The Consequences of Financial Leverage: Certified B Corporations' Advantages Compared to Common Commercial Firms.

Firms usually need to attract debt to form and grow, but increasing financial leverage also entails increased risks and costs for stakeholders, such as customers and employees. Accordingly, past research suggests that for common commercial firms (CCFs), which prioritize profits, higher leverage leads to lower sales growth and higher employment costs. However, Certified B Corporations (CBCs) distinguish themselves by having a credible prosocial mission and, therefore, might be better insulated against the adverse effects of higher leverage. Using a European multi-country matched sample of 136 CBCs and 136 CCFs, we find that the negative relationship between leverage and sales growth and the positive relationship between leverage and employment costs are weaker for CBCs than CCFs. Taken together, due to their certified prosocial mission, CBCs enjoy an advantage in debt financing compared to CCFs. Supplementary Information: The online version contains supplementary material available at 10.1007/s10551-023-05349-5.

N-ACETYLCYSTEINE AND/OR URSODEOXYCHOLIC ACID ASSOCIATED WITH METFORMIN IN NON-ALCOHOLIC STEATOHEPATITIS: AN OPEN-LABEL MULTICENTER RANDOMIZED CONTROLLED TRIAL.

BACKGROUND: Nowadays, pharmacological treatment of non-alcoholic fatty liver disease (NAFLD) is still limited and it is based on the treatment of conditions associated comorbities. Oxidative stress and insulin resistance are the mechanisms that seem to be mostly involved in its pathogenesis. OBJECTIVE: To evaluate the efficacy of N-acetylcysteine (NAC) in combination with metformin (MTF) and/or ursodeoxycholic acid (UDCA) for treatment of non-alcoholic steatohepatitis (NASH). METHODS: Open-label multicenter randomized trial was conducted for 48 weeks. It included patients with biopsy-proven NASH. The patients were randomized into three groups: NAC (1.2 g) + UDCA (15 mg/kg) + MTF (850-1500 mg/day) (n=26); UDCA (20 mg/kg) + MTF (850-1500 mg/day) (n=13); NAC (1.2g) + MTF (850-1500 mg/day) (n=14) for 48 weeks. Clinical, laboratory and the second liver biopsies were performed after 48 weeks. RESULTS: A total of 53 patients were evaluated; 17 (32.1%) were males; median age ±54 (IQR=15, 21-71) years. In the baseline, no difference was seen between groups according clinical and histological parameters. The groups differed only in cholesterol, LDL and triglycerides. No significant differences in biochemical and histologic parameters were found between these the three groups after 48 weeks of treatment. In the intragroup analysis (intention-to-treat) comparing histological and biochemical features, there were significant improvements in the steatosis degree (P=0.014), ballooning (0.027) and, consequently, in the NAFLD Activity Score (NAS) (P=0.005), and in the ALT levels at the end of the treatment only in the NAC + MTF group. No significant evidence of modification in the liver fibrosis could be observed in any of the groups. CONCLUSION: This multicenter study suggests that the association of NAC + MTF could reduce the liver disease activity in patients with NASH. These data stimulate further controlled studies with this therapy for these patients.

N-acetilcisteína e/ou ácido ursodeoxicólico associados à metformina na esteato-hepatite não alcoólica: um estudo aberto, multicêntrico, randomizado controlado / N-acetylcysteine and/or ursodeoxycholic acid associated with metformin in non-alcoholic steatohepatitis: an open-label multicenter randomized controlled trial

