The doublecortin (DCX) gene encodes DCX, a microtubule-associated protein that plays a crucial role in brain development. DCX variants can disrupt microtubule binding and stabilization, interfere with intracellular transport, and affect post-translational modifications. A correlation exists between variant types and clinical severity. Animal models and induced pluripotent stem cell (iPSC) models simulating DCX deficiency revealed the dynamic progression of the disease, which has provided a powerful tool for investigating disease mechanisms and screening therapeutic agents. Currently there is no cure for DCX variants, with treatment primarily relying on anti-epileptic drugs and symptom management. Basic research is now offering new avenues for future therapeutic approaches. This article has summarized the potential pathogenic mechanisms and therapeutic strategies for the DCX variants, with an aim to provide insights for clinical treatment.
Humans ; Doublecortin Protein ; Doublecortin Domain Proteins ; Animals ; Neuropeptides/metabolism* ; Microtubule-Associated Proteins/metabolism* ; Mutation

The pathogenesis of Parkinson's disease is closely related to genetic factors. This article has systematically reviewed the research progress of molecular genetic mechanism on Parkinson's disease by focusing on the role of six high-penetrance pathogenic genes (SNCA, LRRK2, PRKN, PINK1, PARK7, and VPS35) and some risk genes (such as GBA1). These genetic variants eventually converge in three core pathogenic biological pathways, including lysosomal-autophagy pathway disorder, mitochondrial quality control disorder and α-synuclein metabolic abnormality. In-depth understanding of these molecular mechanisms is of great significance for the development of targeted therapy and realization of precision medicine for this disease.
Humans ; Parkinson Disease/metabolism* ; alpha-Synuclein/genetics* ; Leucine-Rich Repeat Serine-Threonine Protein Kinase-2/genetics* ; Genetic Predisposition to Disease ; Protein Kinases/genetics* ; Animals ; Glucosylceramidase/genetics* ; Ubiquitin-Protein Ligases/genetics*

BACKGROUND

Myiasis is a parasitic infestation of humans caused by dipteran flies' larvae, which feed on the host's tissue. It affects various body parts, including the skin, eyes, ears, nose, mouth, and gastrointestinal tract. Cutaneous myiasis is the most common clinical form, while wound myiasis is the main manifestation. Myiasis can be caused by various fly families, including blowflies, flesh flies, and botflies, with different types depending on the site and infestation type. A rare occurrence rarely reported in medical literature, Sarcophaga species infestation within a tracheostomy tube in a patient with laryngeal carcinoma, is presented in this case. Given that the airway is protected and has built-in barriers against external contamination, the presence of flesh flies (Sarcophaga spp.) at a tracheostomy site is extremely uncommon. By showing how weakened respiratory structures, along with particular environmental and patient factors, may make people more susceptible to this uncommon parasitic complication, this report adds to our understanding of the condition. Recognizing such atypical infestations is crucial for clinicians in early diagnosis, prevention, and effective management of similar cases.

CASE PRESENTATION

The study details a rare instance of Sarcophaga species myiasis in a tracheostomy tube in a patient who Had laryngeal carcinoma after radiation therapy. The 71-year-old farmer patient first complained of pruritus, localized warmth, and tightness in his neck. Prior tracheostomy excision and cobalt therapy were part of his medical history. After being treated for pneumonia, the patient experienced severe bleeding at the tracheostomy site, which led to additional testing. Many larvae were seen emerging from necrotic tissues during clinical examination, which raised the possibility of myiasis. Sarcophaga spp., a rare discovery in respiratory structures, were confirmed to be present by species identification. More than 100 larvae were removed during the emergency surgical procedure, which also involved replacing the compromised tracheostomy tube and cutting and draining necrotic areas. Following surgery, there were no more bleeding or reinfestation episodes, and the patient showed signs of stable recovery.

