Brazilian Research Consortium on Obsessive-Compulsive Spectrum Disorders guidelines for the treatment of adult obsessive-compulsive disorder. Part II: cognitive-behavioral therapy

Objectives: To summarize evidence-based cognitive-behavioral therapy (CBT) treatment and propose clinical interventions for adult patients with obsessive-compulsive disorder (OCD). Methods: The literature on CBT interventions for adult OCD, including BT and exposure and response prevention, was systematically reviewed to develop updated clinical guidelines for clinicians, providing comprehensive details about the necessary procedures for the CBT protocol. We searched the literature from 2013-2020 in five databases (PubMed, Cochrane, Embase, PsycINFO, and Lilacs) regarding study design, primary outcome measures, publication type, and language. Selected articles were assessed for quality with validated tools. Treatment recommendations were classified according to levels of evidence developed by the American College of Cardiology and the American Heart Association. Results: We examined 44 new studies used to update the 2013 American Psychiatric Association guidelines. High-quality evidence supports CBT with exposure and response prevention techniques as a first-line treatment for OCD. Protocols for Internet-delivered CBT have also proven efficacious for adults with OCD. Conclusion: High-quality scientific evidence supports the use of CBT with exposure and response prevention to treat adults with OCD.

Randomized trial of the efficacy of trial-based cognitive therapy for obsessive-compulsive disorder: preliminary findings

Abstract Introduction Obsessive-compulsive disorder (OCD) is the fourth most prevalent mental disorder and is a disabling condition. OCD is associated with anatomical and functional changes in the brain, in addition to dysfunctional cognitions. The treatments of choice are selective serotonin reuptake inhibitors, cognitive-behavioral therapy (CBT), and exposure and response prevention (ERP). Trial-based cognitive therapy (TBCT) is a recent and empirically validated psychotherapy with a focus on restructuring dysfunctional negative core beliefs (CBs). The objective of this study was to evaluate the efficacy of TBCT relative to ERP for treatment of OCD. Methods A randomized, single-blind clinical trial was conducted, randomizing 26 patients for individual treatment with TBCT (n = 12) or ERP (n = 14). The groups were evaluated at baseline, at the end of 3 months (12 sessions), and at 3, 6, and 12-month follow-ups. Results Both approaches reduced the severity of symptoms with large effect sizes. These results were maintained at the 12-month follow-up assessment. Conclusion TBCT may be a valid and promising treatment for this disorder.

Basal cell carcinoma-clinico-pathological study in Eastern India in correlation with different risk factors

Objectives: To study the histological variants and mimickers of basal cell carcinoma (BCC) alongwith different risk factors among a group of patients from eastern India. Methods: The specimen for the study was sent by the dermatology department for histopathology after skin biopsy. Results: Out of 42 patients, 15 patients studied were males and the rest of the cases were females. The male to female ratio was 0.55:1. Maximum (15 cases) cases were in the age group of 50–59 years. Apart from sunlight, chronic arsenic exposure is an important risk factor of BCC. Basal cell hyperplasia and squamous cell carcinoma are the histological differential diagnosis of nodular BCC and basosquamous BCC. Conclusion: BCC is a disease of the older age group and with female preponderance in our study. Nodular basal cell carcinoma was the most common histologic type of basal cell carcinoma. The face was the most common site for BCC followed by the scalp. UV radiations and Arsenic do play role in the pathogenesis of BCC. CD10 helps differentiate superficial BCC from basal cell hyperplasia.

Interpretation to the European clinical guidelines of psychological interventions for Tourette syndrome and other tic disorders in 2021 / 中华实用儿科临床杂志

Tic disorders are one of the common neurodevelopmental disorders in children, which are mainly managed by pharmacological and non-pharmacological treatment.Psychological interventions belong to the non-pharmacological treatment, which, however, have not yet been fully recognized and understood in China.The analyses on clinical effectiveness and availability to pediatric patients are limited.This study aims to interpret the clinical guidelines of psychological interventions for Tourette syndrome and other tic disorders by European Society for the Study of Tourette syndrome in the journal of European Child and Adolescent Psychiatry in 2021, aiming to provide reference for the psychological interventions of tic disorders in China.

Current Treatment Strategies of Obsessive- Compulsive Disorder.

