Acceptability of data linkage to identify women at risk of postnatal complication for the development of digital risk prediction tools and interventions to better optimise postnatal care, a qualitative descriptive study design.

BACKGROUND: Pregnancy acts as a cardiovascular stress test. Although many complications resolve following birth, women with hypertensive disorder of pregnancy have an increased risk of developing cardiovascular disease (CVD) long-term. Monitoring postnatal health can reduce this risk but requires better methods to identity high-risk women for timely interventions. METHODS: Employing a qualitative descriptive study design, focus groups and/or interviews were conducted, separately engaging public contributors and clinical professionals. Diverse participants were recruited through social media convenience sampling. Semi-structured, facilitator-led discussions explored perspectives of current postnatal assessment and attitudes towards linking patient electronic healthcare data to develop digital tools for identifying postpartum women at risk of CVD. Participant perspectives were gathered using post-it notes or a facilitator scribe and analysed thematically. RESULTS: From 27 public and seven clinical contributors, five themes regarding postnatal check expectations versus reality were developed, including 'limited resources', 'low maternal health priority', 'lack of knowledge', 'ineffective systems' and 'new mum syndrome'. Despite some concerns, all supported data linkage to identify women postnatally, targeting intervention to those at greater risk of CVD. Participants outlined potential benefits of digitalisation and risk prediction, highlighting design and communication needs for diverse communities. CONCLUSIONS: Current health system constraints in England contribute to suboptimal postnatal care. Integrating data linkage and improving education on data and digital tools for maternal healthcare shows promise for enhanced monitoring and improved future health. Recognised for streamlining processes and risk prediction, digital tools may enable more person-centred care plans, addressing the gaps in current postnatal care practice.

Situational analysis of hypertension management at primary health care level in São Paulo, Brazil: population, healthcare professional and health system perspectives.

BACKGROUND: Government-led, population-wide initiatives are crucial for advancing the management of hypertension - a leading cause of cardiovascular disease (CVD) morbidity and mortality. An urban population health initiative was conducted against this backdrop, focussing on hypertension in the primary health system in São Paulo, Brazil. Within the frame of the initiative and under the supervision and leadership of the municipal health authorities, a situational analysis was conducted on the needs in hypertension management, marking the first phase of a Design Thinking process. This article describes the situational analysis process and presents the identified elements to be strengthened considering hypertension diagnosis, treatment and control. METHODS: First, a mixed-methods approach was used, starting with a literature review of municipal hypertension data followed by meetings (N = 20) with the local public health administration to assess health system level components. To investigate activities on hypertension diagnosis, treatment and control, nine primary healthcare units were selected from two districts of São Paulo city- Itaquera and Penha- which received an online form addressed to managers, participated in conversation circles of staff and patients, and underwent shadowing of community health agents. RESULTS: Data gave rise to two main outputs: (i) a patient care journey map; and (ii) a matrix summarizing the identified needs at patient, healthcare professional and health system level for diagnosis, treatment and control of hypertension. Patient awareness and knowledge of hypertension was found to be insufficient and its management needs to be improved. For health professionals, disease awareness, technical training, more time dedicated to patients, and simplified guidelines and clinical decision-making tools for hypertension management were identified as principal needs. The situational analysis found that the healthcare systems efficiency might be improved by establishing defined treatment and care delivery goals with a focus on outcomes and implemented through action plans. CONCLUSIONS: This situational analysis identified several needs related to hypertension control in São Paulo that are in line with global challenges to improve the control of CVD risk factors. Findings were also confirmed locally in an expansion phase of this situational analysis to additional primary care facilities. As a consequence, solutions were designed, promptly taken up and implemented by the municipal health secretariat.

Injectable Granular Hydrogels Enable Avidity-Controlled Biotherapeutic Delivery.

