Combination of Anterior and Posterior Vaginal Mesh Implants and Delorme Procedure in a 94-year-old female with Pelvic Organ Prolapse.

Pelvic organ prolapse refers to the descent of pelvic floor organs resulting from the weakening of pelvic muscles, fascia and connective tissue. The overall prevalence of pelvic organ prolapse is approximately 41%, including bladder prolapse (25%-34%), uterine prolapse (4%-14%) and rectal prolapse (13%-19%). Various methods are currently employed to repair damaged structures and improve patient symptoms, consequently enhancing their quality of life. This report focuses on a 94-year-old female diagnosed with pelvic organ prolapse, specifically Grade 3 bladder prolapse, Grade 3 uterine prolapse and complete rectal prolapse. A comprehensive surgical treatment was carried out to repair the pelvic organs on all three levels (rectum, uterus and bladder) by combining the Delorme procedure with synthetic graft implants. The surgical outcomes were good, illustrating immediate improvement in symptoms without early complications. A multispeciality approach helps functionally repair pelvic organ prolapse while preserving structural integrity.

Discovery of Clinical Candidate PF-06648671: A Potent γ-Secretase Modulator for the Treatment of Alzheimer's Disease.

Herein, we describe the design and synthesis of γ-secretase modulator (GSM) clinical candidate PF-06648671 (22) for the treatment of Alzheimer's disease. A key component of the design involved a 2,5-cis-tetrahydrofuran (THF) linker to impart conformational rigidity and lock the compound into a putative bioactive conformation. This effort was guided using a pharmacophore model since crystallographic information was not available for the membrane-bound γ-secretase protein complex at the time of this work. PF-06648671 achieved excellent alignment of whole cell in vitro potency (Aß42 IC50 = 9.8 nM) and absorption, distribution, metabolism, and excretion (ADME) parameters. This resulted in favorable in vivo pharmacokinetic (PK) profile in preclinical species, and PF-06648671 achieved a human PK profile suitable for once-a-day dosing. Furthermore, PF-06648671 was found to have favorable brain availability in rodent, which translated into excellent central exposure in human and robust reduction of amyloid ß (Aß) 42 in cerebrospinal fluid (CSF).

Mature beyond their years: young children who escape detection of parasitemia despite living in settings of intense malaria transmission.

Despite having the highest risk of progressing to severe disease due to lack of acquired immunity, the youngest children living in areas of highly intense malaria transmission have long been observed to be infected at lower rates than older children. Whether this observation is due to reduced exposure to infectious mosquito bites from behavioral and biological factors, maternally transferred immunity, genetic factors, or enhanced innate immunity in the young child has intrigued malaria researchers for over half a century. Recent evidence suggests that maternally transferred immunity may be limited to early infancy and that the young child's own immune system may contribute to control of malarial symptoms early in life and prior to the development of more effective adaptive immunity. Prospective studies of active and passive detection of Plasmodium falciparum blood-stage infections have identified young children (<5 years old) who remain uninfected through a defined surveillance period despite living in settings of highly intense malaria transmission. Yet, little is known about the potential immunological basis for this 'aparasitemic' phenotype. In this review, we summarize the observational evidence for this phenotype in field studies and examine potential reasons why these children escape detection of parasitemia, covering factors that are either extrinsic or intrinsic to their developing immune system. We discuss the challenges of distinguishing malaria protection from lack of malaria exposure in field studies. We also identify gaps in our knowledge regarding cellular immunity in the youngest age group and propose directions that researchers may take to address these gaps.

Sex Differences in Clustering Unhealthy Lifestyles Among Survivors of COVID-19: Latent Class Analysis.