In the last decades, the treatment of obsessive-compulsive disorder (OCD) has dramatically improved with the introduction into the clinical practice of the selective serotonin reuptake inhibitors (SSRIs). However, a large part of patients do not respond to first-line drugs and different augmentation strategies have been proposed. More recently, some non-pharmacological techniques have been proposed, but the evidence of effectiveness is just preliminary. In this paper, the most recent works on pharmacological and alternative treatments of OCD will be reviewed.

Parathyroid in situ exposure and protection in differentiated thyroid carcinoma surgery / 中华内分泌外科杂志

Objective To study the application value of parathyrod in situ exposure and protection in differentiated thyroid cancer thyroid carcinoma (DTC) surgery. Methods 500 cases of DTC admitted from Jan. 2012 to Dec. 2014 were selected for the research. According to whether the parathyroid was anatomically exposed during the surgery, the patients were divided into experimental group (exposed group) and the control group (un-exposed group). Then, depending on tumor extent and risk factors, the experimental group were divided into group E1 (lateral affected glandular lobe, isthmus lobe resection and unilateral VI lymph node dissection )and E2 (total or subtotal thyroidectomy and bilateral VI lymph node dissection), while the control group were divided in-to group C1 (surgical treatment same as E1)and group C2 (surgical treatment same as E2). Patients’ postopera-tive nerve and muscle symptoms were observed, such as clinical manifestations of face, lips, hand and foot numb-ness or convulsions. Both preoperatively and postoperatively, patients’ parathyroid hormone (PTH) and serum calcium level indicators were detected before surgery and at the 1st, 3rd, 5th, 7th, 14th and 28th day after surgery. Results The lymph node metastasis rate and number between experimental group and the control group had statistical insignificance (χ2=1.02, 0.79, P=0.14, 0.96). The recurrence rate of the 2 groups had no significant difference during the follow-up (χ2=0.23, P=0.65). Group E1 was significantly lower than Group C1 in postopera-tive parathyroid function decline rate, incidence of hypocalcemia and parathyroid mistakenly cut rate. Group E2 was also obviously lower than Group C2 in all these aspects. The difference had statistical significance (P<0.05). Conclusion Parathyrod in situ exposure and protection assisted by direct vision of the magnifying glass can re-duce the mistakenly cut rate of parathyroid and the temporary hypoparathyroidism, which can effectively avoid the adverse effects caused by total thyroidectomy.

Atención inicial al politraumatizado maxilofacial: evaluación, conducta terapéutica y prevención / Initial care of maxillofacial polytrauma patients: evaluation, therapeutic management and prevention

Introducción: las fracturas maxilofaciales requieren tratamiento de urgencia y de un personal altamente calificado. Pueden aparecer complicaciones que ocasionen la pérdida de la vida del paciente. Objetivo: realizar una revisión bibliográfica sobre la atención al politraumatizado maxilofacial, enfatizando aspectos del soporte vital avanzado de trauma como el manejo del déficit neurológico, de la exposición del paciente y del control de la temperatura, anexos a la valoración primaria, valoración secundaria, tratamiento definitivo, lesiones asociadas, equipo multidisciplinario del trauma, traumatismos maxilofaciales con características distintivas, condiciones que influyen en el manejo del trauma y prevención. Métodos: se realizó una revisión bibliográfica entre diciembre de 2014 y enero de 2015. Se evaluaron revistas de impacto de Web of Sciencies (39), 1 cubana y 5 libros. Se consultaron las bases de datos de los sistemas MEDLINE, PubMed y SciELO. Se utilizaron como descriptores: maxilofacial trauma, advanced trauma life support, secondary survey, associated injuries, multidisciplinary team of trauma, prevention y sus equivalentes en español. Se incluyeron artículos en inglés y español, publicados preferentemente en los últimos 5 años. Se obtuvieron 141 artículos. El estudio estuvo circunscrito solo a 51, que enfocaban estas temáticas de forma más integral. Análisis e integración de la información: al analizar el comportamiento de los artículos atendiendo a su representatividad en las revistas científicas, encontramos que 5,9 por ciento correspondían a la Journal of Craniomaxillofacial Surgery. Conclusiones: es imprescindible que los cirujanos maxilofaciales que se desempeñan en la atención de emergencia puedan reconocer, diagnosticar y establecer el manejo básico de un traumatismo maxilofacial. La falta de diagnóstico y de correcto manejo puede conducir a la pérdida de funciones y al desarrollo de deformidades secundarias difíciles de corregir luego. Esta corrección también podría inducir resultados decepcionantes, que podrían comprometer la vida del paciente(AU)

