RNA sequencing of olfactory bulb in Parkinson's disease reveals gene alterations associated with olfactory dysfunction.

The olfactory bulb is involved early in the pathophysiology of Parkinson's disease (PD), which is consistent with the early onset of olfactory dysfunction. Identifying the molecular mechanisms through which PD affects the olfactory bulb could lead to a better understanding of the pathophysiology and etiology of olfactory dysfunction in PD. We specifically aimed to assess gene expression changes, affected pathways and co-expression network by whole transcriptomic profiling of the olfactory bulb in subjects with clinicopathologically defined PD. Bulk RNA sequencing was performed on frozen human olfactory bulbs of 20 PD and 20 controls without dementia or any other neurodegenerative disorder, from the Arizona Study of Aging and Neurodegenerative disorders and the Brain and Body Donation Program. Differential expression analysis (19 PD vs 19 controls) revealed 2164 significantly differentially expressed genes (1090 upregulated and 1074 downregulated) in PD. Pathways enriched in downregulated genes included oxidative phosphorylation, olfactory transduction, metabolic pathways, and neurotransmitters synapses while immune and inflammatory responses as well as cellular death related pathways were enriched within upregulated genes. An overrepresentation of microglial and astrocyte-related genes was observed amongst upregulated genes, and excitatory neuron-related genes were overrepresented amongst downregulated genes. Co-expression network analysis revealed significant modules highly correlated with PD and olfactory dysfunction that were found to be involved in the MAPK signaling pathway, cytokine-cytokine receptor interaction, cholinergic synapse, and metabolic pathways. LAIR1 (leukocyte associated immunoglobulin like receptor 1) and PPARA (peroxisome proliferator activated receptor alpha) were identified as hub genes with a high discriminative power between PD and controls reinforcing an important role of neuroinflammation in the olfactory bulb of PD subjects. Olfactory identification test score positively correlated with expression of genes coding for G-coupled protein, glutamatergic, GABAergic, and cholinergic receptor proteins and negatively correlated with genes for proteins expressed in glial olfactory ensheathing cells. In conclusion, this study reveals gene alterations associated with neuroinflammation, neurotransmitter dysfunction, and disruptions of factors involved in the initiation of olfactory transduction signaling that may be involved in PD-related olfactory dysfunction.

The effect of GLP-1RA exenatide on idiopathic intracranial hypertension: a randomized clinical trial.

Therapeutics to reduce intracranial pressure are an unmet need. Preclinical data have demonstrated a novel strategy to lower intracranial pressure using glucagon-like peptide-1 (GLP-1) receptor signalling. Here, we translate these findings into patients by conducting a randomized, placebo-controlled, double-blind trial to assess the effect of exenatide, a GLP-1 receptor agonist, on intracranial pressure in idiopathic intracranial hypertension. Telemetric intracranial pressure catheters enabled long-term intracranial pressure monitoring. The trial enrolled adult women with active idiopathic intracranial hypertension (intracranial pressure >25 cmCSF and papilloedema) who receive subcutaneous exenatide or placebo. The three primary outcome measures were intracranial pressure at 2.5 h, 24 h and 12 weeks and alpha set a priori at less than 0.1. Among the 16 women recruited, 15 completed the study (mean age 28 ± 9, body mass index 38.1 ± 6.2 kg/m2, intracranial pressure 30.6 ± 5.1 cmCSF). Exenatide significantly and meaningfully lowered intracranial pressure at 2.5 h -5.7 ± 2.9 cmCSF (P = 0.048); 24 h -6.4 ± 2.9 cmCSF (P = 0.030); and 12 weeks -5.6 ± 3.0 cmCSF (P = 0.058). No serious safety signals were noted. These data provide confidence to proceed to a phase 3 trial in idiopathic intracranial hypertension and highlight the potential to utilize GLP-1 receptor agonist in other conditions characterized by raised intracranial pressure.

