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1.
Brain ; 146(8): 3484-3499, 2023 08 01.
Article in English | MEDLINE | ID: mdl-36811945

ABSTRACT

Chronic post-concussive symptoms are common after mild traumatic brain injury (mTBI) and are difficult to predict or treat. Thalamic functional integrity is particularly vulnerable in mTBI and may be related to long-term outcomes but requires further investigation. We compared structural MRI and resting state functional MRI in 108 patients with a Glasgow Coma Scale (GCS) of 13-15 and normal CT, and 76 controls. We examined whether acute changes in thalamic functional connectivity were early markers for persistent symptoms and explored neurochemical associations of our findings using PET data. Of the mTBI cohort, 47% showed incomplete recovery 6 months post-injury. Despite the absence of structural changes, we found acute thalamic hyperconnectivity in mTBI, with specific vulnerabilities of individual thalamic nuclei. Acute fMRI markers differentiated those with chronic post-concussive symptoms, with time- and outcome-dependent relationships in a sub-cohort followed longitudinally. Moreover, emotional and cognitive symptoms were associated with changes in thalamic functional connectivity to known serotonergic and noradrenergic targets, respectively. Our findings suggest that chronic symptoms can have a basis in early thalamic pathophysiology. This may aid identification of patients at risk of chronic post-concussive symptoms following mTBI, provide a basis for development of new therapies and facilitate precision medicine application of these therapies.


Subject(s)
Brain Concussion , Brain Injuries , Post-Concussion Syndrome , Humans , Brain Concussion/complications , Brain Concussion/diagnostic imaging , Post-Concussion Syndrome/diagnostic imaging , Thalamus/diagnostic imaging , Emotions , Magnetic Resonance Imaging , Brain
2.
Lymphology ; 55(3): 110-116, 2022.
Article in English | MEDLINE | ID: mdl-36446398

ABSTRACT

Lymphedema is a debilitating disease characterized by abnormal lymphatic drainage, either due to primary maldevelopment of the lymphatic system or to secondary injury. The clinical features of primary and secondary lymphedema differ, with primary lymphedema more often involving progressive bilateral lower extremity disease as compared to secondary lymphedema characteristically having more localized symptoms related to the origin of injury. This case presentation describes a patient who presented with bilateral lower extremity swelling, left greater than the right, with imaging results to support the diagnosis of lymphedema. During the time he was followed in our clinic, our team witnessed rapid progression of his lymphedema despite compliance with conservative management. We believe that the primary mechanism of systemic damage to our patient's lymphatic system is the lenalidomide and bortezomib therapy prescribed to treat multiple myeloma. This review explores the relationship between lenalidomide, bortezomib, and lymphedema in efforts of understanding this unique pathology of iatrogenic lymphedema mimicking primary nature.


Subject(s)
Lymphedema , Multiple Myeloma , Male , Humans , Multiple Myeloma/drug therapy , Lenalidomide/adverse effects , Bortezomib/adverse effects , Lymphedema/diagnosis , Lymphedema/etiology , Lymphedema/therapy , Iatrogenic Disease
3.
Neuroimage ; 245: 118752, 2021 12 15.
Article in English | MEDLINE | ID: mdl-34823024

ABSTRACT

AIMS: Non-invasive measures of brain iron content would be of great benefit in neurodegeneration with brain iron accumulation (NBIA) to serve as a biomarker for disease progression and evaluation of iron chelation therapy. Although magnetic resonance imaging (MRI) provides several quantitative measures of brain iron content, none of these have been validated for patients with a severely increased cerebral iron burden. We aimed to validate R2* as a quantitative measure of brain iron content in aceruloplasminemia, the most severely iron-loaded NBIA phenotype. METHODS: Tissue samples from 50 gray- and white matter regions of a postmortem aceruloplasminemia brain and control subject were scanned at 1.5 T to obtain R2*, and biochemically analyzed with inductively coupled plasma mass spectrometry. For gray matter samples of the aceruloplasminemia brain, sample R2* values were compared with postmortem in situ MRI data that had been obtained from the same subject at 3 T - in situ R2*. Relationships between R2* and tissue iron concentration were determined by linear regression analyses. RESULTS: Median iron concentrations throughout the whole aceruloplasminemia brain were 10 to 15 times higher than in the control subject, and R2* was linearly associated with iron concentration. For gray matter samples of the aceruloplasminemia subject with an iron concentration up to 1000 mg/kg, 91% of variation in R2* could be explained by iron, and in situ R2* at 3 T and sample R2* at 1.5 T were highly correlated. For white matter regions of the aceruloplasminemia brain, 85% of variation in R2* could be explained by iron. CONCLUSIONS: R2* is highly sensitive to variations in iron concentration in the severely iron-loaded brain, and might be used as a non-invasive measure of brain iron content in aceruloplasminemia and potentially other NBIA disorders.


