Survival for Nonshockable Cardiac Arrests Treated With Noninvasive Circulatory Adjuncts and Head/Thorax Elevation.

OBJECTIVES: Cardiac arrests remain a leading cause of death worldwide. Most patients have nonshockable electrocardiographic presentations (asystole/pulseless electrical activity). Despite well-performed basic and advanced cardiopulmonary resuscitation (CPR) interventions, patients with these presentations have always faced unlikely chances of survival. The primary objective was to determine if, in addition to conventional CPR (C-CPR), expeditious application of noninvasive circulation-enhancing adjuncts, and then gradual elevation of head and thorax, would be associated with higher likelihoods of survival following out-of-hospital cardiac arrest (OHCA) with nonshockable presentations. DESIGN: Using a prospective observational study design (ClinicalTrials.gov NCT05588024), patient data from the national registry of emergency medical services (EMS) agencies deploying the CPR-enhancing adjuncts and automated head/thorax-up positioning (AHUP-CPR) were compared with counterpart reference control patient data derived from the two National Institutes of Health clinical trials that closely monitored quality CPR performance. Beyond unadjusted comparisons, propensity score matching and matching of time to EMS-initiated CPR (TCPR) were used to assemble cohorts with corresponding best-fit distributions of the well-established characteristics associated with OHCA outcomes. SETTING: North American 9-1-1 EMS agencies. PATIENTS: Adult nontraumatic OHCA patients receiving 9-1-1 responses. INTERVENTIONS: In addition to C-CPR, study patients received the CPR adjuncts and AHUP (all U.S. Food and Drug Administration-cleared). MEASUREMENTS AND MAIN RESULTS: The median TCPR for both AHUP-CPR and C-CPR groups was 8 minutes. Median time to AHUP initiation was 11 minutes. Combining all patients irrespective of lengthier response intervals, the collective unadjusted likelihood of AHUP-CPR group survival to hospital discharge was 7.4% (28/380) vs. 3.1% (58/1,852) for C-CPR (odds ratio [OR], 2.46 [95% CI, 1.55-3.92]) and, after propensity score matching, 7.6% (27/353) vs. 2.8% (10/353) (OR, 2.84 [95% CI, 1.35-5.96]). Faster AHUP-CPR application markedly amplified odds of survival and neurologically favorable survival. CONCLUSIONS: These findings indicate that, compared with C-CPR, there are strong associations between rapid AHUP-CPR treatment and greater likelihood of patient survival, as well as survival with good neurological function, in cases of nonshockable OHCA.

Supply Costs in Complex and Routine Inferior Vena Cava Filter Retrieval: 10 Years' Data from a Single Center.

PURPOSE: To characterize the medical supply costs associated with inferior vena cava filter retrieval (IVCFR) using endobronchial forceps (EFs), a snare, or Recovery Cone (RC). MATERIALS AND METHODS: In total, 594 of 845 IVCFRs attempted at a tertiary referral hospital between October 1, 2012, and June 20, 2022 were categorized by intended retrieval strategy informed by, rotational cavography as follows: (a) EF (n = 312) for tilted or tip-embedded/strut-embedded filters and for long-dwelling closed-cell filters and (b) a snare (n = 255) or (c) RC (n = 27) for other well-positioned filters with or mostly without hooks, respectively. List prices of relevant supplies at time of retrieval were obtained or, rarely, estimated using a standard procedure. Contrast use, fluoroscopic time, filter type, dwell time, and patient age and sex were recorded. Mean between-group cost differences were estimated by linear regression, adjusting for date. Additional models evaluated filter type, dwell time, and patient-level effects. RESULTS: Of the 594 IVCFRs, 591 were successful, whereas 2 EF and 1 snare retrievals failed. Moreover, 4 EF retrievals were successful with a snare and 2 with smaller EF, 12 snare retrievals were successful with EF, 1 RC retrieval was successful with a snare and 2 with EF. Principal model indicated a significantly lower mean cost of EF ($564.70, SE ± 9.75) than that of snare ($811.29, SE ± 10.83; P < .0001) and RC ($1,465.48, SE ± 47.12; P < .0001) retrievals. Adjusted models yielded consistent results. Had all retrievals been attempted with EF, estimated undiscounted full-period supplies savings would be $87,201.51. CONCLUSIONS: EFs are affordable for complex IVCFR, and extending their use to routine IVCFR could lead to considerable cost savings.

