Behaviour of lactose with the presence of lactic acid and Ca as affected by pH.

Contradictory statements about the effects of pH change on crystallisation behaviour of lactose exist in the literature. Considering the importance of addressing the processability issue of acid whey, a systematic study is required to establish lactose crystallisation behaviour in the presence of LA and Ca at concentrations present in real acid whey waste streams emphasising impact of pH. Structural modifications of lactose were evident at elevated, more neutral pH in the presence of 1% w/w LA and 0·12% w/w Ca. These structural changes led to changes in the anomeric equilibrium of lactose, which manipulated the water-lactose behaviour and increased the crystallinity. Therefore, altering pH to 6·5 may be the solution to proper industrial processing of acid whey, enhancing the ability of lactose to crystallise properly.

Preserved Unconscious Processing in Schizophrenia: The Case of Motivation.

BACKGROUND AND HYPOTHESIS: Motivation deficit is a hallmark of schizophrenia that has a strong impact on their daily life. An alteration of reward processing has been repeatedly highlighted in schizophrenia, but to what extent it involves a deficient amplification of reward representation through conscious processing remains unclear. Indeed, patients with schizophrenia exhibit a disruption of conscious processing, whereas unconscious processing appears to be largely preserved. STUDY DESIGN: To further explore the nature of motivational deficit in schizophrenia and the implication of consciousness disruption in this symptom, we used a masking paradigm testing motivation both under conscious and unconscious conditions in patients with schizophrenia (n = 31) and healthy controls (n = 32). Participants were exposed to conscious or subliminal coin pictures representing money at stake and were subsequently asked to perform an effort-task by squeezing a handgrip as hard as possible to win this reward. STUDY RESULTS: We observed a preserved effect of unconscious monetary rewards on force production in both groups, without any significant difference between them. By contrast, in the conscious condition, patients with schizophrenia were less sensitive to rewards than controls. Our results confirm that unconscious incentives have effects on exerted forces in the general population, and demonstrate that patients with schizophrenia exhibit a dissociation between an impaired conscious motivation and a preserved unconscious motivation. CONCLUSIONS: These findings suggest the existence of several steps in motivational processes that can be differentially affected and might have implication for patient care.

Elevated Effort Cost Identified by Computational Modeling as a Distinctive Feature Explaining Multiple Behaviors in Patients With Depression.

BACKGROUND: Motivational deficit is a core clinical manifestation of depression and a strong predictor of treatment failure. However, the underlying mechanisms, which cannot be accessed through conventional questionnaire-based scoring, remain largely unknown. According to decision theory, apathy could result either from biased subjective estimates (of action costs or outcomes) or from dysfunctional processes (in making decisions or allocating resources). METHODS: Here, we combined a series of behavioral tasks with computational modeling to elucidate the motivational deficits of 35 patients with unipolar or bipolar depression under various treatments compared with 35 matched healthy control subjects. RESULTS: The most striking feature, which was observed independent of medication across preference tasks (likeability ratings and binary decisions), performance tasks (physical and mental effort exertion), and instrumental learning tasks (updating choices to maximize outcomes), was an elevated sensitivity to effort cost. By contrast, sensitivity to action outcomes (reward and punishment) and task-specific processes were relatively spared. CONCLUSIONS: These results highlight effort cost as a critical dimension that might explain multiple behavioral changes in patients with depression. More generally, they validate a test battery for computational phenotyping of motivational states, which could orientate toward specific medication or rehabilitation therapy, and thereby help pave the way for more personalized medicine in psychiatry.

Individual factors influencing the duration of untreated psychosis.

AIM: Duration of untreated psychosis (DUP), or the time between onset of psychosis and treatment initiation, is a prognostic factor of schizophrenia. However, few studies evaluated the relative influence of individual-related factors on this duration. The objective of this study was to evaluate the influence of socio-demographic, clinical and cannabis use on DUP. METHODS: This study was part of a large prospective study in help-seeking individuals referred to our specialized early detection / intervention clinic in the Service Hospitalo-Universitaire of Sainte-Anne Hospital in Paris (ICAAR study). We explored 33 consecutive patients who crossed the CAARMS' threshold of psychosis. The DUP and cannabis consumption history were explored during the baseline comprehensive assessment using all available sources (direct interviews of patients, parents, practitioners). Correlations between socio-demographic, clinical and cannabis use, and DUP were studied. A multiple linear regression model was used to determine the variables that could significantly predict DUP. RESULTS: When considered individually, none of the socio-demographic and disease characteristic factors was associated with DUP, with the exception of level of education. In the multivariate analysis, age at inclusion, negative symptoms and history of cannabis use significantly influenced DUP. CONCLUSION: The determinants of DUP are multi-factorial and include individual centred factors, such as age, cannabis and negative symptoms. The identification of factors resulting in delayed access to care may promote the development of effective strategies to reduce DUP in early psychosis and target effective early intervention.

Pramipexole and Electroconvulsive Therapy in Treatment-Resistant Depression.

BACKGROUND: Major depressive disorder (MDD) is a common disease. Despite appropriate antidepressant treatment, approximately one third of patients do not achieve adequate response. In these patients, electroconvulsive therapy (ECT) is a possible option. Nevertheless, some symptoms may persist even after ECT. METHOD: This is a comparative retrospective study assessing the efficacy and safety of pramipexole in the treatment of resistant depression, in combination to ECT or after a partial ECT efficacy. RESULTS: We recruited 14 patients with severe MDD. Nine patients received ECT and pramipexole conjointly, the latter being introduced after a mean number of 18 ECT sessions. Five patients received pramipexole after failure of ECT. Montgomery-Asberg Depression Rating Scale and Clinical Global Impression scores all improved significantly after the initiation of pramipexole (jointly with ECT or alone). Moreover, the combination of ECT plus pramipexole was well tolerated. Only 1 patient presented a hypomanic episode, which resolved spontaneously. CONCLUSIONS: Pramipexole is a therapeutic option for MDD resistant to ECT. It could be used jointly to ECT or after a partial remission with ECT. More studies are needed to precisely describe the optimal combination of sequential use of ECT and pramipexole in treatment-resistant MDD.

