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Objective: To describe the unique challenges faced by rural pregnant women with intersecting substance use disorder (SUD) and unmet social needs., Design: Secondary qualitative data analysis with an analytic expansion approach., Setting: Hospital system in northern New England., Participants: Four rural women with food insecurity who were in recovery for SUD (three were pregnant and one had given birth in the past 15 weeks)., Methods: In the primary qualitative descriptive study, we interviewed 14 women about their experience of food insecurity during the perinatal period, including facilitators and barriers to being screened and accessing referrals for food insecurity and other social needs during prenatal care. This secondary analysis centered on the perspectives of four participants who reflected specifically on receiving material and mental health support through the integration of prenatal care and SUD treatment., Results: Rural women with SUD who experience social needs during pregnancy have difficulty accessing appropriate prenatal care and maintaining treatment engagement due to intersecting factors (e.g., food and housing insecurity and transportation) and psychological (e.g., mental health challenges, social isolation, and stigma) factors. Participants emphasized the importance of integrating social support within prenatal and substance use care to promote physical and mental health and engagement in SUD treatment., Conclusion: In line with The Joint Commission's 2022 policy recommendations for universal social determinants of health screening, we support one-stop clinical and social care for pregnant women who face intersecting barriers to health, such as SUD and unmet social needs. Nurses can play an important role in care coordination for people with complex medical and social determinants of health screening needs. This approach is especially relevant to rural areas, where food, housing, and transportation insecurity rates are greater than nonrural areas., Competing Interests: Conflict of Interest The authors report no conflicts of interest or relevant financial relationships., (Copyright © 2024 AWHONN, the Association of Women’s Health, Obstetric and Neonatal Nurses. Published by Elsevier Inc. All rights reserved.)

Objective: To describe the experience of food insecurity and food access among women in northern New England during the perinatal period., Design: Qualitative descriptive., Setting: Hospital system in northern New England., Participants: Twelve pregnant women and two women who gave birth., Methods: We interviewed participants during pregnancy and the postpartum period about their experiences of food insecurity, including screening, their willingness and ability to access food programs, and the extent to which their food needs were met through referrals. We analyzed interview transcripts to identify themes related to participants' experiences of food insecurity; food support, including screening and referral; and opportunities for improvement in current food support interventions., Results: Most participants accepted being screened for food insecurity and were satisfied with the food distributed in their perinatal care settings. Food insecurity consistently occurred alongside general financial strain, housing insecurity, and transportation needs, which affirmed the interconnectedness of social determinants of health. Other co-occurring risks included intimate partner violence, substance use, and mental health challenges. Food receipt was facilitated by care team members who were knowledgeable about food distribution programs. Barriers to food receipt included challenges with enrolling in public assistance programs, poor awareness among participants of available resources, the persistence and unpredictability of food insecurity, and stigma. We identified three distinct themes that described participants' experiences with food insecurity during pregnancy and the postpartum period: Experience of Being Screened for Food Insecurity, Intersecting Social Needs, and Experience of Accessing Resources., Conclusion: These findings can be used to inform comprehensive food support programs that reflect the needs and values of women during the perinatal period. Interventions to screen and intervene for food insecurity during and after pregnancy align with the quality standards of The Joint Commission and should be integrated into nursing practice., Competing Interests: Conflict of Interest The authors report no conflicts of interest or relevant financial relationships., (Copyright © 2023 AWHONN, the Association of Women’s Health, Obstetric and Neonatal Nurses. Published by Elsevier Inc. All rights reserved.)

