Exploring the Relationship Between Clinical Presentation in Hallux Valgus and Response to AbobotulinumtoxinA Treatment.

The relationship between pain/disability and angular deviation of the hallux valgus (HV), and the impact of orthotic use, laterality, and pain variability on treatment outcomes remain unclear. This was explored in post hoc analyses of a placebo-controlled trial of abobotulinumtoxinA (aboBoNT-A; Dysport®) for HV-associated pain (NCT03569098). The primary endpoint was not met in this study (change from baseline Numeric Pain Rating Scale [NPRS] score vs placebo at week 8); however, there was a greater reduction from baseline in mean NPRS score at week 12 with aboBoNT-A 500U versus placebo (p = .06). Adults with painful HV without surgery were randomized (1:1:1) to aboBoNT-A 300U, aboBoNT-A 500U, or placebo. NPRS was completed for 7 days before baseline and weeks 4, 8, and 12. Over-the-counter orthoses were permitted. Participants (N = 186) had a mean [standard deviation, SD] age of 48.2 [13.1] years, 18% (33/186) used orthotics, and 67% (124/186) had bilateral HV. No associations between baseline pain severity and angular deviation were identified. Participants with high pain variability at baseline (SD > 2) had a poorer response to aboBoNT-A treatment than those with less variability. In conclusion, no relationship between HV-related pain/disability and angular deviation was observed. PLAIN LANGUAGE SUMMARY: A bunion (medical term: hallux valgus) is a common adult foot problem in which the big toe points inward toward the other toes, and this can be painful. How much the big toe points inward (how deformed the foot is) has been linked to the amount of pain the patient experiences. A better understanding of this foot deformity and bunion pain will help doctors and patients to make the right treatment decisions. A study was completed looking at how injections of a type of botulinum toxin (abobotulinumtoxinA) into specific muscles in the foot may help to reduce bunion pain in patients without surgery. This subsequent analysis of the study data looked at the amount of foot deformity in patients, the bunion pain they experienced, and which factors affected how well abobotulinumtoxinA worked to reduce bunion pain. The results of this study showed that the amount of foot deformity was not linked to the level of bunion pain. When deciding the best treatment option to relieve bunion pain, it is important that doctors not only consider how deformed the foot is, but also other important factors such as foot pain levels.

Evaluation of Newcastle disease virus LaSota strain attenuated by codon pair deoptimization of the HN and F genes for in ovo vaccination.

In ovo vaccination is an attractive immunization approach for the poultry industry. However, commonly used Newcastle disease virus (NDV) vaccines cannot be administered in ovo because of the reduced hatchability and embryo mortality. The codon pair deoptimization (CPD) approach has been used to efficiently and rapidly attenuate viruses by targeting the virulence genes. In this study, we aimed to attenuate the NDV LaSota (LS) vaccine strain for in ovo vaccination by CPD of the fusion (F) or/and hemagglutinin-neuraminidase (HN) genes with approximately 44 % suboptimal codon substitutions. Three NDV LS recombinants expressing codon deoptimized F (rLS/F-d), HN (rLS/HN-d), or both genes (rLS/F+HN-d) were generated using reverse genetics technology. Biological assays showed that the CPD viruses retained similar hemagglutination activity and growth ability to the parental rLS virus. The CPD of the HN gene slightly attenuated the rLS/HN-d and rLS/F+HN-d viruses, whereas the CPD of the F gene marginally increased the rLS/F-d virus pathogenicity compared to rLS. Nevertheless, all three CPD rLS viruses were still lethal to 10-day-old specific-pathogen-free (SPF) chicken embryos. In ovo inoculation of 18-day-old SPF chicken embryos with the CPD viruses severely reduced chicken's hatch and survival rates. These results suggested that the CPD of the surface glycoprotein genes of the LS strain at the current level of suboptimal codon substitutions could not sufficiently attenuate the virus for use as an in ovo vaccine, and codon deoptimizing a greater proportion of the F and HN genes or additional gene(s) may be required for sufficient attenuation of the LS strain.

Pain Reduction With AbobotulinumtoxinA for the Treatment of Hallux Valgus in Adult Participants: Results of a Randomized and Placebo-Controlled Phase 2 Trial.

