Electromechanical convective drug delivery devices for overcoming diffusion barriers.

Drug delivery systems which rely on diffusion for mass transport, such as hydrogels and nanoparticles, have enhanced drug targeting and extended delivery profiles to improve health outcomes for patients suffering from diseases including cancer and diabetes. However, diffusion-dependent systems often fail to provide >0.01-1% drug bioavailability when transporting macromolecules across poorly permeable physiological tissues such as the skin, solid tumors, the blood-brain barrier, and the gastrointestinal walls. Convection-enabling robotic ingestibles, wearables, and implantables physically interact with tissue walls to improve bioavailability in these settings by multiple orders of magnitude through convective mass transfer, the process of moving drug molecules via bulk fluid flow. In this Review, we compare diffusive and convective drug delivery systems, highlight engineering techniques that enhance the efficacy of convective devices, and provide examples of synergies between the two methods of drug transport.

Clinical impact of inferior mesenteric vein preservation during left hemicolectomy with low ligation of the inferior mesenteric artery for distal transverse and descending colon cancers: A comparative study based on computed tomography.

Purpose: Presence of a long remnant sigmoid colon after left hemicolectomy with inferior mesenteric vein (IMV) ligation for distal transverse and descending colon cancers may be a risk factor for venous ischemia. This study aimed to evaluate the clinical impact of IMV preservation in patients who underwent left hemicolectomy with inferior mesenteric artery (IMA) preservation. Methods: We included 155 patients who underwent left hemicolectomy with IMA preservation for distal transverse and descending colon cancers from 2003 to 2020. Technical success of IMV preservation was determined by assessing pre- and post-operative patency of the IMV on computed tomography (CT) by an abdominal radiologist. Intestinal complications comprising ulceration, stricture, venous engorgement, and colitis in remnant colon were compared between the IMV preservation and ligation groups. Results: IMV was preserved in 22 (14.2%) and ligated in 133 (85.8%) patients. Surgical time, postoperative recovery outcomes, and number of harvested lymph nodes were similar in both groups. The technical success of IMV preservation was 81.8%. Intestinal complications were less common in the preservation group than in the IMV ligation group (4.5% vs. 23.3%, P=0.048). The complications in the IMV ligation group were anastomotic ulcer (n=2), anastomotic stricture (n=4), venous engorgement of the remnant distal colon (n=4), and colitis in the distal colon (n=21). Conclusions: IMV preservation may be beneficial after left hemicolectomy with IMA preservation for distal transverse and descending colon cancers. We suggest that IMV preservation might be considered when long remnant sigmoid colon is expected during left hemicolectomy with low ligation of IMA.

Subacute Oral Toxicity Evaluation of Expanded-Polystyrene-Fed Tenebrio molitor Larvae (Yellow Mealworm) Powder in Sprague-Dawley Rats.

Tenebrio molitor larvae, as known as edible insects, has advantages of being rich in protein, and has been recognized as a suitable alternate protein source for broiler and pig feed. Moreover, given their ability to biodegrade polystyrene, a major pollutant, Tenebrio molitor larvae has been proposed as an innovative solution to environmental problems. In the present study, we investigated the toxicity of Tenebrio molitor larvae powder (TMlp) ingested with expanded-polystyrene (W/ eps) through in vitro and in vivo experiments. The objective of this study was to determine whether TMlp W/ eps can be applied as livestock alternative protein source. For in vitro experiments, cytotoxicity test was performed to investigate the effects of TMlp-extract on the viability of estrogen-dependent MCF-7 cells. The possibility of estrogen response was investigated in two groups: Expanded-polystyrene-fed (W/ eps) TMlp group and without expanded-polystyrene-fed (W/o eps) TMlp group. For in vivo experiments, The male Sprague-Dawley rats were divided based on the dosage of TMlp administered and oral administration was performed to every day for 5 weeks. A toxicological assessments were performed, which included clinical signs, food consumption, body and organ weights, hematology, serum chemistry, and hematoxylin and eosin staining of liver and kidney. There were no specific adverse effect of TMlp W/ eps-related findings under the experimental conditions of this study, but further studies on both sexes and animal species differences should be investigated. In conclusion, TMlp W/ eps was considered non-toxic and observed to be applicable as an alternative protein source for livestock feed.

A double crosslinking adhesion mechanism for developing tough hydrogel adhesives.