Penn Healthy Diet survey: pilot validation and scoring.

Though diet quality is widely recognised as linked to risk of chronic disease, health systems have been challenged to find a user-friendly, efficient way to obtain information about diet. The Penn Healthy Diet (PHD) survey was designed to fill this void. The purposes of this pilot project were to assess the patient experience with the PHD, to validate the accuracy of the PHD against related items in a diet recall and to explore scoring algorithms with relationship to the Healthy Eating Index (HEI)-2015 computed from the recall data. A convenience sample of participants in the Penn Health BioBank was surveyed with the PHD, the Automated Self-Administered 24-hour recall (ASA24) and experience questions. Kappa scores and Spearman correlations were used to compare related questions in the PHD to the ASA24. Numerical scoring, regression tree and weighted regressions were computed for scoring. Participants assessed the PHD as easy to use and were willing to repeat the survey at least annually. The three scoring algorithms were strongly associated with HEI-2015 scores using National Health and Nutrition Examination Survey 2017-2018 data from which the PHD was developed and moderately associated with the pilot replication data. The PHD is acceptable to participants and at least moderately correlated with the HEI-2015. Further validation in a larger sample will enable the selection of the strongest scoring approach.

Protein architecture of the human kinetochore microtubule attachment site.

Chromosome segregation requires assembly of kinetochores on centromeric chromatin to mediate interactions with spindle microtubules and control cell-cycle progression. To elucidate the protein architecture of human kinetochores, we developed a two-color fluorescence light microscopy method that measures average label separation, Delta, at <5 nm accuracy. Delta analysis of 16 proteins representing core structural complexes spanning the centromeric chromatin-microtubule interface, when correlated with mechanical states of spindle-attached kinetochores, provided a nanometer-scale map of protein position and mechanical properties of protein linkages. Treatment with taxol, which suppresses microtubule dynamics and activates the spindle checkpoint, revealed a specific switch in kinetochore architecture. Cumulatively, Delta analysis revealed that compliant linkages are restricted to the proximity of chromatin, suggested a model for how the KMN (KNL1/Mis12 complex/Ndc80 complex) network provides microtubule attachment and generates pulling forces from depolymerization, and identified an intrakinetochore molecular switch that may function in controlling checkpoint activity.

Insights from user experience and evaluation of a mobile health nutrition intervention for children with autism: A qualitative study.

BACKGROUND: Children with autism spectrum disorder (ASD) experience high rates of atypical eating behaviours, such as food neophobia. Mobile health (mHealth) interventions have been found to improve communication, behaviour and social skills for children with ASD. However, there is limited evidence examining mHealth nutrition interventions among children with ASD. METHODS: The present study comprised a qualitative descriptive study that used qualitative content analysis to explore parent and child experiences with a novel mHealth nutrition intervention. Ten parent-child dyads provided user feedback and evaluation of the intervention. Data collection tools included a semistructured interview guide and a quantitative questionnaire with open-ended questions. Data analysis of the interview transcripts and open-ended questionnaire responses was an iterative process that continued until saturation was achieved. Descriptive statistics were used to analyse quantitative questionnaire data. RESULTS: Analysis of the qualitative semistructured interviews led to emergence of three themes: (1) positive intervention outcomes; (2) parent suggestions for improvement; and (3) barriers to engagement. Each theme included subthemes. Questionnaire data revealed the ability to pick rewards and the virtual character that reinforced dietary goals ("Nutrition Ninja") were the most liked components of the application. Sending messages within the application and the Nutrition Ninja game were the least liked components of the application. CONCLUSIONS: Collectively, findings indicated that the app served as an interactive tool prompting dietary change and conversations within families. Yet, for some families, the intervention design, resistance to change or child disinterest hindered use and implementation of the intervention.

Comparison of Transthoracic Contrast Echocardiography with High-Resolution Chest CT after Embolization of Pulmonary Arteriovenous Malformation.

