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Aim Proving the Severity of Ethanol Withdrawal Scale (SEWS) significantly reduces Alcohol Withdrawal Syndrome (AWS) treatment Time on Medication Protocol (TOMP). Method Head-to-head Quality Assurance outcome compared separate cohorts of SEWS or Clinical Institute Withdrawal Assessment Alcohol Scale, Revised (CIWA-Ar) data using Student’s t and Wilcoxon tests. Results SEWS-driven treatment (n = 244) reduced TOMP to 2.2 days versus 3.4 days for CIWA-Ar (n = 137); P Conclusion The SEWS is the superior measure of AWS symptoms.

Background Early clinical experience during the COVID-19 pandemic has begun to elucidate that the disease can cause brain function changes that may result in compromised cognition both acutely and during variable recovery periods. Reports on cognitive assessment of patients with COVID-19 are often limited to orientation alone. Further assessment may seem to create an inappropriate burden for patients with acute COVID-19, which is characterized by fatigue and confusion, and may also compromise examiner safety. Objective The aims of this study were to assess cognition in patients with COVID-19 as comprehensively as possible in a brief format, while observing safety precautions, and to establish a clear face value of the external validity of the assessment. Methods We adapted a brief cognitive assessment, previously applied to liver transplant candidates and medical/surgical inpatients, for remote use in patients hospitalized for COVID-19 treatment. Collecting quality assurance data from telephone-administered assessments, this report presents a series of 6 COVID-19 case vignettes to illustrate the use of this 5-minute assessment in the diagnosis and treatment of brain effects. Primary medical teams referred the cases for neuropsychiatric consultation. Results The age of the patients varied over four decades, and none of them were able to engage meaningfully with their surroundings on admission. On follow-up examination 6 to 10 days later, 4 of the 6 patients had recovered working memory, and only 1 had recovered calculation ability. Of the 6 patients, 2 were capable of complex judgment responses, while none of the cases completed frontal executive function testing in the normal range. Conclusions Cognitive assessment in patients with COVID-19 using this remote examination reveals patterns of cognitive recovery that vary among cases and are far more complex than loss of orientation. In this series, testing of specific temporal, parietal, and frontal lobe functions suggests that calculation ability, judgment, and especially frontal executive functions may characterize the effects of COVID-19 on the brain. Used widely and serially, this examination method can potentially inform our understanding of the effects of COVID-19 on the brain and of healing from the virus.

Background: Previously, we reported that the maturity of Psychological Adaptive Mechanism (PAM; alternatively, ego defense mechanism) endorsement, but not depression symptom severity, predicted 5-year survival rates in adult cancer patients and that study controlled for age as a significant variable. In this investigation, we hypothesized that greater PAM maturity would correlate significantly with age and with fewer depression symptoms in a larger sample.Methods: In this cross-section study, adult cancer outpatients (N=293) completed the Defense Style Questionnaire (DSQ), the Beck Depression Inventory (BDI), and provided additional clinical data. Spearman’s correlation and multiple regression modeling provided statistical tests of the study hypotheses.Results: Contrary to our hypothesis, DSQ PAM maturity endorsement did not correlate significantly with increasing age. Greater PAM maturity ratio on the DSQ (pppppConclusion: The results suggest that PAM maturity likely predicts fewer depression symptoms while younger age associates with more depression symptoms in this clinical sample. Centrally, acting cancer medications, such as glucocorticoids, and any history of psychiatric disorder correlated with increased depression symptom frequencies. In this cross-section study, antidepressant medications indicated higher frequencies of depressive symptoms, likely reflecting their use in persons previously diagnosed with depression. Further research should target factors that improve PAM maturity as a potential treatment target, especially in younger age groups.

Early life stress (ELS) is a risk factor for developing a host of psychiatric disorders. Adolescence is a particularly vulnerable period for the onset of these disorders and substance use disorders (SUDs). Here we discuss ELS and its effects in adolescence, especially SUDs, and their correlates with molecular changes to signaling systems in reward and stress neurocircuits. Using a maternal separation (MS) model of neonatal ELS, we studied a range of behaviors that comprise a "drug-seeking" phenotype. We then investigated potential mechanisms underlying the development of this phenotype. Corticotropin releasing factor (CRF) and serotonin (5-HT) are widely believed to be involved in "stress-induced" disorders, including addiction. Here, we show that ELS leads to the development of a drug-seeking phenotype indicative of increased susceptibility to addiction and concomitant sex-dependent upregulation of CRF and 5-HT system components throughout extended brain reward/stress neurocircuits.

