Effectiveness of Cannabidiol to Manage Chronic Pain: A Systematic Review.

OBJECTIVES: Cannabidiol (CBD), a component in Cannabis, is used to treat seizures, anxiety, and pain. Little is known about how effectively CBD works in managing chronic pain, a condition characterized by discomfort that persists beyond 3-6 months or beyond expected normal healing. Therefore, this systematic review aimed to synthesize evidence on the effectiveness of CBD in chronic pain management. DESIGN: A systematic review of literature utilizing PRISMA 2020 guidelines. DATA SOURCES: PubMed/MEDLINE, Web of Science, CINAHL, Academic Search Complete, PsycArticles, PsycINFO, SocINDEX, and CENTRAL. The gray literature search was performed through the World Health Organization, the Centers for Disease Control and Prevention, and the European Centre for Disease Prevention and Control. REVIEW/ANALYSIS METHODS: We searched eight databases and gray literature for relevant studies until August 30, 2022. We gathered original research articles with various study designs published in English that looked at patients who used CBD to manage their chronic pain. Two authors assessed the risk of bias and certainty of evidence using the Grading of Recommendations Assessment, Development, and Evaluation approach. We used narrative synthesis to analyze the results. RESULTS: We included 15 studies among 1,516 identified articles. The majority of the studies indicated pain reduction ranging from 42% - 66% with CBD alone and CBD with Tetrahydrocannabinol. Three studies showed no significant improvement in reducing pain, and one had mixed findings in pain control. The included studies had various methods of measuring pain reduction, mostly through self-reporting and scales such as visual analog scales and verbal numerical scales, among others. CONCLUSION: CBD may be useful in treating chronic pain. Findings should be interpreted with caution due to the small number of included studies and heterogeneity brought about by different study designs and outcome measures. More studies with robust study designs are warranted to evaluate CBD's effectiveness in treating chronic pain.

Pseudomonassin, a New Bioactive Ribosomally Synthesised and Post-Translationally Modified Peptide from Pseudomonas sp. SST3.

Genome mining and metabolomics have become valuable tools in natural products research to evaluate and identify potential new chemistry from bacteria. In the search for new compounds from the deep-sea organism, Pseudomonas sp. SST3, from the South Shetland Trough, Antarctica, a co-cultivation with a second deep-sea Pseudomonas zhaodongensis SST2, was undertaken to isolate pseudomonassin, a ribosomally synthesised and post-translationally modified peptide (RiPP) that belongs to a class of RiPP called lasso peptides. Pseudomonassin was identified using a genome-mining approach and isolated by means of mass spectrometric guided isolation. Extensive metabolomics analysis of the co-cultivation of Pseudomonas sp. SST3 and P. zhaodongensis SST2, Pseudomonas sp. SST3 and Escherichia coli, and P. zhaodongensis SST2 and E. coli were performed using principal component analysis (PCA) and orthogonal projections to latent structures discriminant analysis (OPLS-DA), which revealed potential new metabolites in the outlier regions of the co-cultivation, with other metabolites identified previously from other species of Pseudomonas. The sequence of pseudomonassin was completely deduced using high collision dissociation tandem mass spectrometry (HCD-MS/MS). Preliminary studies on its activity against the pathogenic P. aeruginosa and its biofilm formation have been assessed and produced a minimum inhibitory concentration (MIC) of 63 µg/mL and 28 µg/mL, respectively.

Acceptability and feasibility of HIV self-testing in Southeast Asia: A scoping review.

