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Growing awareness that many who are diagnosed with schizophrenia recover has spurred the development of new psychosocial approaches to treatment. These new approaches include forms of individual and group psychotherapy whose focus extends beyond reducing symptoms and improving skills to subjective outcomes related to sense of self. This paper introduces an issue of In Session which presents six case reports which illustrating these approaches in differing international contexts. First, we explore the larger issues of subjective outcomes from schizophrenia. We then discuss each of the papers separately along with implications of these papers as a group for how treatment might promote the recapturing of a sense of self or place in the world.

Paranoid personality disorder (PPD) is a severe condition, lacking specialized and empirically supported treatment. To provide the clinician with insights into how to treat this condition, we present a case study of a 61-year-old man with severe PPD who presented with ideas of persecution, emotionally charged hostility, and comorbid antisocial personality disorder. The client was treated with 6 months of Metacognitive Interpersonal Therapy, which included: creating a shared formulation of his paranoid attitudes; trying to change his inner self-image of self-as-inadequate and his interpersonal schemas where he saw the others as threatening. Guided imagery and rescripting techniques, coupled with behavioral experiments, were used to promote a change. At the end of the therapy the client reported a reliable change in general symptomatology and, specifically, in interpersonal sensitivity, hostility, and paranoid ideation; he could no longer be diagnosed as PPD and only some paranoid and antisocial characteristics remained.

Objective Burnout may represent a significant source of distress in health care professionals. Many studies have reported its negative effect on career satisfaction and personal life. The aim of the present study was to investigate the relation between burnout and life satisfaction in a large sample of Italian oncologists. Methods An online survey was conducted of 14.5% of the Italian oncologists' population (n = 533) using Copenhagen Burnout Inventory, Satisfaction with Life Scale and additional questions exploring professional and personal factors. Moderated regression analysis was carried out to explore how burnout may relate to life satisfaction. Results One out of 10 (10.5%) oncologists showed significant burnout symptoms, whereas 1 out of 3 (33.8%) reported being at least slightly dissatisfied with their own life. Family concerns significantly moderated the relationship between burnout and life satisfaction. Men and chiefs of cancer units or departments showed lower rates of burnout and life dissatisfaction than women and other oncologists, respectively. Conclusions Reported results are in line with existing data about a limited burnout prevalence in Italian oncologists. We discuss the potential role of gender inequality in explaining our findings. The present study suggests that family concerns may be considered a risk factor for both burnout and life dissatisfaction in oncologists.

Purpose Humans evolved within the mammalian line as a highly social species. Indeed, sociality has been a major driver of human social intelligence. From birth, social relationships have emotional and self-regulating properties and operate through different body systems. This paper will explore how heart rate variability (HRV), an index of the vagal regulation of the heart and a central element of the physiological underpinnings of sociality, is related to mental health problems, with important implications for psychotherapy. Methods We conducted a narrative review of the literature on the bi-directional links between prosocial motivations, HRV, and psychophysiological functioning. Results HRV is associated not only with the ability to downregulate physiological arousal, but also with a variety of psychological and behavioural variables which are usually the target of psychotherapeutic interventions. A modern neurovisceral integration model can be employed to explain the complex intercorrelation between HRV and psychophysiological functioning. In particular, the link between HRV, the experience of inter- and intrapersonal safeness, and the inhibitory function of the prefrontal cortex will be explored in the context of prosocial motives, such as compassion, that alleviate and help prevent mental health difficulties. Conclusions Our knowledge of the social brain and its physiological underpinnings might influence important elements of a therapeutic intervention, from the initial assessment of patient's difficulties to the evaluation of therapy outcomes. Practitioner points Social relationships have emotional and self-regulating properties. The experience of inter- and intrapersonal safeness is connected to prosocial motives, such as compassion, and the inhibitory function of the prefrontal cortex. Social relationships and compassion influence different body systems, such as the vagus nerve. Many forms of psychopathology represent the activation of evolved, defensive strategies especially in contexts where there are few stimuli indicating safeness and social support. Heart rate variability predicts psychotherapy outcome.

