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Genetically encoded DNA recorders noninvasively convert transient biological events into durable mutations in a cell's genome, allowing for the later reconstruction of cellular experiences by DNA sequencing. We present a DNA recorder, peCHYRON, that achieves high-information, durable, and temporally resolved multiplexed recording of multiple cellular signals in mammalian cells. In each step of recording, prime editor, a Cas9-reverse transcriptase fusion protein, inserts a variable triplet DNA sequence alongside a constant propagator sequence that deactivates the previous and activates the next step of insertion. Insertions accumulate sequentially in a unidirectional order, editing can continue indefinitely, and high information is achieved by coexpressing a variety of prime editing guide RNAs (pegRNAs), each harboring unique triplet DNA sequences. We demonstrate that the constitutive expression of pegRNA collections generates insertion patterns for the straightforward reconstruction of cell lineage relationships and that the inducible expression of specific pegRNAs results in the accurate recording of exposures to biological stimuli., Competing Interests: Competing interests The authors declare no competing interests., (© 2024. The Author(s), under exclusive licence to Springer Nature America, Inc.)

Human brain tissue studies have historically used a range of metrics to assess RNA quality. However, few large-scale cross-comparisons of pre-sequencing quality metrics with RNA-seq quality have been published. Here, we analyze how well metrics gathered before RNA sequencing (post-mortem interval (PMI) and RNA integrity number RIN) relate to analyses of RNA quality after sequencing (Percent of counts in Top Ten genes (PTT), 5' bias, and 3' bias) as well as with individual gene counts across the transcriptome. We conduct this analysis across four different human cortical brain tissue collections sequenced with varying library preparation protocols. PMI and RIN have a low inverse correlation, and both PMI and RIN show consistent and opposing correlations with PTT. Unlike PMI, RIN shows strong consistent correlations with measurements of 3' and 5' bias, and RIN also correlates with 3,933 genes across datasets, in comparison to 138 genes for PMI. Neuronal and immune response genes correlate positively and negatively with RIN respectively, suggesting that different gene sets have divergent relationships with RIN in brain tissue. In summary, these analyses suggest that conventional metrics of RNA quality have varying degrees of value, and that PMI has an overall minimal but reproducible effect on RNA quality.

In recent years, multiple groups have shown that what is currently thought of as "Alzheimer's Disease" (AD) may be usefully viewed as several related disease subtypes. As these efforts have continued, a related issue is how common co-pathologies and ethnicity intersect with AD subtypes. The goal of this study was to use a dataset constituting 153 pathologic variables recorded on 666 AD brain autopsies to better define how co-pathologies and ethnicity relate to established AD subtypes. Pathologic clustering suggests 8 subtypes within this cohort, and further analysis reveals that the previously described continuum from hippocampal predominant to hippocampal sparing is well represented in our data. Small vessel disease is overall highest in a cluster with a low hippocampal/cortical tau ratio, and across all clusters small vessel disease segregates separately from Lewy body disease. Two AD clusters are identified with extensive Lewy bodies outside amygdala (one with a high hippocampal/cortical tau ratio and one with a low ratio), and we find an inverse relationship between cortical tau and Lewy body pathology across these two clusters. Finally, we find that brains from persons of Hispanic descent have significantly more AD pathology in multiple neuroanatomic areas. We find that Hispanic ethnicity is not uniformly distributed across clusters, and this is particularly pronounced in clusters with significant Lewy body pathology, where Hispanic donors are only found in a cluster with a low hippocampal/cortical tau ratio. In summary, our analysis of recorded pathologic data across two decades of banked brains reveals new relationships in the patterns of AD-related proteinopathy, co-pathology, and ethnicity, and highlights the utility of pathologic subtyping to classify AD pathology., Competing Interests: Competing Interests: The authors declare no conflicts of interest