Background: Delayed graft function (DGF) is a major adverse complication of deceased donor kidney transplantation. Intravenous fluids are routinely given to patients receiving a transplant to maintain intravascular volume and optimise graft function. Saline (0·9% sodium chloride) is widely used but might increase the risk of DGF due to its high chloride content. We aimed to test our hypothesis that using a balanced low-chloride crystalloid solution (Plasma-Lyte 148) instead of saline would reduce the incidence of DGF., Methods: BEST-Fluids was a pragmatic, registry-embedded, multicentre, double-blind, randomised, controlled trial at 16 hospitals in Australia and New Zealand. Adults and children of any age receiving a deceased donor kidney transplant were eligible; those receiving a multi-organ transplant or weighing less than 20 kg were excluded. Participants were randomly assigned (1:1) using an adaptive minimisation algorithm to intravenous balanced crystalloid solution (Plasma-Lyte 148) or saline during surgery and up until 48 h after transplantation. Trial fluids were supplied in identical bags and clinicians determined the fluid volume, rate, and time of discontinuation. The primary outcome was DGF, defined as receiving dialysis within 7 days after transplantation. All participants who consented and received a transplant were included in the intention-to-treat analysis of the primary outcome. Safety was analysed in all randomly assigned eligible participants who commenced surgery and received trial fluids, whether or not they received a transplant. This study is registered with Australian New Zealand Clinical Trials Registry, (ACTRN12617000358347), and ClinicalTrials.gov (NCT03829488)., Findings: Between Jan 26, 2018, and Aug 10, 2020, 808 participants were randomly assigned to balanced crystalloid (n=404) or saline (n=404) and received a transplant (512 [63%] were male and 296 [37%] were female). One participant in the saline group withdrew before 7 days and was excluded, leaving 404 participants in the balanced crystalloid group and 403 in the saline group that were included in the primary analysis. DGF occurred in 121 (30%) of 404 participants in the balanced crystalloid group versus 160 (40%) of 403 in the saline group (adjusted relative risk 0·74 [95% CI 0·66 to 0·84; p<0·0001]; adjusted risk difference 10·1% [95% CI 3·5 to 16·6]). In the safety analysis, numbers of investigator-reported serious adverse events were similar in both groups, being reported in three (<1%) of 406 participants in the balanced crystalloid group versus five (1%) of 409 participants in the saline group (adjusted risk difference -0·5%, 95% CI -1·8 to 0·9; p=0·48)., Interpretation: Among patients receiving a deceased donor kidney transplant, intravenous fluid therapy with balanced crystalloid solution reduced the incidence of DGF compared with saline. Balanced crystalloid solution should be the standard-of-care intravenous fluid used in deceased donor kidney transplantation., Funding: Medical Research Future Fund and National Health and Medical Research Council (Australia), Health Research Council (New Zealand), Royal Australasian College of Physicians, and Baxter., Competing Interests: Declaration of interests MGC has received research support from Baxter Healthcare, the manufacturer of Plasma-Lyte 148, via a Baxter Investigator-Initiated Research grant that provided fluids for the BEST-Fluids trial (commercial value of US$36 270). DWJ has received consultancy fees, research grants, speaker's honoraria, and travel sponsorships from Baxter Healthcare and Fresenius Medical Care; consultancy fees from AstraZeneca and AWAK; speaker's honoraria and travel sponsorships from ONO; and travel sponsorships from Amgen. DR, LEH, LAV, EMP, CK, and JV are employees of the sponsor, The University of Queensland. KBD's salary was funded by a Better Evidence and Translation in Chronic Kidney Disease (BEAT-CKD) grant' and she is an employee of the ANZDATA Registry. PAC is the Deputy Executive Officer of the ANZDATA Registry. CMH has received fees for research committee activities from Janssen and GlaxoSmithKline paid to her institution; personal fees from Otsuka; research grants from Fresenius, Shire, and PKD Australia outside the submitted work; and research grants from Baxter and the National Health and Medical Research Council of Australia related to the current project. LW works in the Department of Anaesthesia at Austin Health, which has received funding from Baxter Healthcare for investigator-initiated clinical research. PFM has received honoraria for presentations on behalf of AstraZeneca and consultancy fees from Vifor. LW has received honoraria from Baxter Healthcare for consulting activities. All LW's fluid-related research, including study design, execution, data collection, analysis, and reporting, has been conducted independently of Baxter Healthcare and other commercial entities. ZHE has received consultancy fees and travel sponsorships from AstraZeneca. WHL has received honoraria from Alexion and education or research grants from Astellas. SJC has received research support, travel support, speaker fees, or honoraria from AstraZeneca, Bayer, CSL-Behring, Novartis, and Takeda. All other authors declare no competing interests., (Copyright © 2023 Elsevier Ltd. All rights reserved.)

Background: Over the past decade, states have passed several laws on prenatal drug use, including "maltreatment laws" deeming prenatal drug use child maltreatment, "reporting laws" requiring providers to report prenatal drug use to Child Protective Services (CPS) and "criminalization laws" that criminalize prenatal drug use., Method: We examined the association between a 2012 Utah maltreatment law, a 2013 Alabama maltreatment and criminalization law, and a 2014 Maryland reporting law on the rate of infant CPS reports using 2010-2017 National Child Abuse and Neglect Data System data. We conducted an event study comparing CPS reporting pre/post law in each treatment state with reporting in a pool of control states over the same period. Regression models included state and year fixed effects and state-level demographics. We triangulated quantitative results with qualitative interviews of 11 state leaders whose professional responsibilities included implementation of the state law., Results: We found no association between Alabama's simultaneous maltreatment and criminalization laws and infant reporting. Maryland's reporting law (28.2 fewer reports per 1000 infants, 95%CI: [-42.9, -13.6], 4-years post-law) and Utah's maltreatment laws (31.0 fewer CPS reports per 1000 infants, 95%CI: [-61.2, -0.8], 6-years post-law) were associated with declines in infant CPS reports. Qualitative results suggest that the reduced reporting associated with Maryland's reporting and Utah's maltreatment laws may be due to increased perceived stigma resulting from the law, and health providers' distrust of CPS and/or confusion about reporting to CPS., Conclusion: Future research should characterize differential policy implementation across states and counties and identify policy impacts on treatment seeking behavior., Competing Interests: Declarations of Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022. Published by Elsevier B.V.)

Background: Although male breast cancer (MBC) is a rare disease, accounting for <1% of all breast cancers, it has significant oncological, survival and psychosocial implications for patients. The aim of this study is to assess the latest literature in the diagnosis, management, oncological outcomes, and psychosocial impact of MBC., Methods: A systematic literature review was conducted using the PRISMA guidelines (Moher et al., 2009) [1] to explore the management of MBC, with particular focus on investigative imaging, surgical management, oncological outcomes, survival, genetic screening and psychosocial effects. Electronic databases were searched for randomised control trials, cohort studies and case series involving more than 10 patients. Imaging and surgical techniques, local and distant disease recurrence, survival, genetic screening and psychosocial implications in the setting of MBC were assessed., Results: The search criteria identified 199 articles, of which 59 met the inclusion criteria. This included 39,529 patients, with a mean age of 64.5 years (55-71), and a mean follow-up of 66.3 months (26.2-115). Mastectomy remains the most frequently used surgical technique, with an average of 89.6%. Loco-regional and distant recurrence rate was 10.1% and 21.4% respectively. Disease-free survival (DFS) at 5 and 10 years was 66.8% and 54.5% respectively. Disease-specific survival (DSS) at 5 and 10 years was 87.1% and 67.1% respectively. Overall survival (OS) at 5 and 10 years was 72.7% and 50.7% respectively. Genetic screening was conducted in 38.6% of patients of which 4.8% and 15.8% were found to be BRCA1 and BRCA2 carriers respectively. Psychosocial studies were conducted mainly using questionnaire and interview-based methodology focusing primarily on awareness of breast cancer in men, support available and impact on gender identity., Conclusions: This review demonstrates that men present with later stage disease with subsequent impact on survival outcomes. There remains a paucity of high-level evidence and prospective studies are required. There is a need for increasing awareness amongst the public and health care professionals in order to improve outcomes and reduce stigma associated with MBC., (Copyright © 2022 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.)

