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Consumption of refined high-fat, low-fiber diets promotes development of obesity and its associated consequences. Although genetics play an important role in dictating susceptibility to such obesogenic diets, mice with nearly uniform genetics exhibit marked heterogeneity in their extent of obesity in response to such diets. This suggests non-genetic determinants play a role in diet-induced obesity. Hence, we sought to identify parameters that predict, and/or correlate with, development of obesity in response to an obesogenic diet. We assayed behavior, metabolic parameters, inflammatory markers/cytokines, microbiota composition, and the fecal metaproteome, in a cohort of mice (n = 50) prior to, and the 8 weeks following, administration of an obesogenic high-fat low-fiber diet. Neither behavioral testing nor quantitation of inflammatory markers broadly predicted severity of diet-induced obesity. Although, the small subset of mice that exhibited basal elevations in serum IL-6 (n = 5) were among the more obese mice in the cohort. While fecal microbiota composition changed markedly in response to the obesogenic diet, it lacked the ability to predict which mice were relative prone or resistant to obesity. In contrast, fecal metaproteome analysis revealed functional and taxonomic differences among the proteins associated with proneness to obesity. Targeted interrogation of microbiota composition data successfully validated the taxonomic differences seen in the metaproteome. Although future work will be needed to determine the breadth of applicability of these associations to other cohorts of animals and humans, this study nonetheless highlights the potential power of gut microbial proteins to predict and perhaps impact development of obesity.
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Fezes/microbiologia , Microbioma Gastrointestinal/fisiologia , Obesidade/etiologia , Proteoma/metabolismo , Animais , Composição Corporal , Dieta Hiperlipídica/efeitos adversos , Dieta Ocidental/efeitos adversos , Feminino , Flagelina/metabolismo , Microbioma Gastrointestinal/genética , Imunoglobulina A/sangue , Mediadores da Inflamação/metabolismo , Lipocalina-2/metabolismo , Síndrome Metabólica/etiologia , Síndrome Metabólica/microbiologia , Camundongos Endogâmicos C57BL , Obesidade/microbiologia , Proteoma/análise , RNA Ribossômico 16SRESUMO
Circumstantial evidence supports the hypothesis that the sexually dimorphic vasopressin (AVP) innervation of the brain tempers sickness behavior in males. Here we test this hypothesis directly, by comparing sickness behavior in animals with or without ablations of BNST AVP cells, a major source of sexually dimorphic AVP in the brain. We treated male and female AVP-iCre+ and AVP-iCre- mice that had been injected with viral Cre-dependent caspase-3 executioner construct into the BNST with lipopolysaccharide (LPS) or sterile saline, followed by behavioral analysis. In all groups, LPS treatment reliably reduced motor behavior, increased anxiety-related behavior, and reduced sucrose preference and consumption. Male mice, whose BNST AVP cells had been ablated (AVP-iCre+), displayed only minor reductions in LPS-induced sickness behavior, whereas their female counterparts displayed, if anything, an increase in sickness behaviors. All saline-treated mice with BNST AVP cell ablations consumed more sucrose than did control mice, and males, but not females, with BNST AVP cell ablations showed reduced preference for novel conspecifics compared to control mice. These data confirm that BNST AVP cells control social behavior in a sexually dimorphic way, but do not play a critical role in altering sickness behavior.
