The association between gut microbiome and growth in infants with cystic fibrosis.

BACKGROUND: In cystic fibrosis (CF), pathophysiologic changes in the gastrointestinal tract lead to malnutrition and altered gut microbiome. Microbiome alterations have been linked to linear growth, gut inflammation and respiratory manifestations. Elucidating these gut microbiome alterations may provide insight into future nutritional management in CF. METHODS: Infants were followed for 12-months at four sites in the United States (US-CF) and Australia (AUS-CF). 16S rRNA gene sequencing was performed on longitudinal stool samples. Associations between microbial abundance and age, antibiotic prophylaxis, malnutrition, and breast feeding were evaluated using generalized linear mixed models. Taxonomic and predictive functional features were compared between groups. RESULTS: Infants with CF (N = 78) were enrolled as part of a larger study. AUS-CF infants had higher mean weight-for-age z-scores than US-CF infants (p = 0.02). A subset of participants (CF N = 40, non-CF disease controls N = 10) provided stool samples for microbiome analysis. AUS-CF infants had lower stool alpha diversity compared to US-CF infants (p < 0.001). AUS-CF infants had higher relative abundance of stool Proteobacteria compared to US-CF infants which was associated with antibiotic prophylaxis (p < 0.001). Malnutrition (weight-for-age <10th percentile) was associated with depleted Lactococcus (p < 0.001). Antibiotic prophylaxis (p = 0.002) and malnutrition (p = 0.012) were linked with predicted decreased activity of metabolic pathways responsible for short chain fatty acid processing. CONCLUSIONS: In infants with CF, gut microbiome composition and diversity differed between the two continents. Gut microbial diversity was not linked to growth. The relationship between malnutrition and antibiotic prophylaxis with reduced SCFA fermentation could have implications for gut health and function and warrants additional investigation.

Normal Neurodevelopmental Outcomes in PNPO Deficiency: A Case Series and Literature Review.

Pyridox(am)ine 5'-phosphate oxidase deficiency results in an early-onset neonatal encephalopathy that can be fatal if not detected and treated early. The condition is rare, can result in preterm delivery, and can mimic hypoxic ischemic encephalopathy. Thus, suspicion of the diagnosis, appropriate investigations, and therapeutic trials with pyridoxal-5'-phosphate are often delayed. In this paper we report four cases of pyridox(am)ine 5'-phosphate oxidase deficiency, two of whom are siblings. Three were treated with pyridoxal-5'-phosphate in the first few days of life and the fourth within the first month. One of the siblings was electively treated from birth until a diagnosis was secured. Our cases demonstrate that early diagnosis and treatment can be associated with normal neurodevelopment in childhood. We suggest that a low threshold for investigating for pyridox(am)ine 5'-phosphate oxidase deficiency and electively treating with pyridoxal-5'-phosphate is considered in any neonate with encephalopathy, including those with presumed hypoxic ischemic encephalopathy in whom the degree of encephalopathy is not expected from perinatal history, cord gases and/or neuroimaging.

New structural brain imaging endophenotype in bipolar disorder.

Neuroimaging studies suggest anterior-limbic structural brain abnormalities in patients with bipolar disorder (BD), but few studies have shown these abnormalities in unaffected but genetically liable family members. In this study, we report morphometric correlates of genetic risk for BD using voxel-based morphometry. In 35 BD type I (BD-I) patients, 20 unaffected first-degree relatives (UAR) of BD patients and 40 healthy control subjects underwent 3 T magnetic resonance scanner imaging. Preprocessing of images used DARTEL (diffeomorphic anatomical registration through exponentiated lie algebra) for voxel-based morphometry in SPM8 (Wellcome Department of Imaging Neuroscience, London, UK). The whole-brain analysis revealed that the gray matter (GM) volumes of the left anterior insula and right inferior frontal gyrus showed a significant main effect of diagnosis. Multiple comparison analysis showed that the BD-I patients and the UAR subjects had smaller left anterior insular GM volumes compared with the healthy subjects, the BD-I patients had smaller right inferior frontal gyrus compared with the healthy subjects. For white matter (WM) volumes, there was a significant main effect of diagnosis for medial frontal gyrus. The UAR subjects had smaller right medial frontal WM volumes compared with the healthy subjects. These findings suggest that morphometric brain abnormalities of the anterior-limbic neural substrate are associated with family history of BD, which may give insight into the pathophysiology of BD, and be a potential candidate as a morphological endophenotype of BD.

Sequential combination of self-report, breath carbon monoxide, and saliva cotinine to assess smoking status.

