Impact of Nicotine Replacement Therapy on Breast Surgery Outcomes.

BACKGROUND: Smoking cessation therapy, including nicotine replacement therapy (NRT), is used perioperatively to assist patients to reduce their tobacco smoke intake and consequently decrease their risk of smoking-associated complications. There are, however, theoretical concerns that nicotine-induced peripheral vasoconstriction could impair wound healing. This study investigated the effect of NRT on postoperative outcomes in patients undergoing breast surgery. METHODS: A retrospective chart review of patients undergoing breast surgery within the Yale New Haven Health System from the years 2014 to 2020 was performed. Documented smoking status within 6 months before surgery, use or prescription of NRT, type of surgery, and surgical complications of infection, wound dehiscence, tissue necrosis, hematoma, seroma, fat necrosis, and return to operating room within 30 days were recorded. Demographic and complication data were compared between patients with NRT usage and those without using t-tests and chi-square analyses. Multivariable logistic regression models were created to predict the effect of NRT usage on the occurrence of any complication. RESULTS: A total of 613 breast procedures met inclusion criteria, of which 105 (17.2%) had documented NRT use. The NRT cohort and the non-NRT cohort were well balanced with respect to demographics and procedural variables. Upon multivariable modeling for risk of any surgical complication, NRT was not a significant predictor (odds ratio [OR]: 1.199, p = 0.607 and OR: 0.974, p = 0.912, respectively), whereas procedure type, increased body mass index, and increased age were. CONCLUSION: NRT use was not associated with an increased risk of postoperative complications compared with not using NRT as part of smoking cessation therapy prior to operation.

TNF-α Preconditioning Promotes a Proangiogenic Phenotype in hiPSC-Derived Vascular Smooth Muscle Cells.

Introduction: hiPSC-VSMCs have been suggested as therapeutic agents for wound healing and revascularization through the secretion of proangiogenic factors. However, methods of increasing cell paracrine secretion and survivability have thus far yielded inconsistent results. This study investigates the effect of pre-conditioning of hiPSC-VSMCs with TNF-α and their integration into 3D collagen scaffolds on cellular viability and secretome. Methods: hiPSC-VSMCs were dual-plated in a 2D environment. TNF-α was introduced to one plate. Following incubation, cells from each plate were divided and added to type-I collagen scaffolds. TNF-α was introduced to two sets of scaffolds, one from each 2D plate. Following incubation, scaffolds were harvested for their media, tested for cell survivability, cytotoxicity, and imaged. Intra-media VEGF and bFGF levels were evaluated using ELISA testing. Results: hiPSC-VSMCs exposed to TNF-α during collagen scaffold proliferation and preconditioning showed an increase in cell viability and less cytotoxicity compared to non-exposed cells and solely-preconditioned cells. Significant increases in bFGF expression were found in pre-conditioned cell groups with further increases found in cells subsequently exposed during intra-scaffold conditioning. A significant increase in VEGF expression was found in cell groups exposed during both pre-conditioning and intra-scaffold conditioning. Fibroblasts treated with any conditioned media demonstrated increased migration potential. Conclusions: Conditioning hiPSC-VSMCs embedded in scaffolds with TNF-α improves cellular viability and increases the secretion of paracrine factors necessary for wound healing mechanisms such as migration. Supplementary Information: The online version contains supplementary material available at 10.1007/s12195-023-00764-0.

Insulin secretory actions of ethanolic extract of Acacia arabica bark in high fat-fed diet-induced obese Type 2 diabetic rats.

Acacia arabica commonly known as 'babul' has been widely used for the treatment of numerous diseases, including diabetes due to their potential pharmacological actions. The aim of the present study was to investigate the insulinotropic and antidiabetic properties of ethanol extract of Acacia arabica (EEAA) bark through in vitro and in vivo studies in high fat-fed (HFF) rats. EEAA at 40-5000 µg/ml significantly increased (P<0.05-0.001) insulin secretion with 5.6 and 16.7 mM glucose, respectively, from clonal pancreatic BRIN BD11 ß-cells. Similarly, EEAA at 10-40 µg/ml demonstrated a substantial (P<0.05-0.001) insulin secretory effect with 16.7 mM glucose from isolated mouse islets, with a magnitude comparable to 1 µM glucagon-like peptide-1 (GLP-1). Diazoxide, verapamil, and calcium-free conditions decreased insulin secretion by 25-26%. The insulin secretory effect was further potentiated (P<0.05-0.01) with 200 µM isobutylmethylxanthine (IBMX; 1.5-fold), 200 µM tolbutamide (1.4-fold), and 30 mM KCl (1.4-fold). EEAA at 40 µg/ml, induced membrane depolarization and elevated intracellular Ca2+ as well as increased (P<0.05-0.001) glucose uptake in 3T3L1 cells and inhibited starch digestion, glucose diffusion, dipeptidyl peptidase-IV (DPP-IV) enzyme activity, and protein glycation by 15-38%, 11-29%, 15-64%, and 21-38% (P<0.05, 0.001), respectively. In HFF rats, EEAA (250 mg/5 ml/kg) improved glucose tolerance, plasma insulin, and GLP-1 levels, and lowered DPP-IV enzyme activity. Phytochemical screening of EEAA revealed the presence of flavonoids, tannins and anthraquinone. These naturally occurring phytoconstituents may contribute to the potential antidiabetic actions of EEAA. Thus, our finding suggests that EEAA, as a good source of antidiabetic constituents, would be beneficial for Type 2 diabetes patients.

