Loss of Uncoupling Protein 1 Expression in the Subcutaneous Adipose Tissue Predicts Childhood Obesity.

Stimulation of thermogenesis by inducing uncoupling protein 1 (UCP1) expression in adipocytes is thought to promote weight loss by increasing energy expenditure, and it is postulated that the human newborn has thermogenic subcutaneous fat depots. However, it remains unclear whether a relevant number of UCP1-expressing (UCP1+) adipocytes exist in the early postnatal life. Here we studied the distribution of UCP1 and the expression of thermogenic genes in the subcutaneous adipose tissues of the human fetus, infant and child. We show that the deep layer of human fetal and neonatal subcutaneous fat, particularly the abdominal wall, is rich in UCP1+ adipocytes. These adipocytes develop in the late third trimester and persist throughout childhood, expressing a panel of genes linked to mitochondrial biogenesis and thermogenesis. During the early childhood adiposity rebound-a critical phase that determines obesity risk later in life-the absence of adipose tissue UCP1 expression in children with normal body mass index (BMI) correlates with an obesity-associated gene expression signature. Finally, UCP1 expression is negatively correlated with BMI z-score and adipocyte size in infants and children. Overall, our results show that the absence of UCP1 expression in adipose tissue is an early indicator of adipose tissue expansion in children.

Stimulator of Interferon Genes (STING) Triggers Adipocyte Autophagy.

Innate immune signaling in adipocytes affects systemic metabolism. Cytosolic nucleic acid sensing has been recently shown to stimulate thermogenic adipocyte differentiation and protect from obesity; however, DNA efflux from adipocyte mitochondria is a potential proinflammatory signal that causes adipose tissue dysfunction and insulin resistance. Cytosolic DNA activates the stimulator of interferon response genes (STING), a key signal transducer which triggers type I interferon (IFN-I) expression; hence, STING activation is expected to induce IFN-I response and adipocyte dysfunction. However, we show herein that mouse adipocytes had a diminished IFN-I response to STING stimulation by 2'3'-cyclic-GMP-AMP (cGAMP). We also show that cGAMP triggered autophagy in murine and human adipocytes. In turn, STING inhibition reduced autophagosome number, compromised the mitochondrial network and caused inflammation and fat accumulation in adipocytes. STING hence stimulates a process that removes damaged mitochondria, thereby protecting adipocytes from an excessive IFN-I response to mitochondrial DNA efflux. In summary, STING appears to limit inflammation in adipocytes by promoting mitophagy under non-obesogenic conditions.

Medium-Term Results of Staged Laparoscopic Traction Orchiopexy for Intra-abdominal Testes: A Multicenter Analysis.

BACKGROUND: Staged laparoscopic traction orchiopexy (SLTO) is a novel technique for the intra-abdominal testis (IAT) based on elongation of the testicular vessels without separating them. This multicenter study evaluated the medium-term results of this technique. METHODS: Data of SLTO performed in three pediatric surgical centers between 2013 and 2020 were analyzed retrospectively. In 2021, physical and Doppler ultrasound examinations were performed to determine the position and viability of testes. Success was defined as an intra-scrotal testicle without atrophy. RESULTS: SLTO was performed on 48 cases (55 testes, 7 bilateral). Mean age at first stage was 2.9 (0.8-12.6) years. High intra-abdominal testes were found in 16.4% and in 60% morphological abnormalities were observed. To fix the testes to the abdominal wall monofilament suture was used in 67.3%, braided in 29.1%. Mean time between the two stages was 16.4 weeks; three testes required redo traction. Perioperative complications occurred in 21 patients (38.2%) including insufficient fixation (11), testicular atrophy (4), wound complications (4), adhesion of the spermatic cords (1) and hydrocele (1). In case of insufficient fixation monofilament sutures were used in 90.9%. In 2021 38 patients (43 testes) had physical and 36 patients (41 testes) had ultrasound examinations. Mean follow-up was 2.7 (0.34-7.9) years. Altogether five atrophies were identified, and three testicular ascents (7.0%) occurred. The overall success rate was 82.2%. CONCLUSIONS: SLTO may be a feasible alternative to conventional treatments of IATs. Additionally, braided suture seems to be a better option to fix the testicle to the abdominal wall. LEVEL OF EVIDENCE: LEVEL IV.

Mitochondrial RNA stimulates beige adipocyte development in young mice.

