Three-dimensional reconstruction of renal tumor anatomy for preoperative planning of robotic partial nephrectomy in renal cell carcinoma cases with duplex kidney: a case report.

BACKGROUND: The duplex kidney is one of the common congenital anomalies of the kidney and urinary tract. We present two cases of renal tumor accompanied with ipsilateral duplex kidney. The image of the tumor, renal artery system and collecting system were rendered by AI software (Fujifilm's Synapse® AI Platform) to support the diagnosis and surgical planning. CASE PRESENTATION: Two Vietnamese patients (a 45-year-old man and a 54-year-old woman) with incidental cT1 renal cell carcinoma (RCC) were confirmed to have ipsilateral duplex kidneys by 3D reconstruction AI technique. One patient had a Renal score 9ah tumor of left kidney while the other had a Renal score 9 × tumor of right kidney in which a preoperative CT scan failed to identify a diagnosis of duplex kidney. Using the Da Vinci platform, we successfully performed robotic partial nephrectomy without any damage to the collecting system in both cases. CONCLUSION: RCC with duplex kidneys is a rare condition. By utilizing a novel AI reconstruction technique with adequate information, two patients with RCC in duplex kidneys were successfully performed robotic partial nephrectomy without complication.

Morphological Changes of 3T3 Cells under Simulated Microgravity.

BACKGROUND: Cells are sensitive to changes in gravity, especially the cytoskeletal structures that determine cell morphology. The aim of this study was to assess the effects of simulated microgravity (SMG) on 3T3 cell morphology, as demonstrated by a characterization of the morphology of cells and nuclei, alterations of microfilaments and microtubules, and changes in cycle progression. METHODS: 3T3 cells underwent induced SMG for 72 h with Gravite®, while the control group was under 1G. Fluorescent staining was applied to estimate the morphology of cells and nuclei and the cytoskeleton distribution of 3T3 cells. Cell cycle progression was assessed by using the cell cycle app of the Cytell microscope, and Western blot was conducted to determine the expression of the major structural proteins and main cell cycle regulators. RESULTS: The results show that SMG led to decreased nuclear intensity, nuclear area, and nuclear shape and increased cell diameter in 3T3 cells. The 3T3 cells in the SMG group appeared to have a flat form and diminished microvillus formation, while cells in the control group displayed an apical shape and abundant microvilli. The 3T3 cells under SMG exhibited microtubule distribution surrounding the nucleus, compared to the perinuclear accumulation in control cells. Irregular forms of the contractile ring and polar spindle were observed in 3T3 cells under SMG. The changes in cytoskeleton structure were caused by alterations in the expression of major cytoskeletal proteins, including ß-actin and α-tubulin 3. Moreover, SMG induced 3T3 cells into the arrest phase by reducing main cell cycle related genes, which also affected the formation of cytoskeleton structures such as microfilaments and microtubules. CONCLUSIONS: These results reveal that SMG generated morphological changes in 3T3 cells by remodeling the cytoskeleton structure and downregulating major structural proteins and cell cycle regulators.

Urethral Recurrence After Cystectomy and Orthotopic Bladder Reconstruction: A Rare Case of Recurrent Bladder Cancer After 12 Years and Review of the Literature.

Introduction: Radical cystectomy combined with orthotopic urinary diversion is a chosen approach for treating invasive bladder cancer. However, urothelial cell carcinoma is characterized by its potential for recurrence and the development of multiple tumors in the urinary tracts. In the natural progression of transitional cell carcinoma, the remaining ureteral stump is considered a predicted site for possible recurrence after radical cystectomy. Currently, there is no specific recommendation for the diagnosis and management of this condition. Objective: We report a rare case in a 74-year-old male patient who was diagnosed with anterior urethral carcinoma following a history of radical cystectomy and Hautmann ileal neobladder reconstruction. Additionally, we summarize some novel findings regarding risk factors, diagnosis, treatment, and prognosis in patients with recurrent bladder cancer in the urethra after radical cystectomy. Methods: A case report and mini review. Results: The patient was diagnosed with recurrent bladder cancer in the urethral after radical cystectomy using magnetic resonance imaging of the pelvis, cystoscopy, and biopsy. Complete urethrectomy and creation of a permanent percutaneous urinary diversion were performed. No intraoperative or postoperative complications were recorded. The patient was discharged 3 days after the surgery. Conclusion: Urethral cancer following radical cystectomy for bladder cancer treatment is a rare condition. Risk factors for this occurrence include male gender, non-use of orthotopic neobladder reconstruction technique, invasive tumors in the prostatic urethra, and multifocal tumors. The treatment of these tumors can be determined based on the extent of invasion and histological characteristics, leading to the choice between radical urethrectomy or alternative conservative treatments.

