Constructing Physiological Defense Systems against Infectious Disease with Metal-Organic Frameworks: A Review.

The swift and deadly spread of infectious diseases, alongside the rapid advancement of scientific technology in the past several centuries, has led to the invention of various methods for protecting people from infection. In recent years, a class of crystalline porous materials, metal-organic frameworks (MOFs), has shown great potential in constructing defense systems against infectious diseases. This review addresses current approaches to combating infectious diseases through the utilization of MOFs in vaccine development, antiviral and antibacterial treatment, and personal protective equipment (PPE). Along with an updated account of MOFs used for designing defense systems against infectious diseases, directions are also suggested for expanding avenues of current MOF research to develop more effective approaches and tools to prevent the widespread nature of infectious diseases.

Biomechanical Comparison of Medio-Plantar and Plantar Plate Fixation for First Tarsometatarsal Joint Arthrodesis.

Plantar plate positioning has been demonstrated as biomechanically superior. However, some operators remain resentful about the morbidity of the surgical approach. To provide improved plate fixation for first tarsometatarsal joint arthrodesis with respect to the tibialis anterior tendon, a medio-plantar plate was developed. The purpose of this biomechanical study was to compare its construct stability to that of a plantar plate construct. Twelve pairs of fresh frozen human specimens were used in a matched pair test. Each pair was fixed with a 4 mm compression screw and either a plantar locking plate or a medio-plantar locking plate. A cantilever beam test was performed in dorsiflexion. Before and after cyclic loading (5000 cycles; 40 N), bending stiffness and relative movements at the joint space were monitored in a quasi-static test including optical motion tracking. Maximum load and bending moment to failure were investigated in a load-to-failure ramp test. The bending stiffness of both groups did not significantly differ before (plantar 49.9 N/mm ± 19.2; medio-plantar 53.9 N/mm ± 25.4, p = 0.43) or after (plantar 24.4 N/mm ± 9.7; medio-plantar 35.3 N/mm ± 22.0, p = 0.08) cyclic loading but decreased significantly in both groups (p < 0.01) after cyclic loading. Relative movement increased significantly during cyclic testing in both groups (p < 0.01) but did not differ significantly between the groups before (p = 0.29) or after (p = 0.16) cyclic loading. Neither load nor bending moment to failure were significantly different (plantar 225 N ± 78, 10.8 Nm; medio-plantar 210 N ± 86, 10.1 Nm, p = 0.61). Both plate constructs provided equivalent construct stability, both being well suited for Lapidus arthrodesis.

A novel XPA splice-site mutation identified in a 4-year-old Filipino girl with xeroderma pigmentosum.

We herein report a case of a 4-year-old Filipino girl initially seen through online consultation from a general physician. She was born to a 22-year-old primigravid mother, with no birth complications nor a history of consanguinity in the family. During the 1st month of life, she developed hyperpigmented macules over the face, neck, upper back, and limbs, which were exacerbated by sun exposure. At 2 years old, she developed a solitary erythematous papule on the nasal area, which gradually enlarged within one year and developed into an exophytic ulcerating tumor extending to the right supra-alar crease. Xeroderma pigmentosum and squamous cell carcinoma were confirmed by whole-exome sequencing and skin biopsy, respectively.

Inflammation in Wound Healing and Pathological Scarring.

Significance: The aberrant inflammation during wound healing results in pathological scarring, such as hypertrophic scars and keloids. This adversely affects the quality of life of patients due to the disfiguring appearance as well as the symptoms of itch and pain. This review summarizes the up-to-date knowledge of the immunopathogenesis and treatment options for pathological scars. Recent Advances: With the advent of new technologies, combined with in vitro and in vivo wound models, several inflammatory cells have been shown to have both direct and indirect effects on both wound healing and pathological scarring. Critical Issues: Expansion of pro-fibrotic immune cells such as M2 macrophages, dendritic cells, mast cells, and Th2 cells leads to fibroblast transition to myofibroblasts via transforming growth factor-ß1 signaling pathway. Appropriate management of such inflammatory responses during wound healing remains a critical issue during clinical practice. Future Directions: Regulating inflammation response during wound healing may be a potential therapeutic option for avoiding or reducing pathological scars.

Sometimes Your Heart Says 'I Don't Know': Insights From Parents of Undervaccinated Children.

