Effect of single versus grouped culture of human cumulus-oocyte complexes in PCOS women treated with biphasic in vitro maturation: A sibling oocyte pilot study.

Purpose: This study investigated the differences in the maturation rate of single versus grouped cumulus-oocyte complexes (COCs) culture methods for capacitation in vitro maturation (CAPA-IVM) in women with polycystic ovary syndrome (PCOS). Methods: This study was performed at My Duc Phu Nhuan Hospital, Vietnam from October 1, 2020 to October 24, 2021. Women aged 18-37 years with a diagnosis of PCOS were recruited. COCs from each woman were randomly divided into two groups: single or grouped culture during CAPA-IVM culture. The primary outcome was the maturation rate. Results: A total of 322 COCs from 15 eligible women included were randomly assigned to the two study groups. The maturation rate was comparable between the single and grouped culture groups (61.3% vs. 64.8%; p = 0.56). There were no significant differences in the number of 2-pronuclei fertilized oocytes, number of day-3 embryos, and number of good-quality embryos in the two culture method groups. In the single culture group, COCs morphology was associated with the day-3 embryo formation rate but not the maturation rate. Conclusions: Comparable oocyte maturation and embryology outcomes between single and grouped COCs culture utilizing sibling COCs derived from women with PCOS suggest the feasibility of both methods for CAPA-IVM culture.

Clinicopathological and Molecular Features of Penile Melanoma With a Proposed Staging System.

Penile melanomas (PM) are an exceedingly rare subtype of mucosal melanoma (MM), and we reviewed the clinicopathologic features and molecular profile in 8 PMs. The patient ages ranged from 46 to 78 (mean: 62.8) years with involvement on the glans (n=5; 62.5%), penile urethra (n=2; 25%), and foreskin (n=1, 12.5%). Tumor depth ranged from 1.6 to 10.0 (mean: 5.25) mm. Most of the patients underwent partial penectomy (n=6; 75%) and sentinel lymph node (LN) biopsy N=7; 87.5%). Seven patients had metastatic disease at diagnosis, 6 involving LNs and 1 the adrenal gland, and 4 died of disease with a mean follow-up period of 40.5 (2 to 95) months. Five of 7 (71%) cases identified 15 molecular alterations within KIT, CDKN2A, NF1, PTEN, and APC (n=2 each), and NRAS, MAP3K1, CDH1, MSH6, and TERT (n=1 each). Two cases were not found to harbor genetic aberrations, and 1 case failed testing. In addition, we reviewed the English literature and included 93 cases with a reported depth of invasion and follow-up. A total of 101 PMs were analyzed for prognostic parameters, and the overall survival was significantly worse in patients with LN metastasis (P=0.0008), distant metastasis (P=0.0016), and greater depth of invasion (P=0.0222) based upon T-stage. While T4 conferred substantially worse survival, the delineation of the survival curves between T2 and T3 was less clear, and combining T2+T3 disease had a strong prognostic impact (P=0.0024). Prognostic parameters used in the staging of cutaneous melanomas may also be used in PMs. An alternative staging system expanding the inclusion criteria for T2 might provide a more accurate prognostic stratification.

Cutaneous Intravascular Hematolymphoid Entities: A Review.

Intravascular lymphomas are rare disease conditions that exhibit neoplastic lymphoid cells that are confined mainly to the lumens of small capillaries and medium-sized vessels. The majority of the intravascular lymphomas are of B-cell origin, but they can include NK/T-cell and CD30+ immunophenotypes. In the histologic differential diagnosis are benign proliferations such as intralymphatic histiocytosis and intravascular atypical CD30+ T-cell proliferation. In this review, we discuss the clinical, histopathologic, and molecular findings of intravascular B-cell lymphoma, intravascular NK/T-cell lymphoma, intralymphatic histiocytosis, and benign atypical intravascular CD30+ T-cell proliferation.

Post-traumatic Acetabulum Open Reduction Internal Fixation in a Patient with a BMI of 77: A Case Report.