PURPOSE: To compare postembolotherapy follow-up graded transthoracic contrast echocardiography (TTCE) and high-resolution computed tomography (CT) of the chest and to evaluate the use of graded TTCE in the early postembolic period. MATERIALS AND METHODS: Thirty-five patients (6 men and 29 women; mean age, 56 years; range, 27-78 years) presenting for postembolotherapy follow-up between 2017 and 2021 with concurrent high-resolution CT and graded TTCE were analyzed retrospectively. Untreated pulmonary arteriovenous malformations (PAVMs) with a feeding artery of ≥2 mm were considered treatable. RESULTS: Ninety-four percent of patients (33 of 35) did not have treatable PAVMs on high-resolution CT. TTCE was negative for shunts (Grade 0) in 34% of patients (n = 12). Of patients with a TTCE positive for shunts (23 of 35, 66%), 83% had a Grade 1 shunt, 13% had a Grade 2 shunt, and 4% had a Grade 3 shunt. No patient with a Grade 0 or 1 shunt had a treatable PAVM on high-resolution CT. Of the 2 patients with PAVMs requiring treatment, one had a Grade 2 shunt and one had a Grade 3 shunt. TTCE grade was significantly associated with the presence of a treatable PAVM on high-resolution CT (P < .01). CONCLUSIONS: Graded TTCE predicts the need for repeat embolotherapy and does so reliably in the early postembolotherapy period. This suggests that graded TTCE can be utilized in the postembolotherapy period for surveillance, which has the potential to lead to a decrease in cumulative radiation in this patient population.

Psychometric Analysis of the Health Self-Care Neglect Scale.

OBJECTIVES: The Health Self-Care Neglect (HSCN) scale is a measure of self-care neglect developed for use in informal caregivers, where self-care is defined as behaviors undertaken to maintain health. There was no formal psychometric analysis of the scale, so we tested a 9-item, dichotomous-response version of the HSCN scale in a sample of 250 informal caregivers of adults with chronic heart failure. METHODS: As the indicators of self-care neglect were considered formative (influencing the latent variable directly) rather than reflective (influenced by the latent variable), we used a procedure for the specification of formative measurement models. First, maximally correlated composites of indicators were identified for the latent variable, and optimal scoring weights were developed. Then, the reflective factor was tested with confirmatory factor analysis, and longitudinal invariance of the factorial structure was tested by introducing model constraints. Reliability was assessed with composite reliability model-based estimates. Concurrent validity was assessed by correlating the HSCN scale total score with the maintenance scale score of the Self-Care Inventory. RESULTS: Strict invariance, the highest level possible, was achieved. Reliability was 0.81 at baseline. Concurrent validity was demonstrated (r = -0.475, P < .0001). CONCLUSION: The results of this analysis indicate that the HSCN scale is reliable, stable, and valid as a measure of health self-care neglect when tested in a sample of caregivers. The HSCN scale measures the successful performance of self-care, whereas existing measures of self-care reflect intention. Understanding both intention and behavior is useful, so we recommend using the HSCN scale in addition to existing measures of self-care.

Development of the Penn Healthy Diet screener with reference to adult dietary intake data from the National Health and Nutrition Examination Survey.

BACKGROUND: There is a need for a feasible, user-friendly tool that can be employed to assess the overall quality of the diet in U.S. CLINICAL SETTINGS: Our objectives were to develop the Penn Healthy Diet (PHD) screener, evaluate screener item correlations with Healthy Eating Index (HEI)-2015 components, and develop a simple scoring algorithm. METHODS: National Health and Nutrition Examination Survey (NHANES) 2017-18 dietary recall data in adults were used to define food examples in screener food groups based on components of the HEI-2015, Diet Approach to Stop Hypertension, and Alternative Mediterranean diet approaches. Instrument Content Validity Index (I-CVI) was used to evaluate the clarity and relevance of the screener. Patient acceptability was evaluated by completion time and response rates. NHANES 2017-18 food recall data were used to simulate responses to the screener items, which were evaluated for association with HEI-2015 components. A scoring algorithm was developed based on screener items moderately or strongly associated with HEI-2015 components. Reproducibility was tested using NHANES 2015-16 data. RESULTS: The screener had strong clarity (I-CVI = 0.971) and relevance for nutrition counseling (I-CVI = 0.971). Median (IQR) completion time was 4 (3-5) minutes on paper and 4 (4-8) minutes online, and 73% of patients invited online completed the survey. Based on simulated NHANES participant screener responses, 15 of the 29 screener items were moderately or strongly associated with HEI-2015 components, forming the basis of the scoring algorithm with a range of 0-63 points, where higher score indicates a healthier diet. The median (IQR) screener and HEI-2015 scores were 14.96 (11.99-18.36) and 48.96 (39.51-59.48), respectively. The simulated PHD score was highly correlated with the HEI-2015 score (Spearman rho 0.75) in NHANES 2017-18 and confirmed in NHANES 2015-16 data (Spearman rho 0.75). CONCLUSIONS: The Penn Healthy Diet screener may be a useful tool for assessing diet quality due to its acceptable content validity, ease of administration, and ability to distinguish between servings of key food groups associated with a healthy versus unhealthy diet according to the HEI-2015. Additional research is needed to further establish the instrument's validity, and to refine a scoring algorithm.

