Human continuous glucose monitors for measurement of glucose in dairy cows.

If validated for use in dairy cattle, interstitial continuous glucose monitors (CGMs) could be easily implemented, informative tools for research, clinical, and perhaps even on-farm applications. To evaluate their efficacy, 2 experiments were conducted, during which lactating Holstein cows were fit with indwelling jugular catheters, as well as FreeStyle Libre (FSL; Abbott) and Dexcom G6 (DexCom Inc.) CGMs secured either behind their polls, lateral to their ears, or beneath their pin bones on their upper rear legs. During the first experiment, blood (measured with a handheld glucometer) and interstitial glucose measurements were collected from 13 cows every 4 h for 96 h. In the second experiment, the same measurements were collected from 8 cows every 15 min for 6 h. At the mid-point of the sampling period (3 h), cows received a bolus dose of dextrose to facilitate comparisons across a broad range of glucose concentrations. Results from both experiments determined that functional longevity of the sensors was greatest for those sensors secured near the ear. Likewise, interstitial measurements from the ear sensors were most closely correlated with blood glucose concentrations (r = 0.82 and r = 0.71 for FSL ear and Dexcom G6 ear, respectively). Unfortunately, accuracy calculated as absolute relative error was low, at 60.7% or less. As a result of the low accuracy, even though both ear sensors detected an increase in glucose concentrations following the bolus dose, neither produced results exactly matching blood glucose measurements. The results of this work indicate that the FSL and Dexcom G6 CGMs are not currently capable of replacing blood-based glucose measurements.

Comparison of production-related responses to hyperinsulinemia and hypoglycemia induced by clamp procedures or heat stress of lactating dairy cattle.

Hyperinsulinemia concurrent with hypoglycemia is one of a myriad of physiological changes typically experienced by lactating dairy cows exposed to heat stress, the consequences of which are not yet well defined or understood. Therefore, the objective of this experiment was to separate the production-related effects of hyperinsulinemia with hypoglycemia from those of a hyperthermic environment. Multiparous lactating Holstein cows (n = 23; 58 ± 4 d in milk, 3.1 ± 0.3 lactations) were housed in temperature-controlled rooms and all were subjected to 4 experimental periods as follows: (1) thermoneutral (TN; temperature-humidity index of 65.1 ± 0.2; d 1-5), (2) TN + hyperinsulinemic-hypoglycemic clamp (HHC; insulin infused at 0.3 µg/kg of BW per h, glucose infused to maintain 90 ± 10% of baseline blood glucose for 96 h; d 6-10), (3) heat stress (HS; temperature-humidity index of 72.5 ± 0.2; d 16-20), and (4) HS + euglycemic clamp (EC; glucose infused to reach 100 ± 10% of TN baseline blood glucose for 96 h; d 21-25). Cows were fed and milked twice daily. Feed refusals were collected once daily for calculation of daily dry matter intake, and milk samples were collected at the beginning and end of each period for component analyses. Circulating insulin concentrations were measured in daily blood samples, whereas glucose concentrations were measured more frequently and variably in association with clamp procedures. Rectal temperatures and respiration rates were greater during HS than TN, as expected, and states of hyperinsulinemia and hypoglycemia were successfully induced by the HHC and high ambient temperatures (HS and EC). Feed intake differed based upon thermal environment as it was similar during TN and HHC periods, and declined for HS and EC. Milk production was not entirely reflective of feed intake as it was greatest during TN, intermediate during HHC, and lowest during HS and EC. All milk components differed with the experimental period, primarily in response to the thermal environment. Interestingly, TN baseline glucose concentrations were highly correlated with the change in glucose from TN to HS, and were related to glycemic status during HS. Furthermore, although few in number, those cows that failed to become hypoglycemic during HS tended to have a greater reduction in milk yield. The work presented here addresses a critical knowledge gap by broadening our understanding of the physiological response to heat stress and the related changes in glycemic state. This broadened understanding is fundamental for the development of novel, innovative management strategies as the dairy industry is compelled to become increasingly efficient in spite of global warming.

