Racial/ethnic and income disparities in neighborhood-level broadband access in 905 US cities, 2017-2021.

OBJECTIVES: Broadband access is an essential social determinant of health, the importance of which was made apparent during the COVID-19 pandemic. We sought to understand disparities in broadband access within cities and identify potential solutions to increase urban access. STUDY DESIGN: This was a descriptive secondary analysis using multi-year cross-sectional survey data. METHODS: Data were obtained from the City Health Dashboard and American Community Survey. We studied broadband access in 905 large US cities, stratifying neighborhood broadband access by neighborhood median household income and racial/ethnic composition. RESULTS: In 2017, 30% of urban households across 905 large US cities did not have access to high-speed broadband internet. After controlling for median household income, broadband access in majority Black and Hispanic neighborhoods was 10-15% lower than in majority White or Asian neighborhoods. Over time, lack of broadband access in urban households decreased from 30% in 2017 to 24% in 2021, but racial and income disparities persisted. CONCLUSIONS: As an emerging social determinant, broadband access impacts health across the life course, affecting students' ability to learn and adults' ability to find and retain jobs. Resolving lack of broadband access remains an urban priority. City policymakers can harness recent infrastructure funding opportunities to reduce broadband access disparities.

Modeling Groundwater Inflow to the New Crater Lake at Kilauea Volcano, Hawai'i.

During the 2018 eruption of Kilauea Volcano, Hawai'i, scientists relied heavily on a conceptual model of explosive eruptions triggered when lava-lake levels drop below the water table. Numerical modeling of multiphase groundwater flow and heat transport revealed that, contrary to expectations, liquid water inflow to the drained magma conduit would likely be delayed by months to years, owing to the inability of liquid water to transit a zone of very hot rock. The summit of Kilauea subsequently experienced an ∼2-month period of consistent repeated collapses, and the crater now extends below the equilibrium position of the water table. Liquid water first emerged into the deepened crater in late July 2019. The timing of first appearance of liquid water (about 14 months postcollapse) and the rate of crater lake filling (currently ∼27 kg/s) were well-predicted by the numerical modeling done in late spring 2018, which forecast liquid inflow after 3 to 24 months at rates of 10 to 100 kg/s. A second-generation groundwater model, reflecting the current crater geometry, forecasts lake filling over the next several years. The successful 2018 to present forecasts with both models are based on unadjusted in situ permeability estimates (1 to 6 × 10-14  m2 ) and water-table elevations (600 to 800 m) from a nearby research drillhole and geophysical surveys. Important unknowns that affect the reliability of longer-term forecasts include the equilibrium water-table geometry, the rate of evaporation from the hot and growing crater lake (currently ∼29,000 m2 at 70-80 °C), and heterogenous permeability changes caused by the 2018 collapse.

Minimally invasive right colectomy with transrectal natural orifice extraction: could this be the next step forward?

BACKGROUND: The transvaginal natural orifice specimen extraction (NOSE) approach for right-side colon surgery has been proven to exhibit favorable short-term outcomes. However, thus far, no study has reported the advantages of transrectal NOSE for right-side colon surgery. The aim of this study was to compare the technical feasibility, safety, and short-term outcomes of minimally invasive right hemicolectomy using the transrectal NOSE method and those of conventional mini-laparotomy specimen extraction. METHODS: A study was conducted on consecutive patients who had minimally invasive right hemicolectomy either for malignancy or benign disease at Chang Gung Memorial Hospital, Linkou, Taiwan, between January 2017 and December 2018. The patients were divided into two groups: conventional surgery with specimen extraction using mini-laparotomy and NOSE surgery. Surgical outcomes, including complications, postoperative short-term recovery, and pain intensity, were analyzed. RESULTS: We enrolled 297 patients (151 males, mean age 64.9 ± 12.8 years) who had minimally invasive right hemicolectomy. Of these 297 patients, 272 patients had conventional surgery with specimen extraction through mini-laparotomy and 25 patients had NOSE surgery (23 transrectal, 2 transvaginal). The diagnosis of colon disease did not differ significantly between the conventional and NOSE groups. Postoperative morbidity and mortality rates were comparable. The postoperative hospital stay was significantly (p = 0.004) shorter in the NOSE group (median 5 days, range 3-17 days) than in the conventional group (median 7 days, range 3-45 days). Postoperative pain was significantly (p = 0.026 on postoperative day 1 and p = 0.002 on postoperative day 2) greater in the conventional group than in the NOSE group. CONCLUSIONS: NOSE was associated with acceptable short-term surgical outcomes that were comparable to those of conventional surgery. NOSE results in less postoperative wound pain and a shorter hospital stay than conventional surgery. Larger studies are needed.