BACKGROUND: HIV self-testing (HIVST) policies in Southeast Asia are under development. This scoping review aimed to systematically synthesize the available literature on the acceptability and feasibility of HIVST in Southeast Asia. METHODS: Systematic search was conducted on January 20, 2022, in eight databases: PubMed/MEDLINE, CINAHL, Web of Science, Academic Search Complete, SocINDEX, PsycINFO, PsycArticles, and CENTRAL. Acceptability (HIV testing frequency, willingness to pay, use, and recommend the test, ease of use, preference over standard tests, and partner testing) and feasibility (error rate, readability, and diagnostic performance) parameters were followed for the inclusion of articles. A narrative synthesis was done to present findings from included studies on the acceptability and feasibility of HIVST. RESULTS: A total of 5091 records were identified through database search, and 362 were deleted after deduplication. The screening process resulted in 18 studies that met the inclusion criteria. Results indicated a high acceptability rate due to convenience, increasing awareness about HIVST, availability, and affordability of test kits, and confidentiality of test results. A high feasibility rate was reported due to a low occurrence of errors in self-testing, interpretability of results, and a low percentage of invalid and false-reactive results. Issues identified include costs of HIVST for individual use, distribution mode, type of supervision, counseling, geographic location, and socioeconomic status. CONCLUSIONS: Evidence supports the acceptability and feasibility of HIVST in Southeast Asia. There is a need to regulate and license HIVST in Southeast Asia to have better recognition as a supplement to HTS.

Lived experiences and resilience of hospital pharmacists during the COVID-19 pandemic: An interpretative phenomenological analysis.

Background: Globally, the COVID-19 pandemic has challenged the overall healthcare system. Healthcare workers are an essential workforce during a pandemic as they have been involved in treating patients with COVID-19. They have been exposed to detrimental effects such as high infection and death rates, chronic stress, and fear of uncertainty. Their adaptability in providing care and maintaining psychological equilibrium under unprecedented crises like COVID-19 is poorly understood. Objectives: This study aimed to explore the lived experiences and resilience of hospital pharmacists in the Philippines during the COVID-19 pandemic. Methods: A qualitative study was conducted among hospital pharmacists in Metro Manila, Philippines. In-depth interviews were conducted virtually using a semi-structured topic guide. Interview transcripts were transcribed verbatim and analyzed using interpretative phenomenological analysis. Results: The two themes that emerged from the data were challenges during the COVID-19 pandemic and the resilience of hospital pharmacists. Under challenges, it was subdivided into workplace and personal challenges. As for resilience, it was composed of positive coping mechanisms and positive outlooks of hospital pharmacists. Conclusions: Hospital pharmacists faced many challenges and learned to adapt to the continued impact of the pandemic. Hospitals are encouraged to implement measures to prepare for future public health crises and provide resources for both physical and mental health meant for hospital pharmacists.

Participación de la sociedad civil en el proceso de paz con las Fuerzas Armadas Revolucionarias de Colombia -FARC-ep- (2012-2016) / Participation of civil society in the peace process with the Revolutionary Armed Forces of Colombia (2012-2016) / Participação da sociedade civil no processo de paz com as Forças Armadas Revolucionárias da Colômbia -FARCep- (2012-2016)

RESUMEN El artículo analiza los mecanismos de participación de las organizaciones de la sociedad civil en la fase de negociación en proceso de paz con las Fuerzas Armadas Revolucionarias de Colombia (Farc-ep), entre 2012 y 2016. A través del uso de fichas bibliográficas y documentales, y de agregación y codificación de información, el trabajo identifica siete modelos de la participación de las organizaciones de la sociedad civil en el proceso. Muestra, como en Colombia durante la fase de negociación se exploró, como nunca, una variedad amplia de mecanismos de participación, dándole a la sociedad civil un papel esencial: este actor ayudó a enriquecer la Mesa de Conversaciones de La Habana con sus propuestas y aportó legitimidad y aceptación ciudadana al proceso de paz.

ABSTRACT The article analyzes the mechanisms of participation of civil society organizations in the negotiation phase in the peace process with the Revolutionary Armed Forces of Colombia (Farc-ep), between 2012 and 2016. Through the use of bibliographic records and Documentary, and aggregation and coding of information, identifiable work seven models of participation of civil society organizations in the process. It shows, as in Colombia during the negotiation phase, as never before, a wide variety of participation mechanisms was explored, giving civil society an essential role: this actor helped enrich the Havana Conversation Table with his proposals and contributed legitimacy and acceptance of citizenship to the peace process.