AbobotulinumtoxinA (aboBoNT-A, Dysport® [Ipsen, Paris, France]) inhibits acetylcholine release at the neuromuscular junction and may modulate pain signaling in hallux valgus (HV). This randomized study (NCT03569098) included a double-blind phase (aboBoNT-A 300U, 500U or placebo injections into forefoot muscles) and an open-label aboBoNT-A treatment period in participants with an HV diagnosis and no HV surgery. The primary endpoint was change from baseline in numeric pain rating scale (NPRS) score at week 8. Secondary endpoints included change in NPRS (other time points) and proportion of participants with ≥20% reduction from baseline NPRS (responders). Post-hoc analyses assessed number of days in a 7-day evaluation period that participants spent in a lower pain state than at baseline. Participants received aboBoNT-A 300U (n = 63), 500U (n = 60) or placebo (n = 63). Superiority to placebo was not observed with either aboBoNT-A dose at week 8, thus the primary endpoint was unmet. At week 12, a trend toward efficacy was observed with aboBoNT-A 500U versus placebo and the proportion of participants with ≥20% reduction from baseline NPRS was greater with aboBoNT-A 500U versus placebo (p = .006). Participants in the aboBoNT-A 500U group spent more days with lower NPRS than their lowest baseline score, and with NPRS ≥2 points lower than their mean baseline NPRS at weeks 8 and 12 versus placebo (all p < .05; post-hoc). AboBoNT-A was well tolerated. Although the primary endpoint was unmet, other endpoints showed a nominal advantage for aboBoNT versus placebo for treatment of HV-related pain, particularly at week 12. Further clinical evaluation is needed to establish whether botulinum toxins represent a viable non-operative treatment option for HV-associated pain. PLAIN LANGUAGE SUMMARY: Hallux valgus is the medical name for a bunion, a foot deformity that can worsen over time. Patients with bunions experience pain and walking can become difficult, which can affect their quality of life. Foot support aids (e.g., braces, splints and inserts) are available, but surgery is the standard treatment. This study looked at how injections of a specific type of botulinum toxin, called abobotulinumtoxinA or "aboBoNT-A", into the foot may help to reduce pain in patients with bunions. The study included 186 patients aged 18 to 75 years who had not had surgery on their bunion. The researchers looked at how well the injections worked using scales that measure the pain levels the patient experienced. The main outcome was whether patients who had aboBoNT-A injections had less pain after 8 weeks than they did before treatment. The study included patients who were injected with saltwater (no treatment) to check that any treatment effect was real. Researchers also looked at the results after 12 weeks, as well as how many patients had less pain after treatment than before and how many days in a given week patients experienced less pain after treatment than they did before. There was no reduction in pain levels with aboBoNT-A injections after 8 weeks compared with no treatment. However, the other study outcomes suggested that aboBoNT-A resulted in a small benefit compared with no treatment, especially after 12 weeks. Further medical research is needed to establish whether botulinum toxins represent an alternative treatment to surgery for the pain associated with bunions.

Effects of Nonperiodized and Linear Periodized Combined Training on Health-Related Physical Fitness in Adults With Obesity: A Randomized Controlled Trial.

ABSTRACT: Streb, AR, Passos da Silva, R, Leonel, LdS, Possamai, LT, Gerage, AM, Turnes, T, and Del Duca, GF. Effects of nonperiodized and linear periodized combined training on health-related physical fitness in adults with obesity: a randomized controlled trial. J Strength Cond Res 36(9): 2628-2634, 2022-The aim of this randomized controlled trial study was to compare the effects of 16 weeks of linear periodized and nonperiodized combined training (CT) in cardiorespiratory fitness, muscle strength, and body composition indicators of adults with obesity. Thirty-four obese adults of both sexes (36.6 ± 4.4 years; body mass index, 32.9 ± 2.7 kg·m -2 ) were divided into nonperiodized (NG; n = 8), linear periodized (PG; n = 11), and control (CG; n = 15) groups. The NG and PG groups performed 3 weekly sessions of CT over 16 weeks in different ways. Anthropometric measures, maximal strength for leg press and barbell bench press, maximal oxygen uptake (V̇ o2 max), and ventilatory thresholds were determined before and after intervention. The generalized estimation equation was used, with the applied level of significance for the interaction of 0.10 and the isolated effect of time or group or both of 0.05. Significant and similar increases were observed in the 1-repetition maximum test for bench press (NG: 48.8 ± 5.7 to 55.0 ± 6.1 kg; PG: 48.7 ± 5.7 to 53.8 ± 5.9 kg; p = 0.001) and leg press (NG: 235.2 ± 18.7 to 268.3 ± 19.7 kg; PG: 223.1 ± 25.3 to 253.3 ± 23.1 kg; p = 0.05) in trained groups. Relative V̇ o2 max improved only in PG (27.8 ± 1.3 to 32.0 ± 1.4 mL·kg·min -1 ; p = 0.05), while ventilatory thresholds improved in NG and CG ( p = 0.004 and p = 0.06). There was an increase in body mass in CG (97.6 ± 3.4 to 99.1 ± 2.9 kg) and NG (92.5 ± 5.4 to 93.5 ± 5.4 kg; p = 0.05). Combined training improved maximal upper-body and lower-body strength, regardless of periodization. However, for improvement in V̇ o2 max, linear periodization may be superior to nonperiodization in obese adults.

Characterization of Md5-BAC-REV-LTR virus as Marek's disease vaccine in commercial meat-type chickens: protection and immunosuppression.

Md5-BAC-REV-LTR is a recombinant Marek's disease virus (MDV), with an insertion of the long terminal repeat (LTR) of reticuloendotheliosis virus (REV) into the genome of the highly virulent MDV strain rMd5. It has been shown that Md5-BAC-REV-LTR does not induce tumours and confers high protection against challenge with MDV in 15 × 7 chickens. The objective of the present study was to evaluate the protection and safety (in terms of oncogenicity and immunosuppression) of Md5-BAC-REV-LTR in commercial meat-type chickens bearing maternal antibodies against MDV. Our results show that sub-cutaneous administration of Md5-BAC-REV-LTR at 1 day of age conferred high protection (protection index PI = 84.2) against an early challenge (1 day) by contact exposure to shedder birds infected with the vv+ MDV 648A strain. In such stringent challenge conditions, Md5-BAC-REV-LTR was more protective than a commercial CVI988 (PI = 12.4) and similar to the experimental vaccine Md5-BACΔmeq (PI = 92.4). Furthermore, Md5-BAC-REV-LTR did not induce either tumours or immunosuppression in this study. Immunosuppression was evaluated by the relative lymphoid organ weights and also by the ability of the vaccine to induce late-MDV-induced immunosuppression associated with reactivation of the virus. This study shows that Md5-BAC-REV-LTR has the potential to be used as a MD vaccine and is highly protective against early challenge with vv+ MDV.RESEARCH HIGHLIGHTSMd5-BAC-REV-LTR is highly protective against early challenge with vv+ MDV in commercial meat-type chickens.Md5-BAC-REV-LTR does not cause early immunosuppression.Md5-BAC-REV-LTR does not cause late immunosuppression.Unlike other serotype 1 vaccines, Md5-BAC-REV-LTR is not detected in feather pulp at 7 days post vaccination.

