positive correlation with the Mankin score. X-ray analysis of cartilage-specific CCN3 overexpression mice (Tg) revealed deformation of the femoral and humeral head in the early stage, and immunohistochemical analysis showed accumulated aggrecan neoepitope staining as well as CCN3 staining and the roughening of the joint surface in Tg femoral and humeral heads. Primary chondrocytes from the Tg femoral head showed enhanced expression of Ccn3, Adamts5, p16, Il-6, and Tnfα, and decreased expression of Col2a1 and -an. These findings indicate a correlation between OA degenerative changes and the expression of CCN3, irrespective of age and mechanical loading. Furthermore, the Mankin score indicates that the expression level of Ccn3 correlates with the progression of OA.


Consumption Habits and Brand Loyalty of Belgian Coffee Consumers.
Coffee is usually subjected to a roasting process which is responsible for the formation of aroma and flavours but also of some undesirable compounds such as furan and alkyl furans. These compounds are known as process contaminants of the roasting process and exhibit some harmful effects. In order to evaluate the exposure to these compounds in coffee, it is necessary to know the levels of contamination as well as consumption habits. The degree of consumers' loyalty to specific coffee brands could also be an important driver affecting the level of exposure. This research aimed to evaluate the levels of consumption and the degree of loyalty to coffee brands available in Belgian markets, as well as the factors affecting the choice and the consumption of coffee products and coffee brands. Data were collected in Belgium through an online survey. The results show that for the 1930 participants, 87% reported daily coffee consumption and 13% never or occasionally consumed coffee. The global median coffee consumption was 3 cups per day, and the median for individual daily consumers only was 4 cups per day. The level of consumption of ground coffee was about twice higher than coffee beans, followed by instant coffee and relatively very low consumption of coffee substitutes. In total, 78% of participants reported brand loyalty but to different degrees. Two coffee brands sold in Belgian regions were listed together by more than 20% of the survey participants. The most frequent criteria for selecting a specific coffee brand were taste and price, followed by tradition and habit. The age of coffee consumers and several sociodemographic characteristics have significant effects on coffee consumption. The type of coffee product, the degree of loyalty, and also the type of packaging should be further considered (when available) in the exposure assessment to furan compounds.


Relations of biomarkers of extracellular matrix remodeling to incident cardiovascular events and mortality.
To evaluate if biomarkers reflecting left ventricular/vascular extracellular matrix remodeling are associated with cardiovascular disease (CVD) and death in the community. In 922 Framingham Study participants (mean age, 58 years; 56% women), we related circulating concentrations of matrix metalloproteinase-9 (binary variable: detectable versus undetectable), log of tissue inhibitor of matrix metalloproteinase-1, and log of procollagen type III aminoterminal peptide (PIIINP) to incident CVD and death. On follow-up (mean, 9.9 years), 51 deaths and 81 CVD events occurred. Each SD increment of log of tissue inhibitor of matrix metalloproteinase-1 and log-PIIINP was associated with multivariable-adjusted hazards ratios of 1.72 (95% CI, 1.30 to 2.27) and 1.47 (95% CI, 1.11 to 1.96), respectively, for mortality risk. Log-PIIINP concentrations were also associated with CVD risk (hazard ratio [95% CI] per SD, 1.35 [1.05 to 1.74]). Death and CVD incidence rates were 2-fold higher in participants with both biomarkers higher than the median (corresponding hazard ratio [95% CI], 2.78 [1.43 to 5.40] and 1.77 [1.04 to 3.03], respectively) compared with those with either or both less than the median. The inclusion of both biomarkers improved the C-statistic (for predicting mortality) from 0.78 to 0.82 (P=0.03). Matrix metalloproteinase-9 was unrelated to either outcome. Higher circulating tissue inhibitor of matrix metalloproteinase-1 and PIIINP concentrations are associated with mortality, and higher PIIINP is associated with incident CVD, in the community.


Effectiveness of polyherbal formulations for the treatment of type 2 Diabetes mellitus - A systematic review and meta-analysis.
The mortality and morbidity rate of diabetes patients is increasing worldwide which requires an ideal treatment to prevent the disease worsening. Traditional medicine is gaining more attention in diabetes due to its efficacy and safety. We, therefore performed a systematic review study of clinical trials to assess the comparative effect of polyherbal formulations in type 2 Diabetes mellitus. To find the effectiveness of polyherbal formulations in blood sugar and lipid level for type 2 Diabetes mellitus. PubMed, Scopus and CINAHL databases for clinical trials investigating the effect of polyherbal formulations in Type 2 Diabetes mellitus patients were searched. Meta-analysis of eligible trials was conducted employing Revman 5.2 software. Fourteen randomized controlled trials were found eligible for meta-analysis. Meta-analysis of findings showed a significant effect of polyherbal formulations on blood sugar level compared to control group. The estimated standard mean changes at 95% confidence interval, following polyherbal formulations treatment were -0.59, (-0.91 to - 0.27) mg/dL; for fasting blood sugar(p < 0.001), -0.69, (-1.18 to -0.21) mg/dL; for postprandial blood sugar (p = 0.005) and -0.46, (-0.88 to -0.04) gm%; for glycated haemoglobin (p = 0.03). The reduction in postprandial sugar and glycated haemoglobin was statistically significant with polyherbal formulations compared to metformin treatment but not for fasting sugar. Similarly in lipid profile the reduction for total cholesterol and triglycerides was statistically significant with polyherbal formulations compared to control group but was not significant for HDL and LDL whereas in other group of polyherbal formulations and metformin only HDL was favouring polyherbal formulations. Polyherbal formulations occurred to be effective in lowering blood sugar level in Type 2 diabetes but their further efficacy in managing diabetes needs to be validated. Therefore, a qualitative, long term, randomized placebo-controlled trials of adequate sample size are necessary to determine the efficacy of polyherbal formulation in managing diabetes.