Protein therapeutics represent a rapidly growing class of pharmaceutical agents that hold great promise for the treatment of various diseases such as cancer and autoimmune dysfunction. Conventional systemic delivery approaches, however, result in off-target drug exposure and a short therapeutic half-life, highlighting the need for more localized and controlled delivery. We have developed an affinity-based protein delivery system that uses guest-host complexation between ß-cyclodextrin (CD, host) and adamantane (Ad, guest) to enable sustained localized biomolecule presentation. Hydrogels were formed by the copolymerization of methacrylated CD and methacrylated dextran. Extrusion fragmentation of bulk hydrogels yielded shear-thinning and self-healing granular hydrogels (particle diameter = 32.4 ± 16.4 µm) suitable for minimally invasive delivery and with a high host capacity for the retention of guest-modified proteins. Bovine serum albumin (BSA) was controllably conjugated to Ad via EDC chemistry without affecting the affinity of the Ad moiety for CD (KD = 12.0 ± 1.81 µM; isothermal titration calorimetry). The avidity of Ad-BSA conjugates was directly tunable through the number of guest groups attached, resulting in a fourfold increase in the complex half-life (t1/2 = 5.07 ± 1.23 h, surface plasmon resonance) that enabled a fivefold reduction in protein release at 28 days. Furthermore, we demonstrated that the conjugation of Ad to immunomodulatory cytokines (IL-4, IL-10, and IFNγ) did not detrimentally affect cytokine bioactivity and enabled their sustained release. Our strategy of avidity-controlled delivery of protein-based therapeutics is a promising approach for the sustained local presentation of protein therapeutics and can be applied to numerous biomedical applications.

The Womb Cancer Awareness Measure (WCAM): development of an instrument to assess public awareness of endometrial cancer.

OBJECTIVE: To develop and test a novel instrument to assess public awareness of endometrial cancer symptoms and risk factors in a UK population. METHODS: A 36-item questionnaire was developed through literature review and extraction from cancer awareness materials. The Womb Cancer Awareness Measure (WCAM) was tested for content validity in 65 self-identified female research participants and 10 endometrial cancer experts prior to UK-wide field testing using social media. Test-retest reliability was assessed over 2 weeks, construct validity was assessed by comparing womb cancer experts and non-medical academics, and sensitivity to change was assessed by comparing scores of participants who read an endometrial cancer leaflet with those given a control leaflet. RESULTS: Fifty-two percent of the items in the test-retest reliability showed >80% agreement. Construct validity was demonstrated; endometrial cancer experts achieved higher scores (median 79 (IQR 18)) than non-medical academics (median 50 (IQR 18)) (p<0.001). The WCAM was sensitive to change; volunteers who read an endometrial cancer leaflet showed greater awareness (median 73 (IQR 9)) than those who read the control leaflet (median 59 (IQR 9)) (p<0.001). Knowledge of endometrial cancer red flag symptoms and risk factors was poor in the 847 UK-based participants. CONCLUSIONS: Our findings support the validity and reliability of the Womb Cancer Awareness Measure in assessing public awareness of endometrial cancer. In a UK population sample, knowledge of warning symptoms and risk factors was low, highlighting the need for public awareness campaigns.

Lactate activates the mitochondrial electron transport chain independently of its metabolism.

Lactate has long been considered a cellular waste product. However, we found that as extracellular lactate accumulates, it also enters the mitochondrial matrix and stimulates mitochondrial electron transport chain (ETC) activity. The resulting increase in mitochondrial ATP synthesis suppresses glycolysis and increases the utilization of pyruvate and/or alternative respiratory substrates. The ability of lactate to increase oxidative phosphorylation does not depend on its metabolism. Both L- and D-lactate are effective at enhancing ETC activity and suppressing glycolysis. Furthermore, the selective induction of mitochondrial oxidative phosphorylation by unmetabolized D-lactate reversibly suppressed aerobic glycolysis in both cancer cell lines and proliferating primary cells in an ATP-dependent manner and enabled cell growth on respiratory-dependent bioenergetic substrates. In primary T cells, D-lactate enhanced cell proliferation and effector function. Together, these findings demonstrate that lactate is a critical regulator of the ability of mitochondrial oxidative phosphorylation to suppress glucose fermentation.

Lactate activates the mitochondrial electron transport chain independent of its metabolism.