The purpose of this analysis was to develop an algorithm for the cost effective and accurate assessment of smoking during the previous few days by combining self-report, breath carbon monoxide (BCO), and saliva cotinine (sCOT). These measurements are convenient, quantitative, and do not require invasive procedures. The data used to devise the algorithm were gathered during a treatment trial of participants seeking to stop smoking. Self-report of smoking was determined using a written questionnaire, BCO was measured with a handheld breathalyzer, and sCOT was quantified using a high sensitivity ELISA. Participants were 130 males and 97 females between the ages of 19 and 67 years who reported smoking at least 15 cigarettes a day and had a BCO level ≥ 15 ppm. Self-reports and BCO levels were collected at each of 6 visits (V0-V5) and sCOT levels were determined at V0 and V5. Based on the data collected, we recommend that the sequential determination of self-reported smoking, BCO level, and sCOT level be employed to assess smoking during the previous few days to minimize the higher cost and longer turnaround time associated with the sCOT test while maximizing accuracy.

Use of argatroban during multi-organ procurement: pharmacokinetics and sequelae in recipient of transplanted liver.

This report illustrates potential concerns regarding the administration of Argatroban (AGN), a small molecule, direct thrombin inhibitor, within the setting of multi-organ procurement (MOP). Herein, we outline the case of a large AGN bolus to the donor during MOP, and the passive transfer of a coagulopathy to the recipient of the transplanted liver. From this, we conclude that caution should be exercised when AGN is used in the setting of MOP.

Occupational, domestic and environmental mesothelioma risks in the British population: a case-control study.

We obtained lifetime occupational and residential histories by telephone interview with 622 mesothelioma patients (512 men, 110 women) and 1420 population controls. Odds ratios (ORs) were converted to lifetime risk (LR) estimates for Britons born in the 1940s. Male ORs (95% confidence interval (CI)) relative to low-risk occupations for >10 years of exposure before the age of 30 years were 50.0 (25.8-96.8) for carpenters (LR 1 in 17), 17.1 (10.3-28.3) for plumbers, electricians and painters, 7.0 (3.2-15.2) for other construction workers, 15.3 (9.0-26.2) for other recognised high-risk occupations and 5.2 (3.1-8.5) in other industries where asbestos may be encountered. The LR was similar in apparently unexposed men and women (approximately 1 in 1000), and this was approximately doubled in exposed workers' relatives (OR 2.0, 95% CI 1.3-3.2). No other environmental hazards were identified. In all, 14% of male and 62% of female cases were not attributable to occupational or domestic asbestos exposure. Approximately half of the male cases were construction workers, and only four had worked for more than 5 years in asbestos product manufacture.

Fronto-limbic brain structures in suicidal and non-suicidal female patients with major depressive disorder.

Our knowledge about the neurobiology of suicide is limited. It has been proposed that suicidal behavior generally requires biological abnormalities concomitant with the personality trait of impulsivity/aggression, besides an acute psychiatric illness or psychosocial stressor. We investigated fronto-limbic anatomical brain abnormalities in suicidal and non-suicidal adult female patients with unipolar depression. Our sample consisted of seven suicidal unipolar patients, 10 non-suicidal unipolar patients and 17 healthy female comparison subjects. The criterion for suicidality was one or more documented lifetime suicide attempts. A 1.5T GE Signa Imaging System running version Signa 5.4.3 software was used to acquire the magnetic resonance imaging images. All anatomical structures were measured blindly, with the subjects' identities and group assignments masked. We used analysis of covariance with age and intracranial volume as covariates and the Tukey-Kramer procedure to compare suicidal patients, non-suicidal patients and healthy comparison subjects. Suicidal patients had smaller right and left orbitofrontal cortex gray matter volumes compared with healthy comparison subjects. Suicidal patients had larger right amygdala volumes than non-suicidal patients. Abnormalities in the orbitofrontal cortex and amygdala in suicidal patients may impair decision-making and predispose these patients to act more impulsively and to attempt suicide.

Prefrontal hyperactivation during working memory task in untreated individuals with major depressive disorder.