Subject(s)
Brain/diagnostic imaging , Brain/metabolism , Ceruloplasmin/deficiency , Iron Metabolism Disorders/diagnostic imaging , Iron Metabolism Disorders/metabolism , Iron/metabolism , Magnetic Resonance Imaging/methods , Neurodegenerative Diseases/diagnostic imaging , Neurodegenerative Diseases/metabolism , Autopsy , Ceruloplasmin/metabolism , Humans , Male , Middle Aged , Netherlands , Phenotype
4.
J Clin Psychiatry ; 82(3)2021 05 25.
Article in English | MEDLINE | ID: mdl-34033709

ABSTRACT

Objective: To evaluate the efficacy of psychosocial treatments for posttraumatic stress disorder (PTSD) among individuals with a comorbid severe mental illness (SMI; ie, schizophrenia, bipolar disorder, major depressive disorder).Data Sources: PubMed, PsycINFO, CINAHL, and Cochrane Library were searched from January 1998 to March 2020 using keywords related to PTSD, treatment, and severe mental illness.Study Selection: All clinical trials for PTSD psychotherapy among individuals with SMI were included. From 38 potentially eligible studies, a total of 14 clinical trials across 684 individuals with comorbid SMI and PTSD were identified and included in the analysis.Data Extraction: Data on demographic, SMI diagnosis, symptom severity, sample attrition, and treatment protocol received were extracted. Effect size calculations and subsequent meta-analyses were conducted using the Meta-Analysis Package for R (metafor) version 2.1-0 in R (3.6.0).Results: PTSD treatments had a large effect on PTSD outcomes among individuals with SMI, with patients experiencing a standard deviation reduction in PTSD symptomatology pre- to post-treatment (g = -1.009, P < .001, k = 34). Prolonged exposure (g = -1.464; P < .001; SE = 0.276; k = 5), eye movement desensitization and reprocessing (g = -1.351; P < .001; SE = 0.276; k = 5), and brief treatment program (g = -1.009; P < .001; SE = 0.284; k = 5) had the largest effects on PTSD symptoms.Conclusions: Although underrepresented in the PTSD literature, PTSD psychotherapies are effective for individuals with SMI. Treatments with an exposure-based component may have greater efficacy in this clinical population.


Subject(s)
Bipolar Disorder/therapy , Depressive Disorder, Major/therapy , Outcome Assessment, Health Care , Psychotherapy/statistics & numerical data , Schizophrenia/therapy , Stress Disorders, Post-Traumatic/epidemiology , Stress Disorders, Post-Traumatic/therapy , Bipolar Disorder/epidemiology , Comorbidity , Depressive Disorder, Major/epidemiology , Eye Movement Desensitization Reprocessing/statistics & numerical data , Humans , Implosive Therapy/statistics & numerical data , Psychotherapy, Brief/statistics & numerical data , Schizophrenia/epidemiology
5.
Poult Sci ; 99(10): 5065-5069, 2020 Oct.
Article in English | MEDLINE | ID: mdl-32988543

ABSTRACT

The objective of this study was to investigate the effect of different durations of time delay when sampling digesta from the gizzard and ileum of broilers on the degradation of myo-inositol hexakisphosphate (InsP6) and digestibility of phosphorus (P). There was 1 experimental diet with a supplemental phytase activity of 1,212 phytase units/kg feed, which was provided to birds from day 13 to 18 after hatching. The diet was formulated to provide 6.6 g/kg Ca and 1.9 g/kg nonphytate P and fed to 24 cages of 6 birds. The 24 cages of birds were further randomly divided into 6 subgroups of 4 cages from which the digesta samples in the gizzard and ileum were collected at 0, 5, 10, or 20 min postmortem. The results showed that the concentration of InsP6 decreased linearly (P = 0.002), InsP5 decreased quadratically (P = 0.038), and the summation of concentrations of P in InsP6-4 decreased linearly (P = 0.028) in the gizzard digesta with the increasing delay of sampling. In the ileum, the digestibility of phytate P tended to decrease linearly (P = 0.087), and the digestibility of total P decreased linearly (P = 0.026) with prolonged delay. In conclusion, delay in sampling could alter the measured profile of InsP esters in gizzard digesta probably because of a continued effect of supplemental phytase, while the ileal digestibility of total P could diminish. Therefore, standard sampling procedures should be implemented to minimize variance.


Subject(s)
6-Phytase , Chickens , Dietary Supplements , Digestion , Gizzard, Avian , Phosphorus, Dietary , Phytic Acid , 6-Phytase/metabolism , Animal Feed/analysis , Animal Nutritional Physiological Phenomena , Animals , Chickens/physiology , Diet/veterinary , Digestion/physiology , Gizzard, Avian/chemistry , Ileum/metabolism , Phosphorus, Dietary/metabolism , Phytic Acid/chemistry , Phytic Acid/metabolism , Random Allocation , Time Factors
6.
Orphanet J Rare Dis ; 15(1): 105, 2020 04 25.
Article in English | MEDLINE | ID: mdl-32334607