The effects on children of depressed mothers' remission and relapse over 9 months.

BACKGROUND: The high rate of depression among children of depressed mothers is well known. Suggestions that improvement in maternal acute depression has a positive effect on the child have emerged. However, data on the mechanisms of change have been sparse. The aim was to understand how remission and relapse in the mother might explain the changes in the child's outcome. METHOD: Participants were 76 depressed mothers who entered into a medication clinical trial for depression and 135 of their eligible offspring ages 7-17 years. The mothers and children were assessed at baseline and periodically over 9 months by independent teams to understand the relationship between changes in children's symptoms and functioning and maternal remission or relapse. The main outcome measures were, for mothers, the Hamilton Depression Rating Scale (HAMD), the Social Adjustment Scale (SAS) and the Parental Bonding Instrument (PBI) and, for children, the Children's Depression Inventory (CDI), the Columbia Impairment Scale (CIS), the Multidimensional Anxiety Scale for Children (MASC) and the Children's Global Assessment Scale (CGAS). RESULTS: Maternal remission was associated with a decrease in the child's depressive symptoms. The mother's subsequent relapse was associated with an increase in the child's symptoms over 9 months. The effect of maternal remission on the child's improvement was partially explained by an improvement in the mother's parenting, particularly the change in the mother's ability to listen and talk to her child, but also reflected in her improvement in parental bonding. These findings could not be explained by the child's treatment. CONCLUSIONS: A depressed mother's remission is associated with her improvement in parenting and a decrease in her child's symptoms. Her relapse is associated with an increase in her child's symptoms.

Contribution of serum inflammatory markers to changes in bone mineral content and density in postmenopausal women: a 1-year investigation.

Bone formation and resorption are influenced by inflammatory processes. We examined the relationships among inflammatory markers and bone mineral content (BMC) and density (BMD) and determined the contribution of inflammatory markers to 1-yr changes in BMC and BMD in healthy postmenopausal women. This analysis included 242 women at baseline from our parent Soy Isoflavones for Reducing Bone Loss project who were randomly assigned to 1 of 3 treatment groups: placebo, 80 mg/d soy isoflavones, or 120 mg/d soy isoflavones. BMD and BMC from the lumbar spine (LS), total proximal femur (hip), and whole body were measured by dual energy X-ray absorptiometry and the 4% distal tibia by peripheral quantitative computed tomography. Serum inflammatory markers (C-reactive protein, interleukin [IL]-1 beta, IL-6, tumor necrosis factor-alpha [TNF-alpha], and white blood cell count [WBC]) were measured at baseline, 6, and 12 mo. Because of attrition or missing values, data analysis at 12 mo includes only 235 women. Significant associations among IL-6, TNF-alpha, and WBC were observed with percent change in LS, hip, and whole body BMC and BMD. Multiple regression analysis indicated that in combination inflammatory markers accounted for 1.1-6.1% of the variance to the observed 12-mo changes in BMC and BMD. Our results suggest that modifying inflammatory markers, even in healthy postmenopausal women, may possibly reduce bone loss.

Atypical depression: current status and relevance to melancholia.

OBJECTIVE: The Diagnostic and Statistical Manual, Fourth Edition (DSM-IV, 1994) included atypical features as an illness specifier for major depression and dysthymia. We asked whether subsequent literature supported its validity and addressed the relationship between depression with atypical features and melancholia. METHOD: Literature review focusing on studies addressing the validity of atypical depression, supplemented by the authors' previously unpublished data. RESULTS: Most studies support the discriminant validity of depression with atypical features relative to melancholia and depression having neither melancholic nor atypical features. However, studies addressing illness course suggest that criteria for depression with atypical features define a heterogeneous patient population. CONCLUSION: DSM-IV criteria for depression with atypical features define a valid, but heterogeneous disorder. Criteria including age of onset and chronicity may define a more homogeneous group that is distinct from both melancholia and other depressed patients.