Introduction: maxillofacial fractures require emergency treatment by highly qualified personnel. Complications may occur which may cause the death of the patient. Objective: carry out a bibliographic review about the care of maxillofacial polytrauma patients, highlighting the following aspects of advanced trauma life support: management of neurological deficit, exposure and temperature control, annexes to primary assessment, secondary assessment, definitive treatment, associated injuries, multidisciplinary trauma team, maxillofacial traumas with distinctive characteristics, conditions influencing trauma management and prevention. Methods: a bibliographic review was conducted from December 2014 to January 2015. The evaluation included high impact journals from the Web of Sciences (39 journals), as well as one Cuban journal and five books. The databases MEDLINE, PubMed and SciELO were consulted, using the search terms maxillofacial trauma, advanced trauma life support, secondary survey, associated injuries, multidisciplinary trauma team, prevention, and their Spanish counterparts. The review included papers in English and Spanish, preferably published the last five years. Of the 141 papers obtained, the reviewers selected the 51 which approached the study topics in a more comprehensive manner. Data analysis and integration: analysis of the representativeness of papers in scientific journals revealed that 5.9 percent corresponded to the Journal of Craniomaxillofacial Surgery. Conclusions: it is indispensable for emergency maxillofacial surgeons to be able to recognize, diagnose and determine the basic management of maxillofacial trauma. Lack of a diagnosis or inappropriate management may lead to the loss of functions and the development of secondary deformities difficult to correct in the future. Such correction could also lead to disappointing results which may risk the patient's life(AU)

MicroRNA let-7f mediates mitochondrial respiratory deficit induced by repeated ethanol exposure and withdrawal in HT22 cells.

Aims: The expression of gene and gene product is typically inhibited by a small noncoding RNA (microRNA) or DNA methylation. The aim of this study is to investigate mechanisms involving microRNA let-7f by which the repeated cycles of ethanol exposure and withdrawal provoke mitochondrial respiratory damage. Study Design: The rat or cell model of repeated withdrawal from a high dose of ethanol exposure was used to mimic human alcoholics who repeat the cycles of heavy drinking and unsuccessful attempts at abstaining. Place and Duration of Study: Department of Pharmacology and Neuroscience University of North Texas Health Science Center at Fort Worth, between June 2011 and March 2014. Methodology: Male adult rats received an ethanol program, consisting of two cycles of ethanol exposure (4 weeks) and withdrawal (2 weeks). At the end of the ethanol program, one hemisphere of each rat was used to measure the level of let-7f using TaqMan let-7f primers and qPCR. The other hemisphere was used to measure the methylation of cytosine in let-7f gene using bisulfite conversion and pyrosequencing. Separately, HT22 cells (mouse hippocampal cells) were exposed to an ethanol program, consisting of two cycles of ethanol exposure (20 hours) and withdrawal (4 hours). During the entire ethanol program, the cells were treated with let-7f antagomir (inhibitor) or a methylation-inducing methyl-donor. The role of let-7f in mitochondria was assessed by quantifying a mitochondrial enzyme, cytochrome c oxidase-IV (COX subunit IV) and realtime mitochondrial respiration using an immunoblot method and XF respirometry, respectively. Results: The level of let-7f increased (2.4±0.5 fold increase), whereas the methylation of let-7f gene decreased in the brain of rats that underwent repeated ethanol exposure and withdrawal (called “repeated-ethanol/withdrawal”). The methyl-donor treatment completely abolished the increase in let-7f induced by repeated-ethanol/withdrawal. let-7f antagomir treatment also abolished the inhibiting effect of repeated-ethanol/withdrawal on COX-IV and mitochondrial respiration. Conclusion: These data suggest that repeated-ethanol/withdrawal provokes the dysregulation of let-7f, thereby damaging brain mitochondria. Mitochondria-associated microRNA may be a potential research and drug target to manage alcoholism.