Clinical and Psychosocial Predictors of Urological Chronic Pelvic Pain Symptom Change in 1 Year: A Prospective Study from the MAPP Research Network.
We examined baseline clinical and psychosocial characteristics that predict 12-month symptom change in men and women with urological chronic pelvic pain syndromes. A total of 221 female and 176 male patients with urological chronic pelvic pain syndromes were recruited from 6 academic medical centers in the United States and evaluated at baseline with a comprehensive battery of symptom, psychosocial and illness-impact measures. Based on biweekly symptom reports, a functional clustering procedure classified participant outcome as worse, stable or improved on pain and urinary symptom severity. Cumulative logistic modeling was used to examine individual predictors associated with symptom change as well as multiple predictor combinations and interactions. About 60% of participants had stable symptoms with smaller numbers (13% to 22%) showing clear symptom worsening or improvement. For pain and urinary outcomes the extent of widespread pain, amount of nonurological symptoms and poorer overall health were predictive of worsening outcomes. Anxiety, depression and general mental health were not significant predictors of outcomes but pain catastrophizing and self-reported stress were associated with pain outcome. Prediction models did not differ between men and women and for the most part they were independent of symptom duration and age. These results demonstrate for the first time in a large multisite prospective study that presence of widespread pain, nonurological symptoms and poorer general health are risk factors for poorer pain and urinary outcomes in men and women. The results point to the importance of broad based assessment for urological chronic pelvic pain syndromes and future studies of the mechanisms that underlie these findings.


High abundance of JS-1- and Chloroflexi-related Bacteria in deeply buried marine sediments revealed by quantitative, real-time PCR.
Sequences of members of the bacterial candidate division JS-1 and the classes Anaerolineae and Caldilineae of the phylum Chloroflexi are frequently found in 16S rRNA gene clone libraries obtained from marine sediments. Using a newly designed quantitative, real-time PCR assay, these bacterial groups were jointly quantified in samples from near-surface and deeply buried marine sediments from the Peru margin, the Black Sea, and a forearc basin off the island of Sumatra. In near-surface sediments, sequences of the JS-1 as well as Anaerolineae- and Caldilineae-related Bacteria were quantified with significantly lower 16S rRNA gene copy numbers than the sequences of total Bacteria. In contrast, in deeply buried sediments below approximately 1 m depth, similar quantities of the 16S rRNA gene copies of these specific groups and Bacteria were found. This finding indicates that JS-1 and Anaerolineae- and Caldilineae-related Bacteria might dominate the bacterial community in deeply buried marine sediments and thus seem to play an important ecological role in the deep biosphere.


Surgical shunts and TIPS for variceal decompression in the 1990s.
In the 1990s, liver transplantations and transjugular intrahepatic portosystemic shunts (TIPS) have become the most common methods to decompress portal hypertension. This center has continued to use surgical shunts for variceal bleeding in good-risk patients who continue to bleed through endoscopic and pharmacologic treatment. This article reports this center's experience with surgical shunts and TIPS shunts from 1992 through 1999. Sixty-three patients (Child A, 43 patients; Child B, 20 patients) received surgical shunts: distal splenorenal, 54 patients; splenocaval, 4 patients; coronary caval, 1 patient; and mesocaval, 4 patients. Sixty-two patients had refractory variceal bleeding, and 1 patient had ascites with Budd-Chiari syndrome. Two hundred patients (Child A, 24 patients; Child B, 62 patients; Child C, 114 patients) received TIPS shunts. One hundred forty-nine patients had refractory variceal bleeding, and 51 patients had ascites, hydrothorax, or hepatorenal syndrome. Data were collected by prospective databases, protocol follow-up, and phone contact. The 30-day mortality rate was 0% for surgical shunts and 26% for TIPS shunts; the overall survival rate was 86% (median follow-up, 36 months) for surgical shunts and 53% (median follow-up, 40 months) for TIPS shunts. For surgical shunts, the portal hypertensive rebleeding rate was 6.3%; the overall rebleeding rate was 14.3%. For TIPS shunts, the overall rebleeding rate was 25.5% (30-day, 9.4%; late, 22.4%). There were 4 reinterventions for surgical shunts (6.3%); the reintervention rate for TIPS shunts in the bleeding group was 33%, and the reintervention rate in the ascites group was 9.5%. Encephalopathy was severe in 3.1% of the shunt group and mild in 17.5%; this was not systematically evaluated in the TIPS shunts patients. Surgical shunts still have a role for patients whose condition was classified as Child A and B with refractory bleeding, who achieve excellent outcomes with low morbidity and mortality rates. TIPS shunts have been used in high-risk patients with significant early and late mortality rates and have been useful in the control of refractory bleeding and as a bridge to transplantation. The comparative role of TIPS shunts versus surgical shunt in patients whose condition was classified as Child A and B is under study in a randomized controlled trial.


Human T cell responses to human papillomavirus type 16 L1 and E6 synthetic peptides: identification of T cell determinants, HLA-DR restriction and virus type specificity.
Four T cell determinants in the major capsid protein of human papillomavirus (HPV) type 16 L1 and one in the E6 protein associated with cellular transformation were defined using synthetic peptides to stimulate peripheral blood mononuclear cells from asymptomatic individuals. HLA-DR restriction was defined using murine L cells transfected with HLA-DR genes to present antigen. Responses to two of the five determinants by T cell lines and clones were shown to be specific for HPV-16 based on the lack of cross-recognition of the corresponding sequences of other known papillomavirus sequences (types 1a, 5, 6b, 8, 11, 18 and 33). The T cells raised against two of the other peptides cross-reacted with corresponding peptides from other strains to varying extents, depending on their structural homology. The implications of these results regarding the prevalence of HPV-16 infection in the population and the possible diagnostic role of these responses in papillomavirus infection is discussed.


Influence of brain angiotensin on thermoregulation and hydromineral balance during pregnancy in rats.
During mammalian pregnancy, body temperature decreases and there are changes in fluid and electrolyte balance. Angiotensin signaling mechanisms in the brain have been shown to influence thermoregulation and body fluid balance in the nonpregnant state. We hypothesized that brain angiotensin is also implicated in adjusting these physiological systems in the pregnant rat. We compared core temperature and fluid regulation in three groups of pregnant rats: untreated rats, rats receiving continuous infusion of an AT(1) antagonist candesartan (5 microg.kg(-1).day(-1)) into a lateral cerebral ventricle to block brain AT(1) receptors, and rats receiving vehicle [artificial cerebrospinal fluid (aCSF)] vehicle. Untreated and aCSF-treated rats showed a decrease in colonic temperature (-0.5 and -0.8 degrees C respectively) by day 20 of gestation. However, rats treated with candesartan had increased colonic temperature compared with baseline (+0.9 degrees C), and their temperature was significantly higher on days 7 (P < 0.05), 17 (P < 0.05), and 20 (P < 0.001) compared with the other groups (aCSF and untreated). Daily food and water intakes and body weight were not different between the three groups. Similarly, litter sizes and pup weights were equal in all groups. Finally, the expected decreases in plasma Na(+) and osmolality during pregnancy were equivalent in all groups. This study suggests that brain angiotensin mediates the progressive decrease in body temperature that occurs during pregnancy. However, the changes in fluid balance associated with pregnancy are not dependent on brain angiotensin.