ABSTRACT

BACKGROUND: Aceruloplasminemia is a rare genetic iron overload disorder, characterized by progressive neurological manifestations. The effects of iron chelation on neurological outcomes have only been described in case studies, and are inconsistent. Aggregated case reports were analyzed to help delineate the disease-modifying potential of treatment. METHODS: Data on clinical manifestations, treatment and neurological outcomes of treatment were collected from three neurologically symptomatic Dutch patients, who received deferiprone with phlebotomy as a new therapeutic approach, and combined with other published cases. Neurological outcomes of treatment were compared between patients starting treatment when neurologically symptomatic and patients without neurological manifestations. RESULTS: Therapeutic approaches for aceruloplasminemia have been described in 48 patients worldwide, including our three patients. Initiation of treatment in a presymptomatic stage of the disease delayed the estimated onset of neurological manifestations by 10 years (median age 61 years, SE 5.0 vs. median age 51 years, SE 0.6, p = 0.001). Although in 11/20 neurologically symptomatic patients neurological manifestations remained stable or improved during treatment, these patients were treated significantly shorter than patients who deteriorated neurologically (median 6 months vs. median 43 months, p = 0.016). Combined iron chelation therapy with deferiprone and phlebotomy for up to 34 months could be safely performed in our patients without symptomatic anemia (2/3), but did not prevent further neurological deterioration. CONCLUSIONS: Early initiation of iron chelation therapy seems to postpone the onset of neurological manifestations in aceruloplasminemia. Publication bias and significant differences in duration of treatment should be considered when interpreting reported treatment outcomes in neurologically symptomatic patients. Based on theoretical grounds and the observed long-term safety and tolerability in our study, we recommend iron chelation therapy with deferiprone in combination with phlebotomy for aceruloplasminemia patients without symptomatic anemia.


Subject(s)
Chelation Therapy , Iron Metabolism Disorders , Ceruloplasmin/deficiency , Humans , Iron , Iron Metabolism Disorders/drug therapy , Middle Aged , Neurodegenerative Diseases
7.
Poult Sci ; 98(12): 6742-6750, 2019 Dec 01.
Article in English | MEDLINE | ID: mdl-31287893

ABSTRACT

Phytase is of importance to the poultry industry because of its ability to hydrolyze phytate and release phosphorus (P) for use by poultry. However, the effect of age on phytase efficacy is not fully understood. A total of 864 day-old broiler chicks were used to investigate the effect of age and feeding length on phytase efficacy using growth performance, mineral utilization, and tibia ash as response criteria of evaluation. The experiment was arranged as a 3 × 2 × 2 factorial in a randomized complete block design with 3 diets including; a positive control (PC; 0.4% non-phytate P (nPP)), a negative control (NC; 0.2% nPP) and a NC diet supplemented with phytase at 2,000 FYT/kg; 2 ages (i.e., days 14 and 22); and 2 feeding lengths (i.e., 2 and 5 D) with 8 replicates each. Birds fed the NC had decreased (P < 0.01) body weight gain and feed efficiency compared with birds fed the PC regardless of age or feeding length. Similarly, birds fed the phytase-supplemented diet had improved (P < 0.01) performance as compared to birds fed the NC regardless of age. There were no significant differences in P utilization between birds fed for 2 to 14 D or 22 D and birds fed for 5 D to both ages. However, phytase was more efficacious at day 14 than day 22 when mineral utilization was considered because the super dose of phytase elicited greater response in birds fed the phytase supplemented diet for 2 D until day 14. In contrast, percentage tibia ash improved (P < 0.01) in birds fed phytase supplemented diet for 5 D at both ages as compared with birds fed for 2 D. In conclusion, testing phytase products, even at high doses, for 2 D during the second week in the life cycle of broiler chicks, can be recommended from the results of this study.


Subject(s)
6-Phytase/metabolism , Chickens/physiology , Weight Gain/drug effects , 6-Phytase/administration & dosage , Age Factors , Animal Feed/analysis , Animals , Chickens/growth & development , Diet/veterinary , Dietary Supplements/analysis , Dose-Response Relationship, Drug , Male , Random Allocation , Time Factors
8.
Poult Sci ; 98(6): 2588-2597, 2019 Jun 01.
Article in English | MEDLINE | ID: mdl-30753622