Laparoscopic retroperitoneal heminephrectomy for renal cell carcinoma in horseshoe kidney: a case report and review of the literature.

INTRODUCTION: In this case report, we demonstrate our technique of a retroperitoneal laparoscopic heminephrectomy for a T1b right hilar tumor in a horseshoe kidney. CASE PRESENTATION: A 77-year-old Vietnamese woman presented to the hospital because of right flank pain. On presentation, her serum creatinine was 0.86 mg/dL and glomerular filtration rate was 65.2 mL/minute/1.73 m2. According to her renal scintigraphy, glomerular filtration rates of the right and left moieties were 24.2 and 35.5 mL/minute, respectively. Computed tomography imaging demonstrated a 5.5 × 5.0 cm solid hilar mass with a cT1bN0M0 tumor stage was in the right moiety. After discussion, the patient elected a minimally invasive surgery to treat her malignancy. The patient was placed in a flank position. We used Gaur's balloon technique to create the retroperitoneal working space, and four trocar ports were planned for operation. Three arteries were dissected, including two arteries feeding the right moiety, one artery feeding the isthmus, and one vein, which was clipped and divided by Hem-o-lok. The isthmusectomy was performed with an Endostapler. Consequently, the ureter was clipped and divided. Finally, the whole right segment of the horseshoe kidney was mobilized and taken out via the flank incision. RESULTS: The total operative time was 250 min with an estimated blood loss of 200 mL. The patient's serum creatinine after surgery was 1.08 mg/dL, and glomerular filtration rate was 49.47 mL/minute/1.73 m2. The patient was discharged on postoperative day #4 without complication. Final pathologic examination of the tumor specimen revealed a Fuhrman grade II clear cell renal cell carcinoma, capsular invasion, with negative surgical margins. After a three-month follow-up, the serum creatinine was 0.95 mg/dL, and glomerular filtration rate was 57.7 mL/minute/1.73 m2. Local recurrence or metastasis was not detected by follow-up computed tomography imaging. CONCLUSIONS: Retroperitoneal laparoscopic heminephrectomy is a safe and feasible technique for patients with renal cell carcinoma in a horseshoe kidney and may be particularly useful in low income settings without access to robotic technology.

Combined PD-L1/TGFß blockade allows expansion and differentiation of stem cell-like CD8 T cells in immune excluded tumors.

TGFß signaling is associated with non-response to immune checkpoint blockade in patients with advanced cancers, particularly in the immune-excluded phenotype. While previous work demonstrates that converting tumors from excluded to inflamed phenotypes requires attenuation of PD-L1 and TGFß signaling, the underlying cellular mechanisms remain unclear. Here, we show that TGFß and PD-L1 restrain intratumoral stem cell-like CD8 T cell (TSCL) expansion and replacement of progenitor-exhausted and dysfunctional CD8 T cells with non-exhausted T effector cells in the EMT6 tumor model in female mice. Upon combined TGFß/PD-L1 blockade IFNγhi CD8 T effector cells show enhanced motility and accumulate in the tumor. Ensuing IFNγ signaling transforms myeloid, stromal, and tumor niches to yield an immune-supportive ecosystem. Blocking IFNγ abolishes the anti-PD-L1/anti-TGFß therapy efficacy. Our data suggest that TGFß works with PD-L1 to prevent TSCL expansion and replacement of exhausted CD8 T cells, thereby maintaining the T cell compartment in a dysfunctional state.

pH-temperature Responsive Hydrogel-Mediated Delivery of Exendin-4 Encapsulated Chitosan Nanospheres for Sustained Therapeutic Efficacy in Type 2 Diabetes Mellitus.