Antibacterial activity of viable and heat-killed probiotic strains against oral pathogens.

Probiotics can stabilize gut flora, regulate intestinal immunity and protect the host from enteric diseases; however, their roles in oral health have received little attention compared to their roles in gut health. Nowadays, the prevalence of sugar-sweetened foods and abuse of antibiotics contribute towards dysbiosis of oral microbiota and drug resistance development in oral pathogens, resulting in various intractable oral diseases. We screened the antibacterial activities of viable and heat-killed probiotic strains against the oral pathogens Streptococcus mutans, Porphyromonas gingivalis, Fusobacterium nucleatum and Aggregatibacter actinomycetemcomitans. The probiotic strains Lactobacillus salivarius subsp. salicinius AP-32, L. rhamnosus CT-53, L. paracasei ET-66 and Bifidobacterium animalis subsp. lactis CP-9 displayed strong antipathogenic activities, whereas heat-killed AP-32, CT-53 and ET-66 displayed high levels of pathogen inhibition. The antibacterial activities of these probiotics were not associated with their H2 O2 production; L. acidophilus TYCA02 produced high levels of H2 O2 but merely exhibited moderate antibacterial activities. Oral tablets containing probiotics showed positive inhibitory effects against oral pathogens, particularly those containing viable probiotics. Our results indicate that probiotics prevent the growth of oral pathogens and improve oral health, providing insights into the antipathogenic efficacy of different probiotic species and their potential role in functional foods that improve oral health. SIGNIFICANCE AND IMPACT OF THE STUDY: Our study provides insights into the antipathogenic efficacy of different probiotic species and their potential roles in developing functional foods to improve oral health. We showed that the probiotic strains Lactobacillus salivarius subsp. salicinius AP-32, L. rhamnosus CT-53, L. paracasei ET-66 and Bifidobacterium animalis subsp. lactis CP-9 have great potential for use in the development of functional foods to improve oral health. Since active probiotics may provide strong and long-term protection, the development of functional food products should favour the use of viable bacteria.

Synovial fluid interleukin-16, interleukin-18, and CRELD2 as novel biomarkers of prosthetic joint infections.

OBJECTIVES: Prosthetic joint infection (PJI) diagnosis is a major challenge in orthopaedics, and no reliable parameters have been established for accurate, preoperative predictions in the differential diagnosis of aseptic loosening or PJI. This study surveyed factors in synovial fluid (SF) for improving PJI diagnosis. METHODS: We enrolled 48 patients (including 39 PJI and nine aseptic loosening cases) who required knee/hip revision surgery between January 2016 and December 2017. The PJI diagnosis was established according to the Musculoskeletal Infection Society (MSIS) criteria. SF was used to survey factors by protein array and enzyme-linked immunosorbent assay to compare protein expression patterns in SF among three groups (aseptic loosening and first- and second-stage surgery). We compared routine clinical test data, such as C-reactive protein level and leucocyte number, with potential biomarker data to assess the diagnostic ability for PJI within the same patient groups. RESULTS: Cut-off values of 1473 pg/ml, 359 pg/ml, and 8.45 pg/ml were established for interleukin (IL)-16, IL-18, and cysteine-rich with EGF-like domains 2 (CRELD2), respectively. Receiver operating characteristic curve analysis showed that these factors exhibited an accuracy of 1 as predictors of PJI. These factors represent potential biomarkers for decisions associated with prosthesis reimplantation based on their ability to return to baseline values following the completion of debridement. CONCLUSION: IL-16, IL-18, and CRELD2 were found to be potential biomarkers for PJI diagnosis, with SF tests outperforming blood tests in accuracy. These factors could be useful for assessing successful debridement based on their ability to return to baseline values following the completion of debridement.Cite this article: M-F. Chen, C-H. Chang, L-Y. Yang, P-H. Hsieh, H-N. Shih, S. W. N. Ueng, Y. Chang. Synovial fluid interleukin-16, interleukin-18, and CRELD2 as novel biomarkers of prosthetic joint infections. Bone Joint Res 2019;8:179-188. DOI: 10.1302/2046-3758.84.BJR-2018-0291.R1.

