Lymphoma of the central nervous system originating from the septum pellucidum region: Two case reports with literature review.

RATIONALE: Central nervous system lymphoma (CNSL) originating from the septum pellucidum is exceptionally rare, presenting unique diagnostic and therapeutic complexities. This case report aims to elucidate the diagnostic challenges, treatment strategies, and outcomes of this rare manifestation. By documenting this case, we seek to enhance understanding within the medical community and contribute valuable insights to the management of CNSL, particularly in atypical locations. PATIENT CONCERNS: A 45-year-old female presented with persistent headaches, blurred vision, and motor weakness, prompting a thorough neurological evaluation. Imaging revealed an enhancing mass in the septum pellucidum, leading to the diagnosis of CNSL. The patient's concerns encompassed not only the physical symptoms but also the emotional impact of her diagnosis and treatment journey. DIAGNOSES: Diagnostic confirmation of CNSL involved cerebrospinal fluid analysis and imaging findings, highlighting the challenge of distinguishing lymphoma from other intracranial pathologies. The case underscores the importance of comprehensive diagnostic evaluation in rare CNSL presentations. INTERVENTIONS: Multidisciplinary management included high-dose methotrexate-based chemotherapy and corticosteroids, with consideration for neurosurgical intervention. Psychosocial support and self-care strategies were integrated into the treatment plan to address holistic patient needs. OUTCOMES: Monitoring revealed a positive treatment response, with a reduction observed in the septum pellucidum mass. Regular assessments ensured adherence to interventions and management of treatment-related side effects, contributing to favorable outcomes and improved quality of life for the patient. LESSONS: This case emphasizes the significance of meticulous diagnostic evaluation and personalized treatment approaches in managing rare CNSL presentations. Collaboration among specialists and comprehensive patient support is paramount in optimizing outcomes and addressing the multifaceted challenges posed by CNSL in unique anatomical locations.

Validation of Quantitative HPLC Method for Bacosides in KeenMind.

Brahmi (Bacopa monnieri) has been used by Ayurvedic medical practitioners in India for almost 3000 years. The pharmacological properties of Bacopa monnieri were studied extensively and the activities were attributed mainly due to the presence of characteristic saponins called "bacosides." Bacosides are complex mixture of structurally closely related compounds, glycosides of either jujubogenin or pseudojujubogenin. The popularity of herbal medicines and increasing clinical evidence to support associated health claims require standardisation of the phytochemical actives contained in these products. However, unlike allopathic medicines which typically contain a single active compound, herbal medicines are typically complex mixtures of various phytochemicals. The assay for bacosides in the British Pharmacopoeia monograph for Bacopa monnieri exemplifies that only a subset of bacosides present are included in the calculation of total bacosides. These results in calculated bacoside values are significantly lower than those attained for the same material using more inclusive techniques such as UV spectroscopy. This study illustrates some of the problems encountered when applying chemical analysis for standardisation of herbal medicines, particularly in relation to the new method development and validation of bacosides from KeenMind.

Hypnosis for treatment of HIV neuropathic pain: a preliminary report.

OBJECTIVE: Painful HIV distal sensory polyneuropathy (HIV-DSP) is the most common nervous system disorder in HIV patients. The symptoms adversely affect patients' quality of life and often diminish their capacity for independent self-care. No interventions have been shown to be consistently effective in treating the disorder. The purpose of the present study was to determine whether hypnosis could be a useful intervention in the management of painful HIV-DSP. METHOD: Participants were 36 volunteers with HIV-DSP who received three weekly training sessions in self-hypnosis. Participants were followed for pain and its sequelae for 7 weeks prior to the intervention, and for 7 weeks postintervention. Participants remained on the same standard-of-care pain regimen for the entire 17 weeks of the protocol. The primary outcome measure was the Short Form McGill Pain Questionnaire cale (SFMPQ) total pain score. Other outcome measures assessed changes in affective state and quality of life. RESULTS: Mean SFMPQ total pain scores were reduced from 17.8 to 13.2 (F[1, 35] = 16.06, P < 0.001). The reductions were stable throughout the 7-week postintervention period. At exit, 26 out of 36 (72%) had improved pain scores. Of the 26 who improved, mean pain reduction was 44%. Improvement was found irrespective of whether or not participants were taking pain medications. There was also evidence for positive changes in measures of affect and quality of life. CONCLUSION: Brief hypnosis interventions have promise as a useful and well-tolerated tool for managing painful HIV-DSP meriting further investigation.