BACKGROUND: The COVID-19 pandemic has underscored the significance of adopting healthy lifestyles to mitigate the risk of severe outcomes and long-term consequences. OBJECTIVE: This study focuses on assessing the prevalence and clustering of 5 unhealthy lifestyle behaviors among Vietnamese adults after recovering from COVID-19, with a specific emphasis on sex differences. METHODS: The cross-sectional data of 5890 survivors of COVID-19 in Vietnam were analyzed from December 2021 to October 2022. To examine the sex differences in 5 unhealthy lifestyle behaviors (smoking, drinking, unhealthy diet, physical inactivity, and sedentary behavior), the percentages were plotted along with their corresponding 95% CI for each behavior. Latent class analysis was used to identify 2 distinct classes of individuals based on the clustering of these behaviors: the "less unhealthy" group and the "more unhealthy" group. We examined the sociodemographic characteristics associated with each identified class and used logistic regression to investigate the factors related to the "more unhealthy" group. RESULTS: The majority of individuals (male participants: 2432/2447, 99.4% and female participants: 3411/3443, 99.1%) exhibited at least 1 unhealthy behavior, with male participants being more susceptible to multiple unhealthy behaviors. The male-to-female ratio for having a single behavior was 1.003, but it escalated to 25 for individuals displaying all 5 behaviors. Male participants demonstrated a higher prevalence of combining alcohol intake with sedentary behavior (949/2447, 38.8%) or an unhealthy diet (861/2447, 35.2%), whereas female participants tended to exhibit physical inactivity combined with sedentary behavior (1305/3443, 37.9%) or an unhealthy diet (1260/3443, 36.6%). Married male participants had increased odds of falling into the "more unhealthy" group compared to their single counterparts (odds ratio [OR] 1.45, 95% CI 1.14-1.85), while female participants exhibited lower odds (OR 0.65, 95% CI 0.51-0.83). Female participants who are underweight showed a higher likelihood of belonging to the "more unhealthy" group (OR 1.11, 95% CI 0.89-1.39), but this was not observed among male participants (OR 0.6, 95% CI 0.41-0.89). In both sexes, older age, dependent employment, high education, and obesity were associated with higher odds of being in the "more unhealthy" group. CONCLUSIONS: The study identified notable sex differences in unhealthy lifestyle behaviors among survivors of COVID-19. Male survivors are more likely to engage in unhealthy behaviors compared to female survivors. These findings emphasize the importance of tailored public health interventions targeting sex-specific unhealthy behaviors. Specifically, addressing unhealthy habits is crucial for promoting post-COVID-19 health and well-being.

Innate immune activation restricts priming and protective efficacy of the radiation-attenuated PfSPZ malaria vaccine.

A systems analysis was conducted to determine the potential molecular mechanisms underlying differential immunogenicity and protective efficacy results of a clinical trial of the radiation-attenuated whole sporozoite PfSPZ Vaccine in African infants. Innate immune activation and myeloid signatures at pre-vaccination baseline correlated with protection from Pf parasitemia in placebo controls. These same signatures were associated with susceptibility to parasitemia among infants who received the highest and most protective PfSPZ Vaccine dose. Machine learning identified spliceosome, proteosome, and resting dendritic cell signatures as pre-vaccination features predictive of protection after highest-dose PfSPZ vaccination, whereas baseline CSP-specific IgG predicted non-protection. Pre-vaccination innate inflammatory and myeloid signatures were associated with higher sporozoite-specific IgG Ab response but undetectable PfSPZ-specific CD8+ T-cell responses post-vaccination. Consistent with these human data, innate stimulation in vivo conferred protection against infection by sporozoite injection in malaria-naïve mice while diminishing the CD8+ T-cell response to radiation-attenuated sporozoites. These data suggest a dichotomous role of innate stimulation for malaria protection and induction of protective immunity of whole-sporozoite malaria vaccines. The uncoupling of vaccine-induced protective immunity achieved by Abs from more protective CD8+ T cell responses suggest that PfSPZ Vaccine efficacy in malaria-endemic settings may be constrained by opposing antigen presentation pathways.

Impact of Various Concentrations of Low-Dose Atropine on Pupillary Diameter and Accommodative Amplitude in Children with Myopia.