Lactate has long been considered a cellular waste product. However, we found that as extracellular lactate accumulates, it also enters the mitochondrial matrix and stimulates mitochondrial electron transport chain (ETC) activity. The resulting increase in mitochondrial ATP synthesis suppresses glycolysis and increases the utilization of pyruvate and/or alternative respiratory substrates. The ability of lactate to increase oxidative phosphorylation does not depend on its metabolism. Both L- and D-lactate are effective at enhancing ETC activity and suppressing glycolysis. Furthermore, the selective induction of mitochondrial oxidative phosphorylation by unmetabolized D-lactate reversibly suppressed aerobic glycolysis in both cancer cell lines and proliferating primary cells in an ATP-dependent manner and enabled cell growth on respiratory-dependent bioenergetic substrates. In primary T cells, D-lactate enhanced cell proliferation and effector function. Together, these findings demonstrate that lactate is a critical regulator of the ability of mitochondrial oxidative phosphorylation to suppress glucose fermentation.

The First Cold Atmospheric Plasma Phase I Clinical Trial for the Treatment of Advanced Solid Tumors: A Novel Treatment Arm for Cancer.

Local regional recurrence (LRR) remains the primary cause of treatment failure in solid tumors despite advancements in cancer therapies. Canady Helios Cold Plasma (CHCP) is a novel Cold Atmospheric Plasma device that generates an Electromagnetic Field and Reactive Oxygen and Nitrogen Species to induce cancer cell death. In the first FDA-approved Phase I trial (March 2020-April 2021), 20 patients with stage IV or recurrent solid tumors underwent surgical resection combined with intra-operative CHCP treatment. Safety was the primary endpoint; secondary endpoints were non-LRR, survival, cancer cell death, and the preservation of surrounding healthy tissue. CHCP did not impact intraoperative physiological data (p > 0.05) or cause any related adverse events. Overall response rates at 26 months for R0 and R0 with microscopic positive margin (R0-MPM) patients were 69% (95% CI, 19-40%) and 100% (95% CI, 100-100.0%), respectively. Survival rates for R0 (n = 7), R0-MPM (n = 5), R1 (n = 6), and R2 (n = 2) patients at 28 months were 86%, 40%, 67%, and 0%, respectively. The cumulative overall survival rate was 24% at 31 months (n = 20, 95% CI, 5.3-100.0). CHCP treatment combined with surgery is safe, selective towards cancer, and demonstrates exceptional LRR control in R0 and R0-MPM patients. (Clinical Trials identifier: NCT04267575).

Population health impact and economic evaluation of the CARDIO4Cities approach to improve urban hypertension management.

Cardiovascular disease (CVD) is the leading cause of mortality worldwide, with 80% of that mortality occurring in low- and middle-income countries. Hypertension, its primary risk factor, can be effectively addressed through multisectoral, multi-intervention initiatives. However, evidence for the population-level impact on cardiovascular (CV) event rates and mortality, and the cost-effectiveness of such initiatives is scarce as long-term longitudinal data is often lacking. Here, we model the long-term population health impact and cost-effectiveness of a multisectoral urban population health initiative designed to reduce hypertension, conducted in Ulaanbaatar (Mongolia), Dakar (Senegal), and in the district of Itaquera in São Paulo (Brazil) in collaboration with the local governments. We based our analysis on cohort-level data among hypertensive patients on treatment and control rates from a real-world effectiveness study of the CARDIO4Cities approach (built on quality of care, early access, policy reform, data and digital, Intersectoral collaboration, and local ownership). We built a decision tree model to estimate the CV event rates during implementation (1-2 years) and a Markov model to project health outcomes over 10 years. We estimated the number of CV events averted and quality-adjusted life-years gained (QALYs through the initiative and assessed its cost-effectiveness based on the costs reported by the funder using the incremental cost effectiveness ratio (ICER) and published thresholds. A one-way sensitivity analysis was performed to assess the robustness of the results. The modelled patient cohorts included 10,075 patients treated for hypertension in Ulaanbaatar, 5,236 in Dakar, and 5,844 in São Paulo. We estimated that 3.3-12.8% of strokes and 3.0-12.0% of coronary heart disease (CHD) events were averted during 1-2 years of implementation in the three cities. We estimated that over the subsequent 10 years, 3.6-9.9% of strokes, 2.8-7.8% of CHD events, and 2.7-7.9% of premature deaths would be averted. The estimated ICER was USD 748 QALY gained in Ulaanbaatar, USD 3091 in Dakar, and USD 784 in São Paulo. With that, the intervention was estimated to be cost-effective in Ulaanbaatar and São Paulo. For Dakar, cost-effectiveness was met under WHO-CHOICE standards, but not under more conservative standards adjusted for purchasing power parity (PPP) and opportunity costs. The findings were robust to the sensitivity analysis. Our results provide evidence that the favorable impact of multisector systemic interventions designed to reduce the hypertension burden extend to long-term population-level CV health outcomes and are likely cost-effective. The CARDIO4Cities approach is predicted to be a cost-effective solution to alleviate the growing CVD burden in cities across the world.