Long-term multicentre randomised controlled study of high frequency chest wall oscillation versus positive expiratory pressure mask in cystic fibrosis.

BACKGROUND: Positive expiratory pressure (PEP) is the most commonly used method of airway clearance (AC) in Canada for patients with cystic fibrosis (CF) whereas, in some countries, high frequency chest wall oscillation (HFCWO) is the preferred form of AC. There have been no long-term studies comparing the efficacy of HFCWO and PEP in the CF population. OBJECTIVES: To determine the long-term efficacy of HFCWO compared with PEP mask therapy in the treatment of CF as measured by the number of pulmonary exacerbations (PEs). METHODS: A randomised controlled study was performed in 12 CF centres in Canada. After a 2-month washout period, subjects were randomised to perform either HFCWO or PEP mask therapy for 1 year. RESULTS: 107 subjects were enrolled in the study; 51 were randomised to PEP and 56 to HFCWO. There were 19 dropouts within the study period, of which 16 occurred prior to or at the time of randomisation. There were significant differences between the groups in the mean number of PEs (1.14 for PEP vs 2.0 for HFCWO) and time to first PE (220 days for PEP vs 115 days for HFCWO, p=0.02). There was no significant difference in lung function, health-related quality of life scores or patient satisfaction scores between the two groups. PEP mask therapy required a shorter treatment time. CONCLUSIONS: The results of this study favour PEP and do not support the use of HFCWO as the primary form of AC in patients with CF. CLINICAL TRIAL REGISTRATION NUMBER: NCT00817180.

Aging and the survival of quiescent and non-quiescent cells in yeast stationary-phase cultures.

In this chapter, we argue that with careful attention to cell types in stationary-phase cultures of the yeast, S. cerevisiae provide an excellent model system for aging studies and hold much promise in pinpointing the set of causal genes and mechanisms driving aging. Importantly, a more detailed understanding of aging in this single celled organism will also shed light on aging in tissue-complex model organisms such as C. elegans and D. melanogaster. We feel strongly that the relationship between aging in yeast and tissue-complex organisms has been obscured by failure to notice the heterogeneity of stationary-phase cultures and the processes by which distinct cell types arise in these cultures. Although several studies have used yeast stationary-phase cultures for chronological aging, the majority of these studies have assumed that cultures in stationary phase are homogeneously composed of a single cell type. However, genome-scale analyses of yeast stationary-phase cultures have identified two major cell fractions: quiescent and non-quiescent, which we discuss in detail in this chapter. We review evidence that cell populations isolated from these cultures exhibit population-specific phenotypes spanning a range of metabolic and physiological processes including reproductive capacity, apoptosis, differences in metabolic activities, genetic hyper-mutability, and stress responses. The identification, in S. cerevisiae, of multiple sub-populations having differentiated physiological attributes relevant to aging offers an unprecedented opportunity. This opportunity to deeply understand yeast cellular (and population) aging programs will, also, give insight into genomic and metabolic processes in tissue-complex organism, as well as stem cell biology and the origins of differentiation.

Cystic fibrosis adolescent transition care in Canada: A snapshot of current practice.

Cystic fibrosis (CF) adolescent transition is not a new health care issue, yet progress in many areas associated with the transition process has been slow. In Canada, the status of CF transition has not been previously reported. The aim of the present study was to describe the transition from paediatric to adult health care for CF patients in Canada, specifically: availability of adult CF clinic services; average age of transfer from paediatric to adult CF health care; and existing CF transition practices. Results show that access to appropriate adult CF health care in Canada is universal; however, the availability, quantity and quality of CF transition care vary among CF clinics. Over a four-year period, the number of CF clinics using formal transition protocols almost doubled, but more work remains to be performed.