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Arginina Vasopressina/metabolismo , Encéfalo/citologia , Caracteres Sexuais , Comportamento Social , Animais , Encéfalo/metabolismo , Ingestão de Alimentos , Feminino , Masculino , Camundongos , Sacarose/metabolismoRESUMO
PURPOSE: Preference-based measures can provide measurements of health-related quality of life and be utilized for cost-effectiveness analyses of interventions in individuals with chronic obstructive pulmonary disease (COPD). The purpose of this study is to evaluate whether generic preference-based measures are reliable, valid, and responsive in COPD. METHODS: A systematic review was performed using the Consensus-based Standards for the selection of health Measurement Instruments (COSMIN) guidelines. Three databases were searched: MEDLINE, EMBASE, and CINAHL. Studies were included if the sample represented individuals with COPD and the aim was to evaluate one or more psychometric properties or the interpretability of generic preference-based measures. RESULTS: Six hundred and sixty-seven abstracts were screened, 65 full-text articles were reviewed and 24 articles met the inclusion criteria. Measures which emerged from the search were the EQ-5D, the SF-6D, the Quality of Well-being scale, the 15D, and the Health Utilities Index 3. Evidence for the test-retest reliability of these measures was limited. Construct validity of the measures was well supported with correlations with generic health profiles being 0.37-0.68, and correlations with COPD-specific health profiles being 0.53-0.75. Evidence for known-groups validity of these measures was poor and data on responsiveness were mixed. CONCLUSION: Generic preference-based measures' sensitivity to change and ability to discriminate between different disease severities in COPD was poorly supported. Future research may consider examining the development of COPD-specific preference-based measures that may allow for a more accurate detection of change and discrimination among disease severities to facilitate cost-effectiveness evaluations.
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Análise Custo-Benefício/métodos , Psicometria/economia , Doença Pulmonar Obstrutiva Crônica/economia , Qualidade de Vida/psicologia , Humanos , Inquéritos e QuestionáriosAssuntos
Antipsicóticos/intoxicação , Overdose de Drogas/terapia , Emulsões Gordurosas Intravenosas/administração & dosagem , Fumarato de Quetiapina/intoxicação , Adulto , Transtorno Bipolar/tratamento farmacológico , Terapia Combinada , Overdose de Drogas/diagnóstico , Overdose de Drogas/etiologia , Feminino , Humanos , Infusões Intravenosas , Pessoa de Meia-Idade , Norepinefrina/administração & dosagem , Fisostigmina/administração & dosagem , Respiração Artificial , Choque/induzido quimicamente , Choque/diagnóstico , Choque/terapia , Estado Epiléptico/induzido quimicamente , Estado Epiléptico/diagnóstico , Estado Epiléptico/terapia , Resultado do TratamentoRESUMO
Introduction: Chronic disease management programs (CDMP) that include education and exercise enhance outcomes and reduce healthcare costs. Remote CDMP have the potential to provide convenient, cost-effective, and accessible options for individuals, but it is unclear how to best implement programs that include education and exercise. This review identified and synthesized resources for implementing remote CDMP programs that incorporate education and exercise. Methods: Peer-reviewed and grey literature were systematically searched from January 1998 to May 2022. Covidence software was used for screening and extraction. The data were synthesized and presented in a narrative and tabular format. Results: Six peer-reviewed manuscripts and six grey literature documents published between 2006-2022 were included. All resources described individual programs targeting various chronic conditions. Provider training, consent, participant screening, and safety considerations were identified. Conclusions: Guidelines for remote CFMP programs are lacking. Additional work is needed to design remote CDMP guidelines incorporating education and exercise.
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Purpose: The purpose of this study was to determine current physiotherapy practice for managing chronic low back pain (LBP). Method: We administered a cross-sectional survey to all physiotherapists working in Eastern Health (EH) Regional Health Authority, Newfoundland and Labrador, by email. To ascertain how physiotherapists assessed and treated patients with LBP, the survey included multiple-choice and open-ended questions, along with case vignettes. We explored the respondents' confidence about implementing all aspects of guideline-based care, as well as their use of treatment outcome measures. Results: A total of 76 physiotherapists responded to the survey (84% response rate); 56 (74%) reported that they treated patients with LBP as part of their regular practice. More than half had managed LBP for more than 10 years. The most frequently used treatments were self-management advice, followed by home and supervised exercise. The majority of respondents lacked confidence about implementing cognitive-behavioural treatment techniques. The Numeric Pain Rating Scale was the most commonly used outcome measure; disability outcome measures were not frequently used. Conclusions: The majority of LBP management in EH aligns with guideline recommendations. Increased uptake of guidelines recommending assessment and management of LBP using a bio-psychosocial approach will require training and support.
