Shedding light on the effects of supportive techniques on nonverbal synchrony and their moderators in psychotherapy for depression.

Objective: Accumulating research demonstrates the importance of utilizing supportive techniques in psychotherapy; however, little is known about therapeutic processes that are set in motion following the use of supportive techniques. The present study examined the effects of supportive techniques on nonverbal synchrony, both at the sample level and at the individual differences level.Method: The sample consisted of 86 patients from a randomized controlled trial for treatment of depression. Supportive techniques were rated by patients and therapists after every session, and nonverbal synchrony was quantified by motion energy analysis (MEA) for each session. The ability of supportive techniques to predict subsequent nonverbal synchrony was examined using polynomial regression and response surface analysis.Results: The findings suggest that, at the sample level, greater use of supportive techniques was a significant predictor of subsequent higher levels of nonverbal synchrony. At the individual differences level, this effect was significant for patients with low levels of depression severity and personality disorders, yet not significant for patients with high levels.Conclusion: The present study demonstrates that greater use of supportive techniques in treatment may facilitate a process that manifests as higher levels of synchrony, especially for patients with lower levels of personality disorders and depression.

Quality of Patient-Reported Outcome Studies Utilizing the BREAST-Q: A Systematic Review.

BACKGROUND: Patient-reported outcome (PRO) studies are essential in the assessment of surgical procedures in plastic surgery. One accepted and validated questionnaire is the BREAST-Q. OBJECTIVES: The aim of this study was to assess the quality of PRO studies in plastic surgery utilizing the BREAST-Q questionnaire. METHODS: This study involved 2 steps: (1) a systematic review of 23 key criteria assessing the quality of survey research in studies utilizing the BREAST-Q that were published between 2015 and 2018; (2) a review of current guidance for survey research in journals related to plastic surgery and breast surgery which were included in the systematic review. RESULTS: Seventy-nine studies were included in the systematic review. Many key criteria were poorly reported: 51.9% of the studies did not provide a defined response rate and almost 90% did not provide a method for analysis of nonresponse error; 67.1% lacked a description of the sample's representativeness of the population of interest, and 82.3% did not present a sample size calculation. The methods used to analyze data were not described in 11.4% of the papers; in 27.8% the data analysis presented could not allow replication of the results. Of the 16 journals in the fields of plastic surgery and breast surgery for which the "instructions to authors" were reviewed, 15 (93.7%) did not provide any guidance for survey reporting. CONCLUSIONS: The majority of key criteria are underreported by authors publishing their survey research in peer-reviewed journals in the fields of plastic and breast surgery. There is an urgent need to construct well-developed reporting guidelines for survey research in plastic surgery, and particularly in breast surgery.

Glucose-Dependent Insulinotropic Polypeptide Receptor Deficiency Leads to Impaired Bone Marrow Hematopoiesis.

The bone marrow (BM) contains controlled specialized microenvironments, or niches, that regulate the quiescence, proliferation, and differentiation of hematopoietic stem and progenitor cells (HSPC). The glucose-dependent insulinotropic polypeptide (GIP) is a gut-derived incretin hormone that mediates postprandial insulin secretion and has anabolic effects on adipose tissue. Previous studies demonstrated altered bone microarchitecture in mice deficient for GIP receptor (Gipr-/- ), as well as the expression of high-affinity GIP receptor by distinct cells constructing the BM HSPC niche. Nevertheless, the involvement of GIP in the process of BM hematopoiesis remains elusive. In this article, we show significantly reduced representation and proliferation of HSPC and myeloid progenitors in the BM of Gipr-/- mice. This was further manifested by reduced levels of BM and circulating differentiated immune cells in young and old adult mice. Moreover, GIP signaling was required for the establishment of supportive BM HSPC niches during HSPC repopulation in radioablated BM chimera mice. Finally, molecular profiling of various factors involved in retention, survival, and expansion of HSPC revealed significantly lower expression of the Notch-receptor ligands Jagged 1 and Jagged 2 in osteoblast-enriched bone extracts from Gipr-/- mice, which are important for HSPC expansion. In addition, there was increased expression of CXCL12, a factor important for HSPC retention and quiescence, in whole-BM extracts from Gipr-/- mice. Collectively, our data suggest that the metabolic hormone GIP plays an important role in BM hematopoiesis.