Purpose: To assess over 2 weeks, the effect of 3 different low concentrations of atropine on pupillary diameter and accommodative amplitude in children with myopia. Methods: Fifty-eight children with myopia [spherical equivalent (SE) of -0.50 diopters (D) or worse, astigmatism of less than or equal to 2.00 D] were randomly allocated to 3 groups receiving 0.01%, 0.02%, or 0.03% atropine eye drops, once nightly for 2 weeks. The primary outcome was the change from baseline in pupillary diameter and accommodative amplitude with each of the concentrations. Results: Fifty-seven participants (114 eyes), aged between 6 and 12 years, completed the 2-week trial (mean age 9.3 ± 1.7 years and mean SE -3.53 ± 1.79 D). After 2 weeks of use, all the 3 concentrations were found to have a statistically significant effect on both the pupillary diameter and accommodative amplitude. Accommodative amplitude reduced by an average of 5.23 D, 9.28 D, and 9.32 D, and photopic pupil size increased by an average of 0.95 ± 1.05 mm, 1.65 ± 0.93 mm, and 2.16 ± 0.88 mm with 0.01%, 0.02%, and 0.03%, respectively. Of the eyes, a total of 5.3% and 5.9% of the eyes on 0.02% and 0.03% atropine had a mean residual accommodative amplitude of <5 D. The percentage of eyes having a pupillary dilation >3 mm were 4.8%, 10.5%, and 23.5% for 0.01%, 0.02%, and 0.03% atropine, respectively. Conclusions: Low-dose atropine had an effect on pupillary diameter and accommodative amplitude. With the highest concentration assessed, that is, 0.03% nearly 1 of 4 eyes had pupillary dilation of >3 mm. Clinical Trial Registration number: NCT03699423.

Piezoelectric and Dielectric Electrospun Fluoropolymer Membranes for Oral Mucosa Regeneration: A Comparative Study.

Wound healing of the oral mucosa is an urgent problem in modern dental surgical practice. This research article presents and compares the findings of the investigations of the structural, physicochemical, and biological characteristics of two types of polymeric membranes used for the regeneration of oral mucosa. The membranes were prepared from poly(tetrafluoroethylene) (PTFE) and a copolymer of vinylidene fluoride and tetrafluoroethylene (VDF-TeFE) and analyzed via scanning electron microscopy, atomic force microscopy, X-ray diffraction analysis, and Fourier transform infrared spectroscopy. Investigation results obtained indicate that both types of membranes are composed of thin fibers: (0.57 ± 0.25) µm for PTFE membranes and (0.43 ± 0.14) µm for VDF-TeFE membranes. Moreover, the fibers of VDF-TeFE membranes exhibit distinct piezoelectric properties, which are confirmed by piezoresponse force microscopy and X-ray diffraction. Both types of membranes are hydrophobic: (139.7 ± 2.5)° for PTFE membranes and (133.5 ± 2.0)° for VDF-TeFE membranes. In vitro assays verify that both membrane types did not affect the growth and division of mice fibroblasts of the 3T3-L1 cell line, with a cell viability in the range of 88-101%. Finally, in vivo comparative experiments carried out using Wistar rats demonstrate that the piezoelectric VDF-TeFE membranes have a high ability to regenerate oral mucosa.

Unsteady wetting of soft solids.

HYPOTHESIS: Spreading of liquids on soft solids often occurs intermittently, i.e., the liquid's wetting front switches between sticking and slipping. Studies of this so-called stick-slip wetting on soft solids mostly are confined within quasi-static or forced spreading conditions. In these situations, because the sticking duration is set much larger than the viscoelastic relaxation time of the solid, a ridge is persistently and fully developed at the wetting front as the soft solid yields to the liquid's surface tension. The sticking duration and spreading velocity, therefore, were shown to have little impact to the contact angle change required for stick-to-slip transitions. For unsteady wetting of soft solids, a commonly encountered but largely unexplored situation, we hypothesize that the stick-to-slip transition is controlled not only by a combination of sticking duration and the spreading velocity, but also by an increasing depinning threshold caused by the growing ridge at the wetting front. EXPERIMENT: We performed unsteady wetting experiment on soft solids by letting water droplets spread freely on soft solid surfaces of various stiffness. We capture both the stick-slip spreading behavior and growing wetting ridges using synchronous high-speed imaging and high-speed interferometry. Recorded data of liquid spreading and solid deforming at the wetting front were analyzed to shed light on the relation between stick-slip characteristics and the growing wetting ridge. FINDINGS: We find that intermittent wetting on a soft solid surface results from a competition between three key factors: liquid inertia, capillary force change during sticking, and growing pinning force caused by the solid's viscoelastic response. We theoretically formulate their quantitative contributions to predict how stick-to-slip transitions occur, i.e., how the contact angle change and sticking duration depend on the liquid's spreading velocity and the solid's viscoelastic characteristics. This provides a mechanistic understanding and methods to control unsteady wetting phenomena in diverse applications, from tissue engineering and fabrication of flexible electronics to biomedicine.