Type 2 Diabetes Mellitus (T2D) is a chronic, obesity-related, and inflammatory disorder characterize by insulin resistance, inadequate insulin secretion, hyperglycemia, and excessive glucagon secretion. Exendin-4 (EX), a clinically established antidiabetic medication that acts as a glucagon-like peptide-1 receptor agonist, is effective in lowering glucose levels and stimulating insulin secretion while significantly reducing hunger. However, the requirement for multiple daily injections due to EX's short half-life is a significant limitation in its clinical application, leading to high treatment costs and patient inconvenience. To address this issue, an injectable hydrogel system is developed that can provide sustained EX release at the injection site, reducing the need for daily injections. In this study, the electrospray technique is examine to form EX@CS nanospheres by electrostatic interaction between cationic chitosan (CS) and negatively charged EX. These nanospheres are uniformly dispersed in a pH-temperature responsive pentablock copolymer, which forms micelles and undergoes sol-to-gel transition at physiological conditions. Following injection, the hydrogel gradually degraded, exhibiting excellent biocompatibility. The EX@CS nanospheres are subsequently released, maintaining therapeutic levels for over 72 h compared to free EX solution. The findings demonstrate that the pH-temperature responsive hydrogel system containing EX@CS nanospheres can be a promising platform for the treatment of T2D.

A Review of the In Vitro Inhibition of α-Amylase and α-Glucosidase by Chalcone Derivatives.

Diabetes mellitus is a chronic metabolic disease relating to steady hyperglycemia resulting from the impairment of the endocrine and non-endocrine systems. Many new drugs having varied targets were discovered to treat this disease, especially type 2 diabetes. Among those, α-glucosidase inhibitors showed their effects by preventing the digestion of carbohydrates through their inhibition against α-amylase and α-glucosidase. Recently, chalcones have attracted considerable attention as they have a simple structure, are easily synthesized as well as have a variety of derivatives. Some reports suggested that chalcone and its derivates could inhibit α-amylase and α-glucosidase. This narrative review provides a comprehensive evaluation of the inhibition of chalcone and its derivatives against α-amylase and α-glucosidase that were reviewed and reported in published scientific articles. Twenty-eight articles were reviewed after screening 207 articles found in four databases, including PubMed, Google Scholar, VHL (Virtual Health Library), and GHL (Global Health Library). This review presented the inhibitory effects of varied chalcones, including chalcones with a basic structural framework, azachalcones, bis-chalcones, chalcone oximes, coumarin-chalcones, cyclohexane chalcones, dihydrochalcones, and flavanone-coupled chalcones. Many of these chalcones had significant inhibition against α-amylase as well as α-glucosidase that were comparable to or even stronger than standard inhibitors. This suggested that such compounds could be potential candidates for the discovery of new anti-diabetic remedies in the years to come.

Highly Prolonged Release of the Cancer Vaccine and Immunomodulator via a Two-Layer Biodegradable Microneedle for Prophylactic Treatment of Metastatic Cancer.

Simultaneous sustained release of cancer vaccines and immunomodulators may effectively trigger durable immune responses and avoid multiple administrations. Here, we established a biodegradable microneedle (bMN) based on a biodegradable copolymer matrix made of polyethylene glycol (PEG) and poly(sulfamethazine ester urethane) (PSMEU). This bMN was applied to the skin and slowly degraded in the epidermis/dermis layers. Then, the complexes composed of a positively charged polymer (DA3), cancer DNA vaccine (pOVA), and toll-like receptor 3 agonist poly(I/C) were synchronously released from the matrix in a pain-free manner. The whole microneedle patch was fabricated with two layers. The basal layer was formed using polyvinyl pyrrolidone/polyvinyl alcohol that could be rapidly dissolved upon applying the microneedle patch to the skin, whereas the microneedle layer was formed by complexes encapsulating biodegradable PEG-PSMEU, which was stuck at the injection site for sustained release of therapeutic agents. According to the results, 10 days is the time for the complexes to be completely released and express specific antigens in antigen-presenting cells in vitro and in vivo. It is noteworthy that this system could successfully elicit cancer-specific humoral immune responses and inhibit metastatic tumors in the lungs after a single shot of immunization.

Single-port and multiport robot-assisted radical prostatectomy: A meta-analysis.