The process of change in psychotherapy with a pregnant patient following perinatal losses: An analysis of a case study.

AIM: Despite research suggesting increased anxiety and depressive symptoms after a perinatal loss and during future pregnancies, little knowledge exists to guide clinicians treating pregnant women after perinatal loss. This case study explores processes that facilitated therapeutic change for a pregnant patient with major depressive disorder (MDD) and posttraumatic stress disorder after perinatal losses. METHOD: The study integrated quantitative and narrative analyses in a single case derived from the pilot phase of a randomized controlled trial on supportive-expressive therapy for MDD. RESULTS: The quantitative and narrative analyses suggest that an improvement in maladaptive interpersonal patterns toward the therapist, in the form of attachment avoidance, made it possible to form a strong alliance, which in turn led to a successful outcome. CONCLUSIONS: The findings highlight the importance of improving maladaptive interpersonal patterns as a prerequisite to enable patients after pregnancy losses to develop and maintain a corrective therapeutic experience.

Recapitulating the clinical scenario of BRCA-associated pancreatic cancer in pre-clinical models.

Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal malignancies. BRCA-associated PDAC comprises a clinically relevant subtype. A portion of these patients are highly susceptible to DNA damaging therapeutics, however, responses are heterogeneous and clinical resistance evolves. We have developed unique patient-derived xenograft (PDX) models from metastatic lesions of germline BRCA-mutated patients obtained at distinct time points; before treatment and at progression. Thus, closely mimicking clinical scenarios, to further investigate treatment naïve and resistant patients. DNA was isolated from six BRCA-mutated PDXs and classified by whole-genome sequencing to stable-genome or homologous recombination deficient (HRD)-genome. The sensitivity to DNA-damaging agents was evaluated in vivo in three BRCA-associated PDAC PDXs models: (1) HRD-genome naïve to treatments; (2) stable-genome naïve to treatment; (3) HRD-genome resistant to treatment. Correlation between disease course at tissue acquisition and response to PARP inhibitor (PARPi)/platinum was demonstrated in PDXs in vivo. Only the HRD-genome PDX, naïve to treatment, was sensitive to PARP inhibitor/cisplatin treatments. Our results demonstrate heterogeneous responses to DNA damaging agents/PARPi in BRCA-associated PDX thus reflecting the wide clinical spectrum. An HRD-genome PDX generated from a naïve to treatment biopsy was sensitive to platinum/PARPi whereas no benefit was observed in treating a HRD-genome PDXs generated from a patient that had acquired resistance nor stable-genome PDXs.

Correction to: Regulation of diabetic cardiomyopathy by caloric restriction is mediated by intracellular signaling pathways involving 'SIRT1 and PGC-1α'.

Unfortunately, after publication of this article [1], it was noticed that Table 1 contained errors introduced during the production process. In the WT + AT column, the FS value is 21 ± 7 and the Body Weight value is 25 ± 2. In the WT + AT + CR column, the FS value is 46 ± 14 and the Body Weight value is 19 ± 1. The original article has been updated to reflect this.

Regulation of diabetic cardiomyopathy by caloric restriction is mediated by intracellular signaling pathways involving 'SIRT1 and PGC-1α'.

