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Background. The aim of this pilot study was to assess the feasibility of a pharmacodynamics assay that measures Nuclear Factor of Activated T Cell–dependent cytokines expressed as % mean residual expression (MRE) to adjust tacrolimus (tac) dose (intervention [INT] arm) in comparison with the standard of care of tac trough levels (control [CTL] arm). Methods. We conducted a single-center randomized controlled trial involving 40 stable kidney transplant recipients over 1 year. In the INT arm, the dose of tac was reduced by 15% if the MRE was less than 20% and was increased by 15% if the MRE was greater than 60%. Controls were adjusted based on tac trough levels. Results. There was a median of 2 tac dose changes per arm. Ten subjects had 1 or more infections in the INT arm and 6 subjects had 1 or more infection in the CTL arm. Rates for hospitalizations, rejections, malignancies and death were similar in both arms. In subjects whose tac dose was not adjusted in the first 6 months, those with infections had a lower MRE at enrollment compared with those without infections (P = 0.049). This was not true for tac trough levels (P = 0.80). There was no correlation between MRE and rejection. Conclusions. Our study suggests that adjusting tac based on this pharmacodynamics assay is feasible. Quantitative analysis of nuclear factor of activated T-regulated gene expression may serve as a reliable assay to lower tac dosing. Further studies with larger populations are needed.

Purpose/objectives: The onset of the coronavirus disease 2019 pandemic increased the demand for inpatient services and led to widespread staffing shortages in the acute and post-acute setting, contributing to delayed inpatient throughput and leading to capacity crises. Novel strategies are needed to facilitate the efficient progression of hospitalized patients when medically ready for lower levels of care. The authors have developed a foundational strategic framework for patient progression to ensure capture of patient progression data, enhance efficiency, and optimal utilization of post-acute resources in increasingly complex and resource-constrained acute and post-acute environments., Primary Practice Settings: Interventions were implemented, and metrics of success tracked as part of an overarching framework to test new models of care or optimize existing assets related to barriers to patient progression. Brigham and Women's Hospital (BWH) and Brigham and Women's Faulkner Hospital (BWFH) comprise an academic medical center and a community hospital, respectively, that are affiliated with Massachusetts General Brigham (MGB), a nonprofit health care system in Massachusetts. Key interventions include (1) screening to prioritize patients needing case management services through a modified early screening for discharge planning tool and process; (2) communicating, documenting, identifying patient progression status, barriers to discharge and post-acute needs through interdisciplinary care optimization rounds, a novel tool in the electronic health record, and an associated dashboard; (3) managing active high-risk patients through a novel complex care team and post-acute strategy development; (4) developing novel transportation and hospice pathways; and (5) establishing community hospital repatriation and a physical therapy "Why Not Home" campaign., Findings: Key metrics of success were (1) modified discharge planning tool resulting in screening out low-risk patients (53%) and impacting length of stay (0.55-day reduction, p = .083) during a 3-month intervention versus control study; (2) documentation adherence in more than 98% of patients 10 months postimplementation; (3) complex care team achieving a 2.5% reduction in Case Mix Index-adjusted length of stay 6 months postimplementation; (4) use of care van offsetting ambulance/chair car in 10% of cases, and earlier discharge time/length of stay in 21% of cases 3 months postimplementation; and (5) implementation of community repatriation impacting delay days to discharge (10-month pilot, 40 patients accounting for 1,000 delay days)., Conclusions: Implementation of a novel comprehensive framework focusing on optimizing patient progression resulted in increased operational efficiency and positively impacted length of stay at our academic and community hospitals. Additional study is actively ongoing to understand long-term benefit of the innovations that the authors have developed. Further interventions are needed to wholly mitigate evolving capacity challenges in the acute and post-acute settings., Implications for Case Management Practice: The authors' implementation of the Brigham framework for progression demonstrates that innovative approaches to case management can help address the evolving challenges in care transitions planning. Notable opportunities include approaches that empower case managers as multidisciplinary team leaders, improve workflow, utilize patient progression data, prioritize patients with complex care needs support key patient populations, and promote post-acute collaboration., Competing Interests: Conflicts of Interest: Dr. Laura Smith serves on the advisory board for New England Life Care, not relevant to the contents of this article. For the remaining authors none are declared. The authors report no conflicts of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Objective: To report safety and efficacy of ixekizumab (IXE) from the COAST program at 3 years, including 1 year from the originating studies (COAST-V, COAST-W, and COAST-X), and 2 years from COAST-Y., Methods: In COAST-Y, patients continued with the dose received at the end of the originating study at week 52: 80 mg IXE either every 4 weeks (Q4W) or every 2 weeks (Q2W). Placebo-treated patients from COAST-X received IXE Q4W in COAST-Y. Starting at week 116 (week 64 of COAST-Y), patients receiving IXE Q4W could be escalated to Q2W. Safety for patients receiving ≥ 1 dose of IXE and efficacy for patients receiving ≥ 1 dose of IXE Q4W was assessed. Data are summarized as observed., Results: For the 932 patients who received ≥ 1 dose of IXE (Q2W or Q4W) through 3 years, treatment-emergent adverse events (TEAEs) occurred at an incidence rate (IR) of 38.0 per 100 patient-years (PYs). The most frequently reported were infections (IR 25.7 per 100 PYs) and injection site reactions (IR 7.4 per 100 PYs); the majority of TEAEs were mild or moderate in severity. In total, 7.1% of TEAEs led to discontinuation (IR 3.1 per 100 PYs). All patient groups receiving IXE Q4W assessed through 3 years saw sustained improvements in Ankylosing Spondylitis Disease Activity Score, clinically important improvement, and other efficacy end points., Conclusion: The 3-year safety profile of IXE in the COAST program is consistent with the previously established long-term safety profile. IXE Q4W provided sustained improvement of disease activity in patients who received treatment through 3 years. (ClinicalTrials.gov: NCT02696785 [COAST-V], NCT02696798 [COAST-W], NCT02757352 [COAST-X], and NCT03129100 [COAST-Y])., (Copyright © 2023 by the Journal of Rheumatology.)