STUDY OBJECTIVE: To explore drivers of suboptimal vaccination rates by understanding why parents without strong antivaccine beliefs do not fully vaccinate their children. METHODS: Four focus groups were conducted in Washington state with 41 parents of children aged 24 to 48 months who delayed, declined, or missed some but not all vaccines. During the focus groups, parents were asked about reasons their child was undervaccinated, information that might address their concerns, and additional support they needed. Transcripts were analyzed using template analysis with deductive and inductive codes. RESULTS: Focus groups identified multiple reasons for parents deciding to delay or decline vaccines for their children, including issues of individualism and control. The groups emphasized the impact of personal circumstances, such as changes in insurance, on whether children were vaccinated. Our data also shed light on the reasons that parents do vaccinate their children, including school vaccination requirements, negative experiences with vaccine-preventable diseases, and a family tradition of vaccinating. Focus group participants offered suggestions for improving vaccine communication with parents such as having more parent/patient-friendly vaccine information, providing forums to discuss their concerns, and offering vaccination information in advance of well-child appointments. CONCLUSIONS: To achieve the full benefit of vaccines on individual and community health, we need better ways to address vaccine hesitancy and decrease barriers. We suggest that many hesitant parents would benefit from more dialog with health care providers about vaccines, more approachable educational materials, and enforcement of existing policies requiring vaccines in schools and childcare facilities.

Characterisation of Crassicauda fuelleborni nematode infection in Indo-Pacific finless porpoises (Neophocaena phocaenoides) using postmortem computed tomography.

Nematodes of the genus Crassicauda are parasites that infect various body tissues of cetaceans, including the mammary glands which can influence the reproductive output and hence threaten the survival of endangered cetacean populations. In this study, postmortem computed tomography (PMCT) was used to characterise lesions related to Crassicauda fuelleborni infections in stranded Indo-Pacific finless porpoises (Neophocaena phocaenoides) from Hong Kong waters. Using PMCT and subsequently verified by conventional necropsy, Crassicauda-related lesions were found in 52% of finless porpoises examined (n = 13/25), including both males and females. These parasitic lesions were mostly located in the ventral abdominal muscles in both sexes and situated in proximity to the mammary glands in females. C. fuelleborni infections were also found in the male reproductive organs, which to our knowledge have not been reported in this cetacean species previously. PMCT characteristics of the lesions were also correlated with the gross appearance observed at necropsy and the chronicity of the parasitic infections. In conclusion, this study established the use of virtopsy, particularly PMCT, to characterise C. fuelleborni infections in stranded finless porpoises for the first time, which is non-invasive and can be used prior to conventional necropsy to aid disease diagnosis and targeted sampling. This technique can be extended to other species of cetaceans and parasites, as well as being used in the retrospective analysis of past PMCT scans to deepen our understanding of the prevalence, health impacts, and ecological implications of parasitic infection in cetaceans.

Nature and Children's Health: A Systematic Review.

CONTEXT: Daily outdoor play is encouraged by the American Academy of Pediatrics. Existing evidence is unclear on the independent effect of nature exposures on child health. OBJECTIVE: We systematically evaluated evidence regarding the relationship between nature contact and children's health. DATA SOURCES: The database search was conducted by using PubMed, Cumulative Index to Nursing and Allied Health Literature, PsychInfo, ERIC, Scopus, and Web of Science in February 2021. STUDY SELECTION: We followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. In all searches, the first element included nature terms; the second included child health outcome terms. DATA EXTRACTION: Of the 10 940 studies identified, 296 were included. Study quality and risk of bias were assessed. RESULTS: The strongest evidence for type of nature exposure was residential green space studies (n = 147, 50%). The strongest evidence for the beneficial health effects of nature was for physical activity (n = 108, 32%) and cognitive, behavioral, or mental health (n = 85, 25%). Physical activity was objectively measured in 55% of studies, and 41% of the cognitive, behavioral, or mental health studies were experimental in design. LIMITATIONS: Types of nature exposures and health outcomes and behaviors were heterogenous. Risk of selection bias was moderate to high for all studies. Most studies were cross-sectional (n = 204, 69%), limiting our ability to assess causality. CONCLUSIONS: Current literature supports a positive relationship between nature contact and children's health, especially for physical activity and mental health, both public health priorities. The evidence supports pediatricians in advocating for equitable nature contact for children in places where they live, play, and learn.

MORPHOLOGICAL FEATURES OF THE UTERUS IN WOMEN AT DIFFERENT TIME INTERVALS OF THE POSTMORTEM PERIOD AS DIAGNOSTIC CRITERIA FOR ESTABLISHING THE POSTMORTEM INTERVAL.

