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A comparison between two rTMS protocols as augmentation strategies in patients with treatment-resistant depression
- L. Larini, M. Castiglioni, E. Piccoli, C. Scarpa, M. Renne, S. Torriero, M. Bosi, B. Benatti, A. Varinelli, M. Vismara, B. Dell’Osso
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- Journal:
- European Psychiatry / Volume 66 / Issue S1 / March 2023
- Published online by Cambridge University Press:
- 19 July 2023, pp. S114-S115
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Introduction
Repetitive transcranial magnetic stimulation (rTMS) is an evidence-based treatment and rTMS protocols have been included in international guidelines for patients with treatment-resistant depression (TRD). The daily administration of standard rTMS protocols, typically over several weeks, could be a limiting factor (e.g., time off from work, commuting issues). To intensify the antidepressant response and to reduce the number of stimulation days, it has been proposed that increasing the number of rTMS sessions performed per day could be more effective and help to reduce the burden for patients and clinicians. Although there is much interest in accelerated TMS protocols, little is known about their efficacy and tolerability, and the literature on the topic is still scarce.
ObjectivesTo compare the efficacy and tolerability of two rTMS protocols (standard vs. accelerated) as augmentative strategies in patients with TRD.
MethodsIn the present ongoing, open-label, trial 14 patients meeting DSM-5 criteria for major depressive episode (either unipolar or bipolar), classified as partial responders or non-responders to adequate pharmacological treatment, were randomized to receive either standard (one session per day, five days a week, for four weeks; n= 7) or accelerated (two sessions per day, five days a week, for two weeks; n=6) rTMS treatment protocols. In both cases, rTMS was performed on the left dorsolateral prefrontal cortex, high frequency (10 Hz) at 120% of the motor threshold, 3000 pulses per sessions. Primary outcome measures included HAM-D, MADRS, and CGI-S scores at baseline (T0), at the end of rTMS treatment (T1), and after 1 month (T2), as well as tolerability based on adverse effects. Paired Samples t-Test for continuous variables was used to compare psychometric scales at each timepoint, while t-Test was used to compare differences between the two groups.
ResultsWith respect to total sample, in terms of primary outcome measures a significant reduction of HAM-D, MADRS and CGI-S total scores between T0 and T1 (t: 3.01, p<0.05; t: 1.692, p<0.5; t:3.207, p<0.05 respectively), T1 and T2 (t: 3.264, p<0.05: t:2.669, p<0.05; t:.085, p=0.437 respectively) and T0 and T2 (t:5.669, p<0.05; t=4.711, p<0.05; t:2.551, p<0.05 respectively) was found. No significant differences in terms of efficacy were found between the two groups. One patient dropped-out for reasons not related to rTMS treatment. Mild and transient headache during the stimulation was the only side effect reported (4 patients).
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ConclusionsConsistently with previous literature studies, our preliminary results supported the evidence of comparable efficacy and tolerability between accelerated and standard rTMS protocols. In the future, larger, blinded, and controlled trials might support these conclusions and further address treatment parameters of novel accelerated rTMS protocols.
Disclosure of InterestNone Declared
The impact of lifestyle on adherence to treatment in a sample of patients with Major Depression
- D. Conti, N. Girone, S. Vanzetto, M. Cocchi, F. Achilli, S. Leo, M. Bosi, B. Benatti, B. Dell’Osso
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- Journal:
- European Psychiatry / Volume 66 / Issue S1 / March 2023
- Published online by Cambridge University Press:
- 19 July 2023, p. S347
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Introduction
Poor adherence to treatment is currently stated to be one of the causes of depression relapse and recurrence.
ObjectivesAim of the present study was to assess potential differences in terms of clinical and socio-demographic characteristics specifically related to adherence to treatment features, medical comorbidities, and substance abuse in a sample of patients diagnosed with Major Depression in an Italian psychiatric department.
MethodsPatients with a DSM-5 diagnosis of Unipolar or Bipolar Major Depressive Episode, of either gender or any age were recruited from the Psychiatry Department of Luigi Sacco University Hospital in Milan. Main clinical and socio-demographic variables were collected reviewing patients’ medical records. Moreover, adherence to psychopharmacological treatment was assessed using the Clinician Rating Scale (CRS; Kemp et al, 1996; 1998). Adherence was defined as ratings of > or =5 on the CRS. Descriptive and association analyzes were performed, setting the significance level at p<.05.