The lipase inhibitory activity method described here was developed to identify potential anti-obesity properties in milk fermented with different strains of lactic acid bacteria via inhibition of pancreatic lipase and a subsequent decrease in fat digestion and absorption in the gut. The method is based on the hydrolysis of 4-nitrophenyl octanoate by pancreatic lipase and the subsequent release of p-nitrophenol, a coloured product whose absorbance can be measured at 412 nm. Inhibition of lipase leads to a decrease in the amount of p-nitrophenol released and a subsequent reduction in the absorbance with respect to a 100% activity control. The assay was developed by adapting various methods previously described in published literature and includes modifications that are key to adapt the existing protocols to fermented milk samples, in particular the pH issues encountered when analysing acidic samples:•A two buffer system is introduced to allow optimal pH control after addition of fermented milk samples with pH values between 3.5 and 6.5.•A post-clarification filtration step is added for samples where turbidity remains after addition of the clarifying reagent for dairy products.•An absorbance correction factor is calculated and applied to the samples to account for the reduction in the absorbance of p-nitrophenol caused by milk., Graphical abstract Image, graphical abstract

Background This secondary analysis of the VA Augmentation and Switching Treatments for Depression study compared the continuation phase treatment outcomes of three commonly used second-step treatment strategies following at least one prior failed medication treatment attempt. Methods In total, 1522 outpatients with MDD were randomized to switching to bupropion-SR (S-BUP), combining with bupropion-SR (C-BUP), or augmenting with aripiprazole (A-ARI). Following 12 weeks of acute phase treatment, 725 entered the 24-week continuation treatment phase. Depressive symptom severity, relapse, "emergent" remission, anxiety, suicidal ideation, quality of life, health status, and side effects were compared. Results We did not find clinically significant differential treatment effects with the exception that A-ARI was associated with less anxiety than S-BUP or C-BUP. Participants who entered continuation treatment as remitters had milder depressive symptom severity and lower relapse rates than those not in remission; they also experienced more improvement on most other outcomes. A-ARI was associated with less anxiety, insomnia, and dry mouth but more somnolence, extrapyramidal effects, akathisia, abnormal laboratory values, and appetite and weight gain. Conclusions Continuation treatment is a dynamic period. Regardless of the treatment, participants who entered continuation treatment at Week 12 in full remission continued to have better outcomes over the subsequent 24 weeks than those who were not in remission at the start of the continuation phase.

Aims For teams around the world, alcoholic liver disease patients comprise the largest, and clinically most controversial, group applying for liver transplant. And yet evaluation decisions for them remain highly variable by locale. Methods Targeting standardized assessment, we provide guidelines on what information the transplant team should seek, from what sources, and how best to make use of it. This report focuses on 'what to do and how to do it' in providing appropriate assessments for this complex patient group. Results Proper evaluation includes (a) taking the clinical history from the patient and a required, corroborating third person, (b) assessing patient cognition, (c) establishing alcohol/substance use diagnosis to differentiate alcohol dependence, abuse and polysubstance dependence, (d) assessing ambivalence in primary alcohol addiction, (e) measuring social stability and (f) using Vaillant's factors for abstinence prognosis. Conclusions Properly applied, these six factors will allow standardized selection in most cases taken across programs despite differences in resources, available expertise and decision practices. Short summary This report focuses on the essentials of the psychiatric/behavioral evaluation for 'alcoholic' persons referred for liver transplant. Attention to those essentials offers clinical standardization across transplant programs in different locales.

This quality assurance study compared two scales that drive the medicinal treatment of alcohol withdrawal syndrome (AWS): the new Severity of Ethanol Withdrawal Scale (SEWS) and the default Clinical Institute Withdrawal Assessment for Alcohol, revised (CIWA-Ar). Prospectively entered outcome data from medical intensive care (SEWS) and acute psychiatric inpatient (CIWA-Ar) units were collected and analyzed. Measures included scale administration patterns, mean lengths of time on treatment medication, and mean medication doses for the first 24 hours and for the total AWS episode. The administration patterns of the two scales were highly associated despite separate ward locations and personnel. Time-on-medication for SEWS patients shortened on average by one hospital day over the CIWA-Ar group. At the same time, however, total chlordiazepoxide doses, or the first 24 hours and over the total AWS episode, averaged twice the magnitude in the SEWS group over the CIWA-Ar. The data suggest that the SEWS sh...

Cheddar cheese was made using control culture (Lactococcus lactis subsp. lactis), or with control culture plus a galactose-metabolising (Gal+) or galactose-non-metabolising (Gal−) Streptococcus thermophilus adjunct; for each culture type, the pH at whey drainage was either low (pH 6.15) or high (pH 6.45). S. thermophilus affected the levels of residual lactose and galactose, and the volatile compound profile and sensory properties of the mature cheese (270 d) to an extent dependent on the drain pH and phenotype (Gal+ or Gal−). For all culture systems, reducing drain pH resulted in lower levels of moisture and lactic acid, a higher concentration of free amino acids, and higher firmness. The results indicate that S. thermophilus may be used to diversify the sensory properties of Cheddar cheese, for example from a fruity buttery odour and creamy flavour to a more acid taste, rancid odour, and a sweaty cheese flavour at high drain pH.

One of the main causes of obesity is an imbalance between energy intake and expenditure. One approach to facilitate weight loss is to decrease absorption of energy-rich nutrients by inhibition of pancreatic lipase. A spectrophotometric method was developed to evaluate the potential of milk fermented with lactic acid bacteria to inhibit pancreatic lipase in vitro. Fermentates produced with Lactobacillus helveticus strains at 42 °C exhibited the highest levels of lipase inhibition, with strains SC8, SC44 and SC45 inhibiting pancreatic lipase by >49%, significantly higher than the activity of a milk control. In all cases activity was retained after removal of large proteins including casein and in the

Converging lines of evidence point to a significant role of neuroinflammation in a host of psychiatric conditions, including alcohol use disorder, TBI, and PTSD. A complex interaction of both peripheral and central signaling underlies processes involved in neuroinflammation. Calcineurin is a molecule that sits at the nexus of these processes and has been clearly linked to a number of psychiatric disorders including alcohol use disorder (AUD). Like its role in regulating peripheral immune cells, calcineurin (CN) plays an integral role in processes regulating neuroimmune function and neuroinflammatory processes. Targeting CN or elements of its signaling pathways at critical points may aid in the functional recovery from neuroinflammatory related disorders. In this review we will highlight the role of neuroinflammation and calcineurin signaling in AUD, TBI and stress-induced disorders and discuss recent findings demonstrating a therapeutic effect of immunosuppressant-induced calcineurin inhibition in a pre-clinical model of binge alcohol drinking.