Since 1972, the year of the inaugural issue of Journal of Obstetric, Gynecologic, & Neonatal Nursing, substance use during pregnancy has remained a public health concern in the United States. This concern is currently exacerbated by factors such as the opioid and stimulant use crisis and widening health and social inequities for many women and families. The purposes of this historical commentary are to describe trends in the perception of women with substance use disorder and their infants and related sociolegal implications and to trace the evolution of related nursing practice and research during the past 50 years. We provide recommendations and priorities for practice and research, including further integration of support for the mother-infant dyad, cross-sectoral collaborations, and equity-oriented practices and policies., Competing Interests: Conflict of Interest The authors report no conflicts of interest or relevant financial relationships., (Copyright © 2022 AWHONN, the Association of Women’s Health, Obstetric and Neonatal Nurses. Published by Elsevier Inc. All rights reserved.)

The statin family of therapeutics is widely used clinically as cholesterol lowering agents, and their effects to target intracellular mevalonate production is a key mechanism of action. In this study, we performed full transcriptomic RNA sequencing and qPCR to evaluate the effects of mevalonate on the immunoregulatory phenotype of endothelial cells (EC). We find that mevalonate-dependent gene regulation includes a reduction in the expression of multiple pro-inflammatory genes including TNFSF4 (OX40-L) and TNFSF18 (GITR-L) and a co-incident induction of immunoregulatory genes including LGALS3 (Galectin-3) and LGALS9 (Galectin-9). In functional assays, pretreatment of EC with simvastatin to inhibit mevalonate metabolism resulted in a dose-dependent reduction in the costimulation of CD45RO + CD4 + T cell proliferation as well as IL-2, IFNγ and IL-6 production versus vehicle-treated EC. In contrast, pre-treatment of EC with L-mevalonate in combination with simvastatin reversed phenotypic and functional responses. Collectively, these results indicate that relative mevalonate metabolism by EC is critical to sustain EC-dependent mechanisms of immunity. Our findings have broad relevance for the repurposing of statins as therapeutics to augment immunoregulation and/or to inhibit local tissue pro-inflammatory cytokine production following transplantation., (© 2021 The American Society of Transplantation and the American Society of Transplant Surgeons.)

Objectives: Pregnancy is a time when optimization of nutrition is critically important, yet pregnant women with substance use disorders face unique nutritional challenges. The aim of this short communication is to summarize existing knowledge about nutritional interventions used in substance use disorders for pregnant and parenting women with opioid use disorder (OUD) and substance use disorders and to inform program development by maternity care and treatment providers., Study Design: We conducted a narrative review of nutritional interventions for pregnant women with OUD and performed environmental scanning to explore current practice., Methods: To gain knowledge about the unique nutritional needs of pregnant women with OUD, we searched the medical literature using Medical Subject Headings terms and key words combining the concepts of nutrition, pregnancy, and substance use. To explore current practice, we interviewed staff of a geographically diverse sample of 35 programs treating women with substance use disorders across the United Stated and Canada on their approach to prenatal nutrition for clients., Results: Literature review identified two studies evaluating the nutritional status of pregnant women with substance use disorders, but neither described nutritional interventions. Lower body mass index and folate, B12, and iron deficiencies were found in women with OUD compared with women without OUD. Two additional studies integrated nutritional interventions in substance use treatment for non-pregnant populations, resulting in significant improvements in dietary habits and psychological well-being for participants. Of 15 substance use treatment programs that responded to our query, only two incorporated longitudinal nutrition curricula for pregnant women., Conclusions: Pregnancy is a time when a healthy diet is critically important for maternal, fetal, and neonatal health; however, pregnant women with OUD are at significant risk of malnutrition. There is an urgent need to address food insecurity and develop targeted nutrition education programs for pregnant women in early recovery., (Copyright © 2019 The Royal Society for Public Health. Published by Elsevier Ltd. All rights reserved.)

Pneumonia is a leading killer of children younger than 5 years despite high vaccination coverage, improved nutrition, and widespread implementation of the Integrated Management of Childhood Illnesses algorithm. Assessing the effect of interventions on childhood pneumonia is challenging because the choice of case definition and surveillance approach can affect the identification of pneumonia substantially. In anticipation of an intervention trial aimed to reduce childhood pneumonia by lowering household air pollution, we created a working group to provide recommendations regarding study design and implementation. We suggest to, first, select a standard case definition that combines acute (≤14 days) respiratory symptoms and signs and general danger signs with ancillary tests (such as chest imaging and pulse oximetry) to improve pneumonia identification; second, to prioritise active hospital-based pneumonia surveillance over passive case finding or home-based surveillance to reduce the risk of non-differential misclassification of pneumonia and, as a result, a reduced effect size in a randomised trial; and, lastly, to consider longitudinal follow-up of children younger than 1 year, as this age group has the highest incidence of severe pneumonia., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Chronic low back pain (CLBP) afflicts millions of people worldwide, with particularly high prevalence in military veterans. Many treatment options exist for CLBP, but most have limited effectiveness and some have significant side effects. In general populations with CLBP, yoga has been shown to improve health outcomes with few side effects. However, yoga has not been adequately studied in military veteran populations. In the current paper we will describe the design and methods of a randomized clinical trial aimed at examining whether yoga can effectively reduce disability and pain in US military veterans with CLBP. A total of 144 US military veterans with CLBP will be randomized to either yoga or a delayed treatment comparison group. The yoga intervention will consist of 2× weekly yoga classes for 12weeks, complemented by regular home practice guided by a manual. The delayed treatment group will receive the same intervention after six months. The primary outcome is the change in back pain-related disability measured with the Roland-Morris Disability Questionnaire at baseline and 12-weeks. Secondary outcomes include pain intensity, pain interference, depression, anxiety, fatigue/energy, quality of life, self-efficacy, sleep quality, and medication usage. Additional process and/or mediational factors will be measured to examine dose response and effect mechanisms. Assessments will be conducted at baseline, 6-weeks, 12-weeks, and 6-months. All randomized participants will be included in intention-to-treat analyses. Study results will provide much needed evidence on the feasibility and effectiveness of yoga as a therapeutic modality for the treatment of CLBP in US military veterans., (Published by Elsevier Inc.)