More than 422 million people worldwide suffered from diabetes mellitus (DM) in 2021. Diabetic foot is one the most critical complications resultant of DM. Foot ulceration and infection are frequently arisen, which are associated with changes in the mechanical properties of the plantar soft tissues, peripheral arterial disease, and sensory neuropathy. Diabetic insoles are currently the mainstay in reducing the risk of foot ulcers by reducing the magnitude of the pressure on the plantar Here, we propose a novel pressure relieving heel pad based on a circular auxetic re-entrant honeycomb structure by using three-dimensional (3D) printing technology to minimize the pressure on the heel, thus reducing the occurrence of foot ulcers. Finite element models (FEMs) are developed to evaluate the structural changes of the developed circular auxetic structure upon exertion of compressive forces. Moreover, the effects of the internal angle of the re-entrant structure on the peak contact force and the mean pressure acting on the heel as well as the contact area between the heel and the pads are investigated through a finite element analysis (FEA). Based on the result from the validated FEMs, the proposed heel pad with an auxetic structure demonstrates a distinct reduction in the peak contact force (∼10%) and the mean pressure (∼14%) in comparison to a conventional diabetic insole (PU foam). The characterized result of the designed circular auxetic structure not only provides new insights into diabetic foot protection, but also the design and development of various impact resistance products., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Hepatocellular carcinoma (HCC) is a biologically aggressive cancer. Targeted therapy is in need to tackle challenges in the treatment perspective. A growing body of evidence suggests a promising role of pharmacological inhibition of PIM (proviral integration site for Moloney murine leukaemia virus) kinase in some human haematological and solid cancers. Yet to date, the potential application of PIM inhibitors in HCC is still largely unexplored. In the present study we investigated the pre-clinical efficacy of PIM inhibition as a therapeutic approach in HCC. Effects of PIM inhibitors on cell proliferation, migration, invasion, chemosensitivity, and self-renewal were examined in vitro. The effects of PIM inhibitors on tumour growth and chemoresistance in vivo were studied using xenograft mouse models. Potential downstream molecular mechanisms were elucidated by RNA sequencing (RNA-seq) of tumour tissues harvested from animal models. Our findings demonstrate that PIM inhibitors SGI-1776 and PIM447 reduced HCC proliferation, metastatic potential, and self-renewal in vitro. Results from in vivo experiments supported the role of PIM inhibition in suppressing of tumour growth and increasing chemosensitivity of HCC toward cisplatin and doxorubicin, the two commonly used chemotherapeutic agents in trans-arterial chemoembolisation (TACE) for HCC. RNA-seq analysis revealed downregulation of the MAPK/ERK pathway upon PIM inhibition in HCC cells. In addition, LOXL2 and ICAM1 were identified as potential downstream effectors. Taken together, PIM inhibitors demonstrated remarkable anti-tumourigenic effects in HCC in vitro and in vivo. PIM kinase inhibition is a potential approach to be exploited in formulating adjuvant therapy for HCC patients of different disease stages. © 2020 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd., (© 2020 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.)