La transition des adolescents ayant la fibrose kystique (FK) n'est pas un nouveau problème de santé, mais dans de nombreux secteurs, les progrès associés au processus de transition sont lents. Au Canada, on n'a jamais fait de rapport sur la situation de la transition en FK. La présente étude visait à décrire la transition des patients du Canada ayant la FK entre les soins pédiatriques et les soins pour adultes, notamment la disponibilité des services dans les cliniques de FK pour adultes, l'âge moyen du transfert des soins pédiatriques aux soins pour adultes et les pratiques de transition actuelles en FK. Les résultats démontrent qu'au Canada, on jouit d'un accès universel aux soins pour adultes en FK, mais que la disponibilité, la quantité et la qualité des soins de transition varient selon les cliniques. Sur une période de quatre ans, le nombre de cliniques de FK faisant appel à des protocoles de transition officiels a presque doublé, mais il reste beaucoup à faire.

Role of SPI-1 secreted effectors in acute bovine response to Salmonella enterica Serovar Typhimurium: a systems biology analysis approach.

Salmonella enterica Serovar Typhimurium (S. Typhimurium) causes enterocolitis with diarrhea and polymorphonuclear cell (PMN) influx into the intestinal mucosa in humans and calves. The Salmonella Type III Secretion System (T3SS) encoded at Pathogenicity Island I translocates Salmonella effector proteins SipA, SopA, SopB, SopD, and SopE2 into epithelial cells and is required for induction of diarrhea. These effector proteins act together to induce intestinal fluid secretion and transcription of C-X-C chemokines, recruiting PMNs to the infection site. While individual molecular interactions of the effectors with cultured host cells have been characterized, their combined role in intestinal fluid secretion and inflammation is less understood. We hypothesized that comparison of the bovine intestinal mucosal response to wild type Salmonella and a SipA, SopABDE2 effector mutant relative to uninfected bovine ileum would reveal heretofore unidentified diarrhea-associated host cellular pathways. To determine the coordinated effects of these virulence factors, a bovine ligated ileal loop model was used to measure responses to wild type S. Typhimurium (WT) and a ΔsipA, sopABDE2 mutant (MUT) across 12 hours of infection using a bovine microarray. Data were analyzed using standard microarray analysis and a dynamic bayesian network modeling approach (DBN). Both analytical methods confirmed increased expression of immune response genes to Salmonella infection and novel gene expression. Gene expression changes mapped to 219 molecular interaction pathways and 1620 gene ontology groups. Bayesian network modeling identified effects of infection on several interrelated signaling pathways including MAPK, Phosphatidylinositol, mTOR, Calcium, Toll-like Receptor, CCR3, Wnt, TGF-ß, and Regulation of Actin Cytoskeleton and Apoptosis that were used to model of host-pathogen interactions. Comparison of WT and MUT demonstrated significantly different patterns of host response at early time points of infection (15 minutes, 30 minutes and one hour) within phosphatidylinositol, CCR3, Wnt, and TGF-ß signaling pathways and the regulation of actin cytoskeleton pathway.

The proteomics of quiescent and nonquiescent cell differentiation in yeast stationary-phase cultures.

As yeast cultures enter stationary phase in rich, glucose-based medium, differentiation of two major subpopulations of cells, termed quiescent and nonquiescent, is observed. Differences in mRNA abundance between exponentially growing and stationary-phase cultures and quiescent and nonquiescent cells are known, but little was known about protein abundance in these cells. To measure protein abundance in exponential and stationary-phase cultures, the yeast GFP-fusion library (4159 strains) was examined during exponential and stationary phases, using high-throughput flow cytometry (HyperCyt). Approximately 5% of proteins in the library showed twofold or greater changes in median fluorescence intensity (abundance) between the two conditions. We examined 38 strains exhibiting two distinct fluorescence-intensity peaks in stationary phase and determined that the two fluorescence peaks distinguished quiescent and nonquiescent cells, the two major subpopulations of cells in stationary-phase cultures. GFP-fusion proteins in this group were more abundant in quiescent cells, and half were involved in mitochondrial function, consistent with the sixfold increase in respiration observed in quiescent cells and the relative absence of Cit1p:GFP in nonquiescent cells. Finally, examination of quiescent cell-specific GFP-fusion proteins revealed symmetry in protein accumulation in dividing quiescent and nonquiescent cells after glucose exhaustion, leading to a new model for the differentiation of these cells.