Whilst initial rates of insulin independence following islet transplantation are encouraging, long-term function using the Edmonton Protocol remains a concern. The aim of this single-arm, multicenter study was to evaluate an immunosuppressive protocol of initial antithymocyte globulin (ATG), tacrolimus and mycophenolate mofetil (MMF) followed by switching to sirolimus and MMF. Islets were cultured for 24 h prior to transplantation. The primary end-point was an HbA1c of <7% and cessation of severe hypoglycemia. Seventeen recipients were followed for ≥ 12 months. Nine islet preparations were transported interstate for transplantation. Similar outcomes were achieved at all three centers. Fourteen of the 17 (82%) recipients achieved the primary end-point. Nine (53%) recipients achieved insulin independence for a median of 26 months (range 7-39 months) and 6 (35%) remain insulin independent. All recipients were C-peptide positive for at least 3 months. All subjects with unstimulated C-peptide >0.2 nmol/L had cessation of severe hypoglycemia. Nine of the 17 recipients tolerated switching from tacrolimus to sirolimus with similar graft outcomes. There was a small but significant reduction in renal function in the first 12 months. The combination of islet culture, ATG, tacrolimus and MMF is a viable alternative for islet transplantation., (© Copyright 2013 The American Society of Transplantation and the American Society of Transplant Surgeons.)

The extent to which the acute phase response (APR) influences iron status indicators in chronic infections is not well documented. We investigated this relationship using reported recent fever and 2 acute phase proteins (APP), C-reactive protein (CRP), and alpha-1-acid glycoprotein (AGP). In a sample of 690 children matched on age and helminth infection status at baseline, we measured plasma for AGP, CRP, ferritin, transferrin receptor (TfR), and erythropoietin (EPO) and whole blood for hemoglobin (Hb) concentration, zinc protoporphyrin (ZPP), and malaria parasite density, and we obtained maternal reports of recent fever. We then examined the influence of the APR on each iron status indicator using regression analysis with Hb as the outcome variable. Ferritin was inversely related to Hb in the APR-unadjusted model. Adjusting for the APR using reported recent fever alone was not sufficient to reverse the inverse Hb-ferritin relationship. However, using CRP and/or AGP resulted in the expected positive relationship. The best fit model included reported recent fever, AGP and CRP (R(2) = 0.241; P < 0.001). The best fit Hb-ZPP, Hb-TfR, and Hb-EPO models included reported recent fever and AGP but not CRP (R(2) = 0.253, 0.310, and 0.292, respectively; P < 0.001). ZPP, TfR, and EPO were minimally influenced by the APR, whereas ferritin was immensely affected. Reported recent fever alone cannot be used as a marker for the APR. Either AGP or CRP is useful for adjusting if only 1 APP can be measured. However, AGP best predicted the APR in this population.

The present study examined the effect of continuous vision and its occlusion in timing of pre-landing actions during free falls. When vision is occluded, muscle activation is hypothesized to start relative to onset of the fall. However, when continuous vision is available onset of action is hypothesized to be relative to the moment of touchdown. Six subjects performed 6 randomized sets of 6 trials after becoming familiar with the task. The 36 trials were divided in 2 visual conditions (vision and blindfold) and 3 heights of fall (15, 45 and 75 cm). EMG activity was recorded from the gastrocnemius and rectus femoris muscles during the falls. The latency of onset (L(o)) and the lapse from EMG onset to touchdown (T(c)) were obtained from these muscles. Vertical forces were recorded to assess the effects of pre-landing activity on the impacts at collision with and without continuous vision. Peak amplitude (F(max)), time to peak (T(max)) and peak impulse normalized to momentum (I(norm)) were used as outcome measures. Within flight time ranges of approximately 50-400 ms, the results showed that L(o) and T(c) follow a similar linear trend whether continuous vision was available or occluded. However, the variability of T(c) for each of the muscles was larger in the vision occluded condition. Analyses of variance showed that the rectus femoris muscle started consistently earlier in no vision trials. Finally, impact forces were not different in vision or blindfold conditions, and thus, they were not affected by minor differences in the timing of muscles prior to landing. Thus, it appears that knowing the surroundings before falling may help to reduce the need for a continuous visual input. The relevance of such input cannot be ruled out for falls from high landing heights, but cognitive factors (e.g., attention to specific cues and anticipation of a fall) may play a dominant role in timing actions during short duration falls encountered daily.

While the positive uses for video games in an educational setting have also been established, the educational aim is usually made explicit. The goal of this research was to develop a video game wherein the educational aspect was implicitly embedded in the video game, such that the gaming activity remained interesting and relevant. Following a pilot study to confirm the usability of an in-house developed game, two studies were conducted with 11-17 year old hockey players (N(1)=130, N(2)=39). Results demonstrated that participants playing the experimental version of the video game scored significantly higher on a concussion symptoms questionnaire, in a significantly faster time, than participants playing the control version of the game. Most participants indicated that they enjoyed the game and would play it again. These results suggest that educational material can be conveyed successfully and in an appealing manner via video game play.

