A dive into the bath: embedded 3D bioprinting of freeform in vitro models.

Designing functional, vascularized, human scale in vitro models with biomimetic architectures and multiple cell types is a highly promising strategy for both a better understanding of natural tissue/organ development stages to inspire regenerative medicine, and to test novel therapeutics on personalized microphysiological systems. Extrusion-based 3D bioprinting is an effective biofabrication technology to engineer living constructs with predefined geometries and cell patterns. However, bioprinting high-resolution multilayered structures with mechanically weak hydrogel bioinks is challenging. The advent of embedded 3D bioprinting systems in recent years offered new avenues to explore this technology for in vitro modeling. By providing a stable, cell-friendly and perfusable environment to hold the bioink during and after printing, it allows to recapitulate native tissues' architecture and function in a well-controlled manner. Besides enabling freeform bioprinting of constructs with complex spatial organization, support baths can further provide functional housing systems for their long-term in vitro maintenance and screening. This minireview summarizes the recent advances in this field and discuss the enormous potential of embedded 3D bioprinting technologies as alternatives for the automated fabrication of more biomimetic in vitro models.

Synthesis and characterization of stimuli-responsive hydrogels: evaluation of external stimuli influence on L929 fibroblast viability.

In this study, poly(2-hydroxyethyl methacrylate) [p(HEMA)] based hydrogels responsive to the pH, temperature and magnetic field were synthesized. The surface properties of p(HEMA) were improved by designing the stimuli-responsive hydrogels made of MAGA, NIPAAm and methacrylate-decorated magnetite nanoparticles as a function of pH-, thermo- and magnetic responsive cell culture surfaces. These materials were then modified an abundant extracellular matrix component, type I collagen, which has been considered as a biorecognition element to increase the applicability of hydrogels to cell viability. Based on results from scanning electron microscopy (SEM) and thermal gravimetric analysis (TGA), stimuli-responsive hydrogel demonstrated improved non-porous structures and thermal stability with a high degree of cross-linking. Mechanical analyses of the hydrogels also showed that stimuli-responsive hydrogels are more elastomeric due to the polymeric chains and heterogeneous amorphous segments compared to plain hydrogels. Furthermore, surface modification of hydrogels with collagen provided better biocompatibility, which was confirmed with L929 fibroblast cell adhesion. Produced stimuli-responsive hydrogels modulated cellular viability by changing pH and magnetic field.

Rose petal topography mimicked poly(dimethylsiloxane) substrates for enhanced corneal endothelial cell behavior.

Low proliferation capacity of corneal endothelial cells (CECs) and worldwide limitations in transplantable donor tissues reveal the critical need of a robust approach for in vitro CEC growth. However, preservation of CEC-specific phenotype with increased proliferation has been a great challenge. Here we offer a biomimetic cell substrate design, by optimizing mechanical, topographical and biochemical characteristics of materials with CEC microenvironment. We showed the surprising similarity between topographical features of white rose petals and corneal endothelium due to hexagonal cell shapes and physiologically relevant cell density (≈ 2000 cells/mm2). Polydimethylsiloxane (PDMS) substrates with replica of white rose petal topography and cornea-friendly Young's modulus (211.85 ± 74.9 kPa) were functionalized with two of the important corneal extracellular matrix (ECM) components, collagen IV (COL 4) and hyaluronic acid (HA). White rose petal patterned and COL 4 modified PDMS with optimized stiffness provided enhanced bovine CEC response with higher density monolayers and increased phenotypic marker expression. This biomimetic approach demonstrates a successful platform to improve in vitro cell substrate properties of PDMS for corneal applications, suggesting an alternative environment for CEC-based therapies, drug toxicity investigations, microfluidics and organ-on-chip applications.

Impact of Poly(dimethylsiloxane) Surface Modification with Conventional and Amino Acid-Conjugated Self-Assembled Monolayers on the Differentiation of Induced Pluripotent Stem Cells into Cardiomyocytes.