Tough hydrogel adhesives that consist of a robust gel network and can strongly adhere to wet tissues have shown great promise as the next generation of bioadhesives. While a variety of chemistries can be utilized to construct the tough gel network, the covalent conjugation methods for tissue adhesion are still limited. Here we report, for the first time, the use of side product-free amine-thiolactone chemistry which initiates a double crosslinking adhesion mechanism to develop tough gel adhesives. Thiolactone groups can conjugate with tissue-surface amines via a ring-opening reaction. The resultant thiol end groups can be further crosslinked into disulfide linkages, enabling the formation of a robust and stable adhesion layer. The thiolactone-bearing tough hydrogel composed of methacrylate-modified gelatin, acrylic acid, and thiolacone acrylamide exhibited good biocompatibility and mechanical properties, and strong adhesion to various types of engineering solids and tissues. We also demonstrated its ability to function as a tissue sealant and drug depot. The novel adhesion mechanism will diversify future design of bioadhesives for hemostasis, drug delivery, tissue repair, and other applications. STATEMENT OF SIGNIFICANCE: Tough hydrogel adhesives with excellent tissue-adhesive and mechanical properties have demonstrated tremendous promise for hemostasis, tissue repair, and drug delivery applications. However, the covalent chemistry for tissue adhesion has been limited, which narrows the choice of materials for the design of bioadhesives and may pose a safety concern. Here, for the first time, we report the use of side product-free amine-thiolactone chemistry, which involves a double crosslinking adhesion mechanism, for developing tough hydrogel adhesives. We demonstrate that thiolactone-bearing tough hydrogels exhibit favorable biocompatibility and mechanical properties, and superior adhesion to both engineering solids and tissues. Our new adhesion technology will greatly facilitate future development of advanced bioadhesives for numerous biomedical applications.

A carbon-black-embedded poly(dimethylsiloxane)-paper hybrid device for energy-efficient nucleic-acid amplification in point-of-care testing.

A paper-based device patterned with a carbon-black-poly(dimethylsiloxane) (PDMS) mixture is developed as a heating platform for nucleic-acid amplification tests. The photothermal effect of carbon black under 808 nm laser irradiation is used to conduct loop-mediated isothermal amplification (LAMP) to detect Escherichia coli (E. coli) O157:H7, a foodborne pathogen. We characterize the heat generation of carbon black by changing its concentration and the hardness of PDMS. Then, we optimize the minimum laser power required to perform LAMP. The proposed paper-based device requires less than 15 min to perform LAMP, and the result can be confirmed based on the color change observed by the naked eye. The rfbE gene of E. coli O157:H7 is specifically amplified, with a detection limit of 102 CFU mL-1. Amplification is also performed by using a laboratory-made laser-diode device, which consumes only 2 W h during its operation. The low cost, disposability, and easy fabrication of the paper-based device make it a powerful tool for point-of-care testing.

Review of Inhalation Health Risks Involving Chloromethylisothiazolinone (CMIT) and Methylisothiazolinone (MIT) Used as Disinfectants in Household Humidifiers.

The association between lung injury and exposure to humidifier disinfectant (HD) containing a mixture of chloromethylisothiazolinone (CMIT) and methylisothiazolinone (MIT) has been controversial in South Korea. This study conducts a literature review in order to evaluate the likelihood of CMIT/MIT reaching the lower part of the respiratory tract and causing lung injury. A literature review focused on the inhalation risk of HD containing a mixture of CMIT and MIT. The major contents included the physicochemical properties of CMIT and MIT contained in HDs and methodological reviews on substance analysis, toxicity tests and clinical cases. HD products marketed in South Korea have been reported to contain approximately 1-2% CMIT and 0.2-0.6% MIT along with magnesium nitrate (20-25%), magnesium chloride (0.2-1.0%), and water (70-75%). The types of CMIT and MIT dispersed into the air and deposited in the respiratory tract are assumed to be either gaseous substances or nanoparticles mixed with magnesium salts. The result of the literature review including clinical cases of lung injury among CMIT/MIT HD product users, demonstrated that these chemicals likely reach the lower respiratory tract and accordingly cause lung injury. A number of humidifier disinfectant-associated lung injury cases with clinical evidence should be prioritized in risk assessment of HD containing CMIT and MIT, even though there might be insufficient evidence in all related areas, including inhalation exposure assessment studies, animal testing, and epidemiological studies.

