Evaluation of two transposases for improving expression of recombinant proteins in Chinese hamster ovary cell stable pools by co-transfection and supertransfection approaches.

Transposons are genetic elements capable of cutting and pasting genes of interest via the action of a transposase and offer many advantages over random or targeted integration of DNA in the creation of Chinese hamster ovary (CHO) cell lines for recombinant protein expression. Unique transposases have different recognition sites, allowing multiple transposases to be co-transfected together. They also allow for supertransfection (transfection on a previously transfected pool or cell line) with a second transposase to integrate additional copies of the same gene or an additional gene without disruption of the previously integrated DNA which to our knowledge has not been previously described in literature. Two fluorescent proteins, EGFP and tagRFP657, were either co-transfected or supertransfected into CHO cells using two unique transposases and showed high expression efficiency with similar expression levels (measured as mean fluorescence intensity), regardless of whether the genes were co-transfected or supertransfected onto an existing stable pool. Additionally, dual selection of the genes, both in the absence of L-glutamine and the presence of puromycin, led to higher expression levels than single selection alone. These results demonstrate that supertransfection using unique transposases could be a useful strategy for increasing titers of existing cell lines or for overexpressing helper (non-therapeutic) genes to improve expression and/or product quality of existing pools and cell lines, potentially saving significant time and resources.

Fibrous Dysplasia of the Parietal Bone with Focal Motor Seizures: A Case Report.

BACKGROUND Monostotic fibrous dysplasia is a benign proliferation of fibrous and osseous tissues that expand medullary bone to cause symptoms due to compression of adjacent organs and anatomical structures. Focal seizures are rarely the first sign of this kind of lesion. This report describes a young female patient with left-sided focal motor seizures associated with fibrous dysplasia presenting as a mass in the right parietal bone. CASE REPORT An 18-year-old female student with left-sided focal motor seizures presented with a mass in the right parietal bone. Computed tomography revealed an expansile mixed-density lesion on the right parietal bone, a relatively homogeneous ground-glass appearance in the outer circumferential portion, and a lucent eccentric area with thinned but sclerotic borders. Magnetic resonance imaging revealed a homogeneously hypointense signal on T1WI, a small hyperintense signal on T2WI, and avid enhancement signal intensity on post-contrast T1. Electroencephalogram showed inter-ictal epileptiform activities derived from the right fronto-central lobe. Surgical en bloc resection with a margin of normal bone and cranioplasty were performed. Histopathology showed features indicative of fibrous dysplasia, including osteoid trabeculae arranged haphazardly in a dense fibroblastic stroma, irregular trabeculae lacking conspicuous osteoblastic rimming, and intervening fibrous stroma containing cytologically bland spindle cells. The patient achieved seizure control and has remained neurologically intact. CONCLUSIONS This report has highlighted the importance of early diagnosis of fibrous dysplasia of bone to exclude primary bone malignancy or bone metastasis, to ensure rapid management and symptom control.

A new species of the Cyrtodactyluschauquangensis species group (Squamata, Gekkonidae) from Lao Cai Province, Vietnam.

We describe a new species of the genus Cyrtodactylus based on five adult specimens from Bac Ha District, Lao Cai Province, northern Vietnam. Cyrtodactyluslucisp. nov. is distinguished from the remaining Indochinese bent-toed geckos by a combination of the following morphological characteristics: medium size (SVL up to 89.5 mm); dorsal tubercles in 17-19 irregular transverse rows; ventral scales in 32-34 longitudinal rows at midbody; precloacal pores present in both sexes, 9 or 10 in males, 8 or 9 in females; 12-15 enlarged femoral scales on each thigh; femoral pores 9-12 in males, 5-10 in females; postcloacal tubercles 2-4; lamellae under toe IV 21-23; dorsal pattern consisting of 5 or 6 irregular dark bands, a thin neckband without V-shape or triangle shape in the middle, top of head with dark brown blotches; subcaudal scales transversely enlarged. Molecular phylogenetic analyses recovered the new species as the sister taxon to C.gulinqingensis from Yunnan Province, China, with strong support from all analyses and the two taxa are separated by approximately 8.87-9.22% genetic divergence based on a fragment of the mitochondrial ND2 gene. This is the first representative of Cyrtodactylus known from Lao Cai Province.