Consumers' Ability to Distinguish Between Milk Types: Results of Blind Taste Testing.

The objective of this study was to assess consumers' ability to correctly identify different types of milk in a blind taste test and correlates of plans to purchase lower fat milk. Adults from 8 supermarkets in low-income neighborhoods tasted 3 types of unlabeled lower fat or fat-free milk samples and guessed the type of each sample. Of the 1074 participants, only 7.6% were able to identify all 3 unlabeled samples correctly. Most adults in this study reported consuming higher fat milk and could not correctly identify milk type by taste alone. Blind taste tests may encourage consumers to drink lower fat milk.

Role alteration predicts anxiety and depressive symptoms in parents of infants with congenital heart disease: a pilot study.

BACKGROUND: Parents of infants born with critical congenital heart disease are at risk for adverse mental health symptoms. The purpose of this study was to identify infant-, parent-, and environmental-based stressors for mothers and fathers after their infants' cardiac surgery, and to explore relationships between stressors and mental health symptoms of anxiety and depression. METHODS: This study enrolled 28 biological mother-father dyads from families admitted to the paediatric cardiac intensive care unit for cardiac surgery at one free-standing children's hospital in the Northeast. Paired t-tests were used to examine group differences between mothers and fathers on perceived stressors and mental health symptoms, while linear mixed effects modelling was used to explore the predictive relationship between perceived stressors, personal factors, and mental health symptoms. RESULTS: Mothers reported higher perceived stressor scores of parental role alteration (t = 4.03, p < 0.01) and infant appearance and behaviour (t = 2.61, p = 0.02), and total perceived stress (t = 2.29 p = 0.03), compared to fathers. Mothers also reported higher anxiety (t = 2.47, p = 0.02) and depressive symptoms (t = 3.25, p < 0.01) than fathers. In multivariable analysis, parental role alteration significantly predicted anxiety (t = 5.20, p < 0.01, d = 0.77) and depressive symptoms (t = 7.09, p < 0.01, d = 1.05) for mothers and fathers. The consensus subscale of the Dyadic Adjustment Scale also significantly predicted depressive symptoms (t = -2.42, p = 0.02, d = 0.04). CONCLUSION: Parents were distressed during their infant's admission for surgical repair for critical congenital heart disease. Parental role alteration was significantly associated with parental anxiety and depressive symptoms, while poor relationship quality was associated with depressive symptoms, highlighting areas for potential nursing-led psychosocial led interventions.

Spontaneous Dislodgement of Tunneled Dialysis Catheters after De Novo versus Over-The-Wire-Exchange Placement.

PURPOSE: To evaluate dislodgement of tunneled dialysis catheters (TDCs) in de novo (DN) placement with ultrasound versus over-the-wire exchange (OTWE). MATERIALS AND METHODS: Data were collected retrospectively on all TDC placements at this institution from 2001 to 2019 and were excluded if no removal date was recorded or if dwell time was more than 365 days. Information on TDC brand, placement, insertion/removal, and removal reason were collected. Multiple logistic regression evaluated factors associated with TDC dislodgement. DN placement and OTWE were compared for rate of dislodgement (generalized estimating equations method) and TDC dwell time (survival analysis). RESULTS: In total, 5328 TDCs were included with 66% (3522) placed DN and 32% (1727) via OTWE. Mean dwell time was 65 ± 72 days, and dislodgement occurred in 4% (224). TDC dislodgement rates in the DN and OTWE groups were 0.48 and 0.93 per 1000 catheter days, respectively. Brand (Ash Split vs. VectorFlow), placement technique (OTWE vs. DN), laterality (left vs. right), and site (left vs. right internal jugular vein) were significant predictors of dislodgement. OTWE placement exhibited 1.7 times the odds of dislodgement (95% confidence interval, 1.2-2.6; P = .004) compared to DN and had significantly higher probability of dislodgement across time (hazard ratio = 2.0; P < .001) compared to DN. Dislodgement rates for OTWE vs. DN were 8% vs. 3% (3 months), 13% vs. 6% (6 months), and 38% vs. 17% (1 year). CONCLUSIONS: TDC spontaneous dislodgement rates were significantly and consistently higher after OTWE compared to DN placement. These data support more careful attention to catheter fixation after OTWE placement.