Assessment of metal and nutrient concentrations in river water and sediment collected from the cities in the Pearl River Delta, South China.
The effects of anthropogenic activities, industrialization and urbanization on the accumulation of heavy metals and nutrients in sediments and water of rivers in the Pearl River Delta region were examined. Most sediments were seriously contaminated with Cd, Pb, and Zn in accordance with the classification by Hong Kong Environmental Protection Department. Total phosphorus (P) and nitrogen (N) concentrations in sediments ranged from 0.02% to 0.12% and 0.06% to 0.64%, respectively. High carbon (C), N, P and sulphur (S) levels at Yuen Long Creek were related to the discharge of industrial effluents along the river. The enrichment of P and ammoniacal-nitrogen (NH4+-N) in water were obvious. For most sites, the P concentration exceeded 0.1 mg/l, which is the recommended concentration in flowing water to encourage excessive growth of aquatic plants. Nine out of the 16 sites studied had NH4+-N concentration over 2 mg/l. The rivers in the south of Deep Bay (Hong Kong) had high nutrient exports compared with the rivers in the east region and western oceanic water. The concentrations of nitrate-nitrogen NO3--N in surface water were under the maximum contaminant level in public drinking water supplies (10 mg/l) except for one site. Although the concentrations of heavy metals in overlying water were low, their accumulations were significant. High contents of nickel (Ni) and zinc (Zn) in water were found at certain locations, suggesting the occurrence of some local contamination. These preliminary results indicated that river and sediment transported pollutants is likely one of the factors for the water quality degradation of Deep Bay water.


Unilateral versus bilateral iliac screws for spinopelvic fixation: are two screws better than one?
Long-segment spinal instrumentation ending at the sacrum places substantial biomechanical stress on sacral screws. Iliac (pelvic) screws relieve some of this stress by supplementing the caudal fixation. It remains an open question whether there is any clinically significant difference in sacropelvic fixation with bilateral versus unilateral iliac screws. The primary purpose of this study was to compare clinical and radiographic complications in the use of bilateral versus unilateral iliac screw fixation. The authors retrospectively reviewed 102 consecutive spinal fixation cases that extended to the pelvis at a single institution (University of California, San Francisco) in the period from 2005 to 2012 performed by the senior authors. Charts were reviewed for the following complications: reoperation, L5-S1 pseudarthrosis, sacral insufficiency fracture, hardware prominence, iliac screw loosening, and infection. The t-test, Pearson chi-square test, and Fisher exact test were used to determine statistical significance. The mean follow-up was 31 months. Thirty cases were excluded: 12 for inadequate follow-up, 15 for lack of L5-S1 interbody fusion, and 3 for preoperative osteomyelitis. The mean age among the 72 remaining cases was 62 years (range 39-79 years). Forty-six patients underwent unilateral and 26 bilateral iliac screw fixation. Forty-one percent (n = 19) of the unilateral cases and 50% (n = 13) of the bilateral cases were treated with reoperation (p = 0.48). In addition, 13% (n = 6) of the unilateral and 19% (n = 5) of the bilateral cases developed L5-S1 pseudarthrosis (p = 0.51). There were no sacral insufficiency fractures. Thirteen percent (n = 6) of the unilateral and 7.7% (n = 2) of the bilateral cases developed postoperative infection (p = 0.70). In a retrospective single-institution study, single versus dual pelvic screws led to comparable rates of reoperation, iliac screw removal, postoperative infection, pseudarthrosis, and sacral insufficiency fractures. For spinopelvic fixation, placing bilateral (vs unilateral) pelvic screws produced no added clinical benefit in most cases.


Age-related changes in thyroid hormone levels of bonobos and chimpanzees indicate heterochrony in development.
We present information on age related changes of thyroid hormone levels in bonobos (N = 96) and chimpanzees (N = 100) ranging between one and 56 years of age. Fresh urine samples were used for hormone measurements with a commercial competitive total triiodothyronine (T3) ELISA. In both species, immature individuals had higher TT3 levels than adults and there was a marked decrease in TT3 levels between age classes. The two species differed in terms of the timing of TT3 level changes, with chimpanzees experiencing a significant decline in TT3 levels after 10 years of age and bonobos after 20 years of age. The decline of TT3 in chimpanzees appears to coincide with the time when somatic growth terminates while TT3 values in bonobos decrease much later. This temporal asymmetry in urinary thyroid hormone levels indicates heterochrony in the ontogenetic changes of the two sister species and developmental delay in bonobos. The prolongation of high TT3 levels in bonobos, which is characteristic of immatures of both Pan species may affect the behavior of bonobos; namely, the low intensity of aggression they display. Given that developmental studies are often based on post-mortem analyses of skeletons, measures of urinary thyroid hormones offer a non-invasive tool for exploring ontogenetic changes in living wild and captive hominoids.


Complex supramolecular tessellations with on-surface self-synthesized C60 tiles through van der Waals interaction.
Supramolecular tessellation with self-synthesized (C60)7 tiles is achieved based on a cooperative interaction between co-adsorbed C60 and octanethiol (OT) molecules. Tile synthesis and tiling take place simultaneously on a gold substrate leading to a two-dimensional lattice of (C60)7 tiles with OT as the binder molecule filling the gaps between the tiles. This supramolecular tessellation is featured with simultaneous on-site synthesis of tiles and self-organized tiling. In the absence of specific functional groups, the key to ordered tiling for the C60/OT system is the collective van der Waals (vdW) interaction among a large number of molecules. This bicomponent system herein offers a way for the artificial synthesis of 2D complex vdW supramolecular tessellations.