Cardiomyocytes, differentiated from induced pluripotent stem cells (iPSCs), have the potential to produce patient- and disease-specific pharmacological and toxicological platforms, in addition to their cardiac cell therapy applications. However, the lack of both a robust and a simple procedure for scalable cell substrate production is one of the major limitations in this area. Mimicking the natural healthy myocardium extracellular matrix (ECM) properties by altering the cell substrate properties, such as stiffness and chemical/biochemical composition, can significantly affect cell substrate interfacial characteristics and potentially influence cellular behavior and differentiation of iPSCs to cardiomyocytes. Here, we propose a systematic and biomimetic approach, based on the preparation of poly(dimethylsiloxane) (PDMS) substrates having the similar stiffness as healthy heart tissue and a well-defined surface chemistry obtained by conventional [(3-aminopropyl)triethoxysilane (APTES) and octadecyltrimethoxysilane (OTS)] and amino acid (histidine and leucine)-conjugated self-assembled monolayers (SAMs). Among a wide range of different concentrations, the 50:1 prepolymer cross-linker ratio of PDMS allowed adaptation of the myocardium stiffness with a Young's modulus of 23.79 ± 0.61 kPa. Compared with conventional SAM modification, amino acid-conjugated SAMs greatly improved iPSC adhesion, viability, and cardiac marker expression by increasing surface biomimetic properties, whereas all SAMs enhanced cell behavior, with respect to native PDMS. Furthermore, leucine-conjugated SAM modification provided the best environment for cardiac differentiation of iPSCs. This optimized approach can be easily adapted for cardiac differentiation of iPSCs in vitro, rendering a very promising tool for microfluidics, drug screening, and organ-on-chip platforms.

The prevalence and diagnostic criteria of health-care associated infections in neonatal intensive care units in Turkey: A multicenter point- prevalence study.

BACKGROUND: Healthcare-acquired infections (HAIs) in the neonatal period cause substantial morbidity, mortality, and healthcare costs. Our purpose was to determine the prevalence of HAIs, antimicrobial susceptibility of causative agents, and the adaptivity of the Centres for Disease Control and Prevention (CDC) criteria in neonatal HAI diagnosis. METHODS: A HAI point prevalence survey was conducted in the neonatal intensive care units (NICUs) of 31 hospitals from different geographic regions in Turkey. RESULTS: The Point HAI prevalence was 7.6%. Ventilator-associated pneumonia (VAP) and central line-associated bloodstream infections (CLABSI) and late onset sepsis were predominant. The point prevalence of VAP was 2.1%, and the point prevalence of CLABSI was 1.2% in our study. The most common causative agents in HAIs were Gram-negative rods (43.0%), and the most common agent was Klebsiella spp (24.6%); 81.2% of these species were extended spectrum beta-lactamase (ESBL) (+). Blood culture positivity was seen in 33.3% of samples taken from the umbilical venous catheter, whereas 0.9% of samples of peripherally inserted central catheters (PICCs) were positive. In our study, 60% of patients who had culture positivity in endotracheal aspirate or who had purulent endotracheal secretions did not have any daily FiO2 change (p = 0.67) and also 80% did not have any increase in positive end-expiratory pressure (PEEP) (p = 0.7). On the other hand, 18.1% of patients who had clinical deterioration compatible with VAP did not have endotracheal culture positivity (p = 0.005). CONCLUSIONS: Neonatal HAIs are frequent adverse events in district and regional hospitals. This at-risk population should be prioritized for HAI surveillance and prevention programs through improved infection prevention practices, and hand hygiene compliance should be conducted. CDC diagnostic criteria are not sufficient for NICUs. Future studies are warranted for the diagnosis of HAIs in NICUs.

A facile surface modification of poly(dimethylsiloxane) with amino acid conjugated self-assembled monolayers for enhanced osteoblast cell behavior.

Polydimethylsiloxane (PDMS) is a biocompatible synthetic polymer and used in various applications due to its low toxicity and tunable surface properties. However, PDMS does not have any chemical cues for cell binding. Plasma treatment, protein coating or surface modification with various molecules have been used to improve its surface characteristics. Still, these techniques are either last for a very limited time or have very complicated experimental procedures. In the present study, simple and one-step surface modification of PDMS is successfully accomplished by the preparation of hydrophilic and hydrophobic amino acid conjugated self-assembled monolayers (SAMs) for enhanced interactions at the cell-substrate interface. Synthesis of histidine and leucine conjugated (3-aminopropyl)-triethoxysilane (His-APTES and Leu-APTES) were confirmed with proton nuclear magnetic resonance spectroscopy (1H NMR) and optimum conditions for the modification of PDMS with SAMs were investigated by X-ray photoelectron spectroscopy (XPS) analysis, combined with water contact angle (WCA) measurements. Results indicated that both SAMs enhanced cellular behavior in vitro. Furthermore, hydrophilic His-APTES modification provides a superior environment for the osteoblast maturation with higher alkaline phosphatase activity and mineralization. As histidine, leucine, and functional groups of these SAMs are naturally found in biological systems, modification of PDMS with them increases its cell-substrate surface biomimetic properties. This study establishes a successful modification of PDMS for in vitro cell studies, offering a biomimetic and easy procedure for potential applications in microfluidics, cell-based therapies, or drug investigations.