Introduction: Normal pressure hydrocephalus (NPH) patients undergoing cortical shunting frequently show early Alzheimer's disease (AD) pathology on cortical biopsy, which is predictive of progression to clinical AD. The objective of this study was to use samples from this cohort to identify cerebrospinal fluid  (CSF) biomarkers for AD-related central nervous system (CNS) pathophysiologic changes using tissue and fluids with early pathology, free of post mortem artifact., Methods: We analyzed Simoa, proteomic, and metabolomic CSF data from 81 patients with previously documented pathologic and transcriptomic changes., Results: AD pathology on biopsy correlates with CSF β-amyloid-42/40, neurofilament light chain (NfL), and phospho-tau-181(p-tau181)/β-amyloid-42, while several gene expression modules correlate with NfL. Proteomic analysis highlights seven core proteins that correlate with pathology and gene expression changes on biopsy, and metabolomic analysis of CSF identifies disease-relevant groups that correlate with biopsy data., Discussion: As additional biomarkers are added to AD diagnostic panels, our work provides insight into the CNS pathophysiology these markers are tracking., Highlights: AD CSF biomarkers correlate with CNS pathology and transcriptomic changes. Seven proteins correlate with CNS pathology and gene expression changes. Inflammatory and neuronal gene expression changes correlate with YKL-40 and NPTXR, respectively. CSF metabolomic analysis identifies pathways that correlate with biopsy data. Fatty acid metabolic pathways correlate with β-amyloid pathology., (© 2024 The Author(s). Alzheimer's & Dementia published by Wiley Periodicals LLC on behalf of Alzheimer's Association.)

Many Minnesotans with asthma participate in recreational and competitive sports. If asthma is undiagnosed or if it is poorly controlled, its symptoms can compromise health, impair athletic performance, and limit sports participation. It can even lead to death. Asthma-related deaths during sports participation, while not common, have occurred in Minnesota. Having asthma should not limit an athlete's ability to compete and win at the highest levels of competition. This article briefly reviews asthma and exercise-induced bronchoconstriction, discusses the impact of asthma on sports participation and outlines asthma management strategies for team physicians, coaches, and athletic trainers.

Introduction: Asthma mortality rates are based on deaths for which asthma is coded as the underlying cause on the death certificate. We conducted an asthma mortality review to evaluate this surveillance measure for Minnesota residents who were aged 55 years or older, Methods: We enlisted an expert panel to review transcribed interviews from the next-of-kin and case histories for decedents whose deaths were attributed to asthma. In addition, we examined death certificates to determine whether the certifier had intended asthma to be the underlying cause., Results: In the age group of Minnesotans we examined, 55 deaths were attributed to asthma during the 1-year study period. Of the 35 deaths for which adequate information was available for review, 2 were determined to be due to asthma. On 33 of the 55 death certificates, the certifier had chosen asthma as the underlying cause; on the rest, the certifier had not chosen asthma, but inconsistencies in death certificate completion had resulted in "asthma" automatically overriding the underlying cause that had been chosen., Conclusion: Asthma mortality rates for older Minnesotans may be overestimated because of inaccurate reporting of the underlying cause of death on death certificates.

Objective: We present a rare and clinically relevant anomaly of the sphenopalatine artery in relation to its blood supply of the nasal mucosa, with implications for the management of epistaxis., Method: Case report and review of the world literature, using Medline through Pub Med (1950-2005), EMBASE (1980-2005) and Ovid (1958-2005), searching for papers using a combination of terms including 'spheno-palatine artery', 'anterior ethmoidal artery' and 'epistaxis'., Results: In the presented case of refractory epistaxis, endoscopic and subsequent endovascular management failed to identify a significant supply from the sphenopalatine arteries bilaterally. The main supply was found to be from the anterior ethmoidal arteries., Conclusion: After a detailed search, the authors failed to locate any similar case in the English literature.

Ion mobility spectrometry (IMS) is proven core technology for the gas-phase detection of chemical warfare (CW) agents. One disadvantage of IMS technology is that ions of similar mobility cannot readily be resolved, resulting in false alarm responses and a loss of user confidence. High field asymmetric waveform spectrometry (HiFAWS) is an emerging technology for the gas-phase detection of CW agents. Of particular interest is the potential of a HiFAWS-based platform to reduce the number of false alarms by resolving ions that cannot be discriminated using IMS. It has been demonstrated that a water clustering/declustering mechanism can be a dominant process in HiFAWS. Ions that cannot be discriminated in IMS because they possess the same low field mobility value can be resolved using HiFAWS due to differences in the extent of low field ion solvation and high field ion desolvation. When operating in complex environments such as those potentially experienced in military and security arenas, IMS systems commonly employ internal dopants to reduce the number of background responses. It is possible that HiFAWS systems may also require the use of internal dopants for the same reason. It has been demonstrated that dopants employed for use in IMS may not be suitable for use in HiFAWS.

