In situ tumour arrays reveal early environmental control of cancer immunity.

The immune phenotype of a tumour is a key predictor of its response to immunotherapy1-4. Patients who respond to checkpoint blockade generally present with immune-inflamed5-7 tumours that are highly infiltrated by T cells. However, not all inflamed tumours respond to therapy, and even lower response rates occur among tumours that lack T cells (immune desert) or that spatially exclude T cells to the periphery of the tumour lesion (immune excluded)8. Despite the importance of these tumour immune phenotypes in patients, little is known about their development, heterogeneity or dynamics owing to the technical difficulty of tracking these features in situ. Here we introduce skin tumour array by microporation (STAMP)-a preclinical approach that combines high-throughput time-lapse imaging with next-generation sequencing of tumour arrays. Using STAMP, we followed the development of thousands of arrayed tumours in vivo to show that tumour immune phenotypes and outcomes vary between adjacent tumours and are controlled by local factors within the tumour microenvironment. Particularly, the recruitment of T cells by fibroblasts and monocytes into the tumour core was supportive of T cell cytotoxic activity and tumour rejection. Tumour immune phenotypes were dynamic over time and an early conversion to an immune-inflamed phenotype was predictive of spontaneous or therapy-induced tumour rejection. Thus, STAMP captures the dynamic relationships of the spatial, cellular and molecular components of tumour rejection and has the potential to translate therapeutic concepts into successful clinical strategies.

T cell-dependent bispecific antibodies alter organ-specific endothelial cell-T cell interaction.

Preclinical and clinical studies demonstrate that T cell-dependent bispecific antibodies (TDBs) induce systemic changes in addition to tumor killing, leading to adverse events. Here, we report an in-depth characterization of acute responses to TDBs in tumor-bearing mice. Contrary to modest changes in tumors, rapid and substantial lymphocyte accumulation and endothelial cell (EC) activation occur around large blood vessels in normal organs including the liver. We hypothesize that organ-specific ECs may account for the differential responses in normal tissues and tumors, and we identify a list of genes selectively upregulated by TDB in large liver vessels. Using one of the genes as an example, we demonstrate that CD9 facilitates ICAM-1 to support T cell-EC interaction in response to soluble factors released from a TDB-mediated cytotoxic reaction. Our results suggest that multiple factors may cooperatively promote T cell infiltration into normal organs as a secondary response to TDB-mediated tumor killing. These data shed light on how different vascular beds respond to cancer immunotherapy and may help improve their safety and efficacy.

Diffusiophoretic Transport of Charged Colloids in Ionic Surfactant Gradients Entirely below versus Entirely above the Critical Micelle Concentration.

When placed in an ionic surfactant gradient, charged colloids will undergo diffusiophoresis at a velocity, uDP = MDP∇ ln S, where MDP is the diffusiophoretic mobility and S is the surfactant concentration. The diffusiophoretic mobility depends in part on the charges and diffusivities of the surfactants and their counterions. Since micellization decreases surfactant diffusivity and alters charge distributions in a surfactant solution, MDP of charged colloids in ionic surfactant gradients may differ significantly when surfactant concentrations are above or below the critical micelle concentration (CMC). The role of micelles in driving diffusiophoresis is unclear, and a previously published model that accounts for micellization suggests the possibility of a change in the sign of MDP above the CMC [Warren, P. B.; . Soft Matter 2019, 15, 278-288]. In the current study, microfluidic channels were used to measure the transport of negatively charged polystyrene colloids in sodium dodecyl sulfate (SDS) surfactant gradients established at SDS concentrations that are either fully above or fully below the CMC. Interpretation of diffusiophoresis was aided by measurements of the colloid electrophoretic mobility as a function of SDS concentration. A numerical transport model incorporating the prior diffusiophoretic mobility model for ionic surfactant gradients was implemented to elucidate signatures of positive and negative diffusiophoretic mobilities and compare with experiments. The theoretically predicted sign of the diffusiophoretic mobility below the CMC was determined to be particularly sensitive to uncertainty in colloid and surfactant properties, while above the CMC, the mobility was consistently predicted to be positive in the SDS concentration range considered in the experiments conducted here. In contrast, experiments only showed signatures of a negative diffusiophoretic mobility for these negatively charged colloids with no change of sign. Colloid diffusiophoretic transport measured in micellar solutions was more extensive than that below the CMC with the same ∇ ln S.