Objective: To compare the perioperative, oncological, and functional outcomes between single-port robot-assisted radical prostatectomy (SP-RARP) and multiport robot-assisted radical prostatectomy (MP-RARP) via a meta-analysis. Methods: For relevant articles, three electronic databases, including PubMed, Scopus, and Web of Science, were searched from their inception until January 15, 2022. A meta-analysis has been reported in line with PRISMA 2020 and AMSTAR Guidelines. The risk ratio and weighted mean difference (MD) were applied for the comparison of dichotomous and continuous variables with 95% confidence intervals (CI). Results: Of the 368 retrieved abstracts, 41 underwent full-text review, and seven studies were included in the final analysis, comprising a total cohort of 1,934 cases of RARP (355 SP-RARP cases and 1,579 MP-RARP cases). Compared to MP-RARP, the SP-RARP group had less postoperative pain score (MD = -0.7, 95% CI -1 to -0.4, P<0.001), morphine milligram equivalents usage (MD = -3.8, 95% CI -7.5 to -0.1, P=0.04), hospital stay (MD = -1, 95% CI -1.8 to -0.1, P=0.019), and urinary catheterization time (MD = -1.1, 95% CI -1.9 to -0.3, P=0.008). However, the SP-RARP group had a longer console time than the MP-RARP group (MD = 5.3, 95% CI 2.6 to 7.9, P<0.001). Conclusions: Our study demonstrated that early results were mostly equivalent with the single-port approach. This technology may help to reduce the hospital stay and postoperative pain for patients undergoing radical prostatectomy compared to MP-RARP, without compromising the functional and early oncological outcomes.

LRRC15+ myofibroblasts dictate the stromal setpoint to suppress tumour immunity.

Recent single-cell studies of cancer in both mice and humans have identified the emergence of a myofibroblast population specifically marked by the highly restricted leucine-rich-repeat-containing protein 15 (LRRC15)1-3. However, the molecular signals that underlie the development of LRRC15+ cancer-associated fibroblasts (CAFs) and their direct impact on anti-tumour immunity are uncharacterized. Here in mouse models of pancreatic cancer, we provide in vivo genetic evidence that TGFß receptor type 2 signalling in healthy dermatopontin+ universal fibroblasts is essential for the development of cancer-associated LRRC15+ myofibroblasts. This axis also predominantly drives fibroblast lineage diversity in human cancers. Using newly developed Lrrc15-diphtheria toxin receptor knock-in mice to selectively deplete LRRC15+ CAFs, we show that depletion of this population markedly reduces the total tumour fibroblast content. Moreover, the CAF composition is recalibrated towards universal fibroblasts. This relieves direct suppression of tumour-infiltrating CD8+ T cells to enhance their effector function and augments tumour regression in response to anti-PDL1 immune checkpoint blockade. Collectively, these findings demonstrate that TGFß-dependent LRRC15+ CAFs dictate the tumour-fibroblast setpoint to promote tumour growth. These cells also directly suppress CD8+ T cell function and limit responsiveness to checkpoint blockade. Development of treatments that restore the homeostatic fibroblast setpoint by reducing the population of pro-disease LRRC15+ myofibroblasts may improve patient survival and response to immunotherapy.

Prevalence and Risk Factors of Mortality in Emphysematous Pyelonephritis Patients: A Meta-Analysis.

BACKGROUND: Emphysematous pyelonephritis (EP) is a severe necrotizing infection of the renal parenchyma which is associated with significant case mortality. We sought to identify the incidence and predictive risk factors associated with EP mortality. METHODS: Two electronic databases, PubMed and Web of Science, were searched from their inception until June 06, 2021 for relevant articles. Two independent teams reviewed abstracts and extracted data from the selected manuscripts. A meta-analysis has been reported in line with PRISMA 2020 and AMSTAR Guidelines. RESULTS: Of the 1080 retrieved abstracts, 79 underwent full-text review and 45 studies were included in the final analysis, comprising a total cohort of 1303 patients and 177 mortalities. The pooled prevalence of mortality among the patients with EP disease was 13%. Our analysis found a significantly decreasing trend in mortality rates, an increasing trend in minimally invasive intervention and decreasing trends in emergency nephrectomy in the EP studies from 1985 to 2020. Significant risk factors that were associated with a negative impact on survival of EP patients included sepsis (OR = 15.99), shock (OR = 15.57), disturbance of consciousness (OR = 12.11), thrombocytopenia (OR 7.85), acute renal failure (OR = 5.41), Wan classification I (OR = 4.57), emergency nephrectomy (OR = 3.73), Huang-Tseng classification III-IV (OR = 2.4) and medical management alone (OR = 2.04). Female sex (OR = 0.52) and minimally invasive intervention (OR = 0.47) (percutaneous nephrostomy or ureteral stent placement) were associated with decreased mortality rates. CONCLUSIONS: Our study results demonstrated several significant risk factors that could help guide treatment to reduce the mortality risk of EP patients. Clinically, early treatment with a combination of minimally invasive intervention and appropriate medical management may be protective for reducing mortality risk in EP patients.