Arsenite removal from groundwater by aerated electrocoagulation reactor with Al ball electrodes: Human health risk assessment.

The application of conventional electrocoagulation (EC) process for removal of As(III) from groundwater suffers from the need of external oxidation agent for oxidation of As(III) to As(V). To tackle this limitation, an aerated EC reactor for the removal of As(III) from groundwater was evaluated in this study. The effect of initial pHi, air flow rate, applied current, and electrode height in the EC reactor was examined. The experimental results showed that removal of arsenic mostly dependent on the applied current, electrode height in EC reactor, and air flow rate. The As(III) removal efficiency (99.2%) was maximum at pHi of 7.5, air flow rate of 6 L min-1, applied current of 0.30 A, and electrode height in EC reactor of 5 cm, with an total operating cost of 0.583 $ m-3. Furthermore, the carcinogenic risk (CR) and non-carcinogenic risk of arsenic (As) was in the range of tolerable limits at all operating conditions except applied current of 0.075 A at the end of the aerated EC process to remove As from groundwater. The present EC reactor process is able to remove As(III) from groundwater to below 10 µg L-1, which is maximum contaminant level of arsenic in drinking water according to the World Health Organization (WHO).

Reopening of the ductus arteriosus in preterm infants; Clinical aspects and subsequent consequences.

OBJECTIVE: Patent ductus arteriosus is a common problem frequently encountered in preterm infants. We aimed to study the risk factors associated with reopening of patent ductus arteriosus and their short term outcomes in preterm infants. METHODS: A total of 162 preterm infants born between November 2013 and December 2015 with gestaional age less than 32 weeks and treated for hemodynamically significant patent ductus arteriosus are included in our study. RESULTS: 113(69.8%) showed permanent closure and 49(30.2%) infants revealed symptoms of reopening after effective closure of patent ductus arteriosus. Low birth weight and small gestational age were more common in reopening group. Multivariete analysis showed that sepsis and multiple courses of drug treatment were independent factors affecting reopening of hemodynamically significant patent ductus arteriosus (OR: 3.01, 95% CI 1.48-6.13, p = 0.002) and (OR: 2.67, 95% CI 1.23-5.82, p = 0.013) respectively. Reopened group had a remarkable higher rate of developing necrotising nnterocolitis, bronchopulmonary dysplasia and retinopathy of prematurity than the closed group. (16.3% vs 4.4%, p = 0.01, 55.1% vs 28.3%, p = 0.001 and 55.1% vs 23.0%, p = 0.0001 respectively). CONCLUSION: Late neonatal sepsis and the need of multiple drug courses to close patent ductus arteriosus are risk factors affecting the reopening of patent ductus arteriosus in preterm infants.

Effect of maternal cervical bacterial colonization on neonatal outcome in high-risk pregnancies: results from a tertiary maternity center in Turkey.

PURPOSE: To evaluate and compare the morbidity and mortality of neonates born to pregnant women with positive and negative cervical cultures. MATERIALS AND METHODS: The demographic and clinical features of mothers included in this study, along with details of the microorganisms isolated on maternal cervical cultures and the number of days between a positive cervical culture and delivery were recorded. Neonates were stratified into two groups based on cervical culture results of their mothers--Group 1, positive cervical culture; Group 2, negative cervical culture. RESULTS: A total of 216 women who delivered 242 infants were included in the study. Group 1 consisted of 90 neonates while Group 2 had 152 newborns. The difference between the groups with demographic characteristics was statistically insignificant. Mean levels of the acute phase reactants, CRP, and IL-6, obtained six hours after delivery were significantly higher in Group 1 compared to Group 2 (p < 0.05 for C-reactive protein (CRP) andp < 0.001 for IL-6). Although there was no difference between groups in terms of duration of respiratory support, mean duration of hospitalization, as well as mortality rate were significantly higher in Group 1 (p < 0.001, p < 0.05, respectively). CONCLUSIONS: Women diagnosed with a high-risk pregnancy should be treated with antibiotics immediately after a positive cervical culture result, and delivery should be delayed until the success of antibiotic treatment can be evaluated. Early initiation of maternal antibiotic therapy is associated with shorter durations of hospital stay for newborns. Close follow-up of mothers with high-risk pregnancies and extension of treatment duration are critical for determining prognosis in newborn infants.