Mechanisms of mTORC1 activation by RHEB and inhibition by PRAS40.

The mechanistic target of rapamycin complex 1 (mTORC1) controls cell growth and metabolism in response to nutrients, energy levels, and growth factors. It contains the atypical kinase mTOR and the RAPTOR subunit that binds to the Tor signalling sequence (TOS) motif of substrates and regulators. mTORC1 is activated by the small GTPase RHEB (Ras homologue enriched in brain) and inhibited by PRAS40. Here we present the 3.0 ångström cryo-electron microscopy structure of mTORC1 and the 3.4 ångström structure of activated RHEB-mTORC1. RHEB binds to mTOR distally from the kinase active site, yet causes a global conformational change that allosterically realigns active-site residues, accelerating catalysis. Cancer-associated hyperactivating mutations map to structural elements that maintain the inactive state, and we provide biochemical evidence that they mimic RHEB relieving auto-inhibition. We also present crystal structures of RAPTOR-TOS motif complexes that define the determinants of TOS recognition, of an mTOR FKBP12-rapamycin-binding (FRB) domain-substrate complex that establishes a second substrate-recruitment mechanism, and of a truncated mTOR-PRAS40 complex that reveals PRAS40 inhibits both substrate-recruitment sites. These findings help explain how mTORC1 selects its substrates, how its kinase activity is controlled, and how it is activated by cancer-associated mutations.

Moderate to Vigorous-intensity Continuous Training versus Highintensity Interval Training for Improving VO2max in Women: A Systematic Review and Meta-analysis.

Traditional continuous training and high-intensity interval training (HIIT) can increase maximal oxygen uptake (V̇O2max). However, there is conflicting evidence regarding which form of training demonstrates the greatest improvements to V̇O2max, and data in women is sparse. We conducted a systematic review and meta-analyses to assess whether moderate to vigorous-intensity continuous training (MVICT) or HIIT was superior at improving V̇O2max in women. Randomised controlled and parallel studies examined the influence of MVICT and/or HIIT on V̇O2max in women. There was no statistical difference in V̇O2max improvements after training between women in the MVICT and HIIT cohorts (mean difference [MD]: -0.42, 95%CI: -1.43 to 0.60, p>0.05). Both MVICT and HIIT increased V̇O2max from baseline (MD: 3.20, 95% CI: 2.73 to 3.67 and MD: 3.16, 95% CI 2.09 to 4.24, respectively, p<0.001). Greater improvements in V̇O2max were observed in women who participated in more training sessions in both training formats. Long-HIIT was superior to short-HIIT protocols at increasing V̇O2max. Although MVICT and long-HIIT sessions elicited greater increases in V̇O2max in younger women compared to short-HIIT protocols, these differences were negligible in older women. Our findings suggest MVICT and HIIT are equally effective strategies for improving V̇O2max and indicate an effect of age on its response to training in women.

Inflammatory molecular endotypes of nasal polyps derived from White and Japanese populations.

BACKGROUND: Emerging evidence suggests that chronic rhinosinusitis with nasal polyps (CRSwNP) is a highly heterogeneous disease with disparate inflammatory characteristics between different racial groups and geographies. Currently, little is known about possible underlying distinguishing factors between these inflammatory differences. OBJECTIVE: Our aim was to interrogate differences in CRSwNP disease between White/non-Asian patients and Japanese patients by using whole transcriptome and single-cell RNA gene expression profiling of nasal polyps (NPs). METHODS: We performed whole transcriptome RNA sequencing with endotype stratification of NPs from 8 White patients (residing in the United States) and 9 Japanese patients (residing in Japan). Reproducibility was confirmed by quantitative PCR in an independent validation set of 46 White and 31 Japanese patients. Single-cell RNA sequencing (scRNAseq) was used to stratify key cell types for contributory transcriptional signatures. RESULTS: Unsupervised clustering analysis identified 2 major endotypes that were present within both cohorts of patients with NPs and had previously been reported at the cytokine level: (1) type 2 endotype and (2) non-type 2 endotype. Importantly, there was a statistically significant difference in the proportion of these endotypes between these geographically distinct subgroups with NPs (P = .03). Droplet-based single-cell RNA sequencing further identified prominent type 2 inflammatory transcript expression: C-C motif chemokine ligand 13 (CCL13) and CCL18 in M2 macrophages, as well as cystatin SN (CST1) and CCL26 in basal, suprabasal, and secretory epithelial cells. CONCLUSION: NPs from both racial groups harbor the same 2 major endotypes, which we have determined to be present in differing ratios between each cohort with CRSwNP disease. Distinct inflammatory and epithelial cells contribute to the type 2 inflammatory profiles observed.