Childhood obesity is a serious public health crisis and a critical factor that determines future obesity prevalence. Signals affecting adipocyte development in early postnatal life have a strong potential to trigger childhood obesity; however, these signals are still poorly understood. We show here that mitochondrial (mt)RNA efflux stimulates transcription of nuclear-encoded genes for mitobiogenesis and thermogenesis in adipocytes of young mice and human infants. While cytosolic mtRNA is a potential trigger of the interferon (IFN) response, young adipocytes lack such a response to cytosolic mtRNA due to the suppression of IFN regulatory factor (IRF)7 expression by vitamin D receptor signalling. Adult and obese adipocytes, however, strongly express IRF7 and mount an IFN response to cytosolic mtRNA. In turn, suppressing IRF7 expression in adult adipocytes restores mtRNA-induced mitobiogenesis and thermogenesis and eventually mitigates obesity. Retrograde mitochondrion-to-nucleus signalling by mtRNA is thus a mechanism to evoke thermogenic potential during early adipocyte development and to protect against obesity.

Characterization of technical skill progress in a standardized rabbit model for training in laparoscopic duodenal atresia repair.

BACKGROUND: Laboratory skills training is an essential step before conducting minimally invasive surgery in clinical practice. Our main aim was to develop an animal model for training in clinically highly challenging laparoscopic duodenal atresia repair that could be useful in establishing a minimum number of repetitions to indicate safe performance of similar interventions on humans. MATERIALS AND METHODS: A rabbit model of laparoscopic duodenum atresia surgery involving a diamond-shaped duodeno-duodenostomy was designed. This approach was tested in two groups of surgeons: in a beginner group without any previous clinical laparoscopic experience (but having undergone previous standardized dry-lab training, n = 8) and in an advanced group comprising pediatric surgery fellows with previous clinical experience of laparoscopy (n = 7). Each participant performed eight interventions. Surgical time, expert assessment using the Global Operative Assessment of Laparoscopic Skills (GOALS) score, anastomosis quality (leakage) and results from participant feedback questionnaires were analyzed. RESULTS: Participants in both groups successfully completed all eight surgeries. The surgical time gradually improved in both groups, but it was typically shorter in the advanced group than in the beginner group. The leakage rate was significantly lower in the advanced group in the first two interventions, and it reached its optimal level after five operations in both groups. The GOALS and participant feedback scores showed gradual increases, evident even after the fifth surgery. CONCLUSIONS: Our data confirm the feasibility of this advanced pediatric laparoscopic model. Surgical time, anastomosis quality, GOALS score and self-assessment parameters adequately quantify technical improvement among the participants. Anastomosis quality reaches its optimal value after the fifth operation even in novice, but uniformly trained surgeons. A minimum number of wet-lab operations can be determined before surgery can be safely conducted in a clinical setting, where the development of further non-technical skills is also required.

Pituitary Adenylate Cyclase Activating Polypeptide Has Inhibitory Effects on Melanoma Cell Proliferation and Migration In Vitro.

Pituitary adenylate cyclase activating polypeptide (PACAP) is an endogenous neuropeptide which is distributed throughout the body. PACAP influences development of various tissues and exerts protective function during cellular stress and in some tumour formation. No evidence is available on its role in neural crest derived melanocytes and its malignant transformation into melanoma. Expression of PACAP receptors was examined in human skin samples, melanoma lesions and in a primary melanocyte cell culture. A2058 and WM35 melanoma cell lines, representing two different stages of melanoma progression, were used to investigate the effects of PACAP. PAC1 receptor was identified in melanocytes in vivo and in vitro and in melanoma cell lines as well as in melanoma lesions. PACAP administration did not alter viability but decreased proliferation of melanoma cells. With live imaging random motility, average speed, vectorial distance and maximum distance of migration of cells were reduced upon PACAP treatment. PACAP administration did not alter viability but decreased proliferation capacity of melanoma cells. On the other hand, PACAP administration decreased the migration of melanoma cell lines towards fibronectin chemoattractant in the Boyden chamber. Furthermore, the presence of the neuropeptide inhibited the invasion capability of melanoma cell lines in Matrigel chambers. In summary, we provide evidence that PACAP receptors are expressed in melanocytes and in melanoma cells. Our results also prove that various aspects of the cellular motility were inhibited by this neuropeptide. On the basis of these results, we propose PACAP signalling as a possible target in melanoma progression.

Intensity correlation-based calibration of FRET.