Waterfalls are conspicuous geomorphological features with heterogeneous structure, complex dynamics and multiphase flows. Swifts, dippers and starlings are well-known to nest behind waterfalls, and have been reported to fly through them. For smaller fliers, by contrast, waterfalls seem to represent impenetrable barriers, but associated physical constraints and the kinematic responses of volant animals during transit are unknown. Here, we describe the flight behaviour of hummingbirds (the sister group to the swifts) and of various insect taxa as they fly through an artificial sheet waterfall. We additionally launched plastic balls at different speeds at the waterfall so as to assess the inertial dependence of sheet penetration. Hummingbirds were able to penetrate the waterfall with reductions in both their translational speed, and stroke amplitude. The body tilted more vertically and exhibited greater rotations in roll, pitch and yaw, along with increases in tail spread and pitch. The much smaller plastic balls and some flies moving at speeds greater than 2.3 m s -1 and 1.6 m s -1 , respectively, also overcame effects of surface tension and water momentum and passed through the waterfall; objects with lower momentum, by contrast, entered the sheet but then fell along with the moving water. Waterfalls can thus represent impenetrable physical barriers for small and slow animal fliers, and may also serve to exclude both predators and parasites from nests of some avian taxa., Competing Interests: We declare we have no competing interests, (© 2020 The Authors.)

Accumulating evidence illustrates the significance of cell plasticity in the molecular biology of liver cancer. Reprogramming of mature parenchymal cells to a less differentiated state by key molecular targets contributes to the pathogenesis of hepatocellular carcinoma (HCC). Hereby, we investigated the role of GATA6, a transcription factor implicated in hepatocyte lineage specification, in HCC. Our results demonstrated a lower expression of GATA6 in HCC tissues compared to the corresponding nontumoral liver tissues. Moreover, GATA6 underexpression, as observed in about 50% cases in our clinical cohort, was associated with a poorer degree of tumor cell differentiation and worse disease-free survival outcome. In vitro, silencing of GATA6 in HCC cells augmented cell migration and invasion abilities of HCC cells by activating epithelial-mesenchymal transition. Self-renewal was also enhanced in vitro. Consistently, in vivo tumorigenicity and self-renewal was promoted upon GATA6 knockdown. Notably, suppression of GATA6 converts HCC cells to a metabolic phenotype recapitulating stem-cell state. Expression of glycolytic markers was elevated in GATA6-knockdown clones accompanied by increased glucose uptake; while overexpression of GATA6 resulted in opposite effects. Further to this, we identified that GATA6 bound to the promoter region of PKM gene and regulated PKM2 transcription. Taken together, downregulation of GATA6 directs HCC cells to glycolytic metabolism and fosters tumorigenicity, self-renewal and metastasis. GATA6 is a transcriptional regulator and a genetic switch that converts the phenotypic reprogramming of HCC cells. It is a potential prognostic biomarker and therapeutic target for liver cancer., (© 2019 UICC.)

Interactions between bacteria and bacteriophage viruses (phages) are known to influence pathogen growth and virulence, microbial diversity and even biogeochemical cycling. Lytic phages in particular infect and lyse their host cells, and can therefore have significant effects on cell densities as well as competitive dynamics within microbial communities. Despite the known impacts of lytic phages on the ecology and evolution of bacteria in free-living communities, little is known about the role of lytic phages in host-associated microbiomes. We set out to characterize the impact of phages in the tomato phyllosphere, that is the bacteria associated with above-ground plant tissues, by transferring microbial communities from field-grown tomato plants to juvenile plants grown under mostly sterile conditions in either the presence or absence of their associated phage community. In three separate experiments, we found that the presence of phages affects overall bacterial abundance during colonization of new host plants. Furthermore, bacterial community analysis using 16S rRNA amplicon sequencing shows that phages significantly alter the relative abundance of dominant community members and can influence both within- and among-host diversity. These results underscore the importance of lytic phages in host-associated microbiomes and are relevant to microbiome transplantation approaches, as they suggest transferring nonbacterial components of the microbiome among hosts is likely to have a strong impact on growth of both the resident and colonizing microbiota., (© 2018 John Wiley & Sons Ltd.)