Isotype switching in human memory B cells sets intrinsic antigen-affinity thresholds that dictate antigen-driven fates.

Memory B cells (MBCs) play a critical role in protection against homologous and variant pathogen challenge by either differentiating to plasma cells (PCs) or to germinal center (GC) B cells. The human MBC compartment contains both switched IgG+ and unswitched IgM+ MBCs; however, whether these MBC subpopulations are equivalent in their response to B cell receptor cross-linking and their resulting fates is incompletely understood. Here, we show that IgG+ and IgM+ MBCs can be distinguished based on their response to κ-specific monoclonal antibodies of differing affinities. IgG+ MBCs responded only to high-affinity anti-κ and differentiated almost exclusively toward PC fates. In contrast, IgM+ MBCs were eliminated by apoptosis by high-affinity anti-κ but responded to low-affinity anti-κ by differentiating toward GC B cell fates. These results suggest that IgG+ and IgM+ MBCs may play distinct yet complementary roles in response to pathogen challenge ensuring the immediate production of high-affinity antibodies to homologous and closely related challenges and the generation of variant-specific MBCs through GC reactions.

Chemical tools for the Gid4 subunit of the human E3 ligase C-terminal to LisH (CTLH) degradation complex.

We have developed a novel chemical handle (PFI-E3H1) and a chemical probe (PFI-7) as ligands for the Gid4 subunit of the human E3 ligase CTLH degradation complex. Through an efficient initial hit-ID campaign, structure-based drug design (SBDD) and leveraging the sizeable Pfizer compound library, we identified a 500 nM ligand for this E3 ligase through file screening alone. Further exploration identified a vector that is tolerant to addition of a linker for future chimeric molecule design. The chemotype was subsequently optimized to sub-100 nM Gid4 binding affinity for a chemical probe. These novel tools, alongside the suitable negative control also identified, should enable the interrogation of this complex human E3 ligase macromolecular assembly.

Outcomes of Scleral Buckling After Failed Pneumatic Retinopexy.

Purpose: To assess the visual and anatomic outcomes of eyes that had secondary scleral buckle (SB) surgery after unsuccessful pneumatic retinopexy (PR) for rhegmatogenous retinal detachment (RRD). Methods: A retrospective study, performed over a 12-year period, comprised patients who had secondary SB procedures after failed primary PR. Clinical parameters (eg, best-corrected visual acuity [BCVA], lens status, macula status, details of RRD and subretinal fluid) were assessed at presentation, before additional procedures, and at follow-up (6 months, 1 year, and last visit). Statistical comparisons were made using Brown-Forsythe and Welch analysis-of-variance tests, with significance levels set at P < .05. Results: Fifty-four eyes with adequate follow-up were included. Forty-four (81.5%) of 54 eyes had successful retinal reattachment with secondary SB alone. The remaining eyes had subsequent pars plana vitrectomy (PPV). Patients presenting with macula-on RRD who had successful secondary SB had no statistically significant change in BCVA from baseline (mean final, 0.23 ± 0.25 logMAR [Snellen 20/34]; P = .999). There was a statistically significant improvement in BCVA in patients presenting with macula-off RRD who had successful secondary SB (mean final, 0.32 ± 0.36 logMAR [20/42]; P < .001 and mean change, -1.06 ± 0.85 logMAR). Ten patients presenting with macula-off RRD who had failed secondary SB had a significant improvement in the final BCVA (mean final, 0.22 ± 0.28 logMAR [20/33]; P = .044), despite the need for an additional PPV to achieve reattachment. Conclusions: Secondary SB remains a good option for RRD repair after unsuccessful PR and may avoid the need for PPV.

Subclinical Inflammation in Asymptomatic Schoolchildren With Plasmodium falciparum Parasitemia Correlates With Impaired Cognition.