Dual-laser flow cytometric resonance energy transfer (FCET) is a statistically efficient and accurate way of determining proximity relationships for molecules of cells even under living conditions. In the framework of this algorithm, absolute fluorescence resonance energy transfer (FRET) efficiency is determined by the simultaneous measurement of donor-quenching and sensitized emission. A crucial point is the determination of the scaling factor α responsible for balancing the different sensitivities of the donor and acceptor signal channels. The determination of α is not simple, requiring preparation of special samples that are generally different from a double-labeled FRET sample, or by the use of sophisticated statistical estimation (least-squares) procedures. We present an alternative, free-from-spectral-constants approach for the determination of α and the absolute FRET efficiency, by an extension of the presented framework of the FCET algorithm with an analysis of the second moments (variances and covariances) of the detected intensity distributions. A quadratic equation for α is formulated with the intensity fluctuations, which is proved sufficiently robust to give accurate α-values on a cell-by-cell basis in a wide system of conditions using the same double-labeled sample from which the FRET efficiency itself is determined. This seemingly new approach is illustrated by FRET measurements between epitopes of the MHCI receptor on the cell surface of two cell lines, FT and LS174T. The figures show that whereas the common way of α determination fails at large dye-per-protein labeling ratios of mAbs, this presented-as-new approach has sufficient ability to give accurate results. Although introduced in a flow cytometer, the new approach can also be straightforwardly used with fluorescence microscopes.

Intraoperative tissue identification using rapid evaporative ionization mass spectrometry.

Rapid evaporative ionization mass spectrometry (REIMS) is an emerging technique that allows near-real-time characterization of human tissue in vivo by analysis of the aerosol ("smoke") released during electrosurgical dissection. The coupling of REIMS technology with electrosurgery for tissue diagnostics is known as the intelligent knife (iKnife). This study aimed to validate the technique by applying it to the analysis of fresh human tissue samples ex vivo and to demonstrate the translation to real-time use in vivo in a surgical environment. A variety of tissue samples from 302 patients were analyzed in the laboratory, resulting in 1624 cancerous and 1309 noncancerous database entries. The technology was then transferred to the operating theater, where the device was coupled to existing electrosurgical equipment to collect data during a total of 81 resections. Mass spectrometric data were analyzed using multivariate statistical methods, including principal components analysis (PCA) and linear discriminant analysis (LDA), and a spectral identification algorithm using a similar approach was implemented. The REIMS approach differentiated accurately between distinct histological and histopathological tissue types, with malignant tissues yielding chemical characteristics specific to their histopathological subtypes. Tissue identification via intraoperative REIMS matched the postoperative histological diagnosis in 100% (all 81) of the cases studied. The mass spectra reflected lipidomic profiles that varied between distinct histological tumor types and also between primary and metastatic tumors. Thus, in addition to real-time diagnostic information, the spectra provided additional information on divergent tumor biochemistry that may have mechanistic importance in cancer.

[Successful treatment of retrohepatic inferior vena cava injury: report of two cases]. / Retrohepaticus vena cava sérülés két sikeresen operált esete.

UNLABELLED: Authors present two cases of successfully operated patients with retrohepatic inferior vena cava (IVC) injury. In the first case a 79 year old female patient suffered from multiple stab wounds in the area of the 4th segment of the right lung as well as in the retrohepatic region in close proximity to the IVC. At the time of the first surgery the IVC injury was not identified. During a second operation, however, the IVC was isolated from the liver using an anterior dissection of the parenchyma with finger-fracture technique and the injury was oversawn finally. Successful haemostasis of the liver was achieved by packing of the perihepatic space, which was removed three days later. In the second case a 25 year-old male patient had suffered blunt abdominal trauma. He underwent laparotomy and packing on the site of the hepatic injury, which had to be repeated seven more times. Later on, another urgent laparotomy was carried out for recurring intraabdominal bleeding and bile leakage, and cholecystectomy was performed due to gallbladder perforation. Another two days later a further emergency laparotomy was indicated for ongoing intraabdominal bleeding, when the bleeding source - an injury (3 mm in diameter) of the retrohepatic IVC - was oversawn. After relatively long postoperative stay both patients were fully recovered and discharged from hospital. CONCLUSIONS: penetrating injuries of the IVC are associated with high mortality rate of approximately 78%. Proper management of these injuries requires experience in both vascular and liver surgery. Retrohepatic IVC injury needs to be considered in the differential diagnosis of ongoing bleeding in penetrating or blunt liver trauma. Packing of the liver is a reliable haemostatic method if bleeding persists due to division of the liver parenchyma.

Identification of biological tissues by rapid evaporative ionization mass spectrometry.

The newly developed rapid evaporative ionization mass spectrometry (REIMS) provides the possibility of in vivo, in situ mass spectrometric tissue analysis. The experimental setup for REIMS is characterized in detail for the first time, and the description and testing of an equipment capable of in vivo analysis is presented. The spectra obtained by various standard surgical equipments were compared and found highly specific to the histological type of the tissues. The tissue analysis is based on their different phospholipid distribution; the identification algorithm uses a combination of principal component analysis (PCA) and linear discriminant analysis (LDA). The characterized method was proven to be sensitive for any perturbation such as age or diet in rats, but it was still perfectly suitable for tissue identification. Tissue identification accuracy higher than 97% was achieved with the PCA/LDA algorithm using a spectral database collected from various tissue species. In vivo, ex vivo, and post mortem REIMS studies were performed, and the method was found to be applicable for histological tissue analysis during surgical interventions, endoscopy, or after surgery in pathology.