Correlation of Presynaptic and Postsynaptic Proteins with Pathology in Alzheimer's Disease.

Synaptic transmission is essential for nervous system function and the loss of synapses is a known major contributor to dementia. Alzheimer's disease dementia (ADD) is characterized by synaptic loss in the mesial temporal lobe and cerebral neocortex, both of which are brain areas associated with memory and cognition. The association of synaptic loss and ADD was established in the late 1980s, and it has been estimated that 30-50% of neocortical synaptic protein is lost in ADD, but there has not yet been a quantitative profiling of different synaptic proteins in different brain regions in ADD from the same individuals. Very recently, positron emission tomography (PET) imaging of synapses is being developed, accelerating the focus on the role of synaptic loss in ADD and other conditions. In this study, we quantified the densities of two synaptic proteins, the presynaptic protein Synaptosome Associated Protein 25 (SNAP25) and the postsynaptic protein postsynaptic density protein 95 (PSD95) in the human brain, using enzyme-linked immunosorbent assays (ELISA). Protein was extracted from the cingulate gyrus, hippocampus, frontal, primary visual, and entorhinal cortex from cognitively unimpaired controls, subjects with mild cognitive impairment (MCI), and subjects with dementia that have different levels of Alzheimer's pathology. SNAP25 is significantly reduced in ADD when compared to controls in the frontal cortex, visual cortex, and cingulate, while the hippocampus showed a smaller, non-significant reduction, and entorhinal cortex concentrations were not different. In contrast, all brain areas showed lower PSD95 concentrations in ADD when compared to controls without dementia, although in the hippocampus, this failed to reach significance. Interestingly, cognitively unimpaired cases with high levels of AD pathology had higher levels of both synaptic proteins in all brain regions. SNAP25 and PSD95 concentrations significantly correlated with densities of neurofibrillary tangles, amyloid plaques, and Mini Mental State Examination (MMSE) scores. Our results suggest that synaptic transmission is affected by ADD in multiple brain regions. The differences were less marked in the entorhinal cortex and the hippocampus, most likely due to a ceiling effect imposed by the very early development of neurofibrillary tangles in older people in these brain regions.

Utilizing a HRSA Training Grant to Promote PMHNP Student Resilience: Answering the Call to Enhance Trauma-Informed Teaching and Learning Practices in Nursing Education.

Nursing burnout has reached a new level of prevalence among professionals and is rising among nursing students and can impact student success in the classroom and clinical areas. Among advanced practice nurses, psychiatric-mental health nurse practitioners have the least favorable combination of low compassion satisfaction and high secondary traumatic stress, placing them at even greater risk for burnout compared to other specialties. Trauma informed teaching and learning principles can serve to prevent burnout and have a positive impact on learning outcomes. Through these teaching methods, nurse educators have the opportunity to both support students during their nursing education and prepare students for the professional stressors that contribute to burnout. This quality improvement project involved implementation and evaluation of a HRSA funded program to train PMHNP students interested in working in rural and underserved areas. The training intervention included didactic curricular enhancements, a trauma resiliency training and a longitudinal clinical practicum. Qualitative program outcomes indicated that trainees were implementing trauma-informed principles and skills with patients and for self-care during their nursing training and at one year follow-up. The program may offer practical upstream solutions for nurse educators and future studies should explore concepts more formally to develop best practice models.

Differential phase contrast for quantitative imaging and spectro-microscopy at a nanoprobe beamline.