Multi-ligand molecular docking, simulation, free energy calculations and wavelet analysis of the synergistic effects between natural compounds baicalein and cubebin for the inhibition of the main protease of SARS-CoV-2.

Combination drugs have been used for several diseases for many years since they produce better therapeutic effects. However, it is still a challenge to discover candidates to form a combination drug. This study aimed to investigate whether using a comprehensive in silico approach to identify novel combination drugs from a Chinese herbal formula is an appropriate and creative strategy. We, therefore, used Toujie Quwen Granules for the main protease (Mpro) of SARS-CoV-2 as an example. We first used molecular docking to identify molecular components of the formula which may inhibit Mpro. Baicalein (HQA004) is the most favorable inhibitory ligand. We also identified a ligand from the other component, cubebin (CHA008), which may act to support the proposed HQA004 inhibitor. Molecular dynamics simulations were then performed to further elucidate the possible mechanism of inhibition by HQA004 and synergistic bioactivity conferred by CHA008. HQA004 bound strongly at the active site and that CHA008 enhanced the contacts between HQA004 and Mpro. However, CHA008 also dynamically interacted at multiple sites, and continued to enhance the stability of HQA004 despite diffusion to a distant site. We proposed that HQA004 acted as a possible inhibitor, and CHA008 served to enhance its effects via allosteric effects at two sites. Additionally, our novel wavelet analysis showed that as a result of CHA008 binding, the dynamics and structure of Mpro were observed to have more subtle changes, demonstrating that the inter-residue contacts within Mpro were disrupted by the synergistic ligand. This work highlighted the molecular mechanism of synergistic effects between different herbs as a result of allosteric crosstalk between two ligands at a protein target, as well as revealed that using the multi-ligand molecular docking, simulation, free energy calculations and wavelet analysis to discover novel combination drugs from a Chinese herbal remedy is an innovative pathway.

Identification and targeting of novel CDK9 complexes in acute myeloid leukemia.

Aberrant activation of mTOR signaling in acute myeloid leukemia (AML) results in a survival advantage that promotes the malignant phenotype. To improve our understanding of factors that contribute to mammalian target of rapamycin (mTOR) signaling activation and identify novel therapeutic targets, we searched for unique interactors of mTOR complexes through proteomics analyses. We identify cyclin dependent kinase 9 (CDK9) as a novel binding partner of the mTOR complex scaffold protein, mLST8. Our studies demonstrate that CDK9 is present in distinct mTOR-like (CTOR) complexes in the cytoplasm and nucleus. In the nucleus, CDK9 binds to RAPTOR and mLST8, forming CTORC1, to promote transcription of genes important for leukemogenesis. In the cytoplasm, CDK9 binds to RICTOR, SIN1, and mLST8, forming CTORC2, and controls messenger RNA (mRNA) translation through phosphorylation of LARP1 and rpS6. Pharmacological targeting of CTORC complexes results in suppression of growth of primitive human AML progenitors in vitro and elicits strong antileukemic responses in AML xenografts in vivo.

Phytochemistry, pharmacodynamics, and pharmacokinetics of a classic Chinese herbal formula Danggui Beimu Kushen Wan: A review.