Gitelman's syndrome: a pathophysiological and clinical update.
Gitelman's syndrome (GS), also known as familial hypokalemic hypomagnesemia, is a rare autosomal recessive hereditary salt-losing tubulopathy, characterized by hypokalemic metabolic alkalosis, hypomagnesemia, and hypocalciuria, which is usually caused by mutations in the SLC12A3 gene encoding the thiazide-sensitive sodium chloride contrasporter. Because 18-40% of suspected GS patients carry only one SLC12A3 mutant allele, large genomic rearrangements must account for unidentified mutations. The clinical manifestations of GS are highly variable in terms of age at presentation, severity of symptoms, and biochemical abnormalities. Molecular analysis in our sibling's patients revealed compound heterozygous mutations in the coding region of SLC12A3 as underlying their disease. Such compound heterozygosity can result in disease phenotype for such loss of function mutations in the absence of homozygosis through consanguineous inheritance of mutant alleles, identical by descent. Missense mutations account for approximately 70% of the mutations in GS, and there is a predisposition to large rearrangements caused by the presence of repeated sequences within the SLC12A3. We report two adult male siblings of Jewish origin with late onset GS, who presented in their fifth decade of life with muscle weakness, hypokalemia, hypomagnesaemia, and metabolic alkalosis. Rapid clinical and biochemical improvement was achieved by replacement therapy with potassium and magnesium.


The toxic and stress responses of cultured human retinal pigment epithelium (ARPE19) and human glial cells (SVG) in the presence of triamcinolone.
To compare the cytotoxic effect of TA on human retinal pigment epithelium (ARPE19) and human glial (SVG) cells over a range of concentrations and durations of exposure. TA (0.01-1 mg/mL) or vehicle (benzyl alcohol, 0.025%) was added to the ARPE19 and SVG cultures on day 0 and then subsequently for 1, 3, or 5 days. The amount of cell proliferations with or without TA treatment was performed using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. All samples were read in triplicate (n = 4 in all cases). c-Fos, c-jun, caspase-3, c-myc, and p53 expression was determined after TA treatments after 0, 10, 20, 30, 40, 50, 60, and 90 minutes. All results were analyzed with ANOVA. TA (0.01-1 mg/mL) caused a significant reduction in ARPE19 cells that had been exposed to it for more than 1 day. Significant reductions in the number of SVG cells were observed as early as day 1 at 0.1 and 1 mg/mL TA. In general, the level of remaining SVG cells was less than that of the APRE19 cells over the 5 days. SVG cells appeared more susceptible to TA. Caspase-3 was elevated in both ARPE19 and SVG cells after TA treatment. c-Fos and c-jun expression was also increased in ARPE19 cells but not in SVG. The vehicle of TA had no effect, and there was no change in p53 or c-myc expression. TA was cytotoxic to both SVG and ARPE19 cells, with higher efficacy on SVG. TA caused the activation of the caspase-3 pathway more readily than the cell-protective c-fos and c-jun pathways in SVG cells, making those cells more vulnerable than the ARPE19 cells. The results suggest that TA toxicity in one cell type may not reliably indicate its toxicity in other cells. Different cells within the retina may react to TA differently, or TA may cause changes in the gene expressions differentially with different concentrations of the same stimulus.


Fungal artillery of zombie flies: infectious spore dispersal using a soft water cannon.
Dead sporulating female fly cadavers infected by the house fly-pathogenic fungus Entomophthora muscae are attractive to healthy male flies, which by their physical inspection may mechanically trigger spore release and by their movement create whirlwind airflows that covers them in infectious conidia. The fungal artillery of E. muscae protrudes outward from the fly cadaver, and consists of a plethora of micrometric stalks that each uses a liquid-based turgor pressure build-up to eject a jet of protoplasm and the initially attached spore. The biophysical processes that regulate the release and range of spores, however, are unknown. To study the physics of ejection, we design a biomimetic 'soft cannon' that consists of a millimetric elastomeric barrel filled with fluid and plugged with a projectile. We precisely control the maximum pressure leading up to the ejection, and study the cannon efficiency as a function of its geometry and wall elasticity. In particular, we predict that ejection velocity decreases with spore size. The calculated flight trajectories under aerodynamic drag predict that the minimum spore size required to traverse a quiescent layer of a few millimetres around the fly cadaver is approximately 10 µm. This corroborates with the natural size of E. muscae conidia (approx. 27 µm) being large enough to traverse the boundary layer but small enough (less than 40 µm) to be lifted by air currents. Based on this understanding, we show how the fungal spores are able to reach a new host.


Build better bones with exercise: protocol for a feasibility study of a multicenter randomized controlled trial of 12 months of home exercise in women with a vertebral fracture.
Our goal is to conduct a multicenter randomized controlled trial (RCT) to investigate whether exercise can reduce incident fractures compared with no intervention among women aged ≥65 years with a vertebral fracture. This pilot study will determine the feasibility of recruitment, retention, and adherence for the proposed trial. The proposed RCT will be a pilot feasibility study with 1:1 randomization to exercise or attentional control groups. Five Canadian sites (1 community hospital partnered with an academic center and 4 academic hospitals or centers affiliated with an academic center) and 2 Australian centers (1 academic hospital and 1 center for community primary care, geriatric, and rehabilitation services). One hundred sixty women aged ≥65 years with vertebral fracture at 5 Canadian and 2 Australian centers will be recruited. The Build Better Bones With Exercise (B3E) intervention includes exercise and behavioral counseling, delivered by a physical therapist in 6 home visits over 8 months, and monthly calls; participants are to exercise ≥3 times weekly. Controls will receive equal attention. Primary outcomes will include recruitment, retention, and adherence. Adherence to exercise will be assessed via calendar diary. Secondary outcomes will include physical function (lower extremity strength, mobility, and balance), posture, and falls. Additional secondary outcomes will include quality of life, pain, fall self-efficacy, behavior change variables, intervention cost, fractures, and adverse events. Analyses of feasibility objectives will be descriptive or based on estimates with 95% confidence intervals, where feasibility will be assessed relative to a priori criteria. Differences in secondary outcomes will be evaluated in intention-to-treat analyses via independent Student t tests, chi-square tests, or logistic regression. The Bonferroni method will be used to adjust the level of significance for secondary outcomes so the overall alpha level is .05. No assessment of bone mineral density will be conducted. The proposed definitive trial will require a large sample size. The viability of a large-scale exercise trial in women with vertebral fractures will be evaluated, as well as the effects of a home exercise program on important secondary outcomes.