ABSTRACT

A total of 1,408 male broiler chickens were used to evaluate the impact of age and duration of feeding low-phosphorus (P) diet on the efficacy of phytase using growth performance, nutrient utilization, tibia ash, and plasma indices. Diets were formulated with 2 non-phytate P (nPP) concentrations (i.e., 0.20 and 0.40%) and 2 phytase concentrations (i.e., 1,000 and 2,000 FTU/kg) added to the 0.20% nPP diet. Four dietary treatments with 8 replicate cages each were fed to broiler chicks at different ages and for different duration. Specifically, these were days 6 to 8 (12 birds per replicate), 12 to 14, 9 to 14, 20 to 22, or 6 to 22 (8 birds per replicate). Parameters were measured on the last day of each period. Duration of feeding effect was examined by comparing responses of birds fed for 2 or 5 D at day 14 and for 2 or 16 D at day 22; age effect was determined by comparing responses of birds fed for 2 D at age 8, 14 and 22 D post-hatching. Body weight gain and gain-to-feed ratio were increased (P < 0.01) in birds fed diets supplemented with phytase; however, an increase in duration of feeding improved (P < 0.01) feed efficiency with birds fed for 16 D performing better than birds fed for 2 D at day 22. In addition, phytase supplementation improved (P < 0.01) apparent P and calcium digestibility and retention, but the age effect on phytase efficacy was more apparent at day 14 and the duration of feeding effect was evident in birds fed for 2 D due to the increased levels of mineral utilization at that age/duration of feeding as compared with the other groups. The results of this study show that phytase efficacy was at optimum in birds fed low-P diet for 2 D at day 14. This period can be recommended for further bioefficacy studies of phytase.


Subject(s)
6-Phytase/pharmacology , Age Factors , Chickens/metabolism , Diet/veterinary , 6-Phytase/administration & dosage , Animal Feed/analysis , Animal Nutritional Physiological Phenomena , Animals , Calcium/metabolism , Chickens/growth & development , Male , Phosphorus/metabolism
9.
Poult Sci ; 98(3): 1302-1309, 2019 Mar 01.
Article in English | MEDLINE | ID: mdl-30285128

ABSTRACT

The objective was to determine effects of adding phytase, amylase, and a cocktail of non-starch polysaccharide-degrading enzymes (NSPase) individually or in combinations to corn-soybean meal-based diet for broilers on apparent ileal digestibility (AID) of nutrients and dietary AMEn value. Four hundred and eighty male broiler chicks were divided into 80 groups and fed 8 diets in a completely randomized design (10 groups/diet) from day 15 to 21 of age. The diets were basal diet unsupplemented or supplemented with phytase (1,500 FTU/kg; Ronozyme HiPhos), amylase (80 KNU/kg, Ronozyme HiStarch), and NSPase (75 g/metric ton, Ronozyme Multigrain) individually or in all possible combinations. The basal diet contained the phytase at 1,000 FTU/kg, and was formulated to meet the NRC (1994) recommended nutrient requirements for broiler chickens except for ME, Ca, and non-phytate P, which were reduced by 150 kcal/kg, 0.18%, and 0.15%, respectively. Addition of phytase to the basal diet increased (P < 0.05) AID of P from 40.4 to 59.3%. Addition of amylase, NSPase or a combination of amylase and NSPase to the phytase-supplemented basal diet further increased (P < 0.05) AID of P to 63.4, 69.9, and 67.3%, respectively. Addition of phytase, amylase or a combination of amylase and NSPase to the basal diet did not affect dietary AMEn value. However, addition of NSPase alone or a combination of phytase and amylase or of phytase and NSPase to the basal diet improved (P < 0.05) dietary AMEn value from 3,203 to 3,339, 3,309 or 3,289 kcal/kg, respectively. In conclusion, it is more beneficial (with regard to AID of P and dietary AMEn) to add amylase and NSPase to phytase-supplemented diets for broilers. Because the basal diet contained phytase at 1,000 FTU/kg, the increase in AID of P due to supplemental phytase (1,500 FTU/kg) indicates that supplemental phytase at 2,500 FTU/kg is more beneficial with regard to improving AID of P than supplemental phytase at 1,000 FTU/kg.


Subject(s)
Animal Feed/analysis , Chickens/physiology , Energy Intake/drug effects , Enzymes/administration & dosage , 6-Phytase/administration & dosage , Amylases/administration & dosage , Animal Nutritional Physiological Phenomena , Animals , Diet/veterinary , Digestion/physiology , Ileum/drug effects , Male
10.
Transl Psychiatry ; 8(1): 222, 2018 10 15.
Article in English | MEDLINE | ID: mdl-30323205

ABSTRACT

Placebo responses in depression exemplify how expectancies and appraisals impact mood. Cognitive and neural mechanisms underlying these responses are still poorly understood, partly due to the difficulty of simulating antidepressant effects and manipulating mood experimentally. To address these challenges, we developed an acute antidepressant placebo experiment involving the intravenous administration of a "fast-acting antidepressant" and a trial-by-trial sham fMRI "neurofeedback" manipulation, purporting to reveal mood-relevant neural responses. Twenty volunteers with major depression underwent this experiment while rating their expected and actual mood improvement. Mixed-effects analyses of trial-by-trial ratings revealed that the "drug" infusion cues induced higher expectancies of mood improvement, while both the "drug" infusion cue and the sham neurofeedback induced a reported mood improvement. Neurofeedback of greater magnitude, compared to lower magnitude, recruited the lateral prefrontal cortex (lPFC). Individuals with greater lPFC responses to neurofeedback displayed: (1) greater effect of previous mood improvement on expectancy ratings and (2) greater effect of sham neurofeedback on mood improvement. Behavioral antidepressant placebo effects were additionally moderated by changes in peripheral ß-endorphin plasma levels and depressive symptomatology. These data demonstrate the feasibility of trial-by-trial manipulation of antidepressant placebo-associated expectancies and their reinforcement. We provide initial insights into the role of the lPFC in the interplay between placebo-induced expectancies and mood, as well as preliminary evidence for the role of the opioid system in antidepressant placebo effects.