Increase in human immunodeficiency virus and syphilis prevalence and incidence among men who have sex with men, vietnam 2015 - 2020.

INTRODUCTION: We assessed trends in HIV and syphilis prevalence, HIV incidence, related risk factors, and preventive behaviors among men who have sex with men (MSM) in Vietnam from 2015 to 2020. METHODS: Data originated from the HIV Sentinel Surveillance Plus system, which sampled MSM at venues and hotspots in seven of Vietnam's 63 provinces in 2015, 2016, 2018, and 2020 (N = 1100-1445 per year; ∼150-300 per province per year). RESULTS: HIV prevalence estimates increased from 6.6% (95% CI 4.5-9.6) in 2015 to 13.8% (95% CI 10.5-18.2, p = .001 for trend) in 2020 overall, and separately in An Giang, Can Tho, Hai Phong, and Khanh Hoa provinces but not in Ho Chi Minh City, Hanoi, or Kien Giang. Syphilis prevalence increased from 2.7% (95% CI 1.4-5.1) in 2015 to 12.6% (95% CI 8.7-18.0) in 2020 overall (p < .001 for trend), and separately in An Giang, Can Tho, and Hai Phong provinces but not in Ho Chi Minh City or Kien Giang. We calculated time-at-risk from first anal sex to first HIV-positive or last HIV-negative test to estimate HIV incidence. Estimated HIV incidence suggested increasing rates of seroconversion from 1.36 per 100 person-years experienced by participants in 2015 to 2.61 per 100 person-years among participants in 2020 (hazard ratio per year 1.13, 95% CI 1.08-1.18, p < .001). There was a statistically significant increase in HIV testing, STI testing, and receipt of free condoms over the period (p < .05 for trend), and a statistically significant decrease in amphetamine use (p = .043 for trend). CONCLUSIONS: Despite prevention efforts and improvements in some risk indicators, consecutive cross-sectional sampling results provide evidence of increasing incidence of HIV and syphilis among MSM in Vietnam, especially outside the major cities. Aggressive HIV prevention and treatment services can be expanded while conducting deeper investigations into the causes of these increases.

GP perspectives on a psychiatry phone line in Western Australia's Great Southern region: implications for addressing rural GP workload.

BACKGROUND: Mental illness is a public health challenge disproportionately affecting rural Australians. GPs provide most of the mental health care, and they report increasing levels of burnout and unsustainable workload in the context of increased patient complexity. This may be more salient in rural settings characterised by resource constraints. In this paper, we use evaluation data from a GP psychiatry phone line established in Western Australia's Great Southern region in 2021 to describe GPs' perspectives on the service and reflect on how it may help alleviate rural GP workload. METHODS: The sample was recruited among GPs practicing in the region. Data were collected through an online survey and semistructured interviews. Descriptive statistics were used to analyse the survey data. Interview data were subjected to thematic analysis; qualitative survey data were used for triangulation. RESULTS: A total of 45GPs completed the survey and 14 were interviewed. Interview data yielded three themes: the criticality of timeliness; the building blocks of confidence; and trust. GPs were highly satisfied with the service, and timeliness and trust were the characteristics underpinning its effectiveness. The service built GPs' confidence in managing mental health and alcohol and other drug use issues through strengthening knowledge and providing reassurance. CONCLUSIONS: Our results suggest that a telephone line operated by trusted, local psychiatrists with knowledge of the local mental health ecosystem of support can reduce rural GP workload through building confidence and strengthening personal agency, helping GPs navigate the ethical and clinical labyrinth of managing patient complexity in rural settings.

A new species of Cyrtodactylus (Squamata: Gekkonidae) from Phu Yen Province, Vietnam.