ABSTRACT BACKGROUND: Nowadays, pharmacological treatment of non-alcoholic fatty liver disease (NAFLD) is still limited and it is based on the treatment of conditions associated comorbities. Oxidative stress and insulin resistance are the mechanisms that seem to be mostly involved in its pathogenesis. OBJECTIVE: To evaluate the efficacy of N-acetylcysteine (NAC) in combination with metformin (MTF) and/or ursodeoxycholic acid (UDCA) for treatment of non-alcoholic steatohepatitis (NASH). METHODS: Open-label multicenter randomized trial was conducted for 48 weeks. It included patients with biopsy-proven NASH. The patients were randomized into three groups: NAC (1.2 g) + UDCA (15 mg/kg) + MTF (850-1500 mg/day) (n=26); UDCA (20 mg/kg) + MTF (850-1500 mg/day) (n=13); NAC (1.2g) + MTF (850-1500 mg/day) (n=14) for 48 weeks. Clinical, laboratory and the second liver biopsies were performed after 48 weeks. RESULTS: A total of 53 patients were evaluated; 17 (32.1%) were males; median age ±54 (IQR=15, 21-71) years. In the baseline, no difference was seen between groups according clinical and histological parameters. The groups differed only in cholesterol, LDL and triglycerides. No significant differences in biochemical and histologic parameters were found between these the three groups after 48 weeks of treatment. In the intragroup analysis (intention-to-treat) comparing histological and biochemical features, there were significant improvements in the steatosis degree (P=0.014), ballooning (0.027) and, consequently, in the NAFLD Activity Score (NAS) (P=0.005), and in the ALT levels at the end of the treatment only in the NAC + MTF group. No significant evidence of modification in the liver fibrosis could be observed in any of the groups. CONCLUSION: This multicenter study suggests that the association of NAC + MTF could reduce the liver disease activity in patients with NASH. These data stimulate further controlled studies with this therapy for these patients.

RESUMO CONTEXTO: Atualmente, o tratamento farmacológico da doença hepática gordurosa não alcoólica (DHGNA) ainda é limitado e baseia-se no tratamento de condições associadas às comorbidades. O estresse oxidativo e a resistência à insulina são os mecanismos que parecem estar mais envolvidos em sua patogênese. OBJETIVO: Avaliar a eficácia da N-acetilcisteína (NAC) em associação à metformina (MTF) e/ou ácido ursodesoxicólico (UDCA) no tratamento da EHNA. MÉTODOS: Estudo randomizado, multicêntrico e aberto, conduzido por 48 semanas. Incluiu pacientes com esteato-hepatite não alcoólica (EHNA) comprovada por biópsia. Os pacientes foram distribuídos aleatoriamente em três grupos: NAC (1,2 g) + UDCA (15 mg/kg) + MTF (850-1500 mg/dia) (n=26); UDCA (20 mg/kg) + MTF (850-1500 mg/dia) (n=13); NAC (1,2 g) + MTF (850-1500 mg/dia) (n=14) durante 48 semanas. Os dados clínicos, laboratoriais e as segundas biópsias hepáticas foram realizados após 48 semanas. RESULTADOS - Um total de 53 pacientes foram avaliados; 17 (32,1%) eram do sexo masculino; idade mediana de ±54 (IQR=15, 21-71) anos. No baseline, nenhuma diferença foi observada entre os grupos de acordo com parâmetros clínicos e histológicos. Os grupos diferiram apenas em colesterol, LDL e triglicerídeos. Não foram encontradas diferenças significativas nos parâmetros bioquímicos e histológicos entre os três grupos após 48 semanas de tratamento. Contudo, na análise intragrupos (intenção de tratar) comparando características histológicas e bioquímicas, houve melhora significativa no grau de esteatose (P=0,014), balonização (P=0,027) e, consequentemente, no NAFLD Activity Score (NAS) (P=0,005), e nos níveis de ALT no final do tratamento apenas no grupo NAC+MTF. Nenhuma evidência significativa de modificaçãona fibrose hepática pôde ser observada em nenhum dos grupos. CONCLUSÃO: - Este estudo multicêntrico sugere que a associação de NAC+MTF poderia reduzir a atividade da doença hepática em pacientes com EHNA. Esses dados estimulam estudos adicionais controlados com essa terapia para esses pacientes.