CASE: We present the case of a 25-year-old man with body mass index of 77 who underwent open reduction internal fixation (ORIF) of a displaced fracture dislocation of the acetabulum after a high-speed motor vehicle accident. Remarkably, he achieved full weight-bearing with minimal hip pain and has returned to independent mobility and meaningful work. CONCLUSION: ORIF of an acetabular fracture in a patient with class III obesity presents many challenges. Positioning, surgical approach, fracture manipulation, and postoperative morbidity and mortality can be managed through interdisciplinary collaboration and preoperative communication.

Outcomes of operatively managed periprosthetic distal femur fractures compared to fractures in patients with native knees.

Introduction: With the increasing incidence of total knee arthroplasty (TKA), there is an expected rise in rate of periprosthetic fractures in the coming years. It is unclear how the outcomes of patients with distal femur fractures (DFF) and a total knee arthroplasty compare to patients of the same age group with native knees (NK). Materials and methods: A retrospective review was completed for distal femur fractures treated with surgical fixation from January 2019-March 2021. We excluded patients <50 years old, non-ambulatory patients, revision surgeries, and patients with less than 90 days of follow-up. A chart review was performed to collect age, gender, BMI, smoking status, American Society of Anesthesiology (ASA) classification, fracture type, fixation method, time to full weight bearing, and complications. Comparisons between the TKA vs native knee groups were performed using t-test, chi-square, and Fisher's exact test where appropriate. Results: 138 patients were included in our study with a mean age of 74 years. 69 DFF ipsilateral to a TKA were included in the study group and 71 DFF were included in the native knee group. Age, sex, BMI, smoking status, and ASA class were similar between the groups. All patients with periprosthetic femur fractures had 33A AO/OTA fracture classification. Patients with native knees were more likely to receive dual implant fixation, 15.5% compared to 4.3% (p = 0.02). Full weight bearing was achieved at 8.5 vs 8.6 weeks between the NK and TKA groups (p = 0.64). The complication rate was 16.9% in the NK group vs. 7.2% in the TKA group (p = 0.21). Conclusion: Patients with periprosthetic femur fractures have similar time to weight bearing and complications rate with patients with distal femur fracture in native knees. We found a higher utilization rate of dual implant fixation in the native knee group.

Modular air-liquid interface aerosol exposure system (MALIES) to study toxicity of nanoparticle aerosols in 3D-cultured A549 cells in vitro.

We present a novel lung aerosol exposure system named MALIES (modular air-liquid interface exposure system), which allows three-dimensional cultivation of lung epithelial cells in alveolar-like scaffolds (MatriGrids®) and exposure to nanoparticle aerosols. MALIES consists of multiple modular units for aerosol generation, and can be rapidly assembled and commissioned. The MALIES system was proven for its ability to reliably produce a dose-dependent toxicity in A549 cells using CuSO4 aerosol. Cytotoxic effects of BaSO4- and TiO2-nanoparticles were investigated using MALIES with the human lung tumor cell line A549 cultured at the air-liquid interface. Experiments with concentrations of up to 5.93 × 105 (BaSO4) and 1.49 × 106 (TiO2) particles/cm3, resulting in deposited masses of up to 26.6 and 74.0 µg/cm2 were performed using two identical aerosol exposure systems in two different laboratories. LDH, resazurin reduction and total glutathione were measured. A549 cells grown on MatriGrids® form a ZO-1- and E-Cadherin-positive epithelial barrier and produce mucin and surfactant protein. BaSO4-NP in a deposited mass of up to 26.6 µg/cm2 resulted in mild, reversible damage (~ 10% decrease in viability) to lung epithelium 24 h after exposure. TiO2-NP in a deposited mass of up to 74.0 µg/cm2 did not induce any cytotoxicity in A549 cells 24 h and 72 h after exposure, with the exception of a 1.7 fold increase in the low exposure group in laboratory 1. These results are consistent with previous studies showing no significant damage to lung epithelium by short-term treatment with low concentrations of nanoscale BaSO4 and TiO2 in in vitro experiments.

Utilizing PTEN immunohistochemistry as a screening test for Cowden syndrome.