Results80 patients with a diagnosis of Unipolar Major depressive episode (48.9%) and Bipolar Major Depressive Episode (51.1%) were included. For the purposes of the study, the total sample was divided into two subgroups based on adherence to pharmacological treatment (A+ vs A-). Significantly higher rates of inpatients from psychiatric ward were A- compared to A+ patients (84.6% vs 48.1%, p=.011). A- patients were significantly more unemployed (57.9% vs 23.8%, p=.015), were mostly living in their family of origin (50% vs 21.4%, p=.027), and had fewer years of education compared to A+ subgroup (10.52±3.28 vs 12.2±3.1 years, p=.053). Higher rates of Bipolar Depression diagnosis and a prevalent manic polarity lifetime emerged in A- compared to the A+ group (73.1% vs 42.3%, p=.010; 30.8% vs 3%, p=.011, respectively). Moreover, A+ reported significantly higher rates of depressive prevalent polarity lifetime (72.7% vs 30.8%, p=.011). A- reported significantly higher rates of comorbidity with alcohol or other substance use disorders lifetime (46.2% vs 5.7%, p=.006) and almost one involuntary commitment lifetime (23.1% vs 11.1%, p=.013).
ConclusionsIn our sample adherence to treatments showed significant differences in terms of clinical and socio-demographic characteristics. Low levels of adherence have been associated with higher hospitalization rates, involuntary commitments, greater comorbidity with alcohol or drugs. Our data therefore seem to suggest that less adherence leads to a worse disease course and a worse quality of life. It therefore appears useful to include an assessment of adherence in the clinical practice and implement interventions to improve therapeutic adherence and ensure a better quality of life.
Disclosure of InterestNone Declared
Mental health evaluation of patients with Inflammatory Bowel Disease and psychiatric comorbidities during the COVID-19 pandemic
- S. Vanzetto, M. Vismara, A. Frediani, N. Cassina, G. Maconi, M. Bosi, C. Viganò, B. Dell’Osso
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- Journal:
- European Psychiatry / Volume 65 / Issue S1 / June 2022
- Published online by Cambridge University Press:
- 01 September 2022, pp. S289-S290
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Introduction
The mental health of subjects with chronic medical illnesses, such as Inflammatory Bowel Disease (IBD- Crohn’s Disease and Ulcerative Colitis), is typically compromised and the current COVID-19 pandemic might have additionally increased this burden.
ObjectivesThe aim of the present study was to investigate, during the COVID-19 pandemic, if the presence of a comorbid psychiatric disorder has played a role as an aggravating factor on mental health in patients with IBD.
MethodsTwenty Five patients with psychiatric comorbidities (PC+) and twenty five without (PC-) comparable for age and gender, were recruited at the Gastroenterology department at Sacco University Hospital in Milan. Participants were assessed a psychiatric evaluation, collecting socio-demographic variables and measures of anxiety and depression [on the Hospital Anxiety Depression Scale (HADS)], sleep patterns [on the Insomnia Severity Index (ISI)] and general health status [on the Short Form Health Survey 36 (SF-36)].
Comparative statistical analyses were performed with t test with Bonferroni correction.
ResultsPC+ (n=25) showed more severe anxiety and depressive symptoms compared with PC- (n=25) (p <.001) and worse sleep pattern (p<.05). With respect to general health status, PC+ showed reduced physical activities (p<.05), social activities (p<.05), mental health (p<.01) and role limitations due to physical health (p<.05).
ConclusionsThe present findings showed a worse mental health in subjects with IBD and psychiatric comorbidities during Covid-19 pandemic, highlighting the importance of screening and treatment of psychiatric symptoms disorders in these patients.
DisclosureNo significant relationships.
Immunohistopathological response against anisakid nematode larvae and a coccidian in Micromesistius poutassou from NE Atlantic waters
- B. Sayyaf Dezfuli, E. Simoni, G. Bosi, M. Palomba, S. Mattiucci, L. Giulietti, M. Bao, A. Levsen, P. Cipriani
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- Journal of Helminthology / Volume 95 / 2021
- Published online by Cambridge University Press:
- 10 March 2021, e14
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A survey on Anisakis simplex (sensu stricto (s.s.)) from blue whiting, Micromesistius poutassou, in the north-eastern Atlantic Ocean revealed the occurrence of high infection levels of third larval stages in visceral organs and flesh. Larvae were genetically identified with a multilocus approach as A. simplex (s.s.). Histochemical, immunohistochemical and ultrastructural observations were conducted on 30 M. poutassou specimens. Gonads, pyloric caeca and flesh harboured encapsulated larvae of A. simplex (s.s.) but no intense host reaction was encountered around the parasite in the above organs. In the liver, the most infected organ, the larvae co-occurred with the coccidian Goussia sp. Within the granuloma around the A. simplex (s.s.) larvae, two concentric layers were recognized, an inner mostly comprising electron-dense epithelioid cells and an outer layer made of less electron-dense epithelioid cells. Macrophages and macrophage aggregates (MAs) were abundant out of the granulomas, scattered in parenchyma, and inside the MAs, the presence of engulfed Goussia sp. was frequent. In liver tissue co-infected with Goussia sp. and A. simplex (s.s.), hepatocytes showed cytoplasmic rarefaction and acute cell swelling. Results suggest that the host-induced encapsulation of A. simplex (s.s.) larvae is a strategic compromise to minimize collateral tissue damage around the larval infection sites, to facilitate the survival of both parasite and host.