Objectif : déterminer les pratiques de physiothérapie actuelles pour traiter les douleurs lombaires chroniques. Méthodologie : les chercheurs ont distribué un sondage transversal par courriel à tous les physiothérapeutes de l'Autorité régionale de la santé de l'Est (SE) de Terre-Neuve-et-Labrador. Pour déterminer la manière dont les physiothérapeutes évaluent et traitent les patients ayant des douleurs lombaires, le sondage incluait des questions à choix multiples, des questions ouvertes et des scénarios de cas. Les chercheurs ont exploré la confiance des répondants envers l'adoption de tous les aspects des soins reposant sur des directives, de même qu'envers les mesures de résultat des traitements. Résultats : au total, 76 physiothérapeutes ont répondu au sondage, pour un taux de réponse de 84 %; 56 (74 %) ont déclaré traiter des patients ayant des douleurs lombaires dans le cadre de leur pratique régulière. Plus de la moitié traitaient des douleurs lombaires depuis plus de dix ans. Les traitements les plus utilisés étaient des conseils d'autogestion, suivis par des exercices à domicile et des exercices supervisés. La majorité des répondants n'avaient pas assez confiance pour adopter des techniques de thérapie cognitivo-comportementale. L'échelle numérique d'évaluation de la douleur était la mesure de résultat la plus utilisée, tandis que les mesures de résultats des incapacités étaient peu utilisées. Conclusion : à la SE, le traitement de la majorité des douleurs lombaires est conforme aux directives. Pour accroître les mises à jour des directives recommandant d'évaluer et de traiter les douleurs lombaires au moyen d'une approche biopsychosociale, il faudra une formation et un soutien.
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INTRODUCTION: This protocol describes the methods for a mixed study systematic review aiming to explore the definitions and measurements of recovery in patients with low back pain, and how perspectives of recovery differ between patients and providers. This review will be the first to review the concept of recovery in patients with low back pain across both quantitative and qualitative literature. METHODS AND ANALYSIS: This protocol has been designed and reported in line with Preferred Reporting Items of Systematic Reviews and Meta-Analyses Protocols. The following databases will be electronically searched from database inception until 30 November 2021: Medline, EMBASE, CINAHL, Cochrane, PEDro. Grey literature will be searched for through targeted searching of ProQuest Dissertations and Theses and handsearching of the references of all included studies. Studies will be included if they include a patient population of >50% with low back pain (with or without leg pain), and mention the concept of recovery within the abstract, methods or results. The Mixed Methods Appraisal Tool will be used for quality assessment of both quantitative and qualitative included studies. Two independent reviewers will conduct the search, screen titles/abstracts and extract relevant data from full texts. Discrepancies between reviewers will be settled by a third reviewer with spinal pain expertise. For syntheses, thematic analysis will be used to analyse both qualitative and quantitative investigations to explore meanings, measurement and perspectives of recovery from a diverse evidence base. There is no clinical trial associated with this protocol. ETHICS AND DISSEMINATION: There are no ethical issues associated with this systematic review, and ethics approval was not required. Once completed, the results of this review will be published in a peer-reviewed journal within the realm of spinal pain to help guide future research inquiries. PROSPERO REGISTRATION NUMBER: CRD42022295804.
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Dor Lombar , Humanos , Dor Lombar/terapia , Pesquisa Qualitativa , Projetos de Pesquisa , Literatura de Revisão como Assunto , Revisões Sistemáticas como AssuntoRESUMO
Objective: The aim of this study was to refine the items of a preference-based amyotrophic lateral sclerosis health-related quality of life scale (PB-ALS HRQL scale) based on domains generated in a previous study. Methods: Survey methodology was used to assess item importance rating (IR) and independence. Median importance was calculated for each item and a rating of "very important" was required for the item to remain. Correlations were used to examine item independence. Highly correlated items (rs > 0.7) were considered for removal. Cognitive debriefing (CD) interviews, conducted by Zoom, telephone, or email based on participant preference and communication needs, were used to identify potential issues. Participants provided feedback about wording, clarity, response options, and recall period on randomly selected items. Items were considered finalized when three sequential CD participants approved the item with no revisions. Results: Thirty-four people with ALS (PALS, n = 16 females; age range 44-78 years; ALS Functional Rating Scale-Revised [ALSFRS-R] range 0-48) in Canada completed the survey; a subset of 18 PALS completed CD interviews (n = 8 female; age range 44-71 years; ALSFRS-R range 0-48). Four items were highly correlated with one or more items, were not rated as very important, or were not approved via CD and were removed. Conclusions: The final four-response option PB-ALS Scale includes eight items: recreation and leisure, mobility, interpersonal interactions and relationships, eating and swallowing, handling objects, communicating, routine activities, and mood. The next step is to translate the PB-ALS Scale into French and develop a scoring algorithm based on PALS' preferences.