The interaction of a focused X-ray beam with a sample in a scanning probe experiment can provide a variety of information about the interaction volume. In many scanning probe experiments X-ray fluorescence (XRF) is supplemented with measurements of the transmitted or scattered intensity using a pixelated detector. The automated extraction of different signals from an area pixelated detector is described, in particular the methodology for extracting differential phase contrast (DPC) is demonstrated and different processing methods are compared across a range of samples. The phase shift of the transmitted X-ray beam by the sample, extracted from DPC, is also compared with ptychography measurements to provide a qualitative and quantitative comparison. While ptychography produces a superior image, DPC can offer a simple, flexible method for phase contrast imaging which can provide fast results and feedback during an experiment; furthermore, for many science problems, such as registration of XRF in a lighter matrix, DPC can provide sufficient information to meet the experimental aims. As the DPC technique is a quantitative measurement, it can be expanded to spectroscopic studies and a demonstration of DPC for spectro-microscopy measurements is presented. Where ptychography can separate the absorption and phase shifts by the sample, quantitative interpretation of a DPC image or spectro-microscopy signal can only be performed directly when absorption is negligible or where the absorption contribution is known and the contributions can be fitted.

Measuring Up: A Comparison of TapeStation 4200 and Bioanalyzer 2100 as Measurement Tools for RNA Quality in Postmortem Human Brain Samples.

The determination of RNA integrity is a critical quality assessment tool for gene expression studies where the experiment's success is highly dependent on the sample quality. Since its introduction in 1999, the gold standard in the scientific community has been the Agilent 2100 Bioanalyzer's RNA integrity number (RIN), which uses a 1-10 value system, from 1 being the most degraded, to 10 being the most intact. In 2015, Agilent launched 4200 TapeStation's RIN equivalent, and reported a strong correlation of r2 of 0.936 and a median error < ±0.4 RIN units. To evaluate this claim, we compared the Agilent 4200 TapeStation's RIN equivalent (RINe) and DV200 to the Agilent 2100 Bioanalyzer's RIN for 183 parallel RNA samples. In our study, using RNA from a total of 183 human postmortem brain samples, we found that the RIN and RINe values only weakly correlate, with an r2 of 0.393 and an average difference of 3.2 RIN units. DV200 also only weakly correlated with RIN (r2 of 0.182) and RINe (r2 of 0.347). Finally, when applying a cut-off value of 6.5 for both metrics, we found that 95.6% of samples passed with RIN, while only 23.5% passed with RINe. Our results suggest that even though RIN (Bioanalyzer) and RINe (TapeStation) use the same 1-10 value system, they should not be used interchangeably, and cut-off values should be calculated independently.

Micron-sized biogenic and synthetic hollow mineral spheres occlude additives within single crystals.

Incorporating additives within host single crystals is an effective strategy for producing composite materials with tunable mechanical, magnetic and optical properties. The type of guest materials that can be occluded can be limited, however, as incorporation is a complex process depending on many factors including binding of the additive to the crystal surface, the rate of crystal growth and the stability of the additives in the crystallisation solution. In particular, the size of occluded guests has been restricted to a few angstroms - as for single molecules - to a few hundred nanometers - as for polymer vesicles and particles. Here, we present a synthetic approach for occluding micrometer-scale objects, including high-complexity unicellular organisms and synthetic hollow calcite spheres within calcite single crystals. Both of these objects can transport functional additives, including organic molecules and nanoparticles that would not otherwise occlude within calcite. Therefore, this method constitutes a generic approach using calcite as a delivery system for active compounds, while providing them with effective protection against environmental factors that could cause degradation.

Recurrence and survival after curative-intent treatment for colorectal liver metastases: Implications for adjuvant liver-directed regional chemotherapy.