OBJECTIVES: Cowden syndrome (CS) is a multisystem disease with an elevated lifetime risk of internal malignancy. We aim to assess the role of PTEN immunostain as a screening test for CS in a variety of common CS-associated neoplasms, with a particular focus on cutaneous tumors. METHODS: We retrospectively searched for patients meeting criteria for CS and/or demonstrating germline PTEN mutation from 2008 to 2022. We then performed PTEN immunostains on tumors of these patients as well as control cases. RESULTS: Our study included 30 patients with CS who had a total of 25 CS-associated malignancies (13 thyroid, 8 breast, and 4 endometrial carcinomas). Specifically, there were 11 patients with biopsy-confirmed CS-associated cutaneous neoplasms, including 1 patient with multiple trichilemmomas and 3 with multiple sclerotic fibromas. In total, 45 CS-associated tumors (6 trichilemmomas, 7 sclerotic fibromas, 5 thyroid carcinomas, 18 adenomatous thyroid nodules, 6 breast carcinomas, and 3 endometrial carcinomas) and 31 non-CS cases (9 trichilemmomas, 5 sclerotic fibromas, 8 adenomatous thyroid nodules, and 3 thyroid, 3 breast, and 3 endometrial carcinomas) were available for PTEN immunohistochemical staining. PTEN expression was lost in 43 (96%) of 45 CS-associated lesions and retained in 30 (97%) of 31 sporadic tumors. The overall sensitivity and specificity of PTEN loss of expression as a screening test for CS were 96% and 97%, respectively. CONCLUSIONS: PTEN immunohistochemistry on CS-associated tumors, especially trichilemmomas, can serve as a readily accessible and cost-effective screening test for CS.

Pertussis seasonal variation in Northern Vietnam: the evidence from a tertiary hospital.

BACKGROUND: Pertussis is a highly contagious and dangerous respiratory disease that threatens children's health in many countries, including Vietnam, despite vaccine coverage. From 2015 to 2018, Vietnam experienced an increasing number of pertussis patients. Therefore, this study aimed to investigate the trend and examine the seasonal variations of pertussis in North Vietnam. METHODS: Data were collected from medical records of all under-5-year-old inpatients admitted to the National Children's Hospital in Hanoi, Vietnam (VNCH) 2015-2018. A descriptive analysis was performed to describe the distribution of incident cases by year and season. Linear multivariable regression was conducted to investigate the association between the incidence of cases and seasonality adjusted by age and vaccination status. RESULTS: We identified 1063 laboratory-confirmed patients during 2015-2018, including 247 (23.2%) severe patients. The number of pertussis patients admitted to VNCH per 1000 hospitalizations was 3.2 in 2015, compared to 1.9, 3.1, and 2.1 in 2016, 2017, and 2018, respectively. Outbreaks occurred biennially; however, there was no significant difference in the number of severe patients over this period. Most cases occurred in the hot season (509 patients, or nearly half of the study population). With the adjustment of the vaccination rate and average age, the risk of pertussis-associated hospitalization in the mild season and the hot season was 21% (95% CI [0.12; 0.3]) and 15% (95% CI [0.05; 0.25]) higher than that in the warm season, respectively. The rate of hospitalizations was high in the mild season (28.9%) and the warm season (30.8%), nearly twice as much as that in the hot season; nevertheless, the death rate was only striking high in the mild season, about 5-6 times as much as those in the other seasons. CONCLUSION: The pertussis incidence in Northern Vietnam varied between seasons, peaking in the hot season (April-July). However, severe patients and deaths increased in the mild season (December-March). Interventions, for example, communication activities on pertussis and vaccination, are of immense importance in lowering the prevalence of pertussis. In addition, early diagnoses and early warnings performed by health professionals should be encouraged.

Preventing Static Biofilm Formation of Staphylococcus aureus on Different Types of Surfaces Using Microbubbles.