Association between characteristics of physical activity in leisure time and obesity in Brazilians adults and elderly.

OBJECTIVE: To verify the association of obesity with volume, intensity and types of physical activity in leisure time among Brazilian adults and elderly. STUDY DESIGN: Cross-sectional study, with a secondary analysis of data from "Surveillance of Risk Factors and Protection for Chronic Diseases by Telephone Survey". METHODS: The target population comprised adults aged ≥18 years. The outcome was obesity (BMI≥30.0 ​​kg/m²) and the exposures were the volume, intensity, and main type of physical activity in leisure time. Binary logistic regression was used and the results were expressed as odds ratio (OR) and 95% confidence intervals (CI95%), with a significance level of 5%. RESULTS: Compared to inactive, the highest volume of leisure time physical activity (≥300min/week) had a lower occurrence of obesity in adults (OR=0.76; CI95%: 0.63, 0.92; p=0.001) and elderly (OR=0.62; CI95%: 0.46, 0.82; p=0.001). In adults, vigorous activities (OR=0.65; CI95%: 0.55, 0.78; p<0.001) and, in the elderly, light/moderate activities (OR=0.75; CI95%: 0.62, 0.89; p<0.001) and vigorous (OR=0.54; CI95%: 0.37, 0.78; p<0.001) presented protective effect for obesity. Among the types of physical activity, running was the most strongly associated with a lower occurrence of obesity in adults (OR=0.54; CI95%: 0.32, 0.92; p=0.024) and elderly (OR=0.27; CI95%: 0.10, 0.69; p=0.006). In adults, strength training (p<0.001), gymnastics (p=0.032) and sports (p=0.013) and in elderly, walking (p=0.001) and sports (p=0.003) also had protective effect. CONCLUSION: A greater volume, vigorous intensity and physical activities of a structuring character and intensity progression, such as running, were associated with the lower occurrence of obesity.

Codon Deoptimization of UL54 in meq-Deleted Marek's Disease Vaccine Candidate Eliminates Lymphoid Atrophy but Reduces Vaccinal Protection.

Marek's disease (MD) is an oncogenic, lymphoproliferative, and highly contagious disease of chickens. Its etiologic agent is the alphaherpesvirus Marek's disease virus (MDV, Gallid alphaherpesvirus 2), and it is a chronic and ubiquitous problem for the poultry industry with significant economic impact in the United States and worldwide. We have previously demonstrated that MDV attenuated by dicodon deoptimization of the UL54 gene results in reduced gene product accumulation in vitro, with reduced viral genome copy number upon infection and reduced atrophy of bursa and thymus in vivo as well. In this report we detail our attempts to use the same attenuation strategy on a meq-deleted MDV mutant, rMd5B40ΔMeq. Unlike the wild-type rMd5B40 virus the rMd5B40ΔMeq is no longer oncogenic, but infected birds experience an unacceptable amount of bursa and thymus atrophy (BTA). We produced two meq-deleted MDV recombinants with a dicodon-deoptimized UL54 (rMd5B40ΔMeq/UL54deop1 and -deop2) and tested their tendency to cause BTA and to serve as a protective vaccine. We found that, although dicodon deoptimization of the UL54 gene results in a virus that spares the infected animal from atrophy of the bursa and thymus, the meq-deleted UL54-deoptimized recombinant is also less protective than the meq-deleted virus without UL54 deoptimization, the HVT + SB1 combination vaccine, or the Rispens (CVI988) vaccine.

[Association between the practice of physical activity of different types and the use of insulin in adult and elderly diabetics in Brazil]. / Associação entre a prática de atividade física em diferentes domínios e o uso de insulina em adultos e idosos com diabetes no Brasil.

The scope of this paper was to verify the association between the practice of physical activity of different types and the use of insulin in adults and the elderly. This is a cross-sectional population-based study with data from the survey entitled Surveillance of risk factors and protection for chronic diseases by telephone (VIGITEL 2013). The sample consisted of individuals aged ≥18 years, living in the 27 Brazilian capitals and diagnosed with diabetes. The practice of physical activity in commuting, the home, leisure, work and the use of insulin were self-reported. Binary logistic regression was used in crude and adjusted analyses for sociodemographic factors. Of the 4,593 subjects with diabetes, insulin use was reported by 16.2% and 25.5% of adults and the elderly, respectively. The practice of physical activity in the home (OR: 0.61, 95%CI: 0.40; 0.94) and at work (OR: 0.38, 95%CI: 0.18; 0.78) were associated with the lowest use of insulin among the elderly. There was a tendency to reduce insulin use as the number of physically active domains increased among the elderly (p = 0.003). The conclusion drawn was that physical activity practiced alone or in a cumulative way in different domains was associated with lower insulin use among the elderly.