Background: Hepatocellular carcinoma (HCC) is the most common type of liver cancer worldwide. Previously, we reported that cadherin-17 (CDH17) and its related CDH17/β-catenin axis may be responsible for inducing HCC in a subset of patients exhibiting CDH17 over-expression. Here we aimed at obtaining a better understanding of the CDH17-related HCC biology and to obtain further indications for the design of targeted therapies in CDH17 over-expressing HCC patients., Results: We found that SPINK1 acts as a downstream effector of the CDH17/β-catenin axis in HCC. In addition, we found that SPINK1 expression exhibited a positive correlation with CDH17 expression in human HCCs and was over-expressed in up to 70% of the tumors. We identified SPINK1 as a downstream effector of the CDH17/β-catenin axis using a spectrum of in vitro assays, including gene expression modulation and inhibitor assays, bioinformatics analyses and luciferase reporter assays. These in vitro results were validated in primary human HCCs, including the observation that alteration in β-catenin expression (a core component of the CDH17/β-catenin axis) in tumors affects SPINK1 serum levels in HCC patients. Similar to CDH17, SPINK1 expression in HCC cells was found to be associated with specific tumor-related properties via activating the c-Raf/MEK/ERK pathway., Conclusions: Our current data substantiate our knowledge on the role of CDH17 in the biology of HCC and suggest that components of the CDH17/β-catenin axis may serve as therapeutic targets in CDH17 over-expressing HCC patients.

Exposure to 17β-estradiol (E2) influences the regulation of multiple signaling pathways, and E2-mediated disruption of signaling events during early development can lead to malformations such as cardiac defects. In this study, we investigated the potential role of the G-protein estrogen receptor 1 (GPER) in E2-induced developmental toxicity. Zebrafish embryos were exposed to E2 from 2h post fertilization (hpf) to 76 hpf with subsequent transcriptional measurements of heart and neural crest derivatives expressed 2 (hand2), leucine rich repeat containing 10 (lrrc10), and gper at 12, 28 and 76 hpf. Alteration in the expression of lrrc10, hand2 and gper was observed at 12 hpf and 76 hpf, but not at 28 hpf. Expression of these genes was also altered after exposure to G1 (a GPER agonist) at 76 hpf. Expression of lrrc10, hand2 and gper all coincided with the formation of cardiac edema at 76 hpf as well as other developmental abnormalities. While co-exposure of G1 with G36 (a GPER antagonist) rescued G1-induced abnormalities and altered gene expression, co-exposure of E2 with G36, or ICI 182,780 (an estrogen receptor antagonist) did not rescue E2-induced cardiac deformities or gene expression. In addition, no effects on the concentrations of downstream ER and GPER signaling molecules (cAMP or calcium) were observed in embryo homogenates after E2 treatment. These data suggest that the impacts of E2 on embryonic development at this stage are complex and may involve multiple receptor and/or signaling pathways., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Objective: To systematically review and assess the quality of cost-effectiveness analyses (CEAs) of pharmaceutical therapies for metastatic colorectal cancer (mCRC)., Data Sources: The MEDLINE, EMBASE, Cochrane, and EconLit databases were searched for the Medical Subject Headings or text key words quality-adjusted, QALY, life-year gained (LYG), and cost-effectiveness (January 1, 1999-December 31, 2009)., Study Selection: Original CEAs of mCRC pharmacotherapy published in English were included. CEAs that measured health effects in units other than quality-adjusted life years or LYG and letters to the editor, case reports, posters, and editorials were excluded., Data Extraction: Each article was independently assessed by 2 trained reviewers according to a quality checklist created by the Panel on Cost-Effectiveness in Health and Medicine., Results: Twenty-four CEA studies pertaining to pharmaceutical therapies for mCRC were identified. All studies showed a wide variation in methodologic approaches, which resulted in a different range of incremental cost-effectiveness ratios reported for each regimen. We found common methodologic flaws in a significant number of CEA studies, including lack of clear description for critique of data quality; lack of method for adjusting costs for inflation and methods for obtaining expert judgment; no results of model validation; wide differences in the types of perspective, time horizon, study design, cost categories, and effect outcomes; and no quality assessment of data (cost and effectiveness) for the interventions evaluation., Conclusions: This study has shown a wide variation in the methodology and quality of cost-effectiveness analysis for mCRC. Improving quality and harmonization of CEA for cancer treatment is needed. Further study is suggested to assess the quality of CEA methodology outside the mCRC disease state.

We report the design and fabrication of a nanoantenna structure on the surface of a 3D nanoliter-scale container for the development of communicable nanoliter-scale chemical delivery systems. The porous container was self-assembled, after which the nanoantenna was fabricated on the top of the microcontainer using focused ion beam (FIB) ion-induced metal deposition. The nanoantenna was structured as a rectangular metal coil composed of platinum (Pt) nanowires (70 nm in width). The response of the nanoantenna structure was simulated using finite element software and showed a strong resonant feature at 10.8 GHz, which was confirmed by high frequency measurements.