Post-transplant lymphoproliferative disorder (PTLD) is a potentially life-threatening complication of solid organ transplantation. Reduction in immunosuppression is usually the first line of therapy and is often curative. While undergoing treatment, imaging studies including MRI and CT scans are commonly used to follow the disease course. Laboratory studies such as lactate dehydrogenase and Epstein-Barr virus PCR can also be used to monitoring disease status. We report here a case of PTLD developing 48 months post renal transplant. A monoclonal protein (M protein) was demonstrated at diagnosis with a corresponding antibody expressed on the malignant lymphocytes. The patient was followed with serial serum protein electrophoreses (SPEP) to monitor his response to therapy. The amount of M protein paralleled the disease course, decreasing as the clinical symptoms improved. This case illustrates the utility of using SPEP to monitor patients with PTLD.

Delayed rejection of pig kidney xenografts by primates is associated with vascular injury that may be accompanied by a form of consumptive coagulopathy in recipients. Using a life-supporting pig-to-baboon renal xenotransplantation model, we have tested the hypothesis that treatment with recombinant human antithrombin III would prevent or at least delay the onset of rejection and coagulopathy. Non-immunosuppressed baboons were transplanted with transgenic pig kidneys expressing the human complement regulators CD55 and CD59. Recipients were treated with an intravenous infusion of antithrombin III eight hourly (250 units per kg body weight), with or without low molecular weight heparin. Antithrombin-treated recipients had preservation of normal renal function for 4-5 days, which was twice as long as untreated animals, and developed neither thrombocytopenia nor significant coagulopathy during this period. Thus, recombinant antithrombin III may be a useful therapeutic agent to ameliorate both early graft damage and the development of systemic coagulation disorders in pig-to-human xenotransplantation.

Purpose: The development of bacterial keratitis after laser in situ keratomileusis (LASIK) has been described in only a few isolated cases. We report the development of bacterial keratitis as a postoperative complication of LASIK in three subjects., Design: A retrospective interventional small case series., Participants: Three patients who underwent LASIK for correction of myopia during July and August 1998 and had bacterial keratitis develop after surgery., Methods: Bacterial keratitis was encountered in the operated eyes between 1 and 22 days after surgery. Topical antibiotic therapy was administered. In one eye, which had significant opacification and irregularity of the flap was developed, lamellar keratoplasty was performed., Main Outcome Measures: Postoperative inflammation was followed clinically and photographically until it resolved. Visual acuity was measured at intervals throughout the follow-up period., Results: Keratitis resolved within 3 to 16 days of starting antibiotic therapy. The final best-corrected visual acuities were 20/30, 20/15, and 20/25., Conclusions: Although infectious keratitis after LASIK is an infrequently reported event, it should be discussed preoperatively with patients as a possible complication.

The first method using high-performance liquid chromatography (HPLC) has been developed for the determination of trans-resveratrol in human plasma. The method involves a liquid--liquid extraction followed by reversed-phase HPLC with UV detection. The detection limit of trans-resveratrol in human plasma was 5.0 ng/ml. Standard curves are linear over the concentration range of 5.0-5000.0 ng/ml. Intra-assay variability ranged from 1.9 to 3.7% and inter-assay variability ranged from 2.5 to 4.0% at the concentration range of 15.0-4000.0 ng/ml.

Our laboratory has reported that adipose tissue and adipocytes are importantly involved in retinoid storage and metabolism. To gain further insight, we examined factors that may regulate CRBP mRNA levels in primary cultures of rat epididymal and murine BFC-1 beta adipocytes. Northern blot analysis revealed that retinoic acid is a potent inducer of CRBP mRNA, causing a 7.5-fold rise in mRNA levels in primary adipocytes and a 9.5-fold rise in BFC-1 beta adipocytes. This induction of CRBP mRNA was dose-dependent at retinoic acid concentrations ranging between 10(-8) and 10(-5) M. Retinoic acid induction of CRBP mRNA levels showed a short lag period (6 h) and reached a maximal level of induction by 12 h in BFC-1 beta adipocytes and by 48 h in primary epididymal adipocytes. Nuclear run-on transcription assays of retinoic acid-induced BFC-1 beta adipocytes indicated that the rate of CRBP gene transcription is enhanced 3.6- to 4.3-fold by retinoic acid. In contrast, dexamethasone markedly down-regulated CRBP expression in a dose-dependent manner at concentrations ranging between 10(-9) and 10(-6) M. CRBP mRNA levels in primary and BFC-1 beta adipocytes declined, respectively, by 90% and 80% when adipocytes were exposed to 10(-6) M dexamethasone for 24 h. Studies of mRNA half-life indicated that dexamethasone acts to lessen CRBP expression through the specific destabilization of CRBP mRNA. Treatment of both primary and BFC-1 beta adipocytes with triiodothyronine alone had no effect on CRBP mRNA levels; however, when adipocytes were treated with a mixture of triiodothyronine and retinoic acid, the induction of CRBP mRNA levels by retinoic acid was reduced. In summary, these studies indicate that CRBP gene expression is regulated by retinoic acid, dexamethasone, and triiodothyronine; thus suggesting that retinol uptake, intracellular transport, and metabolism are dynamically regulated in adipocytes.

Objective: Our purpose was to determine the detection and false-positive rates for maternal serum alpha-fetoprotein measurement to screen for fetal Down syndrome and other chromosomal abnormalities in women > or = 35 years old., Study Design: A total of 3896 women had serum maternal serum alpha-fetoprotein levels measured routinely before amniocentesis for the indication of advanced maternal age., Results: Eighty-five percent (28/33) of fetal Down syndrome pregnancies had second-trimester risks of > or = 1:270 on the basis of a combination of maternal serum alpha-fetoprotein measurement and maternal age. Risks were also > or = 1:270 in 63% of the unaffected pregnancies. Sex chromosome aneuploidies, translocations, and other nonautosomal chromosome abnormalities in this study population were not associated with altered maternal serum alpha-fetoprotein levels; 51.9% (14/27) of these, however, were also assigned risks of > or = 1:270., Conclusions: Maternal serum alpha-fetoprotein screening is more accurate than age alone for assigning individual Down syndrome risk in pregnant women > or = 35 years old. Counseling for women in this age group should include information regarding the lower sensitivity of maternal serum alpha-fetoprotein screening for detecting fetal Down syndrome and other chromosomal abnormalities (especially sex chromosome aneuploidies) compared with offering amniocentesis to these women.