BACKGROUND: Metabolic disorders such as obesity, insulin resistance and type 2 diabetes mellitus (DM2) are all linked to diabetic cardiomyopathy that lead to heart failure. Cardiomyopathy is initially characterized by cardiomyocyte hypertrophy, followed by mitochondrial dysfunction and fibrosis, both of which are aggravated by angiotensin. Caloric restriction (CR) is cardioprotective in animal models of heart disease through its catabolic activity and activation of the expression of adaptive genes. We hypothesized that in the diabetic heart; this effect involves antioxidant defenses and is mediated by SIRT1 and the transcriptional coactivator PGC-1α (Peroxisome proliferator-activated receptor-γ coactivator). METHODS: Obese Leptin resistant (db/db) mice characterized by DM2 were treated with angiotensin II (AT) for 4 weeks to enhance the development of cardiomyopathy. Mice were concomitantly either on a CR diet or fed ad libitum. Cardiomyocytes were exposed to high levels of glucose and were treated with EX-527 (SIRT1 inhibitor). Cardiac structure and function, gene and protein expression and oxidative stress parameters were analyzed. RESULTS: AT treated db/db mice developed cardiomyopathy manifested by elevated levels of serum glucose, cholesterol and cardiac hypertrophy. Leukocyte infiltration, fibrosis and an increase in an inflammatory marker (TNFα) and natriuretic peptides (ANP, BNP) gene expression were also observed. Oxidative stress was manifested by low SOD and PGC-1α levels and an increase in ROS and MDA. DM2 resulted in ERK1/2 activation. CR attenuated all these deleterious perturbations and prevented the development of cardiomyopathy. ERK1/2 phosphorylation was reduced in CR mice (p = 0.008). Concomitantly CR prevented the reduction in SIRT activity and PGC-1α (p < 0.04). Inhibition of SIRT1 activity in cardiomyocytes led to a marked reduction in both SIRT1 and PGC-1α. ROS levels were significantly (p < 0.03) increased by glucose and SIRT1 inhibition. CONCLUSION: In the current study we present evidence of the cardioprotective effects of CR operating through SIRT1 and PGC-1 α, thereby decreasing oxidative stress, fibrosis and inflammation. Our results suggest that increasing SIRT1 and PGC-1α levels offer new therapeutic approaches for the protection of the diabetic heart.

Chemical and thyroid hormone profile of the bone marrow interstitial fluid in hematologic disorders and patients without primary hematologic disorders.

Bone marrow interstitial fluid (BMIF) has not been well characterized. BMIF was isolated from 60 patients including plasma cell dyscrasias (PCD, n = 33), other primary hematologic disorders (OHD, n = 15), and patients with secondary or nonhemtologic disorders (NHD, n = 12) and analyzed for an array of chemical constituents. These included total cholesterol, glucose, phosphate, creatinine, urea, total protein, albumin, globulins, total bilirubin, aspartate aminotransferase, lactate dehydrogenase, sodium, osmolarity, free triiodothyronine (free T3), total triiodothyronine (total T3), and free tetraiodothyronine (free T4). Levels of BMIF components were compared between patient groups and to plasma levels. Compared with plasma, total cholesterol, total protein, total bilirubin, sodium, and calculated osmolarity were lower in BMIF in all groups (P < 0.05). Calculated globulins and aspartate aminotransferase were lower in BMIF of PCD patients and patients with NHD. Albumin was lower in BMIF of patients with PCD and patients with OHD. Lastly, free T4 was significantly higher in BMIF of patients with PCD and patients with OHD. Similar results were demonstrated in a separate analysis performed in patients with multiple myeloma. To conclude, the chemical and thyroid hormone composition of BMIF differs significantly from plasma in several key constituents.

Caloric restriction ameliorates cardiomyopathy in animal model of diabetes.

BACKGROUND: The db/db mouse is an animal model of diabetes in which leptin receptor activity is deficient resulting accelerated cardiomyopathy when exposed to angiotensin (AT). Toll-like receptors 4 and 2 (TLR4, TLR2) are pattern recognition receptors, that recognize pathogen-associated molecular patterns and exacerbate and release inflammatory cytokines. Fetuin A (Fet A) is a fatty acid carrier which affects inflammation and insulin resistance in obese humans and animals through TLRs. The aim of this study was to investigate the effect of caloric restriction (CR) on free fatty acids (FFA) level and the inflammatory response in diabetic cardiomyopathy. METHODS AND RESULTS: Left ventricular hypertrophy, increased fibrosis and leukocytes infiltration were observed in db/db AT treated hearts. Serum glucose, FFA, and cholesterol levels were elevated in db/db AT treated mice. Cardiac expression of PPARα increased while AKT phosphorylation was decreased. CONCLUSIONS: Cumulatively, CR elevated cardiac PPARα improved the utilization of fatty acids, and reduced myocardial inflammation as seen by reduced levels of Fet A. Thus CR negated cardiomyopathy associated with AT in an animal model of diabetes suggesting that CR is an effective therapeutic approach in the treatment of diabetes and associated cardiomyopathy.