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Esclerose Lateral Amiotrófica , Humanos , Feminino , Adulto , Pessoa de Meia-Idade , Idoso , Esclerose Lateral Amiotrófica/psicologia , Qualidade de Vida , Inquéritos e Questionários , Deglutição/fisiologia , IdiomaRESUMO
OBJECTIVE: The aim of this review was to synthesize the psychometric properties of generic preference-based measures (PBMs) of health-related quality of life (HRQL) in Amyotrophic Lateral Sclerosis (ALS). METHODS: A systematic review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Four databases were searched from inception to April 2019: OVID Medline, Embase, PsycINFO, and CINAHL. Studies were included if (1) the sample represented individuals with ALS, (2) a generic PBM was utilized and reported on, and (3) information on the psychometric property of a generic PBM was provided. RESULTS: Ninety-one articles were screened, and 39 full-text articles were reviewed. Seven full-text articles were included in this review. The mean age of participants ranged from 58.1 to 63.8 years, and mean time since diagnosis ranged from 20.5 to 44.6 months. Two generic PBMs were found, the EQ-5D-3L (n = 6) and the Quality of Well-Being Self-Administered (QWB-SA) scale (n = 1). Convergent validity of the EQ-5D-3L was large against a global scale of self-perceived health (r = 0.60) and small to large against ALS specific HRQL measures (r = 0.19 to 0.75). For the QWB-SA scale, correlations were small against a generic measure (r = 0.21) and large against ALS specific measures (r = 0.55). The EQ-5D-3L discriminated across different disease severity; however, floor effects were reported. CONCLUSION: This review highlights the need for more rigorously designed studies to assess the psychometric properties of generic PBMs in ALS and the development of an ALS specific PBM that adequately reflects the health concerns of individuals with ALS.
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OBJECTIVE: The objectives of this study were to 1) assess the content validity of generic preference-based measures (GPBMs), and (2) examine the convergent validity of the EuroQol 5 Dimension 5 Level (EQ-5D-5L), against the Patient Generated Index (PGI) in Amyotrophic Lateral Sclerosis (ALS). METHODS: Participants were recruited from 3 clinical sites across Canada. The PGI, EQ-5D-5L and Amyotrophic Lateral Sclerosis Functional Rating Scale-Revised (ALSFRS-R) were administered through an online or hardcopy survey and scores compared for convergent validation. Domains nominated by participants as important to their health-related quality of life were generated using the PGI, classified using the International Classification of Functioning, Disability and Health (ICF) and mapped onto GPBMs to determine content coverage. RESULTS: Fifty-two participants (N=28 female; 61.3 ± 11.6 mean age ± standard deviation (SD); 3.5 ± 2.9 mean ± SD years since diagnosis) completed this study. The top three ICF domains identified by participants were recreation and leisure, lower limb mobility, and interpersonal relationships. The Quality of Well-Being Self-Administered (QWB-SA) scale had the highest content coverage (87%) and the Health Utilities Index 3 (HUI3) had the lowest (33%). Two domains were covered by all GPBMs and no GPBM included all domains identified as important by participants. A moderate correlation coefficient of 0.52 between the PGI and EQ-5D-5L was found. CONCLUSION: The majority of GPBMs covered only approximately half of the domains important to individuals with ALS suggesting the need for an ALS specific preference-based measure to better reflect the health-related quality of life of this population.
