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The text is a report on clinical trials and trial design in the field of Amyotrophic Lateral Sclerosis (ALS) and Frontotemporal Degeneration (FTD). It is authored by a large number of researchers and experts in the field. The report provides a comprehensive overview of ongoing clinical trials, trial design considerations, and potential future directions for research in ALS and FTD. It is a valuable resource for library patrons conducting research on these specific topics. [Extracted from the article]

Potent partnerships among researchers, policymakers, and community members have potential to produce positive changes in communities on a range of topics, including behavioral health. The paper provides a brief illustrative review of such partnerships and then describes the development and evolution of one partnership in particular in Virginia. The origin of the partnership is traced, along with its founding vision, mission, and values. Some of its several projects are described, including (a) needs assessment for implementation of evidence-based programs (EBPs) pursuant to the Family First Prevention Services Act; (b) statewide fidelity monitoring of key EBPs; and (c) projects to synergize state investments in specific EBPs, like multisystemic therapy, functional family therapy, and high fidelity wraparound. The paper concludes with some themes around which the center has evolved to serve the state and its citizens more effectively., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Southam-Gerow, Sale, Robinson, Sanborn, Wu, Boggs, Riso, Scalone and Sandman.)

The parent-infant relationship is critical for socioemotional development and is adversely impacted by perinatal substance use. This systematic review posits that the mechanisms underlying these risks to mother-infant relationships center on 3 primary processes: (1) mothers' childhood maltreatment experiences; (2) attachment styles and consequent internal working models of interpersonal relationships; and (3) perinatal substance use. Further, the review considers the role of hyperkatifeia, or hypersensitivity to negative affect which occurs when people with substance use disorders are not using substances, and which drives the negative reinforcement in addiction. The authors performed a systematic review of articles (published 2000-2022) related to these constructs and their impact on mother-infant relationships and offspring outcomes, including original clinical research articles addressing relationships between these constructs, and excluding case studies, reviews, non-human animal studies, intervention studies, studies with fewer than 30% female-sex participants, clinical guidelines, studies limited to obstetric outcomes, mechanistic/biological studies, and studies with methodological issues precluding interpretation. Overall 1844 articles were screened, 377 were selected for full text review, and data were extracted from 157 articles. Results revealed strong relationships between mothers' childhood maltreatment experiences, less optimal internal working models, and increased risk for perinatal substance use, and importantly, all of these predictors interacted with hyperkatifeia and exerted a marked impact on mother-infant relationships with less data available on offspring outcomes. These data strongly support the need for future studies addressing the additive impact of maternal childhood maltreatment experiences, suboptimal internal working models, and perinatal substance use, with hyperkatifeia as a potential moderator, and their interacting effects on mother-infant socioemotional outcomes., Competing Interests: The author(s) declared no conflicts of interest with respect to the research, authorship, and/or publication of this article.The authors report the following disclosures which are unrelated to this work: disclosures, Dr. Aviva K. Olsavsky serves as a Consultant to the American Heart Association, has received speaking Honoraria from (HMP Global), and her spouse is employed by Thermo Fisher Scientific. Dr. Charles Zeanah has received royalties from Guilford Press and Harvard University Press as well as periodic honoraria for speaking engagements to professional groups. Dr. C. Neill Epperson is a Consultant to Asarina Pharma and Sage Therapeutics, has received research funding from Sage Therapeutics and HealthRhythms, and is a Scientific Advisor for Babyscripts., (© The Author(s) 2023.)