Are behaviour change techniques and intervention features associated with effectiveness of digital cardiac rehabilitation programmes? A systematic review protocol.
Background: Cardiovascular disease (CVD) is the leading cause of death worldwide. Cardiac rehabilitation (CR) is a complex intervention that aims to stabilise, slow, or reverse the progression of CVD and improve patients' functional status and quality of life. Digitally delivered CR has been shown to be effective and can overcome many of the access barriers associated with traditional centre-based delivered CR programmes. However, there is a limited understanding of the behaviour change techniques (BCTs) and intervention features that maximise the effectiveness of digital programmes. Therefore, this systematic review will aim to identify the BCTs that have been used in digital CR programmes and to determine which BCTs and intervention features are associated with programme effectiveness. Methods: PubMed, MEDLINE (Ovid), EMBASE, CINHAL, PsycINFO and Cochrane Central Register of Controlled Trials will be searched from inception to June 2021 for randomised controlled trials of digital CR with CVD patients. Screening, data extraction, intervention coding and risk of bias will be performed by one reviewer with a second reviewer independently verifying a random 20% of the articles. Intervention content will be coded using the behaviour change technique taxonomy v1 and the Template for Intervention Description and Replication (TIDieR) checklist and intervention features will be identified. A meta-analysis will be conducted to calculate the pooled effect size of each outcome, and meta-regression analyses will investigate whether intervention features and the presence and absence of individual BCTs in interventions are associated with intervention effectiveness. Discussion: The review will identify BCTs and intervention features that are associated with digital CR programmes and adopt a systematic approach to describe the content of these programmes using the BCT taxonomy (v1) and TIDieR checklist. The results will provide key insights into the content and design of successful digital CR programmes, providing a foundation for further development, testing and refinement.


Coronary sinus lead extraction.
Complications are reported more frequently with the implantation of coronary sinus (CS) than other types of leads, and attempts to extract CS leads may also be associated with increased risks. The authors have performed nonthoracotomy lead extraction (LE) since 1981 and maintained a detailed database. By November 2001, 796 leads had been removed from 401 patients. We undertook review of our CS-LE experience to evaluate prevalence, safety, and efficacy. Of 14 patients referred for CS-LE, 7 were treated in the last year. In six the lead had been placed in the CS intentionally, and in eight inadvertently. One recent patient treated with biventricular pacing was septic and died before LE was undertaken. In nine men and four women (mean age 66 years) had one each CS lead and a total of 34 LEs (2.6/patient). Four CS leads had been in place for < 6 months (mean 1.5 month), whereas nine had been in place for between 6 months and 27 years. Several LE methods were used, from simple traction to the use of intraluminal locking stylets and powered sheaths. Complete removal of all leads was achieved in all patients. CS-LE required a mean of 13 minutes, including 1.8 minutes of fluoroscopy. There were no serious complications during the procedures, and the mean hospital stay was 4 days.


[Spread of rectal cancer in the distal mesorectum: a report of 46 cases].
Total mesorectum excision (TME) for rectal cancer may reduce local recurrence by complete eradication of metastatic foci in the distal mesorectum. While the spread regulation of rectal cancer in the distal mesorectum and ideal length of mesorectum resection are still unclear. This study was to investigate the spread of rectal cancer in the distal mesorectum. The whole-mount section with HE staining was used to detect tumor spread in the mesorectum of 46 rectal cancer patients. The correlation of tumor spread to clinicopathologic parameters was analyzed by Logistic regression. The occurrence rate of distal mural invasion of rectal cancer was 10.9% with the maximal distance of 1.5 cmû that of distal mesorectum spread was 21.7% with the maximal distance of 4.0 cm, which included metastasis in lymph nodes, solitary tumor foci, vessel and perineural invasion. Multivariate analysis showed that TNM stage was the only significant factor influencing distal spread of rectal cancer. Spread of rectal cancer in the distal mesorectum is common. Resecting at least 5 cm of the mesorectum distal to rectal cancer is recommended.


How effective are family-based and institutional nutrition interventions in improving children's diet and health? A systematic review.
Effective strategies to improve dietary intake in young children are a priority to reduce the high prevalence of chronic non-communicable diseases in adulthood. This study aimed to assess the impact of family-based and school/preschool nutrition programs on the health of children aged 12 or younger, including the sustainability of these impacts and the relevance to socio-economic inequalities. A systematic review of literature published from 1980 to December 2014 was undertaken. Randomised controlled trials involving families with children aged up to 12 years in high income countries were included. The primary outcomes were dietary intake and health status. Results were presented in a narrative synthesis due to the heterogeneity of the interventions and outcomes. The systematic search and assessment identified 39 eligible studies. 82% of these studies were set in school/preschools. Only one school study assessed the impact of involving parents systematically. The family-based programs which provided simple positive dietary advice to parents and regular follow-up reduced fat intake significantly. School and family-based studies, if designed and implemented well, increased F&V intake, particularly fruit. Effective school-based programs have incorporated role-models including peers, teachers and heroic figures, rewards and increased access to healthy foods. School nutrition programs in disadvantaged communities were as effective as programs in other communities. Family and school nutrition programs can improve dietary intake, however evidence of the long-term sustainability of these impacts is limited. The modest overall impact of even these successful programs suggest complementary nutrition interventions are needed to build a supportive environment for healthy eating generally.


Views of city, county, and state policy makers about childhood obesity in New York State, 2010-2011.
No single solution exists to reduce rates of childhood obesity in the United States, but public policy action is essential. A greater understanding of policy maker views on childhood obesity would provide insight into ways that public health advocates can overcome barriers to propose, enact, and implement obesity prevention policies. We conducted 48 in-depth, qualitative interviews with town/city, county, and state policy makers in the state of New York from December 14, 2010, through June 10, 2011. We used a semistructured interview protocol to solicit policy maker views on the causes of, solutions to, and responsibility for addressing the issue of childhood obesity. Most policy makers considered the issue of childhood obesity to be of high importance. Respondents cited changes to family structures as a major cause of childhood obesity, followed by changes in the external environment and among children themselves. Respondents offered varied solutions for childhood obesity, with the most common type of solution being outside of the respondent's sphere of policy influence. Policy makers cited the need for joint responsibility among parents, government, schools, and the food industry to address childhood obesity. Beliefs of many policy makers about childhood obesity are similar to those of the general public. Findings highlight the need for future research to inform the development of communication strategies to promote policy action among those with authority to pass and implement it.