Multiple chemical sensitivity caused by exposure to ignition coal fumes: a case report

BACKGROUND: Although multiple chemical sensitivity (MCS) is a well-known disorder caused by environmental exposures, MCS caused by occupational exposure has been reported in Korea. Therefore, we report a MCS case caused by environmental exposure to ignition coal after a differential diagnosis to exclude other diseases. CASE REPORT: Since 2011, a 55-year-old woman had experienced edema, myalgia, and other symptoms when she smelled ignition coal near her workplace. She had been diagnosed with fibromyalgia syndrome(FMS) and was treated, with no improvement of symptoms. Since then, she showed the same symptoms after exposure to city gas, the smell of burning, and exhaust gas. To avoid triggering substances, she moved to a new house and used an air purifier. She quit her job in November 2012. After visiting our hospital, she underwent a differential diagnosis for FMS, chronic fatigue syndrome, and somatization disorder. She was diagnosed with MCS by the Korean version of the Quick Environment Exposure Sensitivity Inventory (QEESI). She was educated about the disease and to avoid triggering substances. She received ongoing treatment for her symptoms. CONCLUSION: This case showed that symptoms began after smelling ignition coal. After that, her triggers was increased such as the smell of city gas, burning, and exhaust gas. This case is the first reported in Korea of MCS due to environmental exposure after ruling out other diseases.

HIV/AIDS e sífilis entre gestantes adolescentes e adultas jovens: fatores de exposição e risco dos atendimentos de um programa de dst/hiv/aids na rede pública de saúde SUS, Bahia, Brasil / HIV /AIDS and syphilis among pregnant adolescents and young adults:exposure and risk factors in STD/HIV/AIDS program dates of the public health system Bahia / Brazil / HIV/ SIDA y la sífilis entre las adolescentes embarazadas y adultas jóvenes: factores de exposición y riesgo en los atendimientos de um programa de ETS/HIV/SIDA, en la red pública de salud/SUS, Bahia, Brasil

The sexual behavior of adolescents and young people is configured as a challenge to public health, especially during pregnancy, due to multiple factors and risk of exposure to HIV / AIDS and syphilis, as well as the psychosocial and economic repercussions in the individual, families and social contexts. The objective is to study risk factors and exposure to HIV/AIDS and syphilis among pregnant adolescents and young women, registered in Feira de Santana s STD/AIDS Program. It is a descriptive study using data from the Information System Center of Testing (CTA), regarding referrals for serological screening of SUS over the period 2004/2008. We studied exposure and risk factors by age groups of pregnant women, according to casual and steady partners, being calculated prevalence and prevalence ratio (PR), with an interval of 95percent and p less than 0.05percent. It was found that pregnant teenagers and young women showed high proportions of conjugal union, for a steady partner, 90percent of the pregnant of the three age groups denied habitual use of condoms, with significant association linked to the partner (trust, non-acceptance), the youngest age group (less than 16 years) showed higher interference from external factors (lack of availability of condoms and relationship unplanned). To a casual partner was found significant proportions of habitual use, however, with high proportions ofoccasional use linked to personal factors (not believe, want children, do not appreciate use) (29percent to 41percent). The prevalence of seropositivity for HIV (0,3percent) and syphilis (1,5percent) agreed with literature. Results suggest a need for awareness of vulnerable groups, with emphasis on issues of gender and lifestyle inherent in youth.

El comportamiento sexual de los adolescentes y jóvenes se fijaron un desafío para la salud pública, especialmente durante el embarazo, debido a múltiples factores y el riesgo de exposición al VIH / SIDA y la sífilis, así como las repercusiones psicosociales y económicas en los contextos de los individuos, las familias y sociales. El objetivo es estudiar los factores de riesgo y la exposición al HIV/SIDA y sífilis entre embarazadas adolescentes y adultas jóvenes, inscriptos em El Programa Nacional de ITS / HIV / SIDA en Feira de Santana, Bahia. Este es un estudio descriptivo con los datos del Centro de Información del Sistema para la prueba (CTA), referencias con respecto del tamizaje serológico del SUS en el período 2004/2008. Se estudiaron los factores de exposición y el riesgo por grupos de edad de la mujer embarazada, según compañero fijo o constante, se calculó la razón de la prevalencia y la prevalencia (RP), con un intervalo de 95por ciento p menos que 0,05por ciento. Se encontró que los adolescentes y adultas jóvenes muestran una alta proporción de la unión conyugal, de pareja estable, el 90por ciento de los pacientes de los tres grupos de edad negó el uso habitual de condones, con asociación significativa vinculados a su compañero (la confianza, la no aceptación), el grupo de edad más jóvenes (menos que 16 años) mostraron una mayor interferencia de factores externos (falta de disponibilidad de preservativos y la relación no planificada). Para una pareja ocasional se encontró una proporción significativa de uso habitual, sin embargo, con un alto porcentaje de uso ocasional vinculado a factores personales (no creer, desear hijos, no aprecian el uso) (29por ciento a 41por ciento). La prevalencia de seropositividad para el HIV (03por ciento) y la sífilis (1,5por ciento) está de acuerdo con la literatura. Los resultados sugieren la necesidad de sensibilización de los grupos vulnerables, com énfasis en temas de género y estilo de vida inherente a la juventud.