Use of olmesartan and enteropathy outcomes: a multi-database study.

BACKGROUND: Multiple case reports suggest that olmesartan may be linked to sprue-like enteropathy; however, few epidemiological studies have examined this association and results have been mixed. AIM: To assess whether olmesartan is associated with a higher rate of enteropathy vs other angiotensin II receptor blockers (ARBs). METHODS: We conducted a cohort study among ARB initiators in 5 US claims databases representing different health insurance programmes. Cox regression models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for enteropathy-related outcomes, including coeliac disease, malabsorption, concomitant diagnoses of diarrhoea and weight loss, and non-infectious enteropathy, comparing olmesartan initiators to initiators of other ARBs after propensity score (PS) matching. RESULTS: We identified 1 928 469 eligible patients. The unadjusted incidence rates were 0.82, 1.41, 1.66 and 29.20 per 1000 person-years for coeliac disease, malabsorption, concomitant diagnoses of diarrhoea and weight loss, and non-infectious enteropathy respectively. HRs after PS matching comparing olmesartan to other ARBs were 1.21 (95% CI, 1.05-1.40), 1.00 (95% CI, 0.88-1.13), 1.22 (95% CI, 1.10-1.36) and 1.04 (95% CI, 1.01-1.07) for each outcome. HRs were larger for patients aged 65 years and older (eg for coeliac disease, 1.57 [95% CI, 1.20-2.05]), for patients receiving treatment for more than 1 year (1.62 [95% CI, 1.24-2.12]), and for patients receiving higher cumulative olmesartan doses (1.78 [95% CI, 1.33-2.37]). CONCLUSIONS: This large-scale, multi-database study found a higher rate of enteropathy in olmesartan initiators as compared to initiators of other ARBs, although the absolute incidence rate was low in both groups.

Risk-benefit perception of pregnancy among breast cancer survivors.

Helping breast cancer patients who desire a pregnancy after cancer treatment is a vital issue. Little is known about the complex context of the decision to become pregnant after breast cancer treatment. The purpose of this study was to understand the risk-benefit perception of choosing conception or contraception after treatment in Taiwan. We applied grounded theory to guide this exploratory qualitative study. Data were collected through in-depth interviews with 16 breast cancer patients. Pregnancy was addressed in the context of cancer as a potentially life-threatening diagnosis and its treatment. The verbatim transcriptions were analysed using constant comparative analysis and methods of open, axial and selective coding. The core theme that described the risk perception of pregnancy among patients with breast cancer after treatment focused on "reaching the balance of life." Seven dimensions of risk-benefit perception of pregnancy, including perceived health status, safety, expected gain, harm, loading, support and time were explored among women treated for breast cancer. We found that women treated for breast cancer applied risk-benefit perceptions to decide whether to become pregnant. Implementing contextual counselling could help to decrease perceived barriers to choose pregnancy and increase the quality of pregnancy care.

Strengthening teachers' abilities to implement a vision health program in Taiwanese schools.