BACKGROUND: This study investigates tumor recurrence patterns and their effect on postrecurrence survival following curative-intent treatment of colorectal liver metastases (CRLM) to identify those who stand to benefit the most from adjuvant liver-directed therapy. METHODS: This is a retrospective analysis of all patients that underwent liver resection and/or ablation for CRLM between 2007 and 2019. Postrecurrence survival was compared between recurrence locations. Risk factors for liver recurrence were sought. RESULTS: The study included 227 patients. Majority were treated with resection (71.0%) while combination resection/ablation (18.9%) and ablation alone (11.0%), were less common. At a median follow-up of 3.0 years, recurrence was observed in 151 (66.5%) patients. Of those, liver, lung, and peritoneal recurrence were most common at 66.9%, 49.6%, and 9.2%, respectively. Median postrecurrence survival after liver, lung, and multisite recurrence was 39.6-, 68.4-, and 33.6 months, respectively. High tumor grade (p < 0.014), perineural invasion (p = 0.002), and N0 node status (p = 0.017) of primary tumor correlated with liver recurrence on multivariate analysis. CONCLUSIONS: Tumor grade, perineural invasion, and N0 node status of the primary tumor are associated with increased risk of liver recurrence after CRLM resection and represent a target population that may benefit the most from adjuvant liver-directed regional chemotherapy.

The Impact of an Educational Intervention on Nursing Staff Attitudes Toward Patients Experiencing Homelessness and Mental Illness.

OBJECTIVE: Patients who experience homelessness and have mental illness can have frequent and challenging hospitalizations. Nurses caring for this vulnerable population may have negative attitudes, which can be mitigated by education and improved for the benefit of patients. This study aimed to assess the impact of an educational intervention on the attitudes of nursing staff toward individuals experiencing homelessness and mental illness. METHODS: Using a pre-post design, a revised version of the Health Professionals' Attitudes Toward the Homeless Inventory (HPATHI) assessed 23 nursing staff working on inpatient medicine units surrounding a brief educational session about persons experiencing homelessness and mental illness. Data were also collected from open-ended questions. RESULTS: There was a small positive increase in mean HPATHI scores postintervention (74.783 [SD = 5.485] to 77.13 [SD = 6.312]) indicating more positive participant attitudes toward homeless individuals. The HPATHI also revealed a 6% increase in score for participant comfortability providing care for homeless persons with major mental illness postintervention. Some participants likely interpreted their answers as displaying more positive and less cynical attitudes based on their comments, while the HPATHI scored them as more negative. Qualitative feedback revealed both positive and negative attitudes toward this patient population, and various associated barriers to care. CONCLUSIONS: Nursing staff will likely provide care for patients who experience homelessness with concomitant mental illness. Educating nurses about the needs of this population is feasible and could be beneficial for patient care.

Problem Solving Training for Veterans with Complex Comorbidities: Treatment Delivery Adaptations during COVID-19.

OBJECTIVES: To summarize adaptations due to COVID-19 for VA Problem Solving Training (PST) for clinicians serving medically complex patients and to compare patient mental health outcomes in the year before (2019) and during COVID-19 (2020). METHODS: Clinicians attended a multi-day workshop and up to 6 months of small-group consultation for two training cases. In 2019 and 2020, 122 Veteran patients completed baseline and posttreatment measures of depression (Patient Health Questionnaire-9), anxiety (Generalized Anxiety Disorder-7 item), and negative problem-solving beliefs (Negative Problem Orientation Questionnaire). Qualitative data were collected on clinician's pandemic-related treatment implementation challenges. RESULTS: Program adaptations during COVID-19 addressed challenges due to delivering treatment by telephone, video, or in person; Veteran patient recruitment barriers; and privacy issues for telephone and video. Veterans in both pre-pandemic and COVID-19 cohorts had significant improvements in depression, anxiety, and negative problem-solving beliefs, with no significant differences in the amount of improvement between the two cohorts. CONCLUSIONS: Flexibilities afforded to clinicians delivering the PST training program during the pandemic addressed key obstacles and barriers to recruitment, and implementation did not diminish the effectiveness of the intervention. CLINICAL IMPLICATIONS: Findings support continued implementation of the PST training program with added flexibility to treatment delivery beyond the pandemic.

Epidemiology of disease-activity related ophthalmological manifestations in Systemic Lupus Erythematosus: A systematic review.