The prefrontal cortex, a part of the limbic-thalamic-cortical network, participates in regulation of mood, cognition and behavior and has been implicated in the pathophysiology of major depressive disorder (MDD). Many neuropsychological studies demonstrate impairment of working memory in patients with MDD. However, there are few functional neuroimaging studies of MDD patients during working memory processing, and most of the available ones included medicated patients or patients with both MDD and bipolar disorder. We used functional magnetic resonance imaging (fMRI) to measure prefrontal cortex function during working memory processing in untreated depressed patients with MDD. Fifteen untreated individuals with Diagnostic and Statistical Manual of Mental Disorders-Fourth Edition recurrent MDD (mean age+/-s.d.=34.3+/-11.5 years) and 15 healthy comparison subjects (37.7+/-12.1 years) matched for age, sex and race were studied using a GE/Elscint 2T MR system. An echo-planar MRI sequence was used to acquire 24 axial slices. The n-back task (0-back, 1-back and 2-back) was used to elicit frontal cortex activation. Data were analyzed with a multiple regression analysis using the FSL-FEAT software. MDD patients showed significantly greater left dorsolateral cortex activation during the n-back task compared to the healthy controls (P<0.01), although task performance was similar in the two groups. Furthermore, the patients showed significant anterior cingulate cortex activation during the task, but the comparison subjects did not (P<0.01). This study provides in vivo imaging evidence of abnormal frontolimbic circuit function during working memory processing in individuals with MDD.

Trait impulsivity in patients with mood disorders.

BACKGROUND: Impulsivity is a key component of the manic behavior of bipolar disorder and is reported to occur in bipolar patients as a stable characteristic, i.e. a trait. Nevertheless, impulsivity has not been widely studied in depressed bipolar patients. We assessed impulsivity in depressed and euthymic bipolar and unipolar patients and healthy controls. We hypothesized that bipolar subjects would have higher levels of trait impulsivity than the comparison groups. METHODS: Twenty-four depressed bipolar, 24 depressed unipolar, 12 euthymic bipolar, and 10 euthymic unipolar patients, as well as 51 healthy subjects were evaluated with the Barratt Impulsiveness Scale (BIS). Analysis of covariance with age and sex as covariates was used to compare mean group differences. RESULTS: Depressed bipolar, euthymic bipolar, and depressed unipolar patients did not differ, and showed greater impulsivity than healthy controls on all of the BIS scales. Euthymic unipolar patients scored higher than healthy controls only on motor impulsivity. LIMITATIONS: Higher number of past substance abusers in the bipolar groups, and no control for anxiety and personality disorders, as well as small sample sizes, limit the reach of this study. CONCLUSIONS: This study replicates prior findings of stable trait impulsivity in bipolar disorder patients, and extends them, confirming that this trait can be demonstrated in depressed patients, as well as manic and euthymic ones. Trait impulsivity may be the result of repeated mood episodes or be present prior to their onset, either way it would influence the clinical presentation of bipolar disorder.

Multi-center randomized clinical trials in oral and maxillofacial surgery: modeling of fixed and random effects.

The multi-center randomized clinical trial (MCCT) is an important tool to evaluate treatment of rare diseases. An important and challenging analytic consideration is how to model the variability of the set of clinical centers composing an MCCT. The purpose of this paper was to demonstrate how changing the assumptions regarding the variability (fixed effect versus random effect) of the set of clinical centers may alter the results. The data for this paper were derived from a recently completed MCCT. The MCCT was designed as a prospective, randomized clinical trial comparing the stability of two techniques, i.e., wire versus rigid internal fixation (RIF), for stabilizing the mandible after bilateral sagittal split ramus osteotomy (BSSO) for patients requiring mandibular advancement. Three treatment centers were involved. The key outcome variable was change in mandibular position (B-point) over time. We developed two different analytic models by varying the underlying statistical assumptions regarding the variability of the clinical treatment centers, i.e., random or fixed effects. Analyses based on the random-effects model demonstrated no significant difference between treatment groups in terms of relapse (P=0.13). With the fixed-effects model, however, wire fixation had significantly more relapse at B-point over time than RIF (P=0.02). The results from these two sets of analyses demonstrate how changing assumptions regarding the variability of the set of clinical centers can alter the interpretation of the treatment effect. The choice of statistical modeling of the set of clinical centers is an important consideration when performing analyses of MCCTs and it is a decision that should be made prior to initiating the study.

Oral function and diet quality in a community-based sample.

Overall diet quality indices, such as the Healthy Eating Index (HEI), are preferred for epidemiological studies, yet studies in dentistry have focused on isolated dietary components. This study investigated the influence of socio-demographic and masticatory variables (masticatory performance, bite force, number of posterior functional tooth units, TMJ disorder, and dentition status) on overall diet quality in a community-based sample (n = 731). Cross-sectional data were derived from clinical examinations, bite force recordings, masticatory performance measurements, and two 24-hour dietary recalls. Females, European-Americans, and older subjects had better HEI scores than males, Mexican-Americans, and younger subjects, respectively. Income, education, and the masticatory variables were not related to diet quality. Analyses according to dentition status (good dentition, compromised dentition, partial denture, and complete dentures) showed no inter-group differences for HEI except for the age groups. The results suggest that the chewing-related factors evaluated in this sample are not predictors of overall diet quality across the socio-demographic groups.