Bacterial fouling and biofilm formation on surfaces have been ongoing problems in real life as well as in the medical field. Different approaches have been taken to tackle the issues, from costly surface modification to antibiotic-delivering strategies. In this study, we examined the potential of using stabilized microbubbles (MBs) to shield against bacterial adhesion. Three types of surfaces were tested: hydrophilic glass (hydrophilic surface), neutral hydrophobic polystyrene (PS)-coated surfaces, and negatively charged hydrophobic octadecyltrichlorosilane (OTS)-coated surfaces. By evaluating the colony-forming unit (CFU) values from each surface, MBs stabilized by 0.05 mM SDS were shown to only produce significant reduction of Staphylococcus aureus adhesion on PS surfaces, up to 60.29 and 82.32% compared to no-MB PS surfaces, and no-MB uncoated surfaces, correspondingly, due to the appropriate size, stability, and negative charges of the MB shielding layer. On the other hand, OTS coatings had an intrinsic antiadhesion effect (69.83% compared to uncoated surface), given that the negatively charged OTS-aqueous interface or surface porosity nature of the coating prohibited the attachment of MBs, leading to the elimination of the antifouling effect of MBs. Ultimately, MBs gave better shielding results than surface modification when compared to uncoated surfaces and hence can be applied more widely.

Epigenetic variation in neonatal tissues in infants conceived using capacitation-in vitro maturation vs. in vitro fertilization.

OBJECTIVE: To investigate alterations of the global DNA methylation profile in placenta, cord blood, and neonatal buccal smears in infants conceived using in vitro maturation (IVM) with a prematuration step (capacitation-IVM [CAPA-IVM]) vs. in vitro fertilization (IVF). DESIGN: Analysis of data from the offspring of participants in a randomized controlled trial. SETTING: Private clinic. PATIENTS: Forty-six women with polycystic ovary syndrome and/or high antral follicle count and their offspring (58 newborns). INTERVENTION(S): Women with polycystic ovary syndrome and/or a high antral follicle count participating in the clinical trial were randomized to undergo CAPA-IVM or conventional IVF. MAIN OUTCOME MEASURE(S): At delivery, biological samples including cord blood, placental tissue, and a neonatal buccal smear were collected. Genome-wide DNA methylation was determined using the Illumina Infinium MethylationEPIC BeadChip. Variability in methylation was also considered, and mean variances for the two treatment categories were compared. RESULTS: In neonatal buccal smears, there were no significant differences between the CAPA-IVM and conventional IVF groups on the basis of the CpG probe after linear regression analysis using a significant cut-off of false-discovery rate <0.05 and |Δß|≥0.05. In cord blood, only one CpG site showed a significant gain of methylation in the CAPA-IVM group. In the placenta, CAPA-IVM was significantly associated with changes in methylation at five CpG sites. Significantly more variable DNA methylation was found in five probes in the placenta, 54 in cord blood, and two in buccal smears after IVM of oocytes. In cord blood samples, 20 CpG sites had more variable methylation in the conventional IVF vs. IVM group. Isolated CpG sites showing differences in methylation in cord blood were not associated with changes in gene expression of the overlapping genes. CONCLUSION(S): Capacitation-IVM appeared to be associated with only a small amount of epigenetic variation in cord blood, placental tissue, and neonate buccal smears. CLINICAL TRIAL REGISTRATION NUMBER: NCT03405701 (www. CLINICALTRIALS: gov).

SATB2, CKAE1/AE3, and synaptophysin as a sensitive immunohistochemical panel for the detection of lymph node metastases of Merkel cell carcinoma.