Changes in tapered endotracheal tube cuff pressure after changing position to hyperextension of neck: A randomized clinical trial.

BACKGROUND: Endotracheal tube (ETT) with a tapered-shaped cuff had an improved sealing effect when compared to ETTs with a conventional cylindrical-shaped cuff. Positional change and neck movement typically displace an ETT and change the intracuff pressure. The aim of the current study was to compare the ETT cuff pressure in the TaperGuard ETT vs the conventional ETT after a change from the supine, neutral position to the extension of the neck and semi-Fowler position for thyroid surgery. METHODS: This prospective, randomized clinical trial included 50 patients undergoing thyroidectomy. Patients were randomly allocated into one of the 2 groups: tracheal intubation with the TaperGuard ETT or with a conventional ETT. The ETT cuff was inflated with air and the ETT cuff pressure was set initially at 20 cmH2O using a calibrated cuff manometer. ETT cuff pressure and distance from carina to ETT tip were measured at supine and semi-Fowler positions with neck extension. RESULTS: After the position change, the ETT tip migrated cephalad and cuff pressure increased in the majority of cases. ETT cuff pressure was significantly higher in the TaperGuard group than the conventional group (28.0 ±â€Š6.6 cmH2O and 22.8 ±â€Š4.5 cmH2O, respectively, P = .001). The degree of cephalad displacement of the ETT tip was comparable between the 2 groups (19.4 ±â€Š6.31 mm in TaperGuard group and 21.9 ±â€Š6.9 mm in conventional group, P = .12). CONCLUSIONS: After the position change from supine to hyperextension of the neck, the ETT cuff pressure was higher in the TaperGuard ETT than in the conventional ETT, although the extent of displacement of the ETT was comparable between the 2 groups.

Relationship of epidural patient-controlled analgesia with postoperative bleeding after unilateral total knee arthroplasty: a propensity score-matching analysis.

Although epidural patient-controlled analgesia (PCA) to control postoperative pain after total knee arthroplasty (TKA), the relationship of epidural PCA with postoperative bleeding remains controversial. Therefore, we aimed to evaluate the effect of epidural and intravenous PCA on postoperative bleeding in patients undergoing unilateral TKA. Total of 2467 patients who underwent TKA were divided to intravenous PCA (n = 2339) or epidural PCA (n = 128) group. After 1:1 propensity score-matching, 212 patients were analyzed to assess the associations between the perioperative blood loss and epidural PCA between the groups. Mean postoperative blood loss was significantly greater in epidural PCA than in intravenous PCA (900.9 ± 369.1 mL vs. 737.8 ± 410.1 mL; P = 0.007). The incidence of red blood cell (RBC) administration (> 3 units) was significantly higher in epidural PCA than in intravenous PCA (30.2% vs. 16.0%; OR 2.5; 95% CI 1.201-5.205; P = 0.014). Epidural PCA may be strongly related to postoperative bleeding and the incidence of RBC transfusion of more than 3 units after unilateral TKA, as compared to intravenous PCA. Therefore, the use of epidural PCA may be carefully considered for postoperative pain management in TKA.

A Prospective Randomized Comparison of Postoperative Pain and Complications after Thyroidectomy under Different Anesthetic Techniques: Volatile Anesthesia versus Total Intravenous Anesthesia.

While the postoperative outcome is favorable, post-thyroidectomy pain is considerable. Reducing the postoperative acute pain, therefore, is considered important. This study investigated whether the pain intensity and need for rescue analgesics during the immediate postoperative period after thyroidectomy differ according to the methods of anesthesia. Seventy-two patients undergoing total thyroidectomy under general anesthesia were examined. Patients were randomly assigned to undergo either total intravenous anesthesia with remifentanil and propofol (TIVA, n = 35) or propofol induction and maintenance with desflurane and nitrous oxide (volatile anesthesia [VA], n = 37). The mean administered dose of remifentanil was 1977.7 ± 722.5 µg in the TIVA group, which was approximately 0.268 ± 0.118 µg/min/kg during surgery. Pain scores based on a numeric rating scale (NRS) and the need for rescue analgesics were compared between groups at the postoperative anesthetic care unit (PACU). The immediate postoperative NRS values of the TIVA and VA groups were 5.7 ± 1.7 and 4.7 ± 2.3, respectively (P = 0.034). Postoperative morphine equianalgesic doses in the PACU were higher in the TIVA group than in the VA group (16.7 ± 3.8 mg vs. 14.1 ± 5.9 mg, P = 0.027). The incidence of immediate postanesthetic complications did not differ significantly between groups. In conclusion, more rescue analgesics were required in the TIVA group than in the VA group to adequately manage postoperative pain while staying in the PACU after thyroidectomy.