Background and Purpose: Describe an inpatient teleneurology consultation service novel to our hospital system, and capture feedback from patients, ordering providers, and consulting neurologists. Methods : A single cohort of teleneurology consult patients was surveyed via telephone. Ordering and consulting providers completed online surveys. Quantitative survey data was reported using descriptive statistics and free-response survey data was summarized. Patient demographics and consult data were gathered via retrospective chart review. Results : Telephone survey was obtained from 25 of 53 patients receiving teleneurology consults from June 1-September 30, 2020. Patient-reported benefits included better understanding of condition (72%) and ability to remain close to home. Online surveys were completed by 11 ordering providers and by consulting neurologists on 20 telemedicine encounters. Ordering providers reported they were likely to use the service again (98.7%), agreed it added value to patient care (91%) and was valued by patients (82%), with concern for missed diagnosis (46%) and potential patient transfer (36%) without the service. In contrast, fewer consulting neurologists predicted need for transfer (5%) or missed diagnosis (10%) in the absence of teleneurology, though 20% indicated that length of stay may increase without the service. Conclusion: We confirm feasibility of an inpatient teleneurology service run by an academic medical center. Satisfaction was high among all key stakeholders, with few transfers to a tertiary care center. This service is valuable to patients, ordering providers, and potentially the hospital network, as a community based care model of neurological care, centered on the needs of the patient and hospitalist., Competing Interests: Declaration of Conflicting Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2022.)

Background: Previous studies suggest the rate of positive surgical margin (PSM) after lumpectomy for breast cancer is approximately 20 %. The risk of PSM at time of resection is often a source of fear for patients, driving some to elect to undergo mastectomy. This study describes rates and predictors of positive margins for invasive breast cancers in the National Cancer Database (NCDB)., Materials and Methods: From 2004 to 2013, patients with non-metastatic invasive breast cancers who underwent breast conservation surgery were identified from the NCDB. Patients' demographic, clinical, and facility of treatment characteristics were collected and compared. Per SSO-ASTRO-ASCO criteria, margin negative is defined as no gross or microscopic disease (i.e. no tumor on ink). Bivariate tests and multivariate logistic regression were conducted to identify independent predictors of patients with PSM at the time of resection., Results: A total of 707,798 patients were identified with non-metastatic invasive breast tumors who underwent lumpectomy. Rate of PSM across the entire cohort was 5.02 %. Over time, the rate of PSM decreased significantly from 6.54 % in 2004 to 3.91 % in 2013 (p < 0.001). Pure lobular histology predicted for the highest rate of PSM compared with IDC (8.63 vs 4.55 %; p < 0.001). In adjusted analysis, high grade, non-ductal histology and HER2 amplification were significantly associated with PSM with breast conservation while estrogen and progesterone status were not., Conclusion: This study demonstrates a 5 % risk of PSM at time of breast conservation surgery using a large, modern national database. Patients with invasive lobular and mixed histology have a nearly two-fold risk of PSM compared to invasive ductal cancers. These results provide important data points to help appropriately counsel patients regarding the risk of PSM., Competing Interests: Declaration of competing interest DHB declares research support, speaker honoraria, and consultant work from Novocure Inc. and Varian Medical Systems. No other authors declare conflicts of interest., (Copyright © 2021 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Purpose: Mendelian disorders are most commonly caused by mutations identifiable by DNA sequencing. Exonic deletions and duplications can go undetected by sequencing, and their frequency in most Mendelian disorders is unknown., Methods: We designed an array comparative genomic hybridization (CGH) test with probes in exonic regions of 589 genes. Targeted testing was performed for 219 genes in 3,018 patients. We demonstrate for the first time the utility of exon-level array CGH in a large clinical cohort by testing for 136 autosomal dominant, 53 autosomal recessive, and 30 X-linked disorders., Results: Overall, 98 deletions and two duplications were identified in 53 genes, corresponding to a detection rate of 3.3%. Approximately 40% of positive findings were deletions of only one or two exons. A high frequency of deletions was observed for several autosomal dominant disorders, with a detection rate of 2.9%. For autosomal recessive disorders, array CGH was usually performed after a single mutation was identified by sequencing. Among 138 individuals tested for recessive disorders, 10.1% had intragenic deletions. For X-linked disorders, 3.5% of 313 patients carried a deletion or duplication., Conclusion: Our results demonstrate that exon-level array CGH provides a robust option for intragenic copy number analysis and should routinely supplement sequence analysis for Mendelian disorders.