Relation of CAG Repeat Polymorphism of AR Gene in Men of Han Nationality from Northern China to the Effectiveness of Hypoxic Training / 中国运动医学杂志

Objective To investigate the distribution characteristics of (CAG)n polymorphism in the exonl of the androgen receptor (AR) gene and its relation to the sensitivity of hypoxic training in men of Han nationality from northern China. Methods Sixty five healthy young men of Han nationality completed HiHiLo training under simulated normobaric hypoxic environment for 4 weeks. They stayed under the condition of 14.3-14.8% O_2 (simulating 2800～3000m) during nighttime and carried out hypoxic training under the condition of 14.8-15.4% O_2 (simulating 2500～2800m) 3 times per week at the intensity of 75% individual VO_2max. VO_2max and body weight of the subjects were measured. GeneScan method was used to identify the repeat alleles (genotypes) of CAG polymorphism. Results (1) Fifteen alleles (CAG)12,(CAG)16-28,(CAG)30 repeat alleles (genotypes) were observed in the subjects, in which (CAG)22 was the most common allele; (2) When 21 and 22 alleles were used as the cut point, the baseline of body weight in those carrying shorter genotypes was significantly lower than that in those carrying longer genotypes; (3) △VO_2max and △rVO_2max in men carrying shorter genotypes were significantly higher than that in men carrying longer genotypes after hypoxic training. Conclusion The result reveals that AR (CAG)n polymorphism is associated with the sensitivity of simulated normobaric hypoxic HiHiLo training in men of Han nationality from northern China, especially in those carrying shorter genotypes of AR CAG.

Tratamiento Cognitivo Conductual para las ideas sobrevaloradas en pacientes que padecen un Trastorno Obsesivo Compulsivo / Cognitive behavioural therapy of overvalued ideas in patients suffering of obsessive-compulsive disorder

Se examinarán las ideas sobrevaloradas en el Trastorno Obsesivo Compulsivo (TOC), ya que éstas son consideradas uno de los impedimentos más importantes para el progreso del tratamiento, particularmente para la implementación de la técnica de exposición y prevención de respuesta (EPR). Las cogniciones disfuncionales características del TOC, como ser hiperresponsabilidad, sobrestimación de las ideas, necesidad de control, sobrestimación del peligro, perfeccionismo e intolerancia a la incertidumbre son tratadas vía maniobras de disputa y psicoeducacionales. La psicoeducación, las técnicas cognitivas y la exposición y prevención de respuesta (EPR) son desarrolldas a lo largo del artículo, ya que son el abordaje de elección para el tratamiento del TOC.

In this paper we examined the overvalued ideas in Obsessive Compulsive Disorder (OCD), because they are considered an impediment to progress in the treatment, particularly for exposure and response prevention interventions (ERP). Maladaptive cognitions in OCD, involving excessive responsibility, over-importance of thoughts, need to control thoughts, overestimation of threat, perfectionism and intolerance for uncertainty is the core of illness. Cognitive change via disputing and education are also the key to symptom remission. Educational, cognitive therapy and ERP approaches are the treatment of choice for OCD.

