Diffuse intrinsic pontine glioma (DIPG) is a deadly paediatric brain cancer. Transient response to radiation, ineffective chemotherapeutic agents and aggressive biology result in rapid progression of symptoms and a dismal prognosis. Increased availability of tumour tissue has enabled the identification of histone gene aberrations, genetic driver mutations and methylation changes, which have resulted in molecular and phenotypic subgrouping. However, many of the underlying mechanisms of DIPG oncogenesis remain unexplained. It is hoped that more representative in vitro and preclinical models–using both xenografted material and genetically engineered mice–will enable the development of novel chemotherapeutic agents and strategies for targeted drug delivery. This review provides a clinical overview of DIPG, the barriers to progress in developing effective treatment, updates on drug development and preclinical models, and an introduction to new technologies aimed at enhancing drug delivery.
Biology ; Brain Neoplasms ; Brain Stem Neoplasms ; Carcinogenesis ; Glioma ; Heterografts ; Histones ; Hope ; In Vitro Techniques ; Methylation ; Molecular Biology ; Prognosis

Many advances have been made in understanding the molecular biology of brain tumors through progress in cell and developmental biology. The molecular characterization of rare genetic disorders and tumors shed light on several common tumorigenic mechanisms: mitogenic signaling, cell cycle control, development, and cell surface-cytoskeleton interactions. Discovery of many new molecular markers and the recent identification of brain tumor stem cells offer new directions in future research for tumor molecular diagnostics and therapies.
Brain Neoplasms* ; Brain* ; Cell Cycle Checkpoints ; Developmental Biology ; Glioma ; Medulloblastoma ; Meningioma ; Molecular Biology* ; Pathology, Molecular ; Stem Cells

OBJECTIVE: Malaria is a life-threatening, mosquito-borne disease that continues to cause numerous deaths worldwide. In the Philippines, malaria remains an important problem, with five provinces having >1000 cases of malaria a year. The objective of this cross-sectional analytical study was to determine the association of selected factors with non-compliance to anti-malarial treatment among malaria patients in Puerto Princesa, Palawan, specifically: perceived susceptibility to malaria, perceived seriousness and severity of malaria, perceived benefits of medication, perceived barriers to treatment compliance and cues to action.

METHODS: Using an interviewer-administered structured questionnaire, 320 individuals diagnosed with and treated for malaria from January to October 2010 were interviewed regarding compliance to anti-malarial treatment and the factors related to compliance. Descriptive statistics and multiple logistic regression were used to analyze the data.

RESULTS: The rate of non-compliance to anti-malaria treatment was 17% (95% Cl 12.1%-21.2%). After multivariate analysis using logistic regression, symptom perception as a cue to action and forgetfulness as a perceived barrier to treatment compliance were found to be significantly associated with non-compliance to treatment. The odds of non-compliance were three times higher for individuals who perceived that an improvement in symptoms implied cure of malaria. An individual who forgot to take at least one dose of medication was 17 times more likely to be non-compliant with treatment compared to someone who did not forget to take a single dose.

CONCLUSION: Given the factors found to be associated with non­compliance to treatment, more effective ways of ensuring compliance with anti-malaria treatment may be explored e.g., doing directly observed treatment and utilizing treatment partners that may help address the problem of forgetfulness. The fact that symptom improvement is not equivalent to cure must be stressed when advising patients. Emphasizing compliance to treatment and the consequences of noncompliance when conducting patient education activities may also help boost treatment compliance.

Human ; Male ; Female ; Aged ; Middle Aged ; Adult ; Young Adult ; Adolescent ; Malaria-therapeutics, therapy, drug therapy ; Patient Compliance

This study aimed to measure the levels of interferon-gamma (IFN-gamma), tumor necrosis factor-alpha (TNF-alpha), interleukin 1 (IL-1), interleukin 6 (IL-6), and nitrite/nitrate (NOx) in serum of dogs experimentally infected with Rangelia vitalii. Twelve female mongrel dogs were divided into 2 groups; group A (uninfected controls) composed by healthy dogs (n=5) and group B consisting of dogs inoculated with R. vitalii (n=7). Animals were monitored by blood smear examinations, which showed intraerythrocytic forms of the parasite on day 5 post-infection (PI). Blood samples were collected through the jugular vein on days 0, 10, and 20 PI to determine the serum levels of IFN-gamma, TNF-alpha, IL-1, IL-6, and NOx. Cytokines were assessed by ELISA quantitative sandwich technique, and NOx was measured by the modified Griess method. Cytokine levels (IFN-gamma, TNF-alpha, IL-1, and IL-6) were increased (P<0.01) in serum of infected animals. Serum levels of NOx were also increased on days 10 PI (P<0.01) and 20 PI (P<0.05) in infected animals. Therefore, the infection with R. vitalii causes an increase in proinflammatory cytokines and nitric oxide content. These alterations may be associated with host immune protection against the parasite.
Animals ; Chemistry Techniques, Analytical ; Cytokines/*blood ; Disease Models, Animal ; Dogs ; Enzyme-Linked Immunosorbent Assay ; Female ; Nitric Oxide/*blood ; Piroplasmida/*immunology ; Protozoan Infections/*immunology/parasitology/pathology ; Serum/chemistry