Use of dental drill handpiece to remove steel nut causing penile strangulation: a case report and review of the literature.

BACKGROUND: Penile strangulation is an uncommon urological emergency that requires prompt intervention to avoid potentially serious sequelae including loss of the distal penis secondary to ischemia and subsequent gangrene. We present a case report of a patient who presented to the hospital with penile strangulation injury of 10-hour duration secondary to the presence of a thick hexagonal steel nut. This case is presented in accordance with Consensus Surgical Case Report guidelines. CASE PRESENTATION: A 24-year-old Vietnamese man presented to the emergency room with urinary retention and decreased penile sensation following a 10-hour history of penile strangulation due to the presence of a thick hexagonal steel nut that he had placed around the shaft of the penis for the purpose of sexual enhancement during masturbation. The hexagonal nut was tightly entrapping the penile shaft, resulting in edema, congestion, and swelling of the distal 5 cm of the phallus. Given the thickness of the foreign body as well as the degree of penile swelling, we were unable to remove the hexagonal nut using traditional methods of alleviating penile strangulation injuries. Following consultation with a dental colleague, a dental diamond drill handpiece was utilized to cut the foreign body without injury to the underlying penile skin. Subsequent follow-up in clinic demonstrated no significant urinary or sexual sequalae from this episode. CONCLUSION: We report a case of penile strangulation requiring novel instrumentation and collaboration for successful treatment.

Polymeric Systems for Cancer Immunotherapy: A Review.

Immunotherapy holds enormous promise to create a new outlook of cancer therapy by eliminating tumors via activation of the immune system. In immunotherapy, polymeric systems play a significant role in improving antitumor efficacy and safety profile. Polymeric systems possess many favorable properties, including magnificent biocompatibility and biodegradability, structural and component diversity, easy and controllable fabrication, and high loading capacity for immune-related substances. These properties allow polymeric systems to perform multiple functions in immunotherapy, such as immune stimulants, modifying and activating T cells, delivery system for immune cargos, or as an artificial antigen-presenting cell. Among diverse immunotherapies, immune checkpoint inhibitors, chimeric antigen receptor (CAR) T cell, and oncolytic virus recently have been dramatically investigated for their remarkable success in clinical trials. In this report, we review the monotherapy status of immune checkpoint inhibitors, CAR-T cell, and oncolytic virus, and their current combination strategies with diverse polymeric systems.

Pre-decision regret before transition of dependents with severe dementia to long-term care.

BACKGROUND: To place a dependent with severe dementia in a nursing home is a painful and difficult decision to make. In collectivistic oriented societies or families, children tend to be socialised to care for ageing parents and to experience guilt and shame if they violate this principle. Leaving the care to professional caregivers does not conform with the cultural expectations of many ethnic groups and becomes a sign of the family's moral failure. RESEARCH DESIGN: Qualitative design with individual in-depth interviews with nurses, family members and dementia care coordinators in Norway, Montenegro, Serbia and South Africa. Braun and Clarke's six analytic phases were used. ETHICAL CONSIDERATIONS: The project was approved by the Regional Committee for Research, South-Eastern Norway; the Norwegian Centre for Research Data; the Ethics Committee; University of Limpopo, MEDUNSA Campus, South Africa; and by the local heads of the respective nursing homes or home care services. Interviewees were informed orally and in writing and signed an informed consent form. FINDINGS: Healthcare professionals tend to be contacted only when the situation becomes unmanageable. Interviewees talked about feelings of obligation, shame and stigma in their societies regarding dementia, particularly in connection with institutionalisation of family members. Many lacked support during the decision-making process and were in a squeeze between their own needs and the patients' need of professional care, and the feeling of duty and worry about being stigmatised by their surroundings. This conflict may be a source of pre-decision regret. CONCLUSION: Family caregivers need help to understand the behaviours of persons with dementia and how to access the formal and informal services available. Thus, they may provide effective support to patients and family carers alike. Supportive interventions for caregivers need to be tailored to meet the individual needs of both the caregiver and the persons with dementia.