Correlation of Intraoperative End-Tidal Carbon Dioxide Concentration on Postoperative Hospital Stay in Patients Undergoing Pylorus-Preserving Pancreaticoduodenectomy.

BACKGROUND: Hypocapnia has been traditionally advocated during general anesthesia, even though it may induce deleterious physiological effects that result in unfavorable outcomes in patients. This study investigated the association between intraoperative end-tidal carbon dioxide (EtCO2) and length of hospital stay (LOS) in patients who underwent pylorus-preserving pancreaticoduodenectomy (PPPD). METHODS: The medical records of 759 patients from 2006 to 2015 were reviewed. The patients were divided into two groups based on the mean EtCO2 value during general anesthesia: the hypocapnia group (< 35 mmHg) and the normocapnia group (≥ 35 mmHg). The primary outcome was LOS between the groups. Secondary outcomes included the length of intensive care unit (ICU) stay, postoperative 30-day, 1-year, and 2-year mortality, and perioperative factors associated with LOS. RESULTS: A total of 727 patients were finally analyzed. The median LOS of the hypocapnia group was significantly longer than that of the normocapnia group (22 days vs. 18 days, respectively; p < 0.001). Postoperative mortality did not differ between the groups. Cox regression analysis revealed that hypocapnia was an independent risk factor for longer LOS (hazard ratio [HR], 1.61; 95% confidence interval [CI], 1.37-1.89; p < 0.001). Age and postoperative pancreatic fistula were also risk factors for a longer LOS. CONCLUSIONS: It was concluded that low levels of intraoperative EtCO2 during general anesthesia were associated with an increased LOS for patients undergoing PPPD.

Comparison of Monotherapy Versus Combination of Intravenous Ibuprofen and Propacetamol (Acetaminophen) for Reduction of Postoperative Opioid Administration in Children Undergoing Laparoscopic Hernia Repair: A Double-Blind Randomized Controlled Trial.

BACKGROUND: Extensive efforts have been made toward reducing postoperative opioid use in children. In this study, we assessed whether propacetamol, or a nonsteroidal anti-inflammatory drug (NSAID), or their combination could effectively reduce opioid use in children after laparoscopic inguinal hernia repair. METHODS: This randomized, double-blind clinical trial included 159 children aged 6 months to 6 years. Children were allocated into 1 of the following 3 groups: group I was treated with 10 mg·kg-1 ibuprofen, group P was treated with 30 mg·kg-1 propacetamol, and group I + P was treated with both drugs in their respective concentrations. If the face-legs-activity-crying-consolability (FLACC) score was ≥4 during the postanesthesia care unit stay, 1.0 µg·kg-1 fentanyl was administered as a rescue analgesic. The number of patients who received rescue fentanyl in the postanesthesia care unit was defined as the primary outcome; this was analyzed using the χ2 test. The secondary outcomes included the FLACC and the parents' postoperative pain measure (PPPM) scores until the 24-hour postoperative period. RESULTS: Among the 144 enrolled patients, 28.6% in group I, 66.7% in group P, and 12.8% in group I + P received rescue fentanyl in the postanesthesia care unit (P < .001). The highest FLACC score was lower in group I + P than in either group I or P (P = .007 and P < .001, respectively). Group I + P presented significantly lower PPPM scores than group P at 4 and 12 hours postoperative (P = .03 and .01, respectively). CONCLUSIONS: The use of ibuprofen plus propacetamol immediately following laparoscopic hernia repair surgery in children resulted in the reduced use of an opioid drug compared with the use of propacetamol alone.

The Effect of Different Posture on Normal Saline Injection in Optic Nerve Sheath Diameter in Thoracic Epidural Anesthesia.

