Conventional weight loss therapy in morbid obesity during COVID-19 pandemic: degree of burdens at baseline and treatment efficacy.

Introduction: COVID-19 affected global physical and psychological health. The purpose of this study was to explore the pandemics impact on health-related quality of life (HRQoL), mental health (anxiety, depression, and perceived stress) and eating behavior in people with severe obesity participating in a multimodal conservative behavioral weight loss (BWL) program conducted via videoconferencing. Additionally, the efficacy of the six-month BWL program in a virtual video-based setting during the pandemic was examined. Methods: 297 participants of a face-to-face multimodal behavioral weight loss program prior to the pandemic (PrePAN, May 2014-September 2019) and 146 participants of the in terms of content same intervention in a videoconference-based setting during the pandemic (PAN, July 2020-April 2022) were questioned and compared using standardized questionnaires for HRQoL, symptoms of depressive and anxiety disorders, perceived stress, and eating behavior at baseline and at the end of treatment. Results: Symptoms for anxiety, depression and perceived stress were similar between PrePAN and PAN at baseline. In addition, PAN tended to show lower disinhibition of eating behavior and feelings of hunger than PrePAN. During the pandemic, the BWL intervention resulted in body weight loss (67%) or stabilization (16%) in most of the participants. It also contributed by improving physical HRQoL, lower worries, and improved eating behaviors compared to baseline. Conclusion: During the COVID-19 pandemic, baseline mental health of people with morbid obesity was not worse than before the pandemic. Additionally, the BWL intervention in the virtual video-based setting stabilized and improved physical and mental health during the COVID-19 pandemic.

Attitude Matters! How Attitude towards Bariatric Surgery Influences the Effects of Behavioural Weight Loss Treatment.

INTRODUCTION: Multidisciplinary obesity services at university hospitals usually treat patients with more complex and severe obesity. In addition, patients with Class 3 obesity, in particular, have different attitudes regarding the choices of therapy. METHODS: This explorative study investigated the effect of patient attitudes towards bariatric surgery on body weight change (primary outcome) and psychological improvement (secondary outcomes: quality of life, depression, anxiety, and eating behaviour) in a 6-month moderate behavioural weight loss (BWL) programme in a university outpatient setting. RESULTS: 297 patients with mostly Class 3 obesity participated in the programme. The patients did not yet have any indications for bariatric surgery. Of the participants, 37% had a positive attitude towards bariatric surgery (POS), whereas 38% had a negative attitude (NEG). The drop-out rate was 8%. NEG participants lost significantly more body weight than the POS participants (intention-to-treat population: 4.5 [SD: 6.3] kg versus 0.4 [SD: 5.8] kg; p < 0.001). In both subgroups, anxiety, depression, the mental score for quality of life, and eating behaviour improved. CONCLUSION: A BWL treatment in a clinical setting identified 2 distinct groups with different attitudes towards bariatric surgery that were associated with different body weight change outcomes. These groups may require differently targeted programmes to achieve the best body weight loss results.

Ultrastaging Using Ex Vivo Sentinel Lymph Node Mapping and One-Step Nucleic Acid Amplification (OSNA) in Gastric Cancer: Experiences of a European Center.

BACKGROUND: In this study, the effectiveness of One-step nucleic acid amplification (OSNA) in combination with ex vivo SLN mapping is compared with conventional histology including immunohistochemistry. METHODS: LNs were retrieved from gastrectomy specimens in an unfixed state. After ex vivo SLN mapping using methylene-blue, LNs were sliced to provide samples for histology and OSNA. RESULTS: In total, 334 LNs were retrieved in the fresh state from 41 patients. SLN detection was intended in 40 cases but was successful in only 29, with a correct LN status prediction in 23 cases (79%). Excluding one case out of 41 with a failure likely caused by a processing error, OSNA showed a high effectiveness with sensitivity, specificity, and accuracy rates of 85.4%, 93.5%, and 92.4%, respectively. The LN status could be predicted in all but one case, in which the single positive LN was not eligible for OSNA testing. Moreover, OSNA evaluation led to upstaging from N0 to N+ in three cases (14%). CONCLUSION: The ex vivo SLN protocol used resulted in a relatively poor detection rate. However, the OSNA method was not hampered by this detection rate and proved its potential to increase the sensitivity of metastases detection.

Gut Microbiota, Probiotics and Psychological States and Behaviors after Bariatric Surgery-A Systematic Review of Their Interrelation.