CONCLUSION

The parasitic infestation known as myiasis, which is brought on by dipteran fly larvae, is usually linked to exposed wounds and weakened tissue. Flesh flies, or Sarcophaga species, are drawn to recently opened, exudative wounds, which makes them more likely to infest susceptible people. Although myiasis commonly occurs in cutaneous wounds, ocular, and nasopharyngeal sites, it is extremely uncommon to occur in tracheostomy incisions, especially in tropical areas like the Philippines. The need for increased clinical awareness of this uncommon complication is highlighted by this case, which shows an unusual manifestation of Sarcophaga species myiasis within a tracheostomy tube of a patient who had laryngeal carcinoma following radiation therapy. Prioritizing preventive measures, such as thorough wound hygiene, efficient fly control techniques, and ongoing postoperative monitoring, is necessary due to the grave consequences of tracheostomy-associated myiasis. Parasitic infestations are more likely to occur in patients recuperating from head and neck surgery, especially those who have had extended wound exposure. Patient outcomes can be improved and morbidity can be considerably decreased by teaching family members and caregivers about wound surveillance, early detection, and prompt intervention. To reduce the chance of infestation, preventive measures like appropriate wound dressing, environmental sanitation, and fly management must be strengthened. In order to develop more focused preventive measures, more research is necessary to identify the endemic distribution of rare myiasis-causing species and to characterize them. Clinicians can establish more efficient management procedures by identifying particular environmental factors and patient vulnerabilities that contribute to atypical myiasis cases. The knowledge gathered from this report adds to the body of knowledge on tracheostomy-associated myiasis and is a useful
guide for early detection and treatment of similar cases.

Human ; Animals ; Male ; Female ; Aged: 65-79 Yrs Old ; Research Report ; Patients ; Carcinoma ; Sarcophagidae ; Tracheostomy

BACKGROUND AND OBJECTIVES

Orthodontic tooth movement is driven by bone remodeling influenced by systemic factors, including caffeine and ethanol. This study aimed to investigate the effects of caffeine and ethanol on the expression of Receptor Activator of Nuclear Factor κβ (RANK) and Osteoprotegerin (OPG), key bone remodeling biomarkers, during orthodontic tooth movement.

METHODS

A laboratory experimental study was conducted on 30 male Wistar rats divided into three groups: K1 (orthodontic force only), K2 (force + caffeine), and K3 (force + ethanol). Orthodontic force was applied using Ni-Ti coil springs. Caffeine and ethanol were administered orally daily. On days 7 and 14, maxillary tissues were collected and analyzed via immunohistochemistry for RANK and OPG expression. Data were analyzed using One-Way ANOVA and Independent Sample T-tests with significance at pRESULTS

Caffeine and ethanol administration increased RANK and OPG expression compared to controls; however, only the ethanol group showed a significant increase in RANK expression on day 14 (p = 0.044). OPG expression was significantly higher in treatment groups at both time points (pCONCLUSION

Caffeine and ethanol modulate bone remodeling marker expression during orthodontic force application, with ethanol significantly increasing RANK expression at later stages. Further studies are needed to clarify the clinical implications for orthodontic treatment.

Animals ; Tooth Movement Techniques ; Tooth Movement ; Osteoprotegerin ; Role ; Movement ; Ethanol ; Bone Remodeling ; Caffeine ; Immunohistochemistry

OBJECTIVE

Given that rabies remains endemic in the Philippines despite government interventions and the pandemicrelated restrictions have hampered its surveillance, this study aimed to estimate the effect of human population, anti-rabies vaccination efforts, and COVID-19 situation on the spread of rabies cases in the districts of Davao City, Philippines.

METHODS

A retrospective study of the canine records at Davao City Veterinarians’ Office was done from January 2018 to June 2021. Monthly rabies cases were ascertained, and the effect of the human population, COVID-19 season, and vaccination ratio on rabies cases was estimated using panel regression models adjusting for confounding factors.