The Impact of Routine Evaluation of Gastric Residual Volumes on the Time to Achieve Full Enteral Feeding in Preterm Infants.

OBJECTIVE: To evaluate the time to full enteral feedings in preterm infants after a practice change from routine evaluation of gastric residual volume before each feeding to selective evaluation of gastric residual volume , and to evaluate the impact of this change on the incidence of necrotizing enterocolitis (NEC). STUDY DESIGN: Data were collected on all gavage-fed infants born at ≤34 weeks gestational age (GA) for 2 years before (n = 239) and 2 years after the change (n = 233). RESULTS: The median GA was 32.0 (IQR: 29.7-33.0) weeks before and 32.4 (30.4-33.4) weeks after the change (P = .02). Compared with historic controls, infants with selective evaluations of gastric residual volumes weaned from parenteral nutrition 1 day earlier (P < .001) and achieved full enteral feedings (150 cc/kg/day) 1 day earlier (P = .002). The time to full oral feedings and lengths of stay were similar. The rate of NEC (stage ≥ 2) was 1.7% in the selective gastric residual volume evaluation group compared with 3.3% in the historic control group (P = .4). Multiple regression analyses showed that the strongest predictor of time to full enteral feedings was GA. Routine evaluation of gastric residual volume and increasing time on noninvasive ventilation both prolonged the attainment of full enteral feedings. Findings were consistent in the subgroup with birth weights of <1500 g. Increased weight at discharge was most strongly associated with advancing postmenstrual, age but avoidance of routine evaluations of gastric residual volume also was a significant factor. CONCLUSIONS: Avoiding routine evaluation of gastric residual volume before every feeding was associated with earlier attainment of full enteral feedings without increasing risk for NEC.

[THE INVOLVEMENT OF THYROID HORMONES IN CANCER].

The possible association between thyroid hormones and cancer has been reported over the years in pre-clinical and clinical studies. These studies suggest that high levels of hormones induce cancer cell proliferation while low levels slow disease progress. A context in which to interpret such findings is the recent description of a plasma membrane receptor for the thyroid hormone on cancer cells and dividing tumor-associated endothelial cells.

Atrophic thyroid follicles and inner ear defects reminiscent of cochlear hypothyroidism in Slc26a4-related deafness.

Thyroid hormone is essential for inner ear development and is required for auditory system maturation. Human mutations in SLC26A4 lead to a syndromic form of deafness with enlargement of the thyroid gland (Pendred syndrome) and non-syndromic deafness (DFNB4). We describe mice with an Slc26a4 mutation, Slc26a4 (loop/loop) , which are profoundly deaf but show a normal sized thyroid gland, mimicking non-syndromic clinical signs. Histological analysis of the thyroid gland revealed defective morphology, with a majority of atrophic microfollicles, while measurable thyroid hormone in blood serum was within the normal range. Characterization of the inner ear showed a spectrum of morphological and molecular defects consistent with inner ear pathology, as seen in hypothyroidism or disrupted thyroid hormone action. The pathological inner ear hallmarks included thicker tectorial membrane with reduced ß-tectorin protein expression, the absence of BK channel expression of inner hair cells, and reduced inner ear bone calcification. Our study demonstrates that deafness in Slc26a4 (loop/loop) mice correlates with thyroid pathology, postulating that sub-clinical thyroid morphological defects may be present in some DFNB4 individuals with a normal sized thyroid gland. We propose that insufficient availability of thyroid hormone during inner ear development plays an important role in the mechanism underlying deafness as a result of SLC26A4 mutations.

Influence of changes in the evaluation of neonatal jaundice.

OBJECTIVE: To study the influence of policy changes in the evaluation of neonatal hyperbilirubinemia on discharge process from the nursery. Changes included early assessment of risk factors by universal umbilical blood sampling for blood type, Coombs test, and glucose-6-phosphate dehydrogenase (G6PD) and universal noninvasive transcutaneous bilirubinometry at discharge. STUDY DESIGN: The 1,569 newborns (≥ 36 weeks' gestation) admitted after the implementation of changes were compared with the 1,822 born before. RESULTS: Policy changes improved the diagnosis of G6PD deficiency and ABO incompatibility and decreased the number of referrals from the community for jaundice follow-up. The average number of needlesticks per baby as well as the time required for the analysis of serum bilirubin levels on discharge day decreased. Changes did not significantly increase costs. CONCLUSION: Changes seem to have improved the quality of medical care, including early identification of risk factors and better follow-up of neonatal hyperbilirubinemia with reduction of pain and increased efficiency.