Subject(s)
Antidepressive Agents/therapeutic use , Depressive Disorder, Major/physiopathology , Depressive Disorder, Major/therapy , Placebo Effect , Prefrontal Cortex/physiopathology , Reinforcement, Psychology , Adolescent , Adult , Brain Mapping , Depressive Disorder, Major/drug therapy , Female , Humans , Magnetic Resonance Imaging , Male , Middle Aged , Neurofeedback , Treatment Outcome , Young Adult
11.
Ecol Appl ; 28(7): 1924-1934, 2018 10.
Article in English | MEDLINE | ID: mdl-30184292

ABSTRACT

Wild bee populations have undergone declines in recent years across much of the Western world, and these declines have the potential to limit yield in pollination-dependent crops. Highbush blueberry, Vaccinium corymbosum, and tart cherry, Prunus cerasus, are spring-blooming crops that rely on the movement of pollen by bees and other insects for pollination. Wild bee populations can be increased on farmland by providing floral resources, but whether the addition of these plants translates into increased pollinator density on crop flowers has not been documented in most cropping systems. To determine the importance of providing additional floral resources for wild bee pollinator communities, we selected blueberry fields and tart cherry orchards with and without herbaceous floral enhancements in western Michigan, USA. The bee communities visiting crop flowers, enhancements and control grassy field margins were sampled over a 5-yr period. In addition, the pollen diets of the most abundant wild bee crop pollinators were quantified across Michigan to better understand their foraging niches and to identify potentially important alternative host plants. The presence of floral enhancements did not increase the abundance of wild bees on either blueberry or cherry flowers during bloom. The bee community visiting blueberry was evenly composed of short-season bees that fly only during the spring and long-season bees that fly in both spring and summer. In contrast, the bee community visiting cherry was dominated by short-season spring bees. The majority of pollen collected by the wild bee communities visiting blueberry and cherry was from spring-flowering woody plants, with limited use of the herbaceous enhancements. Enhancements attracted greater abundance and species richness of bees compared to control areas, including twice as many floral specialists. Conserving summer-flying, grassland-associated bees is an appropriate goal for pollinator conservation programs. However, herbaceous enhancements may not provide adequate resources for the wild bees that pollinate spring-flowering crops. This study demonstrates that an examination of the pollen collected by wild bees across their flight periods can identify plant species to help them persist in intensively managed landscapes.


Subject(s)
Bees/physiology , Biodiversity , Diet , Plants , Pollen , Animals , Crops, Agricultural , Feeding Behavior , Flowers , Michigan , Seasons
12.
Ann R Coll Surg Engl ; 100(4): 326-329, 2018 Apr.
Article in English | MEDLINE | ID: mdl-29543050

ABSTRACT

Introduction Transurethral resection of the prostate (TURP) is considered the gold standard surgical treatment for lower urinary tract symptoms (LUTS) secondary to benign prostatic hyperplasia. The number of TURPs performed has declined significantly over the last three decades owing to pharmaceutical therapy. TURP data from a single institution for the years 1990, 2000 and 2010 were compared to assess the difference in performance. Methods A retrospective analysis was undertaken of all patients who underwent TURP between January and December 2010. These findings were compared with historical data for the years 1990 and 2000: 100 sets of case notes were selected randomly from each of these years. Results The number of TURPs performed fell from 326 in 1990 to 113 in 2010. The mean age of patients increased from 70.6 years to 74.0 years. There was also a significant increase in the mean ASA grade from 1.9 to 2.3. The most common indication for TURP shifted from LUTS to acute urinary retention. No significant change in operating time was observed. The mean resection weight remained constant (22.95g in 1990, 22.55g in 2000, 20.76g in 2010). A reduction in transfusion rates was observed but there were higher rates of secondary haematuria and bladder neck stenosis. There was an increase from 2% to 11.5% of patients with long-term failure to void following TURP. Conclusions The number of TURPs performed continues to decline, which could lead to potential training issues. Urinary retention is still by far the most common indication. However, there has been a significant rise in the percentage of men presenting for TURP with high pressure chronic retention. The number of patients with bladder dysfunction who either have persistent storage LUTS or eventually require long-term catheterisation or intermittent self-catheterisation has increased markedly, which raises the question of what the long-term real life impact of medical therapy is on men with LUTS secondary to benign prostatic hyperplasia who eventually require surgery.