Introducing robot-assisted laparoscopic donor nephrectomy after experience in retroperitoneal endoscopic approach: a matched propensity score analysis.

OBJECTIVES: To assess the safety and efficacy of introducing robotic-assisted laparoscopic donor nephrectomy (RALDN) to the standard retroperitoneal endoscopic donor nephrectomy (REDN). METHODS: Data were collected prospectively from 124 consecutive living kidney donors (93 for REDN subgroup and 31 for RALDN subgroup) from February 2018 to December 2020. Donor baseline demographics, perioperative outcomes and recipient outcomes were recorded, and these parameters were compared between the two subgroups before and after propensity-score matching. RESULTS: Mean age was 51.1 ± 9.1 years; 42.7% were males; mean body mass index was 22.7 ± 2.4; and there were 109 (88%) left kidneys. The following data of REDN and RALDN was, respectively, recorded: operative time (213 ± 43 versus 216 ± 39 min, p = 0.721), warm ischemic time (4.7 ± 1.2 versus 4.9 ± 1.4 min, p = 0.399), postoperative complications (5.4% versus 6.5%, p = 1), haemoglobin (g/L) drop (9.4 ± 7.2 versus 9.7 ± 6.6, p = 0.836), blood creatinine at 6 month (1.15 ± 0.23 versus 1.13 ± 0.24 mg/dL, p = 0.734) and at 1 year (1.09 ± 0.22 versus 1.17 ± 0.28 mg/dL, p = 0.591). In post-propensity score matched analyses, there was no significant differences between the two groups including intraoperative and postoperative complications. CONCLUSIONS: RALDN could be safely introduced into a living donor program experienced in laparoscopic donor nephrectomy. The outcomes of our study comparing these minimally invasive techniques are mostly similar in terms of intraoperative and postoperative outcomes for kidney donors.

The Efficacy of Silver-Based Electrospun Antimicrobial Dressing in Accelerating the Regeneration of Partial Thickness Burn Wounds Using a Porcine Model.

(1) Background: Wounds with damages to the subcutaneous are difficult to regenerate because of the tissue damages and complications such as bacterial infection. (2) Methods: In this study, we created burn wounds on pigs and investigated the efficacy of three biomaterials: polycaprolactone-gelatin-silver membrane (PCLGelAg) and two commercial burn dressings, Aquacel® Ag and UrgoTulTM silver sulfadiazine. In vitro long-term antibacterial property and in vivo wound healing performance were investigated. Agar diffusion assays were employed to evaluate bacterial inhibition at different time intervals. Minimum inhibitory concentration (MIC), minimum bactericidal concentration (MBC) and time-kill assays were used to compare antibacterial strength among samples. Second-degree burn wounds in the pig model were designed to evaluate the efficiency of all dressings in supporting the wound healing process. (3) Results: The results showed that PCLGelAg membrane was the most effective in killing both Gram-positive and Gram-negative bacteria bacteria with the lowest MBC value. All three dressings (PCLGelAg, Aquacel, and UrgoTul) exhibited bactericidal effect during the first 24 h, supported wound healing as well as prevented infection and inflammation. (4) Conclusions: The results suggest that the PCLGelAg membrane is a practical solution for the treatment of severe burn injury and other infection-related skin complications.

Investigating the effect of multi-coated hydrogel layer on characteristics of electrospun PCL membrane coated with gelatin/silver nanoparticles for wound dressing application.

In this study, the effect of coated hydrogel layer on characteristics of the whole gelatin/silver nanoparticles multi-coated polycaprolactone membrane (PCLGelAg) was investigated through systematic and typical wound dressing characterizations to select the optimal number of layers for practical applications. Scanning electron microscopy, free swell absorptive capacity and tensile test in both wet and dry conditions were conducted to characterize all fabricated membranes of six coating times. In vitro cytotoxicity and agar diffusion evaluation were also carried out to assess the biocompatibility and antibacterial activity of the membranes. The findings illustrated that as the coated layers increase, the absorptive capacity, and degradation rate were higher, the membranes were stiffer in dry state while the tensile strength in wet state, elongation, and cell viability were significantly decreased. PCLGelAg3 was chosen to be the best fit for wound healing since it maintained quite sufficient maximum buffer uptake, elasticity, cell viability along with inducing abnormalities in bacterial morphology and preventing biofilm formation.