BACKGROUND: Thoracolumbar or caudal epidural anesthesia affects intracranial pressure (ICP) in both animals and humans. Epidural injection increases ICP at least transiently. Measurement of the optic nerve sheath diameter (ONSD) using ultrasonography is one of the noninvasive methods for ICP assessment. OBJECTIVES: The purpose of this study was to investigate the effect of the different posture during epidural saline injection to the ONSD under awake conditions. STUDY DESIGN: Prospective, randomized trial. SETTING: An interventional pain management practice in South Korea. METHODS: This study included 44 patients receiving thoracic epidural catheterization for pain management after upper abdominal or thoracic surgery. Following successful epidural space confirmation, patients were randomized to receive epidural saline while supine (A group) or in sitting position (B group), respectively. Transorbital sonography was performed for the measurement of the ONSD, and the ONSD was measured at 3 mm posterior to the optic nerve head. RESULTS: Both A and B groups showed significant increases of ONSD according to time. Mean ONSD values measured at T10, T20, and T40 significantly increased from the baseline value (T0) (*P < 0.05 vs. T0, †P < 0.001 vs. T0, ‡P < 0.005 vs. T0). The mean ONSD values measured at any of the time points and degrees of changes (T10-T0, T20-T0, and T40-T0) between groups A and B did not show any significant changes. LIMITATIONS: Epidural pressure and ONSD measurement can make this study more reliable. Further study showing changes of epidural pressure with ONSD measurement is required. CONCLUSIONS: Thoracic epidural injection of 10 mL of normal saline resulted in a significant increase of ONSD compared with the baseline. However, the different posture did not affect the increase of ONSD.

Characteristics of Exposure to Chloromethylisothiazolinone (CMIT) and Methylisothiazolinone (MIT) among Humidifier Disinfectant-Associated Lung Injury (HDLI) Patients in South Korea.

This study aimed to quantify both chloromethylisothiazolinone (CMIT) and methylisothiazolinone (MIT) dissolved in different product brands and to characterize the exposure to these chemicals among humidifier disinfectant-associated lung injury (HDLI) patients. Both CMIT and MIT dissolved in different humidifier disinfectant (HD) products were quantified using gas chromatography-mass spectrometry. The inhalation level of CMIT and MIT was estimated based on HD-associated factors as reported by HDLI patients. A total of eleven HD products marketed until the end of 2011 were found to contain CMIT and/or MIT. The level of combined CMIT and/or MIT dissolved in these HD products ranged from 12 to 353 ppm. The level varied among HD products and the year of manufacture. The average inhalation levels were estimated to be 7.5, 4.1, and 3.2 µg/m3 for the definite, probable, and possible groups, respectively. If probable and possible groups were collapsed together, the inhalation level of the collapsed group was significantly different from that of the definite group (p < 0.001). All HDLI patients responded as having used HD not only while sleeping, but also as having a humidifier treated with HD within close proximity every day in insufficiently ventilated spaces. These HD use characteristics of patients may be directly/indirectly linked to the HDLI development.

von Willebrand factor to protein C ratio-related thrombogenicity with systemic inflammation is predictive of graft dysfunction after liver transplantation: Retrospective cohort study.

INTRODUCTION: Early allograft dysfunction (EAD) is known to be a prototype of graft failure and ultimately influences long-term graft failure or death. We hypothesized that pretransplant thrombogenicity evaluated by procoagulant and anticoagulant, von Willebrand factor (vWF), factor Ⅷ (FⅧ), protein C (PC) and their imbalance ratio of vWF-to-PC (vWFPCR) and FVIII-to-PC (FⅧPCR), is associated with EAD and 90-day graft failure after living-related liver transplantation (LDLT) and contributes to further exacerbation of graft dysfunction when coexists with systemic inflammation. MATERIAL AND METHODS: Of 1199 prospectively registered LDLT patients, 698 with measurements of each thrombogenicity parameters were analyzed. Risk factors for EAD development were searched and subsequent best cut-offs was calculated according to the receiver operator characteristic curve analysis. When comparing the outcome, multivariable regression analysis and inverse probability of treatment weighting (IPTW) of the propensity score were performed. RESULTS: The prevalence of EAD was 10.7% (n = 75/698) after LDLT. Of parameters, vWFPCR had highest predictivity potential of EAD with the best cut-off of 8.06. The relationship between vWFPCR≥8.06 showed significant association with EAD development (OR [95%CI], 2.55[1.28-5.09], P = 0.008) and 90-day graft failure (HR [95%CI], 2.24 [1-4.98], P = 0.043) after IPTW-adjustment. Furthermore, risk of EAD increased proportionally with increasing C-reactive protein as a continuous metric of systemic inflammation, and more steeply in those with higher thrombogenicity (i.e., higher vWFPCR). Adding vWFPCR to MELD score improved EAD risk prediction by 21.9%. CONCLUSIONS: Pretransplant thrombogenicity assessed by imbalance of pro- and anticoagulant, was significantly associated with EAD and 90-day graft failure after LDLT and this association was worsened by systemic inflammation.