Prevalence and Characterization of Interaction of Retrievable Inferior Vena Cava Filters with the Spine in Patients Undergoing Complex Filter Removal.

PURPOSE: To examine spinal interaction types and prevalence of inferior vena cava (IVC) filters in patients presenting for complex filter removal. MATERIALS AND METHODS: The records of 447 patients presenting for complex removal of IVC filters were reviewed, including patient demographics, IVC filter dwell time, filter fracture status, and computed tomography (CT) evidence of filter interaction with the spine. Spinal interaction was defined as a filter strut touching or penetrating into the vertebral body or disc. Patients with evidence of filter penetration and spinal interaction had abdominal CT that preceded filter removal assessed by 2 interventional radiologists to categorize the type of spinal interaction, including bony reaction and osteophyte formation. RESULTS: CT evidence of spinal interaction by the filter was found in 18% of patients (80/447). Interaction with the spine was more common in single point of fixation filters than filters with rails (P = .007) and was more likely in filters with round wires than flat wires (P = .0007). Patients with interaction had longer dwell times (mean [SD] 5.7 [4.46] y) compared with patients without interaction (mean [SD] 3.2 [3.85] y); this relationship was significant (P < .0001). Women were more likely than men to experience filter/spine interaction (P = .04). Filters with spinal interaction were more likely to be fractured (P = .001). Filter interaction was found in 38% (30/78) of patients with symptoms, including chest and back pain, compared with 14% (50/369) of patients without symptoms (P < .0001, odds ratio 3.99). CONCLUSIONS: Retrievable IVC filters may interact with the spine. These interactions are associated with longer filter dwell times, female sex, and round wire filter construction.

Skin-to-Skin Care Is a Safe and Effective Comfort Measure for Infants Before and After Neonatal Cardiac Surgery.

OBJECTIVES: To determine the effect of skin-to-skin care on stress, pain, behavioral organization, and physiologic stability of infants with critical congenital heart disease before and after neonatal cardiac surgery. DESIGN: A baseline response-paired design was used, with infants acting as their own controls before, during, and after skin-to-skin care at two distinct time points: once in the preoperative period (T1) and once in the postoperative period (T2). SETTING: Cardiac ICU and step-down unit in a large metropolitan freestanding children's hospital. SUBJECTS: Convenience sample of 30 infants admitted preoperatively for critical congenital heart disease. INTERVENTIONS: Eligible infants were placed into skin-to-skin care for 1 hour with their biological mothers once each at T1 and T2. MEASUREMENTS AND MAIN RESULTS: Measurements of stress (salivary cortisol), pain and behavior state (COMFORT scale), and physiologic stability (vital signs) were assessed immediately before skin-to-skin care, 30 minutes into skin-to-skin care, and 30 minutes after skin-to-skin care ended.At both T1 and T2, infant pain scores were significantly decreased (p < 0.0001) and infants moved into a calmer behavior state (p < 0.0001) during skin-to-skin care as compared to baseline. At T1, infants also had significantly reduced heart rate (p = 0.002) and respiratory rate (p < 0.0001) and increased systolic blood pressure (p = 0.033) during skin-to-skin care. At both T1 and T2, infant cortisol remained stable and unchanged from pre-skin-to-skin care to during skin-to-skin care (p = 0.096 and p = 0.356, respectively), and significantly increased from during skin-to-skin care to post-skin-to-skin care (p = 0.001 and p = 0.023, respectively). Exploratory analysis revealed differences in cortisol reactivity for infants with higher baseline cortisol (> 0.3 µg/dL) versus lower (≤ 0.3 µg/dL) prior to skin-to-skin care. Infants with higher baseline cortisol at T2 experienced significantly reduced cortisol during skin-to-skin care (p = 0.025). No significant differences in demographics or baseline variables were found between infants in either group. CONCLUSIONS: Skin-to-skin care is a low-cost, low-risk intervention that promotes comfort and supports physiologic stability in infants before and after neonatal cardiac surgery.