RESULTS

The reporting of rabies cases was lower during COVID-19 than during the non-COVID-19 season, with an IRR of 0.52 [95% confidence interval (CI): 0.33–0.82]. Furthermore, rabies cases increased by 2.23% (95% CI: 0.60–3.89) per 1% increase in vaccination ratio. Additionally, high-population districts recorded more rabies cases than low-population districts.

CONCLUSION

Consistency in monitoring rabies cases during the pandemic is suggested as a roadmap for future program initiatives. Vaccination efforts should be reinforced to increase rabies awareness and ensure early response to emerging diseases. Moreover, highpopulated districts should be prioritized in implementing rabies control interventions to gain optimal development.

Human ; Animals ; Rabies ; Covid-19 ; Vaccination

BACKGROUND AND OBJECTIVE

Rabies continues to be a challenge in Davao City despite the efforts of the city’s local government to vaccinate primarily the non-stray dog population. Meanwhile, studies have shown that time-dependent vaccination strategy is considered a prime factor for a cost-effective rabies control strategy. Hence, this study aims to provide information that will determine the optimal vaccination strategy targeted to the stray dog population that minimizes the rabies-infected dog population and vaccination costs using optimal control theory (OCT).

METHODS

OCT is used to identify the optimal level of key rabies control, i.e., vaccination. Here, OCT was applied to a modified Susceptible-Exposed-Infectious-Vaccinated (SEIV) compartmental model. The study's key parameters were derived from published articles on rabies in Davao City and similar regions, along with the city's rabies reports.

RESULTS

The findings revealed that while rabies remains endemic in the city, it is possible to reduce the number of cases through consistent implementation of vaccination programs to the exposed and susceptible dog populations. Nevertheless, the feasibility of these findings relies to the effective targeting of vaccine coverage for the dog population. From the simulations performed, the exposed dog population (i.e., pre-rabid dogs) was able to reach zero observation when the transmission rate (?) is 0.001 for all values of anti-rabies vaccine coverages for exposed (?) and susceptible (b) dog populations and ? = 0.01 only when ? = 0.7 and b = 0.7, ? = 0.7 and b = 0.5, and ? = 0.5 and b = 0.7. Consequently, the number of infectious dogs will thereby decrease. Moreover, a nonlinear correspondence was also observed in all scenarios between the vaccination rate and the number of rabies-exposed dogs such that the reduction in the incidence of rabies cases becomes apparent only when the vaccination rate is at least 0.9995.

CONCLUSION

In high rabies transmissibility scenarios, a time-dependent vaccination strategy demonstrated a reduction in the number of rabies-infected dogs. However, this approach involves a trade-off, limiting the period during which monthly vaccinations can be relaxed. Consequently, a robust and timely vaccination program for dogs is crucial to manage high rabies transmission rates. Lastly, the model simulation underscores the importance of initiating monthly vaccinations.

Animals ; Rabies

INTRODUCTION

Rabies is a public health concern in the Philippines, where gaps in animal bite prevention and control persist despite national mandates. The One Health approach is a framework which recognizes the interconnectedness of human, animal, and environmental health. Although the Anti-Rabies Act of 2007 aligns with the One Health strategies, its implementation at the local level faced many challenges in coordination, delivery of service, and program sustainability.

OBJECTIVE

This study aimed to determine the factors influencing the acceptability of One Health approach among key stakeholders as a strategy in the prevention and control of animal bites and rabies in the municipality of Alaminos, Laguna.

METHODOLOGY

A qualitative Grounded Theory design was used in the study. Eleven key informants from the provincial, municipal, and barangay levels were interviewed.

RESULTS AND DISCUSSIONCONCLUSION

Thematic analysis of key informants’ responses revealed that, despite limited awareness of the One Health approach, multi-sectoral coordination aids program implementation, although operational gaps remain. Fragmented program delivery, lack of formal training and certification, unclear roles, poor communication, inactive task forces, outdated ordinances, weak enforcement, limited community engagement, and low prioritization of rabies prevention collectively hinder effective implementation.