Histopathological evaluation of lymph nodes in Merkel cell carcinoma has become crucial in progression estimation and treatment modification. This study was undertaken to determine the most sensitive immunohistochemical panel for detecting MCC nodal metastases. We included 56 patients with 102 metastatic MCC lymph nodes, which were tested with seven antibodies: cytokeratin (CKAE1/AE3), CK20, chromogranin A, synaptophysin, INSM1, SATB2, and neurofilament (NF). Tissue microarrays (TMA) composed of 2-mm tissue cores from each nodal metastasis were constructed. A semiquantitative 5-tier scoring system (0%, < 25%, 25-74%, 75-99%, 100% positive MCC cells with moderate to strong reactivity) was implemented. In the statistical assessment, we included Merkel cell polyomavirus (MCPyV) status and expression heterogeneity between lymph nodes from one patient. A cumulative percentage of moderate to strong expression ≥ 75% of tumoral cells was observed for single cell markers as follows: 91/102 (89.2%) SATB2, 85/102 (83%) CKAE1/AE3, 80/102 (78.4%) synaptophysin, 75/102 (75.5%) INSM1, 68/102 (66.7%) chromogranin A, 60/102 cases (58.8%) CK20, and 0/102 (0%) NF. Three markers presented a complete lack of immunoreactivity: 8/102 (7.8%) CK20, 7/102 (6.9%) chromogranin A, and 6/102 (5.9%) NF. All markers showed expression heterogeneity in lymph nodes from one patient; however, the most homogenous was INSM1. The probability of detecting nodal MCC metastases was the highest while using SATB2 as a first-line marker (89.2%) with subsequential adding CKAE1/AE3 (99%); these results were independent of MCPyV status. Synaptophysin showed a superior significance in confirming the neuroendocrine origin of metastatic cells. This comprehensive analysis allows us to recommend simultaneous evaluation of SATB2, CKAE1/AE3, and synaptophysin in the routine pathologic MCC lymph node protocol.

Combinations of EGFR and MET inhibitors reduce proliferation and invasiveness of mucosal melanoma cells.

Mucosal melanoma (MM) is a very rare and aggressive type of cancer for which immunotherapy or targeted therapy such as BRAF/MEK inhibitors, used in cutaneous melanoma, usually fail. Due to our earlier experience showing the high effectiveness of epidermal growth factor receptor (EGFR) and hepatocyte growth factor receptor (MET) inhibitors in reducing the activation of the MAPK and PI3K/AKT signalling pathways, we aim to test whether these drugs would also be effective for mucosal melanoma. Cells representing two commercially available mucosal melanoma cell lines (GAK and HMVII) and one cell line obtained from a patient's vaginal melanoma were treated with MET or EGFR inhibitors, or combinations of these agents. The dual-inhibitor treatment strategy resulted in a decrease of cell proliferation, migration and invasion. Moreover, combinations of inhibitors led to reduction of pEGFR/EGFR and pMET/MET ratio and downregulation of PI3K/AKT and MEK/ERK1/2-based signalling pathways. Our findings indicate a potential therapeutic strategy based on EGFR and MET inhibitors in mucosal melanoma, which should be further evaluated in vivo and in clinical experiments. They also suggest that targeting multiple receptor tyrosine kinases may block signalling crosstalk and possibly delay the appearance of resistance to kinase inhibitors in mucosal melanoma cells.

Ki67 is a better marker than PRAME in risk stratification of BAP1-positive and BAP1-loss uveal melanomas.

BACKGROUND: Accurate risk stratification of uveal melanoma (UM) patients is important for determining the interval and frequency of surveillance. Loss of BAP1 expression has been shown to be strongly associated with UM-related death and metastasis. METHODS: In this study of 164 enucleated UMs, we assessed the prognostic role of preferentially expressed antigen in melanoma (PRAME) expression and Ki67 proliferation index measured by digital quantitation using QuPath programme in patients with BAP1-positive and BAP1-loss UMs. RESULTS: In univariate analyses with log-rank tests and Kaplan-Meier curves, PRAME further stratified only overall survival (OS) in BAP1-positive and BAP1-loss tumour groups. However, Ki67 further stratified both OS and disease-free survival (DFS) in BAP1-positive and BAP1-loss tumour groups. In multivariate analyses, Ki67 percentage and BAP1 were independent survival predictors for both OS and DFS, whereas PRAME was not a significant covariate. In model comparisons, combined Ki67 and BAP1 performed better than combined PRAME and BAP1 in risk-stratifying patients for both OS and DFS. Ki67 was better than PRAME in risk stratification of BAP1-positive UMs. Low Ki67 index correlated with significantly prolonged DFS in BAP1-loss UMs. CONCLUSION: A panel of Ki67 and BAP1 could be a helpful risk stratification strategy for UM.

Ankle fractures: High implant cost is not associated with better patient reported outcomes.

