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We examined preadipocyte differentiation in obese and nonobese individuals and the effect of cytokines and wingless-type MMTV (mouse mammary tumor virus) integration site family, member 3A (Wnt3a) protein on preadipocyte differentiation and phenotype. Abdominal subcutaneous adipose tissue biopsies were obtained from a total of 51 donors with varying BMI. After isolation of the adipose and stromalvascular cells, inflammatory cells (CD14- and CD45-positive cells) were removed by immune magnetic separation. CD133-positive cells, containing early progenitor cells, were also isolated and quantified. The CD14- and CD45-negative preadipocytes were cultured with tumor necrosis factor (TNF)-alpha, interleukin (IL)-6, resistin, or Wnt3a with or without a differentiation cocktail. The number of preadipocytes able to differentiate to adipose cells was negatively correlated with both BMI and adipocyte cell size of the donors, whereas the number of CD133-positive cells was positively correlated with BMI, suggesting an impaired differentiation of preadipocytes in obesity. Cultured preadipocytes, like freshly isolated mature adipocytes, from obese individuals had an increased expression of mitogen-activated protein 4 kinase 4 (MAP4K4), which is known to inhibit peroxisome proliferator-activated receptor-gamma induction. TNF-alpha, but not IL-6 or resistin, increased Wnt10b, completely inhibited the normal differentiation of the preadipocytes, and instead induced a proinflammatory and macrophage-like phenotype of the cells. The apparent number of preadipocytes in the abdominal subcutaneous tissue that can undergo differentiation is reduced in obesity with enlarged fat cells, possibly because of increased MAP4K4 levels. TNF-alpha promoted a macrophage-like phenotype of the preadipocytes, including several macrophage markers. These results document the plasticity of human preadipocytes and the inverse relationship between lipid storage and proinflammatory capacity.

Caesarean sections carry the risk of urinary bladder injury due to formation of adhesions obscuring pelvic planes. Visualizing bladder during retro-fill (cystoinflation) makes it recognizable as it rises into the abdomen taking a tense rounded contour. We conducted a prospective randomized controlled trial to find out whether improved identification of bladder margins by cystoinflation could decrease bladder injury rate and blood loss without causing urological complications. This study included 214 healthy women with previous operative deliveries undergoing elective caesarean section and found to have dense pelvic adhesions. The subjects were randomly allocated into cystoinflation and control groups. Adhesiolysis was performed using bladder retro-fill with 300 cc saline in cystoinflation group, and without retro-fill in control. The bladder injury rate was significantly lower in cystoinflation group compared to control (2.8% vs 20.6%, P < .0001) with lesser blood loss in cystoinflation group (585.33 cc vs 797.10 cc, P < .0001). Mean operative time was similar in both groups. Urinary tract infection and micturition problems occurred more frequently in control group than cystoinflation group (16.8% vs 1.9%, P = .001 and .47 ± 1.63% vs 077 ± .633%, P = .021 respectively) with fistula in one subject compared to none in cystoinflation group. In this study, cystoinflation was effective to significantly reduce bladder injury rate and blood loss. This technique may also prove useful in the fields of surgery, urology and urogynecology.

Background The extralevator abdominoperineal excision (ELAPE) has been proposed as oncologically superior to standard abdominoperineal excision (SAPE). However, little is known regarding comparative margins achieved in ELAPE and SAPE. The purpose of this study was to compare patterns of tissue removal between these two groups that can aid patient selection. Methods Twenty APE specimens, comprising 10 SAPEs and 10 ELAPEs, were selected randomly from a single UK centre. Transverse slices of pathological specimens were matched to corresponding axial MRI images obtained from conventional pelvic MRI imaging. Measurements from the muscularis propria to the resection margin [muscularis to margin (MTM) distance] were recorded by height (from anal verge) and quadrant for each surgical group. MTM distances achieved on histopathological assessment were also compared to MRI assessed distances necessary to achieve a clear CRM. Results ELAPE specimens had a greater mean MTM distance than for SAPE (7.75 vs. 5.61 mm, p  = 0.02). ELAPE had significantly greater MTM distances in lateral and posterior quadrants ( p  < 0.05) than SAPE at 30–49 mm. There was no significant difference in mean anterior distances (1.57 vs. 1.16 mm, p  = 0.507) with the smallest difference at a height of 60–69 mm. Two (2 %) of pathological MTM distances within ELAPE group failed to achieve the minimum MRI assessed distance compared with 30 (23 %) in the SAPE group, which had higher CRM positivity. Conclusions ELAPE appears to confer oncological benefit over SAPE but with notable exceptions, including tumours located above and below the puborectalis sling and anteriorly at the level of prostate where exenteration may be more appropriate.