Determinants of masticatory performance in dentate adults.

Masticatory performance results from a complex interplay of direct and indirect effects, yet most studies employ univariate models. This study tested a multivariate model of masticatory performance for dentate subjects. Explanatory variables included number of functional tooth units, bite force, sex, age, masseter cross-sectional area, presence of temporomandibular disorders, and presence of diabetes mellitus. The population-based sample consisted of 631 dentate subjects aged 37-80 years. Covariance structure analysis showed that 68% of the variability in masticatory performance could be explained by the combined effects of the explanatory variables. Age and sex did not show a strong effect on masticatory performance, either directly or indirectly through masseter cross-sectional area, temporomandibular disorders, and bite force. Number of functional tooth units and bite force were confirmed as the key determinants of masticatory performance, which suggests that their maintenance may be of major importance for promoting healthful functional status.

Positional change of the hyoid bone after bilateral sagittal split osteotomy with rigid and wire fixation.

The purpose of this study was to compare positional changes of the hyoid bone and the amount of postsurgical compensation in mandibular position in patients who received either wire or rigid fixation after surgery. Data were analyzed from 97 patients (25 males and 72 females) who were randomized to receive wire (43) or rigid (54) fixation after mandibular advancement surgery as part of a multicenter clinical trial. Radiographs were digitized before surgery (T2), immediately after surgery (T3), and 8 weeks (T4), 6 months (T5), 1 year (T6), and 2 years (T7) after surgery. The wire group had greater sagittal relapse of the hyoid bone at T6 (P =.007), which persisted at T7 (P =.02). Both groups showed upward movement of the hyoid bone after surgery. There was no relationship between the vertical change in the the hyoid bone position and the vertical position of mandible (B point y coordinate, mandibular plane). However, there was a relationship between the horizontal hyoid bone position and B point during the postsurgical period (rigid, r = 0.450; wire, r = 0.517). The direct distance from the hyoid bone to basion increased (P <.001) in both groups at T3 and then recovered its original length after 8 weeks (P <.001). The rigid group showed no significant change in distance from the hyoid to the genial tubercles, but the wire group showed recovery of the muscle length at T6 (P <.05) and T7 (P <.05).

Mandibular range of motion after bilateral sagittal split ramus osteotomy with wire osteosynthesis or rigid fixation.

OBJECTIVES: An analysis was conducted to compare mandibular range of motion among Class II patients treated with wire osteosynthesis or rigid internal fixation after surgical mandibular advancement. STUDY DESIGN: Patients randomly received wire osteosynthesis and 8 weeks of maxillomandibular fixation (n = 49) or rigid internal fixation (n = 78). Mandibular range of motion was measured 2 weeks before surgery and 8 weeks, 6 months, and 1, 2, and 5 years after surgery. RESULTS: Both groups showed decreased mobility in all movement dimensions that progressively recovered to near presurgical levels over the 5-year follow-up period. The difference in range of motion between treatment groups was not statistically significant. Changes in proximal and distal segment position could not explain decreased mobility. CONCLUSIONS: Similar decreases in mandibular mobility occurred with wire and rigid fixation of a bilateral sagittal split ramus osteotomy after surgery. Long-term changes were statistically, but not clinically, significant.

Is use of exogenous estrogen associated with temporomandibular signs and symptoms?

BACKGROUND: Studies of historical data suggest a link between exogenous estrogen use and referral for treatment for temporomandibular disorders, or TMDs. The purpose of the authors' study was to determine the association between exogenous estrogen use and signs and symptoms of TMD assessed by direct physical examination in a randomly selected community sample of primarily postmenopausal women. METHODS: A calibrated clinical examiner examined a stratified random sample of 510 women aged 37 to 82 years using the Craniomandibular Index, or CMI. All medications that subjects were taking at the time of the examination were identified by interview and examination of subjects' medication containers on two occasions. One hundred seventy-four subjects were taking medications containing estrogen, and 336 were taking no such medications. RESULTS: The muscle and joint signs and symptoms of women taking and not taking estrogen were not significantly different after the authors controlled for sociocultural, demographic and health care utilization variables. Estrogen use also failed to distinguish women receiving relatively high and low scores on the CMI. CONCLUSION: Estrogen replacement therapy does not place women at increased risk of developing TMDs. CLINICAL IMPLICATIONS: Clinicians need not be concerned that patients taking oral contraceptives or replacement estrogens are at increased risk of developing TMDs.

Combined effects of estrogen and progesterone on the anterior cruciate ligament.