INTRODUCTION: Ankle fractures comprise 9% of all fractures and are among the most common fractures requiring operative management. Open reduction and internal fixation (ORIF) with plates and screws is the gold standard for the treatment of unstable, displaced ankle fractures. While performing ORIF, orthopaedic surgeons may choose from several fixation methods including locking versus nonlocking plating and whether to use screws or suture buttons for syndesmotic injuries. Nearly all orthopaedic surgeons treat ankle fractures but most are unfamiliar with implant costs. No study to date has correlated the cost of ankle fracture fixation with health status as perceived by patients through patient reported outcomes (PROs). The purpose of this study was to determine whether there is a relationship between increasing implant cost and PROs after a rotational ankle fracture. METHODS: All ankle fractures treated with open reduction internal fixation (ORIF) at a level I academic trauma center from January 2018 to December 2022 were identified. Inclusion criteria included all rotational ankle fractures with a minimum 6-month follow-up and completed 6-month PRO. Patients were excluded for age <18, polytrauma and open fracture. Variables assessed included demographics, fracture classifications, Foot and Ankle Ability Measure-Activities of Daily Living (FAAM-ADL) score, implant type, and implant cost. RESULTS: There was a statistically significant difference in cost between fracture types (p < 0.0001) with trimalleolar fractures being the most expensive. The mean FAAM-ADL score was lowest for trimalleolar fractures at 78.9, 95% CI [75.5, 82.3]. A diagnosis of osteoporosis/osteopenia was associated with a decrease in cost of $233.3, 95% CI [-411.8, -54.8]. There was no relationship between syndesmotic fixation and implant cost, $102.6, 95% CI [-74.9, 280.0]. There was no correlation between implant cost and FAAM-ADL score at 6 months (p = 0.48). CONCLUSIONS: The utilization of higher cost ankle fixation does not correlate with better FAAM-ADL scores. Orthopaedic surgeons may choose less expensive implants to improve the value of ankle fixation without impacting patient reported outcomes.

Comparisons of Procedures Performed in Training vs in Early Practice by Orthopaedic Trauma Surgeons.

INTRODUCTION: The Orthopaedic Trauma Association (OTA) has maintained an accreditation process of orthopaedic trauma fellowships with various requirements including an annually reviewed list of qualifying trauma cases in the form of American Medical Association Current Procedural Terminology (CPT) codes. The correlation between these established and monitored CPTs and the actual practices of orthopaedic trauma surgeons has not been studied. METHODS: American Board of Orthopaedic Surgery part II case logs (trauma subspecialty) (2012 to 2018) were compared with OTA fellowship case logs (2015 to 2019). Case logs from 447 surgeons and 166 trauma fellowship programs were compared. Four CPT code categories were defined: complex trauma (OTA required CPT codes, excluding Accreditation Council for Graduate Medical Education [ACGME] orthopaedic residency requirements), general trauma (ACGME residency required trauma codes), general orthopaedics (nontrauma ACGME residency requirements), and others (codes not included in residency or trauma fellowship requirements). RESULTS: OTA fellows performed a higher median percentage of complex trauma compared with American Board of Orthopaedic Surgery candidates (34% vs. 21%, P < 0.001): Both cohorts performed a similar percentage of general trauma (23%). OTA fellows performed more general orthopaedics (40% vs. 1%, P < 0.001). Several OTA required codes were performed infrequently (0 to 3 during board collection) by most surgeons, and several procedures are being performed that are not included in current CPT code requirements. DISCUSSION: Early-career traumatologists are performing orthopaedic trauma procedures they were trained on during residency and fellowship, with varying complexity. Trauma fellows perform a higher percentage of complex trauma compared with early-career trauma surgeons. Continued surveillance is necessary such that educational improvements can be made to maximize the quality of trauma fellowship education. LEVEL OF EVIDENCE: Level III, therapeutic study. See Instructions for Authors for a complete description of levels of evidence.

Why do consumers choose private over public health services? Reflective accounts of health providers in Vietnam.