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Dietary emulsifiers carboxylmethylcellulose (CMC) and polysorbate 80 (P80) alter the composition of the intestinal microbiota and induce chronic low-grade inflammation, ultimately leading to metabolic dysregulations in mice. As both gut microbiota and intestinal health can influence social and anxiety-like behaviors, we investigated whether emulsifier consumption would detrimentally influence behavior. We confirmed that emulsifier exposure induced chronic intestinal inflammation, increased adiposity, and altered gut microbiota composition in both male and female mice, although the specific microboal taxa altered following emulsifier consumption occurred in a sex-dependent manner. Importantly, emulsifier treatment altered anxiety-like behaviors in males and reduced social behavior in females. It also changed expression of neuropeptides implicated in the modulation of feeding as well as social and anxiety-related behaviors. Multivariate analyses revealed that CMC and P80 produced distinct clustering of physiological, neural, and behavioral effects in male and female mice, suggesting that emulsifier treatment leads to a syndrome of sex-dependent changes in microbiota, physiology, and behavior. This study reveals that these commonly used food additives may potentially negatively impact anxiety-related and social behaviors and may do so via different mechanisms in males and females.
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Ansiedade/induzido quimicamente , Carboximetilcelulose Sódica/toxicidade , Emulsificantes/toxicidade , Inflamação/induzido quimicamente , Polissorbatos/toxicidade , Adiposidade , Animais , Comportamento Animal , Feminino , Microbioma Gastrointestinal , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Comportamento SocialRESUMO
Airway epithelial cells (AECs) display remarkable plasticity in response to infectious stimuli and their functional adaptations are critical for antimicrobial immunity. However, the roles of AECs and humoral mediators to host defense in non-communicable lung inflammation remain elusive. We dissected pulmonary defense against Streptococcus pneumoniae in hosts with pre-existing inflammatory conditions (SPC-HAxTCR-HA mice). Lung tissue transcriptomics and bronchoalveolar lavage fluid (BALF) proteomics revealed an induction of humoral defense mechanisms in inflamed lungs. Accordingly, besides antibacterial proteins and complement components being overrepresented in inflamed lungs, elevated polymeric immunoglobulin receptor (pIgR)-expression in AECs correlated with increased secretory immunoglobulin (SIg) transport. Consequently, opsonization assays revealed augmented pneumococcal coverage by SIgs present in the BALF of SPC-HAxTCR-HA mice, which was associated with enhanced antipneumococcal resistance. These findings emphasize the immunologic potential of AECs as well as their central role in providing antibacterial protection and put forward pIgR as potential target for therapeutic manipulation in infection-prone individuals.
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Perfilação da Expressão Gênica/métodos , Pneumonia/imunologia , Proteômica/métodos , Streptococcus pneumoniae/imunologia , Animais , Líquido da Lavagem Broncoalveolar/química , Líquido da Lavagem Broncoalveolar/microbiologia , Modelos Animais de Doenças , Imunoglobulina A Secretora/genética , Imunoglobulina A Secretora/metabolismo , Camundongos , Análise de Sequência com Séries de Oligonucleotídeos , Pneumonia/genética , Pneumonia/microbiologia , Receptores de Imunoglobulina Polimérica/genética , Receptores de Imunoglobulina Polimérica/metabolismo , Análise de Sequência de RNARESUMO
Over the past 3 decades, a large body of evidence has accumulated demonstrating that the neuropeptide arginine vasopressin (AVP) plays a critical role in regulating social behavior. The overwhelming majority of this evidence comes from adults, leaving a gap in our understanding of the role of AVP during development. Here, we investigated the effect of chronic AVP deficiency on a suite of juvenile social behaviors using Brattleboro rats, which lack AVP due to a mutation in the Avp gene. Social play behavior, huddling, social investigation & allogrooming, and ultrasonic vocalizations (USVs) of male and female rats homozygous for the Brattleboro mutation (Hom) were compared with their wild-type (WT) and heterozygous (Het) littermates during same-sex, same-genotype social interactions. Male and female Hom juveniles exhibited less social play than their Het and WT littermates throughout the rise, peak, and decline of the developmental profile of play. Hom juveniles also emitted fewer prosocial 50 kHz USVs, and spectrotemporal characteristics (call frequency and call duration) of individual call types differed from those of WT and Het juveniles. However, huddling behavior was increased in Hom juveniles, and social investigation and 22 kHz USVs did not differ across genotypes, demonstrating that not all social interactions were affected in the same manner. Collectively, these data suggest that the Avp gene plays a critical role in juvenile social development.