In cheese, a negative oxidation-reduction (redox) potential is required for the stability of aroma, especially that associated with volatile sulphur compounds. To control the redox potential during ripening, redox agents were added to the salted curd of Cheddar cheese before pressing. The control cheese contained only salt, while different oxidising or reducing agents were added with the NaCl to the experimental cheeses. KIO3 (at 0·05, 0·1 and 1%, w/w) was used as the oxidising agent while cysteine (at 2%, w/w) and Na2S2O4 (at 0·05 and 0·1%, w/w) were used as reducing agents. During ripening the redox potential of the cheeses made with the reducing agents did not differ significantly from the control cheese (Eh ≈ −120 mV) while the cheeses made with 0·1 and 0·05% KIO3 had a significantly higher and positive redox potential in the first month of ripening. Cheese made with 1% KIO3 had positive values of redox potential throughout ripening but no starter lactic acid bacteria survived in this cheese; however, numbers of starter organisms in all other cheeses were similar. Principal component analysis (PCA) of the volatile compounds clearly separated the cheeses made with the reducing agents from cheeses made with the oxidising agents at 2 month of ripening. Cheeses with reducing agents were characterized by the presence of sulphur compounds whereas cheeses made with KIO3 were characterized mainly by aldehydes. At 6 month of ripening, separation by PCA was less evident. These findings support the hypothesis that redox potential could be controlled during ripening and that this parameter has an influence on the development of cheese flavour.

This article is a response to unfounded assessments of the value and effectiveness of Alcoholic Anonymous (AA) as an agent of recovery from alcohol/other drug disorders. Three recent examples are identified: Dodes and Dodes (2014), Glaser (2015), and Mohammad (2016). To challenge these assessments, three publications offering scientific support for AA are presented: Emrick et al. (1993); Vaillant (2012); and Humphreys, Blodgett, and Wagner (2014). A detailed examination is then undertaken of how Dodes and Dodes arrive at the conclusion that AA’s long-term sobriety rate is between 5% and 8%. Our review of the studies cited by Dodes and Dodes reveals that long-term abstinence rates for actively involved members of AA and other 12-Step groups are impressively high.

Objective:The study addressed whether a collaborative model for chronic care, described in part I (this issue), improves outcome for bipolar disorder.Methods:The intervention was designed to improve outcome by enhancing patient self-management skills with group psychoeducation; providing clinician decision support with simplified practice guidelines; and improving access to care, continuity of care, and information flow via nurse care coordinators. In an effectiveness design veterans with bipolar disorder at 11 Veterans Affairs hospitals were randomly assigned to three years of care in the intervention or continued usual care. Blinded clinical and functional measures were obtained every eight weeks. Intention-to-treat analysis (N=306) with mixed-effects models addressed the hypothesis that improvements would accrue over three years, consistent with social learning theory.Results:The intervention significantly reduced weeks in affective episode, primarily mania. Broad-based improvements were demonstrated i...

AIMS: Abstinence among alcohol dependent liver graft recipients is remarkably high. The routine use of anti-immune agents in these patients led to rodent studies showing that immunosuppressants acting through inhibition of calcineurin (CLN) are highly effective in decreasing alcohol consumption. It remained unclear, however, whether the decreased alcohol consumption in rodent models is mediated through peripheral suppression of immune response or centrally through direct inhibition of cyclophilin-CLN in the brain. We tested the hypothesis that direct brain inhibition of CLN with intracerebroventricular (ICV) injections of the immunosuppressant cyclosporine A (CsA) is sufficient to decrease ethanol consumption in a rodent model of binge-like drinking. METHODS: Male C57BL/6NHsd mice were put through a modified ‘drinking in the dark’ (DID) paradigm. Effects of both peripheral (IP) and central (ICV) injections of CsA on ethanol consumption were assessed. RESULTS: Here, as in earlier work, IP CsA administration significantly decreased alcohol consumption. Supporting our hypothesis, central administration of CsA was sufficient to decrease alcohol consumption in a dose-dependent manner. There was no significant effect of CsA on water or sucrose consumption. CONCLUSIONS: These results clearly implicate a CLN-mediated mechanism in brain in the inhibitory effects of CsA on ethanol consumption and provide novel targets for investigation of treatment for Alcohol Use Disorders (AUD). These results also add to the growing body of literature implicating neuroimmune mechanisms in the etiology, pathophysiology and behaviors driving AUD. SHORT SUMMARY: The unusually high abstinence rate and routine use of immunosuppressants in AUD liver graft recipients led us to rodent studies showing that immunosuppressants acting through inhibition of calcineurin (CLN) are highly effective in decreasing drinking. Here we demonstrate that this effect is mediated by brain rather than peripheral immune mechanisms.