Clozapine and long-acting injectable antipsychotic combination: A retrospective one-year mirror-image study.

To evaluate efficacy and tolerability of the combination of clozapine with an antipsychotic long-acting injectable (LAI) in multi-episode patients with schizophrenia or schizoaffective disorder. Efficacy and tolerability were assessed in seventeen patients admitted to a hospital in Paris between January 2010 and June 2015, using a one-year mirror-image design. Number and length of hospitalizations significantly decreased after introducing the combination (2.1 vs 0.8, p=0.004 and 155.4days vs 26.6days, p<0.001 respectively). No major adverse events occurred in terms of increased weight, agranulocytosis, hyperglycemia and/or dyslipidemia. This combination can be beneficial and safe in multi-episode patients.

HER2/CEP17 Ratios and Clinical Outcome in HER2-Positive Early Breast Cancer Undergoing Trastuzumab-Containing Therapy.

BACKGROUND: Adjuvant therapy comprising the HER2 receptor antagonist trastuzumab is associated with a significant improvement in disease-free and overall survival as compared to chemotherapy alone in localized HER2-positive breast cancer (BC). However, a subset of HER2-positive tumors seems to respond less favorably to trastuzumab. Various mechanisms have been proposed for trastuzumab resistance, such as high HER2 to Chromosome 17 FISH (HER2/CEP17) ratios and the possibility that single agent trastuzumab may not suffice to efficiently block HER2 downstream signaling thresholds. In a retrospective analysis we evaluated whether HER2/CEP17 ratios might have an impact on disease-free survival (DFS). METHODS: Clinical records of Stage I-III BC patients with HER2-positive tumors were reviewed at our institution from 2007-2013. We analyzed demographics, tumor characteristics including tumor size and grade, lymph node involvement and estrogen receptor expression as well as treatment with respect to chemotherapeutic regimens from the clinical charts. HER2/CEP17 ratios were determined by routine pathology analysis using in situ fluorescent hybridization (FISH). Upon statistical preview we defined three groups of HER2 amplification based on FISH ratio (2.2 to 4, >4 to 8, >8), in order to evaluate an association between HER2 gene amplification and DFS with trastuzumab containing therapies. DFS was analyzed using Cox-regression. RESULTS: A total of 332 patients with HER2-positive BC were reviewed. Median age was 54 (range 23-89) years. The majority of tumors were classified T1 (50%) or T2 (39%), node negative (52%) and of high grade G3 histology (70%). We identified 312 (94%) tumors as immunohistochemistry (IHC) score 3+ and HER2/CEP17 ratios were available from 278 patients (84%). 30% (N = 84) had tumors with high HER2/CEP17 ratios (>8). Univariate analysis found no correlation between outcome, age, histological grade, sequence as well as anthracycline content of chemotherapy. However, a prognostic impact was detected for tumor size (p = 0.02), nodal status (p<0.01), proliferation index (p<0.01), level (≥20%) of estrogen receptor expression (p = 0.03) and neoadjuvant therapeutic setting (p = 0.03), respectively. Importantly, univariate and multivariable analysis revealed that standard trastuzumab containing chemotherapy resulted in impaired disease free survival among tumors with FISH ratio >8 (p<0.01). Although less pronounced, a similar association was found also with respect to high HER2 gene copy numbers (>12) and DFS (p = 0.01). CONCLUSIONS: In early BC patients, tumors with high HER2 amplification ratios (>8), may less likely respond to standard trastuzumab-containing therapies. Although, we obtained a similar effect for high HER2 gene copy numbers, this provides only an indirect speculation and not a proof that high HER2/CEP17 ratios may induce HER2 resistance.

Symptoms of depression and anxiety in anorexia nervosa: links with plasma tryptophan and serotonin metabolism.

Depressive, anxiety and obsessive symptoms frequently co-occur with anorexia nervosa (AN). The relationship between these clinical manifestations and the biological changes caused by starvation is not well understood. It has been hypothesised that reduced availability of tryptophan (TRP) could reduce serotonin activity and thus trigger these comorbid symptoms. The aim of this study, during re-feeding in individuals with AN, was to analyse covariations across measures of nutritional status, depressive and anxiety symptoms, and peripheral serotonin markers. Depressive and anxiety symptoms, nutritional status and serotonin markers--whole blood serotonin content, plasma TRP and the ratio between TRP and large neutral amino acids--were assessed for 42 AN participants at admission to inpatient treatment and after re-feeding. Biological measures were compared to those obtained in 42 non-eating disordered subjects. For those with AN, psychological, nutritional and biological parameters improved significantly during hospitalisation. Levels of serotonin markers were significantly lower in the AN group compared to the control group, at admission and at discharge. Increase in the TRP/LNAA ratio was correlated with a decrease in depressive symptoms. In addition, there was a positive correlation between serotonin levels and symptoms of both anxiety and depression at discharge. We speculate that enhanced TRP availability during re-feeding, as a result of the increase in the TRP/LNAA ratio, could restore serotonin neurotransmission and lead to a decrease in depressive symptoms. The association between serotonin and anxiety and depressive symptoms would be consistent with numerous observations indicating abnormal functioning of the serotoninergic system in AN.