CONCLUSION

The study highlights the complex challenges of implementing the One Health approach for animal bites and rabies control in rural communities. Effective implementation requires strengthened stakeholder capacity-building and training, enhanced community engagement, improved access to veterinary services, reinforced intersectoral coordination and policy enforcement through revitalized task forces, and ongoing monitoring of progress through vaccination coverage and incidence data.

Animals ; One Health ; Public Health ; Environmental Health ; Program Evaluation ; Bites And Stings ; Rabies

Screening carbonyl reductases with the ability to catalyze the reduction of complex carbonyl compounds is of great significance for the biosynthesis of R-tolvaptan(R-TVP). In this study, the target carbonyl reductase in the crude enzyme extract of rabbit liver was separated, purified, and identified by ammonium sulfate precipitation, gel-filtration chromatography, ion exchange chromatography, affinity chromatography, and protein mass spectrometry. With the rabbit liver genome as the template, the gene encoding the carbonyl reductase rlsr5 was amplified by PCR and the recombinant strain was successfully constructed. After RLSR5 was purified by affinity chromatography, its enzymatic properties were characterized. The results indicated that the gene sequence of rlsr5 was 972 bp, encoding a protein with a molecular weight of 40 kDa. RLSR5 was a dimeric protein, and each monomer was composed of a (α/β)₈-barrel structure. RLSR5 could asymmetrically reduce 7-chloro-1-[2-methyl-4-[(2- methylbenzoyl)amino]benzoyl]-5-oxo-2,3,4,5-tetrahydro-1H-1-benzazepine (prochiral ketone, PK) to synthesize R-TVP. The specific activity of the enzyme was 36.64 U/mg, and the optical purity of the product was 99%. This enzyme showcased the optimal performance at pH 6.0 and 30 °C. It was independent of metal ions, with the activity enhanced by Mn²⁺. This study lays a foundation for the biosynthesis of tolvaptan of optical grade.
Animals ; Rabbits ; Alcohol Oxidoreductases/biosynthesis* ; Recombinant Proteins/metabolism* ; Escherichia coli/metabolism* ; Liver/enzymology*

Ensuring food security requires new green pesticides. Double-stranded RNA (dsRNA) pesticides trigger RNA interference by exogenous dsRNA specifically targeting pests and diseases. They can inhibit the expression of key genes in pathogens or pests, thereby achieving effective control of specific pests and diseases. DsRNA pesticides are environmentally friendly, with strong specificity and efficient gene silencing ability, while they have problems such as high production costs. Using engineering strains to produce dsRNA is a feasible strategy, whereas currently there is no cost-effective engineering strain for producing dsRNA. This article reviews the research progress and production strategies of using microorganisms to produce dsRNA, hoping to provide reference for dsRNA production.
RNA, Double-Stranded/genetics* ; Genetic Engineering/methods* ; RNA Interference ; Pesticides ; Animals

With the continuous development of messenger RNA (mRNA) technology, mRNA-based drugs have shown broad application prospects in recent years. Since mRNA is easy to be degraded and difficult to enter cells directly, the mRNA delivery vectors have always been one of the focuses in the development of mRNA-based drugs. Although lipid nanoparticles (LNPs) have been widely used for the delivery of mRNA, they tend to accumulate in the liver, and repeated administration can easily induce inflammatory response which leads to tissue damage. Compared with LNPs, virus-like particles (VLPs) have the advantages of high biocompatibility and safety, being expected to offer new solutions for mRNA delivery. Based on the practical application requirements, this review summarized the research progress in VLPs according to the mRNA delivery steps: particle assembly, delivery into cells, and intracellular release. We hope to provide a basis and design ideas for the development of new VLPs as delivery vectors, promote the application of VLPs in mRNA delivery, and provide new possibilities for the research and application of mRNA-based therapeutics.
RNA, Messenger/administration & dosage* ; Humans ; Nanoparticles/chemistry* ; Genetic Vectors ; Lipids/chemistry* ; Drug Delivery Systems/methods* ; Virion ; Animals ; Gene Transfer Techniques ; Liposomes