Co-occurring schizophrenia spectrum disorder and International Statistical Classification of Diseases, 10th Revision cocaine dependence present a particularly destructive constellation that is often difficult to treat. Both conditions raise dopamine transmission effects in the brain. Traditional neuroleptics block dopamine receptors, whereas aripiprazole modulates dopamine activity as an agonist/antagonist. We tested whether dopamine modulation is superior to dopamine blocking in dual-diagnosis patients.In a randomized, double-blind, comparison design, cocaine-dependent schizophrenic subjects actively using cocaine received either aripiprazole or perphenazine in an 8-week trial. Primary outcome targeted cocaine-free urine sample proportions, whereas cocaine craving scores were a secondary variable.Subjects (N = 44) randomized (n = 22 per group) did not differ at baseline. The proportion of cocaine-free urine samples did not differ by medication group. Contrasting weeks 3 to 5 vs 6 to 8 revealed significant late reductions in craving with aripiprazole. On the respective 5-point subscales, craving intensity decreased by 1.53 ± 0.43 (P0.0005) points, craving frequency by 1.4 ± 0.40 (P0.0004) points, and craving duration by 1.76 ± 0.44 (P0.0001) points.A drug effect of aripiprazole on craving items appeared at week 6 of treatment, on average, and was not seen before that length of drug exposure. The data suggest that dopamine modulation reduces cocaine cravings but requires an acclimation period. To understand the mechanism of action better, a trial of depot aripiprazole may be useful. Clinically, a reduction in craving potentially offers a clearer focus for ongoing behavioral treatment. It may also offer a longer-term treatment effect with respect to the severity of relapse.

Importance Less than one-third of patients with major depressive disorder (MDD) achieve remission with their first antidepressant. Objective To determine the relative effectiveness and safety of 3 common alternate treatments for MDD. Design, Setting, and Participants From December 2012 to May 2015, 1522 patients at 35 US Veterans Health Administration medical centers who were diagnosed with nonpsychotic MDD, unresponsive to at least 1 antidepressant course meeting minimal standards for treatment dose and duration, participated in the study. Patients were randomly assigned (1:1:1) to 1 of 3 treatments and evaluated for up to 36 weeks. Interventions Switch to a different antidepressant, bupropion (switch group, n = 511); augment current treatment with bupropion (augment-bupropion group, n = 506); or augment with an atypical antipsychotic, aripiprazole (augment-aripiprazole group, n = 505) for 12 weeks (acute treatment phase) and up to 36 weeks for longer-term follow-up (continuation phase). Main Outcomes and Measures The primary outcome was remission during the acute treatment phase (16-item Quick Inventory of Depressive Symptomatology-Clinician Rated [QIDS-C 16 ] score ≤5 at 2 consecutive visits). Secondary outcomes included response (≥50% reduction in QIDS-C 16 score or improvement on the Clinical Global Impression Improvement scale), relapse, and adverse effects. Results Among 1522 randomized patients (mean age, 54.4 years; men, 1296 [85.2%]), 1137 (74.7%) completed the acute treatment phase. Remission rates at 12 weeks were 22.3% (n = 114) for the switch group, 26.9% (n = 136)for the augment-bupropion group, and 28.9% (n = 146) for the augment-aripiprazole group. The augment-aripiprazole group exceeded the switch group in remission (relative risk [RR], 1.30 [95% CI, 1.05-1.60]; P = .02), but other remission comparisons were not significant. Response was greater for the augment-aripiprazole group (74.3%) than for either the switch group (62.4%; RR, 1.19 [95% CI, 1.09-1.29]) or the augment-bupropion group (65.6%; RR, 1.13 [95% CI, 1.04-1.23]). No significant treatment differences were observed for relapse. Anxiety was more frequent in the 2 bupropion groups (24.3% in the switch group [n = 124] vs 16.6% in the augment-aripiprazole group [n = 84]; and 22.5% in augment-bupropion group [n = 114]). Adverse effects more frequent in the augment-aripiprazole group included somnolence, akathisia, and weight gain. Conclusions and Relevance Among a predominantly male population with major depressive disorder unresponsive to antidepressant treatment, augmentation with aripiprazole resulted in a statistically significant but only modestly increased likelihood of remission during 12 weeks of treatment compared with switching to bupropion monotherapy. Given the small effect size and adverse effects associated with aripiprazole, further analysis including cost-effectiveness is needed to understand the net utility of this approach. Trial Registration clinicaltrials.gov Identifier:NCT01421342

The psychological adaptive mechanism (PAM) model for systematic clinical assessment can be applied in any human setting in which individuals adapt to the conditions of their lives. This report focuses on applying the PAM assessment technique to the stress and anxiety of physical illness. To do so, we must consider maturity of PAMs simultaneously in relation to the cognitive functioning of the brain as assessed either in the office or at bedside. After considering case examples to illustrate this application, the discussion proceeds to include larger patient groups to which clinical PAM assessment might be applied, with special reference to cognitive function. The report concludes with suggestions for further improvement of the PAM clinical recognition method as well as its current practical applicability as an acquired clinical skill designed for use in everyday practice.