Danggui Beimu Kushen Wan (DBKW) is a classic herbal formula for difficult urination and has been widely used for urinary-related disorders and cancers in current clinical practice. This study aimed to comprehensively review the phytochemistry, pharmacodynamics, and pharmacokinetics of DBKW in experimental studies. We searched 21 databases to identify experimental studies of DBKW. We also searched 11 databases to identify and summarize compounds from DBKW's ingredients. A total of 423 studies of DBKW were identified and 15 studies were included. For Angelicae Sinensis Radix (ASR) and Sophorae Flavescentis Radix (SFR), 2,425 and 2,843 studies were identified, and 42 and 33 studies were included, respectively. Eight compounds were found in the whole formula, 408 compounds from ASR, and 277 compounds from SFR. DBKW may have anticancer effects (inhibiting the growth of tumors, regulating cell proliferation, inducing tumor cell apoptosis, suppressing invasion and metastasis of cancer, enhancing the therapeutic effects of chemotherapy, and relieving toxicity of chemotherapy) and have benefits on chronic prostatitis (reducing inflammation, inhibiting oxidation, regulating sex hormone, and stimulating immune system). The pharmacokinetics of the seven primary compounds from DBKW were also summarized. DBKW contains multiple compounds that may act on more than one pathway of the conditions simultaneously.

Oral application of Chinese herbal medicine for allergic rhinitis: A systematic review and meta-analysis of randomized controlled trials.

Chinese herbal medicine (CHM) has long been used for allergic rhinitis (AR). This systematic review aimed to investigate the clinical effects and safety of oral CHM for AR by comparing it to Western medications (WM). Nineteen databases were searched up to May 27, 2020. Randomized controlled trials (RCTs) assessing the effects of CHM on the primary or secondary outcomes comparing to WM, in any age of the patients, were included. The pooled results were expressed as mean difference, standardized mean difference, or odds ratio with 95% confidence intervals. Eighteen RCTs were included and 17 of them were evaluated in the meta-analysis. CHM may improve total nasal symptom scores, individual symptom scores (rhinorrhea, nasal congestion, sneezing, and nasal itching), quality of life, and recurrence rate, compared to antihistamines (loratadine and chlorpheniramine). Only mild and transient adverse events of CHM were reported. However, there were no significant differences in some subgroup analyses in total nasal symptom scores, rhinorrhea, nasal obstruction, sneezing, nasal itching, and SF-36. Due to the small number of included studies, poor quality of trial design, and substantial heterogeneities, the potential of CHM for AR should be validated in large, multicenter, and well-designed RCTs in the future.

Online Reviews in a Major City: Who Will Choose You?

OBJECTIVE: A large factor influencing a patient's choice of aesthetic plastic surgeons is online patient reviews. METHODS/TECHNIQUE: Plastic surgeons whose practices are located in counties within the New York metro area were included. Selected surgeons were divided into private and academic surgeons (defined as having a residency program). For each surgeon, the quantity and quality of their Google reviews were collected. RESULTS/COMPLICATIONS: A total of 145 aesthetic surgeons from the New York area were included in the study, both private (n = 126) and academic (n = 19). Given the small size of the latter cohort, 19 private aesthetic surgeons were randomly selected, and compared with the academic surgeons, it was shown that private surgeons had both higher average quality and quantity of online patient Google reviews (confidence interval, 95%; P = 0.0223). Similar results were found when comparing all private American Society for Aesthetic Plastic Surgery (ASAPS) surgeons (n = 126) with all academic ASAPS surgeons (n = 19); private ASAPS surgeons had a higher average rating and number of reviews when compared with academic surgeons, again representing a statistically significant difference for the quality of online reviews between private and academic surgeons (confidence interval, 95%; P = 0.031975). CONCLUSIONS: There is a statistically significant difference in both the quality and quantity of online ratings for private and academic aesthetic surgeons.

Rumex japonicus Houtt.: A phytochemical, pharmacological, and pharmacokinetic review.

Rumex japonicus Houtt. (RJH-Yang Ti) RJH has been used as a folk medicine in East Asian countries for thousands of years. It has a wide range of therapeutic effects in terms of anti-microorganic, anti-oxidant, anti-inflammatory, and antitumor effects. Therefore, it is urgent to thoroughly review the existing knowledge for this herb from phytochemical, pharmacological, and pharmacokinetic perspectives. "Yang Ti" and its English, botanical and pharmaceutical names used as keywords to perform database search which included the Encyclopaedia of traditional Chinese Medicines, PubMed, EMBASE, AMED, CINAHL, Cochrane Library, MEDLINE, Science Direct, Scopus, Web of Science, and China Network Knowledge Infrastructure. Forty-five compounds identified from RJH. Besides, the therapeutic effects of RJH have been summarized as well. The root of RJH contains derivatives of anthraquinones, phytosterols, nepodin, oxanthrone c-glycosides, phenolic acid, cinnamic acid, flavonoid, epoxynaphthoquinol, triterpenoids, methoxynaphthalene, trihydroxybenzene, anthracene-9,10-dione, and other compounds. The extract of RJH and its chemical compounds showed the potentials as a complementary agent to exert antioxidant, antimicrobial, antisepsis, anticancer, anti-haematological disease, anti-dermatological disease, and antidiabetic activities. For the record, there is no study conducted on RJH regarding its pharmacokinetic aspect. Notably, Emodin may require additional attention due to its multiple organ toxicity concerns.