We have shown previously that a plasma fentanyl concentration of 1.67 ng ml-1 reduced the MAC of isoflurane by 50%. By comparing equal degrees of MAC reduction by sufentanil, we may determine the potency ratio of these opioids. Seventy-six patients were allocated randomly to receive predetermined infusions of sufentanil, and end-tidal concentrations of isoflurane in oxygen. Blood samples were obtained 10 min after the start of the infusion, and just before and after skin incision. Any purposeful movement by the patient was recorded. The MAC reduction of isoflurane produced by sufentanil was obtained using a logistic regression model. A sufentanil plasma concentration of 0.145 ng ml-1 (95% confidence limits 0.04, 0.26 ng ml-1) resulted in a 50% reduction in the MAC of isoflurane. At a plasma concentration greater than 0.5 ng ml-1, sufentanil exhibited a ceiling effect.

The effect of insulin and insulin like growth factors I and II on sunflower, watermelon and cucumber cotyledons has been examined. Each peptide stimulates an increase in the activity of several glyoxysomal enzymes which catalyze the conversion of fat to carbohydrate. These results provide the first evidence for the action of insulin and insulin like growth factors in plants.

Risk assessment for 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) has been based in part on the incidences of liver neoplasms in female Sprague-Dawley (SD) rats reported in a 2-year study conducted by Dow Chemical Corporation and published in 1978. In the years subsequent to the Dow report, the criteria for the diagnosis of proliferative hepatocellular lesions in the rat have been refined based upon ongoing study of these lesions. Because of this, PATHCO, Inc., was requested to conduct an independent review of the liver slides from the Dow TCDD study in order to assess how the current terminology might impact on interpretation of proliferative liver lesions in rats compared to the terminology used in the past. In March 1990, a pathology working group (PWG) was convened to review proliferative lesions in the livers of the female rats. The results of the PWG's evaluation of the microslides indicated a trend in tumor incidence similar to that published in 1978 but with a lower incidence of tumors in the middle and high dose females. Based on the morphologic findings, including the fact that the tumors were predominantly benign and usually associated with lesions of hepatic toxicity, the PWG considered this study to demonstrate a weak oncogenic effect of TCDD in the livers of female SD rats. As a result of its review, the PWG noted that in order to establish a relationship between the toxic hepatitis and the hepatocellular neoplasms, an independent review and grading of the toxic lesions in all female rats would be required.(ABSTRACT TRUNCATED AT 250 WORDS)

Using a prospective case-control study design, baseline levels of plasma selenium, retinol, and retinol-binding protein, and baseline blood uric acid levels were compared in 136 case patients who subsequently died from cancer and 238 matched control subjects. Subjects were followed for an average of 8 1/2 years. In matched analyses, selenium levels were lower in case patients with gastrointestinal or prostate cancer; retinol levels, lower in those with gastrointestinal or breast cancer; retinol-binding protein levels, lower in case patients with gastrointestinal cancer; and uric acid levels, lower in a group with "other" cancers. However, only the uric acid association with "other" cancers and the retinol-binding protein association with gastrointestinal cancer were statistically significant (P < or = .02) in conditional logistic regression analyses controlling for multiple potential covariates. Relationships for each of the substances varied by cancer site, and although some relationships were suggestive, our results point to the need for larger studies with adequate numbers for site-specific analyses.

Studies were conducted to explore the tissue- and cell-specific regulation of cellular retinoic acid-binding protein (CRABP) expression in the rat. Two studies were carried out. The first explored the regulation of CRABP mRNA levels in selected rat tissues by dietary retinoid status, and the relationship between CRABP mRNA and protein levels in different tissues. The second examined the cellular localization of CRABP expression in the testis. In order to conduct these experiments, a cDNA encoding CRABP was isolated and characterized. The DNA sequence of the coding region had 96% identity with that of the mouse CRABP cDNA and encodes a protein identical to mouse and bovine CRABP. CRABP mRNA and protein levels were quantified in five tissues from normal, retinoid-deficient, and retinol-repleted rats. Tissue CRABP and CRABP mRNA levels were highly correlated (P less than 0.01) indicating that inter-tissue variability of CRABP levels mainly results from regulation of CRABP mRNA levels. Neither CRABP protein nor mRNA levels were affected by retinol deficiency, in marked contrast with results previously demonstrated with cellular retinol-binding protein (CRBP) (J. Lipid Res. 1990. 31: 821-829). 35S-labeled CRABP cRNA probes were used to localize CRABP mRNA within the testis of adult rats by in situ hybridization. CRABP mRNA was localized selectively in the periphery of the seminiferous tubules, primarily in type A spermatogonia. The localization of CRABP mRNA differs from that of CRABP protein, which is known to be enriched in maturing and more mature germinal cells. This difference suggests that CRABP in germ cells may be highly stable, remaining in the maturing germ cells without degradation long after CRABP mRNA levels have declined to very low levels. The specific localization of CRABP mRNA and protein presumably reflects the biological roles of retinoic acid in the development and/or later function of germinal cells.