Ancient DNA reveals admixture history and endogamy in the prehistoric Aegean.

The Neolithic and Bronze Ages were highly transformative periods for the genetic history of Europe but for the Aegean-a region fundamental to Europe's prehistory-the biological dimensions of cultural transitions have been elucidated only to a limited extent so far. We have analysed newly generated genome-wide data from 102 ancient individuals from Crete, the Greek mainland and the Aegean Islands, spanning from the Neolithic to the Iron Age. We found that the early farmers from Crete shared the same ancestry as other contemporaneous Neolithic Aegeans. In contrast, the end of the Neolithic period and the following Early Bronze Age were marked by 'eastern' gene flow, which was predominantly of Anatolian origin in Crete. Confirming previous findings for additional Central/Eastern European ancestry in the Greek mainland by the Middle Bronze Age, we additionally show that such genetic signatures appeared in Crete gradually from the seventeenth to twelfth centuries BC, a period when the influence of the mainland over the island intensified. Biological and cultural connectedness within the Aegean is also supported by the finding of consanguineous endogamy practiced at high frequencies, unprecedented in the global ancient DNA record. Our results highlight the potential of archaeogenomic approaches in the Aegean for unravelling the interplay of genetic admixture, marital and other cultural practices.

Diagnosis and Management of Monogenic Diabetes in Pregnancy.

Monogenic diabetes occurs in up to 3% of people with diabetes. Mutations in over 40 different genes are responsible. The most common genes affected are HNF1A, HNF4A, GCK, and HNF1B. Additionally, other types of diabetes with a genetic aetiology include neonatal diabetes and diabetes plus syndrome. Each of these genetic subtypes has a different phenotype and requires distinctive treatments. Due to the overlap of monogenic diabetes with type 1 and 2 diabetes and even gestational diabetes, they can often be misdiagnosed. During pregnancy, individual subtypes require treatment that is different from standard diabetes care, so recognition and prompt diagnosis of monogenic diabetes are important to avoid inadequate treatment. We describe the management of monogenic diabetes for the most significant subtypes, focussing on the impact on and management in pregnancy. A genetic diagnosis of diabetes can alter long-term treatment in those with diabetes. In pregnancy and the postnatal period, this can involve specific management changes determined by the gene affected and whether there is a fetal inheritance of the gene. Where inheritance of the genotype influences the outcomes, cell-free fetal testing will hopefully soon become a diagnostic tool for early recognition of fetal mutations.

Implementing a multisector public-private partnership to improve urban hypertension management in low-and middle- income countries.

BACKGROUND: Cardiovascular disease presents an increasing health burden to low- and middle-income countries. Although ample therapeutic options and care improvement frameworks exist to address its prime risk factor, hypertension, blood pressure control rates remain poor. We describe the results of an effectiveness study of a multisector urban population health initiative that targets hypertension in a real-world implementation setting in cities across three continents. The initiative followed the "CARDIO4Cities" approach (quality of Care, early Access, policy Reform, Data and digital technology, Intersectoral collaboration, and local Ownership). METHOD: The approach was applied in Ulaanbaatar in Mongolia, Dakar in Senegal, and São Paulo in Brazil. In each city, a portfolio of evidence-based practices was implemented, tailored to local priorities and available data. Outcomes were measured by extracting hypertension diagnosis, treatment and control rates from primary health records. Data from 18,997 patients with hypertension in primary health facilities were analyzed. RESULTS: Over one to two years of implementation, blood pressure control rates among enrolled patients receiving medication tripled in São Paulo (from 12·3% to 31·2%) and Dakar (from 6·7% to 19·4%) and increased six-fold in Ulaanbaatar (from 3·1% to 19·7%). CONCLUSIONS: This study provides first evidence that a multisectoral population health approach to implement known best-practices, supported by data and digital technologies, and relying on local buy-in and ownership, can improve hypertension control in high-burden urban primary care settings in low-and middle-income countries.