Long-term comparative trial of two different physiotherapy techniques; postural drainage with percussion and autogenic drainage, in the treatment of cystic fibrosis.

UNLABELLED: In N. America, over the past decade, various airway clearance techniques (ACT) have been introduced for the treatment of cystic fibrosis (CF). We hypothesized that autogenic drainage (AD), an ACT developed in Belgium would be as effective as postural drainage with percussion (PD) in treating patients with CF. METHODS: Thirty-six CF patients, aged 12-18 years, with Shwachman score 65-98, were enrolled in a 2-year cross-over trial. Patients were matched as pairs and members of each pair were randomly assigned to two groups. For the first study year, Group A performed PD while Group B performed AD. At the end of 1 year Groups A and B crossed over physiotherapy techniques. Clinical status and pulmonary function (FVC, FEV(1), FEF(25-75)) were measured at 3 monthly intervals. Only results from the first year of the study are reported, as 10 out of 17 patients who had completed performing AD for the first year refused to change back to PD for the second year. RESULTS: During the first year of the study, both the AD and PD groups demonstrated improved pulmonary function with no significant difference between the two groups. Change in FVC and FEV(1) percent predicted for Groups A and B was 0.47 ± 1.65(se) versus 2.35 ± 1.51(se) and 2.09 ± 2.2(se) versus 0.92 ± 2.25(se). However, CF patients exhibited a marked preference for the AD technique. Results suggest that both AD and PD are effective methods of performing physiotherapy for CF patients and that the benefits of either technique are enhanced by measures which encourage adherence.

Identification of novel cluster groups in pediatric high-risk B-precursor acute lymphoblastic leukemia with gene expression profiling: correlation with genome-wide DNA copy number alterations, clinical characteristics, and outcome.

To resolve the genetic heterogeneity within pediatric high-risk B-precursor acute lymphoblastic leukemia (ALL), a clinically defined poor-risk group with few known recurring cytogenetic abnormalities, we performed gene expression profiling in a cohort of 207 uniformly treated children with high-risk ALL. Expression profiles were correlated with genome-wide DNA copy number abnormalities and clinical and outcome features. Unsupervised clustering of gene expression profiling data revealed 8 unique cluster groups within these high-risk ALL patients, 2 of which were associated with known chromosomal translocations (t(1;19)(TCF3-PBX1) or MLL), and 6 of which lacked any previously known cytogenetic lesion. One unique cluster was characterized by high expression of distinct outlier genes AGAP1, CCNJ, CHST2/7, CLEC12A/B, and PTPRM; ERG DNA deletions; and 4-year relapse-free survival of 94.7% ± 5.1%, compared with 63.5% ± 3.7% for the cohort (P = .01). A second cluster, characterized by high expression of BMPR1B, CRLF2, GPR110, and MUC4; frequent deletion of EBF1, IKZF1, RAG1-2, and IL3RA-CSF2RA; JAK mutations and CRLF2 rearrangements (P < .0001); and Hispanic ethnicity (P < .001) had a very poor 4-year relapse-free survival (21.0% ± 9.5%; P < .001). These studies reveal striking clinical and genetic heterogeneity in high-risk ALL and point to novel genes that may serve as new targets for diagnosis, risk classification, and therapy.

Improving extreme-scale problem solving: assessing electronic brainstorming effectiveness in an industrial setting.