Resistant starch reduces large intestinal pH and promotes fecal lactobacilli and bifidobacteria in pigs
- B. U. Metzler-Zebeli, N. Canibe, L. Montagne, J. Freire, P. Bosi, J. A. M. Prates, S. Tanghe, P. Trevisi
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Dietary resistant starch (RS) may have prebiotic properties but its effects on fermentation and the microbial population are inconsistent. This meta-analysis aimed to quantify the relationship between RS type 2 (RS2) and intestinal short-chain fatty acids (SCFA) and pH as well as certain key bacterial taxa for intestinal health in pigs. From the 24 included articles with sufficient information about the animal, and dietary and physiological measurements published between 2000 and 2017, individual sub-data sets for fermentation metabolites, pH, bacterial abundances and apparent total tract digestibility were built and used to parameterize prediction models on the effect of RS2, accounting for inter- and intra-study variability. In addition, the effect of pig’s BW at the start of the experiment and duration of the experimental period on response variables were also evaluated using backward elimination analysis. Dietary RS levels ranged from 0% to 78.0% RS, with median and mean RS levels of 28.8% and 23.0%, respectively. Negative relationships could be established between dietary RS and pH in the large intestine (P<0.05), with a stronger effect in the mid and distal colon, and feces (R2=0.64 to 0.81; P<0.001). A dietary level of 15% RS would lower the pH in the proximal, mid-, distal colon and feces by 0.2, 0.6, 0.4 and 0.6 units, respectively. Increasing RS levels, however, did not affect SCFA concentrations in the hindgut, but enhanced the molar proportion of propionate in mid-colon and reduced those of acetate in mid-colon and of butyrate in mid- and distal colon (R2=0.46 to 0.52; P<0.05). Backward elimination indicated an age-related decrease in mid-colonic propionate proportion and increase in mid- and distal colonic butyrate proportion (P<0.05), thereby modulating RS2 effects. In feces, increasing RS levels promoted fecal lactobacilli (R2=0.46; P<0.01) and bifidobacteria (R2=0.57; P<0.01), whereby the slope showed the need for a minimal RS level of 10% for a 0.5 log unit-increase in their abundance. Best-fit equations further supported that a longer experimental period increased fecal lactobacilli but decreased fecal bifidobacteria (P<0.05). In conclusion, dietary RS2 seems to effectively decrease digesta pH throughout the large intestine and increase lactic acid-producing bacteria in feces of pigs which may limit the growth of opportunistic pathogens in the hindgut. To achieve these physiologically relevant changes, dietary RS should surpass 10% to 15%.
Nutritional and nutraceutical aspects of KAMUT® khorasan wheat grown during the last two decades
- A. DI LORETO, R. DI SILVESTRO, G. DINELLI, V. BREGOLA, V. STENICO, R. E. SFERRAZZA, I. MAROTTI, R. QUINN, S. BOSI
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- The Journal of Agricultural Science / Volume 155 / Issue 6 / August 2017
- Published online by Cambridge University Press:
- 14 February 2017, pp. 954-965
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Recently, organic farming systems have attracted the attention of consumers because of their low environmental impact. Organic agriculture is a valid alternative to conventional farming and ancient wheat, such as KAMUT® khorasan wheat (T. turgidum ssp. turanicum), has emerged as an industry leader for its nutritional and functional properties (anti-inflammatory, antioxidant and prebiotic).
The aim of the present study was to evaluate environmental effects on the quality of KAMUT® khorasan grains harvested in the last two decades (1989–2012) on one farm in Montana (USA), through the evaluation of phytochemical accumulation. Results revealed high variability in the amounts of macronutrients and nutraceuticals. In particular, from 1989 to 2012, there was a decreasing trend in starch content (ranging from 70·87 to 50·54/100 g) and amylose (from 41·48 to 31·46% of total starch) with a slight increase of insoluble dietary fibre (from 12·14 to 17·75/100 g). The soluble dietary fibre content varied among the years of cultivation even if the general trend remained constant (4·57–2·82/100 g). High variability of total polyphenols content was observed with the free soluble fraction present at lower levels than bound polyphenols (BP). Moreover, an inverse correlation between free and BP was observed. The results obtained in the present study show that the influence of environmental conditions plays a fundamental role in the accumulation of primary and secondary metabolites in wheat kernels and strongly modulate the nutritional and nutraceutical value of flour.