Determinação do limiar anaeróbio pela variabilidade da frequência cardíaca de pacientes com DPOC durante exercício em cicloergômetro / Determining anaerobic threshold through heart rate variability in patients with COPD during cycloergometer exercise

INTRODUÇÃO: A Doença Pulmonar Obstrutiva Crônica (DPOC) é caracterizada por alterações estruturais do parênquima pulmonar, acarretando manifestações sistêmicas. Além disso, esses pacientes podem apresentar marcada alteração do controle autonômico cardíaco. Nesse contexto, estudos investigando a variabilidade da frequência cardíaca (VFC) em pacientes com DPOC durante a realização de exercício físico em cicloergometro têm sido pouco explorados. OBJETIVO: Determinar o limiar anaeróbio por meio da VFC com o propósito de estabelecer parâmetros de avaliação e prescrição da intensidade de exercício desses pacientes em cicloergômetro. MATERIAIS E MÉTODOS: Foram avaliados oito pacientes do sexo masculino com diagnóstico de DPOC com idade média de 69,5 ± 7,6 anos. A frequência cardíaca foi analisada no repouso e em diferentes intensidades do exercício. O teste foi realizado em um cicloergômetro e consistiu em um período de aquecimento de quatro minutos em uma potência mínima. Foram, também, realizados degraus com potência inicial de 4W, com acréscimos de 5 em 5W, até que o paciente atingisse o limiar anaeróbio. RESULTADOS: Os pacientes que apresentaram maiores valores de VEF1 apresentaram maiores potências no cicloergômetro. Houve redução significativa da VFC durante o exercício físico se comparado ao repouso sentado p < 0,05. CONCLUSÃO: Os pacientes estudados apresentaram um severo descondicionamento físico reafirmado pela impossibilidade determinada pelo LA de 50% da amostra.

INTRODUCTION: Chronic Obstructive Pulmonary Disease (COPD) is characterized by structural alterations of lung parenchyma resulting in systemic manifestations. These patients may have marked change in cardiac autonomic control. In this context, studies investigating heart rate variability (HRV) in patients with COPD during physical exercise cycloergometers have been little explored. OBJECTIVE: To determine the anaerobic threshold through HRV in order to establish parameters of evaluation and prescription of exercise intensity in these patients on a cycloergometer. MATERIALS AND METHODS: Eight male patients diagnosed with COPD, mean age 69.5 ± 7.6 years were studied. Heart rate was analyzed at rest and at different intensities of exercise. The test was performed on a cycloergometer and consisted of a warm-up period of four minutes at a minimum power. Steps were performed with initial power of 4W, with increments of 5 in 5W, until the patient reached the anaerobic threshold. RESULTS: Patients that presented higher values of FEV1 showed greater powers during the cycloergometer. Additionally, there was significant reduction in HRV during exercise compared to rest sitting p < 0.05. CONCLUSION: Patients had a severe physical deconditioning reaffirmed the impossibility determined by the anaerobic threshold of 50% of the sample.

Signal-morphology impedance cardiography during incremental cardiopulmonary exercise testing in pulmonary arterial hypertension.

BACKGROUND: Haemodynamic responses to exercise are related to physical impairment and worse prognosis in patients with pulmonary arterial hypertension (PAH). It is clinically relevant, therefore, to investigate the practical usefulness of non-invasive methods of monitoring exercise haemodynamics in this patient population. METHODS: Using a novel impedance cardiography (ICG) approach that does not require basal impedance estimations and relies on a morphological analysis of the impedance signal (Signal-Morphology-ICG(™)), stroke volume (SV) and cardiac index (CI) were evaluated in 50 patients and 21 age-matched controls during a ramp-incremental cardiopulmonary exercise testing. RESULTS: Technically unacceptable readings were found in 12 of 50 (24%) patients. In the remaining subjects, early decrease (N = 9) or a 'plateau' in SV (N = 8) and Δ (peak-unloaded exercise) SV <10 ml were markers of more advanced PAH (P<0.05). ΔCI ≤ 1.5-fold and early estimated lactate threshold were the only independent predictors of a severely reduced peak oxygen uptake (VO(2)) in patients (R(2) = 0.71, P<0.001). The finding of ΔCI ≤ 1.5-fold plus peak VO(2) < 50% predicted was associated with a number of clinical and functional markers of disease severity (P<0.001). In addition, abnormal SV responses and ΔCI ≤ 1.5-fold were significantly related to 1-year frequency of PAH-related adverse events (death and balloon atrial septostomy, N = 8; P<0.05). CONCLUSIONS: 'Qualitative' and 'semi-quantitative' signal-morphology impedance cardiography(™) (PhysioFlow(™)) during incremental exercise provided clinically useful information to estimate disease severity and short-term prognosis in patients with PAH in whom acceptable impedance signals could be obtained.