BACKGROUND: In Vietnam and many developing countries, private healthcare is increasingly being leveraged by governments to complement public services and increase health service access and utilisation. Extensive understanding of patterns of utilisation of private over public health services, and the rationale for such consumer decisions, is important to ensure and promote safe, affordable and patient-centred care in the two sectors. Few studies within the Southeast Asian Region have explored how private and public providers interact (via social networks, marketing, and direct contact) with consumers to affect their service choices. This study investigates providers' views on social factors associated with the use of private over public health services in Vietnam. METHOD: A thematic analysis was undertaken of 30 semi-structured interviews with experienced health system stakeholders from the Vietnam national assembly, government ministries, private health associations, health economic association, as well as public and private hospitals and clinics. RESULTS: Multiple social factors were found to influence the choice of private over public services, including word-of-mouth, the patient-doctor relationship and relationships between healthcare providers, healthcare staff attitudes and behaviour, and marketing. While private providers maximise their use of these social factors, most public providers seem to ignore or show only limited interest in using marketing and other forms of social interaction to improve services to meet patients' needs, especially those needs beyond strictly medical intervention. However, private providers faced their own particular challenges related to over-advertisement, over-servicing, excessive focus on patients' demands rather than medical needs, as well as the significant technical requirements for quality and safety. CONCLUSIONS: This study has important implications for policy and practice in Vietnam. First, public providers must embrace social interaction with consumers as an effective strategy to improve their service quality. Second, appropriate regulations of private providers are required to protect patients from unnecessary treatments, costs and potential harm. Finally, the insights from this study have direct relevance to many developing countries facing a similar challenge of appropriately managing the growth of the private health sector.

Amphiphiles Formed from Synthetic DNA-Nanomotifs Mimic the Stepwise Dispersal of Transcriptional Clusters in the Cell Nucleus.

Stem cells exhibit prominent clusters controlling the transcription of genes into RNA. These clusters form by a phase-separation mechanism, and their size and shape are controlled via an amphiphilic effect of transcribed genes. Here, we construct amphiphile-nanomotifs purely from DNA, and we achieve similar size and shape control for phase-separated droplets formed from fully synthetic, self-interacting DNA-nanomotifs. Increasing amphiphile concentrations induce rounding of droplets, prevent droplet fusion, and, at high concentrations, cause full dispersal of droplets. Super-resolution microscopy data obtained from zebrafish embryo stem cells reveal a comparable transition for transcriptional clusters with increasing transcription levels. Brownian dynamics and lattice simulations further confirm that the addition of amphiphilic particles is sufficient to explain the observed changes in shape and size. Our work reproduces key aspects of transcriptional cluster formation in biological cells using relatively simple DNA sequence-programmable nanostructures, opening novel ways to control the mesoscopic organization of synthetic nanomaterials.

Contribution of private health services to universal health coverage in low and middle-income countries: Factors affecting the use of private over public health services in Vietnam.

The private sector's contribution to Universal health coverage (UHC) has been increasingly recognised by policymakers in low- and middle-income countries. This study aimed to identify service-provider and consumer-level factors affecting choice of private over public health services in Vietnam. A concurrent mixed-method design was adopted. A quantitative phase explored consumers' health service choice by analysing data from a random national sample of 10,354 individuals aged 16 and over. The qualitative phase investigated how private and public providers organise their services to influence consumer choices by conducting interviews with policymakers, hospital and clinic managers, and health practitioners. The combined results demonstrate that at the individual level, absence of any type of health insurance was the factor most closely associated with the use of private services. Private health services were more likely to be used by people from ethnic majority groups compared to ethnic minorities (odds ratio [OR]: 1.6, 95% CI: 1.4-2.0), and by people living in urban compared to rural areas (OR: 1.1, 95% CI: 1.0-1.3). The service providers suggested that consumers opted for private services that were perceived to have poorer quality in the public sector, such as counselling, physical therapy and rehabilitative care. Additional motivational factors include the private sector's more flexible working hours, shorter waiting times, flexible pricing of services, personalised care and better staff behaviour. The findings can inform national health system planning and coordination activities in Vietnam and other countries that aim to harness the attributes of both the public and private sectors to achieve UHC.