We designed a school-based, nationwide program called the 'New Era in Eye Health' to strengthen teacher training and to examine whether the existence of a government vision care policy influenced teachers' vision care knowledge and students' behavior. Baseline data and 3-month follow-up data were compared. A random sample of teachers (n = 660) from school vision health clusters in 22 cities/counties in Taiwan were invited to participate in our study and 436 agreed to participate (response rate = 66.1%). The mean age of participant teachers was 41.2 years, while the length of service mean was 14.6 years. For monitoring teacher outcomes, five cities/counties were selected as the intensely monitored group based on certain criteria. Sunlight diaries (n = 5434) were distributed and 3342 (61.5%) were returned. Teachers showed significant improvements in knowledge and behavior on the school vision health questionnaire. At the 3-month follow-up, the number of recesses as recorded by students' 'sunlight diary' increased. When teachers had better knowledge and behavior, recesses also increased. This study provided valuable insights to guide dissemination efforts for school vision health interventions and to help teachers implement research into their school vision health activities.

Pre-operative serum albumin level substantially predicts post-operative morbidity and mortality among patients with colorectal cancer who undergo elective colectomy.

The quantitative relationship between serum albumin level and surgical outcomes has not been clearly established. This study included 3732 patients with colon cancer who underwent a potentially curative colectomy. Post-operative mortality and morbidity were analysed according to the patients' demographic data, pre-operative comorbidities, and tumour-related factors. Age, asthma, renal impairment, and albumin level were significantly associated with post-operative morbidity and mortality in the multivariate analyses. Logistic regression analysis revealed linear relationships of post-operative morbidity and mortality with albumin level. The morbidity and mortality rates decreased by 7.3% and 15.6%, respectively, for each 0.1 g/dL increase in albumin level. This finding remained significant in the hypoalbuminaemia subgroup but not in the normoalbuminaemia subgroup. That is, the morbidity and mortality rates significantly decreased by 8.7% and 17.7%, respectively (both P < 0.001), in the former group and decreased by 2.7% (P = 0.112) and 11.6% (P = 0.092), respectively, in the latter group. This study demonstrated that serum albumin level linearly predicted the post-operative morbidity and mortality among the colorectal cancer patients. Pre-operative serum albumin level may therefore be used as a continuous rather than a categorical marker of disease severity, especially among patients with hypoalbuminaemia.

Nanoparticle distribution during systemic inflammation is size-dependent and organ-specific.

This study comprehensively investigates the changing biodistribution of fluorescent-labelled polystyrene latex bead nanoparticles in a mouse model of inflammation. Since inflammation alters systemic circulatory properties, increases vessel permeability and modulates the immune system, we theorised that systemic inflammation would alter nanoparticle distribution within the body. This has implications for prospective nanocarrier-based therapies targeting inflammatory diseases. Low dose lipopolysaccharide (LPS), a bacterial endotoxin, was used to induce an inflammatory response, and 20 nm, 100 nm or 500 nm polystyrene nanoparticles were administered after 16 hours. HPLC analysis was used to accurately quantify nanoparticle retention by each vital organ, and tissue sections revealed the precise locations of nanoparticle deposition within key tissues. During inflammation, nanoparticles of all sizes redistributed, particularly to the marginal zones of the spleen. We found that LPS-induced inflammation induces splenic macrophage polarisation and alters leukocyte uptake of nanoparticles, with size-dependent effects. In addition, spleen vasculature becomes significantly more permeable following LPS treatment. We conclude that systemic inflammation affects nanoparticle distribution by multiple mechanisms, in a size dependent manner.

High genetic risk individuals benefit less from resistance exercise intervention.