Objective: To report a new species of sandfly, Sergentomyia (Neophlebotomus) ashwanii sp. nov. (Diptera: Psychodidae) from Western Ghats, India. Methods: A systematic sandfly survey was conducted in the Thrissur and Kollam districts of Kerala, India using mechanical aspirators, light and sticky traps, both indoor and outdoor habitats, for a period of one year. Deoxyribonucleic acid barcoding of samples was performed targeting mitochondrial cytochrome oxidase I (COI) gene and sequence generated was subjected to phylogenetic analysis. Results: Sergentomyia (Neophlebotomus) ashwanii, a new sandfly species is recorded and described in this communication. A single row of 10-12 pointed teeth in the cibarium with 4-6 small denticles or fore-teeth are the key characteristics that is distinctive from other members of the subgenus Neophlebotomus. Mitochondrial COI barcode followed by phylogenetic analysis of the nucleotide sequence confirms that specimens of the species belong to the same taxonomic group while the genetic distance (14.2%) with the congeners established it to be a different species. Conclusions: The Western Ghats' being an important biodiversity hotspot and has dearth of systematic entomological surveys on sandflies. The current study tried to fill the void and also report a new sandfly species.

Objective: The epidemiology of invasive non-typhoidal Salmonella (iNTS) in the Philippines is not well elaborated. The present study describes the serotype distribution and antimicrobial susceptibility patterns of iNTS in the Philippines from 2014 to 2018. Methods: Invasive NTS isolates were collected through the Department of Health’s Antimicrobial Resistance Surveillance Program (ARSP). The identification of the isolates was confirmed using automated (Vitek®, bioMérieux, Marcy l’Étoile, France) and conventional methods. The isolates were serotyped using the slide agglutination method, and susceptibility testing was performed using Clinical and Laboratory Standards Institute guidelines. Demographic data were collected from the ARSP database. Results: There were 138 isolates collected from human invasive specimens with 97.8% from blood samples. The most common serotypes were Salmonella Enteritidis (n = 84, 60.9%) and Salmonella Typhimurium (n = 18, 13.0%). Most of the isolates were from males (n = 88, 63.8%) and from the 0–5-year age group (n = 61, 44.2%). The proportions of iNTS isolates resistant to first-line antibiotics were as follows: ampicillin (23.2%), chloramphenicol (9.6%), ciprofloxacin (8.7%), ceftriaxone (2.2%) and trimethoprim-sulfamethoxazole (8.8%). The proportion of isolates with multi-drug resistance was 13.0% (18/138) with the most common resistance profile being resistance to ampicillin-chloramphenicol-ciprofloxacin from Salmonella Enteritidis isolates (n = 5). Discussion: Resistance to first-line antibiotics limits the therapeutic choices for Salmonella infection. Relevant local antimicrobial resistance data on iNTS may support appropriate empiric therapy among vulnerable populations.

Objective: Acinetobacter baumannii is an opportunistic nosocomial pathogen that has increasingly become resistant to carbapenems worldwide. In the Philippines, rates of carbapenem resistance and multidrug resistance are above 50%. We undertook a genomic study of carbapenem-resistant A. baumannii in the Philippines to characterize the population diversity and antimicrobial resistance mechanisms. Methods: We sequenced the whole genomes of 117 A. baumannii isolates recovered by 16 hospitals in the Philippines between 2013 and 2014. From the genome sequences, we determined the multilocus sequence type, presence of acquired determinants of antimicrobial resistance and relatedness between isolates. We also compared the phenotypic and genotypic resistance results. Result: Carbapenem resistance was mainly explained by acquisition of the class-D Beta-lactamase gene blaOXA-23. The concordance between phenotypic and genotypic resistance to imipenem was 98.15%, and it was 94.97% overall for the seven antibiotics analysed. Twenty-two different sequence types were identified, including 7 novel types. The population was dominated by the high-risk international clone 2 (i.e. clonal complex 92), in particular by ST195 and ST208 and their single locus variants. Using whole-genome sequencing, we identified local clusters representing potentially undetected nosocomial outbreaks, as well as multi-hospital clusters that indicated interhospital dissemination. Comparison with global genomes suggested that the establishment of carbapenem-resistant international clone 2 in the Philippines is likely the result of clonal expansion and geographical dissemination, and at least partly explained by inadequate hospital infection control and prevention. Discussion This is the first extensive genomic study of carbapenem-resistant A. baumannii in the Philippines, and it underscores the importance of hospital infection control and prevention measures to contain high-risk clones.