Metabolomics evidences plasma and serum biomarkers differentiating two heavy pig breeds
- S. Bovo, G. Mazzoni, G. Galimberti, D. G. Calò, F. Fanelli, M. Mezzullo, G. Schiavo, A. Manisi, P. Trevisi, P. Bosi, S. Dall’Olio, U. Pagotto, L. Fontanesi
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In pigs, many production traits are known to vary among breeds or lines. These traits can be considered end phenotypes or external traits as they are the final results of complex biological interactions and processes whose fine biological mechanisms are still largely unknown. This study was designed to compare plasma and serum metabolomic profiles between animals of two heavy pig breeds (12 Italian Large White and 12 Italian Duroc), testing indirectly the hypothesis that different genetic backgrounds might be the determining factors of differences observed on the level of metabolites in the analyzed biofluids between breeds. We used a targeted metabolomic approach based on mass spectrometric detection of about 180 metabolites and applied a statistical validation pipeline to identify differences in the metabolomic profiles of the two heavy pig breeds. Blood samples were collected after jugulation at the slaughterhouse and prepared for metabolomics analysis that was carried out using the Biocrates AbsoluteIDQ p180 Kit, covering five different biochemical classes: glycerophospholipids, amino acids, biogenic amines, hexoses and acylcarnitines. A statistical pipeline that included the selection of the most relevant metabolites differentiating the two breeds by sparse Partial Least Squares Discriminant Analysis (sPLS-DA) was coupled with a stability test and significance test determined with leave one out and permutation procedures. sPLS-DA plots clearly separated the pigs of the two investigated breeds. A few metabolites (a total of five metabolites considering the two biofluids) involved in key metabolic pathways largely contributed to these differences between breeds. In particular, a higher level of the sphingomyelins SM (OH) C14:1 (both in plasma and serum), SM (OH) C16:1 (in serum) and SM C16:0 (in serum) were observed in Italian Duroc than in Italian Large White pigs and the inverse was for the biogenic amine kynurenine (in plasma). The level of another biogenic amine (acetylornithine) was higher in Italian Large White than in Italian Duroc pigs in both analysed biofluids. These results provided biomarkers that could be important to understand the biological differences between these two heavy pig breeds. In particular, according to the functional role played by sphingomyelins in obesity-induced inflammatory responses, it could be possible to speculate that a higher level of sphingomyelins in Italian Duroc might be related to the higher interrmuscular fat deposition of this breed compared with the Italian Large White. Additional studies will be needed to evaluate the relevance of these biomarkers for practical applications in pig breeding and nutrition.
Polymorphisms in an obesity-related gene (PCSK1) are associated with fat deposition and production traits in Italian heavy pigs
- L. Fontanesi, F. Bertolini, E. Scotti, P. Trevisi, L. Buttazzoni, S. Dall'Olio, R. Davoli, P. Bosi, V. Russo
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The proprotein convertase subtilisin/kexin type 1 (PCSK1) gene encodes the prohormone convertase 1/3 enzyme that processes prohormones into functional hormones that, in turn, regulate central and peripheral energy metabolism. Mutations in the human PCSK1 gene cause severe monogenic obesity or confer risk of obesity. We herein investigated the porcine PCSK1 gene with the aim of identifying polymorphisms associated with fat deposition and production traits in Italian heavy pigs. By re-sequencing about 5.1 kb of this gene in 21 pigs of different breeds, we discovered 14 polymorphisms that were organized in nine haplotypes, clearly distributed in two clades of putative European and Asian origin. Then we re-mapped this gene on porcine chromosome 2 and analysed its expression in several tissues including gastric oxyntic mucosa of weanling pigs in which PCSK1 processes the pre-pro-ghrelin into ghrelin, which in turn is involved in the control of feed intake and energy metabolism. Association analyses between PCSK1 single-nucleotide polymorphisms (SNPs) and production, carcass and several other traits were conducted on five groups of pigs from three different experimental designs, for a total of 1221 animals. Results indicated that the analysed SNPs were associated (P < 0.01 or P < 0.05) with several traits including backfat thickness and visible intermuscular fat in Italian Duroc (ID) and growth performances in Italian Large White (ILW) and in ILW × Italian Landrace pigs. However, the effects estimated in the ILW were opposite to the effects reported in the ID pigs. Suggestive association (P < 0.10) was observed with muscle cathepsin B activity, opening, if confirmed, potential applications to reduce the excessive softness defect of the green hams that is of particular concern for the processing industry. The results obtained supported the need to further investigate the PCSK1 gene to fully exploit the value of its variability and apply this information in pig breeding programmes.