The Facial Artery Perforator Flap.

BACKGROUND: Reconstruction of facial melanoma defects can be challenging. Large defects of the midface, cheek, and nasolabial fold are often reconstructed using a cervicofacial flap which requires significant flap elevation and undermining. Surgeons are often hesitant to commit to such a large reconstruction without definitive pathologic evidence of negative margins. However, local perforator flaps may be used as an alternative to large flaps with less dissection and donor site morbidity and may also allow for more facile re-advancement in the event of a positive margin on final pathology. The goal of this study is to evaluate a perforator flap based on the facial artery to determine if it is a safe and cosmetically favorable option to immediately repair oncologic-related defects on the cheek and midface. METHODS: A retrospective review of all melanoma cases performed by the senior author between January 2016 and December 2021 was conducted. Patients who underwent reconstruction using a facial artery perforator flap were included. RESULTS: Sixteen patients were included in our cohort. The average age was 67.3 years and 53% (n=8) were female. Fourteen patients had the primary defect located on the cheek, 1 from the nasolabial fold, and 1 from the distal nasal sidewall. All patients received immediate reconstruction. Excisional margins ranged from 0.5 to 2 cm. Two patients had positive margins following pathology results with one undergoing treatment with imiquimod and the other opting for re-excision. No complications involving the defect or donor site were reported after an average follow-up time of 113.8 days. CONCLUSION: The facial artery perforator flap is a safe and cosmetically favorable option to immediately repair oncologic-related defects on the cheek and midface.

Antidiabetic Actions of Ethanol Extract of Camellia sinensis Leaf Ameliorates Insulin Secretion, Inhibits the DPP-IV Enzyme, Improves Glucose Tolerance, and Increases Active GLP-1 (7-36) Levels in High-Fat-Diet-Fed Rats.

Camellia sinensis (green tea) is used in traditional medicine to treat a wide range of ailments. In the present study, the insulin-releasing and glucose-lowering effects of the ethanol extract of Camellia sinensis (EECS), along with molecular mechanism/s of action, were investigated in vitro and in vivo. The insulin secretion was measured using clonal pancreatic BRIN BD11 ß cells, and mouse islets. In vitro models examined the additional glucose-lowering properties of EECS, and 3T3L1 adipocytes were used to assess glucose uptake and insulin action. Non-toxic doses of EECS increased insulin secretion in a concentration-dependent manner, and this regulatory effect was similar to that of glucagon-like peptide 1 (GLP-1). The insulin release was further enhanced when combined with isobutylmethylxanthine (IBMX), tolbutamide or 30 mM KCl, but was decreased in the presence of verapamil, diazoxide and Ca2+ chelation. EECS also depolarized the ß-cell membrane and elevated intracellular Ca2+, suggesting the involvement of a KATP-dependent pathway. Furthermore, EECS increased glucose uptake and insulin action in 3T3-L1 cells and inhibited dipeptidyl peptidase IV (DPP-IV) enzyme activity, starch digestion and protein glycation in vitro. Oral administration of EECS improved glucose tolerance and plasma insulin as well as inhibited plasma DPP-IV and increased active GLP-1 (7-36) levels in high-fat-diet-fed rats. Flavonoids and other phytochemicals present in EECS could be responsible for these effects. Further research on the mechanism of action of EECS compounds could lead to the development of cost-effective treatments for type 2 diabetes.

Human iPSC-Vascular smooth muscle cell spheroids demonstrate size-dependent alterations in cellular viability and secretory function.