Subject(s)
Blood Transfusion/statistics & numerical data , Lower Urinary Tract Symptoms/surgery , Prostatic Hyperplasia/surgery , Transurethral Resection of Prostate/trends , Urinary Retention/surgery , Adult , Age Factors , Aged , Aged, 80 and over , Blood Loss, Surgical/statistics & numerical data , Hematuria/epidemiology , Hematuria/etiology , Humans , Lower Urinary Tract Symptoms/etiology , Male , Middle Aged , Postoperative Complications/epidemiology , Postoperative Complications/etiology , Prostate/surgery , Prostatic Hyperplasia/complications , Retrospective Studies , Transurethral Resection of Prostate/adverse effects , Transurethral Resection of Prostate/statistics & numerical data , Treatment Outcome , Urinary Bladder Neck Obstruction/epidemiology , Urinary Bladder Neck Obstruction/etiology , Urinary Retention/etiology
13.
J Geriatr Oncol ; 9(3): 214-220, 2018 05.
Article in English | MEDLINE | ID: mdl-29174187

ABSTRACT

OBJECTIVES: To examine the associations of comorbidity and chemotherapy with breast cancer- and non-breast cancer-related death. MATERIALS AND METHODS: Included were women with invasive locoregional breast cancer diagnosed in 2004 from seven population-based cancer registries. Data were abstracted from medical records and verified with treating physicians when there were inconsistencies and missing information on cancer treatment. Comorbidity severity was quantified using the Adult Comorbidity Evaluation 27. Treatment guideline concordance was determined by comparing treatment received with the National Comprehensive Cancer Network guidelines. Kaplan-Meier method and multivariable Cox proportional hazards regressions were employed for statistical analyses. RESULTS: Of 5852 patients, 76% were under 70years old and 69% received guideline concordant adjuvant chemotherapy. Comorbidity was more prevalent in women age 70 and older (79% vs. 51%; p<0.001). After adjusting for tumor characteristics and treatment, severe comorbidity burden was associated with significantly higher cancer-related mortality in older patients (Hazard Ratio [HR]=2.38, 95% CI 1.08-5.24), but not in younger patients (HR=1.78, 95% CI 0.87-3.64). Among patients receiving guideline adjuvant chemotherapy, cancer-related mortality was significantly higher in older patients (HR=2.35, 95% CI 1.52-3.62), and those with severe comorbidity (HR=3.79, 95% CI 1.72-8.33). CONCLUSIONS: Findings suggest that, compared to women with no comorbidity, patients with breast cancer age 70 and older with severe comorbidity are at increased risk of dying from breast cancer, even after adjustment for adjuvant chemotherapy and other tumor and treatment differences. This information adds to risk-benefit discussions and emphasizes the need for further study of the role for adjuvant chemotherapy in these patient groups.


Subject(s)
Breast Neoplasms/mortality , Chemotherapy, Adjuvant/adverse effects , Comorbidity , Severity of Illness Index , Age Factors , Aged , Aged, 80 and over , Breast Neoplasms/drug therapy , Breast Neoplasms/epidemiology , Chemotherapy, Adjuvant/statistics & numerical data , Female , Humans , Kaplan-Meier Estimate , Neoplasm Staging , Practice Guidelines as Topic , Proportional Hazards Models , Registries , Retrospective Studies , Risk Assessment
14.
Subst Use Misuse ; 52(11): 1486-1493, 2017 09 19.
Article in English | MEDLINE | ID: mdl-28471275

ABSTRACT

BACKGROUND: Many youth initiate opioid misuse with prescription opioids and transition over time to more severe substance-using behaviors, including injection. Trait mindfulness is a potentially protective factor. OBJECTIVES: This is a cross-sectional study characterizing a sample of opioid-using youth by level of mindfulness and examines the potential effect modification of emotion regulation on the relationship between mindfulness and progression to injection opioid use. METHODS: A convenience sample of 112 youth (ages 14-24) was recruited during an episode of inpatient detoxification and residential treatment for opioid use disorders. We examined emotion regulation (Difficulties in Emotion Regulation Scale), mindfulness (Child Acceptance and Mindfulness Measure), and opioid use. We completed multivariable regressions stratified by degree of emotion regulation looking at relationship of mindfulness on time to injection use from age of first prescription opioid. RESULTS: Youth had difficulties in emotion regulation (m = 104.2; SD = 2.41) and low mindfulness (m = 19.1;SD = 0.59). While we found overall that mindfulness was associated with time to progression to injection opioid use, there was significant effect modification. Among youth with high levels of difficulty in emotion regulation, those with high mindfulness trait had quicker progressions to injection (-1.31 years; p =.003). In contrast, youth with normal emotion regulation and high mindfulness trait had a slower progression to injection (1.67 years; p =.041). Conclusion/Importance: Our study showed a majority of youth presenting with opioid use disorders have impairments in emotion regulation and deficits in trait mindfulness. The relationship between mindfulness and opioid use is impacted by emotion regulation capacity. More research is needed to understand the various facets of mindfulness and how they interact with emotion regulation in youth.