Purpose: The purpose of this study was to test the efficacy of a social support intervention with parents of children <13 years old newly diagnosed with type 1 diabetes mellitus (T1DM)., Methods: For this randomized, controlled clinical trial, 10 parent mentors of children diagnosed with T1DM >or=1 year and 60 parent participants were recruited from 2 pediatric diabetes centers. Mentors were trained to provide social support (home visits and phone calls) for 12 months to families in the experimental arm (32 mothers). Control group parents (28 mothers) received the phone number of an experienced parent (not trained to give social support) to call as needed. Findings Mothers in the experimental and control arms differed at baseline only in birth order of the child with T1DM. The 2 groups did not differ significantly at 3, 6, or 12 months in parent concern, confidence, worry, impact on the family, or perceived social support. Mothers in the experimental arm identified the parent mentor as someone they would seek for advice and issues regarding growth and development, sleep, eating habits, and identification of community agencies. Parent mentors consistently referred mothers to health care providers for advice on medications and treatments but helped them incorporate this advice into day-to-day management., Conclusion: Mothers in the experimental arm valued the mentors' help in adjusting to the diagnosis, but this value was not measured by the study instruments. Focus group research is under way to clarify the concept of parent mentor social support and to develop a social support measurement tool.

Objective: To evaluate anterolateral thigh flap shrinkage after elevation and to develop a predictive model for flap design., Method: A prospective study was conducted in a university teaching hospital. The skin islands from anterolateral thigh flaps were outlined on a transparent sheet before and after the reconstruction procedure. Dimensions of the stretched flaps were also recorded. These three outlines were scanned and the surface areas computed and compared by tracing and use of AutoCAD. Age, sex, flap dimension, and flap thickness were investigated for association with flap shrinkage., Results: Forty-five anterolateral thigh flaps harvested for head and neck soft tissue reconstruction after tumor resection were studied. Flap size ranged from 4 to 14 cm in width and 8 to 22 cm in length; flap area ranged from 30.6 to 151.0 cm. On average, the flaps shrunk by 25.0% (6.2%-52.6%), a highly significant change (P < .01). Flap width and thickness correlated with the reduction in flap size. The average stretched-flap area was 10.1% (0.4%-29.4%) less than the preflap area, a significant reduction (P < .01). The difference between stretched-flap and preflap areas was independent of all variables. We developed a predictive model using a stepwise multiple linear regression method with a coefficient of determination of 0.495., Conclusions: Anterolateral thigh flaps shrink after harvesting, and flap width and thickness are significant contributing variables. These findings indicate that flap size must take shrinkage into account to ensure sufficient coverage.

Objectives: To determine whether the addition of deep or superficial heating to stretching produces better clinical outcomes than stretching alone in the management of frozen shoulder., Design: A single-blinded, randomized controlled study., Subjects: Thirty subjects suffering from the stiffness phase of frozen shoulder., Methods: Subjects were randomly allocated to receive: (i) deep heating plus stretching; (ii) superficial heating plus stretching; or (iii) stretching alone. Both heating groups received the respective treatments 3 times per week for 4 weeks. All groups received a standard set of shoulder stretching exercises. The American Shoulder and Elbow Surgeons assessment form was recorded at the baseline, sessions 6 and 12, and at the 4-week follow-up session., Results: A significant improvement was seen in all groups in all outcome measures except for that of shoulder flexion range. The improvement in the shoulder score index and in the range of motion was significantly better in the deep heating group than in the superficial heating group., Conclusion: The addition of deep heating to stretching exercises produced a greater improvement in pain relief, and resulted in better performance in the activities of daily living and in range of motion than did superficial heating.

This study evaluated the antimicrobial resistance profile of outpatient urinary Escherichia coli isolated from women obtained throughout Hong Kong during 2004-2005. Of 1067 single patient isolates analyzed, 60.1% were resistant to ampicillin, 34% were resistant to co-trimoxazole, and 22.1% were resistant to ciprofloxacin. Thirty-four (6.6%) of 519 isolates in 2004 and 55 (10%) of 548 isolates in 2005 were extended-spectrum beta-lactamase (ESBL) producers with a CTX-M phenotype. Rates of non-beta-lactam resistance and ESBL production were strongly influenced by patient age. The age-stratified rates for dual co-trimoxazole and ciprofloxacin resistance and for ESBL production were 10.9% and 7.6% in women aged 18-35 years, 13% and 6.9% in women aged 36-50 years, 20.4% and 8.8% in women aged 51-64 years, and 23.7% and 11.8% in women aged > or =65 years, respectively. Nitrofurantoin and fosfomycin remain active against >90% of the isolates, irrespective of the resistance phenotypes for other drugs. Our results documented the emergence of problematic resistance phenotypes among community urinary E. coli and highlight the need to explore strategies for their containment.