Canady Cold Helios Plasma Reduces Soft Tissue Sarcoma Viability by Inhibiting Proliferation, Disrupting Cell Cycle, and Inducing Apoptosis: A Preliminary Report.

Soft tissue sarcomas (STS) are a rare and highly heterogeneous group of solid tumors, originating from various types of connective tissue. Complete removal of STS by surgery is challenging due to the anatomical location of the tumor, which results in tumor recurrence. Additionally, current polychemotherapeutic regimens are highly toxic with no rational survival benefit. Cold atmospheric plasma (CAP) is a novel technology that has demonstrated immense cancer therapeutic potential. Canady Cold Helios Plasma (CHCP) is a device that sprays CAP along the surgical margins to eradicate residual cancer cells after tumor resection. This preliminary study was conducted in vitro prior to in vivo testing in a humanitarian compassionate use case study and an FDA-approved phase 1 clinical trial (IDE G190165). In this study, the authors evaluate the efficacy of CHCP across multiple STS cell lines. CHCP treatment reduced the viability of four different STS cell lines (i.e., fibrosarcoma, synovial sarcoma, rhabdomyosarcoma, and liposarcoma) in a dose-dependent manner by inhibiting proliferation, disrupting cell cycle, and inducing apoptosis-like cell death.

BCL2A1 regulates Canady Helios Cold Plasma-induced cell death in triple-negative breast cancer.

Breast cancer is the leading cause of cancer death among women. Triple-negative breast cancer (TNBC) has a poor prognosis and frequently relapses early compared with other subtypes. The Cold Atmospheric Plasma (CAP) is a promising therapy for prognostically poor breast cancer such as TNBC. The Canady Helios Cold Plasma (CHCP) induces cell death in the TNBC cell line without thermal damage, however, the mechanism of cell death by CAP treatment is ambiguous and the mechanism of resistance to cell death in some subset of cells has not been addressed. We investigate the expression profile of 48 apoptotic and 35 oxidative gene markers after CHCP treatment in six different types of breast cancer cell lines including luminal A (ER+ PR+/-HER2-), luminal B (ER+PR+/-HER2+), (ER-PR-HER2+), basal-like: ER-PR-HER2- cells were tested with CHCP at different power settings and at 4 different incubation time. The expression levels of the gene markers were determined at 4 different intervals after the treatment. The protein expression of BCL2A1 was only induced after CHCP treatment in TNBC cell lines (p < 0.01), whereas the HER2-positive and ER, PR positive cell lines showed little or no expression of BCL2A1. The BCL2A1 and TNF-alpha expression levels showed a significant correlation within TNBC cell lines (p < 0.01). Silencing BCL2A1 mRNA by siRNA increased the potency of the CHCP treatment. A Combination of CHCP and CPI203, a BET bromodomain inhibitor, and a BCL2A1 antagonist increased the CHCP-induced cell death (p < 0.05). Our results revealed that BCL2A1 is a key gene for resistance during CHCP induced cell death. This resistance in TNBCs could be reversed with a combination of siRNA or BCL2A1 antagonist-CHCP therapy.

Canady Helios Cold Plasma Induces Breast Cancer Cell Death by Oxidation of Histone mRNA.

Breast cancer is the most common cancer among women worldwide. Its molecular receptor marker status and mutational subtypes complicate clinical therapies. Cold atmospheric plasma is a promising adjuvant therapy to selectively combat many cancers, including breast cancer, but not normal tissue; however, the underlying mechanisms remain unexplored. Here, four breast cancer cell lines with different marker status were treated with Canady Helios Cold Plasma™ (CHCP) at various dosages and their differential progress of apoptosis was monitored. Inhibition of cell proliferation, induction of apoptosis, and disruption of the cell cycle were observed. At least 16 histone mRNA types were oxidized and degraded immediately after CHCP treatment by 8-oxoguanine (8-oxoG) modification. The expression of DNA damage response genes was up-regulated 12 h post-treatment, indicating that 8-oxoG modification and degradation of histone mRNA during the early S phase of the cell cycle, rather than DNA damage, is the primary cause of cancer cell death induced by CHCP. Our report demonstrates for the first time that CHCP effectively induces cell death in breast cancer regardless of subtyping, through histone mRNA oxidation and degradation during the early S phase of the cell cycle.