Curd was washed to varying degrees during Cheddar cheese manufacture, by partial replacement of whey with water at the early stages of cooking, to give target levels of lactose plus lactic acid in cheese moisture of 5.3 (control), 4.5, 4.3 and 3.9% (w/w). The cheeses were matured at 8 °C for 270 days. While curd washing had little effect on composition or the mean levels of proteolysis (as measured by pH 4.6 soluble nitrogen and levels of free amino acids), it led to cheeses that were, overall, firmer and less brittle. Curd washing resulted in cheeses having lower levels of some volatile compounds, and being less acid, more buttery, sweeter, saltier and creamier than non-washed cheeses that had more 'sweaty', pungent and farmyard-like sensory notes. The results suggest that curd washing during Cheddar manufacture may be used as a means of creating variants with distinctive flavour profiles.

Background Rehospitalization is an important and costly outcome that occurs commonly in several diseases encountered in the medical intensive care unit (ICU). Although alcohol use disorders are present in 40% of ICU survivors and alcohol withdrawal is the most common alcohol-related reason for admission to an ICU, rates and predictors of rehospitalization have not been previously reported in this population. Methods We conducted a retrospective cohort study of medical ICU survivors with a primary or secondary discharge diagnosis of alcohol withdrawal using 2 administrative databases. The primary outcome was time to rehospitalization or death. Secondary outcomes included time to first emergency department or urgent care clinic visit in the subset of ICU survivors who were not rehospitalized. Cox proportional hazard models were adjusted for age, gender, race, homelessness, smoking, and payer source. Results Of 1,178 patients discharged from the medical ICU over the study period, 468 (40%) were readmitted to the hospital and 54 (4%) died within 1 year. Schizophrenia (hazard ratio 2.23, 95% CI 1.57, 3.34, p

Cannabis has been cultivated and used by humans for thousands of years. Research for decades was focused on understanding the mechanisms of an illegal/addictive drug. This led to the discovery of the vast endocannabinoid system. Research has now shifted to understanding fundamental biological questions related to one of the most widespread signaling systems in both the brain and the body. Our understanding of cannabinoid signaling has advanced significantly in the last two decades. In this review, we discuss the state of knowledge on mechanisms of Cannabis signaling in the brain and the modulation of key brain neurotransmitter systems involved in both brain reward/addiction and psychiatric disorders. It is highly probable that various cannabinoids will be found to be efficacious in the treatment of a number of psychiatric disorders. However, while there is clearly much potential, marijuana has not been properly vetted by the medical-scientific evaluation process and there are clearly a range of potentially adverse side-effects-including addiction. We are at crossroads for research on endocannabinoid function and therapeutics (including the use of exogenous treatments such as Cannabis). With over 100 cannabinoid constituents, the majority of which have not been studied, there is much Cannabis research yet to be done. With more states legalizing both the medicinal and recreational use of marijuana the rigorous scientific investigation into cannabinoid signaling is imperative.

Cannabis has been cultivated and used by humans for thousands of years. Research for decades was focused on understanding the mechanisms of an illegal/addictive drug. This led to the discovery of the vast endocannabinoid system. Research has now shifted to understanding fundamental biological questions related to one of the most widespread signaling systems in both the brain and the body. Our understanding of cannabinoid signaling has advanced significantly in the last two decades. In this review, we discuss the state of knowledge on mechanisms of Cannabis signaling in the brain and the modulation of key brain neurotransmitter systems involved in both brain reward/addiction and psychiatric disorders. It is highly probable that various cannabinoids will be found to be efficacious in the treatment of a number of psychiatric disorders. However, while there is clearly much potential, marijuana has not been properly vetted by the medical-scientific evaluation process and there are clearly a range of potentially adverse side-effects-including addiction. We are at crossroads for research on endocannabinoid function and therapeutics (including the use of exogenous treatments such as Cannabis). With over 100 cannabinoid constituents, the majority of which have not been studied, there is much Cannabis research yet to be done. With more states legalizing both the medicinal and recreational use of marijuana the rigorous scientific investigation into cannabinoid signaling is imperative.

Cheddar cheese was manufactured in triplicate from mid-lactation milk and analysed over a 270-day ripening period. The curd was washed in the cheese vat to give target levels of lactose plus lactic acid in cheese moisture (LLAMc) in the final cheese of 5.3 (control), 4.5, 4.3 and 3.9% (w/w); these values correspond to the expected LLAMc levels in non-washed cheeses made from milk with lactose levels of 4.8 (control), 4.6, 4.3 and 3.8% (w/w), respectively. Increasing curd washing from 0 to 33% of milk volume significantly reduced mean levels of total lactate and LLAMc over the ripening period. Conversely, it increased the mean cheese pH by ∼0.3–0.4 at times ≥ 90 days. The LLAMc was ∼1.0–1.6 units lower than predicted based on levels of milk lactose and curd washing. Otherwise, alteration of curd washing generally did not affect gross composition or microbiology of the cheese.

In this study, the growth of chloramphenicol-resistant bacteriocin-sensitive indicator strain Lactobacillus casei DPC 2048CM was evaluated in Cheddar cheese made with bacteriocin-producing Lactobacillus paracasei DPC 4715. No suppression of growth of the indicator strain was observed in the cheese during ripening, and no bacteriocin production by L. paracasei DPC 4715 was detected by the well diffusion method in cheese and cheese extracts. The bacteriocin produced by L. paracasei DPC 4715 was sensitive to chymosin and cathepsin D, and it may have been hydrolysed by the rennet used for cheese manufacture or by indigenous milk proteases.