Bt-toxin uptake by the non-target herbivore, Myzus persicae (Hemiptera: Aphididae), feeding on transgenic oilseed rape in laboratory conditions
- G. Burgio, G. Dinelli, I. Marotti, M. Zurla, S. Bosi, A. Lanzoni
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- Bulletin of Entomological Research / Volume 101 / Issue 2 / April 2011
- Published online by Cambridge University Press:
- 01 November 2010, pp. 241-247
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The potential non-target effects of genetically modified crops are some of the more debated topics within applied biotechnologies in agriculture and environmental risk assessment. The objective of the present research was to study the potential Bt-toxin uptake by the non-target herbivore Myzus persicae Sulzer (Hemiptera: Aphididae) feeding on transgenic oilseed rape plants (Brassica napus cv. ‘Westar’ lines GT 2–4) expressing the Cry1Ac endotoxin. A specific aim was to replicate our previous experiment in controlled laboratory conditions to avoid or minimize the risk of contamination leading to potential false positive results. The toxin levels in vernalized (V) and not-vernalized (not-V) transgenic oilseed rape plants was also monitored to better clarify the role of physiological processes on Bt-toxin expression. Cry1Ac expression in not-V plants (mean concentration±SE=167.8±5.7 μg kg−1 FW) showed a pattern of large variability, in comparison with V plants whose expression (mean concentration±SE=227.7±1.9 μg kg−1 FW) was significantly more stable. Cry1Ac toxin was detected in three aphid samples reared on V plants with a mean toxin concentration±SE of 4.8±0.6 μg Kg−1 FW and in three out of six samples of aphids reared on not-V plants (mean toxin concentration±SE=7.1±1.2 μg kg−1 FW). The mean Bt-toxin concentration of all the positive aphid samples was 5.9±1.0 μg kg−1 FW. Our results confirmed the findings of our previous experiment and highlighted the potential for Cry1Ac toxin uptake by aphids feeding on transgenic oilseed rape plants.
Impact of bioactive substances on the gastrointestinal tract and performance of weaned piglets: a review*
- J. P. Lallès, P. Bosi, P. Janczyk, S. J. Koopmans, D. Torrallardona
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The EU ban on in-feed antibiotics has stimulated research on weaning diets as a way of reducing post-weaning gut disorders and growth check in pigs. Many bioactive components have been investigated but only few have shown to be effective. Amongst these, organic acids (OA) have been shown to exert a bactericidal action mediated by non-dissociated OA, by lowering gastric pH, increasing gut and pancreas enzyme secretion and improving gut wall morphology. It has been postulated that they may also enhance non-specific immune responses and improve disease resistance. In contrast, relatively little attention has been paid to the impact of OA on the stomach but recent data show they can differently affect gastric histology, acid secretion and gastric emptying. Butyrate and precursors of butyric acid have received special attention and although promising results have been obtained, their effects are dependent upon the dose, treatment duration, initial age of piglets, gastrointestinal site and other factors. The amino acids (AA) like glutamine, tryptophan and arginine are supportive in improving digestion, absorption and retention of nutrients by affecting tissue anabolism, stress and (or) immunity. Glutamine, cysteine and threonine are important for maintaining mucin and permeability of intestinal barrier function. Spray-dried plasma (SDP) positively affects gut morphology, inflammation and reduces acquired specific immune responses via specific and a-specific influences of immunoglobulins and other bioactive components. Effects are more pronounced in early-weaned piglets and under poorer health conditions. Little interaction between plasma protein and antibiotics has been found, suggesting distinct modes of action and additive effects. Bovine colostrum may act more or less similarly to SDP. The composition of essential oils is highly variable, depending on environmental and climatic conditions and distillation methods. These oils differ widely in their antimicrobial activity in vitro and some components of weaning diets may decrease their activity. Results in young pigs are highly variable depending upon the product and doses used. These studies suggest that relatively high concentrations of essential oils are needed for beneficial effects to be observed and it has been assumed that these plant extracts mimic most of the effects of antibiotics active on gut physiology, microbiology and immunology. Often, bioactive substances protective to the gut also stimulate feed intake and growth performance. New insights on the effects of selected OA and AA, protein sources (especially SDP, bovine colostrum) and plant extracts with anti-bacterial activities on the gut are reported in this review.