Objetivou-se verificar a associação entre a prática de atividade física em diferentes domínios e o uso de insulina em adultos e idosos. Trata-se de um estudo transversal de base populacional com dados do inquérito Vigilância de fatores de risco e proteção para doenças crônicas por Inquérito Telefônico (VIGITEL 2013). A amostra foi composta por indivíduos com idade ≥18 anos, residentes nas 27 capitais do Brasil e com diagnóstico de diabetes. A prática de atividade física no deslocamento, domicílio, lazer e trabalho, e o uso de insulina foram por autorrelato. Empregou-se regressão logística binária em análises bruta e ajustada para fatores sociodemográficos. Dos 4.593 indivíduos com diabetes, uso de insulina foi relatado por 16,2% e 25,5% dos adultos e idosos, respectivamente. A prática de atividade física no domicílio (RO: 0,61; IC95%: 0,40; 0,94) no trabalho (RO: 0,38; IC95%: 0,18; 0,78) estiveram associadas ao menor uso de insulina em idosos. Houve tendência de redução do uso de insulina à medida que se aumentou a quantidade de domínios fisicamente ativos em idosos (p = 0,003). Conclui-se que, em idosos, a atividade física praticada de forma isolada ou de forma acumulada em diferentes domínios teve associação com o menor uso de insulina.

Associação entre a prática de atividade física em diferentes domínios e o uso de insulina em adultos e idosos com diabetes no Brasil / Association between the practice of physical activity of different types and the use of insulin in adult and elderly diabetics in Brazil

Resumo Objetivou-se verificar a associação entre a prática de atividade física em diferentes domínios e o uso de insulina em adultos e idosos. Trata-se de um estudo transversal de base populacional com dados do inquérito Vigilância de fatores de risco e proteção para doenças crônicas por Inquérito Telefônico (VIGITEL 2013). A amostra foi composta por indivíduos com idade ≥18 anos, residentes nas 27 capitais do Brasil e com diagnóstico de diabetes. A prática de atividade física no deslocamento, domicílio, lazer e trabalho, e o uso de insulina foram por autorrelato. Empregou-se regressão logística binária em análises bruta e ajustada para fatores sociodemográficos. Dos 4.593 indivíduos com diabetes, uso de insulina foi relatado por 16,2% e 25,5% dos adultos e idosos, respectivamente. A prática de atividade física no domicílio (RO: 0,61; IC95%: 0,40; 0,94) no trabalho (RO: 0,38; IC95%: 0,18; 0,78) estiveram associadas ao menor uso de insulina em idosos. Houve tendência de redução do uso de insulina à medida que se aumentou a quantidade de domínios fisicamente ativos em idosos (p = 0,003). Conclui-se que, em idosos, a atividade física praticada de forma isolada ou de forma acumulada em diferentes domínios teve associação com o menor uso de insulina.

Abstract The scope of this paper was to verify the association between the practice of physical activity of different types and the use of insulin in adults and the elderly. This is a cross-sectional population-based study with data from the survey entitled Surveillance of risk factors and protection for chronic diseases by telephone (VIGITEL 2013). The sample consisted of individuals aged ≥18 years, living in the 27 Brazilian capitals and diagnosed with diabetes. The practice of physical activity in commuting, the home, leisure, work and the use of insulin were self-reported. Binary logistic regression was used in crude and adjusted analyses for sociodemographic factors. Of the 4,593 subjects with diabetes, insulin use was reported by 16.2% and 25.5% of adults and the elderly, respectively. The practice of physical activity in the home (OR: 0.61, 95%CI: 0.40; 0.94) and at work (OR: 0.38, 95%CI: 0.18; 0.78) were associated with the lowest use of insulin among the elderly. There was a tendency to reduce insulin use as the number of physically active domains increased among the elderly (p = 0.003). The conclusion drawn was that physical activity practiced alone or in a cumulative way in different domains was associated with lower insulin use among the elderly.

[Simultaneity of risk behaviors for obesity in adults in the capitals of Brazil]. / Simultaneidade de comportamentos de risco para a obesidade em adultos das capitais do Brasil.

The scope of this study was to verify the association between risk behaviors and obesity in adults (18 to 59 years of age) in Brazilian capitals. It involved a cross-sectional population-based study conducted by telephone interview. The self-reported variables were obesity, defined by weight and height (BMI ≥ 30 kg/m²) and risk behaviors: physical inactivity (≤ 149 minutes/week), excess sedentarism (≥ 4 hours/day), frequent consumption of sweets (≥ 5 days/week) and meat with fat and/or chicken with skin (≥ 1 day/week). The simultaneity of risk behaviors was analyzed for reasons of observed and expected prevalence. The Poisson and multinomial logistic regressions were used in crude analyses and adjusted for sociodemographic factors. Among the 35,448 adults, the simultaneous consumption of meat with fat, excess sedentarism and physical inactivity (PR: 1.94, 95% CI: 1.45, 2.60), as well as the presence of the four risk behaviors (PR: 1.72, 95% CI: 1.16, 2.53) were associated with obesity in men. In women, the simultaneous consumption of sweets and meat with fat (PR: 1.77, 95% CI: 1.19, 2.66) was also associated with the outcome. In both sexes, there was an increase in the tendency of obesity according to the sum total of risk behaviors.