OBJECTIVES: Genetic factors have an important role in body mass index (BMI) variation, and also likely have a role in the weight loss and body composition response to physical activity/exercise. With the recent identification of BMI-associated genetic variants, it is possible to investigate the interaction of these genetic factors with exercise on body composition outcomes. METHODS: In a block-randomized clinical trial of resistance exercise among women (n=148), we examined whether the putative effect of exercise on weight and dual-energy x-ray absorptiometry-derived body composition measurements differs according to genetic risk for obesity. Approximately one-half of the sample was randomized to an intervention consisting of a supervised, intensive, resistance exercise program, lasting 1 year. Genetic risk for obesity was defined as a genetic risk score (GRS) comprised of 21 single-nucleotide polymorphisms (SNPs) known to be associated with BMI variation. We examined the interaction of exercise intervention and the GRS on anthropometric and body composition measurements after 1 year of the exercise intervention. RESULTS: We found statistically significant interactions for body weight (P=0.01), body fat (P=0.01), body fat % (P=0.02) and abdominal fat (P=0.02), whereby the putative effect of exercise is greater among those with a lower level of genetic risk for obesity. No single SNP appears to be a major driver of these interactions. CONCLUSIONS: The weight-loss response to resistance exercise, including changes in body composition, differs according to an individual's genetic risk for obesity.

Determinants of Perceived Physical Environment Barriers among Community-Dwelling Elderly in Taiwan.

OBJECTIVES: To test the hypothesis that mobility, activities of daily living, and the interaction between them can play a key role in determining perceived physical environment barriers among community-dwelling elderly. DESIGN: Cross-sectional. SETTING: Community. PARTICIPANTS: One hundred and ninety-seven community-dwelling elderly with more than 7 points on the Short Portable Mental State Questionnaire and less than 7 points on the Geriatric Depression Scale (15 items). INTERVENTION: None. MEASUREMENTS: Time Get-up and Go test (TUG), the subscales of basic activity of daily living (BADL)/instrumental activities of daily living (IADL) of the Hierarchy of Care Required (HCR), and the physical/structural subscale of the Craig Hospital Inventory of Environmental Factors in Community-dwelling Elderly in Taiwan were used to measure mobility, activities of daily living and perceived physical environment barriers, respectively. Hierarchical linear regression analyses were used to test the study hypothesis. RESULTS: Significant and positive relations were found to exist between perceived physical environment barriers and (1) the TUG time (ß=.300, p<.05), and (2) the IADL score for the HCR (ß=.322, p<.05), respectively. A significant and negative relation existed between perceived physical environment barriers and the interaction term (the TUG time and the IADL score for the HCR) (ß=-.211, p<.05). CONCLUSION: Mobility, IADL and the interaction between them are found to be significant determinants of perceived physical environment barriers in the community-dwelling elderly under consideration. Strategies targeting the enhancement of mobility among community-dwelling elderly are suggested to lead to improvements in the degree to which physical environment barriers are perceived. This beneficial effect could be greater in the case of elderly individuals with better IADL function.

A positive bacterial culture from allograft bone at implantation does not correlate with subsequent surgical site infection.

Fresh-frozen allograft bone is frequently used in orthopaedic surgery. We investigated the incidence of allograft-related infection and analysed the outcomes of recipients of bacterial culture-positive allografts from our single-institute bone bank during bone transplantation. The fresh-frozen allografts were harvested in a strict sterile environment during total joint arthroplasty surgery and immediately stored in a freezer at -78º to -68º C after packing. Between January 2007 and December 2012, 2024 patients received 2083 allografts with a minimum of 12 months of follow-up. The overall allograft-associated infection rate was 1.2% (24/2024). Swab cultures of 2083 allografts taken before implantation revealed 21 (1.0%) positive findings. The 21 recipients were given various antibiotics at the individual orthopaedic surgeon's discretion. At the latest follow-up, none of these 21 recipients displayed clinical signs of infection following treatment. Based on these findings, we conclude that an incidental positive culture finding for allografts does not correlate with subsequent surgical site infection. Additional prolonged post-operative antibiotic therapy may not be necessary for recipients of fresh-frozen bone allograft with positive culture findings.

Rheumatoid arthritis patients with hip fracture: a nationwide study.