Subject(s)
Analgesics, Opioid/administration & dosage , Mindfulness , Opioid-Related Disorders/psychology , Personality , Substance Abuse, Intravenous/psychology , Adolescent , Cross-Sectional Studies , Disease Progression , Female , Humans , Male , Young Adult
15.
J Helminthol ; 91(3): 267-277, 2017 May.
Article in English | MEDLINE | ID: mdl-27240605

ABSTRACT

The successful use of helminths as therapeutic agents to resolve inflammatory disease was first recorded 40 years ago. Subsequent work in animal models and in humans has demonstrated that the organisms might effectively treat a wide range of inflammatory diseases, including allergies, autoimmune disorders and inflammation-associated neuropsychiatric disorders. However, available information regarding the therapeutic uses and effects of helminths in humans is limited. This study probes the practices and experiences of individuals 'self-treating' with helminths through the eyes of their physicians. Five physicians monitoring more than 700 self-treating patients were interviewed. The results strongly support previous indications that helminth therapy can effectively treat a wide range of allergies, autoimmune conditions and neuropsychiatric disorders, such as major depression and anxiety disorders. Approximately 57% of the self-treating patients observed by physicians in the study had autism. Physicians reported that the majority of patients with autism and inflammation-associated co-morbidities responded favourably to therapy with either of the two most popular organisms currently used by self-treaters, Hymenolepis diminuta and Trichuris suis. However, approximately 1% of paediatric patients experienced severe gastrointestinal pains with the use of H. diminuta, although the symptoms were resolved with an anti-helminthic drug. Further, exposure to helminths apparently did not affect the impaired comprehension of social situations that is the hallmark of autism. These observations point toward potential starting points for clinical trials, and provide further support for the importance of such trials and for concerted efforts aimed at probing the potential of helminths, and perhaps other biologicals, for therapeutic use.


Subject(s)
Biological Therapy/methods , Hymenolepis diminuta/growth & development , Inflammation/therapy , Self Administration/methods , Trichuris/growth & development , Animals , Humans , Treatment Outcome
16.
Poult Sci ; 96(3): 574-580, 2017 Mar 01.
Article in English | MEDLINE | ID: mdl-27578878

ABSTRACT

Wheat distillers' dried grains with solubles (DDGS) are being used increasingly in the poultry feed industry but their nutritional value is variable. The aim of this experiment was to examine the effect of batch to batch variation of wheat DDGS produced by the same manufacturer on the growth performance, dietary N corrected apparent metabolizable energy (AMEn), energy conversion ratio (ECR), total tract dry matter retention (DMR), nitrogen retention (NR) and fat digestibility (FD) coefficients when fed to broilers in complete diets with and without enzyme supplementation. Six UK wheat DDGS samples, produced by a single manufacturer, were used in a broiler experiment. Six diets containing 150 g/kg of each selected wheat DDGS sample were mixed. Each diet was then split into two batches and one of them was supplemented with commercial enzyme preparation, providing 1220 units xylanase and 152 units of ß-glucanase/kg diet, resulting in 12 experimental diets. Each diet was fed ad libitum to five pens of two male Ross 308 broilers from 7 to 21 d old. Enzyme supplementation improved dietary AMEn, DMR, NR (P < 0.001) and FD (P < 0.05) compared to non-supplemented diets. There was DDGS sample by enzyme interaction (P < 0.05) on daily weight gain and ECR. The results suggest that the variability in AMEn of DDGS samples produced from a single manufacturer is greater than expected compared to the variability of whole wheat samples but substantially lower than expected from wheat DDGS samples from different EU manufacturers. This experiment has shown that the variation in feeding value of wheat DDGS may be explained by the variability in polysaccharide contents.


Subject(s)
Animal Nutritional Physiological Phenomena , Cellulases/metabolism , Chickens/physiology , Diet/veterinary , Dietary Supplements , Endo-1,4-beta Xylanases/metabolism , Triticum/metabolism , Animal Feed/analysis , Animals , Cellulases/administration & dosage , Chickens/growth & development , Dietary Supplements/analysis , Digestion/physiology , Edible Grain/chemistry , Endo-1,4-beta Xylanases/administration & dosage , Energy Metabolism , Male , Nitrogen/metabolism , Nutritive Value , Triticum/chemistry
17.
Plant Biol (Stuttg) ; 18(1): 124-31, 2016 Jan.
Article in English | MEDLINE | ID: mdl-25865269

ABSTRACT

Reproduction is a crucial stage in the naturalisation of introduced plant species. Here, using breeding system experiments and observations of floral visitors, we investigate whether a lack of pollinators or an inability to autonomously self-fertilise limits naturalisation in five Australian Banksia species and the co-familial Hakea salicifolia in South Africa. Banksia species were heavily utilised by native insects and nectar-feeding birds. Although Banksia produced fruit when pollinators were excluded, pollinators significantly increased seed set in four of the five species. H. salicifolia flowers were visited by 11 insect species; honeybees (Apis mellifera) were the main visitors. Flowers in naturalised H. salicifolia populations received almost four times the number of visits as flowers in non-naturalised populations; the latter showed both pollen limitation (PLI 0.40) and partial self-incompatibility. This should not prevent invasion, since H. salicifolia produces fruits via autonomous selfing in the absence of pollinators. The results suggest a limited role of breeding systems in mediating naturalisation of introduced Proteaceae species. Other factors, such as features of the recipient environments, appear to be more important. Spatial variation in rates of reproduction might, however, explain variation in the extent and rate of naturalisation of different populations.