Fatores preditores de resultados no tratamento do transtorno obsessivo-compulsivo com as terapias comportamental e cognitivo-comportamental: uma revisão sistemática: [revisão] / Outcome predictor factors in the treatment of obsessive-compulsive disorder using behavior and cognitive-behavior therapies: a systematic review: [revision]

INTRODUÇÃO: As terapias comportamental e cognitivo-comportamental reduzem os sintomas do transtorno obsessivo-compulsivo em mais de 70% dos pacientes. Entretanto, cerca de 30% não obtêm nenhuma melhora. Conhecer fatores associados a esses desfechos poderia auxiliar numa melhor indicação do tratamento, incrementando sua eficácia. MÉTODO: Foram revisados trabalhos que investigaram fatores preditivos de resultados nos tratamentos do transtorno obsessivo-compulsivo, nas fontes PubMed, PsycINFO e LILACS. Termos utilizados na busca: predictive factors OR prediction AND obsessive-compulsive disorder AND exposure response prevention OR ritual prevention OR behav* therapy OR cognitive behav* therapy, resultando em 104 artigos. As referências dos artigos foram analisadas, possibilitando maior número de trabalhos revisados. Excluíram-se artigos que utilizaram apenas farmacoterapia e aqueles que não abordavam o tema, resultando em 29 artigos. DISCUSSÃO: As variáveis demográficas parecem exercer papel indireto, destacando-se sexo masculino e ausência de companheiro(a) como fatores de pior prognóstico. Maior gravidade e início precoce dos sintomas indicariam piores resultados. O transtorno esquizotípico comórbido é potencialmente negativo. Sintomas relacionados ao colecionismo e com conteúdo sexual/religioso indicam pior prognóstico. Maior nível de insight, motivação e colaboração com o tratamento são características favoráveis. Maior intensidade da melhora e a remissão completa são preditores para a não-recaída. CONCLUSÃO: A identificação de fatores preditores de resultados está longe de ser esclarecida. É possível que múltiplos fatores, cujas associações são complexas, atuem em conjunto. Os resultados podem depender de fatores não-específicos, ainda não abordados pelos estudos. A heterogeneidade do transtorno obsessivo-compulsivo e das pesquisas e o uso associado de medicamentos dificultam o estabelecimento de conclusões mais definidas.

INTRODUCTION: Behavioral and cognitive-behavioral therapies reduce symptoms of obsessive-compulsive disorder in over 70% of patients. However, about 30% do not show any improvement. The knowledge of factors associated with these outcomes may inform better treatment indications and improve treatment efficacy. METHOD: Review of studies that investigated predictors of obsessive-compulsive disorder treatment results in PubMed, PsychoINFO and LILACS databases. Terms used in the search were predictive factors OR prediction AND obsessive-compulsive disorder AND exposure response prevention OR ritual prevention OR behav* therapy OR cognitive behav* therapy." The search retrieved 104 studies. The references of retrieved studies were also analyzed to ensure that all relevant studies were included. Studies that used only pharmacotherapy or did not discuss the topic under analysis were excluded, and 29 studies met inclusion criteria. DISCUSSION: Demographic variables seem to play an indirect role in treatment results; male sex and not having partner are factors associated with poor prognosis. Greater severity and early symptom onset also indicate poor outcomes. Comorbid schizotypal disorder is potentially negative. Symptoms associated with hoarding and sexual/religious obsessions predict poor prognosis. Greater insight, motivation and collaboration with treatment are favorable characteristics. Greater improvement and complete remission of symptoms are predictors of no relapse. CONCLUSION: The identification of outcome predictors is still far from complete. Multiple factors may contribute to results, and their associations are complex. Results may depend on unspecific factors not yet investigated. Definite conclusions are difficult to reach because of the heterogeneity of obsessive-compulsive disorder and of the studies investigating it and the combined use of drugs.

Exposure and Ritual Prevention of Obsessive-compulsive Disorder:A Case Study / 中国临床心理学杂志

Objective:To investigate effectiveness of exposure and ritual prevention of patients with obsession-compul-sive disorder(OCD),so as to provide references for professionals in clinical psychology.Methods:One female patient with severe OCD received 3 weeks intensive exposure and ritual prevention treatment.In order to investigate the effectiveness,she completed Symptom Check List 90 and Yale Brown Obsessive Compulsive Scale(SCL-90 and YBOCS) at pre-treat-ment,mid-treatment and post-treatment.Results:After treatment,the patient's scores of questionnaires reduced,such as score on YBOCS reduced from 38 to 9.She reported that her washing time reduced obviously and her own measure of dis-tress index reduced.Conclusion:Exposure and ritual prevention could treat the patient with OCD effectively.Her distress reduced and life function was improved.