Stapled mucosectomy: an alternative technique for the removal of retained rectal mucosa after ileal pouch-anal anastomosis.
Restorative proctocolectomy (RPC), when performed with a stapled ileal pouch-anal anastomosis (IPAA), allows the retention of the rectal mucosa above the dentate line and can result in disease persistence or recurrence, as well as neoplastic lesions in patients with ulcerative colitis (UC). We report the case of a patient with chronic UC who underwent staple mucosectomy, which is an alternative technique that evolved from stapled hemorrhoidopexy, rather than more traditional procedures. The patient had undergone laparoscopic RPC with a stapled IPAA 2 cm above the dentate line and a temporary loop ileostomy. Because the histopathology showed low-grade dysplasia in the proximal rectum, stapled mucosectomy with a 33-mm circular stapler kit at the time of ileostomy closure was scheduled. Following the application of a purse-string suture 1 cm above the dentate line, the stapler was inserted with its anvil beyond the purse-string and was fired. The excised rectal tissue was checked to ensure that it was a complete cylindrical doughnut. Histopathology of the excised tissue showed chronic inflammation. There were no complications during a follow-up period of 5 months. Because it preserves the normal rectal mucosal architecture and avoids a complex mucosectomy surgery, stapled mucosectomy seems to be a technically feasible and clinically acceptable alternative to the removal of rectal mucosa retained after RPC.


Child psychomotor development and its relationship with socio-demographic and family stimulation factors in children from Bariloche, Argentina.
This study analyzed the association between psychomotor development and socio-demographic and family stimulation factors in 3-year-old children from San Carlos de Bariloche. A total of 152 apparently healthy children aged 35-37 months old who attended municipal and private kindergartens were evaluated. Children's performance in personal-social, fne motor, language and gross motor skills development using the National Screening Test was analyzed. The relationship between environmental factors and the achievement of developmental milestones was studied using a multivariate logistic regression model. Twenty seven percent of children did not pass the test. The most common outcome measures associated with altered developmental milestones were no reading, low birth weight, and the parents' lower education level. The association with reading was always positive; and this also occurred in relation to the parents' education level. A low birth weight had a negative association with the possibility of passing four milestones, three of which were gross motor skills. Children who attended municipal kindergartens had a low performance in three language milestones, one personal-social milestone and one fne motor milestone when compared to national profles. The percentage of children who did not pass the test was 27%. The most common outcome measures associated with altered developmental milestones were lack of reading to the child, low birth weight, and the parents' lower education level.


Pathway analysis of dilated cardiomyopathy using global proteomic profiling and enrichment maps.
Global protein expression profiling can potentially uncover perturbations associated with common forms of heart disease. We have used shotgun MS/MS to monitor the state of biological systems in cardiac tissue correlating with disease onset, cardiac insufficiency and progression to heart failure in a time-course mouse model of dilated cardiomyopathy. However, interpreting the functional significance of the hundreds of differentially expressed proteins has been challenging. Here, we utilize improved enrichment statistical methods and an extensive collection of functionally related gene sets, gaining a more comprehensive understanding of the progressive alterations associated with functional decline in dilated cardiomyopathy. We visualize the enrichment results as an Enrichment Map, where significant gene sets are grouped based on annotation similarity. This approach vastly simplifies the interpretation of the large number of enriched gene sets found. For pathways of specific interest, such as Apoptosis and the MAPK (mitogen-activated protein kinase) cascade, we performed a more detailed analysis of the underlying signaling network, including experimental validation of expression patterns.


A Randomized Clinical Trial of Technology-Enhanced Family-Focused Therapy for Youth in the Early Stages of Mood Disorders.
Family-focused therapy (FFT) is associated with enhanced outcomes in youth with bipolar and depressive disorders, but has not been evaluated in conjunction with mobile health tools. In symptomatic adolescents whose parents had histories of mood disorders, we examined whether the effects of telehealth-based FFT were augmented by mobile health apps that emphasized mood tracking and family coping skills. Participants (aged 13-19 years) had active mood symptoms and a parent with major depressive or bipolar disorder. Participants received 12 sessions in 18 weeks of telehealth FFT, with random assignment to (1) a mobile app (MyCoachConnect, MCC) that enabled mood tracking, reviews of session content, and text reminders to practice mood management and family communication skills (FFT-MCC); or (2) a mobile app that enabled mood tracking only (FFT-Track). Independent evaluators assessed youth every 9 weeks over 6 months on depressive symptoms (primary outcome), anxiety, and psychosocial functioning. Participants (N = 65; mean age 15.8 ± 1.6 years) significantly improved in depressive symptoms over 6 months (F1,170 = 45.02, p < .0001; ή2 = 0.21, 95% CI = 0.11-0.31), but there were no effects of treatment condition or treatment by time interactions on depression scores. When secondary outcome measures were considered, the subgroup of youth with bipolar spectrum disorders showed greater improvements in anxiety and global functioning in FFT-MCC compared with FFT-Track. Youth in the early stages of mood disorder may benefit from FFT enhanced by mobile health apps. Collaborations between researchers and information technologists on mobile app design and user experience may lead to increases in engagement among adolescents. Technology Enhanced Family Treatment; https://clinicaltrials.gov/; NCT03913013.


Development of bolometric tomography technique for high-contrast radiation distribution in toroidal devices.
An extended Computed Tomography (CT) technique with a priori information based on Phillips-Tikhonov regularization has been developed to handle a high-contrast radiation distribution, which can result in large reconstruction errors in the region where radiation intensity is low, with few line of sight (LOS) data. Reference profiles generated from LOS data for every time slice are employed as the a priori information. In the extended technique, the weighting parameter for the reference profile is automatically determined from the LOS data, to avoid an inappropriate reference. The extended technique has been examined with a reconstruction test with the previously designed CT system using an infrared imaging video bolometer in JT-60SA. In the reconstructed profile of the high-contrast radiation distribution, the extended technique shows improvement of the weak radiation region, such as the scrape-off layer, without the deterioration of the strong radiation region, such as around the divertor. The results indicate that the extended CT technique can help to handle a high-contrast radiation distribution with few LOS data.