Human-induced pluripotent stem cells (hiPSC) and their differentiated vascular cells have been revolutionizing the field of regenerative wound healing. These cells are shown to be rejuvenated with immense potentials in secreting paracrine factors. Recently, hiPSC-derived vascular smooth muscle cells (hiPSC-VSMC) have shown regenerative wound healing ability via their paracrine secretion. The quest to modulate the secretory function of these hiPSC-VSMC is an ongoing effort and involves the use of both biochemical and biophysical stimuli. This study explores the development and optimization of a reproducible, inexpensive protocol to form hiPSC-VSMC derived spheroids to investigate the implications of spheroid size on viability and paracrine secretion. Our data show the successful formation of different sizes of spheroids using various amount of hiPSC-VSMC. The hiPSC-VSMC spheroids formed with 10,000 cells strike an ideal balance between overall cell health and maximal paracrine secretion. The conditioned medium from these spheroids was found to be bioactive in enhancing human dermal fibroblast cell proliferation and migration. This research will inform future studies on the optimal spheroid size for regenerative wound healing applications.

Human iPSC-Derived Vascular Smooth Muscle Cells in a Fibronectin Functionalized Collagen Hydrogel Augment Endothelial Cell Morphogenesis.

Tissue-engineered constructs have immense potential as autologous grafts for wound healing. Despite the rapid advancement in fabrication technology, the major limitation is controlling angiogenesis within these constructs to form a vascular network. Here, we aimed to develop a 3D hydrogel that can regulate angiogenesis. We tested the effect of fibronectin and vascular smooth muscle cells derived from human induced pluripotent stem cells (hiPSC-VSMC) on the morphogenesis of endothelial cells. The results demonstrate that fibronectin increases the number of EC networks. However, hiPSC-VSMC in the hydrogel further substantiated the number and size of EC networks by vascular endothelial growth factor and basic fibroblast growth factor secretion. A mechanistic study shows that blocking αvß3 integrin signaling between hiPSC-VSMC and fibronectin impacts the EC network formation via reduced cell viability and proangiogenic growth factor secretion. Collectively, this study set forth initial design criteria in developing an improved pre-vascularized construct.

Evaluating humidity sensing response of graphene quantum dots synthesized by hydrothermal treatment of glucose.

Graphene quantum dots (GQDs) were prepared using a single-step hydrothermal treatment of glucose (C6H12O6) powder. X-ray diffraction patterns confirmed the random stacking or amorphous character of GQDs. Additionally, the UV-vis spectra confirmed the formation of GQDs with evident absorption peaks at 237 and 305 nm, which is attributed toπ-π* andn-π* transitions correspondingly. The average size and surface roughness of graphene quantum dots were estimated by atomic force microscopy images and found to be 27.0 ± 1.0 and 2.3 nm, respectively. Afterwards, the effect of increasing relative humidity (RH) from 0%-95%, and frequency, was analyzed using the capacitive and resistive responses of synthesized GQDs. The capacitive output at 0.1 kHz revealed that initially capacitance remains constant (15.0 ± 1.0 pF) up to a humidity level ranging between 0%-50%. Likewise, capacitance also displayed stabilized behavior after frequency levels were increased i.e., 1.0 and 10 kHz, at a humidity ranging from 0%-55%. Moreover, capacitance showed a 115,455, 22,480 and 3,620% improvement from their stable values at each respective frequency level i.e., 0.1, 1.0 and 10 kHz. The capacitive sensitivity decreased to 84.20 and 96.83% at greater frequencies (1.0 and 10 kHz) in comparison to the sensitivity at 0.1 kHz facing similar variations in a humid environment. In contrast, resistance displayed an exponential decline by 99.9900, 99.9796 and 99.9925%, accordingly, when RH increases from 0 to 95% at 0.1, 1.0 and 10 kHz, respectively. However, with the rise in frequency level from 0.1 to 1.0 kHz, resistive sensitivity increased considerably to 69 and 158.5%, respectively, in two prominent humidity ranges i.e., 0 ≤ RH ≤ 25% and 25% ≤ RH ≤ 50%. A further increase in testing frequency to 10 kHz enhances the resistive sensitivity by 598.5 and 178.5% when compared with the lowest sensitivity values at two noticeable humidity levels, 0%-25% and 25%-50%. The response and recovery times of our specimen were better than most of previously fabricated GQDs and other carbon-derived nanomaterials, which makes the nano-GQDs of our study more suitable for RH sensor application.

A non-invasive fibrosis score predicts treatment outcome in chronic hepatitis C virus infection.