The aim of this study was to test whether the availability of committed preadipocytes in abdominal and femoral subcutaneous adipose tissue varies with obesity and body fat distribution. Body composition, fat cell size, committed preadipocytes and macrophages were measured in subcutaneous abdominal and femoral adipose depots of 17 lean, 16 upper-body-obese (UBO) and 13 lower-body-obese (LBO) women. Preadipocytes and macrophages were identified by simultaneous staining with the respective markers aP2 and CD68. In a subset of samples we measured preadipocyte proliferation, differentiation and susceptibility to apoptosis. Abdominal adipocytes were smaller in lean than in obese women. Committed preadipocytes represented a greater fraction of stromovascular cells in lean than in obese women but were similar between UBO and LBO women (abdomen: approximately 30 +/- 3 vs approximately 17 +/- 2%; thigh: approximately 30 +/- 3 vs approximately 17 +/- 2%). Preliminary data suggested that preadipocyte kinetics were similar in LBO and lean women, whereas preadipocytes of UBO women differentiated less and were more susceptible to apoptotic stimuli. The fraction of stromovascular cells that were macrophages was greater in both depots in obese women (UBO and LBO) than in normal-weight women, but the difference was not statistically significant. The proportion of subcutaneous adipose tissue stromovascular cells that are committed preadipocytes is reduced with obesity. This could be due to greater recruitment of preadipocytes to adipogenesis or greater preadipocyte apoptosis, depending upon the obesity phenotype. These data are consistent with the concept that body fat distribution may be regulated partly through differences in adipogenesis.

Purpose The current study aimed to compare the oncologic outcome and pattern of metastasis after abdominoperineal resection (APR) and low anterior resection (LAR) treating lower rectal cancer. Methods A total of 804 patients undergoing curative resection (R0) were enrolled prospectively. The APR and LAR groups ( n  = 402, respectively) were matched for gender, age, and stage, for a retrospectively comparative analysis. Results In a multivariate analysis with potential variables, APR itself was not a risk factor for increased local recurrence (LR) or reduced survival ( P  = 0.243–0.994). Circumferential resection margin (CRM) involvement as an operation-related risk was 1.6-fold more frequent in the APR group and was significantly associated with LR and systemic recurrence (OR, 2.487–4.017; P  < 0.01). Circumferential margin positivity (CRM+) was concurrently correlated with advanced stage, larger tumor (long diameter, >4 cm), and longer sagittal midpelvic diameter (>10 cm) in a multivariate analysis ( P  < 0.001–0.05). The site of metastasis did not differ between the two groups, with the exception of lung metastasis which was more frequent in the APR group (APR vs. LAR: 15.9 vs. 10 %, P  = 0.015). In the APR group, CRM+ and the presence of an infiltrating tumor were correlated with disease-free survival (hazard ratio (HR), 1.644 and 1.654, respectively), whereas elevated serum carcinoembryonic antigen and LVI+ were correlated with overall survival (HR, 1.57 and 1.671, respectively), in a multivariate analysis with potential variables ( P  < 0.05). Conclusions When performed with appropriate skill to achieve R0 resection, APR can be used safely without impairing oncological outcome, although sphincter-preserving surgery should remain the preferred option.

Aim. The aim of this study was to investigate the effect of i.v. infusion of magnesium sulphate during spinal anesthesia on duration of spinal block and postoperative pain. Methods. Forty ASA physical status I and status II, aged between 18 and 65, female patients undergoing abdominal hysterectomy under spinal anesthesia were enrolled in this study. Patients in the magnesium group (Group M, n = 20) received magnesium sulphate 65 mg kg−1 infusion in 250 mL 5% dextrose at 3.5 mL/min rate, and control group (Group C, n = 20) received at the same volume of saline during operation in a double-blind randomized manner. Duration of sensory and motor block, systolic, diastolic, and mean arterial blood pressures, heart rates, pain scores (VAS values), and side effects were recorded for each patient. Blood and CSF samples were taken for analysis of magnesium concentrations. Results. Regression of sensorial block was longer in Group M when compared with that in Group C (175 ± 39 versus 136 ± 32 min) (P < 0.01). The VAS scores were lower in Group M than those in Group C at the 2 time points postoperatively (P < 0.01). Conclusion. 65 mg kg−1 of magnesium sulphate i.v. infusion under spinal anesthesia prolongs spinal sensorial block duration and decreases pain VAS scores without complication in patients undergoing abdominal hysterectomy.