The synergistic effect of Canady Helios cold atmospheric plasma and a FOLFIRINOX regimen for the treatment of cholangiocarcinoma in vitro.

Cholangiocarcinoma (CCA) is a rare biliary tract cancer with a low five-year survival rate and high recurrence rate after surgical resection. Currently treatment approaches include systemic chemotherapeutics such as FOLFIRINOX, a chemotherapy regimen is a possible treatment for severe CCA cases. A limitation of this chemotherapy regimen is its toxicity to patients and adverse events. There exists a need for therapies to alleviate the toxicity of a FOLFIRINOX regimen while enhancing or not altering its anticancer properties. Cold atmospheric plasma (CAP) is a technology with a promising future as a selective cancer treatment. It is critical to know the potential interactions between CAP and adjuvant chemotherapeutics. In this study the aim is to characterize the efficacy of FOLFIRINOX and CAP in combination to understand potential synergetic effect on CCA cells. FOLFIRINOX treatment alone at the highest dose tested (53.8 µM fluorouracil, 13.7 µM Leucovorin, 5.1 µM Irinotecan, and 3.7 µM Oxaliplatin) reduced CCA cell viability to below 20% while CAP treatment alone for 7 min reduced viability to 3% (p < 0.05). An analysis of cell viability, proliferation, and cell cycle demonstrated that CAP in combination with FOLFIRINOX is more effective than either treatment alone at a lower FOLFIRINOX dose of 6.7 µM fluorouracil, 1.7 µM leucovorin, 0.6 µM irinotecan, and 0.5 µM oxaliplatin and a shorter CAP treatment of 1, 3, or 5 min. In conclusion, CAP has the potential to reduce the toxicity burden of FOLFIRINOX and warrants further investigation as an adjuvant therapy.

Don't give up when communication is difficult: Online well-being advice for caregivers of people with Alzheimer's and dementia.

Sixteen million people in the United States are unpaid caregivers to people with Alzheimer's or dementia. Although caregiver investment is associated with personal and relational benefits, there are also emotional, mental, relational, and physical costs. This study explores online well-being advice for nonprofessional caregivers of people with Alzheimer's and dementia, resulting in 332 online resources that offer informational support for nonprofessional caregivers. Although competent communication directly impacts the well-being of caregiving relationships, only 39 of these texts offered advice related to communication strategies. Thematic analysis of these 39 sources resulted in 1,024 discrete pieces of caregiver advice related to three overarching themes: Daily Routine, Care Recipient Well-Being, and Caregiver Self-Care. We examine the Caregiver Self-Care theme to understand informational support available to caregivers. These self-care advice themes reveal a need for intentional focus on the home health quality of nonprofessional caregivers about ways that communication impacts their everyday lives.

Fretting Corrosion, Third-Body Polyethylene Damage, and Cup Positioning in Primary vs Revision Dual Mobility Total Hip Arthroplasty.

BACKGROUND: Dual mobility (DM) articulations were introduced for total hip arthroplasty to reduce the risk of instability for patients who have a high risk of dislocation. The use of DM constructs in both primary and revision total hip arthroplasty has been steadily increasing, leading to concerns regarding potential risks of fretting corrosion, polyethylene wear, metal release, and failure due to component positioning. METHODS: A total of 56 retrieved DM constructs were collected. The inner and outer polyethylene liner surfaces were assessed for 7 damage mechanisms, and fretting corrosion was evaluated for the femoral stem, head, and modular liner. Three polyethylene liners with the greatest amounts of embedded debris were examined using scanning electron microscopy. Energy-dispersive X-ray spectroscopy was used to determine the elemental content of the debris. Acetabular cup orientation was analyzed radiographically using the EBRA (Einzel-Bild-Roentgen-Analyse) method. RESULTS: The devices were revised most frequently for infection (36%), loosening (21%), and instability/dislocation (18%). The most common polyethylene damage mechanisms were scratching, pitting, burnishing, and embedded debris, and no difference in total damage was found between primary and revision cases. Scanning electron microscopy/energy-dispersive X-ray spectroscopy revealed that debris morphology and composition were consistent with porous titanium coating, resulting from cup loosening or broken screws and augments. A total of 71% and 50% of the constructs were determined to be within the Lewinnek safe zone for inclination and anteversion, respectively. CONCLUSION: The most notable mechanisms of surface damage were due to third-body debris, especially for the polyethylene surfaces which articulate against cobalt-chromium femoral heads and acetabular liners. Scratching of the femoral head and the metal liner from this debris may support the clinical use of ceramic for DM bearing surfaces in the future.