Objectives: To conduct a territory-wide study of extended-spectrum beta-lactamases (ESBLs) among community isolates of urinary Escherichia coli from women in Hong Kong., Methods: Up to 50 consecutive single-patient E. coli isolates, collected from 13 laboratories in 2004, were studied. The ESBLs were characterized by PCR sequencing using specific primers. The epidemiological relationship of the isolates was studied by PFGE and phylogenetic group PCRs., Results: Forty-two ESBL producers were found among 600 consecutive isolates tested. The ESBL prevalence was 7.3% (15/205) for women aged 18-35 years, 5% (11/219) for women aged 36-50 years, 6.3% (4/63) for women aged 51-64 years and 10.6% (12/113) for women aged >or=65 years (P=0.3). The ESBL-producing isolates were often multidrug-resistant and CTX-M-14 was found in 37 isolates, CTX-M-15 in 3 isolates and CTX-M-3 in 2 isolates. PFGE revealed no significant clusters among the ESBL producers. Overall, CTX-M-14 producers were significantly more likely to belong to group D than non-ESBL producers [18/37 (48.6%) versus 13/57 (22.8%), P=0.009]. However, 7 of 13 (53.8%) CTX-M-14 producers from women aged 18-35 years represented phylogenetic group B2, compared with 7 of 24 (29.2%) for women of all other ages (P=0.1)., Conclusions: The study documented the community emergence of CTX-M as the predominant ESBL type among urinary isolates from women. The spread of CTX-M enzymes among isolates from young women is concerning and deserves close monitoring.

Resistance to passive movement in children with spastic cerebral palsy was assessed by two raters using the Modified Ashworth Scale and the Modified Tardieu Scale. Four muscle groups in the lower limbs were tested using a standardized procedure. Interrater reliability of the scales was evaluated by the intraclass correlation coefficient. Seventeen children, with a mean age of 7 years 9 months, were included. Two children were rated twice. The intraclass correlation coefficients of both scales were low and did not reach the acceptable limit of 0.75. Caution should be used when these scales are applied.

Background: A disproportionate number of women diagnosed with cervical cancer are from low-income and/or ethnically diverse groups. This study was designed to evaluate the effectiveness of an outreach and counseling intervention at improving the rate of follow-up of abnormal Pap smears among women at Alameda County Medical Center, Oakland, CA., Methods: Between September 1, 1999 and August 31, 2001, 348 women with abnormal Pap test results were randomly assigned to intervention or usual care. The main outcome was rate of follow-up., Results: The intervention produced a significant increase in the rate of follow-up visits within 6 months. Women in the intervention group were much more likely to obtain timely follow-up at Highland Hospital than were those in the control group (61% vs. 32%, P = 0.001). The intervention was equally effective when delivered to women in the control group who had no follow-up by 6 months. Overall, we were able to contact 90% of women in the intervention group., Conclusions: An outreach intervention is highly effective at increasing follow-up of abnormal Pap smears in a public hospital setting. Institutions offering cervical cancer screening to low-income, high-risk women should consider the use of outreach workers to reduce loss to follow-up.

Axon guidance molecules and related proteins such as semaphorin 3A, neuropilin-1, plexin-1, netrin-1, growth-associated protein, olfactory marker protein, cypin and collapsin response mediator proteins guide the development of neural circuits in the olfactory bulb. In this study, transcriptions of these genes were examined in the olfactory bulb of female, male and neonatal testosterone propionate-treated female rats at the ages of 2, 5, 10, 15, 20, 25, 30 and 45 days. The semaphorin 3A, neuropilin-1, growth-associated protein and collapsin response mediator protein 1-5 genes were expressed significantly higher during the early development stages than in adulthood while the opposite is true for the olfactory marker protein. The expression profile of cypin and netrin-1 was relatively constant through development. A late effect of the neonatal testosterone propionate treatment on netrin-1, growth-associated protein, olfactory marker protein, collapsin response mediator proteins 1, 3, 4 and cypin gene expression was observed. The expression profiles of collapsin response mediator proteins and their related genes in the developing olfactory bulb confirmed most studies on the relationship between collapsin response mediator proteins and development in the brain. Sex differences of semaphorin 3A, neuropilin-1 as well as collapsin response mediator protein 3 at the early development stage and the late effect of neonatal testosterone propionate treatment on the expressions of netrin-1, growth-associated marker protein, cypin and collapsin response mediator proteins 1, 3 and 5 genes may indicate a possible role of these molecules on sexual differentiation of the olfactory bulb.