Somatization as a predictor of medication discontinuation due to adverse events.

Medication discontinuation due to intolerable side-effects remains a significant clinical problem in the treatment of depression. We were unable to locate studies which found predictors of medication cessation due to side-effects. We posited that an identifiable subgroup of medically healthy, depressed adults who discontinued medication because of adverse events would have higher pre-treatment somatic symptoms than patients who completed a course of treatment. The sample (n =940) was drawn from a series of double-blind, placebo-controlled studies of antidepressants (imipramine, phenelelzine, L-deprenyl, mianserin and desipramine). Within the medication group, side-effect dropouts had more somatic symptoms than study completers and those who discontinued treatment for miscellaneous reasons. Within the placebo-treated group, the small number of subject who discontinued treated because of side-effects precluded valid statistical analyses, but the findings were in the same direction as those in the medication group. Clearly, further research is required to determine whether these results, obtained from a series of university-based clinical trials with healthy subjects, are generalizable to patients with significant comorbid medical and/or psychiatric disorders, treated with newer antidepressants agents in a general clinical practice setting.

Pork with a high content of polyunsaturated fatty acids lowers LDL cholesterol in women.

BACKGROUND: Animal products contribute significantly to the saturated fat and cholesterol content of the American diet. Contrary to dietary advice, consumers have not limited their consumption of animal products. Thus, an alternative approach might be to modify the fatty acid composition of animal products. OBJECTIVE: We tested the hypothesis that modified pork with a high content of polyunsaturated fatty acids (PUFAs) and a low content of saturated fatty acids (SFAs) would lower plasma LDL-cholesterol concentrations in women. DESIGN: Twenty women aged 19-24 y completed a crossover study with 2 diets. Nutritionally complete diets containing 42% of energy from fat differed only in the inclusion of either standard or modified pork. Venous blood samples were collected at weeks 0, 4, and 8. RESULTS: The diet containing modified pork significantly lowered total plasma (P < 0.0076) and LDL (P < 0.0382) cholesterol. The modified diet also resulted in an increase in the PUFA and a decrease in the SFA and monounsaturated fatty acid contents of the cholesteryl ester, free fatty acid, phospholipid, and triacylglycerol lipid classes in both plasma and erythrocytes. Plasma concentrations of glucose, insulin, triacylglycerol, and free fatty acids did not change significantly. CONCLUSIONS: Consumption of pork with a high PUFA content resulted in a decrease in the subjects' total plasma and LDL cholesterol and shifted the fatty acid composition from SFAs to PUFAs in the plasma and erythrocytes. Modification of the fatty acid composition of animal foods will be a useful approach to lowering the saturated fat consumption of Americans.

Atypical and non-atypical subtypes of depression: comparison of social functioning, symptoms, course of illness, co-morbidity and demographic features.

BACKGROUND: There are scant data regarding the demographic and psychosocial characteristics of outpatients with Atypical Depression (AD). METHODS: The demographic characteristics, rates of chronic dysphoria, baseline Symptom Check List Revised, and Social Adjustment Scale scores of 320 moderately depressed patients with and without AD were compared. RESULTS: ADs had a higher number of self-reported symptoms, greater impairments in functioning, and higher rates of chronic dysphoria and bipolar II than patients without Atypical Depression (NAD). LIMITATIONS: Variables used in this study were mostly cross-sectional, and the analyses were performed post-hoc. CONCLUSIONS: These data suggest ADs had a more pernicious course of illness than NADs, and that patients with AD were more symptomatic and dysfunctional at admission.

Electroencephalographic and perceptual asymmetry differences between responders and nonresponders to an SSRI antidepressant.