A review of the evidence to support interim reference level for dietary lead exposure in adults.

FDA developed the interim reference level (IRL) for lead of 3 µg/day in children and 12.5 µg/day in women of childbearing age (WOCBA) to better protect the fetus from lead toxicity. These IRLs correspond to a blood lead level (BLL) of 0.5 µg/dL in both populations. The current investigation was performed to determine if the IRL for WOCBA should apply to the general population of adults. A literature review of epidemiological studies was conducted to determine whether a BLL of 0.5 µg/dL is associated with adverse effects in adults. Some studies reported adverse effects over a wide range of BLLs that included 0.5 µg/dL adding uncertainty to conclusions about effects at 0.5 µg/dL; however, no studies clearly identified this BLL as an adverse effect level. Results also showed that the previously developed PTTDI for adults of 75 µg/day lead may not be health protective, supporting use of a lower reference value for lead toxicity in this population group. Use of the 12.5 µg/day IRL as a benchmark for dietary lead intake is one way FDA will ensure that dietary lead intake in adults is reduced.

Frontal theta brain activity varies as a function of surgical experience and task error.

OBJECTIVE: Investigations into surgical expertise have almost exclusively focused on overt behavioral characteristics with little consideration of the underlying neural processes. Recent advances in neuroimaging technologies, for example, wireless, wearable scalp-recorded electroencephalography (EEG), allow an insight into the neural processes governing performance. We used scalp-recorded EEG to examine whether surgical expertise and task performance could be differentiated according to an oscillatory brain activity signal known as frontal theta-a putative biomarker for cognitive control processes. DESIGN SETTING AND PARTICIPANTS: Behavioral and EEG data were acquired from dental surgery trainees with 1 year (n=25) and 4 years of experience (n=20) while they performed low and high difficulty drilling tasks on a virtual reality surgical simulator. EEG power in the 4-7 Hz range in frontal electrodes (indexing frontal theta) was examined as a function of experience, task difficulty and error rate. RESULTS: Frontal theta power was greater for novices relative to experts (p=0.001), but did not vary according to task difficulty (p=0.15) and there was no Experience × Difficulty interaction (p=0.87). Brain-behavior correlations revealed a significant negative relationship between frontal theta and error in the experienced group for the difficult task (r=-0.594, p=0.0058), but no such relationship emerged for novices. CONCLUSION: We find frontal theta power differentiates between surgical experiences but correlates only with error rates for experienced surgeons while performing difficult tasks. These results provide a novel perspective on the relationship between expertise and surgical performance.

U.S. Food and Drug Administration's interim reference levels for dietary lead exposure in children and women of childbearing age.

Reducing lead exposure is a public health priority for the US Food and Drug Administration as well as other federal agencies. The goals of this research were to 1) update the maximum daily dietary intake of lead from food, termed an interim reference level (IRL), for children and for women of childbearing age (WOCBA) and 2) to confirm through a literature review that with the exception of neurodevelopment, which was not evaluated here, no adverse effects of lead consistently occur at the blood lead level (BLL) associated with the IRL. Because no safe level of lead exposure has yet been identified for children's health, the IRLs of 3 µg/day for children and 12.5 µg/day for WOCBA were derived from the Centers for Disease Control and Prevention reference value of 5 µg/dL BLL, the level at which public health actions should be initiated. The literature review showed that no adverse effects of lead consistently occurred at the BLL associated with the IRLs (0.5 µg/dL). The IRLs of 3 µg/day for children and 12.5 µg/day for WOCBA should serve as useful benchmarks in evaluating the potential for adverse effects of dietary lead.