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Mutação/genética , Transtornos do Comportamento Social/genética , Comportamento Social , Vasopressinas/deficiência , Vocalização Animal/fisiologia , Fatores Etários , Análise de Variância , Animais , Animais Recém-Nascidos , Feminino , Genótipo , Heterozigoto , Homozigoto , Masculino , Ratos , Ratos Brattleboro , Ratos Long-Evans , Fatores Sexuais , Vasopressinas/genética , Vocalização Animal/classificaçãoAssuntos
Tratamento Farmacológico da COVID-19 , Vacinas contra COVID-19/uso terapêutico , Leucemia Linfocítica Crônica de Células B/imunologia , SARS-CoV-2/efeitos dos fármacos , Vacina de mRNA-1273 contra 2019-nCoV , Adulto , Idoso , Vacina BNT162 , COVID-19/imunologia , COVID-19/patologia , COVID-19/virologia , Vacinas contra COVID-19/imunologia , Feminino , Humanos , Imunidade , Hospedeiro Imunocomprometido , Leucemia Linfocítica Crônica de Células B/tratamento farmacológico , Leucemia Linfocítica Crônica de Células B/patologia , Leucemia Linfocítica Crônica de Células B/virologia , Masculino , Pessoa de Meia-Idade , SARS-CoV-2/imunologiaRESUMO
During sensitive periods, information from the external and internal environment that occurs during particular phases of development is relayed to the brain to program neural development. Hormones play a central role in this process. In this review, we first discuss sexual differentiation of the brain as an example of hormonal programming. Using sexual differentiation, we define sensitive periods, review cellular and molecular processes that can explain their restricted temporal window, and discuss challenges in determining the precise timing of the temporal window. We then briefly review programming effects of other hormonal systems and discuss how programming of these systems interact with sexual differentiation.
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Encéfalo/fisiologia , Hormônios/fisiologia , Sistema Hipotálamo-Hipofisário/fisiologia , Sistema Hipófise-Suprarrenal/fisiologia , Diferenciação Sexual/fisiologia , Animais , Encéfalo/metabolismo , Hormônios/metabolismo , Humanos , Sistema Hipotálamo-Hipofisário/metabolismo , Sistema Hipófise-Suprarrenal/metabolismoRESUMO
Although earlier studies on pregnancies derived through intracytoplasmic sperm injection (ICSI) reported increased non-mosaic aneuploidy among ICSI children, undetected mosaicism, such as confined placental mosaicism (CPM) has not been evaluated. We investigated the incidence of CPM in post-delivery placentas derived from ICSI, evaluated whether CPM was increased and whether it was a contributing factor to negative pregnancy outcome. [Fifty-one post-delivery placentas were collected from patients who underwent ICSI with a normal or negative pregnancy outcome]. Trophoblast and chorionic stroma from three sites were analyzed by comparative genomic hybridization (CGH) and flow cytometry. Detected abnormalities were confirmed by fluorescence in situ hybridization (FISH). The incidence of CPM in the ICSI population was compared to the general population from published data. We detected three cases of CPM in our study. One abnormality was found by CGH analysis; partial trisomy 7q and a partial monosomy Xp limited to the trophoblast at two sites. The abnormality was associated with a child affected by spina bifida. Two cases of mosaic tetraploidy were observed by flow cytometry in pregnancies with a normal outcome. All three abnormalities were confirmed by FISH analysis. The incidence of CPM in the ICSI study population was 5.88% (3/51), which was not statistically different from published reports in the general population (5.88% (42/714), Chi square, P > 0.05). The post-ICSI population was not at risk for CPM in this study.