BACKGROUND: Subclinical inflammation and cognitive deficits have been separately associated with asymptomatic Plasmodium falciparum infections in schoolchildren. However, whether parasite-induced inflammation is associated with worse cognition has not been addressed. We conducted a cross-sectional pilot study to better assess the effect of asymptomatic P. falciparum parasitemia and inflammation on cognition in Kenyan schoolchildren. METHODS: We enrolled 240 children aged 7-14 years residing in high malaria transmission in Western Kenya. Children performed five fluid cognition tests from a culturally adapted NIH toolbox and provided blood samples for blood smears and laboratory testing. Parasite densities and plasma concentrations of 14 cytokines were determined by quantitative PCR and multiplex immunoassay, respectively. Linear regression models were used to determine the effects of parasitemia and plasma cytokine concentrations on each of the cognitive scores as well as a composite cognitive score while controlling for age, gender, maternal education, and an interaction between age and P. falciparum infection status. RESULTS: Plasma concentrations of TNF, IL-6, IL-8, and IL-10 negatively correlated with the composite score and at least one of the individual cognitive tests. Parasite density in parasitemic children negatively correlated with the composite score and measures of cognitive flexibility and attention. In the adjusted model, parasite density and TNF, but not P. falciparum infection status, independently predicted lower cognitive composite scores. By mediation analysis, TNF significantly mediated ~29% of the negative effect of parasitemia on cognition. CONCLUSIONS: Among schoolchildren with PCR-confirmed asymptomatic P. falciparum infections, the negative effect of parasitemia on cognition could be mediated, in part, by subclinical inflammation. Additional studies are needed to validate our findings in settings of lower malaria transmission and address potential confounders that could affect both inflammation and cognitive performance.

Severe Pneumonia Caused by Respiratory Syncytial Virus and Adenovirus in Children from 2 to 24 Months at Children's Hospital 1 in Ho Chi Minh City, Vietnam.

In Vietnam, due to the lack of facilities to detect respiratory viruses from patients' specimens, there are only a few studies on the detection of viral pathogens causing pneumonia in children, especially respiratory syncytial virus (RSV) and adenovirus (Adv). Here, we performed a cross-sectional descriptive prospective study on 138 children patients from 2 to 24 months old diagnosed with severe pneumonia hospitalized at the Respiratory Department of Children's Hospital 1 from November 2021 to August 2022. The number of patients selected in this study was based on the formula n = ([Z(1 - α/2)]2 × P [1 - P])/d2, with α = 0.05, p = 0.5, and d = 9%, and the sampling technique was convenient sampling until the sample size was met. A rapid test was used to detect RSV and Adv from the nasopharyngeal swabs and was conducted immediately after the patient's hospitalization. Laboratory tests were performed, medical history interviews were conducted, and nasotracheal aspirates were collected for multiplex real-time PCR (MPL-rPCR) to detect viral and bacterial pathogens. The results of the rapid test and the MPL-rPCR in the detection of both pathogens were the same at 31.9% (44/138) for RSV and 8.7% (7/138) for Adv, respectively. Using MPL-rPCR, the detection rate was 21% (29/138) for bacterial pathogens, 68.8% (95/138) for bacterial-viral co-infections, and 6.5% (9/138) for viral pathogens. The results showed few distinctive traits between RSV-associated and Adv-associated groups, and the Adv group children were more prone to bacterial infection than those in the RSV group. In addition, the Adv group experienced a longer duration of treatment and a higher frequency of re-hospitalizations compared to the RSV group. A total of 100% of Adv infections were co-infected with bacteria, while 81.82% of RSV co-infected with bacterial pathogens (p = 0.000009). This study might be one of the few conducted in Vietnam aimed at identifying viral pathogens causing severe pneumonia in children.

Fracture behaviour assessment of high-performance fibre-reinforced concrete at high strain rates using interpretable modelling approaches.