We describe a new species of the genus Cyrtodactylus based on six adult specimens from Lac Dao forests, Phu Yen Province, southern Vietnam. Cyrtodactylus tayhoaensis sp. nov. is distinguished from the remaining Indochinese bent-toed geckos by a combination of the following characters: medium size (SVL up to 94.2 mm); nasal scales 5-6; internasal single or double; ciliaria 29-34; dorsal tubercles in 20-22 irregular transverse rows; ventral scale in 37-41 longitudinal rows at midbody; ventrolateral folds present without interspersed tubercles; precloacal pores absent in females, precloacal pores 4 or 5 in males; 10 or 11 enlarged femoral scales on each thigh; femoral pores 3-7 in males, absent in females; postcloacal tubercles 3 or 4; lamellae under toe IV 22-24; dorsal pattern consisting of unclear transverse bands formed by irregularly shaped dark-brown blotches, a discontinuous neckband with V-shape or triangle shape in the middle, dorsal head surface with dark-brown blotches; subcaudal scales transversely enlarged. In the phylogenetic analyses, the new species is recovered as a sister taxon to C. kingsadai with approximately 4% genetic divergence between the two species based on a fragment of the COI gene. This is the second species of Cyrtodactylus known from Phu Yen Province located in southern Vietnam.

Achalinus quangi, a new odd-scaled snake species from Vietnam.

Based on morphological and molecular analyses, we herein describe a new species of Achalinus from northern Vietnam. Achalinus quangi sp. nov. differs from its sister taxon, A. emilyae, and other members of the genus Achalinus by at least 4% in terms of genetic divergence based on fragments of the mitochondrial COI and Cytb genes and a combination of the following morphological characters: (1) maxillary teeth 27-29; (2) suture between the internasals distinctly longer than that between the prefrontals; (3) loreal not fused with prefrontal, extending from the nasal to the eye; (4) supralabials six; (5) infralabials five; (6) postocular absent, temporals 2+2, only the upper one in broad contact with eye; (7) dorsal scales in 25(23)-23-23(21) rows, keeled; (8) ventrals 139-141 in males, 141-154 in females; (9) subcaudals 75-84 in males, 69 in the female, all unpaired; (10) cloacal entire; (11) dorsum reddish brown to brown. Achalinus quangi sp. nov. consists of two subclades, the first one occurring on the northern side of the Da River in Son La and Tuyen Quang provinces and another subclade found on the southern side in Thanh Hoa, Nghe An, and Ha Tinh provinces. These two subclades are separated from each other by 1.8 to 2.3% genetic divergence and are slightly differing in ventral scalation.

Developing fit-for-purpose funding models for rural settings: Lessons from the evaluation of a step-up/step-down service in regional Australia.

Introduction: Sub-acute mental health community services provide a bridging service between hospital and community care. There is limited understanding of the local factors that influence success, and of the funding implications of delivering services in rural areas. Methods: This paper draws from quantitative and qualitative evaluation data from a regional Western Australian service to explore these issues. Results: Consumers satisfaction with the service was high and, overall, admission to the service resulted in positive outcomes. High re-admission rates may be linked to limited community support services following discharge. Discussion: Our results suggest that outcomes may be enhanced by implementing flexible approaches that address the resource limitations of the rural context, and that the current funding model for sub-acute mental health services in rural Australian may not be fit for purpose. More needs to be understood about how these services can be better integrated with existing support services, and how they can be better funded.

Descriptive Study of Ambulance Attendances for Older Adults with and without Dementia in Western Australia.

OBJECTIVE: To describe and compare characteristics of ambulance attendances for older adults with and without dementia. METHODS: A retrospective cohort study was conducted using electronic patient care records from the main ambulance service in Western Australia. All attendances for people aged 65 years or older in the years 2019-21 were included. Dementia status was adjudicated from the clinical history and medication lists. Patient and case characteristics of those with and without dementia were compared and stratified by type of residence. RESULTS: There were 277,996 emergency ambulance attendances made by 124,711 older adults, of whom 23.5% had dementia. The mean number of attendances per person was 3.3 in the dementia cohort vs 2.0 in those without dementia. Falls were the leading reason for ambulance attendance. People with dementia were significantly frailer, required longer at-scene intervals, were less likely to be transported as the highest priority, and had lower 30-day survival. CONCLUSIONS: Dementia is common amongst older adults attended by paramedics and is associated with higher ambulance utilization per person. People with dementia attended by paramedics have stronger signals of vulnerability, such as increased frailty. As the number of people living with dementia increases in the future, there are implications for workforce training and service planning. There are opportunities for developing alternatives to emergency department transportation for some people with dementia.