Mechanisms of Action of Cassiae Semen for Weight Management: A Computational Molecular Docking Study of Serotonin Receptor 5-HT2C.

Overweight and obesity is a growing global health concern. Current management of obesity includes lifestyle intervention, bariatric surgery and medication. The serotonin receptor, 5-HT2C, is known to mediate satiety, appetite and consumption behaviour. Lorcaserin, an appetite control drug, has demonstrated efficacy in appetite control by targeting 5-HT2C but causes undesirable side effects. This study aimed to explore the potential usage of Cassiae semen (CS), a well-known traditional Chinese medicine used to treat obesity. A computational molecular docking study was performed to determine the binding mechanism of CS compounds to the 5-HT2C receptors in both active, agonist-bound and inactive, antagonist-bound conformations. By comparing binding poses and predicted relative binding affinities towards the active or inactive forms of the receptor, we hypothesise that two of the CS compounds studied may be potent agonists which may mimic the appetite suppression effects of lorcaserin: obtusifoliol and cassiaside B2. Furthermore, two ligands, beta-sitosterol and juglanin, were predicted to bind favourably to 5-HT2C outside of the known agonist binding pocket in the active receptor, suggesting that such ligands may serve as positive allosteric modulators of 5-HT2C receptor function. Overall, this study proposed several CS compounds which may be responsible for exerting anti-obesity effects via appetite suppression by 5-HT2C receptor activation.

Phytochemistry, Ethnopharmacology, Pharmacokinetics and Toxicology of Cnidium monnieri (L.) Cusson.

Cnidium monnieri (L.) Cusson (CMC) is a traditional Chinese herbal medicine that has been widely grown and used in Asia. It is also known as "She chuang zi" in China (Chinese: ), "Jashoshi" in Japan, "Sasangia" in Korea, and "Xa sang tu" in Vietnam. This study aimed to provide an up-to-date review of its phytochemistry, ethnopharmacology, pharmacokinetics, and toxicology. All available information on CMC was collected from the Encyclopedia of Traditional Chinese Medicines, PubMed, EMBASE, ScienceDirect, Scopus, Web of Science, and China Network Knowledge Infrastructure. The updated chemical structures of the compounds are those ones without chemical ID numbers or references from the previous review. A total of 429 chemical constituents have been elucidated and 56 chemical structures have been firstly identified in CMC with traceable evidence. They can be categorized as coumarins, volatile constituents, liposoluble compounds, chromones, monoterpenoid glucosides, terpenoids, glycosides, glucides, and other compounds. CMC has demonstrated impressive potential for the management of various diseases in extensive preclinical research. Since most of the studies are overly concentrated on osthole, more research is needed to investigate other chemical constituents.

Traditional medicines for asthma in children and adults: A systematic review of placebo-controlled studies.

BACKGROUND: Traditional medicines (TMs) adjunctive to conventional medications are widely used for asthma in east-Asia and have gained popularity in western countries. OBJECTIVE: To assess the efficacy and safety of TMs for asthma in children and adults based on placebo-controlled trials in order to inform physicians and assist them in discussions with patients. METHODS: Seventeen electronic databases were searched. Participants had acute or chronic asthma. Interventions included orally administered traditional medicines used in east-Asia. Outcomes included lung function, symptoms, quality of life, exacerbations, medication use and safety. RevMan 5.3 (random effect model) was used for meta-analysis. Baseline values were assessed for balance and asthma severity. Within-group changes were calculated to assess minimal clinically important difference (MCID). RESULTS: Eighteen studies (2080 participants) were included. All combined TMs with conventional medicines. The single study of acute asthma (n = 300) showed an improvement. For chronic asthma, severity at baseline ranged from very mild to severe. When asthma was mild, significant differences in lung function (FEV1%, PEF/R) were not detectable. When participants had moderate and/or severe asthma at baseline improvements were more evident. For measures of lung function, improvements within the TM groups tended to be greater when the asthma was more severe. Some studies showed MCIDs. No serious adverse events or interactions were reported but safety data were incomplete. CONCLUSIONS: The application of certain traditional herbal medicines used in east-Asia as adjuncts to conventional medications improved outcomes in acute and chronic asthma, but most evidence was based on single trials. Therefore, no single TM could be recommended. Effect sizes varied according to asthma severity at baseline. Future studies should consider baseline severity when enrolling participants.