RESUMO O artigo analisa os mecanismos de participação das organizações da sociedade civil na fase de negociação do processo de paz com as Forças Armadas Revolucionárias da Colômbia (FARC-EP), entre 2012 e 2016. Através da utilização de ficheiros bibliográficos e documentais, e da agregação e codificação da informação, o documento identifica sete modelos de participação das organizações da sociedade civil no processo. Mostra que, tal como na Colômbia durante a fase de negociação, foi explorada uma grande variedade de mecanismos de participação, dando à sociedade civil um papel essencial: este actor ajudou a enriquecer a Mesa Redonda de Havana com as suas propostas e trouxe legitimidade e aceitação cidadã ao processo de paz.

Screening Fungal Endophytes Derived from Under-Explored Egyptian Marine Habitats for Antimicrobial and Antioxidant Properties in Factionalised Textiles.

Marine endophytic fungi from under-explored locations are a promising source for the discovery of new bioactivities. Different endophytic fungi were isolated from plants and marine organisms collected from Wadi El-Natrun saline lakes and the Red Sea near Hurghada, Egypt. The isolated strains were grown on three different media, and their ethyl acetate crude extracts were evaluated for their antimicrobial activity against a panel of pathogenic bacteria and fungi as well as their antioxidant properties. Results showed that most of the 32 fungal isolates initially obtained possessed antimicrobial and antioxidant activities. The most potent antimicrobial extracts were applied to three different cellulose containing fabrics to add new multifunctional properties such as ultraviolet protection and antimicrobial functionality. For textile safety, the toxicity profile of the selected fungal extract was evaluated on human fibroblasts. The 21 strains displaying bioactivity were identified on molecular basis and selected for chemical screening and dereplication, which was carried out by analysis of the MS/MS data using the Global Natural Products Social Molecular Networking (GNPS) platform. The obtained molecular network revealed molecular families of compounds commonly produced by fungal strains, and in combination with manual dereplication, further previously reported metabolites were identified as well as potentially new derivatives.

Whole genome sequencing of four bacterial strains from South Shetland Trench revealing biosynthetic and environmental adaptation gene clusters.

Whole genome sequences of four bacterial strains Dietzia maris SST1, Pseudomonas zhaodongensis SST2, Pseudomonas sp. SST3 and Halomonas sulfidaeris SST4, recovered from the South Shetland Trench sediment in Antarctica were analyzed using Ion Torrent sequencing technology. The respective sizes of their genomes (3.88, 4.99, 5.60 and 4.25 Mb) and GC contents (70.0, 60.3, 59.9 and 53.8%) are in agreement with these values of other strains of the species. The bacterial strains displayed promising antimicrobial activity against a number of pathogenic bacterial and fungal species. Whole genomes have been assembled and biosynthetic gene clusters (BGCs) have been identified using the antibiotics and Secondary Metabolite Analysis Shell (antiSMASH) web platform. Comparative analysis of the genome sequences revealed that the strains host abundant BGCs encoding for terpenes, siderophores, arylpolyene, bacteriocins, and lassopeptides. Furthermore, the key stress-related genes were identified and their distribution provided an insight into how these isolates adapt to key marine environmental conditions. This comprehensive study is a contribution to understanding the nature of life on the deep-sea environments.

Glucogenosis Hepática. Características clínicas, laboratoriales e imagenológicas en pacientes pediátricos menores de 15 años / Hepatic glycogenosis. Clinical, laboratory and imaging characteristics in pediatric patients under 15 years old