Game theory and fuzzy programming approaches for bi-objective optimization of reservoir watershed management: a case study in Namazgah reservoir.

In this study, game theory and fuzzy programming approaches were used to balance economic and environmental impacts in the Namazgah reservoir, Turkey. The main goals identified were to maximize economic benefits of land use and to protect water quality of reservoir and land resources. Total phosphorous load (kg ha(-1) year(-1)) and economic income (USD ha(-1) year(-1)) from land use were determined as environmental value and economic value, respectively. The surface area of existing land use types, which are grouped under 10 headings according to the investigations on the watershed area, and the constraint values for the watershed were calculated using aerial photos, master plans, and basin slope map. The results of fuzzy programming approach were found to be very close to the results of the game theory model. It was concluded that the amount of fertilizer used in the current situation presents a danger to the reservoir and, therefore, unnecessary fertilizer use should be prevented. Additionally, nuts, fruit, and vegetable cultivation, instead of wheat and corn cultivation, was found to be more suitable due to their high economic income and low total phosphorus (TP) load. Apart from agricultural activities, livestock farming should also be considered in the area as a second source of income. It is believed that the results obtained in this study will help decision makers to identify possible problems of the watershed.

Hypercalcemia due to subcutaneous fat necrosis in a newborn after total body cooling.

Subcutaneous fat necrosis is an inflammatory disorder of adipose tissue. Although patients need long-term follow-up to prevent hypercalcemia, the prognosis is generally favorable. We herein present a case of a newborn who developed subcutaneous fat necrosis-related hypercalcemia after hypothermia treatment for hypoxic ischemic encephalopathy. Widespread use of hypothermia treatment for hypoxic ischemic encephalopathy in the neonatal intensive care unit may increase the risk of developing subcutaneous fat necrosis and subsequently hypercalcemia. Great care should be taken to recognize skin findings early in newborns receiving hypothermia treatment, and those diagnosed with subcutaneous fat necrosis require close follow-up because they are at risk for developing hypercalcemia.

Jarcho-Levin syndrome presenting with severe hydrocephalus: a report of three cases.

Jarcho-Levin syndrome (JLS) is a genetic disorder characterized by defects of spine formation, abnormal fusion of the ribs at the costovertebral and costochondral junction due to abnormal vertebral and costal segmentation. There are two subtypes associated with different distribution and severity of defects in JLS. While vertebral segmentation abnormalities are frequent in spondylo-thoracic subtype costal segmentation and fusion abnormalities are frequent in spondylo-costal subtype. Neural tube defects with severe hydrocephalus are rare findings in this syndrome. Herein we report three infants with severe hydrocephalus associated with Jarcho-Levin syndrome.

Severe semilobar holoprosencephaly and lissencephaly associated with cebocephaly in a newborn.

Holoprosencephaly is frequently accompanied by midline facial abnormalities such as hypotelorism, cyclopia, etmocephaly and cebocephaly. Cebocephaly is a very rare congenital anomaly combining with semilobar holoprosencephaly. Chromosomal analysis shows normal karyotyping. Lissencephaly and holoprosencephaly are rare associations, that have not been reported yet with cebocephaly. Herein we present the first case of cebocephaly with severe semilobar holoprosencephaly and lissencephaly.

A preterm infant with prolonged respiratory problems due to Ritscher-Schinzel syndrome.

Ritscher-Schinzel also known as cranio-cerebello-cardiac (3C) syndrome is a very rare clinical entity. The striking features of this syndrome are cerebellar, cardiac and craniofacial abnormalities. Life threatening features of this syndrome are generally associated with cardiac abnormalities. We here present prolonged respiratory problems due to pulmonary hypertension in a preterm baby with Ritscher-Schinzel syndrome.

Congenital mirror hand deformity.

Ulnar dimelia or commonly called mirror hand is a rare congenital anomaly of upper extremity characterized by duplication of ulna, absence of the radius with symmetrical polydactyly. This anomaly may be associated with shoulder dislocation, fibular dimelia, idiopathic scoliosis, cirrhosis, pyloric hypertrophy or polycystic kidney. We report a new case of this rare congenital anomaly which was not associated with any other malformation.