Properties of Polyhexamethylene Guanidine (PHMG) Associated with Fatal Lung Injury in Korea.

The use of humidifier disinfectant (HD) has been determined to be associated with lung injuries (HDLI) in Korea. Although HD brands containing polyhexamethylene guanidine (PHMG) oligomers have been found to cause more HDLI compared to brands containing other disinfectants, the physicochemical properties of PHMG have been poorly defined. We aimed to quantify the PHMG dissolved in HD brands, characterize the number-average (Mn) and weight-average (Mw) molecular masses, and identify the polymerization degree of PHMG. Analysis of the PHMG oligomers was performed using a matrix-assisted laser desorption/ionization time-of-flight mass spectrometer (MALDI-TOF MS) operated in positive-ion reflectron mode. Eight brands of HD containing PHMG were identified. The PHMG concentrations in these brands ranged from 160 to 37,200 ppm (mean = 3100.9 ppm). Concentration was a significant variable among and within HD brands. The degree of PHMG oligomerization fell within the range of two to four. The averages of Mn and Mw were 517.2 g/mol (range: 422-613 g/mol) and 537.3 g/mol (range: 441.0-678.0 g/mol), respectively. Based on the average molecular weight and the degree of polymerization, the PHMG examined here could be regarded as oligomers, which may be associated with the highest proportion of HDLI being caused by PHMG.

Accelerated Growth of Corynebacterium glutamicum by Up-Regulating Stress- Responsive Genes Based on Transcriptome Analysis of a Fast-Doubling Evolved Strain.

Corynebacterium glutamicum, an important industrial strain, has a relatively slower reproduction rate. To acquire a growth-boosted C. glutamicum, a descendant strain was isolated from a continuous culture after 600 generations. The isolated descendant C. glutamicum, JH41 strain, was able to double 58% faster (td=1.15 h) than the parental type strain (PT, td=1.82 h). To understand the factors boosting reproduction, the transcriptomes of JH41 and PT strains were compared. The mRNAs involved in respiration and TCA cycle were upregulated. The intracellular ATP of the JH41 strain was 50% greater than the PT strain. The upregulation of NCgl1610 operon (a putative dyp-type heme peroxidase, a putative copper chaperone, and a putative copper importer) that presumed to role in the assembly and redox control of cytochrome c oxidase was found in the JH41 transcriptome. Plasmid-driven expression of the operon enabled the PT strain to double 19% faster (td=1.82 h) than its control (td=2.17 h) with 14% greater activity of cytochrome c oxidase and 27% greater intracellular ATP under the oxidative stress conditions. Upregulations of genes those might enhance translation fitness were also found in the JH41 transcriptome. Plasmid-driven expressions of NCgl0171 (encoding a cold-shock protein) and NCgl2435 (encoding a putative peptidyl-tRNA hydrolase) enabled the PT to double 22% and 32% faster than its control, respectively (empty vector: td=1.93 h, CspA: td=1.58 h, and Pth: td=1.44 h). Based on the results, the factors boosting growth rate in C. gluctamicum were further discussed in the viewpoints of cellular energy state, oxidative stress management, and translation.

The Role of the Microenvironment in Controlling the Fate of Bioprinted Stem Cells.

The field of tissue engineering and regenerative medicine has made numerous advances in recent years in the arena of fabricating multifunctional, three-dimensional (3D) tissue constructs. This can be attributed to novel approaches in the bioprinting of stem cells. There are expansive options in bioprinting technology that have become more refined and specialized over the years, and stem cells address many limitations in cell source, expansion, and development of bioengineered tissue constructs. While bioprinted stem cells present an opportunity to replicate physiological microenvironments with precision, the future of this practice relies heavily on the optimization of the cellular microenvironment. To fabricate tissue constructs that are useful in replicating physiological conditions in laboratory settings, or in preparation for transplantation to a living host, the microenvironment must mimic conditions that allow bioprinted stem cells to proliferate, differentiate, and migrate. The advances of bioprinting stem cells and directing cell fate have the potential to provide feasible and translatable approach to creating complex tissues and organs. This review will examine the methods through which bioprinted stem cells are differentiated into desired cell lineages through biochemical, biological, and biomechanical techniques.