Skeletal muscle reoxygenation after high-intensity exercise in mitochondrial myopathy.

This study addressed whether O(2) delivery during recovery from high-intensity, supra-gas exchange threshold exercise would be matched to O(2) utilization at the microvascular level in patients with mitochondrial myopathy (MM). Off-exercise kinetics of (1) pulmonary O(2) uptake VO(2P) (2) an index of fractional O(2) extraction by near-infrared spectroscopy (Δ[deoxy-Hb + Mb]) in the vastus lateralis and (3) cardiac output (Q'(T)) by impedance cardiography were assessed in 12 patients with biopsy-proven MM (chronic progressive external ophthalmoplegia) and 12 age- and gender-matched controls. Kinetics of VO(2P) were significantly slower in patients than controls (τ = 53.8 ± 16.5 vs. 38.8 ± 7.6 s, respectively; p < 0.05). Q'(T), however, declined at similar rates (τ = 64.7 ± 18.8 vs. 73.0 ± 21.6 s; p > 0.05) being typically slower than [Formula: see text] in both groups. Importantly, Δ[deoxy-Hb + Mb] dynamics (MRT) were equal to, or faster than, τVO(2P) in patients and controls, respectively. In fact, there were no between-group differences in τVO(2P)MRTΔ[deoxy-Hb + Mb] (1.1 ± 0.4 vs. 1.0 ± 0.2, p > 0.05) thereby indicating similar rates of microvascular O(2) delivery. These data indicate that the slower rate of recovery of muscle metabolism after high-intensity exercise is not related to impaired microvascular O(2) delivery in patients with MM. This phenomenon, therefore, seems to reflect the intra-myocyte abnormalities that characterize this patient population.

Bronchodilators accelerate the dynamics of muscle O2 delivery and utilisation during exercise in COPD.

BACKGROUND: Expiratory flow limitation and lung hyperinflation promote cardiocirculatory perturbations that might impair O(2) delivery to locomotor muscles in patients with chronic obstructive pulmonary disease (COPD). The hypothesis that decreases in lung hyperinflation after the inhalation of bronchodilators would improve skeletal muscle oxygenation during exercise was tested. METHODS: Twelve non- or mildly hypoxaemic males (forced expiratory volume in 1 s (FEV(1))=38.5+/-12.9% predicted; Pao(2)>60 mm Hg) underwent constant work rate cycle ergometer exercise tests (70-80% peak) to the limit of tolerance (Tlim) after inhaled bronchodilators (salbutamol plus ipratropium) or placebo. Muscle (de)oxygenation (approximately fractional O(2) extraction) was determined in the vastus lateralis by changes (Delta) in the deoxyhaemoglobin/myoglobin signal ([HHb]) from near-infrared spectroscopy, and cardiac output (QT) was monitored by impedance cardiography. RESULTS: Bronchodilators reduced lung hyperinflation and increased Tlim compared with placebo (454+/-131 s vs 321+/-140 s, respectively; p<0.05). On-exercise kinetics of QT and pulmonary O(2) uptake V(o(2))were accelerated with active treatment; Delta[HHb] dynamics, however, were delayed by approximately 78% and the signal amplitude diminished by approximately 21% (p<0.01). Consequently, the ratio between V(o(2)) and Delta[HHb] dynamics decreased, suggesting improved microvascular O(2) delivery (tau-V(o(2))/MRT-Delta[HHb]=4.48+/-1.57 s vs 2.08+/-1.15 s, p<0.05). Of note, reductions in lung hyperinflation were related to faster QT kinetics and larger decrements in tau-V(o(2))/MRT-Delta[HHb] (p<0.01). CONCLUSIONS: Decreases in operating lung volumes after the inhalation of bronchodilators are associated with faster 'central' cardiovascular adjustments to high-intensity exercise with beneficial consequences on muscle oxygenation in patients with moderate to severe COPD.

Effects of tiotropium and formoterol on dynamic hyperinflation and exercise endurance in COPD.