BACKGROUND: Recent reports suggest the value of electroencephalographic and dichotic listening measures as predictors of response to antidepressants. This study examines the potential of electroencephalographic alpha asymmetry and dichotic measures of perceptual asymmetry as predictors of clinical response to 12 weeks of treatment with fluoxetine (Prozac). METHODS: Resting electroencephalography (eyes open and eyes closed) and dichotic listening with word or complex tone stimuli were assessed in depressed outpatients during a pretreatment period. RESULTS: Fluoxetine responders (n = 34) differed from nonresponders (n = 19) in favoring left over right hemisphere processing of dichotic stimuli. They also differed in their resting electroencephalographic alpha asymmetry, particularly in the eyes open condition. Nonresponders showed an alpha asymmetry indicative of overall greater activation of the right hemisphere than the left, whereas responders did not. The relationship between hemispheric asymmetry and treatment response interacted with gender, being evident among depressed women but not men. CONCLUSIONS: The results are consistent with the hypothesis that a characteristic tendency toward greater left than right hemisphere activation is associated with favorable response to fluoxetine, whereas the opposite hemispheric asymmetry predicts poor response.

Isoflavone-rich soy protein isolate attenuates bone loss in the lumbar spine of perimenopausal women.

BACKGROUND: No published studies have directly examined the effect of soy protein with isoflavones on bone or bone turnover in perimenopausal women. OBJECTIVE: Our objective was to determine the effects of 24 wk of consumption of soy protein isolate with isoflavones (80.4 mg/d) in attenuating bone loss during the menopausal transition. DESIGN: Perimenopausal subjects were randomly assigned, double blind, to treatment: isoflavone-rich soy (SPI+; n = 24), isoflavone-poor soy (SPI-; n = 24), or whey (control; n = 21) protein. At baseline and posttreatment, lumbar spine bone mineral density (BMD) and bone mineral content (BMC) were measured by using dual-energy X-ray absorptiometry. At baseline, midtreatment, and posttreatment, urinary N:-telopeptides and serum bone-specific alkaline phosphatase (BAP) were measured. RESULTS: The percentage change in lumbar spine BMD and BMC, respectively, did not differ from zero in the SPI+ or SPI- groups, but loss occurred in the control group (-1.28%, P: = 0.0041; -1.73%, P: = 0.0037). By regression analysis, SPI+ treatment had a positive effect on change in BMD (5.6%; P: = 0.023) and BMC (10.1%; P: = 0.0032). Baseline BMD and BMC (P: < or = 0.0001) negatively affected the percentage change in their respective models; baseline body weight (P: = 0.0036) and bone-free lean weight (P: = 0.016) contributed positively to percentage change in BMD and BMC, respectively. Serum BAP posttreatment was negatively related to percentage change in BMD (P: = 0.0016) and BMC (P: = 0.019). Contrast coding using analyses of covariance with BMD or BMC as the outcome showed that isoflavones, not soy protein, exerted the effect. CONCLUSION: Soy isoflavones attenuated bone loss from the lumbar spine in perimenopausal women.

Predictors of relapse during fluoxetine continuation or maintenance treatment of major depression.

BACKGROUND: The goal was to examine predictors of relapse during continuation/maintenance treatment of major depression that had remitted following 12 to 14 weeks of fluoxetine therapy. METHOD: The study utilizes data collected in a collaborative clinical trial including patients with DSM-III-R major depression at 5 university-affiliated outpatient psychiatry clinics. Three hundred ninety-five patients who remitted with fluoxetine therapy were randomly assigned to 1 of 4 treatments: fluoxetine for 14 weeks followed by placebo for 36 weeks, fluoxetine for 38 weeks followed by placebo for 12 weeks, fluoxetine for 50 weeks, or placebo for 50 weeks. Cox proportional hazard models were used to identify predictors of time to relapse. RESULTS: In addition to the previously reported longitudinal pattern of response during acute treatment, neurovegetative symptom pattern was a predictor of fluoxetine benefit compared with placebo. Greater chronicity predicted poorer survival, which was not differential by treatment. The most robust advantage of fluoxetine was seen for patients with endogenous vegetative symptoms, chronic depression, and acute treatment response characterized by onset in the third week or later and persistence of response once attained. CONCLUSION: Both nonspecific pattern of response and neurovegetative symptoms characteristic of atypical depression were predictive of lack of fluoxetine efficacy in continuation/ maintenance treatment. These findings have importance for both clinical management and analyses of future maintenance trials.