A Multicenter Study of Clinicopathology and Immunohistochemical Distinction between Adult and Pediatric Large B-Cell Lymphoma.

Introduction: Pediatric DLBCL is considered a homogenous group and has superior outcomes compared to adults. This study investigated the clinical pathology and immunohistochemical distinction between adult and pediatric large B-cell lymphoma. Methods: A cross-sectional study of 314 NHLs with the morphology of diffuse pattern, large B-cell, and CD20 expression was investigated. Results: Of 314 cases, there were 6 cases of pleomorphic MCL (all in adults), 19 cases of Burkitt lymphoma (all in children), and 289 cases of DLBCL. Pediatric DLBCL had many striking differences: More frequency in extra-nodal sites; a higher proportion of centroblastic morphology; a predominance of GCB-type; a high proliferation rate; an infrequency of Bcl2 protein expression, and a lack of double-expresser lymphoma. Conclusions: Our study demonstrated the significant biological differences between adult and pediatric DLBCL.

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

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

Emotions in telephone calls to emergency medical services involving out-of-hospital cardiac arrest: A scoping review.

Aims: The purpose of this scoping review was to identify and synthesise existing research evidence on emotions in the context of emergency phone calls to emergency medical services (EMS) involving out-of-hospital cardiac arrest (OHCA). The specific objectives were to identify studies that (1) described emotions during emergency OHCA calls; (2) specified an instrument or method for measuring/assessing emotions; and (3) examined the relationship between emotions and call outcomes or patient outcomes. Methods/Data sources: Five databases were searched on 18 November 2021: Medline, Embase, PsycInfo, CINAHL, and the Cochrane Review Database. Included studies required the following three concepts to be addressed: emotions in the context of EMS calls that involved OHCA. Calls also needed to be made by a 'second-party' caller; and each study needed to address at least one of the three specific objectives, as outlined above.The review was conducted in accordance with the Joanna Briggs Institute guidelines for evidence synthesis for scoping reviews. Results: Thirteen eligible studies were included for synthesis. All studies met Objective 1; six studies met Objective 2; and seven met Objective 3. One study reported patient fatality due to heightened emotions and ensuing ineffective communications between callers and call-takers. Conclusion: The review highlights a significant gap in the evidence base of emotions in emergency OHCA-related calls, and the need for a more comprehensive and effective method in assessing and measuring emotions in this context. Relationships between emotions (their expressions and perceptions) and call outcomes (including patient outcomes) also need more rigorous investigation.

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

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

Targeted EV to Deliver Chemotherapy to Treat Triple-Negative Breast Cancers.

Triple-negative breast cancers (TNBCs) are heterogeneous and metastatic, and targeted therapy is highly needed for TNBC treatment. Recent studies showed that extracellular vesicles (EV) have great potential to deliver therapies to treat cancers. This study aimed to develop and evaluate a natural compound, verrucarin A (Ver-A), delivered by targeted EV, to treat TNBC. First, the surface expression of epidermal growth factor receptor (EGFR) and CD47 were confirmed with immunohistochemistry (IHC) staining of patient tissue microarray, flow cytometry and Western blotting. EVs were isolated from HEK 293F culture and surface tagged with anti-EGFR/CD47 mAbs to construct mAb-EV. The flow cytometry, confocal imaging and live-animal In Vivo Imaging System (IVIS) demonstrated that mAb-EV could effectively target TNBC and deliver the drug. The drug Ver-A, with dosage-dependent high cytotoxicity to TNBC cells, was packed in mAb-EV. The anti-TNBC efficacy study showed that Ver-A blocked tumor growth in both 4T1 xenografted immunocompetent mouse models and TNBC patient-derived xenograft models with minimal side effects. This study demonstrated that the targeted mAb-EV-Ver-A had great potential to treat TNBCs.

Satisfaction with general practitioner obstetrician-led maternity care in rural Western Australia.