The 193-nm excimer laser was used to ablate experimental septate fungal (Fusarium) and an atypical mycobacterial (Mycobacterium fortuitum) keratitis in an animal model. The infections were allowed to proceed for 24 and 72 hours. After incubation, ablation with a 193-nm excimer laser with 5.0-mm treatment zones was performed until all suppurative areas were treated. The corneas were excised, halved, homogenized, and plated. All cultures were negative in the 24-hour group. However, in those corneas in which the infections were allowed to proceed to 72 hours, post-treatment cultures were positive for both organisms. Histopathologic examination confirmed that 24-hour infections had been eradicated and that 72-hour infections had organisms present. Three of the eight eyes in the M. fortuitum group perforated during treatment, even though the treatment depth by computer preselection was only 150 microns. Excimer laser photoablation may be a useful technique to eradicate early, localized microbial infections. However, it is apparent that advanced infections with deep stromal involvement and suppuration cannot be eradicated using this technique. Because corneas may be perforated inadvertently during treatment, excimer laser treatment of infectious keratitis should be approached with caution and used for superficial and well circumscribed lesions.

A study was conducted to determine the levels of cellular retinol-binding protein (CRBP) mRNA and protein in various tissues of the rat, to explore relationship between CRBP mRNA and protein levels in different tissues, and to examine the effects of changes in retinol nutritional status on the tissue distribution and levels of CRBP mRNA. Previous studies have shown that tissue CRBP protein levels are reduced in totally retinoid-deficient rats, but are otherwise minimally affected by changes in retinoid status. Three groups of male rats were compared: normal controls, retinoid-deficient, and retinol-repleted deficient rats. CRBP mRNA levels were measured by RNase protection assay and CRBP protein levels by radioimmunoassay in seven tissues. High levels of both CRBP mRNA and CRBP protein were found in the proximal epididymis, kidney, and liver; lower levels were seen in lung, testis, spleen, and small intestine. Tissue CRBP mRNA and protein levels were highly correlated (P less than 0.01) with each other. Retinoid deficiency did not alter the levels of CRBP mRNA found in the proximal epididymis, kidney, and liver. In contrast, CRBP mRNA levels in the lung, testis, spleen, and small intestine were reduced substantially in retinoid-deficient rats, to values that were only 23% to 50% of the corresponding values in the tissues of control rats. After oral repletion with retinol (4-18 h earlier), CRBP mRNA levels for these latter four tissues were found to have risen to control or near-control levels. The suggestion is raised that retinol repletion may have directly induced the expression of the CRBP gene in these particular tissues.(ABSTRACT TRUNCATED AT 250 WORDS)

Total body turnover of cholesterol was studied in 54 subjects by fitting a three-pool mathematical model to plasma decay curves of 32--49 weeks duration following [14C]cholesterol injection. Fifteen subjects were normal, 10 hypercholesterolemic, 21 hypertriglyceridemic, and 8 had both hypercholesterolemia and hypertriglyceridemia; 21 had a familial form of hyperlipidemia. In every subject in this heterogeneous population, the three-pool model gave the best fit for the data. An extensive search was conducted for relationships between model parameters and physiological variables (body size, serum lipid levels, age, and sex). Both linear and nonlinear relationships, and those involving interactions between pairs of variables, were explored. Fifty different forms of the model parameters and 53 forms of the physiological variables were examined. To guard against declaring statistical significance when none was present, subjects were first randomly divided into two matched groups. In the first (hypothesis-generating) group of 36 subjects, more than 100,000 regression equations were considered for each form of the model parameters. Twenty-one highly significant equations were found that were then tested in the second group (hypothesis-testing, 18 subjects). Eighteen of the 21 equations were found to be significant; of these, 6 were selected that accounted for a large part of the observed variation in the four model parameters for which equations were found (production rate (PR), and the sizes of pool 1, pool 3, and total exchangeable body cholesterol). The major determinant of cholesterol PR was body weight alone (r = 0.80). No function of serum lipid levels significantly influenced PR. Both body weight and serum cholesterol level entered into the equations for cholesterol mass. Age influenced the size of pool 3. Serum triglyceride level only had an effect on the size of pool 1. Since these equations were generated in one group of subjects and tested in another, they can be considered a confirmed set of predictive equations.

Treadmill tests were performed in 19 patients with previously documented idiopathic hypertrophic subaortic stenosis (IHSS). Arrhythmias occurred in 79 percent (15) of the patients, and new arrhythmias not previously documented occurred in over 50 percent (10) of the patients. Paroxysmal supraventricular tachycardia (PSVT), ventricular premature beats (VPBs) (two or more per minute) or atrial premature beats (APBs) (three or more per minute) occurred in 10 of 19 patients. There was no association between treadmill arrhythmias and clinical symptoms, hemodynamic data, or electrocardiographic features. Propranolol administration resulted in failure of exercise to induce PSVT in one patient and had no effect on PSVT in two others, nor any effect on maximum frequency of APBs or VPBs. Treadmill testing is more productive than retrospective analysis of ECGs for characterizing arrhythmias in IHSS.

Pulmonary cavitation is a rare complication of allergic bronchopulmonary aspergillosis in patients with chronic asthma. Such patients frequently manifest mucoid impaction of a bronchus, "central" saccular bronchiectasis and bronchocentric granulomatosis, a specific microscopic pathologic entity. Early recognition of this syndrome in asthmatic patients and vigorous treatment with steroids may obviate surgery.

As the chromophoric component of the visual pigment, retinol plays an essential role in vision. In the plasma, retinol is transported by retinol-binding protein (RBP) in complex with transthyretin (TTR, prealbumin). In previous work we demonstrated intraocular synthesis of TTR. To determine whether RBP is also synthesized in the eye, we performed Northern and Western blot analysis of rat eye, and detected both RBP mRNA and immunoreactive RBP. Regional Northern analysis of bovine eye localized RBP mRNA to ciliary body/iris and retina/RPE. Preliminary immunohistochemical studies revealed a widespread but heterogeneous distribution of RBP in rat eye. We postulate that ocular RBP and TTR are involved in the intraocular translocation of retinol.