Subject(s)
Pollination/physiology , Proteaceae/physiology , Self-Fertilization/physiology , Animals , Australia , Bees , Flowers/physiology , Insecta , Introduced Species , Pollen , Seeds/growth & development , South Africa
18.
Cancer Epidemiol ; 40: 7-14, 2016 Feb.
Article in English | MEDLINE | ID: mdl-26605428

ABSTRACT

PURPOSE: Inflammatory breast cancer (IBC) is an aggressive subtype of breast cancer for which treatments vary, so we sought to identify factors that affect the receipt of guideline-concordant care. METHODS: Patients diagnosed with IBC in 2004 were identified from the Breast and Prostate Cancer Data Quality and Patterns of Care Study, containing information from cancer registries in seven states. Variation in guideline-concordant care for IBC, based on National Comprehensive Cancer Network (NCCN) guidelines, was assessed according to patient, physician, and hospital characteristics. RESULTS: Of the 107 IBC patients in the study without distant metastasis at the time of diagnosis, only 25.8% received treatment concordant with guidelines. Predictors of non-concordance included patient age (≥70 years), non-white race, normal body mass index (BMI 18.5-25 kg/m(2)), patients with physicians graduating from medical school >15 years prior, and smaller hospital size (<200 beds). IBC patients survived longer if they received guideline-concordant treatment based on either 2003 (p=0.06) or 2013 (p=0.06) NCCN guidelines. CONCLUSIONS: Targeting factors associated with receipt of care that is not guideline-concordant may reduce survival disparities in IBC patients. Prompt referral for neoadjuvant chemotherapy and post-operative radiation therapy is also crucial.


Subject(s)
Guideline Adherence/statistics & numerical data , Guidelines as Topic/standards , Inflammatory Breast Neoplasms/therapy , Medical Oncology/statistics & numerical data , Medical Oncology/standards , Aged , Female , Hospitals/statistics & numerical data , Humans , Inflammatory Breast Neoplasms/pathology , Male , Middle Aged , Physicians/statistics & numerical data
19.
J Radiol Prot ; 35(4): 743-62, 2015 Dec.
Article in English | MEDLINE | ID: mdl-26418079

ABSTRACT

Uranium is chemically toxic and radioactive, and both considerations have to be taken into account when limiting intakes of the element, in the context of both occupational and public exposures. Herein, the most recent information available on the chemical toxicity and biokinetics of uranium is used to propose new standards for limiting intakes of the element. The approach adopted allows coherent standards to be set for ingestion and inhalation of different chemical forms of the element by various age groups. It also allows coherent standards to be set for occupational and public exposures (including exposures of different age groups) and for various exposure regimes (including short-term and chronic exposures). The proposed standards are more restrictive than those used previously, but are less restrictive than the Minimal Risk Levels proposed recently by the US Agency for Toxic Substances and Disease Registry. Having developed a set of proposed limits based solely on chemical toxicity considerations, the radiological implications of exposure at those proposed limits are investigated for natural, depleted and enriched uranium.


Subject(s)
Occupational Exposure/statistics & numerical data , Radiation Dosage , Radiation Exposure/statistics & numerical data , Uranium/toxicity , Dose-Response Relationship, Radiation , Humans , Time Factors
20.
Bull Entomol Res ; 105(4): 515-20, 2015 Aug.
Article in English | MEDLINE | ID: mdl-25913190

ABSTRACT

Chinese knotweed (Persicaria chinensis) is of ecological and economic importance as a high-risk invasive species and a traditional medicinal herb. However, the insects associated with P. chinensis pollination have received scant attention. As a widespread invasive plant we would expect P. chinensis to be associated with a diverse group of insect pollinators, but lack of taxonomic identification capacity is an impediment to confirm this expectation. In the present study we aimed to elucidate the insect pollinators of P. chinensis in peninsular Malaysia using DNA barcoding. Forty flower visitors, representing the range of morphological diversity observed, were captured at flowers at Ulu Kali, Pahang, Malaysia. Using Automated Barcode Gap Discovery, 17 morphospecies were assigned to 23 species representing at least ten families and four orders. Using the DNA barcode library (BOLD) 30% of the species could be assigned a species name, and 70% could be assigned a genus name. The insects visiting P. chinensis were broadly similar to those previously reported as visiting Persicaria japonica, including honey bees (Apis), droneflies (Eristalis), blowflies (Lucilia) and potter wasps (Eumedes), but also included thrips and ants.


Subject(s)
DNA Barcoding, Taxonomic , Insecta/genetics , Pollination/physiology , Polygonaceae/physiology , Animals , Insecta/classification , Insecta/physiology , Malaysia
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