OBJECTIVE: An experiment was conducted to compare the effectiveness of individual versus group electronic brainstorming to address difficult, real-world challenges. BACKGROUND: Although industrial reliance on electronic communications has become ubiquitous, empirical and theoretical understanding of the bounds of its effectiveness have been limited. Previous research using short-term laboratory experiments have engaged small groups of students in answering questions irrelevant to an industrial setting. The present experiment extends current findings beyond the laboratory to larger groups of real-world employees addressing organization-relevant challenges during the course of 4 days. METHODS: Employees and contractors at a national laboratory participated, either in a group setting or individually, in an electronic brainstorm to pose solutions to a real-world problem. RESULTS: The data demonstrate that (for this design) individuals perform at least as well as groups in producing quantity of electronic ideas, regardless of brainstorming duration. However, when judged with respect to quality along three dimensions (originality, feasibility, and effectiveness), the individuals significantly (p < .05) outperformed the group. CONCLUSION: When quality is used to benchmark success, these data indicate that work-relevant challenges are better solved by aggregating electronic individual responses rather than by electronically convening a group. APPLICATION: This research suggests that industrial reliance on electronic problem-solving groups should be tempered, and large nominal groups may be more appropriate corporate problem-solving vehicles.

Characterization of differentiated quiescent and nonquiescent cells in yeast stationary-phase cultures.

Cells in glucose-limited Saccharomyces cerevisiae cultures differentiate into quiescent (Q) and nonquiescent (NQ) fractions before entering stationary phase. To understand this differentiation, Q and NQ cells from 101 deletion-mutant strains were tested for viability and reproductive capacity. Eleven mutants that affected one or both phenotypes in Q or NQ fractions were identified. NQ fractions exhibit a high level of petite colonies, and nine mutants affecting this phenotype were identified. Microarray analysis revealed >1300 mRNAs distinguished Q from NQ fractions. Q cell-specific mRNAs encode proteins involved in membrane maintenance, oxidative stress response, and signal transduction. NQ-cell mRNAs, consistent with apoptosis in these cells, encode proteins involved in Ty-element transposition and DNA recombination. More than 2000 protease-released mRNAs were identified only in Q cells, consistent with these cells being physiologically poised to respond to environmental changes. Our results indicate that Q and NQ cells differentiate significantly, with Q cells providing genomic stability and NQ cells providing nutrients to Q cells and a regular source of genetic diversity through mutation and transposition. These studies are relevant to chronological aging, cell cycle, and genome evolution, and they provide insight into complex responses that even simple organisms have to starvation.

Genetic cause of autosomal recessive hereditary nephropathy in the English Cocker Spaniel.

BACKGROUND: Autosomal recessive hereditary nephropathy (ARHN) in the English Cocker Spaniel is caused by a type IV collagen defect, but the underlying mutation is unknown. ANIMALS: One hundred thirty-four English Cocker Spaniels (12 with ARHN, 8 obligate carriers, and 114 others), 3 mixed breed dogs with X-linked hereditary nephropathy (XLHN), and 7 other dogs without hereditary nephropathy were included. METHODS: Diagnosis of ARHN was based on transmission electron microscopy and immunostaining of kidney. Quantitative real time reverse transcriptase polymerase chain reaction (qRT-PCR) was used to compare COL4A3, COL4A4, and COL4A5 mRNA concentrations in the renal cortex from ARHN-affected English Cocker Spaniels, XLHN-affected dogs, and dogs without hereditary nephropathy. The entire coding region of COL4A4 was sequenced in 2 ARHN-affected dogs, 2 obligate carriers, 2 English Cocker Spaniels of unknown status, and 2 healthy mixed breed dogs. The exon containing the mutation was sequenced for all 134 English Cocker Spaniels. RESULTS: Quantitative real time RT-PCR implicated COL4A4 as the gene harboring the mutation, and sequencing identified a single nucleotide substitution at base 115 as the cause of ARHN in English Cocker Spaniels. This mutation, which causes a premature stop codon in exon 3 of COL4A4, was segregated with clinical status in all affected dogs and obligate carriers. The mutation also was identified in 39 of 114 other English Cocker Spaniels with previously unknown status. CONCLUSIONS AND CLINICAL IMPORTANCE: The cause of this disease has been identified, and use of a test for the mutation will permit eradication of ARHN in the English Cocker Spaniel.