OBJECTIVE: The results of a previous study suggest that an index calculated according to the formula (normalized ASAT x PK-INR) x 100/thrombocyte count (x 10(9)/L; GUCI) may reflect liver fibrosis in patients with chronic hepatitis C virus (HCV) infection. The aims of the present study were (i) to validate the association between the Göteborg University Cirrhosis Index (GUCI) score and liver fibrosis and (ii) to evaluate the utility of this index in predicting the outcome of antiviral treatment. MATERIAL AND METHODS: A total of 269 patients with chronic HCV infection, stratified according to HCV genotype (1/4 versus 2/3) participated in a phase III trial using pegylated interferon alpha-2a and ribavirin (DITTO study). Retrospective analyses of the baseline GUCI scores and assessments of pretreatment liver biopsies using the Ishak protocol were performed. Cut-off GUCI scores were calculated to distinguish patients with a high or low probability of sustained viral response (SVR). RESULTS: Striking associations between GUCI and Ishak fibrosis stages (stages 0-2 versus stages 3-4, p = 0.0002, stages 3-4 versus stages 5-6, p = 0.002) were observed. In patients with genotype 1 or 4, a GUCI score below 0.33 was associated with a rapid viral response to antiviral treatment and an SVR rate of 80%. Ninety-two percent of patients (92/101) with a SVR had a pretreatment GUCI score below 1.11. CONCLUSIONS: Our results suggest that the GUCI score appropriately reflects the stage of liver fibrosis in HCV-infected patients, and predicts initial viral kinetics as well as treatment outcome in patients infected with HCV genotype 1 or 4.

Cirrhosis in hepatitis C virus-infected patients can be excluded using an index of standard biochemical serum markers.

OBJECTIVE: Assessment of liver histology is pivotal in prognostication and decision-making regarding therapeutic intervention in patients with chronic hepatitis C virus (HCV). Being an invasive procedure, the liver biopsy is associated with complications, and a non-invasive alternative would be preferable. MATERIAL AND METHODS: Sera samples from 179 patients with chronic HCV infection collected at the time of liver biopsy were analyzed using routinely available biochemical markers of liver disease, and liver histology was evaluated using the Ishak protocol. The relationship between the serum biochemical markers and cirrhosis (Ishak stage > or = 5) as well as bridging fibrosis (Ishak stage > or = 3) was examined. RESULTS: A strong association was found in the multivariate logistic regression analysis between fibrosis stage and aspartate aminotransferase (AST), platelet count and prothrombin-INR (international normalized ratio). An index (the Göteborg University Cirrhosis Index (GUCI)) was calculated using these variables: normalized ASTxprothrombin-INRx100/platelet count (x 10(9)/l). Using a cut-off value of 1.0, the sensitivity was 80% and the specificity 78% for diagnosis of cirrhosis, and the negative predictive values (NPV) and positive predictive values (PPV) were 97% and 31%, respectively. The GUCI score proved slightly superior for sensitivity, specificity, NPV, PPV, and the area under the receiver operating characteristic (ROC) curve for prediction of cirrhosis and bridging fibrosis compared with the AST to platelet ratio index (APRI), which has been reported as a predictor of significant fibrosis and cirrhosis. CONCLUSION: An index using routinely available biochemical markers can with a high degree of accuracy discriminate patients with from those without hepatitis C-related cirrhosis.

Prevalence of methicillin-resistant Staphyloccocus aureus and associated risk factors on admission to a specialist care eye hospital.

BACKGROUND: Staphylococcus aureus is known to be a frequent pathogen in hospital settings, with its well-known and resistant forms to the anti-staphylococcal penicillins. Reports on community carriage outside hospital settings have been feared to be on the increase due to the frequency of reported cases on admission to hospitals. We undertook this study to determine the prevalence of, and to establish predictors for, nasal carriage of methicillin-resistant S. aureus (MRSA) at the time of admission to a specialist care eye hospital. MATERIALS AND METHODS: A prospective survey was conducted at King Khaled Eye Specialist Hospital (KKESH), Riyadh, during three differing weeks randomly selected from the year 1999. The first 100 patients admitted during those three weeks were selected according to inclusion criteria. The hospital is a 220-bed tertiary ophthalmic care facility, with an average 7,500 admissions per year. Nasal bacterial swabs were taken within 48 hours of admission and tested for all strains of S. aureus and sensitivity to methicillin. Detailed interviews were conducted about medical history and habitual environment. RESULTS: Of 306 nasal cultures tested, none was isolated for MRSA and 102 (33%) were sensitive to methicillin (MSSA). We found 0% nasal carriage rate for MRSA. Respondents had difficulty with questions related to antibiotic administration. No identifiable medical or environmental risk factors could be found. CONCLUSION: Nasal swabs of patients admitted to KKESH did not reveal MRSA colonization, indicating that MRSA may not be prevalent in the community at present.