Objetivou-se verificar a associação da simultaneidade de comportamentos de risco com a obesidade em adultos (18 a 59 anos) das capitais do Brasil. Trata-se de um estudo transversal de base populacional, realizado por entrevista telefônica. As variáveis autorrelatadas foram a obesidade, definida pelo peso e altura (IMC ≥ 30 kg/m²) e os comportamentos de risco: inatividade física (≤ 149 min/sem), tempo sentado em excesso (≥ 4h/dia), consumo frequente de doces (≥ 5 dias/sem) e de carnes vermelhas com gordura e/ou frango com pele (≥ 1 dia/sem). A simultaneidade dos comportamentos de risco foi analisada por razões das prevalências observadas e esperadas. Foram utilizadas as regressões de Poisson e logística multinomial, em análises por sexo, brutas e ajustadas por fatores sociodemográficos. Dentre os 35.448 adultos, nos homens, a simultaneidade do consumo de carnes com gordura, tempo sentado em excesso e inatividade física (RP: 1,94; IC95%: 1,45; 2,60), assim como a presença dos quatro comportamentos de risco (RP: 1,72; IC95%: 1,16; 2,53), associaram-se à obesidade. Em mulheres, o consumo simultâneo de doces e de carnes com gordura (RP: 1,77; IC95%: 1,19; 2,66) também se associou ao desfecho. Em ambos os sexos, observou-se aumento da tendência de obesidade conforme o somatório de comportamentos de risco.

Simultaneidade de comportamentos de risco para a obesidade em adultos das capitais do Brasil / Simultaneity of risk behaviors for obesity in adults in the capitals of Brazil

Resumo Objetivou-se verificar a associação da simultaneidade de comportamentos de risco com a obesidade em adultos (18 a 59 anos) das capitais do Brasil. Trata-se de um estudo transversal de base populacional, realizado por entrevista telefônica. As variáveis autorrelatadas foram a obesidade, definida pelo peso e altura (IMC ≥ 30 kg/m²) e os comportamentos de risco: inatividade física (≤ 149 min/sem), tempo sentado em excesso (≥ 4h/dia), consumo frequente de doces (≥ 5 dias/sem) e de carnes vermelhas com gordura e/ou frango com pele (≥ 1 dia/sem). A simultaneidade dos comportamentos de risco foi analisada por razões das prevalências observadas e esperadas. Foram utilizadas as regressões de Poisson e logística multinomial, em análises por sexo, brutas e ajustadas por fatores sociodemográficos. Dentre os 35.448 adultos, nos homens, a simultaneidade do consumo de carnes com gordura, tempo sentado em excesso e inatividade física (RP: 1,94; IC95%: 1,45; 2,60), assim como a presença dos quatro comportamentos de risco (RP: 1,72; IC95%: 1,16; 2,53), associaram-se à obesidade. Em mulheres, o consumo simultâneo de doces e de carnes com gordura (RP: 1,77; IC95%: 1,19; 2,66) também se associou ao desfecho. Em ambos os sexos, observou-se aumento da tendência de obesidade conforme o somatório de comportamentos de risco.

Abstract The scope of this study was to verify the association between risk behaviors and obesity in adults (18 to 59 years of age) in Brazilian capitals. It involved a cross-sectional population-based study conducted by telephone interview. The self-reported variables were obesity, defined by weight and height (BMI ≥ 30 kg/m²) and risk behaviors: physical inactivity (≤ 149 minutes/week), excess sedentarism (≥ 4 hours/day), frequent consumption of sweets (≥ 5 days/week) and meat with fat and/or chicken with skin (≥ 1 day/week). The simultaneity of risk behaviors was analyzed for reasons of observed and expected prevalence. The Poisson and multinomial logistic regressions were used in crude analyses and adjusted for sociodemographic factors. Among the 35,448 adults, the simultaneous consumption of meat with fat, excess sedentarism and physical inactivity (PR: 1.94, 95% CI: 1.45, 2.60), as well as the presence of the four risk behaviors (PR: 1.72, 95% CI: 1.16, 2.53) were associated with obesity in men. In women, the simultaneous consumption of sweets and meat with fat (PR: 1.77, 95% CI: 1.19, 2.66) was also associated with the outcome. In both sexes, there was an increase in the tendency of obesity according to the sum total of risk behaviors.

Comparison of linear periodized and non-periodized combined training in health markers and physical fitness of adults with obesity: Clinical trial protocol.