SMAD3 promotes ELK3 expression following transforming growth factor ß-mediated stimulation of MDA-MB231 cells.

Transforming growth factor-ß (TGFß) is a secreted cytokine whose aberrant spatiotemporal expression is related to cancer progression and metastasis. While TGFß acts as a tumor suppressor in normal and premalignant stages, TGFß functions as a tumor promoter during the malignant phases of tumor progression by prompting cancer cells to undergo epithelial-mesenchymal transition (EMT), which enhances tumor cell invasion and ultimately promotes metastasis to other organs. Extensive studies have been performed to uncover the molecular and cellular mechanisms underlying TGFß inducing EMT in cancer cells. Here, we suggested that ELK3, which encodes a protein that orchestrates invasion and metastasis of triple negative breast cancer cells, is a downstream target of TGFß-SMAD3 in MDA-MB231 cells. ELK3 expression was increased in a time-dependent manner upon TGFß treatment. Chemical and molecular inhibition of the TGFß receptor blocked the ability of TGFß to induce ELK3 expression. Small interfering RNA-mediated suppression analysis revealed that SMAD3 induces TGFß signaling to express ELK3. Moreover, the results of the luciferase reporter assay and chromatin immunoprecipitation analysis showed that SMAD3 directly binds to the SMAD-binding element on the promoter of ELK3 to activate gene expression following TGFß stimulation. We concluded that ELK3 is a novel downstream target of TGFß-SMAD3 signaling in aggressive breast cancer cells.

A Mouse Homolog of a Human TP53 Germline Mutation Reveals a Lipolytic Activity of p53.

The physiological effects of the many germline mutations of TP53, encoding the tumor suppressor protein p53, are poorly understood. Here we report generating a p53 R178C knockin mouse modeling the human TP53 R181C mutation, which is notable for its prevalence and prior molecular characterization. Consistent with its weak cancer penetrance in humans, homozygous p53178C/C mice show a modest increase in tumorigenesis but, surprisingly, are lean with decreased body fat content. They display evidence of increased lipolysis and upregulation of fatty acid metabolism in their inguinal white adipose tissue (iWAT). Gene expression and chromatin immunoprecipitation sequencing (ChIP-seq) analyses show that the mutant p53 bound and transactivated Beta-3-Adrenergic Receptor (ADRB3), a gene that is known to promote lipolysis and is associated with obesity. This study reveals that a germline mutation of p53 can affect fat metabolism, which has been implicated in cancer development.

Occupational Characteristics of Semiconductor Workers with Cancer and Rare Diseases Registered with a Workers' Compensation Program in Korea.

BACKGROUND: The aim of this study was to describe the types of diseases that developed in semiconductor workers who have registered with the Korea Workers' Compensation and Welfare Service (KWCWS) and to identify potential common occupational characteristics by the type of claimed disease. METHODS: A total of 55 semiconductor workers with cancer or rare diseases who claimed to the KWCWS were compared based on their work characteristics and types of claimed diseases. Leukemia, non-Hodgkin lymphoma, and aplastic anemia were grouped into lymphohematopoietic (LHP) disorder. RESULTS: Leukemia (n = 14) and breast cancer (n = 10) were the most common complaints, followed by brain cancer (n = 6), aplastic anemia (n = 6), and non-Hodgkin lymphoma (n = 4). LHP disorders (n = 24) accounted for 43%. Sixty percent (n = 33) of registered workers (n = 55) were found to have been employed before 2000. Seventy-six percent (n = 42) of registered workers and 79% (n = 19) among the registered workers with LHP (n = 24) were found to be diagnosed at a relatively young age, ≤40 years. A total of 18 workers among the registered semiconductor workers were finally determined to deserve compensation for occupational disease by either the KWCWS (n = 10) or the administrative court (n = 8). Eleven fabrication workers who were compensated responded as having handled wafers smaller than eight inches in size. Eight among the 18 workers compensated (44 %) were found to have ever worked at etching operations. CONCLUSION: The distribution of cancer and rare diseases among registered semiconductor workers was closely related to the manufacturing era before 2005, ≤8 inches of wafer size handled, exposure to clean rooms of fabrication and chip assembly operations, and etching operations.