Antecedentes: La glucogenosis (GSD) hepática es una enfermedad hereditaria autosómica recesiva caracterizada por la alteración del depósito de glucógeno en los tejidos. La enfermedad se presenta con hepatomegalia, debilidad muscular y retraso del crecimiento. Esta patología usualmente se diagnostica clínicamente a partir de los 6 meses de edad cuando la ingesta de alimentos del lactante es más espaciada y puede debutar con sintomatología de hipoglicemia. Debido a la inespecificidad de la presentación clínica de la enfermedad es muy importante la sospecha diagnóstica desde los centros de primer nivel de atención y su derivación oportuna a centros de especialidad. Objetivo: Evaluar y describir el perfil nutricional y clínico en pacientes menores de 15 años con Glucogenosis Hepática. Método: Se describe una serie de casos de 14 pacientes menores de 15 años con diagnóstico clínico de GSD hepática, atendidos en la consulta de Gastroenterología y Nutrición Pediátrica del Hospital Carlos Andrade Marín entre 2016 y 2018. El diagnóstico se lo realizó de acuerdo a la clínica que presentó cada paciente como la presencia de distensión abdominal, hepatomegalia, adinamia, retraso en el crecimiento y datos laboratoriales como niveles de glicemia en sangre periférica, transaminasas, y realización de elastografía entre los principales. Se analizaron datos sociodemográficos, antropométricos, de laboratorio (transaminasas, glicemia periférica) y elastografía hepática. Para el análisis de datos se creó una base de datos en Microsoft Excel 2013 y se procesó con el programa Epi Info 7. Resultados: En este grupo de casos, los tipos específicos de GSD hepática fueron tipo IX, 57,14% (8), tipo III, 28,57% (4) y tipo Ia-b, 14,29% (2) pacientes. La prevalencia de características clínicas ante la sospecha de la GSD hepática fueron: hepatomegalia 100% (14), y retraso en el crecimiento el 64,3% (9). De acuerdo a los exámenes de sangre periférica los valores promedio de transaminasas hepáticas (AST/TGO U/L) (ALT/TGP U/L) y glucosa, fueron de 364±384, 302±255 y 61±15 mg/dL, respectivamente. La elastografía con la que se evaluó el nivel de fibrosis hepática al momento del diagnóstico arrojó los siguientes resultados: F0 (no fibrosis hepática) en el 28,57% (4), F1 con el 28,57% (4), F2-F3 con el 35,71% (5), y F4 7,14%. Conclusión: La Glucogenosis es una patología que debería ser sospechada a tiempo en centros del primer nivel de salud para luego referir oportunamente los casos a los centros de referencia. La hepatomegalia y el retardo en el crecimiento son signos cardinales de alerta para la sospecha de esta patología.

Microlitiasis testicular múltiple bilateral asociado a hidrocele izquierdo en un joven de 26 años de edad. Informe de caso y revisión de la literatura / Multiple testicular microlithiasis bilateral associated with left hydrocele in a 26-year-old boy. Case report and literature review

La microlitiasis testicular (TM) es una patología que generalmente se diagnostica de manera incidental. En Ecuador, no existen reportes de esta entidad en adultos. Los informes científicos indican una mayor incidencia en individuos afroamericanos, sin especificar la etiología; La microlitiasis testicular se asocia con subfertilidad e infertilidad. Su relación con las neoplasias testiculares es controvertida. Aquí presentamos un caso clínico, sus diferentes asociaciones clínicas, y una posible conducta terapéutica.

Testicular microlithiasis (TM) is a pathology usually diagnosed incidentally. In Ecuador, there are not reports of this entity in adults. Scientific reports indicate a higher incidence in African-American individuals, without specifying the etiology; testicular microlithiasis is associated with subfertility and infertility. Its relationship with testicular neoplasms is controversial. Here we present a clinical case, it's different clinical associations, and a possible therapeutic conduct.

Massively parallel sequencing of human urinary exosome/microvesicle RNA reveals a predominance of non-coding RNA.

Intact RNA from exosomes/microvesicles (collectively referred to as microvesicles) has sparked much interest as potential biomarkers for the non-invasive analysis of disease. Here we use the Illumina Genome Analyzer to determine the comprehensive array of nucleic acid reads present in urinary microvesicles. Extraneous nucleic acids were digested using RNase and DNase treatment and the microvesicle inner nucleic acid cargo was analyzed with and without DNase digestion to examine both DNA and RNA sequences contained in microvesicles. Results revealed that a substantial proportion (∼87%) of reads aligned to ribosomal RNA. Of the non-ribosomal RNA sequences, ∼60% aligned to non-coding RNA and repeat sequences including LINE, SINE, satellite repeats, and RNA repeats (tRNA, snRNA, scRNA and srpRNA). The remaining ∼40% of non-ribosomal RNA reads aligned to protein coding genes and splice sites encompassing approximately 13,500 of the known 21,892 protein coding genes of the human genome. Analysis of protein coding genes specific to the renal and genitourinary tract revealed that complete segments of the renal nephron and collecting duct as well as genes indicative of the bladder and prostate could be identified. This study reveals that the entire genitourinary system may be mapped using microvesicle transcript analysis and that the majority of non-ribosomal RNA sequences contained in microvesicles is potentially functional non-coding RNA, which play an emerging role in cell regulation.