The role of group education on quality of life in patients with a stoma.

Stoma education has been traditionally given in a one-to-one setting. Since 2007, daily group education programmes were organised for stoma patients and their relatives by our stoma therapy unit. The programmes included lectures on stoma and stoma care, and social activities in which patients shared their experiences with each other. Patients were also encouraged to expand interaction with each other and organise future social events. A total of 72 patients [44 (61.1%) male with a mean (± SD) age of 56.8 ± 13.6 years] with an ileostomy (n= 51, 70.8%), a colostomy (n= 18, 25.0%) or a urostomy (n= 3, 4.2%) were included in the study. Patients were asked to answer a survey (SF-36) face-to-face before the initiation of the programme, which was repeated 3 months later via telephone call. The comparison of pre-education and post-education SF-36 scores revealed a statistically significant improvement in all 8-scale profiles, but not in vitality scale, and both psychometrically-based and mental health summary measures. Analyses disclosed that married patients and those who were living at rural districts seem to have the most improvement in life quality particularly in bodily pain, general health and role-emotional scales and mental health summary measure. In our opinion, group educations may be beneficial for stoma patients, and stoma therapy units may consider organising similar activities.

Laparoscopy for sigmoid colon and rectal cancers in septuagenarians: a retrospective, comparative study.

BACKGROUND: The aim of the study is to analyze the results of laparoscopy in septuagenarians with sigmoid colon or rectal cancer. METHODS: Patients who underwent laparoscopic or hand-assisted laparoscopic sigmoid or rectal resections for cancer were retrospectively selected from the database of our institution. The study group (Lap > 70 group), contained the cancer patients over 70 years old who were treated with laparoscopy. Patients less than 70 years old who underwent a laparoscopic procedure (Lap < 70 group), and those over than 70 years old who underwent conventional surgery (Open > 70 group), were assigned to control groups. Demographics, information regarding tumors, perioperative data, pathological results, and survival in the three groups were compared. RESULTS: There were 56, 166, and 34 patients in the Lap > 70, Lap < 70, and Open > 70 groups, respectively. Patients in the Lap > 70 group were significantly older than other groups. The American Society of Anesthesiologists scores were higher, and the presence of the studied risk factors was more common in the Lap > 70 group than the Lap < 70 group. Intraoperative bleeding and the amount and number of perioperative transfusions required were less in the Lap > 70 group than in the Open > 70 group. The number of harvested lymph nodes was less in the Lap > 70 group than both study groups. Five-year survival in the Lap > 70 group was similar to that in the Lap < 70 group and significantly better than in the Open > 70 group. CONCLUSIONS: Laparoscopy for sigmoid colon and rectal cancer in patients over 70 may be feasible and safe as it is in younger patients. The present study has revealed that laparoscopy in the elderly may be superior to conventional techniques as regards some intraoperative findings and survival.

Mild and severe anal incontinence after lateral internal sphincterotomy: risk factors, postoperative anatomical findings and quality of life.

AIM: This study aims to evaluate the risk factors for incontinence after lateral internal sphincterotomy (LIS) and assess quality of life in different levels of incontinence. METHODS: All consecutive patients (n = 253) with chronic anal fissure who underwent LIS between 2003 and 2006 were retrospectively reviewed. All patients were questioned for possible anal incontinence according to the Wexner Incontinence Score (WIS). Demographics, vaginal delivery history, additional procedures and surgeon's experience were evaluated as risk factors. Endoanal ultrasound (EUS) was performed in incontinent patients to assess the thickness of the remaining internal sphincter and to evaluate any injury in the external sphincter. Quality of life was questioned with SF-36. RESULTS: Twenty-eight (11.7%) patients suffered from incontinence (mean WIS = 3.6 ± 2.5). The search for a risk factor was unsuccessful when continent and incontinent groups were compared. In subgroup analyses, patients were found to be suffering from mild (WIS <5, n = 19) or severe (WIS >5, n = 9) incontinence. Vaginal delivery history was found more often in the severely incontinent subgroup than in the continent group (p < 0.05). Also, vaginal delivery history and the additional procedures were more frequently observed in the severely incontinent subgroup than in the mildly incontinent subgroup. EUS did not find any external sphincter injury in these cases. WIS had negative correlations with the physical and mental component scores of SF-36. CONCLUSION: In our opinion, the threat for incontinence is unpredictable; however, vaginal delivery history may increase the risk of severe incontinence.