Objectives: The objectives of the study were to identify the characteristics of the patients who were commenced in a newly developed opiate substitute prescribing (OSP) programme, to determine their rate of retention and to ascertain the patients' opinions of the service. We also wished to determine rates of blood borne viruses in this population., Methods: Data were collected from three sources: the Shaftesbury Square Hospital Substitute Prescribing Database, patient charts and an anonymous user views questionnaire. We also conducted viral screening. Inclusion criteria were opiate dependence according to ICD-101 for at least one year, in individuals who were 18 years of age or older. The sample comprised the first 80 patients who attended the service, who were followed up over two years., Results: A total of 44% of our original cohort remained engaged with the service two years after commencement. Of the remainder, 18% engaged with OSP elsewhere and 13% completed a successful detoxification from all opiate drug use. Factors which were associated with continuation in the programme were prescription of methadone (as compared with buprenorphine), female sex and higher doses of OSP. Patients reported high levels of satisfaction with the service. Of those who were tested for blood borne viruses, more than half were positive for hepatitis C infection., Conclusions: The response to the development of the opiate substitution programme demonstrated that there was a need in the community which had not been met in the past. Service users who attended the programme reported high levels of satisfaction.

A pilot study was performed to assess the effectiveness of treatment in an opioid dependent population using the Maudsley Addiction Profile (MAP) tool1.The primary outcome of the study was to assess if treatment had an effect on 1. Substance use (quantity and frequency of use), 2. Health risk behaviour (injecting and sharing injecting equipment), 3. Health symptoms (physical and psychological) and 4. Personal /Social functioning (relationships, employment and crime). A secondary outcome was also sought.The study took place in 2007 in an inner city Belfast hospital specialising in the treatment of addiction, over a two month period. Fifteen patients, all opioid dependent and receiving outpatient community treatment, were interviewed at baseline (prior to the commencement of treatment) and at eight weeks follow up.Three patients were lost to follow up. Two patients stopped using altogether. Of the remaining patients, improvements were seen in most areas. There was a decrease in the use of heroin (71.28%), cocaine (99.72%), crack cocaine (100%), cannabis (99.94%) and alcohol (33.17%). There was a reduction in injecting behaviour (60.93%). Improvements were observed in health with a reduction in physical (41.35%) and psychological (35%) symptoms. Overall personal and social functioning improved regarding interactions with family and friends. A reduction in crime was also observed (75%).Opinions and views of staff involved in the study were generally positive.This patient population presents with multiple and complex needs. Effective treatment needs to address these needs and not just drug addiction alone. The Maudsley Addiction Profile tool highlights this.

One of the prominent cell cycle-related modifications of histone proteins whose function remains unresolved is the phosphorylation of linker histone H1. In this work we have used indirect immunofluorescence on human cells with antibodies that are specific for phosphorylated histone H1 to examine the cellular distribution and chromosome association patterns of this protein. With confocal microscopy on whole cells, strong immunofluorescence was seen in association with mitotic chromosomes as well as a prominent punctate pattern of labeling throughout the mitotic cell, whereas interphase cells showed very little, if any, specific fluorescence. Multiple patterns of fluorescence distribution were detected with metaphase chromosomes, ranging from apparent tight colocalization with the DNA to expanded "puffy" mitotic figures to an amorphous network of staining. It was also shown that the ability to label chromosomes could vary drastically with different fixation procedures, adding further complications to interpretation of the potentially complex role of phosphorylated histone H1 in chromatin condensation or decondensation.

