Preparing Future Medicine Physicians to Care for Cancer Survivors: Project ECHO® in a Novel Internal Medicine and Family Medicine Residency Curriculum.

Cancer survivorship education is limited in residency training. The goal of this pilot curriculum was to teach medicine residents a structured approach to cancer survivorship care. During the 2020-2021 academic year, we held eight 45-min sessions in an ambulatory noon conference series for a community family medicine (FM) and internal medicine (IM) residency program. The curriculum used Project ECHO®, an interactive model of tele-education through Zoom video conferencing, to connect trainees with specialists. Each session had a cancer-specific focus (e.g., breast cancer survivorship) and incorporated a range of core survivorship topics (e.g., surveillance, treatment effects). The session format included a resident case presentation and didactic lecture by an expert discussant. Residents completed pre- and post-curricular surveys to assess for changes in attitude, confidence, practice patterns, and/or knowledge in cancer survivorship care. Of 67 residents, 23/24 FM and 41/43 IM residents participated in the curriculum. Residents attended a mean of 3 sessions. By the end of the curriculum, resident confidence in survivorship topics (surveillance, treatment effects, genetic risk assessment) increased for breast, colorectal, and prostate cancers (p < 0.05), and there was a trend toward residents stating they ask patients more often about cancer treatment effects (p = 0.07). Over 90% of residents found various curricular components useful, and over 80% reported that the curriculum would improve their practice of cancer-related testing and treatment-related monitoring. On a 15-question post-curricular knowledge check, the mean correct score was 9.4 (63%). An eight-session curriculum improved resident confidence and perceived ability to provide cancer survivorship care.

Evaluating the Effectiveness of Online Educational Modules and Interactive Workshops in Alleviating Symptoms of Mild to Moderate Depression: A Pilot Trial.

INTRODUCTION: Depression is a common health concern in primary care with barriers to treatment well documented in the literature. Innovative online psychoeducational approaches to address barriers to care have been well received and can be cost effective. This pilot trial evaluated the effectiveness of an online psychoeducation curriculum intended to alleviate symptoms of depression while utilizing minimal staff resources. METHODS: A small (n = 29) randomized control pilot study was conducted. Online psychoeducational content was delivered in 5 to 10-minute videos over 8 weeks. Participants engaged in moderated discussions on workshop topics. The Patient Health Care Questionnaire (PHQ-9) was used to measure pre/post scores. Two Likert scale questions were used to determine subjective changes in understanding of depression and coping skills. RESULTS: Paired T-test analysis showed an average PHQ-9 improvement of 4.37 (P = .01) in the intervention arm and 1.81 (P = .172) in the control group. No significant difference in delta PHQ-9 score was found between groups via difference in difference analysis (P = .185). Effect size was 0.59. No improvement in Likert scores for question 1 or 2 were detected by paired T test in either group. CONCLUSION: This pilot trial of interactive online psychoeducational content shows initial promise as there was a significant improvement in PHQ-9 scores within the intervention arm. The comparison of delta scores between intervention and control arms was not statistically significant although this is likely due to the underpowered nature of the pilot trial. This data trend justifies the need for a larger validation trial of this intervention.

Assessing the effect of patient to provider language discordance on depression screening utilizing the Patient Health Questionnaire: an epidemiology study.

Background: As depression screening becomes a standard in primary care, the question remains of how effective and equitable screening can be implemented to avoid cultural and language-related disparities. Methods: In this retrospective cohort study, rates of depression screening were compared for 3626 adult patients at a family medicine residency-based health centre in Pennsylvania, USA. The PHQ-2/PHQ-9 modality was verbally administered by nursing staff at the time of patient intake as part of a universal screening initiative. Chi-square analysis was used to determine the univariate associations of performed depression screening with variables of language, ethnicity, gender and number of office visits. A binary logistic regression was then performed to measure whether univariate associations remain significant after correction for other variables. Results: Chi-square analysis revealed significant differences in screening based on univariate associations of language, gender and number of office visits. No significant difference was found for age or ethnicity. Binary logistic regression revealed the following odds ratio of being screened for depression for each variable: Spanish language (OR = 0.694, CI = 0.559 to 0.862), female gender (OR = 1.155, CI = 1.005 to 1.328) and office visit frequency of three or more office visits per year (OR = 2.103, CI = 1.835 to 2.410). Conclusions: Spanish-speaking adults were significantly less likely to be screened for depression than their English-speaking counterparts. Women were more likely to be screened than men, and the odds of screening increased with more frequent exposure to the office. Future studies should be directed at validating these findings in multiple clinical settings.

Global screening of potential Candida albicans biofilm-related transcription factors via network comparison.