Caloric compensation and appetite control in children of different weight status and predisposition to obesity.

To prevent childhood obesity it is critical to identify behavioral phenotypes for overeating, especially among children who are predisposed to obesity. We examined caloric compensation and appetite control in 212 normal-weight (NW) and obese (OB) children, ages 7 to 9, who were at high risk (HR) or low risk (LR) for obesity based on maternal obesity. In a within-subjects crossover design, children ate breakfast, lunch, dinner, and snacks in the laboratory once a week for two weeks. Children's percentage compensation index (%COMPX) was computed at breakfast. Twenty-five minutes before breakfast, children received one of two compulsory preloads, which varied in energy density (ED) and caloric content [Low ED (LED): 1.00 kcal/g; 100 kcal; High ED (HED): 1.60 kcal/g; 160 kcal]. Children's appetite was measured hourly using Visual Analog Scales, which were used to compute 3-h post-prandial area under the curve (AUCs) after breakfast and the satiety quotient (SQ), which allows between-group comparisons of a fixed amount of a food's potency to reduce appetite sensations per unit of intake. There were no significant differences in %COMPX, SQ, or AUC among LR-NW, HR-NW, and HR-OB children (P > 0.10). SQs for Hunger and Prospective Consumption were higher and SQ for Fullness lower after consuming the LED compared to the HED preload (P < 0.009). Further, the SQ and AUC for Desire to Eat and AUC for Prospective Consumption significantly predicted energy intake during the remainder of the day (P < 0.03). In this study, HR-NW children did not differ from LR-NW or HR-OB children in their caloric compensation or appetite control. Foods with a high satiating effect may facilitate appetite control and help to moderate daily energy intake in all children, including at-risk children.

Implementing a School Vision Screening Program in Botswana Using Smartphone Technology.

Purpose: Child eye health is a significant public health issue in low- and middle-income countries, such as Botswana, and the need for eye care requires a well-integrated and innovative approach. Traditional vision screening tools are costly, difficult to transport, and reliant on highly trained eye care professionals. Novel smartphone-based vision screening technologies, however, are low cost, portable, and easily operated by trained novice users. Peek Vision is a mobile health (m-Health) organization that creates smartphone applications that screen for visual acuity, generate referrals to eye care professionals, and send phone notifications to those being screened. Methodology: In 2016, the government of Botswana partnered with local and international stakeholders to implement Peek vision screening in a subset of schoolchildren. From June to December of 2016, teachers, health assistants, nurses, and other volunteers in 49 schools in the Goodhope Subdistrict utilized Peek applications to screen schoolchildren, using acuity <6/12 in the better eye as a threshold for visual impairment. Results: Among 12,877 children screened, the application identified 16% (2,065/12,877) as screening positive for visual impairment, and these students were referred for optometric care. Ultimately, 96% (1,985/2,065) attended optometry triage camps, during which 42% (835/1,985) were provided with spectacles, 5% (94/1,985) received ophthalmic medications, and 3% (63/1,985) were referred for ophthalmic care. These findings underscore the need for comprehensive vision screening in schoolchildren in Botswana. Furthermore, the successful implementation of Peek smartphone applications illustrates the potential of m-Health technology for enacting comprehensive vision screening programs at a national level in Botswana and other similar countries.

Profiling ribonucleotide modifications at full-transcriptome level: a step toward MS-based epitranscriptomics.

The elucidation of the biological significance of RNA post-transcriptional modifications is hampered by the dearth of effective high-throughput sequencing approaches for detecting, locating, and tracking their levels as a function of predetermined experimental factors. With the goal of confronting this knowledge gap, we devised a strategy for completing global surveys of all ribonucleotide modifications in a cell, which is based on the analysis of whole cell extracts by direct infusion electrospray ionization mass spectrometry (ESI-MS). Our approach eschews chromatographic separation to promote instead the direct application of MS techniques capable of providing detection, differentiation, and quantification of post-transcriptional modifications (PTMs) in complex ribonucleotide mixtures. Accurate mass analysis was used to carry out database-aided identification of PTMs, whereas multistep tandem mass spectrometry (MS(n)) and consecutive reaction monitoring (CRM) provided the necessary structural corroboration. We demonstrated that heat-map plots afforded by ion mobility spectrometry mass spectrometry (IMS-MS) can provide comprehensive modification profiles that are unique for different cell types and metabolic states. We showed that isolated tRNA samples can be used as controlled sources of PTMs in standard-additions quantification. Intrinsic internal standards enable direct comparisons of heat-maps obtained under different experimental conditions, thus offering the opportunity to evaluate the global effects of such conditions on the expression levels of all PTMs simultaneously. This type of comparative analysis will be expected to support the investigation of the system biology of RNA modifications, which will be aimed at exploring mutual correlations of their expression levels and providing new valuable insights into their biological significance.