Biologic pathways associated with relapse in childhood acute lymphoblastic leukemia: a Children's Oncology Group study.

Outcome for children with childhood acute lymphoblastic leukemia (ALL) who relapse is poor. To gain insight into the mechanisms of relapse, we analyzed gene-expression profiles in 35 matched diagnosis/relapse pairs as well as 60 uniformly treated children at relapse using the Affymetrix platform. Matched-pair analyses revealed significant differences in the expression of genes involved in cell-cycle regulation, DNA repair, and apoptosis between diagnostic and early-relapse samples. Many of these pathways have been implicated in tumorigenesis previously and are attractive targets for intervention strategies. In contrast, no common pattern of changes was observed among late-relapse pairs. Early-relapse samples were more likely to be similar to their respective diagnostic sample while we noted greater divergence in gene-expression patterns among late-relapse pairs. Comparison of expression profiles of early- versus late-relapse samples indicated that early-relapse clones were characterized by overexpression of biologic pathways associated with cell-cycle regulation. These results suggest that early-relapse results from the emergence of a related clone, characterized by the up-regulation of genes mediating cell proliferation. In contrast, late relapse appears to be mediated by diverse pathways.

Gene expression profiling of adult acute myeloid leukemia identifies novel biologic clusters for risk classification and outcome prediction.

To determine whether gene expression profiling could improve risk classification and outcome prediction in older acute myeloid leukemia (AML) patients, expression profiles were obtained in pretreatment leukemic samples from 170 patients whose median age was 65 years. Unsupervised clustering methods were used to classify patients into 6 cluster groups (designated A to F) that varied significantly in rates of resistant disease (RD; P < .001), complete response (CR; P = .023), and disease-free survival (DFS; P = .023). Cluster A (n = 24), dominated by NPM1 mutations (78%), normal karyotypes (75%), and genes associated with signaling and apoptosis, had the best DFS (27%) and overall survival (OS; 25% at 5 years). Patients in clusters B (n = 22) and C (n = 31) had the worst OS (5% and 6%, respectively); cluster B was distinguished by the highest rate of RD (77%) and multidrug resistant gene expression (ABCG2, MDR1). Cluster D was characterized by a "proliferative" gene signature with the highest proportion of detectable cytogenetic abnormalities (76%; including 83% of all favorable and 34% of unfavorable karyotypes). Cluster F (n = 33) was dominated by monocytic leukemias (97% of cases), also showing increased NPM1 mutations (61%). These gene expression signatures provide insights into novel groups of AML not predicted by traditional studies that impact prognosis and potential therapy.

An automated, pressure-driven sampling device for harvesting from liquid cultures for genomic and biochemical analyses.

Here we describe an automated, pressure-driven, sampling device for harvesting 10 to 30 ml samples, in replicate, with intervals as short as 10 s. Correlation between biological replicate time courses measured by microarrays was extremely high. The sampler enables sampling at intervals within the range of many important biological processes.

Analysis of artemisinin by a packed-column supercritical fluid chromatography-atmospheric pressure chemical ionisation mass spectrometry technique.

A packed-column supercritical fluid chromatography-atmospheric pressure chemical ionisation mass spectrometry method was studied for the determination of artemisinin from Artemisia annua L. extracts. The technique does not require any kind of derivatisation prior to the analysis. All samples were simply dissolved in methanol and injected into the mobile phase. Detection was achieved by using mass spectrometry with atmospheric pressure chemical ionisation. The ionisation technique is relatively soft and provides protonated molecular ion and informative structural fragmentation for the compound. Benzophenone was used as a chromatographic standard for the determination of the analytical reproducibility. The supercritical carbon dioxide mobile phase used in the system was modified by 10% methanol. The average absolute retention time was 3.54 min with a standard deviation of 0.017 min and a relative standard deviation of 0.4% with respect to benzophenone for the procedure. The correlation coefficient was 0.998 and detection limit 370 pg on column.