A novel injectable pH-temperature sensitive hydrogel containing chitosan-insulin electrosprayed nanosphere composite for an insulin delivery system in type I diabetes treatment.

A novel insulin composite delivery system was prepared and characterized. The composite consisted of a pH- and temperature-sensitive hydrogel, which is an oligomer serine-b-poly(lactide)-b-poly(ethylene glycol)-b-poly(lactide)-b-oligomer serine (OS-PLA-PEG-PLA-OS) pentablock copolymer, as matrix and chitosan-insulin electrosprayed nanospheres (CIN) as constituent materials. The properties of the OS-PLA-PEG-PLA-OS pentablock copolymer and the chitosan-insulin nanoparticles were characterized. The chitosan-insulin nanospheres uniformly distributed in the matrix had a reinforcing effect on the mechanical properties and prolonged the degradation time of the hydrogel depot under body conditions. The composite solutions accommodating different concentrations of the chitosan-insulin nanospheres were subcutaneously injected into induced diabetic BALB/c mice to study the in vivo insulin-release profile. The result showed that insulin concentrations in blood plasma were maintained at a steady-state level. Furthermore, the bio-properties of the insulin were retained and it showed a blood glucose level reducing effect for more than 60 hours after injection to a streptozotocin (STZ)-induced diabetic mouse model. The results suggested that this injectable pH-temperature sensitive hydrogel containing chitosan-insulin electrosprayed nanosphere composites has promising potential applications for type 1 diabetes treatment.

Dried blood spots perform well to identify patients with active HCV infection in Vietnam.

Recently, treatment advances in direct-acting antivirals have radically changed the management of HCV patients. However, in resource-limited countries, identification of patients with active HCV infection is still challenging in remote settings due to the limited access to laboratories able to measure HCV viral load. This study evaluated whether dried blood spots (DBS) transferred to a central laboratory could overcome this challenge. A total of 315 HCV-infected patients, naïve to anti-HCV treatment, provided each three type of samples: plasma, DBS with calibrated quantities of venous blood and DBS with uncalibrated quantities of capillary blood. Qualitative comparison was conducted in terms of detection of HCV viral load on DBS as opposed to plasma to estimate sensitivity and specificity. Quantitative comparisons were conducted by means of correlation estimation. Of the 250 patients with detected plasma HCV viral load, 245 also had detectable DBS HCV viral load (capillary or venous) leading to a sensitivity of 98.0% (95% confidence interval (CI): 95.4%-99.3%); importantly, all measurements with a plasma HCV viral load >118 IU/mL were also detected in DBS. When HCV was not detected in plasma, it was also not detected in DBS resulting in 100% specificity (95% CI: 94.5%-100%). Quantitative HCV viral load results were very similar when utilizing plasma or DBS sample types as illustrated by correlations >0.99. In conclusion, DBS sample types, with either uncalibrated capillary blood or calibrated venous blood, performed well to distinguish patients with active HCV infection, and who therefore need treatment, from other patients.

Smart injectable biogels based on hyaluronic acid bioconjugates finely substituted with poly(ß-amino ester urethane) for cancer therapy.

Development of implantable material to control the release of chemotherapeutics in the body is a promising approach to control cancer cell proliferation; however, implantation requires surgical intervention. Herein, we propose the in situ formation of injectable biogels (IBGs) for the programmed delivery of potent chemotherapeutic drugs. IBGs are developed via cohesive molecular assembly of a polysaccharide-polymer network comprised of hyaluronic acid-poly(ß-amino urethane). Biocompatible IBGs could be administered subcutaneously through a hypodermic needle in vivo to subsequently assemble into a microporous network. The hyaluronic acid-shielded network mimics the natural extracellular matrix, avoiding rapid degradation of IBGs, with a soft texture and adhesiveness facilitating integration with dermal tissues after subcutaneous implantation. The natural-mimicking architecture confers the IBG network controlled degradation and bioresorbable properties. Subcutaneous administration of IBGs controlled the delivery of a therapeutic agent in a spatio-temporal manner. Therapeutic agents delivered near the tumors in a sustained manner were effectively infiltrated into the thick solid tumors and provide a durable and enhanced anti-tumor response in the B16/OVA melanoma model in vivo. These results indicate that IBGs could be potential medical interventions for the treatment of cancers.