At some point in their careers, most neurologists encounter patients who they find difficult to help.1,2 This experience may arise as a natural reaction to the challenging diagnostic and therapeutic work that so often is a part of work in the clinical neurosciences. Reports of the physician's reactions to difficult patient encounters appear infrequently in the neurology literature but, when offered, are informative and useful.3 Their publication cuts through the sense of being the only one to face such difficult experiences and provides an opportunity to learn from them both personally and in discussion with colleagues. Other patients are experienced as difficult because the neuropsychiatric sequelae of their neurologic conditions, comorbid psychiatric problems, and/or other challenging behaviors provoke strong reactions in the neurologist and his or her staff. Physician reactions in these encounters run the gamut of emotions, but frequently include aversion, anxiety, hopelessness, and anger, and may sometimes even include feelings of malice.4 These kinds of reactions to patients, and sometimes to their caregivers, complicate and can compromise one's ability to provide neurologic care.1,2,5 In the midst of a strong negative reaction to a difficult encounter with a patient or caregiver, one may be tempted to consider dismissing that patient from one's practice. There are circumstances in which such dismissals of patients from neurologic practices are necessary.1 However, patient dismissals are logistically complicated, stress and strain an already damaged physician–patient relationship, and may result in legal and regulatory penalties for the physician if done improperly. Most importantly, the dismissal itself is rarely in the patient's best interest: it fails to address the cause of the patient's behaviors, results in the transfer of a highly upset patient to an entirely unsuspecting or unprepared colleague, and almost ensures that the …

Full-fat Cheddar cheese was high-pressure (HP)-treated (400 MPa for 10 min at room temperature) 1 day post-manufacture. HP treatment resulted in an almost 100-fold reduction in starter bacteria numbers and delayed growth of non-starter lactic acid bacteria (NSLAB). HP treatment had little or no effect on primary proteolysis in cheese, consistent with measured plasmin and chymosin activities, which were unaffected by HP treatment. The mean concentrations of total lactate and d (−)- and l (+)-lactate were significantly reduced in HP-treated cheese relative to the control cheese during ripening. HP-treated cheese also had significantly higher fracture strain and fracture stress values and significantly lower flowability than control cheese throughout ripening. HP-treated cheese had altered colour values and was discriminated from the control cheese by descriptive sensory analysis. Overall, the selected HP treatment of Cheddar cheese seems to be of limited value for acceleration of ripening and, in fact, may be more useful for arresting or slowing down ripening. Industrial relevance To date there have been conflicting reports on the effectiveness of HP treatment in accelerating Cheddar cheese ripening. The aim of this study was to investigate the effects of HP treatment at 400 MPa for 10 min at room temperature on a range of cheese parameters over a 180-day ripening time. The overall conclusion suggests that the selected HP treatment has only minor benefits for manipulating the functional and sensory properties of Cheddar cheese.

Half-fat Cheddar cheese (∼15%, w/w, fat) was manufactured on three occasions from milk pasteurised at 72, 77, 82 or 87 °C for 26 s, and analysed over a 270 day ripening period. Increasing milk pasteurisation temperature significantly increased the levels of moisture (from ∼45% at 72 °C to 50% at 87 °C), total lactate, and D(−)-lactate in cheese over the 270 day ripening period. Conversely, the cheese pH decreased significantly on increasing pasteurisation temperature. Increasing the pasteurisation temperature did not significantly affect the populations of starter or non-starter lactic acid bacteria during maturation. The use of higher pasteurisation temperatures would appear particularly amenable to exploitation as a means of producing high-moisture (e.g., 40–41%), short-ripened, mild-flavoured Cheddar or Cheddar-like cheeses.

The effects of hypercortisolism on hippocampal volume have not been studied in heavy drinkers. Prior work suggested increased hypothalamic-pituitary-adrenal activity in relation to lowered total hippocampus volume (THV) in heavy-drinking alcohol-dependent (AD) subjects. The present study hypothesized the following: (1) that chronic heavy-drinking subjects would demonstrate significantly higher salivary cortisol concentrations than light-drinking control subjects and (2) that data from the whole sample group would present an inverse relationship between cortisol concentration and THV.In carefully selected test and control subject groups matched for age, gender, and ethnicity, we measured salivary cortisol samples at waking, waking + 30 minutes, noon, and 4 PM on the day of magnetic resonance imaging of the brain. We next compared mean cortisol concentrations between groups and assessed the statistical association between cortisol concentration and hippocampus volume measures.Comparison of AD test subjects (n = 8) and non-AD control subjects (n = 8) found significantly higher cortisol concentrations at both morning sampling times (mean [SD] at waking: 0.49 [0.23] vs 0.24 [0.14] microg/dl, p = .012; at waking + 30 minutes: 0.57 [0.37] vs 0.28 [0.11] microg/dl, p = 0.043). Controlling for intracranial volume, there was a significant inverse correlation between waking cortisol concentration and THV (p = .007) in the total sample group (N = 16). However, when analyzed separately, only the control group maintained a strong, inverse association (p = .025). There was no association among the heavy drinking subjects.These early data in a small sample support the view that chronic heavy drinking results in high salivary cortisol concentrations. What remains unclear is whether hypercortisolism exerts a selectively injurious effect that results in observed hippocampus volume loss. Further research in larger groups using more frequent, monitored sampling must address the following: (1) whether this finding can be replicated and (2) if replicated, whether the lack of an association between low hippocampal volumes and high cortisol levels may indicate an extent of injury beyond which a normal association of the two may be lost.