The gastrointestinal (GI) microbiota plays an important role in health and disease, including brain function and behavior. Bariatric surgery (BS) has been reported to result in various changes in the GI microbiota, therefore demanding the investigation of the impact of GI microbiota on treatment success. The goal of this systematic review was to assess the effects of BS on the microbiota composition in humans and other vertebrates, whether probiotics influence postoperative health, and whether microbiota and psychological and behavioral factors interact. A search was conducted using PubMed and Web of Science to find relevant studies with respect to the GI microbiota and probiotics after BS, and later screened for psychological and behavioral parameters. Studies were classified into groups and subgroups to provide a clear overview of the outcomes. Microbiota changes were further assessed for whether they were specific to BS in humans through the comparison to sham operated controls in other vertebrate studies. Changes in alpha diversity appear not to be specific, whereas dissimilarity in overall microbial community structure, and increases in the abundance of the phylum Proteobacteria and Akkermansia spp. within the phylum Verrucomicrobia after surgery were observed in both human and other vertebrates studies and may be specific to BS in humans. Human probiotic studies differed regarding probiotic strains and dosages, however it appeared that probiotic interventions were not superior to a placebo for quality of life scores or weight loss after BS. The relationship between GI microbiota and psychological diseases in this context is unclear due to insufficient available data.

Conventional weight loss interventions across the different BMI obesity classes: A systematic review and quantitative comparative analysis.

OBJECTIVE: The recommendation for conventional body weight loss (BWL) treatment in obesity is 5-10%. It is not clear whether BWL is similar across the three different body mass index (BMI) obesity classes. The aim was to provide an overview on BWL across these classes in moderate lifestyle/diet intervention programs. METHOD: A systematic literature search was conducted and the evidence of randomized controlled trials (RCTs) and pre-post design studies synthesized. The outcome was BWL. RESULTS: For RCTs, mean BWL in the intervention group was 3.6 kg (class I) and 5.3 kg (class II), which equates to 4 and 5% BWL, respectively. None of the assessed class III obesity studies met the inclusion criteria. For pre-post design studies, mean BWL was 5.4 kg (class I), 5.5 kg (class II) and 7.9 kg (class III), with high variation within and across studies in the latter. This equates to 6, 5 and, 6% BWL, respectively. CONCLUSIONS: BWL of moderate BWL programs are similar across the different obesity classes. For class I obesity, the results differ between RCT and pre-post design studies by 2% BWL. The high variation of BWL in class III obesity might reflect different states of motivation such as the attitude towards bariatric surgery.

Current indications for stentless aortic bioprostheses.

The best aortic prostheses have been debated for decades. The introduction of stentless aortic bioprostheses was aimed at improving hemodynamics and potentially the durability of aortic bioprostheses. Despite the good short- and long-term outcomes after implantation of stentless aortic bioprostheses, their use remains limited owing to the technically demanding implantation techniques. Nevertheless, stentless aortic bioprostheses might be of special benefit in certain indications, where they could be a valuable addition to the surgical armamentarium.

Glucocorticoid receptor regulates accurate chromosome segregation and is associated with malignancy.

The glucocorticoid receptor (GR) is a member of the nuclear receptor superfamily, which controls programs regulating cell proliferation, differentiation, and apoptosis. We have identified an unexpected role for GR in mitosis. We discovered that specifically modified GR species accumulate at the mitotic spindle during mitosis in a distribution that overlaps with Aurora kinases. We found that Aurora A was required to mediate mitosis-driven GR phosphorylation, but not recruitment of GR to the spindle. GR was necessary for mitotic progression, with increased time to complete mitosis, frequency of mitotic aberrations, and death in mitosis observed following GR knockdown. Complementation studies revealed an essential role for the GR ligand-binding domain, but no clear requirement for ligand binding in regulating chromosome segregation. The GR N-terminal domain, and specifically phosphosites S203 and S211, were not required. Reduced GR expression results in a cell cycle phenotype, with isolated cells from mouse and human subjects showing changes in chromosome content over prolonged passage. Furthermore, GR haploinsufficient mice have an increased incidence of tumor formation, and, strikingly, these tumors are further depleted for GR, implying additional GR loss as a consequence of cell transformation. We identified reduced GR expression in a panel of human liver, lung, prostate, colon, and breast cancers. We therefore reveal an unexpected role for the GR in promoting accurate chromosome segregation during mitosis, which is causally linked to tumorigenesis, making GR an authentic tumor suppressor gene.

TBX3 Directs Cell-Fate Decision toward Mesendoderm.

Cell-fate decisions and pluripotency are dependent on networks of key transcriptional regulators. Recent reports demonstrated additional functions of pluripotency-associated factors during early lineage commitment. The T-box transcription factor TBX3 has been implicated in regulating embryonic stem cell self-renewal and cardiogenesis. Here, we show that TBX3 is dynamically expressed during specification of the mesendoderm lineages in differentiating embryonic stem cells (ESCs) in vitro and in developing mouse and Xenopus embryos in vivo. Forced TBX3 expression in ESCs promotes mesendoderm specification by directly activating key lineage specification factors and indirectly by enhancing paracrine Nodal/Smad2 signaling. TBX3 loss-of-function analyses in the Xenopus underline its requirement for mesendoderm lineage commitment. Moreover, we uncovered a functional redundancy between TBX3 and Tbx2 during Xenopus gastrulation. Taken together, we define further facets of TBX3 actions and map TBX3 as an upstream regulator of the mesendoderm transcriptional program during gastrulation.