The mental cost of cognitive enhancement.
Noninvasive brain stimulation provides a potential tool for affecting brain functions in the typical and atypical brain and offers in several cases an alternative to pharmaceutical intervention. Some studies have suggested that transcranial electrical stimulation (TES), a form of noninvasive brain stimulation, can also be used to enhance cognitive performance. Critically, research so far has primarily focused on optimizing protocols for effective stimulation, or assessing potential physical side effects of TES while neglecting the possibility of cognitive side effects. We assessed this possibility by targeting the high-level cognitive abilities of learning and automaticity in the mathematical domain. Notably, learning and automaticity represent critical abilities for potential cognitive enhancement in typical and atypical populations. Over 6 d, healthy human adults underwent cognitive training on a new numerical notation while receiving TES to the posterior parietal cortex or the dorsolateral prefrontal cortex. Stimulation to the the posterior parietal cortex facilitated numerical learning, whereas automaticity for the learned material was impaired. In contrast, stimulation to the dorsolateral prefrontal cortex impaired the learning process, whereas automaticity for the learned material was enhanced. The observed double dissociation indicates that cognitive enhancement through TES can occur at the expense of other cognitive functions. These findings have important implications for the future use of enhancement technologies for neurointervention and performance improvement in healthy populations.


Airway epithelial versus immune cell Stat1 function for innate defense against respiratory viral infection.
The epithelial surface is often proposed to actively participate in host defense, but evidence that this is the case remains circumstantial. Similarly, respiratory paramyxoviral infections are a leading cause of serious respiratory disease, but the basis for host defense against severe illness is uncertain. Here we use a common mouse paramyxovirus (Sendai virus) to show that a prominent early event in respiratory paramyxoviral infection is activation of the IFN-signaling protein Stat1 in airway epithelial cells. Furthermore, Stat1-/- mice developed illness that resembled severe paramyxoviral respiratory infection in humans and was characterized by increased viral replication and neutrophilic inflammation in concert with overproduction of TNF-alpha and neutrophil chemokine CXCL2. Poor control of viral replication as well as TNF-alpha and CXCL2 overproduction were both mimicked by infection of Stat1-/- airway epithelial cells in culture. TNF-alpha drives the CXCL2 response, because it can be reversed by TNF-alpha blockade in vitro and in vivo. These findings pointed to an epithelial defect in Stat1-/- mice. Indeed, we next demonstrated that Stat1-/- mice that were reconstituted with wild-type bone marrow were still susceptible to infection with Sendai virus, whereas wild-type mice that received Stat1-/- bone marrow retained resistance to infection. The susceptible epithelial Stat1-/- chimeric mice also exhibited increased viral replication as well as excessive neutrophils, CXCL2, and TNF-alpha in the airspace. These findings provide some of the most definitive evidence to date for the critical role of barrier epithelial cells in innate immunity to common pathogens, particularly in controlling viral replication.


Posteromedial Release versus Ponseti Treatment of Congenital Idiopathic Clubfoot: A Long-Term Retrospective Follow-Up Study into Adolescence.
Although many short-term studies have shown the superiority of Ponseti treatment to surgical treatment, studies with long-term follow-up of patients into adolescence are lacking. The aim of this study was to compare the morphological, functional and radiological results of the two methods into and during adolescent age, when both soft tissue and bony procedures can be performed to correct residual deformities. We retrospectively evaluated two groups of patients diagnosed with congenital idiopathic clubfoot and treated with either the Ponseti method (34 clubfeet) and surgery in the form of posteromedial release (31 clubfeet). All included clubfeet were clinically fully corrected after initial treatment and final plaster removal. Evaluation was performed with the International Clubfoot Study Group (ICFSG) score. The age at follow-up was 12.8±1.6 years in the Ponseti group and 13.5±1.7 years in the surgical group. Excellent or good results were obtained in 26 feet (76%) of the Ponseti group and in 14 feet (45%) in the surgical group. The Ponseti treatment was significantly superior to posteromedial release in terms of the final score (10.58±6.49 versus 17.26±8.83, p<0.001), functional score (p<0.001) and radiological score (p<0.001). Residual deformities were clinically present in both groups but were less frequent and less severe in Ponseti-treated patients. Flat-top talus was found to be present in both groups, but the Ponseti method was more protective than surgical treatment against this outcome (relative risk=0.494, p=0.002). The overall foot and ankle mobility was significantly better in the Ponseti group (p<0.001). The Ponseti method was superior to surgery for treatment of clubfoot and achieved better long-term morphological, functional and radiological results. It preserves better mobility of the foot and ankle, and results in less frequent and less severe residual deformities than surgical treatment.


Perioperative Jehovah's Witnesses: a review.
There are many patient groups who may refuse blood products; the most well known amongst them is the Jehovah's Witness faith. Treatment of anaemia and bleeding in such patients presents a challenge to medical, anaesthetic, and surgical teams. This review examines the perioperative issues and management of Jehovah's Witnesses. The history and beliefs of Jehovah's Witnesses are outlined together with their impact on ethics and the law, and different management options throughout the perioperative period are discussed.