BACKGROUND: It is currently unclear whether the additive effects of a long-acting beta(2)-agonist (LABA) and the antimuscarinic tiotropium bromide (TIO) on resting lung function are translated into lower operating lung volumes and improved exercise tolerance in patients with chronic obstructive pulmonary disease (COPD). METHODS: On a double-blind and cross-over study, 33 patients (FEV(1) = 47.4 +/- 12.9% predicted) were randomly allocated to 2-wk formoterol fumarate 12 microg twice-daily (FOR) plus TIO 18 microg once-daily or FOR plus placebo (PLA). Inspiratory capacity (IC) was obtained on constant-speed treadmill tests to the limit of tolerance (Tlim). RESULTS: FOR-TIO was superior to FOR-PLA in increasing post-treatment FEV(1) and Tlim (1.34 +/- 0.42 L vs. 1.25 +/- 0.39 L and 124 +/- 27% vs. 68 +/- 14%, respectively; p < 0.05). FOR-TIO slowed the rate of decrement in exercise IC compared to FOR-PLA (Deltaisotime-rest = -0.27 +/- 0.40 L vs. -0.45 +/- 0.36 L, p < 0.05). In addition, end-expiratory lung volume (% total lung capacity) was further reduced with FOR-TIO (p < 0.05). Of note, patients showing greater increases in Tlim with FOR-TIO (16/26, 61.6%) had more severe airways obstruction and lower exercise capacity at baseline. Improvement in Tlim with FOR-TIO was also related to larger increases in FEV(1) (p < 0.05). CONCLUSIONS: Compared to FOR monotherapy, FOR-TIO further improved effort-induced dynamic hyperinflation and exercise endurance in patients with moderate-to-severe COPD. These beneficial consequences were more likely to be found in severely-disabled patients with larger resting functional responses to the combination therapy. TRIAL REGISTRATION: Clinicaltrials.gov Identifier: NCT00680056 [ClinicalTrials.gov].

Effects of hyperoxia on the dynamics of skeletal muscle oxygenation at the onset of heavy-intensity exercise in patients with COPD.

This study addressed whether hyperoxia (HiOX=50% O2), compared to normoxia, would improve peripheral muscle oxygenation at the onset of supra-gas exchange threshold exercise in patients with chronic obstructive pulmonary disease (COPD) who were not overtly hypoxemic (resting Pa O2> 60 mmHg ). Despite faster cardiac output and improved blood oxygenation, HiOX did not significantly change pulmonary O2 uptake kinetics ( VO2p ). Surprisingly, however, HiOX was associated with faster fractional O2 extraction ( approximately Delta[deoxy-Hb+Mb] by near-infrared spectroscopy) (p<0.05). In addition, an "overshoot" in Delta[deoxy-Hb+Mb] was found after the initial fast response only in HiOX (7/11 patients) thereby suggesting impaired intra-muscular O2 delivery ( Q'O 2mv)-to-utilization. These data indicate that, despite improved "central" O2 delivery, Q'O2mv adapted at a slower rate than muscle VO2 under HiOX in non-hypoxaemic patients with COPD. Our results question the rationale of using supplemental O2 to improve muscle oxygenation during the transition to high-intensity exercise in this patient sub-population.

Fibras solúveis no tratamento da doença hepática gordurosa não-alcoólica: estudo piloto / Non alcoholic fatty liver disease: treatment with soluble fibres

O presente estudo piloto avaliou a eficácia de fibras solúveis no tratamento da doença hepática gordurosa não-alcoólica. Foram incluídos 12 pacientes que receberam 10 g/dia de fibras solúveis oral por 3 meses. Após o tratamento, observou-se redução nos valores do índice de massa corporal, circunferência da cintura e resistência à insulina em 100 por cento dos casos, redução nos níveis de colesterol em 66,7 por cento e normalização de ALT, AST e GGT em 75 por cento. Os resultados sugerem que a utilização de fibras solúveis pode colaborar no controle de fatores de risco e das enzimas hepáticas em pacientes com doença hepática gordurosa não-alcoólica e estimulam a realização de estudos controlados envolvendo controle histológico.

The pilot study evaluated the efficiency of oral soluble fibers to treat patients with nonalcoholic fatty liver disease. Twelve patients received 10 g/day of soluble fibers during 3 months. After the treatment 100 percent of patients presented reduction in body mass index, waist circumference and insulin resistance index. In 66.7 percent of the patients were observed reduction of the cholesterol levels and 75 percent presented normal liver enzymes (AST, ALT, and GGT). The present study suggests that oral soluble fibers may be useful to control risk factors and liver enzymes in patients with nonalcoholic fatty liver disease. However, future studies with histological controls are considered necessary.