High-performance fibre-reinforced concrete (HPFRC), a type of cementitious composite material known for its exceptional mechanical performance, has widespread applications in structures exposed to severe dynamic loading conditions. However, understanding nonlinear HPFRC fracture behaviour, particularly under high strain rates, remains challenging given the complexities of assessment procedures and cost-intensive nature of experiments. This study presents an interpretable framework for modelling and analysing HPFRC fracture strength at high strain rates. A wide range of machine learning methods, including ensemble techniques, were employed to capture multivariate effects of eight essential input features (e.g., mortar compressive strength, fibre physical and mechanical properties, cross-sectional area, and strain rate) on fracture strength response. To assess the derived models, a novel evaluation procedure was proposed involving a data-based analysis, employing established metrics (i.e., coefficient of determination, root mean squared error, and mean absolute error via K-fold cross-validation) and a domain experts-involved evaluation utilising global sensitivity analysis to discern first-order and higher-order interactions among input factors. The proposed approach efficiently yielded both quantitative and qualitative insights into crucial input factors governing HPFRC fracture strength with limited experimental data. The obtained findings highlight the significance of multivariate effects, such as the interaction between strain rate and fibre tensile strength, and between fibre volume and fibre diameter, on fracture behaviour. The proposed interpretable framework aims to provide a powerful tool for proactive material failure analysis by understanding fracture behaviour and identifying potential weak and strong interactions among input factors of HPFRC-based samples. Moreover, the utilisation of the proposed approach enables researchers and civil engineers to efficiently focus on the most critical input parameters during the early design stage and ensuring the structural integrity and safety of HPFRC-based constructions.

Anti-inflammatory effect of Piper longum L. fruit methanolic extract on lipopolysaccharide-treated RAW 264.7 murine macrophages.

Context: The Piper species was studied several potential properties such as anti-tumor, anti-inflammatory and antioxidant activity. However, the specific anti-inflammatory activity of the extract from the fruits of P. longum L. has not been investigated. Objectives: Our study want to examine the anti-inflammatory effects of P. longum L. fruit methanolic extracts (PLE) on lipopolysachharide (LPS)-stimulated RAW 264.7 murine macrophages to understand the mechanism of this effect. Method: This study examined the chemical profiling of PLE by LC-HRMS analysis and measured the presence of nitric oxide (NO), interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF-α) in the supernatant using the Griess reagent assay and enzyme-linked immunosorbent assay (ELISA), respectively. The mRNA expression of IL-6, TNF-α, cyclooxygenase-2 (COX-2), and inducible nitric oxide synthase (iNOS) were evaluated by using real-time quantitative polymerase chain reaction (RT-qPCR). Furthermore, the protein expression of COX-2, iNOS and the phosphorylation of MAPK family, c-Jun N-terminal kinase (JNK), p38 in protein level were observed by western blotting. Result: PLE have detected 66 compounds which belong to different classes such as alkaloids, flavonoids, terpenoids, phenolics, lactones, and organic acids inhibited nitric oxide products with the IC50 = 28.5 ± 0.91 µg/mL. Moreover, PLE at 10-100 µg/mL up-regulate HO-1 protein expression from 3 to 10 folds at 3 h. It also downregulated the mRNA and protein expression of iNOS, COX-2, decreased IL-6 and TNF-α secretion by modulating the mitogen-activated protein kinase (MAPK) signaling pathway, specifically by decreasing the phosphorylation of p38 and JNK. Conclusion: These results shown chemical profiling of PLE and demonstrated that PLE exhibits anti-inflammatory effects by regulating the MAPK family and could be a potential candidate for the treatment of inflammatory diseases.

Early Experience with the Senhance Surgical System in Bariatric Surgery.

Background and Objectives: Robotic-assisted surgery advancements have paralleled growing bariatric surgery demands. The Senhance robotic platform offers an alternative to the da Vinci surgical system but there are limited studies evaluating the Senhance system in bariatric surgery. This study aims to review a single surgeon's experience comparing outcomes between traditional laparoscopic and Senhance-assisted sleeve gastrectomy. Materials and Methods: All sleeve gastrectomies performed laparoscopically, Senhance-assisted, or da Vinci-assisted by a single surgeon at an academic center from January 2019 to July 2021 were retrospectively reviewed. Primary outcomes and quality measures were 30-day complications, operative times and length of stay. Results: A total of 268 patients, including 162 laparoscopic, 92 Senhance, and 14 da Vinci cases, were included. Operative times were significantly longer with Senhance (115.7 min) and da Vinci (122.7 min), compared to laparoscopic (94.8 min, P < .0001). Length of stay (measured in days) was significantly longer in the Senhance (1.8) and da Vinci (2.2) groups compared to laparoscopic cases (1.5, P < .0001). These differences remained significant after controlling for age, sex and body mass index. 30-day complication rates were 8.7% (n = 8) in the Senhance group, 7.1% (n = 1) in the da Vinci group and 2.5% (n = 4) in the laparoscopic group (P = .0567). Conclusion: Senhance-assisted sleeve gastrectomy is safe in bariatric surgery and comparable to laparoscopic sleeve gastrectomy with respect to 30-day complications.