SUMMARY: The study was to investigate the outcomes of rheumatoid arthritis (RA) patients with hip fractures with a large-scale, population-based, nationwide, case-cohort study using the Taiwan National Health Insurance database. The group has hip fractures at a younger age, higher complication, and mortality rate, which indicate that early intervention is necessary. INTRODUCTION: This study seeks to evaluate the incidence, mortality, and complication rates in RA patients with hip fractures, using a nationwide database. METHODS: Data were collected from the National Health Insurance Research Database of Taiwan. The study group included 117,129 patients with hip fractures diagnosed from January 2004 to December 2010. Matching based on the propensity of RA patients was used. In total, 1,088 hip fractures were reported among patients with RA. Patients with hip fractures were divided into two groups: those without RA (controls) and those with RA (RA group). The incidence of hip fracture and mortality and complication rates after the hip fracture were then compared between the two groups. RESULTS: RA patients had a significantly higher incidence of hip fracture (3,260/100,000 person-years) compared with the general population (72/100,000 person-years). Hip fractures occurred significantly earlier among RA patients (70.6±5.3 years) compared with the control group (76.1±6.2 years). Cumulative mortality rates at 6-month and 1-year follow-up were significantly higher among patients in the RA group (9.47 and 18.47%) compared to the controls (8.47 and 13.62%) and among RA patients without hip fractures (3.24 and 6.16%). There was a significantly higher incidence of osteomyelitis after hip fracture among the RA group than among the body mass index-, comorbidity-, age-, and sex-matched patients in the control group. CONCLUSIONS: Compared to patients without RA, those with RA have a higher incidence of hip fractures at a relatively younger age and with higher complication and mortality rates. Steroid and disease-modifying anti-rheumatic drugs, the most common medicine in Taiwanese RA patients, might contribute to the high incidence of fracture and post-op infection. Appropriate early intervention to prevent hip fractures in RA patients is a critical issue in rheumatology care.

Nationwide cohort study of hip fractures: time trends in the incidence rates and projections up to 2035.

SUMMARY: A growing elderly population is expected worldwide, and the burden of hip fractures on health care system will continue to increase. By 2035, there will be a 2.7-fold increase in the number of hip fractures in Taiwan. The study provides quantitative basis for the future distribution of medical resources. INTRODUCTION: Hip fractures have long been recognized as a major public health concern. The study aimed to determine time trends in the incidence of hip fractures and to forecast the number of hip fractures expected in Taiwan up to 2035. METHODS: A nationwide survey was conducted using data from the Taiwan National Health Insurance Research Database from 2004 to 2011. A total of 141,397 hip fractures were identified, with a mean of 17,675 fractures/year. Annual incidences of hip fractures were calculated and tested for trends. Projections of the incidence rates of hip fractures and bed days associated with hip fractures were calculated using Poisson regression on the historical incidence rates in combination with population projections from 2012 to 2035. RESULTS: The incidence rates of hip fracture during 2004-2011 were 317 and 211 per 100,000 person-years among women and men, respectively. Over this 8-year period, the age-standardized incidence of hip fracture decreased by 13.4% among women and 12.2% among men. Despite the decline in the age-standardized incidence, the absolute number of hip fractures increased owing to the aging population. The number of hip fractures is expected to increase from 18,338 in 2010 to 50,421 in 2035-a 2.7-fold increase. The number of bed days for 2010 and 2035 was estimated at 161,248 and 501,995, respectively, representing a 3.1-fold increase. CONCLUSIONS: The socioeconomic impact of hip fractures will be high in the near future. This study provides a quantitative basis for future policy decisions to serve this need.

Liquid antibiotics in bone cement: an effective way to improve the efficiency of antibiotic release in antibiotic loaded bone cement.