Fluorescence in situ hybridization (FISH) has been shown to discriminate between unreplicated and replicated regions of the genome in interphase nuclei, based on the number of specific fluorescent signals that can be detected. By examining the replication status of hybridizing sequences in large numbers of individual cells from an asynchronously growing population, it is possible to deduce a relative order of replication of different sequences. The availability of well-mapped genomic probes and the ability to compare results from different cell lines make this a convenient approach with which to map domains of replication timing control at any chromosomal position and to relate this to various patterns of gene expression. Since there appear to be important but poorly understood correlations among replication timing, chromatin structure, and transcriptional competence in mammalian cells, this provides a valuable approach to understanding these interrelationships at the molecular level. The procedures for using FISH to examine replication timing in mammalian nuclei are described here in detail, and the advantages and limitations of the approach are discussed. Some other strategies for using high-resolution FISH on chromatin fibers to examine replication properties of specific sequences in situ are also described.

Novel antibodies were generated that are highly selective for either acetylated or unacetylated isoforms of histone H3, or the acetylated form of histone H4 in organisms as diverse as Tetrahymena and humans. Using these antibodies as pair-wise sets in immunocytological analyses, we demonstrate that the inactive X chromosome is hypoacetylated for both histone H3 and H4 in female mammalian cells, whereas the antibody that recognizes the unacetylated form of histone H3 identifies all chromosomes uniformly. These data verify and extend previous results and suggest that hypoacetylation of core histones may be a general feature of the chromatin along the inactive X chromosome.

The nucleotide sequences for isotype 1 beta-tubulin cDNAs cloned from different laboratory strains of Chinese hamster ovary (CHO) cells were compared and found to contain an unexpected number of sequence differences in both translated and untranslated regions of the gene. The results indicate significant changes in the DNA, but not protein, sequence while the cells have been in culture and reveal sequences in the 5' and 3' untranslated regions that have resisted these changes.

Methods for examining altered regions in unstable mutant proteins are described. The strategy is illustrated using assembly defective Chinese hamster beta-tubulin subunits that are rapidly degraded in the cell. These unstable proteins are metabolically labeled to high specific activity and isolated as spots on two-dimensional gels. Conditions for the generation of tryptic peptides from gel pieces containing beta-tubulin and their subsequent resolution by HPLC have been worked out. Through a combination of dual labeling with various tritiated amino acids and [35S]methionine as well as partial sequence analysis, the identification of several HPLC peaks with the known sequence of beta-tubulin has been accomplished. This technique should greatly aid attempts to map the sites of mutational alterations in beta-tubulin polypeptides, and the general strategy should be readily applicable to other mutant proteins.

In conclusion, the teaching program we developed appears to meet the needs originally established by the audit. Nurses are provided with a method of assessment, evaluation, and documentation. The program also provides a means of teaching continuity while following a structured time schedule that allows for recognition and satisfaction of individual patient needs. The patient teaching record provides the final tool as a reference and ongoing source of evaluation.

The effect of the calcium and oxygen contents of a hyperkalemic glucose-containing cardioplegic solution on myocardial preservation was examined in the isolated working rat heart. The cardioplegic solution was delivered at 4 degrees C every 15 minutes during 2 hours of arrest, maintaining a myocardial temperature of 8 degrees +/- 2 degrees C. Hearts were reperfused in the Langendorff mode for 15 minutes and then resumed the working mode for a further 30 minutes. Groups of hearts were given the oxygenated cardioplegic solution containing an ionized calcium concentration of 0, 0.25, 0.75, or 1.25 mmol/L or the same solution nitrogenated to reduce the oxygen content and containing 0 or 0.75 mmol ionized calcium per liter. The myocardial adenosine triphosphate concentrations at the end of arrest in these six groups of hearts were 15.6 +/- 1.2, 9.5 +/- 0.5, 8.2 +/- 1.1, 4.9 +/- 1.8, 10.1 +/- 2.0, and 1.6 +/- 0.4 nmol/mg dry weight, respectively. At 5 minutes of working reperfusion, the percentages of prearrest aortic flow were 80 +/- 2, 62 +/- 4, 33 +/- 6, 37 +/- 5, 48 +/- 7 and 46 +/- 8, respectively. The differences among the groups in adenosine triphosphate concentrations and in functional recovery diminished during reperfusion. In hearts given the hypoxic calcium-containing solution, there was a marked increase in coronary vascular resistance during the administration of successive doses of cardioplegic solution, which was rapidly reversible upon reperfusion. These data indicate that hearts given the acalcemic oxygenated solution had better adenosine triphosphate preservation during arrest and better functional recovery than hearts in any other group. Addition of calcium to the oxygenated cardioplegic solution decreased adenosine triphosphate preservation and functional recovery. Oxygenation of the acalcemic solution increased adenosine triphosphate preservation and functional recovery. The lowest adenosine triphosphate levels at end arrest were observed in hearts given the hypoxic calcium-containing solution. In the setting of hypothermia and multidose administration, the addition of calcium to a cardioplegic solution resulted in increased energy depletion during arrest and depressed recovery.