They live in the land down under: thyroid function and basal metabolic rate in the Blind Mole Rat, Spalax.

The Israeli blind subterranean mole rat (Spalax ehrenbergi superspecies) lives in sealed underground burrows under extreme, hypoxic conditions. The four Israeli Spalax allospecies have adapted to different climates, the cool-humid (Spalax galili, 2 n = 52 chromosomes), semihumid (S. golani, 2 n = 54) north regions, warm-humid (S. carmeli, 2 n = 58) central region and the warm-dry S. judaei, 2 n = 60) southern regions. A dramatic interspecies decline in basal metabolic rate (BMR) from north to south, even after years of captivity, indicates a genetic basis for this BMR trait. We examined the possibility that the genetically-conditioned interspecies BMR difference was expressed via circulating thyroid hormone. An unexpected north to south increase in serum free thyroxine (FT4) and total 3, 5, 3'-triiodo-L-thyronine (T3) (p < 0.02) correlated negatively with previously published BMR measurements. The increases in serum FT4 and T3 were symmetrical, so that the T3:FT4 ratio - interpretable as an index of conversion of T4 to T3 in nonthyroidal tissues - did not support relative decrease in production of T3 as a contributor to BMR. Increased north-to-south serum FT4 and T3 levels also correlated negatively with hemoglobin/hematocrit. North-to-south adaptations in spalacids include decreased BMR and hematocrit/hemoglobin in the face of increasing thyroid hormone levels, arguing for independent control of hormone secretion and BMR/hematocrit/hemoglobin. But the significant inverse relationship between thyroid hormone levels and BMR/hematocrit/hemoglobin is also consistent with a degree of cellular resistance to thyroid hormone action that protects against hormone-induced increase in oxygen consumption in a hostile, hypoxic environment.

Unleashing Natural IL18 Activity Using an Anti-IL18BP Blocker Induces Potent Immune Stimulation and Antitumor Effects.

Recombinant cytokines have limited anticancer efficacy mostly due to a narrow therapeutic window and systemic adverse effects. IL18 is an inflammasome-induced proinflammatory cytokine, which enhances T- and NK-cell activity and stimulates IFNγ production. The activity of IL18 is naturally blocked by a high-affinity endogenous binding protein (IL18BP). IL18BP is induced in the tumor microenvironment (TME) in response to IFNγ upregulation in a negative feedback mechanism. In this study, we found that IL18 is upregulated in the TME compared with the periphery across multiple human tumors and most of it is bound to IL18BP. Bound IL18 levels were largely above the amount required for T-cell activation in vitro, implying that releasing IL18 in the TME could lead to potent T-cell activation. To restore the activity of endogenous IL18, we generated COM503, a high-affinity anti-IL18BP that blocks the IL18BP:IL18 interaction and displaces precomplexed IL18, thereby enhancing T- and NK-cell activation. In vivo, administration of a surrogate anti-IL18BP, either alone or in combination with anti-PD-L1, resulted in significant tumor growth inhibition and increased survival across multiple mouse tumor models. Moreover, the anti-IL18BP induced pronounced TME-localized immune modulation including an increase in polyfunctional nonexhausted T- and NK-cell numbers and activation. In contrast, no increase in inflammatory cytokines and lymphocyte numbers or activation state was observed in serum and spleen. Taken together, blocking IL18BP using an Ab is a promising approach to harness cytokine biology for the treatment of cancer.

Colchicine treatment can be discontinued in a selected group of pediatric FMF patients.