Aim To assess the possible risk of acute kidney injury (AKI) with the use of sodium-glucose co-transporter-2 inhibitors (SGLT2-i) as well as changes in estimated glomerular filtration rate (eGFR), hospitalizations and mortality in a real-world setting. Materials and methods Included in this historical cohort study were patients with type 2 diabetes in a large health organization in Israel who initiated therapy with SGLT2-i or dipeptidyl peptidase-4 inhibitors (DPP-4i) during 1 April 2015 to 30 June 2017. We collected data on serum creatinine measurements taken between 180 days prior to and 24 weeks after therapy initiation. Study endpoints included ≥30% reduction in eGFR, hospitalization with AKI, any hospitalization and all-cause mortality. Results Overall 6418 and 5604 patients initiated SGLT2-i and DPP-4i, respectively. Baseline mean (SD) eGFR was higher among the SGLT2-i group compared with the DPP-4i group (88.3 [17.4] and 82.8 [23.7], respectively) but were similar when stratifying by chronic kidney disease (CKD) stages. The adjusted odds ratio (OR) (95% confidence interval [CI]) for ≥30% reduction in eGFR with SGLT2-i versus DPP4-i was 0.70 (0.49-1.00) and ORs ranged from 1.97 (0.62-6.26) to 0.45 (0.21-0.99) in patients with baseline eGFR 30 to 45 and ≥90 mL/min/1.73 m2 , respectively. Risks of AKI (OR = 0.47, 95% CI 0.27-0.80), hospitalization (OR = 0.66, 95% CI 0.56-0.78) or all-cause mortality (OR = 0.43, 95% CI 0.20-0.95) were lower in patients initiating SGLT2-i versus DPP-4i. Conclusions This real-world data analysis supports reassuring findings from previous randomized clinical trials showing no increased AKI risk among SGLT2-i users. Nevertheless, because of the more prominent decrease in eGFR in patients with moderate CKD, cautious use of SGLT2-i in patients with reduced eGFR is advised.

Cornelia de Lange syndrome (CdLS) is a genetic condition characterized by intellectual disability, peculiar facial dysmorphisms, multiorgan malformations, and growth problems. Majority cases of CdLS are caused by mutations in genes of Cohesin pathway. Although feeding problems are a well-known feature, no specific data have been published about the use of nutritional devices. We analyzed use, type, time of introduction, and duration of nutritional devices in 73 CdLS patients. In total, 29/73 (40%) used a device; nasogastric tube (NGT) in 28/73 (38%) and percutaneous endoscopic gastrostomy (PEG) in 7/73 (10%). NGT was placed during the first days/weeks of life. 19/28 (68%) maintained it for less than 3 months, 7/28 (25%) for a period between 3 and 12 months, while 2/28 (7%) for more than 1 year. PEG was placed within the first year in 4/7 (57%) and removed in two patients after 4 years These data have been matched with a wide number of genetic and clinical variables. Presence of upper limb malformations is positively correlated with the need of a device. From the opposite side, the use of a device positively correlates with a more severe prognosis as regard growth, intellectual development and disease severity. Our data show that nutritional devices are frequently used by CdLS patients, also if the majority of them (93.1%) succeed with time in achieving a normal oral nutrition. Finally, the need, the type of device used and the duration of NGT or/plus PEG can be considered a further sign of worse prognosis of the disease itself.

Background Vildagliptin is a dipeptidyl peptidase-4 inhibitor commonly used as a dual oral agent with metformin, thiazolidinediones, or sulfonylurea for the treatment of type 2 diabetes mellitus (T2DM). The efficacy of dual therapy with vildagliptin and metformin has been established in randomized controlled trials, but there is little evidence from observational studies. The aims of the present study were to evaluate the effectiveness of vildagliptin as an add-on therapy to metformin in reducing HbA1c and its affects on body weight and blood lipids in a real-life setting. Methods Included in the present retrospective cohort were T2DM patients (n = 345) who were uncontrolled on metformin monotherapy and intensified treatment with vildagliptin. The efficacy of at least 90 days of dual therapy with vildagliptin and metformin in reducing HbA1c levels, as well as changes in blood lipids and body weight, were evaluated. Results After 180 days (range 90–365 days) from the index date with a mean daily dose of 92 mg vildagliptin, HbA1c was significantly (P < 0.001) reduced by an average of 0.9% (95% confidence interval −1.0%, −0.7%). The absolute reduction in HbA1c was positively associated with baseline HbA1c levels. In addition to HbA1c, a modest but significant (P < 0.05) decrement was also calculated in the patients' body weight and blood lipids. Conclusions The present analysis of real-world data corroborates the results of previous randomized controlled trials indicating that add-on therapy with vildagliptin in uncontrolled patients on metformin monotherapy is associated with a significant improvement in the control of HbA1c.