During critical periods of development, hypothyroidism causes abnormalities of the central nervous system such as incomplete maturation of neuronal and glial cells, reduction in synaptic densities and myelin deficits. In this study expression of development regulated genes, ie transcription of beta-actin, sema 3F, CRMP 1 to 4, GAP-43, G alpha o1, G alpha o2 and translation of beta-actin, G alpha o, G alpha o1, CRMP-2, CRMP-4 genes were examined in the hippocampus of neonatal methimazole induced hypothyroid rats at the age of day 16. All CRMPs mRNA levels were significantly higher in the hypothyroid rats. Significant higher CRMP-2 protein but not CRMP-4 protein was found in the hypothyroid rats. The neonatal experimental hypothyroid states did not affect the protein levels of beta-actin but up-regulate its mRNA. Transcription of CRMP 1 to 4, GAP-43, G alpha o1 but not G alpha o2 and sema 3F was altered by the neonatal treatment. The only sex difference in gene expression was found in the transcription of CRMP-2 gene.

In this study, expressions of cell-cycle-related genes: p53, retinoblastoma (Rb), p21, bcl-2(alpha), bcl-2(beta); protooncogene c-ski; glial cell marker protein gene S100beta; neurotransmitter gene, substance P and sexual-differentiation-related genes, androgen receptor (AR) and estrogen receptor beta (ER(beta)), are studied in the olfactory bulb of groups of both six female and six male rats at the ages of 3, 10, 20 and 40 days. Expressions of housekeeping genes such as beta-actin, cyclophilin and proliferating cell nuclear antigens (PCNA) are determined using reverse transcription polymerase chain reaction (RT-PCR) for the correction of unequal amount of cDNA added into the samples. Using labeled 32P-dCTP and Phosphorimager technology, relative abundance of radioactivities of the PCR products is obtained by dividing the radioactivity of each individual sample by the corresponding radioactivities of different housekeeping genes. Data evaluated by Two-way ANOVA indicate that only the bcl-2(alpha) gene expression is affected significantly by age, sex and their interactions no matter which of the three housekeeping genes is used for correction. When beta-actin was used for corrections, effects of age but not sex were found in the expressions of p53, Rb, p21, AR, ER(beta), substance P and S100beta genes, but not in bcl-2(beta), c-ski, cyclophilin and PCNA genes. While cyclophilin was used for corrections, only the p53, Rb, AR, ER(beta), substance P and S100beta but not the bcl-2(beta), p21, c-ski, PCNA and beta-actin genes are affected by age. They are all not influenced by sex of the animals. Only the AR, ER(beta) and S100beta genes are age-dependent when PCNA was used for the correction. The other gene expressions are not altered by sex, while the interactions of age and sex were found to be significantly affecting the bcl-2(beta) gene expression. Conclusively, developmental changes of the p53, Rb, AR, ER(beta), substance P and S100beta genes expressions are quite evidenced while only the bcl-2(alpha) gene seems to change significantly during the sexual differentiation of olfactory bulb in rats.

Reverse transcription-polymerase chain reaction using 32P-labeled dCTP with specific primers for putative neurotransmitters related and neuronal growth-related genes (GAP-43, NGF and BDNF) were used to search for evidence of such substances in the Merkel cell. Merkel cell samples were made from sinus hairs in the facial skin of rats. The relative amount of mRNA in a tissue sample concentrated in Merkel cells was compared semiquantitatively to that from nearby tissue without Merkel cells. mRNAs for VIP, tyrosine hydroxylase, substance P were found in higher concentration in Merkel cells than in control tissues. mRNA for genes encoding pro-enkephalin, GAP-43, CGRP, NGF and BDNF were detected in the Merkel cell samples at concentration statistically equivalent to those found in the control tissues. It was concluded that the relative concentration of mRNAs for VIP, tyrosine hydroxylase and substance P is consistent with the possibility that Merkel cell acts as a possible transduction element in mechanical excitation of sense organs in which Merkel cells are present.

The metallo-organic solution deposition (MOSD or sol-gel) technique can be used for preparing lead zirconate titanate (PZT) ceramics with a wide range of compositions and crystal structures for electrooptical applications. Film morphology is affected by the stoichiometry of the film, hydrolysis and polymerization of the sol-gel solution, and thermal treatment of the deposited material. The lattice parameter decreases with the amount of titanium in the PZT, in agreement with ceramic data. A slight initial excess of lead in the coating solution is found to improve film morphology. Unlike traditional powder ceramic processing techniques, MOSD permits the growth of small uniform grains that are conducive to achieving consistent electronic and optical properties. Results show that the properties of films prepared by the MOSD process can be tailored to meet the needs of device applications.