Fritillariae Thunbergii Bulbus: Traditional Uses, Phytochemistry, Pharmacodynamics, Pharmacokinetics and Toxicity.

Fritillariae Thunbergii Bulbus (FTB) has been widely used as an antitussive herb for thousands of years in China. However, FTB's traditional uses, chemical compounds and pharmacological activities have not been systematically reviewed. This study aimed to review its traditional uses, phytochemistry, pharmacodynamics, pharmacokinetics and toxicity. We searched the Encyclopedia of Traditional Chinese Medicine to explore the historical records which indicate that it acts to clear heat, resolve phlegm, relieve cough, remove toxicity and disperse abscesses and nodules. We searched 11 databases to identify potential phytochemical or pharmacological studies. Characteristics of its chemical constituents, pharmacological effects, pharmacokinetic and toxicity were descriptively summarized. A total of 9706 studies were identified and 83 of them were included. As a result, 134 chemical constituents were identified, including 26 alkaloids, 29 compounds found in essential oils, 13 diterpenoids, two carbohydrates, two sterols, 18 amino acids, six nucleosides, four nucleobases, four fatty acids, three lignans, and 27 elements. Thirteen pharmacological effects of FTB were identified, including anti-cancer, tracheobronchial relaxation, antitussive, expectorant, anti-muscarinic, anti-inflammation, anti-thyroid, regulation of blood rheology, antiulcer, anti-diarrhea, pain suppression, antioxidation and neuroprotection. These pharmacological activities may be mainly attributed to the alkaloids in FTB. Further phytochemical, pharmacological and network pharmacological studies are recommended.

Topical application of Chinese herbal medicine for atopic eczema: a systematic review with a meta-analysis.

BACKGROUND: Atopic eczema (AE) affects 10-20% of children in industrialised countries. OBJECTIVE: This review systematically evaluated the effects and safety of topical use of Chinese herbal medicine (CHM) for AE. METHODS: Randomised controlled trials on topical use of CHM were identified through searching electronic databases. Their risk of bias was assessed. Meta-analysis was conducted by employing the RevMan 5.2 software. RESULTS: Ten studies involving 1,058 participants were included. These studies had high risk of bias in randomisation, blinding and outcome data. Meta-analysis showed that topical applications of CHM were superior to conventional medications in total effectiveness rate (risk ratio 1.19; 95% confidence interval 1.04 to 1.36). No significant difference was observed in overall skin lesion score (standardised mean difference -0.05; 95% confidence interval -0.88 to 0.78) compared to corticosteroid creams. CONCLUSIONS: There was no conclusive evidence to demonstrate that topical application of CHM for AE was superior to other control interventions due to methodological weaknesses of the included randomised controlled trials.

The utility of three-dimensional modeling and printing in pediatric surgical patient and family education: a systematic review.