Amyloid deposits in several heredofamilial forms of amyloidosis are known to be chemically related to transthyretin (TTR, the plasma protein usually referred to as prealbumin). A genetic mutation, leading to an abnormal TTR, may be involved. Studies were conducted to investigate whether or not Portuguese patients with familial amyloidotic polyneuropathy (FAP) have an abnormal species of TTR circulating in their plasma and, if so, whether this might have any impact on vitamin A transport and retinol-binding protein (RBP) metabolism in these patients. The initial studies examined the plasma concentrations of TTR, RBP, and retinol in patients with FAP. Significantly reduced (p less than 0.005) levels of TTR were found in patients with FAP. The TTR levels in 24 FAP patients were approximately two thirds of those of a group of 18 control subjects from the same geographic area. In contrast, RBP levels were not reduced, nor was there an abnormality in the ratio of retinol to RBP, in the patients with FAP. Thus there does not appear to be an abnormality in vitamin A transport in Portuguese patients with FAP. There does, however, appear to be an abnormality of TTR metabolism, accounting for the reduced plasma levels of TTR. TTR was isolated from pooled sera of the FAP patients and was characterized in detail. FAP-TTR was indistinguishable from normal TTR with regard to a variety of parameters, including (1) electrophoretic mobility, (2) chromatographic behavior, (3) molecular weight, (4) stability of the TTR tetramer, (5) immunoreactivity in TTR radioimmunoassays using antisera prepared against both normal and FAP-TTR, (6) ability to form a protein-protein complex with RBP and affinity for RBP as assessed by polarization of fluorescence, and (7) overall amino acid composition. The possible explanations are as follows: (1) an abnormal TTR molecule is not produced in this form of FAP; (2) the abnormal molecule is present in only trace amounts (not detectable in the present study) in FAP plasma; or (3) the abnormal TTR is structurally almost identical to normal TTR and does not differ from normal TTR with regard to the various physical and chemical properties investigated in this study. Preliminary observations suggest that FAP patients do produce an abnormal form of TTR that selectively deposits in tissues as amyloid protein.

The turnover of free cholesterol in atheromatous plaque lipid phases was studied in a patient undergoing peripheral vascular surgery. [14C]Cholesterol was injected intravenously 139 days prior to surgery, and [3H]cholesterol was injected 12 days pre-op. The plasma cholesterol specific radioactivity decay curves were determined from the times of isotope injection until surgery. At surgery, atheroma, skin, muscle, and tendon were obtained. Lipid phases of plaque homogenate were isolated by density gradient centrifugation. The top layer of the gradient, layer 1, contained the cholesteryl ester oil droplet phase, layer 2 was enriched in phospholipid bilayer phase, layer 3 contained cholesterol monohydrate crystals and the pellet, layer 4 had more dense plaque components such as collagen and elastin. The tissue:plasma specific radioactivity ratios on days 12 and 139 respectively were muscle, 0.86, 2.47; skin, 0.74, 1.20; tendon, 0.18, 1.45; total plaque, 0.22, 1.39; plaque layer 1, 0.31, 1.50; layer 2, 0.22, 1.53; layer 3, 0.08, 0.61; and layer 4, 0.20, 0.88. Thus, plaque atheroma, which contains physically distinct forms of cholesterol, had correspondingly different rates of cholesterol turnover. Cholesterol solubilized in liquid oil droplets (layer 1) and liquid crystalline phospholipid bilayers (layer 2) had specific radioactivity values similar to those of tendon cholesterol, and represented tissue cholesterol that was undergoing slow equilibration with the plasma cholesterol pool. Pellet cholesterol (layer 4), which is probably connective tissue-associated, had lower specific radioactivity values, well below those of plasma cholesterol even after 5 months. Crystalline cholesterol (layer 3) had the lowest specific radioactivity values of all tissues and plaque fractions. Therefore, cholesterol in the crystalline state is relatively inert. Since crystalline cholesterol can account for over 40% of plaque free cholesterol, resistance to mobilization of this lipid may be an important obstacle to plaque regression.

Studies were conducted to define the subcellular localization of endogenous retinoids (vitamin A), retinoid-binding proteins, and acyl-CoA:retinol acyltransferase (ARAT) in liver and to determine whether their distributions were affected by hepatic vitamin A content. Quantitative subcellular fractionation techniques were used. Rats were fed purified diets either containing or lacking vitamin A to obtain animals with total retinoid stores ranging from 0.5 to 172 micrograms of retinol equivalent per gram of liver. Liver homogenates were fractionated by differential centrifugation to yield nuclear (N), mitochondrial-lysosomal (ML), microsomal (P), and high-speed supernatant (S) fractions. N, ML, and P were washed two more times by resuspension and centrifugation to remove constituents bound nonspecifically. S was further resolved into "floating lipid" and underlying "cytosol" by prolonged ultracentrifugation. The distributions of marker constituents were not affected by vitamin A status. Most of the retinyl ester in the liver was recovered in the S fraction where it was entirely (greater than 95%) associated with floating lipid. About half of the total free retinol was also recovered in the S fraction, but it was mostly (2/3) associated with cytosol per se. A substantial portion (30%) of the free retinol was recovered in the 3 X -washed microsomal (P) fraction. Sufficient binding capacity for retinol was present in both P (as retinol-binding protein) and S (as cellular retinol-binding protein) to quantitatively account for the amounts of free retinol present in the two fractions. ARAT activity in the liver was distributed among the subcellular fractions in a manner identical with an endoplasmic reticulum marker enzyme (NADPH-cytochrome C reductase).(ABSTRACT TRUNCATED AT 250 WORDS)