OBJECTIVES: Familial Mediterranean Fever (FMF) patients are required to adhere to a life-long treatment with colchicine, primarily for preventing amyloidosis. As some patients may be asymptomatic for long periods of time, it remains unclear whether it is possible to discontinue colchicine treatment in a selective group of patients. We aimed to identify predictive characteristics for a successful cessation of colchicine therapy. METHODS: Out of 646 FMF pediatric patients followed in our referral FMF clinic, colchicine treatment was discontinued in 51 patients. In this study we compared the genetic, demographic, and clinical characteristics between patients for whom a successful cessation of therapy was made (Group 1; n = 21) and patients for whom cessation of therapy was deemed a failure (Group 2; n = 30) and consequently had to resume colchicine therapy. RESULTS: Patients for whom a successful cessation of therapy was achieved had no biallelic pathogenic MEFV mutations, were less likely to have "severe attacks" (two or more FMF characteristic symptoms) (24% vs 80%; P = 0.000067) and did not require higher than 1 mg/day of colchicine, prior to the drug cessation. Remission duration under colchicine treatment was significantly higher in group 1 compared with group 2 (4.36 years ±2.12 vs 2.53 years ±2; P = 0.0036). CONCLUSION: This study supports the concept of colchicine free remission in a minority of FMF patients (3%). Holding treatment, under close monitoring, may be reasonable when selecting the appropriate patients.

A multimodal case study utilizing physiological synchrony as indicator of context in which motion synchrony is associated with the working alliance.

Interest in the association between patient and therapist's motion synchrony and the working alliance has been growing in recent years. This interest is part of a larger effort in psychotherapy research to study how the working alliance, being central to the therapeutic process, develops over the course of therapy. However, while previous studies suggest that such an association between motion synchrony and the working alliance exists, there are mixed results regarding the direction of it. The present single-case study seeks to shed light on these mixed results with a multimodal perspective of nonverbal synchrony. That is, through an exploration of a single case, the present study explores physiological synchrony as an indicator of context in which motion synchrony is associated with the working alliance. For this aim, a single case was chosen from a randomized control trial investigating short-term psychodynamic treatment for major depressive disorder. Statistical analysis identified an interaction between physiological synchrony and motion synchrony in predicting working alliance levels. Findings show that in the context of an antiphase pattern of physiological synchrony (negative association between physiological measures of the two participants), there was a positive association between motion synchrony and the working alliance. This study emphasizes the potential of a multimodal approach, while suggesting a possible explanation for mixed results in current literature that focuses on the association between motion synchrony and the working alliance. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

[Liver injury in idiopathic CD4+T-cell lymphocytopenia].

A 48 years old patient was admitted to the Internal Medicine ward due to progressive weakness and abnormal liver function tests. During three months of hospitalization she developed opportunistic infections with Cryptococcus and Pneumocystic jiroveci pneumonia. The CD4+ T-cell lymphocyte count was very low with no evidence of infection with human immunodeficiency virus. Liver disease deteriorated with the appearance of profound jaundice and severe hepatitis. The patient's laboratory and clinical presentation were compatible with the diagnosis of idiopathic CD4 + T-cell lymphocytopenia--ICL. The authors reviewed the literature on ICL and discuss the rare hepatic presentation of this uncommon syndrome.

Israeli Innovations in the Field of Plastic Surgery.

Numerous innovations within the field of plastic surgery have been developed in Israel over the last few decades. Many of these therapeutic devices and techniques have been established globally with demonstrable efficacy and respectable safety profiles. This article offers an overview of recent Israeli cutting-edge medical therapeutic solutions contributing to the global practice of plastic surgery.

Vicarious exposure to trauma and growth in therapists: the moderating effects of sense of coherence, organizational support, and empathy.

Therapists who work with traumatized individuals can experience psychological growth following this vicarious exposure to trauma. The purpose of the present study is to examine the variables that may moderate such vicarious posttraumatic growth. Therapists (N = 118) completed measures of vicarious exposure to trauma and growth, as well as empathy, sense of coherence, and perceived organizational support. Results showed that having a strong sense of coherence negatively predicted growth (ß = -.28, p = .001), whereas empathy was a positive predictor (ß = .37, p < .001). Empathy also moderated the exposure to growth relationship when growth involved relating to others (ß = -.20; p = .018). Organizational support did not predict growth. The results have implications for the recruitment, training, and supervision of therapists working with individuals who have experienced trauma.