Intestinal ischemia reperfusion (I/R) injury is the important pathogenesis for acute intestinal barrier disruption. The STING signaling is associated with gut homeostasis and barrier integrity. However, the biological function and regulation of STING signaling in intestinal I/R injury are not yet fully understood. As the ligand of STING signaling, the mitochondrial DNA (mtDNA) has been found to be associated with necroptosis. It still remains unknown whether mtDNA-STING signaling triggers intestinal necroptosis in intestinal I/R injury. We found that circulating RIPK3 was significantly increased and had a positive correlation with markers of enterocyte injury in critically ill patients with intestinal injury. Moreover, the levels of circulating mtDNA were also associated with the levels of circulating RIPK3. To explore the relationship between mtDNA and intestinal necroptosis, mice were treated with the intraperitoneal injection of mtDNA, and necroptosis signaling was remarkably activated and the inhibition of necroptosis alleviated mtDNA-induced intestinal injury. Furthermore, STING knockout mice showed an alleviated intestinal necroptosis. In intestinal I/R injury, mtDNA was released from IECs and necroptosis was also triggered, companied with a significant decrease of RIPK3 in the intestine. STING knockout mice markedly attenuated intestinal necroptosis and intestinal I/R injury. Finally, we found that mtDNA-mediated STING signaling triggered necroptosis through synergistic IFN and TNF-α signaling in primary IECs. Our results indicated that mtDNA-STING signaling can contribute to intestinal I/R injury by promoting IEC necroptosis. STING-mediated both IFN and TNF-α signaling can trigger intestinal nercroptosis.

Background Castleman disease (CD) is a rare benign disorder characterised by hyperplasia of lymphoid tissue that may develop at a single site or throughout the body. The etiology of this disorder is unclear, although the histopathological presentation can be differentiated into a hyaline vascular variant, a plasma cell variant and a mixed variant. Clinically, it has been recorded that 3 manifestations of CD are characterized: a localized unicentric type, a generalized multicentric type and a mixed form. Surgery remains the main treatment for resectable unicentric CD, since removal of the large node is possible without further complications. No consensus has been reached concerning the most adequate treatment for irresectable unicentric CD. Methods Case report of a 67 year old woman. Results This report, describes the case of a 67-year-old woman with unicentric Castleman disease located in the right lower abdomen. The patient had symptoms of fatigue, dyspnoea and pain in the right lower abdomen. Computed tomography (CT)- examination revealed a tumour, which had grown to form a close relationship with the common iliac vessels and the sacral bone. A Laparotomy procedure revealed that the tumour was an irresectable mass. Neo-adjuvant radiotherapy (40 Gy) was administered in order to downsize the tumour. Six weeks later a new CT-scan revealed a major reduction of the tumour, which enabled a successful radical resection of the tumour to be performed. Histopathological analysis of the tumour showed the hyaline vascular type of CD. Conclusions Neo-adjuvant radiotherapy should be considered in case of an irresectable unicentric CD.

Background. This study aimed to compare the effects of rectal midazolam addition after applying bupivacaine and caudal anesthesia on postoperative analgesia time, the need for additional analgesics, postoperative recovery, and sedation and to find out its adverse effects in children having lower abdominal surgery. Methods. 40 children between 2 and 10 years of ASA I-II were randomized, and they received caudal anesthesia under general anesthesia. Patients underwent the application of caudal block in addition to saline and 1 mL/kg bupivacaine 0.25%. In the postoperative period, Group C (n = 20) was given 5 mL saline, and Group M (n = 20) was given 0.30 mg/kg rectal midazolam diluted with 5 mL saline. Sedation scale and postoperative pain scale (CHIPPS) of the patients were evaluated. The patients were observed for their analgesic need, first analgesic time, and adverse effects for 24 hours. Results. Demographic and hemodynamic data of the two groups did not differ. Postoperative sedation scores in both groups were significantly lower compared with the preoperative period. There was no significant difference between the groups in terms of sedation and sufficient analgesia. Conclusions. We conclude that caudal anesthesia provided sufficient analgesia in peroperative and postoperative periods, and rectal midazolam addition did not create any differences. This trial is registered with ClinicalTrials.gov NCT02127489.

Diagnostic imaging of hepatocellular carcinoma (HCC) requires a liver CT or MRI multiphase acquisition protocol. Patients would benefit from a high-resolution imaging method capable of performing multi-phase imaging in a single acquisition without an increase in radiation dose. Spectral Photon-Counting Computed Tomography (SPCCT) has recently emerged as a novel and promising imaging modality in the field of diagnostic radiology. SPCCT is able to distinguish between two contrast agents referred to as multicolor imaging because, when measuring in three or more energy regimes, it can detect and quantify elements with a K-edge in the diagnostic energy range. Based on this capability, we tested the feasibility of a dual-contrast multi-phase liver imaging protocol via the use of iodinated and gadolinated contrast agents on four healthy New Zealand White (NZW) rabbits. To perform a dual-contrast protocol, we injected the agents at different times so that the first contrast agent visualized the portal phase and the second the arterial phase, both of which are mandatory for liver lesion characterization. We demonstrated a sensitive discrimination and quantification of gadolinium within the arteries and iodine within the liver parenchyma. In the hepatic artery, the concentration of gadolinium was much higher than iodine (8.5 ± 3.9 mg/mL versus 0.7 ± 0.1 mg/mL) contrary to the concentrations found in the liver parenchyma (0.5 ± 0.3 mg/mL versus 4.2 ± 0.3 mg/mL). In conclusion, our results confirm that SPCCT allows in-vivo dual contrast qualitative and quantitative multi-phase liver imaging in a single acquisition.