The literature discusses that combined training, aerobic more resistance exercises in the same session, is a suitable strategy for people with obesity and that exercise periodization leads to positive health outcomes; however, the implication of different periodizations of combined training for health outcomes in obese adults requires further investigation. The aim of the study will be to describe the methodology used to compare the effect of linear periodized and non-periodized combined training on health markers and health-related physical fitness in adults with obesity. This is a blinded randomized controlled clinical trial investigating adults with obesity in the age group 20-50 years. The sample will be non-probabilistic, and participants will be allocated randomly into one of three groups: control group (CG), non-periodized group (NG), and periodized group (PG). The intervention will occur in 60-min sessions, 3 days a week for 16 weeks, with 1 week dedicated to familiarization with the training and 15 weeks of combined training (aerobic followed by resistance in the same session). The PG group will perform three mesocycles of 5 weeks each, progressing in intensity throughout the intervention [aerobic: from 40-49% to 60-69% of heart rate reserve (HRR); strength: from 12 to 14 maximum repetitions (MR) to 8 to 10MR]; the NG group will maintain the same relative intensity throughout the study (aerobic: 50-59% of HRR; strength: 2 sets of 10-12 MR). Participants in the CG group will maintain their usual activities without the proposed intervention. Pre- and post-intervention assessments will be performed for biochemical markers, body composition, cardiovascular parameters, cardiorespiratory fitness, maximum upper and lower limb strength, flexibility, and subjective health-related parameters. This project was approved by the Committee of Ethics and Research with Human Beings of the institution of origin (protocol 2,448,674) and registered in the Brazilian Registry of Clinical Trials (RBR-3c7rt3).

Therapeutic alternatives for addressing pink esthetic complications in single-tooth implants: A proposal for a clinical decision tree.

OBJECTIVE: Esthetic complications in implant therapy today represent a clinical challenge, when the aim is to overcome the sequelae and obtain a pleasing result. The current scientific literature about this topic is scarce and often based on case reports and the personal opinions of clinicians. CLINICAL CONSIDERATIONS: The aim of this article is to introduce a decision tree for diagnosis and treatment of complications, focusing on the pink esthetic of single-tooth implants and based on three diagnostic pillars (3D implant position, peri-implant hard-tissue anatomy, and peri-implant soft-tissue anatomy). Different shortcomings have been identified for each of the three diagnostic areas. CONCLUSIONS: Following this tree, the article proposes treatment alternatives including soft- and hard-tissue reconstruction, implant submergence, orthodontic extrusion, and implant extraction in order to help clinicians establish a logical therapeutic sequence. CLINICAL SIGNIFICANCE: Guidelines for adequate diagnosis and management of single implant-supported restorations with compromised esthetics is mandatory when attempt to overcome shortcoming in the pink esthetic result.

Methodological evaluation of leisure-time physical activity interventions in adults with obesity: a systematic review / Avaliação metodológica de intervenções em atividade física no lazer em adultos com obesidade: revisão sistemática

The aim of the present study was to systematize and analyze the methodological quality of physical activity interventions in leisure time in obese adults. A systematic review was conducted between June and August 2017 through four electronic databases (PubMed, Lilacs, ScienceDirect and Web of Science). A total of two researchers selected articles and, through consensus, analyzed these articles using the RE-AIM framework, which aims to identify the following dimensions: reach, effective-ness, adoption, implementation and maintenance of interventions. Of the 2,334 articles selected, nine met all eligibility criteria. The mean duration of the interventions was 14 weeks, with strategies including mainly aerobic exercises and nutritional monitoring.When the individual studies were taken into consideration, 67% reported at least one category of each dimension. The dimension with the highest reported proportion was "reach", found in 65% of the interventions. The "effectiveness", "adoption" (organizational and staff ), "implementation" and "maintenance" dimensions (individual and organizational) were reported in less than 40% of the items investigated for this information. The conclusion is that most of intervention studies reported the "reach" dimension, while only a few described "maintenance". Thus, it is suggested that future studies should previously look at the pres-entation of the total effect of the intervention and the methods applied, offering detailed information about each procedure. The scientific and practical scenario will provide relevant information about construction, application and subsequent follow-up of the interventions in leisure-time physical ac-tivity for obese adults

O objetivo do estudo foi avaliar sistematicamente a qualidade metodológica de intervenções de atividade física no lazer para adultos com obesidade. Trata-se de uma revisão sistemática conduzida de junho a agosto de 2017, com consulta eletrônica em quatro bases de dados (PubMed, Lilacs, ScienceDirect e Web of Science). Dois investigadores selecionaram os artigos e, mediante ao consenso, analisaram os artigos pelo emprego da ferramenta RE-AIM, que se propõe a identificar cinco dimensões específicas: alcance, efetividade, adoção, implementação e manutenção. Dos 2.334 artigos selecionados, nove atenderam aos critérios de elegibilidade. A duração média das intervenções foi de 14 semanas, com estratégias que continham exercícios aeróbios e acompanhamento nutricional em sua maioria. A dimensão com maior proporção de indicadores reportados foi o alcance, representada em 65% das intervenções. As dimensões de efetividade, adoção (organizacional e staff ), implementação e manutenção (individual e organizacional) foram relatadas em menos de 40% dos indicadores. Um total de 67% dos estudos relatou, no mínimo, um indicador de cada dimensão. Conclui-se que as intervenções abordam com mais profundidade o alcance, ao passo que poucas descrevem informações sobre a manutenção. Dessa forma, sugere-se que estudos futuros atentem para a apresentação do efeito total da intervenção e os métodos utilizados, ofertando informações detalhadas sobre cada passo. Assim, o cenário científico e prático contará com importantes informações sobre a construção, a aplicação e o acompanhamento a posteriori das intervenções em atividade física no lazer para adultos com obesidade

Attenuation of Marek's disease virus by codon pair deoptimization of a core gene.