Determination of cellular clonality in hematological malignancies provides fundamental information that is important in understanding the pathogenesis of these disorders. We present here an extension of one approach to accomplish this that is based on the interpretation of different methylation patterns on active and inactive X chromosomes within the region of the hypoxanthine-guanine phosphoribosyltransferase gene spanned by a restriction fragment length polymorphism. The successful application of the method to determine clonality is described for three female patients with acute nonlymphocytic leukemia.

Twenty-six patients with pancreatic pseudocysts underwent surgical intervention from 1975 through 1979. Chronic alcohol use was associated with pancreatic disease in 84.6 percent of these patients. The clinical findings are not specific, and ultrasonographic examination of the abdomen and computed tomographic scanning have been the most reliable diagnostic tests. External drainage is performed for infected or thin-walled cysts, and carries a complication rate of 72.7 percent in this series. Internal drainage was complicated 31 percent of the time. There were no deaths in this series.

Ornithine transcarbamylase (OTC) (E.C.2.1.3.3) is an X-linked hepatic enzyme in the urea cycle necessary for ammonia detoxification. Deficiency of OTC results in neonatal hyperammonemia, coma, and death in childhood. Because fibroblasts do not express OTC, prenatal diagnosis in the past has required fetal liver biopsy. Using a complementary DNA (cDNA) for OTC for Southern blot analysis of genomic DNA, we have found probands with complete OTC deficiency from two unrelated families in whom the same TaqI restriction endonuclease site has been altered because of independent, but not necessarily identical, mutations in the OTC gene, suggesting that this site may be a relative hotspot for mutation at a location that is critical for normal gene function. This TaqI alteration has allowed the identification of the individual in each family in whom the mutation originated as well as the exclusion of a recurrence of OTC deficiency in a male fetus at risk for the disease. OTC deficiency joins the growing list of genetic disorders for which Southern blot analysis allows accurate heterozygote detection and prenatal diagnosis in conditions for which they were not previously available.

Two anonymous X-specific sequences isolated from a genomic library of flowsorted X chromosomal DNA were selected for study because they revealed restriction fragment length polymorphisms in the region Xq26----qter. One sequence, DXS10, detected a two-allele TaqI polymorphic system with allele frequencies of 0.33 and 0.67. The other, 4D-8, defined an MspI polymorphism with allele frequencies of 0.18 and 0.82. DXS10 is tightly linked to the hypoxanthine phosphoribosyltransferase (HPRT) locus with recombination distance theta = O cM at LOD = 5.55 (95% probability limit theta less than 15 cM). DXS10 maps to Xq26 but is not contained within the HPRT locus itself. 4D-8 shows no detectable linkage to the HPRT locus, with maximum likelihood estimate for theta = 50 cM and a LOD score of -2.61 at theta = 5 cM. These two polymorphisms provide additional chromosomal loci for gene mapping by linkage at the distal end of the long arm of the human X chromosome.