Nucleic acids within urinary exosomes/microvesicles are potential biomarkers for renal disease.

Urinary exosomes or microvesicles are being studied intensively to identify potential new biomarkers for renal disease. We sought to identify whether these microvesicles contain nucleic acids. We isolated microvesicles from human urine in the same density range as that previously described for urinary exosomes and found them to have an RNA integrity profile similar to that of kidney tissue, including 18S and 28S rRNA. This profile was better preserved in urinary microvesicles compared with whole cells isolated from urine, suggesting that microvesicles may protect RNA during urine passage. We were able to detect mRNA in the human urinary microvesicles encoding proteins from all regions of the nephron and the collecting duct. Further, to provide a proof of principle, we found that microvesicles isolated from the urine of the V-ATPase B1 subunit knockout mice lacked mRNA of this subunit while containing a normal amount of the B2 subunit and aquaporin 2. The microvesicles were found to be contaminated with extraneous DNA potentially on their surface; therefore, we developed a rapid and reliable means to isolate nucleic acids from within urine microvesicles devoid of this extraneous contamination. Our study provides an experimental strategy for the routine isolation and use of urinary microvesicles as a novel and non-invasive source of nucleic acids to further renal disease biomarker discovery.

An extended nomenclature for mammalian V-ATPase subunit genes and splice variants.

The vacuolar-type H(+)-ATPase (V-ATPase) is a multisubunit proton pump that is involved in both intra- and extracellular acidification processes throughout the body. Multiple homologs and splice variants of V-ATPase subunits are thought to explain its varied spatial and temporal expression pattern in different cell types. Recently subunit nomenclature was standardized with a total of 22 subunit variants identified. However this standardization did not accommodate the existence of splice variants and is therefore incomplete. Thus, we propose here an extension of subunit nomenclature along with a literature and sequence database scan for additional V-ATPase subunits. An additional 17 variants were pulled from a literature search while 4 uncharacterized potential subunit variants were found in sequence databases. These findings have been integrated with the current V-ATPase knowledge base to create a new V-ATPase subunit catalogue. It is envisioned this catalogue will form a new platform on which future studies into tissue- and organelle-specific V-ATPase expression, localization and function can be based.

A pattern-based method for the identification of MicroRNA binding sites and their corresponding heteroduplexes.

We present rna22, a method for identifying microRNA binding sites and their corresponding heteroduplexes. Rna22 does not rely upon cross-species conservation, is resilient to noise, and, unlike previous methods, it first finds putative microRNA binding sites in the sequence of interest, then identifies the targeting microRNA. Computationally, we show that rna22 identifies most of the currently known heteroduplexes. Experimentally, with luciferase assays, we demonstrate average repressions of 30% or more for 168 of 226 tested targets. The analysis suggests that some microRNAs may have as many as a few thousand targets, and that between 74% and 92% of the gene transcripts in four model genomes are likely under microRNA control through their untranslated and amino acid coding regions. We also extended the method's key idea to a low-error microRNA-precursor-discovery scheme; our studies suggest that the number of microRNA precursors in mammalian genomes likely ranges in the tens of thousands.

Subcellular localization of mammalian type II membrane proteins.

Application of a computational membrane organization prediction pipeline, MemO, identified putative type II membrane proteins as proteins predicted to encode a single alpha-helical transmembrane domain (TMD) and no signal peptides. MemO was applied to RIKEN's mouse isoform protein set to identify 1436 non-overlapping genomic regions or transcriptional units (TUs), which encode exclusively type II membrane proteins. Proteins with overlapping predicted InterPro and TMDs were reviewed to discard false positive predictions resulting in a dataset comprised of 1831 transcripts in 1408 TUs. This dataset was used to develop a systematic protocol to document subcellular localization of type II membrane proteins. This approach combines mining of published literature to identify subcellular localization data and a high-throughput, polymerase chain reaction (PCR)-based approach to experimentally characterize subcellular localization. These approaches have provided localization data for 244 and 169 proteins. Type II membrane proteins are localized to all major organelle compartments; however, some biases were observed towards the early secretory pathway and punctate structures. Collectively, this study reports the subcellular localization of 26% of the defined dataset. All reported localization data are presented in the LOCATE database (http://www.locate.imb.uq.edu.au).