OBJECTIVE: The aim is to identify the morphological features of the uterus layers in women at different time intervals of the postmortem period as diagnostic criteria for establishing the postmortem interval. PATIENTS AND METHODS: Materials and methods: In the study we used surgical and autopsy material - uterine tissue fragments. All materials were divided into two groups. The 1st group (G 1) included surgical material from women (n=6) who underwent removal of the uterus, or uterus with the appendages due to leiomyoma, uterine prolapse. The 2nd group (G 2) included autopsy material from 42 women with known causes of death and postmortem period (from 24 to 48 hours - 6 cases, from 49 to 72 hours - 7 cases, from 73 to 96 hours - 8 cases, from 97 to 120 hours - 6 cases, from 121 to 144 hours - 8 cases, more than 144 hours - 7 cases). Histological and immunohistochemical study methods were used. RESULTS: Results: A comprehensive morphological study of the women uterus revealed a time-dependent increase of postmortem changes in this organ linked with the increase of postmortem period. In cases of postmortem period duration up to 144 hours, the structural elements of the uterine layers were identified. In cases where the duration of the postmortem period was more than 145 hours, microscopically the uterus was represented by eosinophilic fibrous or dusty masses, the histogenesis of which could not be determined. The processes of autolysis occurred more intensely and faster in the mucous membrane of the uterus, in comparison with the muscular and serous membranes, and in the vessels - in their inner membrane, in comparison with the middle and outer membranes. Autolytic changes in the muscular membrane of the uterus and vascular walls occurred more intensely in muscle fibers compared to connective tissue fibers. CONCLUSION: Conclusions: The histological and immunohistochemical features of the women uterus at different postmortem periods have a certain forensic medical significance and can be used for establishing the postmortem interval.

Frequentist rules for regulatory approval of subgroups in phase III trials: A fresh look at an old problem.

BACKGROUND: The number of Phase III trials that include a biomarker in design and analysis has increased due to interest in personalised medicine. For genetic mutations and other predictive biomarkers, the trial sample comprises two subgroups, one of which, say B+ is known or suspected to achieve a larger treatment effect than the other B-. Despite treatment effect heterogeneity, trials often draw patients from both subgroups, since the lower responding B- subgroup may also gain benefit from the intervention. In this case, regulators/commissioners must decide what constitutes sufficient evidence to approve the drug in the B- population. METHODS AND RESULTS: Assuming trial analysis can be completed using generalised linear models, we define and evaluate three frequentist decision rules for approval. For rule one, the significance of the average treatment effect in B- should exceed a pre-defined minimum value, say ZB->L. For rule two, the data from the low-responding group B- should increase statistical significance. For rule three, the subgroup-treatment interaction should be non-significant, using type I error chosen to ensure that estimated difference between the two subgroup effects is acceptable. Rules are evaluated based on conditional power, given that there is an overall significant treatment effect. We show how different rules perform according to the distribution of patients across the two subgroups and when analyses include additional (stratification) covariates in the analysis, thereby conferring correlation between subgroup effects. CONCLUSIONS: When additional conditions are required for approval of a new treatment in a lower response subgroup, easily applied rules based on minimum effect sizes and relaxed interaction tests are available. Choice of rule is influenced by the proportion of patients sampled from the two subgroups but less so by the correlation between subgroup effects.

A historical perspective on porphyrin-based metal-organic frameworks and their applications.

Porphyrins are important molecules widely found in nature in the form of enzyme active sites and visible light absorption units. Recent interest in using these functional molecules as building blocks for the construction of metal-organic frameworks (MOFs) have rapidly increased due to the ease in which the locations of, and the distances between, the porphyrin units can be controlled in these porous crystalline materials. Porphyrin-based MOFs with atomically precise structures provide an ideal platform for the investigation of their structure-function relationships in the solid state without compromising accessibility to the inherent properties of the porphyrin building blocks. This review will provide a historical overview of the development and applications of porphyrin-based MOFs from early studies focused on design and structures, to recent efforts on their utilization in biomimetic catalysis, photocatalysis, electrocatalysis, sensing, and biomedical applications.

Whole-exome sequencing in the clinical setting: Establishing a foothold for precision medicine in genodermatoses and other diseases

@#The concept of “precision medicine” has been a mainstay in discourses about the future of medicine, although it was not until the completion of the Human Genome Project that genetic associations to Mendelian diseases have risen dramatically. Since genetic variations in most (85%) monogenic or oligogenic diseases reside in exons, whole-exome sequencing (WES) serves as a pivotal tool in the identification of causative variants in genodermatoses and other diseases, leading to efficient and timely diagnosis. Here, we share our current diagnosis protocol for genodermatoses using WES as a first-tier solution. Two cases are presented to demonstrate the process of identifying germline variants and one case for a somatic variant. In the first case, a germline missense mutation in COL7A1 (exon73:c.G6127A) was identified for a patient that presented with clinical symptoms of dystrophic epidermolysis bullosa (DEB). Immunofluorescence study revealed decreased collagen VII expression in the dermal-epidermal junction. In case 2, we detected a germline missense mutation in KRT16 (exon1:c.374A>G) in a patient with palmoplantar keratoderma (PPK) and congenital pachyonychia. Sanger sequencing and segregation analysis confirmed the variant detected in WES. For case 3, a patient with linear nevus comedonicus was found to have a somatic missense mutation in NEK9 (exon4:c.500T>C), which was only detected in the lesional DNA sample. Thus, WES shows great potential as a diagnostic tool for monogenic or oligogenic genodermatoses. Since omics is a technology-driven tool, we expect that reaching precision medicine is ever closer.