[Non alcoholic fatty liver disease: treatment with soluble fibres]. / Fibras solúveis no tratamento da doença hepática gordurosa não-alcoólica: estudo piloto.

The pilot study evaluated the efficiency of oral soluble fibers to treat patients with nonalcoholic fatty liver disease. Twelve patients received 10 g/day of soluble fibers during 3 months. After the treatment 100% of patients presented reduction in body mass index, waist circumference and insulin resistance index. In 66.7% of the patients were observed reduction of the cholesterol levels and 75% presented normal liver enzymes (AST, ALT, and GGT). The present study suggests that oral soluble fibers may be useful to control risk factors and liver enzymes in patients with nonalcoholic fatty liver disease. However, future studies with histological controls are considered necessary.

Non-alcoholic fatty liver disease and insulin resistance: importance of risk factors and histological spectrum.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) has been associated with several metabolic conditions (MC) and secondary causes, but the relationship between insulin resistance (IR) and the underlying aetiology of NAFLD has not been extensively explored. OBJECTIVE: To determine the frequency of IR among NAFLD patients and to describe IR according to risk factors and histological findings of the disease. METHODOLOGY: A case-series study of 64 patients with clinical and histological diagnosis of NAFLD. IR was calculated by homeostasis model assessment (HOMA) and IR was considered when HOMA > or = 3. Histological grades of NAFLD were: stage 1, steatosis isolated; stage 2, steatosis and inflammation; stage 3, steatosis and ballooning degeneration; stage 4, steatosis and fibrosis and/or Mallory bodies. Fibrosis was graded 0-4 (cirrhosis). RESULTS: IR was found in 21 (33%) patients. Among those with IR, 16 patients (76%) had associated MC and five patients (24%) had exposure to petrochemicals. The mean value of HOMA varied from 3.5 in NAFLD associated with MC to 1.6 in patients with exposure to petrochemicals (P < 0.03). Waist circumference was the metabolic factor most strongly associated with IR (P < 0.005). Steatohepatitis (NASH) was observed in 54 (84.3%) cases. The HOMA mean value was significantly higher in patients with advanced fibrosis. CONCLUSIONS: IR occurred in 33% of the NAFLD patients, being more frequent among those with MC than among those with exposure to petrochemicals. The presence of IR in cases with advanced fibrosis suggests that it may influence the prognosis of NAFLD.

A influência da altura do step no exercício de subida posterior: estudo eletromiográfico em indivíduos sadios e portadores da síndrome da dor femoropatelar / Step height influence on backward step-up exercise: an electromyographic study in healthy individuals and in those with patellofemoral pain syndrome

O objetivo deste estudo foi avaliar a influência da altura de um step na atividade elétrica dos músculos vasto medial oblíquo (VMO), vasto lateral longo (VLL) e vasto lateral oblíquo (VLO) no exercício de subida posterior. Participaram do estudo 27 indivíduos do sexo feminino, sendo 15 sadios (21,13 ± 2,17 anos) e 12 portadores da Síndrome da Dor Femoropatelar-SDFP (21,08 ± 2,31 anos). A atividade elétrica foi captada por eletrodos de superfície. Os indivíduos subiram o step em duas alturas diferentes (45° e 75° de flexão do joelho) no sentido posterior. A integral do sinal elétrico normalizado pela média das repetições foi utilizada para o estudo da relação de ativação VMO:VLO e VMO:VLL. A ANOVA two-way e o post hoc de Duncan (p < 0,05) mostraram que no grupo SDFP, os valores da relação VMO:VLO e VMO:VLL foram maiores no ângulo de 45° do que a 75°. No grupo Controle, a relação VMO:VLO foi maior a 45° que a 75° enquanto que a relação VMO:VLL foi maior no ângulo de 75°. Os resultados deste estudo sugerem que o exercício de subida posterior no step a 45° está indicado no tratamento da SDFP, pois ativou mais seletivamente o músculo VMO.