This study investigated mother-infant interactions in lowland gorillas (Gorilla gorilla gorilla) with particular focus on the relative role of mothers and infants in creating situations that are potentially conducive to infant social learning. Eleven gorilla mother-infant dyads were focally observed in weekly 1-hr sessions for 12 months. Spatial relationships were affected by age as well as by ambient temperature. Although the youngest infant was encouraged by its mother to walk and climb, mothers showed little or no encouragement in other contexts. In contrast, infants were quite interested in their mothers' activities, on some occasions repeated their mother's behavior, and actively encouraged their mothers to share food, play, or follow them. These findings suggest that gorilla infants are more active than their mothers in creating situations that are potentially conducive to the acquisition of knowledge or skills.

Objective: To determine whether associations exist between body fatness and injury rates in high school football linemen., Design: Prospective, injury surveillance study during a 2-week preseason and 10-week regular season., Setting: 10 public high schools in Texas., Participants: Two hundred fifteen varsity and junior varsity high school football linemen., Main Outcome Measures: Injury rates (injuries per 1000 hours of playing time) for groups of players above a given body fat level and at or below a given body fat level. Rates were computed as the number of injuries per group divided by the group's aggregate playing time (practice + game time). The null hypothesis was that there is no difference in injury rates between players above a given level of body fat and those at or below that level of body fat. Body fat was determined from chest, abdomen, and thigh skinfold measurements using standard conversion equations. Body mass index (BMI) (kg/m2) was also calculated for each player., Results: The overall injury rate was 5.66 injuries per 1000 hours of playing time. Percent body fat ranged from 9.3% to 40.2%. BMI ranged from 19.9 to 46.6 kg/m2. Sixty-seven players sustained 86 injuries, the most common of which were ankle sprains and medial collateral ligament sprains. No difference in overall injury rates between higher and lower fat groups was seen at any body fat level. Players in higher body fat groups, however, had significantly greater lower extremity injury rates than did players in lower fat groups between 18% and 27% body fat and again 32% to 33%, but not at intermediate levels or >33%. Players in higher BMI groups had significantly greater lower extremity injury rates than did players in lower BMI groups throughout the range from 24 to 36 kg/m2, except at 34 kg/m2., Conclusion: Both higher body fatness and BMI were associated with increased rates of lower extremity injury among high school football linemen. BMI appears to be associated more consistently with increased lower extremity injury rates than is body fat.

Objective: To assess the coverage of cervical cytology screening in one general practice surgery according to the criteria in the new Scottish general practitioner contract and to explore the difficulties of defining performance in such screening., Design: Review of annual analysis of uptake of screening during 1984-8., Setting: Suburban general practice surgery in Glasgow serving 3000 patients., Patients: All women aged 35-64 registered in 1984 increasing in 1988 to all women aged 20-64., Main Outcome Measure: Assessment of uptake of smear tests and reasons for smear not being taken and of the effect of these outcomes on the new general practitioner contract., Results: The numbers and percentages of women having a smear test in the previous five and three years were recorded, and the reasons why a smear was not taken were defined in the remainder (hysterectomy, test not offered, risk not known, test declined, patient moved away, and patient unaccounted for). In 1988, 85% (608/719) of the women aged 30-64 and 80% (693/870) of those aged 20-64 had had a smear test in the previous five years. An appropriate or irreducible reason for the lack of a smear test was defined in all the others., Conclusions: The population studied contained a substantial number of women in whom cervical smear was unnecessary, inappropriate, or refused. These factors and the likely demographic variation in the uptake of smear tests have important implications for the setting and achieving of the government's targets for cervical cytology screening.

Sera from 64 patients with primary biliary cirrhosis have been examined for Australia antigen (Au). On immunodiffusion and immunoelectrophoresis all sera were negative. Using a radioimmunoprecipitation technique 15.6% of sera contained antigen compared with an incidence of 3.1% in matched controls, a significant difference (p = 0.015). Anti-Au was found in 9.4% of patients and in 7.8% of controls. In lymphocyte transformation studies lymphocytes from one of 24 patients with primary biliary cirrhosis transformed on stimulation with an Au-rich serum.