BACKGROUND: Three-dimensional (3D) modeling and printing are increasingly being used in surgical settings. This technology has several applications including pre-operative surgical planning, inter-team communication, and patient education and counseling. The majority of research on 3D technology has focused on adult populations, where it has been found to be a useful tool for educating patients across various surgical specialties. There is a dearth, however, of research on the utility of 3D modeling and printing for patient and family education in pediatric populations. Our objective was to systematically review the current literature on how this modality is being utilized in pediatric surgical settings for patient and family education and counselling. METHODS: We conducted a systematic review in accordance with PRISMA and CASP guidelines. The MEDLINE, CINAHL, Embase, and Web of Science databases were searched from inception to October 21, 2023, with no restrictions on language or geographical location. Citation chaining was used to ensure relevant papers were included. Articles were doubly screened and data was extracted independently by two authors. In the case of disagreement, a third author was consulted. Any articles pertaining to 3D modeling and printing in pediatric surgical settings for patient and family education and counseling were included. RESULTS: Six articles met inclusion criteria and were used for qualitative analysis. Two involved questionnaires given to parents of children to assess their understanding of relevant anatomy, surgical procedure, and risks after viewing conventional CT images and again after viewing a 3D-printed model. One involved a quasi-experimental study to assess young patients' pre-operative surgical understanding and anxiety after undergoing conventional teaching as compared to after viewing a 3D storybook. One involved questionnaires given to parents of children in control and study groups to assess the usefulness of 3D printed models compared to conventional CT images in their understanding of relevant anatomy and the surgical procedure. Another study looked at the usefulness of 3D printed models compared to 2D and 3D CT images in providing caregiver understanding during the pre-operative consent process. The last article involved studying the impact of using 3D printing to help patients understand their disease and participate in decision-making processes during surgical consultations. In all six studies, utilizing 3D technology improved transfer of information between surgical team members and their patients and families. CONCLUSION: Our systematic review suggests that 3D modeling and printing is a useful tool for patient and family education and counselling in pediatric surgical populations. Given the very small number of published studies, further research is needed to better define the utility of this technology in pediatric settings.

Exercise training reduces arterial stiffness in women with high blood pressure: a systematic review and meta-analysis.

The acute and long-term benefits of exercise on cardiovascular health are well established, yet the optimal mode of exercise training that improves arterial stiffness in women with high blood pressure remains unclear. The aim of this systematic review and meta-analysis was to assess the influence of aerobic and resistance training on arterial stiffness in women with high blood pressure. After an extensive search of four online databases, six randomized controlled trials met the inclusion criteria and were included in meta-analyses. Data were extracted from six studies examining the influence of exercise on arterial stiffness assessed by pulse wave velocity (PWV) and were expressed as standardized mean difference (SMD). Whereas aerobic exercise significantly reduced arterial PWV in women with high blood pressure after long-term training [SMD -1.87, 95% confidence interval (CI) -2.34 to -1.40], resistance training had a more modest effect that was borderline statistically significant (SMD -0.31, 95% CI -0.65 to 0.03). These findings suggest regular long-term aerobic exercise training (i.e. 12-20 week interventions) reduces arterial stiffness in women with high blood pressure. Although not statistically significant, the modest number of included trials and lack of publication bias encourages further assessments on the efficacy of resistance exercise for improving arterial stiffness in women with high blood pressure. Given the unique benefits of aerobic and resistance training, particularly for postmenopausal women (e.g. bone health and muscular strength), both modes of training should be encouraged for women with high blood pressure to enhance arterial function and support favorable cardiovascular outcomes.

Chatbots as Patient Education Resources for Aesthetic Facial Plastic Surgery: Evaluation of ChatGPT and Google Bard Responses.

Background: ChatGPT and Google Bard™ are popular artificial intelligence chatbots with utility for patients, including those undergoing aesthetic facial plastic surgery. Objective: To compare the accuracy and readability of chatbot-generated responses to patient education questions regarding aesthetic facial plastic surgery using a response accuracy scale and readability testing. Method: ChatGPT and Google Bard™ were asked 28 identical questions using four prompts: none, patient friendly, eighth-grade level, and references. Accuracy was assessed using Global Quality Scale (range: 1-5). Flesch-Kincaid grade level was calculated, and chatbot-provided references were analyzed for veracity. Results: Although 59.8% of responses were good quality (Global Quality Scale ≥4), ChatGPT generated more accurate responses than Google Bard™ on patient-friendly prompting (p < 0.001). Google Bard™ responses were of a significantly lower grade level than ChatGPT for all prompts (p < 0.05). Despite eighth-grade prompting, response grade level for both chatbots was high: ChatGPT (10.5 ± 1.8) and Google Bard™ (9.6 ± 1.3). Prompting for references yielded 108/108 of chatbot-generated references. Forty-one (38.0%) citations were legitimate. Twenty (18.5%) provided accurately reported information from the reference. Conclusion: Although ChatGPT produced more accurate responses and at a higher education level than Google Bard™, both chatbots provided responses above recommended grade levels for patients and failed to provide accurate references.