Objective Fear of recurrence is a crucial issue in cancer care. On the one hand, the increase of cancer-survival rates and complexity of care is exposing patients to this type of fear. On the other hand, it is a distressing and recurrent psychosocial risk that affects quality of life and adherence to follow-up. Patients should have access to targeted psychological interventions aimed at reducing or preventing fear of recurrence. This mixed-methods pilot study reports the preliminary results of a novel mindfulness- and metacognition-based intervention specifically targeting fear of recurrence. Methods The study was composed of an individual (n = 76) and a group (n = 38) intervention, both lasting 8 weeks, that were evaluated through a preassessment and postassessment and a 1-month follow-up. We enrolled women recovering from breast cancer (n = 114) in follow-up care, with significant psychosocial distress. Patients with more severe psychopathology were assigned to the individual treatment, whereas the less severe ones were assigned to the group treatment. We explored the distress and the fear of recurrence through standardized measures and in-depth qualitative interviews. Results Results showed that depressive, anxious, and post-traumatic symptoms were reduced significantly in the entire sample. Patients reported a significant reduction of fear of recurrence, which was described in terms of loss of control, increase of uncertainty, and decrease of metacognitive and interpersonal skills. Conclusions Although further studies are needed, these findings provide preliminary proof-of-concept results for the potential of integrated mindfulness- and metacognition-based interventions to reduce fear of recurrence in cancer patients.

Summary The human immunodeficiency virus (HIV)/hepatitis B virus (HBV) co-infection is likely to be associated with an increased risk of kidney disease, due to the additional factors that may affect renal function in the HIV population. We aimed to evaluate renal toxicity in HIV/HBV and HBV mono-infected patients on long-term therapy with tenofovir (TDF) and to explore the association of polymorphisms in ATP-binding cassette (ABCC)2, ABCC4, ABCC10 with the development of renal dysfunction. From September 2006 to November 2014, 44 HIV/HBV co-infected and 34 HBV mono-infected patients were commenced on TDF. Data of renal safety were retrospectively collected and analyzed. ABCC2, ABCC4 and ABCC10 genotypes were identified by real-time PCR. Over 60 months of observation, there was a significant increase in mean creatinine levels from baseline (P

We have found a significant upregulation of L-type voltage-operated Ca(++) channels (VOCCs) in reactive astrocytes. To test if VOCCs are centrally involved in triggering astrocyte reactivity, we used in vitro models of astrocyte activation in combination with pharmacological inhibitors, siRNAs and the Cre/lox system to reduce the activity of L-type VOCCs in primary cortical astrocytes. The endotoxin lipopolysaccharide (LPS) as well as high extracellular K(+) , glutamate, and ATP promote astrogliosis in vitro. L-type VOCC inhibitors drastically reduce the number of reactive cells, astrocyte hypertrophy, and cell proliferation after these treatments. Astrocytes transfected with siRNAs for the Cav1.2 subunit that conducts L-type Ca(++) currents as well as Cav1.2 knockout astrocytes showed reduce Ca(++) influx by ∼80% after plasma membrane depolarization. Importantly, Cav1.2 knock-down/out prevents astrocyte activation and proliferation induced by LPS. Similar results were found using the scratch wound assay. After injuring the astrocyte monolayer, cells extend processes toward the cell-free scratch region and subsequently migrate and populate the scratch. We found a significant increase in the activity of L-type VOCCs in reactive astrocytes located in the growing line in comparison to quiescent astrocytes situated away from the scratch. Moreover, the migration of astrocytes from the scratching line as well as the number of proliferating astrocytes was reduced in Cav1.2 knock-down/out cultures. In summary, our results suggest that Cav1.2 L-type VOCCs play a fundamental role in the induction and/or proliferation of reactive astrocytes, and indicate that the inhibition of these Ca(++) channels may be an effective way to prevent astrocyte activation. GLIA 2016. GLIA 2016;64:1396-1415.

Objectives Assess the evolution of right-to-left shunt (RLS) after transcatheter patent foramen ovale (PFO) closure. Background Despite the high number of interventional procedures performed worldwide, limited systematic data on the long-term abolition of RLS after percutaneous closure are available. Methods All patients treated at our Institution between February 2001 and July 2009 were included in this single center, prospective study, and were asked to repeat late contrast transcranial Doppler (cTCD). Rate of complete closure, residual RLS (i.e., a shunt that persists after closure), and recurrent RLS (i.e., a shunt that reappears after a previous negative cTCD) was assessed. Results Long-term follow-up was completed in 120 patients (56% male). RLS was still detectable 4.9 ± 2.3 years (range 1.3–10.3) after the procedure in 55 patients; 20 (17%) had residual RLS and 35 (29%) had recurrent RLS. Multivariate analysis revealed that significant predictors of residual RLS included post-procedural shunt at transesophageal echocardiography (OR 3.07, 95%CI 0.97–9.7), use of a bigger device (35 vs 25 mm, OR 3.85, 95%CI 1.22–12.2) and length of follow-up (OR 0.75, 95%CI 0.57–0.98), while only length of follow-up (OR 0.77, 95%CI 0.62–0.95) was associated with recurrent RLS. Neurological recurrences (1 stroke, 6 transient ischemic attacks) were equally distributed between the groups. Conclusion A significant number of recurrent and residual shunts may be observed by cTCD up to 5 years after PFO closure. Management of late RLSs includes periodic re-evaluation, exclusion of device-induced complications or secondary sources of RLS, and optimization of antithrombotic treatment with or without a second intervention. (J Interven Cardiol 2015;28:600–608)