Site-Selective Aliphatic C-H Chlorination Using N-Chloroamides Enables a Synthesis of Chlorolissoclimide.

Methods for the practical, intermolecular functionalization of aliphatic C-H bonds remain a paramount goal of organic synthesis. Free radical alkane chlorination is an important industrial process for the production of small molecule chloroalkanes from simple hydrocarbons, yet applications to fine chemical synthesis are rare. Herein, we report a site-selective chlorination of aliphatic C-H bonds using readily available N-chloroamides and apply this transformation to a synthesis of chlorolissoclimide, a potently cytotoxic labdane diterpenoid. These reactions deliver alkyl chlorides in useful chemical yields with substrate as the limiting reagent. Notably, this approach tolerates substrate unsaturation that normally poses major challenges in chemoselective, aliphatic C-H functionalization. The sterically and electronically dictated site selectivities of the C-H chlorination are among the most selective alkane functionalizations known, providing a unique tool for chemical synthesis. The short synthesis of chlorolissoclimide features a high yielding, gram-scale radical C-H chlorination of sclareolide and a three-step/two-pot process for the introduction of the ß-hydroxysuccinimide that is salient to all the lissoclimides and haterumaimides. Preliminary assays indicate that chlorolissoclimide and analogues are moderately active against aggressive melanoma and prostate cancer cell lines.

Evaluation of a Mobile Health Approach to Tuberculosis Contact Tracing in Botswana.

Tuberculosis (TB) contact tracing is typically conducted in resource-limited settings with paper forms, but this approach may be limited by inefficiencies in data collection, storage, and retrieval and poor data quality. In Botswana, we developed, piloted, and evaluated a mobile health (mHealth) approach to TB contact tracing that replaced the paper form-based approach for a period of six months. For both approaches, we compared the time required to complete TB contact tracing and the quality of data collected. For the mHealth approach, we also administered the Computer System Usability Questionnaire to 2 health care workers who used the new approach, and we identified and addressed operational considerations for implementation. Compared to the paper form-based approach, the mHealth approach reduced the median time required to complete TB contact tracing and improved data quality. The mHealth approach also had favorable overall rating, system usefulness, information quality, and interface quality scores on the Computer System Usability Questionnaire. Overall, the mHealth approach to TB contact tracing improved on the paper form-based approach used in Botswana. This new approach may similarly benefit TB contact tracing efforts in other resource-limited settings.

Site-selective aliphatic C-H bromination using N-bromoamides and visible light.

Transformations that selectively functionalize aliphatic C-H bonds hold significant promise to streamline complex molecule synthesis. Despite the potential for site-selective C-H functionalization, few intermolecular processes of preparative value exist. Herein, we report an approach to unactivated, aliphatic C-H bromination using readily available N-bromoamide reagents and visible light. These halogenations proceed in useful chemical yields, with substrate as the limiting reagent. The site selectivities of these radical-mediated C-H functionalizations are comparable (or superior) to the most selective intermolecular C-H functionalizations known. With the broad utility of alkyl bromides as synthetic intermediates, this convenient approach will find general use in chemical synthesis.

Periprosthetic radius fracture after total wrist arthroplasty: A case report.

Total wrist arthroplasty (TWA) is indicated in select low demand patients with pan-carpal arthritis to decrease pain and preserve motion. Complications of TWA are well described including aseptic loosening, superficial and deep infection, wound issues, component dislocation, stiffness, and both intraoperative and post-operative fracture. With 4th generation implant designs, the incidence of many of these complications have decreased, but these complications remain challenging to address. In particular, sparse literature is available for the treatment of periprosthetic radius fractures after TWA. This report describes the management of an open, periprosthetic distal third radius fracture 18 months after index TWA in a medically complex 53-year-old female with lag screw fixation and a dorsal wrist spanning plate (DSP).