BACKGROUND: Candida albicans is a commonly encountered fungal pathogen in humans. The formation of biofilm is a major virulence factor in C. albicans pathogenesis and is related to antidrug resistance of this organism. Although many factors affecting biofilm have been analyzed, molecular mechanisms that regulate biofilm formation still await to be elucidated. RESULTS: In this study, from the gene regulatory network perspective, we developed an efficient computational framework, which integrates different kinds of data from genome-scale analysis, for global screening of potential transcription factors (TFs) controlling C. albicans biofilm formation. S. cerevisiae information and ortholog data were used to infer the possible TF-gene regulatory associations in C. albicans. Based on TF-gene regulatory associations and gene expression profiles, a stochastic dynamic model was employed to reconstruct the gene regulatory networks of C. albicans biofilm and planktonic cells. The two networks were then compared and a score of relevance value (RV) was proposed to determine and assign the quantity of correlation of each potential TF with biofilm formation. A total of twenty-three TFs are identified to be related to the biofilm formation; ten of them are previously reported by literature evidences. CONCLUSIONS: The results indicate that the proposed screening method can successfully identify most known biofilm-related TFs and also identify many others that have not been previously reported. Together, this method can be employed as a pre-experiment screening approach that reveals new target genes for further characterization to understand the regulatory mechanisms in biofilm formation, which can serve as the starting point for therapeutic intervention of C. albicans infections.

Fungicidal activity of a phospholipase-A2-derived synthetic peptide variant against Candida albicans.

pEM-2, a 13-mer synthetic peptide variant derived from myotoxin II, a phospholipase A(2) homologue present in Bothrops asper snake venom, has shown potent bactericidal activity in previous studies due to the combination of cationic and hydrophobic amino acids, including three tryptophan-substituted residues in its sequence. This study reports that pEM-2 also exerts potent fungicidal activity against a variety of clinically relevant Candida species, killing 100% of yeasts at concentrations near 10 mg/l (5 microM), as indicated by plate counting assays. Thus, this peptide displays a broad-spectrum antimicrobial activity, in the absence of hemolytic activity. The fungicidal action of pEM-2 against Candida can be partially inhibited by increasing concentrations of extracellular divalent cations (Ca(+2) or Mg(+2)), in agreement with its proposed membrane-permeabilizing mechanism of action.

Fungicidal activity of a phospholipase A2-derived synthetic peptide variant against Candida albicans

pEM-2, una variante de péptido sintético derivada de la miotoxina II, un homólogo de la fosfolipasa A2 presente en el veneno de la serpiente Bothrops asper, ha mostrado en estudios previos una potente actividad bactericida debida a la combinación de aminoácidos catiónicos e hidrófobos en su secuencia, incluyendo tres residuos sustituidos por triptófano. Este estudio describe que el pEM-2 también ejerce una potente actividad fungicida contra una variedad de especies de Candida clínicamente relevantes, matando el 100% de las levaduras a concentraciones cercanas a 10 mg/l (5 ìM), mediante ensayos de recuento en placas. De tal modo, este péptido muestra una acción antimicrobiana de amplio espectro, en ausencia de actividad hemolítica. La acción fungicida del pEM-2 sobre Candida es parcialmente inhibida por concentraciones crecientes de cationes divalentes extracelulares (Ca+2 o Mg+2), en concordancia con su mecanismo de acción propuesto, permeabilizante de membranas

pEM-2, a 13-mer synthetic peptide variant derived from myotoxin II, a phospholipase A2 homologue present in Bothrops asper snake venom, has shown potent bactericidal activity in previous studies due to the combination of cationic and hydrophobic amino acids, including three tryptophan-substituted residues in its sequence. This study reports that pEM-2 also exerts potent fungicidal activity against a variety of clinically relevant Candida species, killing 100% of yeasts at concentrations near 10 mg/l (5 ìM), as indicated by plate counting assays. Thus, this peptide displays a broad-spectrum antimicrobial activity, in the absence of hemolytic activity. The fungicidal action of pEM-2 against Candida can be partially inhibited by increasing concentrations of extracellular divalent cations (Ca+2 or Mg+2), in agreement with its proposed membrane- permeabilizing mechanism of action

Genome-wide transcription profiling of the early phase of biofilm formation by Candida albicans.

The ability to adhere to surfaces and develop as a multicellular community is an adaptation used by most microorganisms to survive in changing environments. Biofilm formation proceeds through distinct developmental phases and impacts not only medicine but also industry and evolution. In organisms such as the opportunistic pathogen Candida albicans, the ability to grow as biofilms is also an important mechanism for persistence, facilitating its growth on different tissues and a broad range of abiotic surfaces used in medical devices. The early stage of C. albicans biofilm is characterized by the adhesion of single cells to the substratum, followed by the formation of an intricate network of hyphae and the beginning of a dense structure. Changes in the transcriptome begin within 30 min of contact with the substrate and include expression of genes related to sulfur metabolism, in particular MET3, and the equivalent gene homologues of the Ribi regulon in Saccharomyces cerevisiae. Some of these changes are initiated early and maintained throughout the process; others are restricted to the earliest stages of biofilm formation. We identify here a potential alternative pathway for cysteine metabolism and the biofilm-associated expression of genes involved in glutathione production in C. albicans.

Regulatory networks affected by iron availability in Candida albicans.