Telomerase gene mutations are associated with cirrhosis formation.

UNLABELLED: Telomere shortening impairs liver regeneration in mice and is associated with cirrhosis formation in humans with chronic liver disease. In humans, telomerase mutations have been associated with familial diseases leading to bone marrow failure or lung fibrosis. It is currently unknown whether telomerase mutations associate with cirrhosis induced by chronic liver disease. The telomerase RNA component (TERC) and the telomerase reverse transcriptase (TERT) were sequenced in 1,121 individuals (521 patients with cirrhosis induced by chronic liver disease and 600 noncirrhosis controls). Telomere length was analyzed in patients carrying telomerase gene mutations. Functional defects of telomerase gene mutations were investigated in primary human fibroblasts and patient-derived lymphocytes. An increased incidence of telomerase mutations was detected in cirrhosis patients (allele frequency 0.017) compared to noncirrhosis controls (0.003, P value 0.0007; relative risk [RR] 1.859; 95% confidence interval [CI] 1.552-2.227). Cirrhosis patients with TERT mutations showed shortened telomeres in white blood cells compared to control patients. Cirrhosis-associated telomerase mutations led to reduced telomerase activity and defects in maintaining telomere length and the replicative potential of primary cells in culture. CONCLUSION: This study provides the first experimental evidence that telomerase gene mutations are present in patients developing cirrhosis as a consequence of chronic liver disease. These data support the concept that telomere shortening can represent a causal factor impairing liver regeneration and accelerating cirrhosis formation in response to chronic liver disease.

Dihydroartemisinin induces apoptosis by a Bak-dependent intrinsic pathway.

The sesquiterpene lactone dihydroartemisinin (DHA), a semisynthetic derivative of the herbal antimalaria drug artemisinin, is cytotoxic to human tumor cells. Treatment of Jurkat T-lymphoma cells with DHA induced a breakdown of the mitochondrial transmembrane potential, release of cytochrome c, activation of caspases, and DNA fragmentation indicative of apoptosis induction. Although the absence of FADD or caspase-8 did not alter apoptosis rates in Jurkat cells, overexpression of dominant-negative caspase-9 or of antiapoptotic Bcl-xL or Bcl-2 largely decreased the cytotoxicity of DHA, demonstrating a role of the intrinsic death pathway. The proapoptotic Bcl-2 effector protein Bak and the Bcl-2 homology domain 3-only protein NOXA turned out to be important mediators of DHA-induced apoptosis in Jurkat cells. DHA treatment triggered the expression of NOXA and the activation of Bak. Furthermore, DHA-induced apoptosis was completely abrogated by loss of Bak and largely reduced in cells with siRNA-mediated downregulation of Bak or NOXA. Proapoptotic signaling of DHA also involved the formation of reactive oxygen species and membrane oxidation. Pretreatment with the lipophilic radical scavenger vitamin E or the hydrophilic radical scavengers glutathione and N-acetylcysteine reduced DHA-induced membrane oxidation and apoptosis, respectively. Oxidative changes also occurred in cells with disruption of the mitochondrial death pathway, suggesting a role of reactive oxygen species and oxidative membrane changes in death signaling upstream of the mitochondria. Interestingly, DHA increased the cytotoxic action of ionizing radiation and of the death receptor agonist tumor necrosis factor-related apoptosis-inducing ligand in Jurkat cells, suggesting a potential benefit of DHA in combined treatment strategies.

Impact of gender on outcome after coronary artery bypass surgery.

Following recent studies concerning the increased risk of coronary artery bypass surgery for women, the impact of sex is still a controversial issue. Between 1996 and 2006, 9,527 men and 3,079 women underwent isolated coronary artery bypass in our institute. To adjust for dissimilarities in preoperative risk profiles, propensity score-based matching was applied. Before adjustment, clinical outcomes in terms of operative mortality, arrhythmias, intensive care unit stay, and maximum creatine kinase-MB levels were significantly different for men and women. After balancing the preoperative characteristics, including height, no significant differences in clinical outcomes were observed. However, there was decreased use of internal mammary artery, less total arterial revascularization, and increasing creatine kinase-MB levels with decreasing height. This study supports the theory that female sex per se does not increase operative risk, but shorter height, which is more common in women, affects the outcome, probably due to technical difficulties in shorter patients with smaller internal mammary arteries and coronary vessels. Thus women may especially benefit from sequential arterial grafting.