1. Slowly adapting type I (SAI) and type II (SAII) mechanoreceptors in the skin were studied in anaesthetized cats and rats employing mechanical stimuli every 30 s. Individual stimuli rose within 200 ms to a plateau force which was kept constant through a feedback control unit for 2000 ms. 2. In cats, close arterial infusion of neomycin (2.5 mg/min) as sulphate was given through a side branch into the femoral blood stream for 5, 10 or 20 min at a rate of 0.025 ml/min. At other times saline was infused at the same rate. 3. After 20 min of neomycin infusion (total 50 mg) nervous discharge of cat SAI receptors was suppressed to about 30% of the control responses before neomycin infusion. Nervous responses were reduced more profoundly during the plateau phase of stimulation than during the dynamic phase. The interspike interval histogram was severely distorted. 4. In contrast, cat SAII receptors maintained about 70% of their control response after 20 min of neomycin infusion. The interspike interval histogram showed an orderly shift towards longer intervals maintaining its normal shape. 5. In rats, intradermal microinfusion of neomycin (30 micrograms/min) through a glass micropipette into the immediate vicinity of the receptor under investigation resulted in severe transient suppression of SAI receptor responses to about 10% of the control level. Receptor responses recovered almost completely about 1 h after the end of neomycin application. 6. It is concluded that the observed differences between the two types of slowly adapting mechanoreceptors are consistent with the hypothesis that the SAI receptor functions as a secondary sensory receptor, with a synaptic link between the Merkel cell and the primary afferent neurone.

Epidermal-thyroid relationships were studied in thyroidectomized (Tx) Ptyas korros kept at 23 degrees C by observing changes in shedding frequency (SF), body weight, oxygen consumption rate (OCR), and postsurgical survival. Tx animals showed increased SFs but lost weight and eventually died, as did Tx animals receiving 3-mono-iodotyrosine injections. However, injections of 3, 5-diiodothyronine inhibited shedding and the animals survived longer. OCRs were similar in all control and experimental groups. It is concluded that among thyroid secretions, only iodothyronines inhibit shedding. Snake shedding is concluded not to reflect general metabolic status as it does in lizards.

Single-unit recordings were made from afferent nerve fibres supplying slowly adapting type I (s.a. I) cutaneous mechanoreceptors in anaesthetized vitamin A deficient and control rats. Trains of thirty repetitive mechanical stimuli with 0.1 s rise time, 1.9 s plateau phase, and 0.7 s interstimulus interval were applied. A feed-back mechanism maintained the force of stimulation at 20 mN during the plateau phases and the contact force between stimuli at 0.5 mN. All displacement values in the group of vitamin A deficient rats were significantly larger than the corresponding control values. Residual indentations were increased by 70-100% while maximal indentations were only about 40% higher. These results indicate a non-linear increase in compliance of the skin and underlying tissues. S.a. I receptors were found to be significantly less responsive in vitamin A deficient animals. Mean numbers of impulses were about 25% lower in the vitamin A deficient group than in controls throughout the entire train of thirty stimuli. In vitamin A deficient rats, Merkel cells and adjoining nerve terminals showed signs of degeneration of a variety of cell organelles, particularly the mitochondria. Degenerative changes induced by vitamin A deficiency especially in the Merkel cells appeared to be a major cause of the reduction of responsiveness in s.a. I receptors.

Electrophysiological recordings were made from afferent nerve fibres supplying slowly adapting type I (SA I) cutaneous mechano-receptors in the cat during application of mechanical stimuli (20 mN constant force, 0.2 s rise time and 2 s plateau phase, every 30 s). Close arterial infusion of neomycin (2.5 mg/min for 5 min) strongly depressed the responsiveness of SA I receptors. A direct effect on the receptor is thought to be the mode of action.

Slowly adapting type I (s.a. I) cutaneous mechanoreceptors were studied in young (3-4 months old) and adult (9-11 months old) rats. Trains of thirty repetitive mechanical stimuli with 0.1 s rise time, 1.9 s plateau phase, and 0.7 s interstimulus interval were applied. A feed-back mechanism maintained the force of stimulation at 20 mN during the plateau phases of stimuli and the contact force between stimuli at 0.5 mN. During the first few stimuli in a train residual indentation at contact force increased rapidly. Maximal indentation required to maintain the force of stimulation of 20 mN increased as well but to a smaller extent. Thus, the stroke amplitudes of individual stimuli decreased with increasing stimulus number. All displacement values in the group of adult rats were consistently reduced to 62 +/- 3% of the respective values in the group of young rats, indicating a linear decrease in skin compliance in the force range of 0.5-20 mN. Nervous responses to individual stimuli decreased from about 200 impulses for stimulus number 1 to about 60 impulses for stimulus number 30. Significant differences in the number of impulses between young and adult rats were observed from stimulus number 9 to number 16 only. It is concluded that the design of the s.a. I receptor allows maintained high tactile sensitivity in response to force-related stimuli irrespective of age-induced changes in mechanical properties of the skin and underlying tissues.