Iron, an essential element for almost every organism, serves as a regulatory signal for the expression of virulence determinants in many prokaryotic and eukaryotic pathogens. Using a custom Affymetrix GeneChip representing the entire Candida albicans genome, we examined the changes in genome-wide gene expression in this opportunistic pathogen as a function of alterations in environmental concentrations of iron. A total of 526 open reading frame (ORF) transcripts are more highly expressed when the levels of available iron are low, while 626 ORF transcripts are more highly expressed in high-iron conditions. The transcripts dominantly affected by iron concentration range from those associated with cell-surface properties to others which affect mitochondrial function, iron transport and virulence-related secreted hydrolases. Moreover gene expression as assayed in DNA microarrays confirms and extends reports of alterations in cell-surface antigens and drug sensitivity correlated with iron availability. To understand how these genes and pathways might be regulated, we isolated a gene designated SFU1 that encodes a homologue of the Ustilago maydis URBS1, a transcriptional repressor of siderophore uptake/biosynthesis. Comparisons between wild-type and SFU1-null mutant strains revealed 139 potential target genes of Sfu1p; many of which are iron-responsive. Together, these results not only expand our understanding of global iron regulation in C. albicans, but also provide insights into the potential role of iron availability in C. albicans virulence.

Identification, cloning, and sequencing of different cytokine genes in four species of owl monkey.

Non-human primates could prove to be suitable models for the study of infectious diseases such as malaria, tuberculosis, and hepatitis; the molecules of their immune systems are in the process of being fully characterized. Due to the relevance of cytokines in the modulation of the immune response, a molecular analysis of these proteins in non-human primates from the Aotus genus was carried out. Peripheral blood mononuclear cells from four species of Aotusmonkey were obtained and their mRNAs for interleukin-2 (IL-2), IL-4, IL-6, IL-10, interferon-gamma (IFN), and tumor necrosis factor (TNF)-alpha were characterized. This study shows a high degree of conservation between nucleotide and amino acid sequences of cytokines from different Aotus species and those from humans. The TNF-alpha molecules were identical in amino acid sequences for both.

Metabolic specialization associated with phenotypic switching in Candidaalbicans.

Phase and antigenic variation are mechanisms used by microbial pathogens to stochastically change their cell surface composition. A related property, referred to as phenotypic switching, has been described for some pathogenic fungi. This phenomenon is best studied in Candida albicans, where switch phenotypes vary in morphology, physiology, and pathogenicity in experimental models. In this study, we report an application of a custom Affymetrix GeneChip representative of the entire C. albicans genome and assay the global expression profiles of white and opaque switch phenotypes of the WO-1 strain. Of 13,025 probe sets examined, 373 ORFs demonstrated a greater than twofold difference in expression level between switch phenotypes. Among these, 221 were expressed at a level higher in opaque cells than in white cells; conversely, 152 were more highly expressed in white cells. Affected genes represent functions as diverse as metabolism, adhesion, cell surface composition, stress response, signaling, mating type, and virulence. Approximately one-third of the differences between cell types are related to metabolic pathways, opaque cells expressing a transcriptional profile consistent with oxidative metabolism and white cells expressing a fermentative one. This bias was obtained regardless of carbon source, suggesting a connection between phenotypic switching and metabolic flexibility, where metabolic specialization of switch phenotypes enhances selection in relation to the nutrients available at different anatomical sites. These results extend our understanding of strategies used in microbial phase variation and pathogenesis and further characterize the unanticipated diversity of genes expressed in phenotypic switching.

Isolation, characterization, molecular cloning and amplification of a species-specific M. leprae antigen

A polyclonal serum sample from a lepromatous leprosy (LL) patient, which presented a specific recognition pattern for leprosin, was used to screen a Mycobacterium leprae genomic library constructed with DNA isolated from human lepromas. One clone, designated ML4-1, which expressed a specific antigenic determinant of M. leprae as part of a beta-galactosidase fusion protein, was isolated. The 1.932 bp M. leprae-derived genomic fragment was sequenced, and it had an incomplete open-reading frame shown to code for a 644 amino-acid polypeptide (72.3 kDa). Some partial nucleotide homology to the M. tuberculosis MTCY9C4 cosmid and the M. leprae B1913 cosmid were found. Southern blot assays using the 584 bp Eco RI-Bam HI fragment excised from the ML4-1 clone revealed that this sequence is present only in the M. leprae genome and not in the 24 different mycobacterial DNA tested. Two oligonucleotides based on the genomic sequence were also synthesized and used as amplifiers for a polymerase chain reaction (PCR) test, giving a positive signal exclusively in M. leprae DNA. Furthermore, 32 sequential synthetic peptides, 20 amino-acids long, spanning the entire protein corresponding to the hypothetical ML4-1 clone sequence, were synthesized and evaluated by ELISA. A peptide included in the 221-240 region was significantly recognized by either lepromatous leprosy or healthy tuberculosis contact patient sera. Thus, PCR amplification of this fragment, along with the recognition of its protein sequence by leprosy patient sera, could be a useful tool for a potential diagnostic method in the detection of M. leprae infection in the future.