Phenotypic tests and species-specific polymerase chain reaction (PCR) were used to confirm the classification of 41 isolates of Lactobacillus helveticus obtained from different sources. Randomly amplified polymorphic DNA–PCR (RAPD–PCR) was applied to the differentiation of these isolates, which grouped into nine clusters at the 80% similarity level. To determine if the different clusters had different degrees of autolysis, a representative selection of 14 isolates from different clusters was selected and screened for autolytic characteristics in vitro and also in Cheddar cheesemaking trials. No correlation could be found between the cluster from which the isolate originated, the levels of autolysis in the cheese, or the results of the in vitro screening. It was concluded that cheese manufacture per se is the best method to determine the potential for and the degree of autolysis during cheesemaking for a given isolate.

Psychiatric symptoms are common to many autoimmune disorders. Patients often will have mood disorders, anxiety, cognitive deficits, delirium, and psychosis. These symptoms may reflect the direct or indirect effect of the autoimmune disorder on the central nervous system, may be related to medications used to treat the disorder, or may be a direct psychologic impact from suffering with the autoimmune disorder. Accurately recognizing the psychiatric component and generating a differential diagnosis is a complex task for the treating physician. Treatment of the psychiatric component to the disorder often will include addressing steroid induced side effects, psychotropic medications, psychotherapy, patient and family education, and a strong physician-patient relationship.

The debilitation of schizophrenia (SCHZ) worsens markedly with comorbid cocaine dependence (CD) and alcohol abuse. To date, no medications have conclusively demonstrated effects against both SCHZ and CD (SCHZ + CD) simultaneously. Because of its dopamine-modulating properties, we hypothesized that aripiprazole would alleviate cocaine craving in patients with SCHZ + CD. We conducted a prospective, 8-week, open-label trial in poorly compliant SCHZ + CD subjects. Each received aripiprazole as their sole neuroleptic agent at a maximum dose of 15 mg/d. The Brief Psychiatric Rating Scale (BPRS) and the Brief Substance Craving Scale (BSCS) measured psychosis and subjective cocaine and alcohol cravings. Urine tests for cocaine provided data on actual use. Of 10 male subjects entered, 6 (60%) completed the 8-week trial. In those cases, positive urine tests dropped significantly (P < 0.001) after 2 weeks, when aripiprazole had reached steady state. Mean cocaine craving scores declined significantly (P = 0.026) as did mean alcohol craving scores (P = 0.006). Declining psychosis scores were associated with declining cocaine craving (r = 0.87, P < 0.01) and alcohol craving (r = 0.88, P < 0.01), respectively. This experience suggests possible aripiprazole effects in lowering both desire for and the use of cocaine in comorbid SCHZ subjects. These data suggest double-blind, randomized, comparison study in this severely ill, comorbid patient group.

Background Little is known about medical comorbidity or health-related quality of life (HRQOL) in bipolar disorder across the adult age span, especially in public sector patients. Methods We obtained cross-sectional demographic, clinical, and functional ratings for 330 veterans hospitalized for bipolar disorder with Mini-Mental State score ≥27 and without active alcohol/substance intoxication or withdrawal, who had had at least 2 prior psychiatric admissions in the last 5 years. Structured medical record review identified current/lifetime comorbid medical conditions. SF-36 Physical (PCS) and Mental (MCS) Component Scores, measured physical and mental HRQOL. Univariate and multivariate analyses addressed main hypotheses that physical and mental function decrease with age with decrements due to increasing medical comorbidity. Results PCS decreased (worsened) with age; number of current comorbid medical diagnoses, but not age, explained the decline. Older individuals had higher (better) MCS, even without controlling for medical comorbidity. Multivariate analysis indicated association of MCS with age, current depressed/mixed episode, number of past-year depressive episodes, and current anxiety disorder, but not with medical comorbidity, number of past-year manic episodes, current substance disorder or lifetime comorbidities. Limitations This cross-sectional design studied a predominantly male hospitalized sample who qualified for and consented to subsequent randomized treatment. Conclusions Medical comorbidity is associated with lower (worse) physical HRQOL, independent of age. Surprisingly, younger rather than older subjects reported lower mental HRQOL. This appears due in part to more complex psychiatric presentations, and several mechanisms are discussed. Both results suggest that age-specific assessment and treatment may enhance HRQOL outcome.

Hepatitis C virus (HCV) infects alcohol dependent (AD) individuals disproportionately. Disulfiram for timely abstinence in HCV + AD cases remains controversial. Our literature review suggests that (1) active drinking accelerates HCV-related liver damage and that abstinence is associated both (2) with a slower course of HCV+ hepatic deterioration and (3) with enhanced response to antiviral HCV treatment. Further, (4) the risk of disulfiram liver injury appears much lower than that from alcohol, (5) HCV+AD individuals require close monitoring during the first 6 months of disulfiram treatment, and (6) early discontinuation of disulfiram usually reverses harmful effects when these occur. Although systematic data are sparse, continued drinking appears much more liver toxic than does disulfiram in this group. Disulfiram therapy may allow (1) prolonged abstinence leading to successful antiviral therapy for HCV, and (2) time to begin behavioral treatments that facilitate long-term abstinence. Sizeable prospective studies of HCV + AD treatment are badly needed.