OBJECTIVE: Ophthalmic complications in Systemic Lupus Erythematosus (SLE) are broad and can occur in up to a third of patients. The British Isles Lupus Assessment Group (BILAG) 2004 Index identifies 13 ocular manifestations of active SLE, as opposed to those related to previous disease activity and/or the consequences of therapy. We conducted a systematic review of published literature to determine the frequency of ophthalmic manifestations of active SLE. METHODS: A systematic literature search of Ovid MEDLINE and EMBASE from their respective inceptions to July 2020 was conducted to identify cohort, case-control and cross-sectional studies. RESULTS: 22 studies meeting eligibility criteria were included. Most studies featured small sample sizes and were judged to have a high risk of methodological bias. The number and quality of studies did not allow us to confidently estimate the incidence of the conditions. No studies reported epidemiological data for orbital inflammation/myositis/proptosis. The prevalence of each of the other ocular manifestations, with the exception of retinal vaso-occlusive disease, was consistently less than 5%. Retinal vasculitis, uveitis and isolated cotton wool spots tended to be associated with more active SLE disease. CONCLUSION: The prevalence of eye disease due to SLE activity is uncommon, but clinicians should be aware that some conditions tend to be associated with more active systemic disease. Further studies to determine the incidence and risk factors for these ophthalmic manifestations are needed.

Showcasing Nursing Leadership and Contributions to a University's COVID-19 Student Contact Tracing Process.

The COVID-19 pandemic was an unprecedented event that impacted every segment of healthcare, including universities preparing healthcare professionals. Instituting processes to coordinate student return to campus and ongoing COVID-19 testing and contract tracing challenged university campuses, but also brought opportunities for collaboration. This article reports on the experiences of one nonprofit private higher education university in management of the COVID-19 testing and contact tracing that were led by school of nursing faculty and nursing leadership.

Identification of Interleukin-8-Reducing Lead Compounds Based on SAR Studies on Dihydrochalcone-Related Compounds in Human Gingival Fibroblasts (HGF-1 cells) In Vitro.

Background: In order to identify potential activities against periodontal diseases, eighteen dihydrochalcones and structurally related compounds were tested in an established biological in vitro cell model of periodontal inflammation using human gingival fibroblasts (HGF-1 cells). Methods: Subsequently to co-incubation of HGF-1 cells with a bacterial endotoxin (Porphyromonas gingivalis lipopolysaccharide, pgLPS) and each individual dihydrochalcone in a concentration range of 1 µM to 100 µM, gene expression of interleukin-8 (IL-8) was determined by qPCR and cellular interleukin-8 (IL-8) release by ELISA. Results: Structure-activity analysis based on the dihydrochalcone backbone and various substitution patterns at its aromatic ring revealed moieties 2',4,4',6'-tetrahydroxy 3-methoxydihydrochalcone (7) to be the most effective anti-inflammatory compound, reducing the pgLPS-induced IL-8 release concentration between 1 µM and 100 µM up to 94%. In general, a 2,4,6-trihydroxy substitution at the A-ring and concomitant vanilloyl (4-hydroxy-3-methoxy) pattern at the B-ring revealed to be preferable for IL-8 release inhibition. Furthermore, the introduction of an electronegative atom in the A,B-linker chain led to an increased anti-inflammatory activity, shown by the potency of 4-hydroxybenzoic acid N-vanillylamide (13). Conclusions: Our data may be feasible to be used for further lead structure designs for the development of potent anti-inflammatory additives in oral care products.

The Feasibility and Efficacy of a Behavioral Intervention to Promote Appropriate Gestational Weight Gain.