Short blocks from the noncoding parts of the human genome have instances within nearly all known genes and relate to biological processes.

Using an unsupervised pattern-discovery method, we processed the human intergenic and intronic regions and catalogued all variable-length patterns with identically conserved copies and multiplicities above what is expected by chance. Among the millions of discovered patterns, we found a subset of 127,998 patterns, termed pyknons, which have additional nonoverlapping instances in the untranslated and protein-coding regions of 30,675 transcripts from 20,059 human genes. The pyknons arrange combinatorially in the untranslated and coding regions of numerous human genes where they form mosaics. Consecutive instances of pyknons in these regions show a strong bias in their relative placement, favoring distances of approximately 22 nucleotides. We also found pyknons to be enriched in a statistically significant manner in genes involved in specific processes, e.g., cell communication, transcription, regulation of transcription, signaling, transport, etc. For approximately 1/3 of the pyknons, the intergenic/intronic instances of their reverse complement lie within 380,084 nonoverlapping regions, typically 60-80 nucleotides long, which are predicted to form double-stranded, energetically stable, hairpin-shaped RNA secondary structures; additionally, the pyknons subsume approximately 40% of the known microRNA sequences, thus suggesting a possible link with posttranscriptional gene silencing and RNA interference. Cross-genome comparisons reveal that many of the pyknons have instances in the 3' UTRs of genes from other vertebrates and invertebrates where they are overrepresented in similar biological processes, as in the human genome. These unexpected findings suggest potential unique functional connections between the coding and noncoding parts of the human genome.

Contextual binding of p120ctn to E-cadherin at the basolateral plasma membrane in polarized epithelia.

E-cadherin-catenin complexes mediate cell-cell adhesion on the basolateral membrane of epithelial cells. The cytoplasmic tail of E-cadherin supports multiple protein interactions, including binding of beta-catenin at the C terminus and of p120ctn to the juxtamembrane domain. The temporal assembly and polarized trafficking of the complex or its individual components to the basolateral membrane are not fully understood. In Madin-Darby canine kidney cells at steady state and after treatment with cycloheximide or temperature blocks, E-cadherin and beta-catenin localized to the Golgi complex, but p120ctn was found only at the basolateral plasma membrane. We previously identified a dileucine sorting motif (Leu586-Leu587, termed S1) in the juxtamembrane domain of E-cadherin and now show that it is required to target full-length E-cadherin to the basolateral membrane. Removal of S1 resulted in missorting of E-cadherin mutants (EcadDeltaS1) to the apical membrane; beta-catenin was simultaneously missorted and appeared at the apical membrane. p120ctn was not mistargeted with EcadDeltaS1, but could be recruited to the E-cadherin-catenin complex only at the basolateral membrane. These findings help define the temporal assembly and sorting of the E-cadherin-catenin complex and show that membrane recruitment of p120ctn in polarized cells is contextual and confined to the basolateral membrane.

The mouse secretome: functional classification of the proteins secreted into the extracellular environment.

We have developed a computational strategy to identify the set of soluble proteins secreted into the extracellular environment of a cell. Within the protein sequences predominantly derived from the RIKEN representative transcript and protein set, we identified 2033 unique soluble proteins that are potentially secreted from the cell. These proteins contain a signal peptide required for entry into the secretory pathway and lack any transmembrane domains or intracellular localization signals. This class of proteins, which we have termed the mouse secretome, included >500 novel proteins and 92 proteins <100 amino acids in length. Functional analysis of the secretome included identification of human orthologs, functional units based on InterPro and SCOP Superfamily predictions, and expression of the proteins within the RIKEN READ microarray database. To highlight the utility of this information, we discuss the CUB domain-containing protein family.