Videothoracoscopic treatment of a rare complication of nasojejunal tube insertion.

OBJECTIVE: Intubation of the tracheobronchial tree is the most common type of malposition during the placement of narrow-bore enternal tubes. CASE REPORT: In addition to other treatment components in a 65-year-old female, nasojejunal feeding was started to treat her for severe acute pancreatitis. After the placement of the narrow-bore feeding tube, she developed dyspnea and huskiness. On auscultation and X-ray investigation, the right pneumothorax was detected and the tube was found in the chest cavity. The diagnosis was confirmed by bronchoscopy. Videothoracoscopic resection and closure of the lacerated lung, using a tube thoracostomy, were performed. The patient recovered after postoperative conservative treatment for her pancreatitis. CONCLUSION: Pneumothorax and laceration of the lung-caused by the malposition of narrow-bore enternal tube-can be successfully treated by applying videothoracoscopy.

Laparoscopic treatment of simultaneously occurring Morgagni and paraesophageal hernias.

A paraesophageal hernia was diagnosed in a 67-year-old female patient suffering from epigastric pain and gastroesophageal reflux disease. The patient underwent laparoscopy. Beside the paraesophageal hernia, a Morgagni hernia was also observed, with a significant part of the omentum herniated in the sac. A 360-degree Nissen fundoplication was performed, the Morgagni hernia sac was not resected, and its closure was performed with interrupted sutures. No complications were observed in the postoperative period and on one-year follow-up the patient was free of symptoms.

[Curative surgical treatment of inoperable pancreatic cancer after neoadjuvant therapy]. / Inoperábilis pancreas-carcinoma neo- adjuváns kemoterápiát követo kuratív sebészetének korai tapasztalatai.

In the treatment of pancreatic cancer only curative resection increases the life expectancy. Radical resection is a high risk operation, but it can be performed with low peri-operational mortality in specialist surgical centres. At the time of diagnosis most patients are in stage (TMN of pancreatic cancer UICC 1997) III or IV, thus curative resection cannot be performed. Neo-adjuvant therapy shrinks the tumour in 60-70%, giving new hope for the patients. In this paper authors present two cases of pancreatic cancer resections. Palliative operations were performed in patients with inoperable pancreatic cancer. Later neo-adjuvant chemotherapy was performed--in these cases it meant chemotherapy--and after that a second, this time curative procedure was performed.

[Evaluation of pancreatic anastomoses in the course of radical resection]. / Radikális reszekciós mútétek során a pancreas-szal készített anasztomózisok vizsgálata.

We examine the results of radical resections performed over a 10 year period at the 2nd Department of Surgery of the University of Debrecen Medical and Health Science Center Medical School of Medicine because of chronic inflammation, tumors of the papilla of Vater or tumors of the head of the pancreas. Pancreatoduodenectomy was performed in 134 patients, Whipple-type surgery in 11, and pylorus-preserving pancreatoduodenectomy in 123 patients. Three different types of reconstructive methods were used. In pylorus-preserving pancreatoduodenectomy, the remnant of the pancreas was anastomosed by performing a termino-lateral pancreatojejunostomy in 20 cases, and a pancreatogastrostomy in 89 cases. In 14 patients, the sutures were not satisfactory because of the soft and glandular texture of the pancreas, so a new method was used. After removing the head of the pancreas, the first anastomosis was a pancreatico-jejunostomy, the second was a choledochojejunostomy, and the third was a duodeno-jejunostomy which was fixed approximately 40 centimeters from the pancreatic anastomosis. The most common complication was leaking pancreatogastrostomy. Four patients with this complication were reoperated on. The 14 patients operated on using the new method had no complications.

[The role of D2 lymphadenectomy in the surgical treatment of gastric carcinoma]. / A D2 lymphadenectomia szerepe a gyomorkarcinóma sebészi kezelésében.

The authors examine 145 patients with gastric carcinoma who underwent curative resection with additional D2 lymphadenectomy at the 2nd Surgical Department of DUMHSC between January 1, 1996 and December 31, 2000. Subtotal resection was performed in 103 patients, and total, gastrectomy was performed in 42 patients. Postoperative mortality was 5.5% and disease-related complications occurred in 17.9%. The three-year survival was 49.7%, while in patients with "early" (maximum infiltration to the level of the submucosa) gastric carcinoma 3-year survival rate of was 86.3%. The results correlate with the data in the literature, so the use of D2 lymphadenectomy in the surgical treatment of gastric carcinoma is strongly advised.