OBJECTIVE: To measure satisfaction with general practitioner obstetrician-led maternity care in Western Australia and to explore perspectives of maternity service users DESIGN: Women were recruited at antenatal visits with their general practitioner obstetrician. Participants completed a validated three-part survey about their satisfaction with antenatal, intrapartum and postpartum care. They were all offered a semi-structured interview. SETTING: Nine general practitioner obstetrician practices located in regional Western Australia. PARTICIPANTS: 155 women receiving general practitioner obstetrician-led maternity care within the South West or Great Southern regions of Western Australia. 13 of these women also participated in an interview. MAIN OUTCOME MEASURES: We quantified satisfaction with aspects of antenatal, intrapartum and postpartum care using a Likert scale. Descriptive variables included demographic information and birth outcomes. Qualitative data described valued aspects of maternity care. RESULTS: 116 women completed all 3 surveys. General practitioner obstetrician-led care resulted in high rates of satisfaction across all 3 stages of care, with 78%-100% agreement with positively worded satisfaction statements. Thematic analysis identified four key aspects of care women valued when receiving maternity care: the woman-centred care experience, the skills of the general practitioner obstetrician, support from the health care team and the health care environment. CONCLUSION: General practitioner obstetrician-led maternity care is a highly regarded model of maternity care, valued by rural women with high rates of satisfaction.

Support Needs for Bhutanese Family Members Taking Care of Loved Ones Diagnosed with Advanced Illness.

Background: Palliative care aims to improve the quality of life of patients diagnosed with an advanced illness and their families. Family members, who often play a central role caring for their very ill loved ones, have significant support needs. In Bhutan, where palliative care is an emerging concept, the needs of family members have not been assessed thus far. Objective: This study explored the support needs of Bhutanese family members caring for their loved ones diagnosed with advanced illness. Methods: This is a cross-sectional descriptive study. Setting/Subjects: Study sites included the national referral hospital, the two regional referral hospitals, four district hospitals and Basic Health Units (Grade I and II), spread across Bhutan. Participants were recruited through purposeful and snowball sampling strategies. Data were collected from May to August 2019. The Carer Support Needs Assessment Tools (CSNAT) was used. Results: Despite unforeseen challenges, 46 family members out of 60 identified (77%) participated in the survey. Twenty-three (50%) cared for relatives with advanced cancer and the remainder for loved ones with non-malignant conditions. This study found high support needs among both groups. The priority needs included understanding their relative's illness, managing symptoms, providing personal care, financial aspects, dealing with their own feelings and emotions and knowing what to expect in the future. Conclusion: This study will help inform the World Health Organization recommended public health approach to palliative care modified to the Bhutanese context for enabling a cost-effective intervention to improve the quality of lives of patients and families.

How many more species are out there? Current taxonomy substantially underestimates the diversity of bent-toed geckos (Gekkonidae, Cyrtodactylus) in Laos and Vietnam.

Cyrtodactylus is the most diverse genus of the family Gekkonidae and the world's third largest vertebrate genus. The number of species has increased more than fourfold over the last two decades. Indochina, especially Vietnam and Laos, has witnessed a surge in new species discoveries over the last three decades. The species number reported from Laos and Vietnam has remarkably increased from five in 1997 to 71 species in 2021. However, within the genus, several taxonomic issues have not yet been fully resolved. Based on recently collected samples from Laos and Vietnam, we conducted a comprehensive molecular review of Cyrtodactylus occurring in Laos and Vietnam. Our molecular analysis with support from morphological comparisons showed that C.thuongae is a junior synonym of C.dati and C.rufford is a junior synonym of C.lomyenensis. In total, 68 described species distributed in Laos and Vietnam are undisputed with strong support from both molecular and morphological evidence. On the other hand, the molecular analyses revealed that there are at least seven undescribed species in Vietnam and Laos, one in the C.angularis group, one in the C.chauquangensis, and five in the C.irregularis group. This number will likely increase significantly, as previous work suggested that the C.angularis and C.irregularis groups harbor three and six unnamed lineages, respectively. Based on survey gaps identified in our study, it is clear that additional new species will be discovered in poorly studied regions of central Vietnam and northern and southern Laos. As many species in the genus are facing high extinction risks, several undescribed populations might already be severely threatened by human activities in both countries. Therefore, urgent taxonomic research is needed before conservation assessments of newly discovered taxa can be undertaken to protect them from anthropogenic threats.

A new species of Cyrtodactylus (Squamata: Gekkonidae) from Ninh Thuan Province, southern Vietnam.