Marek's disease virus (MDV) is an oncogenic alphaherpesvirus of Gallus gallus, the domesticated chicken. Control strategies rely upon vaccination with live attenuated viruses of antigenically similar avian herpesviruses or attenuated strains of MDV. Recent studies in other viruses have shown that recoding certain viral genes to employ synonymous but rarely-used codon pairs resulted in viral attenuation. We deoptimized two MDV proteins, UL54/ICP27 and UL49/VP22, and demonstrate that the more severely deoptimized variant of UL54 accumulates significantly less gene product in vitro. Using these UL54 deoptimized mutants, we further demonstrate that animals infected with the UL54-recoded recombinant virus exhibited decreased viral genome copy number in lymphocytes, reduced lymphoid atrophy and reduced tumor incidence. This study demonstrates that codon pair deoptimization of a single viral gene can produce attenuated strains of MDV. This approach may be useful as a rational way of making novel live attenuated virus vaccines for MDV.

Long-term use of lurasidone in patients with bipolar disorder: safety and effectiveness over 2 years of treatment.

BACKGROUND: Bipolar disorder is a chronic illness with a 2-year recurrence rate of approximately 50% among individuals receiving treatment in the community. The aim of this 18-month, open-label, continuation study was to evaluate the long-term safety and effectiveness of lurasidone in patients who initially presented with a major depressive episode associated with bipolar disorder, and who had completed at least 6 months of initial treatment with lurasidone. METHODS: Patients with bipolar I depression were enrolled in one of three 6-week, double-blind, placebo-controlled trials (monotherapy with lurasidone, 1 study; adjunctive therapy with lurasidone; and lithium or valproate, 2 studies). Study completers were eligible for a 6-month, open-label extension study of lurasidone utilizing flexible daily doses of 20-120 mg; extension completers were then eligible for an additional 18 months of continuation treatment with flexible, once-daily doses of lurasidone in the range of 20-80 mg. Concomitant therapy with mood stabilizers was permitted throughout the open-label extension and continuation studies. RESULTS: A total of 1199 patients entered, and 941 (78.5%) completed initial, double-blind, acute treatment, of whom 817/941 (86.8%) entered, and 559 (68.4%) completed the 6-month extension study; 122/559 patients (21.8%) entered the 18-month continuation study, of whom 19.7% of discontinued, including 6.6% due to adverse events and 1.6% due to insufficient efficacy. The mean dose of lurasidone during the 18-month continuation study was 61.8 mg/day, and the modal dose was 60 mg/day. Mean change in weight, from acute baseline to 18-month continuation endpoint was +0.8 kg (completers, n = 55); median changes in cholesterol and triglycerides were -3.0 mg/dL and +26.0 mg/dL, respectively. Based on a Kaplan-Meier analysis, the probability of relapse during 18 months of continuation treatment with lurasidone was estimated to be 18.3% in the monotherapy group and 29.1% in the adjunctive therapy group. Improvement in global illness severity was also maintained during 18 months of continuation therapy (CGI-S at continuation baseline, 2.1; 18-month completers, 1.7; LOCF-endpoint, 1.9). CONCLUSIONS: Up to 2 years of treatment with lurasidone was safe and well tolerated in this bipolar disorder population presenting with an index episode of depression. Improvement in depressive symptoms was maintained in the majority of patients treated with lurasidone, with relatively low rates of relapse, and with minimal effects on weight and metabolic parameters.

Lurasidone Dose Escalation in Early Nonresponding Patients With Schizophrenia: A Randomized, Placebo-Controlled Study.

OBJECTIVE: To assess the effect of dose increase in adult patients with schizophrenia who demonstrate inadequate initial response to standard-dose lurasidone and to evaluate the efficacy of low-dose lurasidone in adult patients with schizophrenia. METHODS: In this randomized, double-blind, placebo-controlled study conducted between May 2013 and June 2014, hospitalized patients with acute schizophrenia (DSM-IV-TR criteria) were randomly assigned to double-blind treatment with lurasidone 20 mg/d (n = 101), lurasidone 80 mg/d (n = 199), or placebo (n = 112). Nonresponders to lurasidone 80 mg/d (Positive and Negative Syndrome Scale [PANSS] score decrease < 20%) at 2 weeks were re-randomized to lurasidone 80 mg/d or 160 mg/d for the remaining 4 weeks of the study. The primary outcome measure was change from baseline to week 6 in PANSS total score. RESULTS: In nonresponders to lurasidone 80 mg/d (n = 95), dose increase to 160 mg/d at week 2 significantly reduced PANSS total score at week 6 study endpoint compared with continuing 80 mg/d (-16.6 vs -8.9; P < .05 [effect size = 0.52]). While a comparable magnitude of improvement was observed in Clinical Global Impression-Severity (CGI-S) score from week 2 to week 6 endpoint for lurasidone 160 mg/d versus 80 mg/d (-1.0 vs -0.6; effect size = 0.44), the difference was not statistically significant (P = .052). Patients receiving lurasidone 20 mg/d did not demonstrate significant improvement compared with placebo at week 6 in PANSS total (-17.6 vs -14.5; P = .26) or CGI-S (-0.93 vs -0.73; P = .17) scores. Few dose-related adverse effects associated with lurasidone were observed. CONCLUSIONS: In adult patients with schizophrenia demonstrating nonresponse to 2 weeks of treatment with lurasidone 80 mg/d, dose increase to 160 mg/d resulted in significant symptom improvement compared with continuing lurasidone 80 mg/d. Lurasidone 20 mg/d was not associated with significant improvement in psychotic symptoms in adult patients with schizophrenia. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT01821378.