Evidence for alteration of the vitamin D-endocrine system in blacks.
As compared with values in white subjects, bone mass is known to be increased and urinary calcium to be diminished in black individuals. To evaluate the possibility that these changes are associated with alterations in the vitamin D-endocrine system, an investigation was performed in 12 black subjects, 7 men and 5 women, and 14 white subjects, 8 men and 6 women, ranging in age from 20 to 35 yr. All of them were hospitalized on a metabolic ward and were given a constant daily diet containing 400 mg of calcium, 900 mg of phosphorus, and 110 meq of sodium. Whereas mean serum calcium, ionized calcium, and phosphate were the same in the two groups, mean serum immunoreactive parathyroid hormone (350 +/- 34 vs. 225 +/- 26 pg/ml, P less than 0.01) and mean serum 1,25-dihydroxyvitamin D (1,25(OH)2D) (41 +/- 3 vs. 29 +/- 2 pg/ml, P less than 0.01) were significantly higher, and mean serum 25-hydroxy-vitamin D (25-OHD) was significantly lower in the blacks than in the whites (6 +/- 1 vs. 20 +/- 2 ng/ml, P less than 0.001). Mean urinary sodium and 24-h creatinine clearance were the same in the two groups, whereas mean urinary calcium was significantly lower (101 +/- 14 vs. 166 +/- 13 mg/d, P less than 0.01) and mean urinary cyclic AMP was significantly higher (3.11 +/- 0.47 vs. 1.84 +/- 0.25 nM/dl glomerular filtrate, P less than 0.01) in the blacks. Further, the blacks excreted an intravenous calcium load, 15 mg/kg body weight, as efficiently as the whites (49 +/- 3 vs. 53 +/- 3%, NS). Mean serum Gla protein was lower in blacks than in whites (14 +/- 2 vs. 24 +/- 3 ng/ml, P less than 0.02), and increased significantly in both groups in response to 1,25(OH)2D3, 4 micrograms/d for 4 d. There was a blunted response of urinary calcium to 1,25(OH)2D3 in the blacks, and mean serum calcium did not change. The results indicate that alteration of the vitamin D-endocrine system with enhanced renal tubular reabsorption of calcium and increased circulating 1,25(OH)2D as a result of secondary hyperparathyroidism may contribute to the increased bone mass in blacks. Their low serum 25-OHD is attributed to diminished synthesis of vitamin D in the skin because of increased pigment.


Clinicopathologic features of adult T-cell leukemias/lymphomas at a North American tertiary care medical center: infrequent involvement of the central nervous system.
Human T-cell lymphotropic virus type 1 is associated with adult T-cell leukemia/lymphoma (ATLL). Published series of ATLLs seen at a United States medical institution are rare. We present the features of 4 ATLLs diagnosed at our North American tertiary care medical center from 1990 to 2012. Despite the absence of a history of origin from an endemic region, all our ATLLs demonstrated evidence of human T-cell lymphotropic virus type 1 infection. Central nervous system (CNS) involvement by ATLL was uncommon in our series, and represented only 1.6% (1/64) of all CNS B-cell or T-cell lymphomas diagnosed over a 20+ year period at our institution. Review of the medical literature reveals that the majority of CNS-involved ATLLs present with the lymphoma or acute subtype, and complete remission is difficult to achieve in these cases. CNS involvement frequently occurs with a systemic disease, which carries an aggressive clinical course with poor prognosis. In addition, CNS involvement by ATLL can be the initial presentation or seen with relapsed disease, can be the only site or be associated with other tissue sites of involvement, and may manifest with variable clinical signs/symptoms. Our retrospective study reveals that ATLLs are rare mature T-cell lymphomas in a native North American population, but the clinical and histopathologic features of ATLLs from this nonendemic region are similar to those seen from other endemic regions. Early recognition of these rare ATLLs involving uncommon sites, such as the CNS, will help optimize treatment for these infrequent mature T-cell lymphomas.


All-in-One Photoactivated Inhibition of Butyrylcholinesterase Combined with Luminescence as an Activation and Localization Indicator: Carbon Quantum Dots@Phosphonate Hybrids.
Photopharmacology is a booming research area requiring a new generation of agents possessing simultaneous functions of photoswitching and pharmacophore. It is important that any practical implementation of photopharmacology ideally requires spatial control of the medicinal treatment zone. Thus, advances in the study of substances meeting all the listed requirements will lead to breakthrough research in the coming years. In this study, CQDs@phosphonate nanohybrids are presented for the first time and combine biocompatible and nontoxic luminescent carbon quantum dots (CQDs) with photoactive phosphonate enabling inhibition of butyrylcholinesterase (BChE), which is a prognostic marker of numerous diseases. The conjunction of these components in hybrids maintains photoswitching and provides enhancement of BChE inhibition. After laser irradiation with a wavelength of 266 nm, CQDs@phosphonate hybrids demonstrate a drastic increase of butyrylcholinesterase inhibition from 38% up to almost 100% and a simultaneous luminescence decrease. All the listed hybrid properties are demonstrated not only for in vitro experiments but also for complex biological samples, i.e., chicken breast. Thus, the most important achievement is the demonstration of hybrids characterized by a remarkable combination of all-in-one properties important for photopharmacology: (i) bioactivity toward butyrylcholinesterase inhibition, (ii) strong change of inhibition degree as a result of laser irradiation, luminescence as an indicator of (iii) bioactivity state, and of (iv) spatial localization on the surface of a sample.


Effects of Subcutaneous Methotrexate in Patients with Refractory Uveitis and Chorioretinitis.
Methotrexate (MTX) is an immunosuppressive agent used to treat noninfectious inflammatory eye conditions and is generally administered orally for ocular inflammatory diseases. When used in rheumatological diseases, subcutaneous administration has been reported to show higher efficacy than oral administration. Therefore, this study aimed to evaluate the effect of subcutaneous MTX in patients with refractory uveitis or choroiditis who did not respond to other immunosuppressive agents. A retrospective case series study was performed between January and December 2018. Patients with uveitis or chorioretinitis who showed little to no treatment response for 6 months or more with conventional immunosuppressive agents were treated with MTX, administered subcutaneously. After 6 months of treatment, patients were evaluated to determine whether complete suppression of inflammation sustained for ≥28 days was achieved in both eyes and whether improvement can be confirmed by fluorescein angiography (FAG). Subcutaneous MTX treatment was performed on 18 patients: 11 had intermediate uveitis and seven had posterior uveitis. In the intermediate uveitis patient group, five patients (50% of the group excluding one patient who dropped out) showed improvement in FAG and three patients (30%) showed complete suppression of inflammation. In the posterior uveitis group, two out of seven patients (excluding two patients who dropped out) showed an improvement, two patients in the group showed little change, and one patient showed aggravation of FAG findings. The study confirmed that in patients with uveitis or chorioretinitis who had a refractory response to treatment with other immunosuppressive agents, subcutaneous MTX showed improved treatment efficacy.