A study was undertaken to determine the effects of high pressure (HP) treatment on the rheological and cooking properties and appearance of reduced-fat Mozzarella cheese (RFMC). RFMC of approx. 10.7% fat was manufactured at pilot-scale. A portion of the cheeses (HP) were tempered at 21 °C for 16 h on day 1, high pressure-treated at 400 MPa for 5 min at 21 °C and then stored at 4 °C for 35 days. The remainder of the cheeses (C) were also tempered at 21 °C for 16 h and then stored at 4 °C for 35 days. There was a significant interactive effect of HP treatment and storage time on non-expressible serum per gram protein (NESP, i.e., an index of protein hydration in the cheese), the levels of which were significantly higher in HP than in C cheeses at day 2 of storage. HP treatment also significantly decreased the L* (reduced whiteness), a* (increased greenness) and b* (reduced yellowness)-values after storage for 1 day, but no effect was observed after 75 days storage. However, HP treatment did not significantly effect composition, pH, proteolysis, rheological properties of the unheated cheese or flowability and stretchability of the heated RFMC. Industrial relevance Mozzarella cheese has become one of the most prominent cheese varieties. Low fat cheeses are desirable and sought after but fat reduction adversely effects texture and cooking properties. Since HP treatment of milk has shown to improve texture of low fat cheeses it was relevant to investigate the impact of HP treatment on appearance and on rheological and cooking behaviour of reduced-fat Mozzarella cheese. Although time dependent changes were observed no clear trends or advantages could be attributed to HP treatment.

In recent years, many dairy product manufacturers pasteurize milk at temperatures higher than 72°C, so as to reduce further the risk of survival of Mycobacterium avium ssp. paratuberculosis. However, little information is available on the effect of these temperatures on cheese quality. Half-fat Cheddar cheeses (∼15%, w/w, fat) were manufactured from milk pasteurized at 72°C, 77°C, 82°C or 87°C for 26 s, and analyzed over a 360 d ripening period. The mean levels of whey protein denaturation in the pasteurized milks were 2.8%, 8.4%, 20.2% and 34.1% of total whey protein, respectively. Increasing pasteurization temperature significantly increased the levels of moisture and non-expressible serum and decreased the levels of protein, fat, calcium and free oil. Pasteurization temperature did not significantly affect the levels of pH 4.6-soluble N but influenced the degradation profiles of αs1- and β-caseins. Increased pasteurization temperature significantly reduced fracture stress, fracture strain and firmness of cheeses. Raising the pasteurization temperature from 72°C to either 82°C or 87°C significantly reduced the flowability and stretchability of the heated cheese and increased its apparent viscosity; in contrast, increasing pasteurization from 72°C to 77°C did not affect these properties.

Previously, we observed that the presence of a court-mandate doubled adherence to supervised disulfiram treatment over voluntary supervised disulfiram treatment during the initial twelve weeks. To assess persistence, we conducted a naturalistic followup study of adherence at 15 months in 19 voluntary and 17 court-ordered patients from the original groups. Treatment adherence, measured by the percentage of completed disulfiram clinic visits during the study period, was significantly higher in court-ordered subjects: 61.0% vs. 18.2% in the voluntary group ( p

The effects of high-pressure (HP) treatment conditions on proteolysis in Cheddar cheese ripening were investigated by response surface analysis. A second-order central composite rotatable design (CCRD) was used to study the influences of pressure and processing time in the range 70–400 MPa and 3.5–81.5 h, respectively, at 25 °C. Separate control samples were maintained for equivalent times at 25 or 8 °C at atmospheric pressure. Urea-PAGE analysis indicated that breakdown of αs1-casein, and concomitant production of αs1-I-casein (f 24–199), was increased by treatment at 100 MPa for 70 h at 25 °C. Accumulation of αs1-I-casein did not increase at >225 MPa and, at 350–400 MPa, decreased accumulation of αs1-I-casein was observed. Response surface models indicated that treatment at pressures

Low-moisture Mozzarella cheese (LMMC) was high pressure (HP) treated at different stages of storage at 4°C and analysed immediately post HP treatment. Confocal laser scanning microscopy of the unheated cheese indicated that HP treatment enhanced the development of age-related swelling of the paracasein matrix. This microstructural change coincided with a reduction in the level of serum expressed on centrifugation and suggests that HP results in an increase in the water holding capacity of the paracasein matrix. Proteolysis, as measured by urea polyacrylamide gel electrophoresis (urea-PAGE), pH 4.6 water soluble nitrogen and total levels of free amino acids (FAA), was largely unaffected by HP treatment of LMMC. HP treatment resulted in an increase in the flowability and a reduction in the melt time on heating at 280°C, especially at storage times ≤15 days. Dynamic measurement of the viscoelastic changes on heating the cheese from 20 to 82°C showed that HP treatment resulted in an increase in the fluidity of the heated cheese, as measured by phase angle, especially in 1-day-old cheese. Thus, accelerated ripening of LMMC was induced by HP treatment, which may lead to the development of an industrial process if cost effective commercial HP equipment were available.