HAT tag, a natural His affinity tag, is one of the most popular fusion tags. However, HAT tag containing three positive charges limited its self-assembly with quantum dots (QDs). Herein, ATTO 590-labeled HAT peptide was synthesized to self-assemble with QDs inside the capillary. QDs and ATTO 590-labeled HAT peptide were sequentially injected into the capillary and probed by fluorescence-coupled CE (CE-FL), showing an obvious Forster resonance energy transfer signal. Online self-assembly, separation, and detection were achieved within 10 min. CE-FL further revealed that imidazole and H6 G6 peptide could partially outcompete with HAT tag on the QDs surface inside the capillary. The displacement intermediates were separated clearly using CE-FL. Our study demonstrates the power of online CE-FL in analyzing the binding interaction between ligands containing positive charges and QDs.

Nanoparticles provide significantly enhanced binding characteristics. However, fast online probing of the self-assembly process remains hard to achieve in practice. Herein, we report a fluorescence coupled CE method for probing the self-assembly events between quantum dots (QDs) and engineered Jumonji domain-containing protein 6 (Jmjd6) enzyme. QDs and Jmjd6 were sequentially injected into the capillary, where the self-assembly took place in a nanoliter scale. In particular, we showed that the Jmjd6/QD ratio, the interval time, and the injection volume had a great effect on the online self-assembly. The current approach may allow for a better understanding of QDs-enzyme self-assembly and enzymatic activity detection.

Wandering spleen is a condition in which an incomplete fusion of the splenic ligaments allows the spleen to move within the abdomen, predisposing it to splenic torsion along its vascular pedicle. Torsion of a wandering spleen is an uncommon occurrence, especially in children, and associated torsion of the distal pancreas is even more unusual, with only four cases having been reported in adults. Non-specific clinical presentation makes radiologic evaluation essential in order to obtain a diagnosis and to send the patient for early surgery before life-threatening complications arise. Here we present a rare case of torsion of wandering spleen together with volvulus of the distal pancreas in a 13-year-old girl. In this case, prompt radiological assessment allowed for an early diagnosis, and the patient was successfully treated with urgent laparoscopic derotation of both the spleen and the distal pancreas as well as mesh splenopexy. To the best of our knowledge, this procedure has never been described in a pediatric setting.

Aims Triplet chemotherapy with fluoropyrimidines, oxaliplatin and irinotecan is a standard therapy for metastatic colorectal cancer (CRC). Single nucleotide polymorphisms (SNPs) in DPYD and UGT1A1 influence fluoropyrimdines and irinotecan adverse events (AEs). Low frequency DPYD variants (c.1905 + 1G > A, c.1679 T > G, c.2846A > T) are validated but more frequent ones (c.496A > G, c.1129-5923C > G and c.1896 T > C) are not. rs895819 T > C polymorphism in hsa-mir-27a is associated with reduced DPD activity. In this study, we evaluated the clinical usefulness of a pharmacogenetic panel for patients receiving triplet combinations.

As a vast number of novel materials in particular inorganic nanoparticles have been invented and introduced to all aspects of life, public concerns about how they might affect our ecosystem and human life continue to arise. Such incertitude roots at a fundamental question of how inorganic nanoparticles self-assemble with biomolecules in solution. Various techniques have been developed to probe the interaction between particles and biomolecules, but very few if any can provide advantages of both rapid and convenient. Herein, we report a systematic investigation on quantum dots (QDs) and protein self-assembly inside a capillary. QDs and protein were injected to a capillary one after another. They were mixed inside the capillary when a high voltage was applied. Online separation and detection were then achieved. This new method can also be used to study the self-assembly kinetics of QDs and protein using the Hill equation, the KD value for the self-assembly of QDs and protein was calculated to be 8.8 μM. The obtained results were compared with the previous out of-capillary method and confirmed the effectiveness of the present method.