Long-term safety and effectiveness of lurasidone in schizophrenia: a 22-month, open-label extension study.

OBJECTIVE: To evaluate the safety and effectiveness of lurasidone in the long-term treatment of patients with schizophrenia. METHODS: Patients who completed a 6-week, double-blind (DB), placebo-controlled trial continued in a 22-month, open-label (OL) study during which they received once-daily, flexible-doses of lurasidone, 40-120 mg. Change in the Positive and Negative Syndrome Scale (PANSS) was analyzed using both observed case (OC) and last observation carried forward (LOCF) analyses. RESULTS: Of the 251 patients who entered the OL extension, 51.4% completed 6 months, 36.7% completed 12 months, and 26.7% completed 22 months of OL treatment. Treatment with lurasidone was associated with a mean change from DB baseline, in weight of +0.4 kg at Month 12 (n=99), and +0.8 kg at Month 24 (n=67; OC analyses). Median change from DB baseline to Month 12 and Month 24, respectively, was -1.0 and -9.0 mg/dL for total cholesterol; 0.0 and -1.0 mg/dL for LDL; +1.0 and -11.0 mg/dL for triglycerides; and 0.0 and +0.1/% for HbA1c (OC analyses). The mean PANSS total score was 96.5 at DB baseline and 69.5 at OL baseline. The mean change from DB baseline in the PANSS total score at Month 24 was -43.6 (OC) and -28.4 (LOCF). Thirty-seven patients (14.7%) discontinued due to an adverse event (AE) during OL treatment. Three AEs occurred in ≥10% of patients: schizophrenia (12.4%), akathisia (10.8%), and somnolence (10.8%); and 19.2% reported at least one movement disorder-related AE. Discontinuations due to AEs occurred in 14.8% of patients. CONCLUSIONS: In this 22-month, open-label extension study, treatment with lurasidone was associated with minimal effects on weight, glucose, lipids, and prolactin. Patients demonstrated sustained improvement in the PANSS total score for up to 24 months of lurasidone treatment.

LURASIDONE IN THE LONG-TERM TREATMENT OF PATIENTS WITH BIPOLAR DISORDER: A 24-WEEK OPEN-LABEL EXTENSION STUDY.

BACKGROUND: The aim of this study was to evaluate the safety and tolerability of 6 months of open-label, uncontrolled extension treatment with lurasidone in patients with a diagnosis of bipolar depression who completed 6 weeks of acute treatment. METHODS: Patients completing 6 weeks of double-blind placebo-controlled treatment with either lurasidone monotherapy (one study) or adjunctive therapy with lithium or valproate (two studies), were treated for 6 months with flexible doses of lurasidone, 20-120 mg/day, in an open-label, uncontrolled extension study (N = 813; monotherapy, 38.9%; adjunctive therapy, 61.1%). Changes in safety parameters were calculated from double-blind, acute-phase baseline to month 6 of the extension phase, using a last observation carried forward (LOCF endpoint) analysis. RESULTS: Five hundred fifty-nine of 817 (68.4%) patients completed the extension study. In the monotherapy and adjunctive therapy groups, 6.9 and 9.0%, respectively, discontinued due to an adverse event. For the monotherapy and adjunctive therapy groups, respectively, changes from double-blind baseline to month 6 were +0.8 and +0.9 kg for weight (mean), 0.0 and +2.0 mg/dL for total cholesterol (median), +5.0 and +5.0 mg/dL for triglycerides (median), -1.0 and 0.0 mg/dL for glucose (median); -22.6 and -21.7 for Montgomery-Asberg Depression Rating Scale (MADRS; mean); whereas change from open-label baseline to month 6 were +0.85 and +0.88 kg for weight (mean), and -6.9 and -6.5 for MADRS (mean). CONCLUSIONS: Six months of treatment with open-label lurasidone was safe and well tolerated with minimal effect on weight and metabolic parameters; continued improvement in depressive symptoms was observed.

Major depressive disorder with subthreshold hypomania (mixed features): Clinical characteristics of patients entered in a multiregional, placebo-controlled study.

Major depressive disorder (MDD) associated with subthreshold hypomanic symptoms (mixed features), has been identified as a distinct nosological entity in the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5). We identified the predominant manic symptoms present at baseline in a multiregional, placebo-controlled trial involving 211 patients with MDD with mixed features (Clinicaltrials.govNCT01421134). Patients with 2 or 3 DSM-5 criteria defined manic symptoms were eligible for the study. At study baseline, increased talkativeness (pressure to keep talking) and flight of ideas (racing thoughts) were endorsed by approximately 65% of patients and a decreased need for sleep was endorsed by 40% of patients. Approximately 60% of patients also endorsed irritability and distractibility at baseline although these symptoms are not generally counted as part of the "mixed" depression diagnosis as they may overlap with criteria for MDD. Thus, five clinical symptoms characterized the manic presentation in the majority of patients diagnosed as having MDD with "mixed" features in this first placebo-controlled trial examining the use of a psychotropic medication (lurasidone) in this population. Our findings support the designation of MDD with mixed features specifier and suggest that this subpopulation of depressed patients may warrant additional medication beyond antidepressants.