Pseudomonas aeruginosa is an opportunistic pathogen often causing nosocomial infections that are resilient to treatment due to an extensive repertoire of intrinsic and acquired resistance mechanisms. In recent years, increasing resistance rates to antibiotics such as carbapenems and extended-spectrum cephalosporins have been reported, as well as multi-drug resistant and possible extremely drug-resistant rates of approximately 21% and 15%, respectively. However, the molecular epidemiology and AMR mechanisms of this pathogen remains largely uncharacterized. We sequenced the whole genomes of 176 P. aeruginosaisolates collected in 2013-2014 by the Antimicrobial Resistance Surveillance Program. The multi-locus sequence type, presence of antimicrobial resistance (AMR) determinants, and relatedness between the isolates were derived from the sequence data. The concordance between phenotypic and genotypic resistance was also determined. Carbapenem resistance was associated namely with loss-of function of the OprD porin, and acquisition of the metallo-?-lactamase VIM. The concordance between phenotypic and genotypic resistance was 93.27% overall for 6 antibiotics in 3 classes, but varied widely between aminoglycosides. The population of P. aeruginosain the Philippines was diverse, with clonal expansions of XDR genomes belonging to multi-locus sequence types ST235, ST244, ST309, and ST773. We found evidence of persistence or reintroduction of the predominant clone ST235 in one hospital, as well as transfer between hospitals. Most of the ST235 genomes formed a distinct Philippine lineage when contextualized with international genomes, thus raising the possibility that this is a lineage unique to the Philippines. This was further supported by long-read sequencing of one representative XDR isolate, which revealed the presence of an integron carrying multiple resistance genes, including blaVIM-2, with differences in gene composition and synteny to other P. aeruginosaclass 1 integrons described before. We produced the first comprehensive genomic survey of P. aeruginosain the Philippines, which bridges the gap in genomic data from the Western Pacific region and will constitute the genetic background to contextualize ongoing prospective surveillance. Our results also highlight the importance of infection control interventions aimed to curtail the spread of international epidemic clone ST235 within the country.

Despite advances in the field of male reproductive health, idiopathic male infertility, in which a man has altered semen characteristics without an identifiable cause and there is no female factor infertility, remains a challenging condition to diagnose and manage. Increasing evidence suggests that oxidative stress (OS) plays an independent role in the etiology of male infertility, with 30% to 80% of infertile men having elevated seminal reactive oxygen species levels. OS can negatively affect fertility via a number of pathways, including interference with capacitation and possible damage to sperm membrane and DNA, which may impair the sperm's potential to fertilize an egg and develop into a healthy embryo. Adequate evaluation of male reproductive potential should therefore include an assessment of sperm OS. We propose the term Male Oxidative Stress Infertility, or MOSI, as a novel descriptor for infertile men with abnormal semen characteristics and OS, including many patients who were previously classified as having idiopathic male infertility. Oxidation-reduction potential (ORP) can be a useful clinical biomarker for the classification of MOSI, as it takes into account the levels of both oxidants and reductants (antioxidants). Current treatment protocols for OS, including the use of antioxidants, are not evidence-based and have the potential for complications and increased healthcare-related expenditures. Utilizing an easy, reproducible, and cost-effective test to measure ORP may provide a more targeted, reliable approach for administering antioxidant therapy while minimizing the risk of antioxidant overdose. With the increasing awareness and understanding of MOSI as a distinct male infertility diagnosis, future research endeavors can facilitate the development of evidence-based treatments that target its underlying cause.
Antioxidants ; Classification ; Clinical Protocols ; Diagnosis ; DNA ; Embryonic Structures ; Female ; Fertility ; Health Expenditures ; Humans ; Infertility ; Infertility, Male ; Male ; Membranes ; Ovum ; Oxidants ; Oxidation-Reduction ; Oxidative Stress ; Reactive Oxygen Species ; Reducing Agents ; Reproductive Health ; Semen ; Spermatozoa ; Subject Headings

Objectives: This scoping review aimed to support a landscape analysis to identify lessons learned about intersectoral collaborations (ISCs) by describing their existing models in the context of dengue, malaria and yellow fever. Methods: A scoping review following the methodology of Joanna Briggs Institute was performed using the following inclusion criteria: studies involving humans; studies discussing intersectoral collaborations, malaria/dengue/yellow fever, and prevention or control at any level; and studies in countries endemic for the aforementioned diseases. Studies were screened using Covidence, while data were extracted using NVivo. Results: Of the 7,535 records retrieved, 69 were included in the qualitative analysis. Most ISCs were initiated by multilateral organizations and ministries of health, and none by communities. Strategies included advocacy, health education, research, public health measures, resource mobilization, service delivery and training; mostly employed on a community level. Monitoring and evaluation were mostly formative, ongoing, and participatory. Gaps included administrative and policy barriers, resource shortages, and inadequate research and training. Conclusions Multiple models of ISC exist in the literature. There is a need to develop a comprehensive framework for an effective and sustainable multisectoral approach for the prevention and control of VBDs ensuring adequate resources, active stakeholders, and strategies that span the entire socio-ecological spectrum.
Dengue ; Disease Vectors ; Intersectoral Collaboration ; Malaria ; Vector Borne Diseases