Detection of gene mutation in the prognosis of a patient with arrhythmogenic right ventricular cardiomyopathy: a case report.

BACKGROUND: Arrhythmogenic right ventricular cardiomyopathy (ARVC), or more recently known as arrhythmogenic cardiomyopathy (ACM), is an heritable disorder of the myocardium characterized by progressive fibrofatty replacement the heart muscle and risk of ventricular arrhythmias and sudden cardiac death (SCD). We report a case study to demonstrate the role of gene mutation detection in risk stratification for primary prevention of SCD in a young patient diagnosed with ARVC. CASE PRESENTATION: A 15-year-old Asian (Vietnamese) male patient with no history of documented tachyarrhythmia or syncope and a family history of potential SCD was admitted due to palpitations. Clinical findings and work-up including cardiac magnetic resonance imaging (MRI) were highly suggestive of ARVC. Gene sequencing was performed for SCD risk stratification, during which PKP2 gene mutation was found. Based on the individualized risk stratification, an ICD was implanted for primary prevention of SCD. At 6 months post ICD implantation, the device detected and successfully delivered an appropriate shock to terminate an episode of potentially fatal ventricular arrhythmia. ICD implantation was therefore proven to be appropriate in this patient. CONCLUSIONS: While gene mutations are known to be an important factor in the diagnosis of ARVC according to the 2010 Task Force Criteria and recent clinical guidelines, their role in risk stratification of SCD remains controversial. Our case demonstrated that when used with other clinical factors and family history, this information could be helpful in identifying appropriate indication for ICD implantation.

Nanoparticles as carriers of photosensitizers to improve photodynamic therapy in cancer.

Photodynamic therapy (PDT) has emerged as a promising non invasive therapeutic approach for cancer treatment, offering unique advantages over conventional treatments. The combination of light activation and photosensitizing agents allows for targeted and localized destruction of cancer cells, reducing damage to surrounding healthy tissues. In recent years, the integration of nanoparticles with PDT has garnered significant attention due to their potential to enhance therapeutic outcomes. This review article aims to provide a comprehensive overview of the current state-of-the-art in utilizing nanoparticles for photodynamic therapy in cancer treatment. We summarized various nanoparticle-based approaches, their properties, and their implications in optimizing PDT efficacy, and discussed challenges and prospects in the field.

Desilification of phytolith exacerbates the release of arsenic from rice straw.

Arsenic (As) turnover in rice paddy agro-ecosystems has received much attention because As can enter the food chain through its accumulation in rice, thereby affecting human health. Returning straw to soil is a common practice to retain nutrients for soil and crops, but it also cycles As within the rice paddy field ecosystems. However, there is still a lack of detailed understanding of the fate of As in rice straw, and how or to what extent it is recycled back into the soil environment. This study aims to elucidate the relationship between the microstructure of rice straw and the release of As during rice straw decomposition. The microstructure of rice straw was found to comprise both organic and silica (phytolith) components. These two constituents are inter-embedded to form a composite-like structure that contains up to 6.48 mg As Kg-1. The 30-day batch experiments revealed that the biochemical release of As simultaneously depends upon the decomposition of the organic component and the desilicification of the silica component. Accompanying the release of As was the release of other elements such as Fe, Al, P and S. These elements can further interact with As to form less mobile compounds. The introduction of either Trichoderma harzianum or Bacillus velezensis was expected to accelerate the decomposition of rice straw, and enhance the silica dissolution, hence contributing to an increase in the As release. Despite these expectations, our observations showed the opposite effects. Microorganisms presumably have facilitated the change in solution chemistry or the inclusion of As into the newly-formed precipitates. The biochemical decomposition process can reduce straw particle size, while the negatively-charge surface will involve microsized straw particles in the electrostatic interaction, thereby favoring the dispersibility state. Therefore, the co-transport of micro-sized straw particles with As under field conditions should not be neglected.