Previous studies from the authors' laboratory have established the presence of estrogen and progesterone receptors in the human anterior cruciate ligament. The purpose of the current study was to investigate the combined effects of 1beta-estradiol and progesterone on cell proliferation and procollagen synthesis of the human anterior cruciate ligament fibroblasts. Fibroblast proliferation and procollagen synthesis in response to logarithmic concentrations of 17beta-estradiol (0.0025 ng/mL, 0.025 ng/mL, 0.25 ng/mL) and progesterone (1 ng/mL, 10 ng/mL, 100 ng/mL) were assessed with the measurement of 3H-thymidine incorporation and Types I and III procollagen specific equilibrium radioimmunoassays. On Days 1, 3, and 5 there was a dose dependent decrease in the fibroblast proliferation and procollagen Type I synthesis with increasing estradiol concentrations. The effect was attenuated with increasing progesterone concentrations. Controlling for estrogen levels, a dose dependent increase in fibroblast proliferation and procollagen Type I synthesis was observed with increasing progesterone concentrations. The effect was more pronounced at lower concentrations of estrogen, suggesting estrogen levels were the dominant factor. The effects of estrogen and progesterone became less apparent by Day 7. No significant differences in Type III procollagen synthesis were seen with varying estradiol concentrations at any of the designated times. These early physiologic changes in fibroblast proliferation and Type I procollagen synthesis may provide a biologic explanation for the increased anterior cruciate ligament injury rate observed in female athletes, suggesting the acute cyclical hormonal variations in the female athlete during menstruation predispose her to ligamentous injury.

Masticatory performance is not associated with diet quality in Class II orthognathic surgery patients.

This study evaluated the association between masticatory function, diet, and digestive system problems in 59 Class II patients 5 years after bilateral sagittal split osteotomy. Dietary intake data were recorded in 4-day diet diaries and analyzed for overall diet quality (Healthy Eating Index) and selected dietary components. Masticatory function was assessed through measurements of masticatory performance, maximum bilateral bite force, and chewing time and number of chewing strokes until the subject felt that the bolus was ready to swallow. Self-reported frequency of digestive system problems was recorded with a 7-point Likert scale questionnaire. Masticatory function was not associated with diet quality or gastrointestinal problems. There was a weak association between intake of foods that require chewing (eg, fiber, protein, meat, and vegetables) and masticatory variables. Fourteen subjects (24%) had a poor diet and 45 subjects (76%) had a diet that needed improvement according to the Healthy Eating Index. Self-reported constipation was the only digestive system problem that was significantly associated with masticatory performance.

The current status of psychological assessment training in graduate and professional schools.

Test-based psychological assessment is threatened by the policies of managed care organizations; however, research has demonstrated that test-based psychological assessment is quite valuable and economically justified when conducted by well-trained psychologists. This surfaces the question of the current status of graduate training in test-based psychological assessment. Results of this study indicate that clinical and counseling students currently receive almost equivalent training in test-based assessment. However, in a larger context, results indicate a lack of sound preparation in test-based assessment training for a large proportion of clinical and counseling students. These findings are discussed in terms of their implications for the field and, more specifically, for graduate and internship training.

Severity, distribution, and correlates of occlusal tooth wear in a sample of Mexican-American and European-American adults.

PURPOSE: The objective of this study was to determine the severity, distribution, and correlates of tooth wear in a sample of Mexican-American and European-American adults drawn from a community-based longitudinal aging study on oral health. MATERIALS AND METHODS: The maxillary teeth of 71 subjects enrolled in a longitudinal aging study were assessed using a previously introduced five-point (0 to 4) ordinal scoring system in which each tooth is given a score describing the severity of wear. The tooth wear scores were compared with data concerning demographic factors, functional/parafunctional habits, soft drink consumption, and bite force measurements to determine specific correlates of tooth wear. RESULTS: The mean wear score for all teeth was 1.50 on the five-point scale. There was a significant difference between the mean wear score of anterior teeth (1.85) and posterior teeth (1.17). Bivariate analyses detected a moderate degree of correlation between maxillary tooth wear and age and bite force. Maxillary tooth wear was significantly greater in males and in subjects with reported teeth clenching/grinding. Multivariate analyses revealed that age, gender, bite force, self-reported teeth clenching/grinding, and number of daily meals/snacks had significant correlations with maxillary tooth wear. CONCLUSION: The overall severity of maxillary tooth wear in this sample of Mexican-American and European-American adults was low, with anterior teeth having a greater degree of wear than posterior teeth. Age, gender, bite force, teeth clenching/grinding, and number of daily meals/snacks are potential factors that may have contributed to tooth wear in the study sample.