A new species of the Cyrtodactylus irregularis group is described from Ninh Thuan Province, southern Vietnam based on molecular divergence and morphological differences. Cyrtodactylus orlovi sp. nov. is distinguished from the remaining Indochinese bent-toed geckos by having the unique combination of the following characters: size medium (SVL 61.077.7 mm); dorsal tubercles in 1620 irregular rows; 3639 ventral scale rows; precloacal pores absent in females, 5 or 6 in males, in a continuous row; femoral pores absent; 38 enlarged femoral scales; postcloacal spurs 1 or 2; lamellae under toe IV 1619; a continuous neckband; a highly irregular transverse banded dorsal pattern; the absence of transversely enlarged median subcaudal scales. In phylogenetic analyses, the new species was revealed to be the sister taxon to a clade consisting of Cyrtodactylus cattienensis and the most recently described species from Vietnam, C. chungi, with 12.112.4% and 11.7 % pairwise genetic divergence from the two species, respectively, based on a fragment of the mitochondrial COI gene.

"I'm sorry, my English not very good": Tracking differences between Language-Barrier and Non-Language-Barrier emergency ambulance calls for Out-of-Hospital Cardiac Arrest.

BACKGROUND: One-fifth of Australia's population do not speak English at home. International studies have found emergency calls with language barriers (LB) result in longer delays to out-of-hospital cardiac arrest (OHCA) recognition, and lower rates of bystander cardiopulmonary resuscitation (CPR) and survival. This study compared LB and non-LB OHCA call time intervals in an Australian emergency medical service (EMS). METHODS: The retrospective cohort study measured time intervals from call commencement for primary outcomes: (1) address acquisition; (2) OHCA recognition; (3) CPR initiation; (4) telecommunicator CPR (t-CPR) compressions, in all identified LB calls and a 2:1 random sample of non-LB EMS calls from January to June 2019. Results for time intervals #1, 2, and 4 were benchmarked against the American Heart Association's (AHA) t-CPR minimal acceptable time standards. Patient survival outcomes were compared. RESULTS: We identified 50 (14%) LB calls from a cohort of 353 calls. LB calls took longer than non-LB calls (n=100) for: address acquisition (median 29 vs 14 secs, p<0.001), OHCA recognition (103 vs 85 secs, p=0.02), and CPR initiation (206 vs 164 secs, p=0.01), but not for t-CPR compressions (292 vs 248 secs, p=0.12). Rates of OHCA recognition and 30-day-survival did not differ but smaller proportions of LB calls met the AHA standards. CONCLUSION: Time delays found in LB calls point to phases of the call which need further qualitative investigation to understand how to improve communication. Overall, training call-takers for LB calls may assist caller understanding and cooperation during OHCAs.

Anti-CD47 Monoclonal Antibody-Drug Conjugate: A Targeted Therapy to Treat Triple-Negative Breast Cancers.

Triple-negative breast cancers (TNBCs) are frequently recurrent due to the development of drug resistance post chemotherapy. Both the existing literature and our study found that surface receptor CD47 (cluster of differentiation 47) was upregulated in chemotherapy-treated TNBC cells. The goal of this study was to develop a monoclonal antibody (mAb)-based targeting strategy to treat TNBC after standard treatment. Specifically, a new mAb that targets the extracellular domain of receptor CD47 was developed using hybridoma technology and produced in fed-batch culture. Flow cytometry, confocal microscopy, and in vivo imaging system (IVIS) showed that the anti-CD47 mAb effectively targeted human and mouse TNBC cells and xenograft models with high specificity. The antibody-drug conjugate (ADC) carrying mertansine was constructed and demonstrated higher potency with reduced IC50 in TNBC cells than did the free drug and significantly inhibited tumor growth post gemcitabine treatment in MDA-MB-231 xenograft NSG model. Finally, whole blood analysis indicated that the anti-CD47 mAb had no general immune toxicity, flow cytometry analysis of lymph nodes revealed an increase of CD69+ NK, CD11c+ DC, and CD4+ T cells, and IHC staining showed tumoral infiltration of macrophage in the 4T1 xenograft BALB/cJ model. This study demonstrated that targeting CD47 with ADC has great potential to treat TNBCs as a targeted therapy.