Double-blind comparison of sertraline, imipramine, and placebo in the treatment of dysthymia: effects on personality.

OBJECTIVE: Although previous studies have shown that dysthymia, or chronic depression, commonly responds to antidepressant medications (with improvements in depressive symptoms and psychosocial functioning), there have been no systematic studies of the impact of antidepressant treatment on personality variables in patients with this disorder. METHOD: In a multicenter study, 410 patients with early-onset primary dysthymia were treated in a randomized prospective fashion with sertraline, imipramine, or placebo. The data were analyzed in terms of the subjects' scores on the Tridimensional Personality Questionnaire, a 100-item self-report instrument that measures four temperamental dimensions: harm avoidance, reward dependence, novelty seeking, and persistence. RESULTS: At baseline, the harm avoidance scores of the dysthymic subjects were approximately 1.5 standard deviations higher than those of a previously reported community sample. After treatment, there was a significant decrease in harm avoidance scores, with no significant between-group differences. Remission of dysthymia was associated with significantly greater improvement in harm avoidance, with the greatest numerical change found in the patients treated with sertraline. Subjects' Tridimensional Personality Questionnaire scores were correlated at a 0.50 level with the Social Adjustment Scale both pre- and posttreatment, suggesting that a high degree of harm avoidance may be associated with poor social functioning. CONCLUSIONS: Before treatment, chronically depressed patients demonstrate an abnormality in temperament, as measured by elevated degrees of harm avoidance. Remission of dysthymia is associated with improvement in this aspect of temperament.

A method to quantify rater bias in antidepressant trials.

Some studies indicate that the blind in clinical trials of the efficacy of antidepressant drugs is less than perfect. It has been suggested that, as a consequence of this incomplete blind, biased raters inflate efficacy and that, in fact, these drugs are relatively ineffective. However, in the literature, we could find no prior attempt to quantify rater bias and, thus, measure its contribution to claims of antidepressant efficacy. We used the distribution of SCL-90 (Symptom Check List) depression scale scores to derive a patient-based effect size, and contrasted this with the clinician-based effect size. We propose the difference between these two effect sizes (patient self-rating and clinician-derived) to be an indirect measure of bias. If patients had a prodrug bias, this method would be invalid. However the response rate from studies with active placebo suggest a patient prodrug bias is unlikely. The effect sizes derived from patient self-ratings are smaller than those derived from clinician ratings. This allows for the possibility that some clinician ratings were biased. However, quantifying the effect of bias suggests that it was insufficient to invalidate the original study conclusions based on clinician ratings, because the proportion of responders, based on patient self-ratings, differed significantly between the two drugs and placebo. Their 95% confidence intervals (CI) did not overlap. This analysis allows that some clinician ratings may be biased. However, the extent of bias appears insufficient to alter conclusions based on clinician ratings regarding efficacy of antidepressant drugs in this trial. Application of our approach in other trials is necessary to establish generalizability.

Divalproex treatment for youth with explosive temper and mood lability: a double-blind, placebo-controlled crossover design.

OBJECTIVE: The authors sought to replicate open-label findings showing that specific criteria for explosive temper and mood lability identify disruptive youth who improve while receiving the anticonvulsant divalproex sodium. METHOD: Twenty outpatient children and adolescents (ages 10-18) with a disruptive behavior disorder (oppositional defiant disorder or conduct disorder) met the specific criteria for explosive temper and mood lability. They received 6 weeks of divalproex treatment and 6 weeks of placebo by random assignment. Independent evaluators blind to group assignment assessed response at the end of each phase. RESULTS: At the end of phase 1, eight of 10 subjects had responded to divalproex; zero of 10 had responded to placebo. Of the 15 subjects who completed both phases, 12 has superior response taking divalproex. CONCLUSIONS: This preliminary study replicates open-label findings showing that divalproex is an efficacious treatment for explosive temper and mood lability in disruptive children and adolescents.