INTRODUCTION: Nearly half of all women gain above gestational weight gain (GWG) recommendations. This study assessed the feasibility and efficacy of a pilot behavioral intervention on GWG and physical activity behaviors. METHODS: Women (n = 45) 14-20 weeks gestation enrolled in a behavioral intervention. Physicians 'prescribed' the intervention to low risk patients. The intervention included self-monitoring, support, and optional walking groups. Process evaluation measures regarding usage and acceptability of study components were obtained. Physical activity was objectively measured at baseline and 35 weeks. The percentage of participants with appropriate GWG was calculated. Control data was obtained from the same clinic where participants were recruited. RESULTS: Overall, the intervention was acceptable to participants; attrition was low (6.7%), weekly contact was high (87%), and self-monitoring was high (Fitbit worn on 82% of intervention weeks; weekly weighing on 81%). Facebook (40% of weeks) and study website use (19%) was low, as was walking group attendance (7% attended a single group). Participants reported a lack of discussions about the study with their physician. Results showed no significant difference between intervention and control participants in the percentage who gained excess weight (p = 0.37). There was a significant decrease in moderate-to-vigorous physical activity in intervention participants (p < 0.0001). DISCUSSION: Continued efforts for promoting physical activity and appropriate GWG are needed. Although acceptable, the intervention was not efficacious. Trainings for, or input from prenatal healthcare providers on how to best encourage and support patients' engagement in healthy behaviors, such as PA, are warranted.

United Kingdom CSF Disorders Day 2018.

The multi-specialty approach to managing patients with cerebrospinal fluid (CSF) disorders requires neurology, neurosurgery, neuroradiology and neuro-ophthalmology. The annual United Kingdom CSF disorders meeting presented the first guidelines for idiopathic intracranial hypertension focusing on protecting the vision, managing the underlying disease and reducing headache morbidity. The most recent scientific concepts in CSF disorders were presented, as was the applied understanding of shunt and valve technology.

Life in the fast lane: Settled pastoralism in the Central Eurasian Steppe during the Middle Bronze Age.

OBJECTIVES: We tested the hypothesis that the purported unstable climate in the South Urals region during the Middle Bronze Age (MBA) resulted in health instability and social stress as evidenced by skeletal response. METHODS: The skeletal sample (n = 99) derived from Kamennyi Ambar 5 (KA-5), a MBA kurgan cemetery (2040-1730 cal. BCE, 2 sigma) associated with the Sintashta culture. Skeletal stress indicators assessed included cribra orbitalia, porotic hyperostosis, dental enamel hypoplasia, and tibia periosteal new bone growth. Dental disease (caries, abscess, calculus, and periodontitis) and trauma were scored. Results were compared to regional data from the nearby Samara Valley, spanning the Early to Late Bronze Age (EBA, LBA). RESULTS: Lesions were minimal for the KA-5 and MBA-LBA groups except for periodontitis and dental calculus. No unambiguous weapon injuries or injuries associated with violence were observed for the KA-5 group; few injuries occurred at other sites. Subadults (<18 years) formed the majority of each sample. At KA-5, subadults accounted for 75% of the sample with 10% (n = 10) estimated to be 14-18 years of age. CONCLUSIONS: Skeletal stress markers and injuries were uncommon among the KA-5 and regional groups, but a MBA-LBA high subadult mortality indicates elevated frailty levels and inability to survive acute illnesses. Following an optimal weaning program, subadults were at risk for physiological insult and many succumbed. Only a small number of individuals attained biological maturity during the MBA, suggesting that a fast life history was an adaptive regional response to a less hospitable and perhaps unstable environment.

Provision of Buprenorphine to Pregnant Women by For-Profit Clinics in an Appalachian City.