OBJECTIVES: The objective of this study was to compare the elution characteristics, antimicrobial activity and mechanical properties of antibiotic-loaded bone cement (ALBC) loaded with powdered antibiotic, powdered antibiotic with inert filler (xylitol), or liquid antibiotic, particularly focusing on vancomycin and amphotericin B. METHODS: Cement specimens loaded with 2 g of vancomycin or amphotericin B powder (powder group), 2 g of antibiotic powder and 2 g of xylitol (xylitol group) or 12 ml of antibiotic solution containing 2 g of antibiotic (liquid group) were tested. RESULTS: Vancomycin elution was enhanced by 234% in the liquid group and by 12% in the xylitol group compared with the powder group. Amphotericin B elution was enhanced by 265% in the liquid group and by 65% in the xylitol group compared with the powder group. Based on the disk-diffusion assay, the eluate samples of vancomycin-loaded ALBC of the liquid group exhibited a significantly larger inhibitory zone than samples of the powder or the xylitol group. Regarding the ALBCs loaded with amphotericin B, only the eluate samples of the liquid group exhibited a clear inhibitory zone, which was not observed in either the xylitol or the powder groups. The ultimate compressive strength was significantly reduced in specimens containing liquid antibiotics. CONCLUSIONS: Adding vancomycin or amphotericin B antibiotic powder in distilled water before mixing with bone cement can significantly improve the efficiency of antibiotic release than can loading ALBC with the same dose of antibiotic powder. This simple and effective method for preparation of ALBCs can significantly improve the efficiency of antibiotic release in ALBCs. Cite this article: Bone Joint Res 2014;3:246-51.

Lower availability of midbrain serotonin transporter between healthy subjects with and without a family history of major depressive disorder - a preliminary two-ligand SPECT study.

PURPOSE: Serotonin transporter (SERT) and dopamine transporter (DAT) levels differ in patients with major depressive disorder (MDD) who are in a depressed state in comparison with healthy controls. In addition, a family history of depression is a potent risk factor for developing depression, and inherited vulnerability to serotonergic and dopaminergic dysfunction is suspected in this. The aim of this study was to examine the availabilities of midbrain SERT and striatal DAT in healthy subjects with and without a first-degree family history of MDD. METHODS: Eight healthy subjects with first-degree relatives with MDD and 16 sex- and age-matched healthy controls were recruited. The availabilities of SERT and DAT were approximated using SPECT, employing [¹²³I] 2-((2-((dimethylamino) methyl) phenyl)thio)-5-iodophenylamine (ADAM) and [(99m)Tc] TRODAT-1 as the ligands, respectively. There are missing data for one participant with a first-degree family history of MDD from the ADAM study, due to a lack of the radio-ligand at the time of experiment. RESULTS: SERT availability in the midbrain was significantly lower in subjects with a first-degree family history of MDD than in healthy subjects. However, DAT availability was no different between two groups. CONCLUSIONS: The results with regard to the midbrain SERT level suggest the heritability of MDD.

Solid freeform-fabricated scaffolds designed to carry multicellular mesenchymal stem cell spheroids for cartilage regeneration.

Three-dimensional (3D) cellular spheroids have recently emerged as a new trend to replace suspended single cells in modern cell-based therapies because of their greater regeneration capacities in vitro. They may lose the 3D structure during a change of microenvironment, which poses challenges to their translation in vivo. Besides, the conventional microporous scaffolds may have difficulty in accommodating these relatively large spheroids. Here we revealed a novel design of microenvironment for delivering and sustaining the 3D spheroids. Biodegradable scaffolds with macroporosity to accommodate mesenchymal stem cell (MSC) spheroids were made by solid freeform fabrication (SFF) from the solution of poly(D,L-lactide-co-glycolide). Their internal surface was modified with chitosan following air plasma treatment in order to preserve the morphology of the spheroids. It was demonstrated that human MSC spheroids loaded in SFF scaffolds produced a significantly larger amount of cartilage-associated extracellular matrix in vitro and in NOD/SCID mice compared to single cells in the same scaffolds. Implantation of MSC spheroid-loaded scaffolds into the chondral defects of rabbit knees showed superior cartilage regeneration. This study establishes new perspectives in designing the spheroid-sustaining microenvironment within a tissue engineering scaffold for in vivo applications.