A placebo-controlled study of fluoxetine versus imipramine in the acute treatment of atypical depression.

OBJECTIVE: The atypical subtype of depression appears to be both well validated and common. Although monoamine oxidase inhibitors are effective in treating atypical depression, their side effects and prescription-associated dietary restrictions reduce their suitability as a first-line treatment. The objective of this study was to estimate the efficacy of the selective serotonin reuptake inhibitor (SSRI) fluoxetine in the treatment of major depression with atypical features. METHOD: One hundred fifty-four subjects with DSM-IV major depression who met the Columbia criteria for atypical depression were randomly assigned to receive fluoxetine, imipramine, or placebo for a 10-week clinical trial. Imipramine was included because its known efficacy for treatment of atypical depression helped to calibrate the appropriateness of the study group. RESULTS: In both intention-to-treat and completer groups, the effectiveness of both fluoxetine and imipramine was significantly better than that of placebo. The two medications did not differ from each other in effectiveness. Significantly more patients dropped out of treatment with imipramine than with fluoxetine. Before treatment, patients on average rated themselves as very impaired on psychological dimensions of general health and moderately impaired on physical dimensions, compared with population norms. The self-ratings of patients who responded to treatment essentially normalized on these measures. CONCLUSIONS: Despite earlier data that SSRIs might be the treatment of choice, fluoxetine appeared to be no better than imipramine in the treatment of atypical depression, although fluoxetine was better tolerated than imipramine.

Do tricyclic responders have different brain laterality?

A previous study showed that depressed patients who improved with tricyclic antidepressant medication had dichotic complex tones test results suggesting right-hemisphere dysfunction relative to nonresponders and controls (G. E. Bruder et al., 1990). A new sample of 68 depressed patients completed dichotic consonant-vowel (CV) and complex tones (CT) tests and then were treated with imipramine or placebo. A significant Ear x Test x Treatment x Response interaction was accounted for by significantly poorer left-ear accuracy for CVs among imipramine responders compared with nonresponders, placebo responders, and controls. CV left-ear accuracy was also significantly greater among placebo responders than placebo nonresponders and controls. The results only partially replicate the prior study in that evidence of right-hemisphere dysfunction in tricyclic responders was seen for the CV test but not the CT test.

Perceptual asymmetry differences between major depression with or without a comorbid anxiety disorder: a dichotic listening study.

Predictions that anxious and nonanxious depression would differ in perceptual asymmetry (PA), as well as in sensitivity for perceiving emotional words, were evaluated using dichotic listening tasks. A total of 149 patients having a major depressive disorder (51 with and 98 without an anxiety disorder) and 57 healthy controls were tested on fused-word and complex tone tasks. The anxious and nonanxious depression groups showed a consistent difference in PA across tasks; that is, the anxious group had a larger left-ear advantage for tones and a smaller right-ear advantage for words when compared with the nonanxious group. There was no group difference in sensitivity for perceiving emotional words. Patients having an anxious depression appear to have a greater propensity to activate right than left-hemisphere regions during auditory tasks, whereas those having a nonanxious depression have the opposite hemispheric asymmetry.

Predictors of therapeutic response to treatments for depression: a review of electrophysiologic and dichotic listening studies.

There are few clinical or biologic predictors of response to treatments for depression. This article reviews growing evidence that electrophysiologic and neurocognitive measures of brain function may be of value as predictors of therapeutic response to antidepressants. Initial studies using dichotic listening, quantitative electroencephalography, or event-related brain potential measures have found differences between treatment responsive and nonresponsive subgroups of depressed patients. The neurophysiologic basis for these differences and the potential clinical utility of electrophysiologic and dichotic predictors of treatment outcome remain to be determined in future studies.