OBJECTIVES: This study was undertaken to confirm that patient reports on buprenorphine medication-assisted therapy in for-profit buprenorphine clinics in our community were personally costly. We contacted all 17 for-profit clinics in our community and confirmed the patient reports that a significant financial payment of ≤$100 was required for each visit. We also found that tapering of buprenorphine dosage in pregnancy was offered by several of the clinics. METHODS: A telephone survey was conducted with the 17 for-profit buprenorphine clinics located in the Johnson City, Tennessee area. The clinic representative who answered the telephone was asked questions regarding patient costs for therapy and availability of tapering programs for pregnant women. RESULTS: Patient reports that the for-profit clinics are costly were confirmed. None of the clinics accepted insurance reimbursement of any type. The most common weekly costs were $100 per visit. A majority of clinics offered biweekly or monthly visits at significantly increased rates. Clinic representatives stated that a majority of clinics would consider buprenorphine tapering programs for pregnant women. CONCLUSIONS: The high cost of for-profit clinics is a barrier for patient access to medication-assisted therapy with buprenorphine. Tapering of buprenorphine dosage in pregnant women has penetrated buprenorphine management practice in our community. Further research is needed to determine whether elimination of cost barrier would have a positive effect on the rates of neonatal abstinence syndrome.

Residents' response to bleeding during a simulated robotic surgery task.

BACKGROUND: The aim of this study was to assess performance measurement validity of our newly developed robotic surgery task trainer. We hypothesized that residents would exhibit wide variations in their intercohort performance as well as a measurable difference compared to surgeons in fellowship training. MATERIALS AND METHODS: Our laboratory synthesized a model of a pelvic tumor that simulates unexpected bleeding. Surgical residents and fellows of varying specialties completed a demographic survey and were allowed 20 minutes to resect the tumor using the da Vinci robot and achieve hemostasis. At a standardized event in the simulation, venous bleeding began, and participants attempted hemostasis using suture ligation. A motion tracking system, using electromagnetic sensors, recorded participants' hand movements. A postparticipation Likert scale survey evaluated participants' assessment of the model's realism and usefulness. RESULTS: Three of the seven residents (postgraduate year 2-5), and the fellow successfully resected the tumor in the allotted time. Residents showed high variability in performance and blood loss (125-700 mL) both within their cohort and compared to the fellow (150 mL blood). All participants rated the model as having high realism and utility for trainees. CONCLUSIONS: The results support that our bleeding pelvic tumor simulator has the ability to discriminate resident performance in robotic surgery. The combination of motion, decision-making, and blood loss metrics offers a multilevel performance assessment, analyzing both technical and decision-making abilities.

Solid-State Transformation of Amorphous Calcium Carbonate to Aragonite Captured by CryoTEM.

Early-stage reaction mechanisms for aragonite-promoting systems are relatively unknown compared to the more thermodynamically stable calcium carbonate polymorph, calcite. Using cryoTEM and SEM, the early reaction stages taking place during aragonite formation were identified in a highly supersaturated solution using an alcohol-water solvent, and an overall particle attachment growth mechanism was described for the system. In vitro evidence is provided for the solid-state transformation of amorphous calcium carbonate to aragonite, demonstrating the co-existence of both amorphous and crystalline material within the same aragonite needle. This supports non-classical formation of aragonite within both a synthetic and biological context.

Replicating the Safer Sex Intervention: 9-Month Impact Findings of a Randomized Controlled Trial.

OBJECTIVES: To test the effects of the Safer Sex Intervention (SSI) on female adolescents' sexual behavior and possible antecedents of behavior such as sexual health attitudes, knowledge, motivation, intentions, and skills. METHODS: A randomized controlled trial compared SSI (n = 1196) with no intervention (n = 613) among female adolescents aged 13 to 20 years at 3 sites across the United States from 2012 to 2015. Intent-to-treat impacts were estimated at 9 months after baseline, overall, and for key subgroups. RESULTS: Compared with control participants, SSI participants were less likely to have sexual intercourse without birth control, more likely to report positive attitudes toward protection and intention to use condoms, and more confident of their ability to refuse sex. SSI did not affect sexual risk knowledge or motivation to delay childbearing. Positive impacts on sexual behavior and sexual risk were observed among key subgroups of youths who were aged 18 years or older, Hispanic, not sexually experienced at baseline, and enrolled at the Minnesota site. CONCLUSIONS: SSI produced meaningful changes in sexual behavior and sexual risk and successfully addressed some potential antecedents of sexual risk behavior.