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Background: Post-overdose outreach programs have proliferated in response to opioid overdose. Implementing these programs is associated with reductions in overdose rates, but the role of specific program characteristics in overdose trends has not been evaluated., Methods: Among 58 Massachusetts municipalities with post-overdose outreach programs, we examined associations between five domains of post-overdose outreach program characteristics (outreach contact rate, naloxone distribution, coercive practices, harm reduction activities, and social service provision or referral) and rates of fatal opioid overdoses and opioid-related emergency medical system responses (i.e., ambulance activations) per calendar quarter from 2013 to 2019 using segmented regression analyses with adjustment for municipal covariates and fixed effects. For both outcomes, each domain was modeled: a) individually, b) with other characteristics, and c) with other characteristics and municipal-level fixed effects., Results: There were no significant associations (p < 0.05) between outreach contact rate, naloxone distribution, coercive practices, or harm reduction activities with municipal fatal overdose trends. Municipalities with programs providing or referring to more social services experienced 21% fewer fatal overdoses compared to programs providing or referring to more social services (Rate Ratio (RR) 0.79, 95% Confidence Interval (CI) 0.66-0.93, p = 0.01). Compared to municipalities in quarters when programs had no outreach contacts, municipalities with some, but less than the median outreach contacts, experienced 14% lower opioid-related emergency responses (RR 0.86, 95% CI 0.78-0.96, p = 0.01). Associations between naloxone distribution, coercive practices, harm reduction practices, or social services and opioid-related emergency responses were not consistently significant across modeling approaches., Conclusion: Municipalities with post-overdose outreach programs providing or referring to more social services had lower fatal opioid overdose rates. Municipalities in quarters when programs outreached to overdose survivors had fewer opioid-related emergency responses, but only among programs with below the median number of outreach contacts. Social service linkage should be core to post-overdose programs. Evaluations should assess program characteristics to optimize program design., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Drs. Kimmel and Walley report financial support from the Massachusetts Department of Public Health as part of the state opioid overdose prevention program., (Copyright © 2023. Published by Elsevier B.V.)

Background: Post-overdose outreach programs engage survivors in harm reduction and treatment to prevent future overdoses. In Massachusetts, these emerging programs commonly deploy teams comprised of police and public health professionals based on 911 call information. Some teams use name/address data to conduct arrest warrant checks prior to outreach visits. We used mixed methods to understand approaches to outreach related to warrant checking, from the perspectives of police and public health outreach agencies and staff., Methods: We analyzed a 2019 statewide survey of post-overdose outreach programs in Massachusetts to classify approaches to warrant checking and identify program and community factors associated with particular approaches. Ethnographic analysis of qualitative interviews conducted with outreach staff helped further contextualize outreach program practices related to warrants., Results: A majority (57% - 79/138) of post-overdose outreach programs in Massachusetts conducted warrant checks prior to outreach. Among programs that checked warrants, we formulated a taxonomy of approaches to handling warrants: 1) performing outreach without addressing warrants (19.6% - 27/138), 2) delaying outreach until warrants are cleared (15.9% - 22/138), 3) arresting the survivor (11/138 - 8.0%), 4) taking a situational approach (10/138 - 7.2%), 5) not performing outreach (9/138 - 6.5%). Program characteristics and staff training did not vary across approaches. From police and public health outreach staff interviews (n = 38), we elicited four major themes: a) diverse motivations precede warrant checking, b) police officers feel tension between dual roles, c) warrants alter approaches to outreach, and d) teams leverage warrants in relationships. Findings from both analyses converged to demonstrate unintended consequences of warrant checking., Conclusion: Checking warrants prior to post-overdose outreach visits can result in arrest, delayed outreach, and barriers to obtaining services for overdose survivors, which can undermine the goal of these programs to engage overdose survivors. With the public health imperative of engaging overdose survivors, programs should consider limiting warrant checking and police participation in field activities., Competing Interests: Declarations of Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: AYW is the medical director of overdose prevention programs at the Massachusetts Department of Public health and signs the statewide naloxone standing order, including multiple police and fire departments in Massachusetts., (Copyright © 2021. Published by Elsevier B.V.)

Background: Naloxone is a prescription medication that reverses opioid overdoses. Allowing naloxone to be dispensed directly by a pharmacist without an individual prescription under a naloxone standing order (NSO) can expand access. The community-level factors associated with naloxone dispensed under NSO are unknown., Methods: Using a dataset comprised of pharmacy reports of naloxone dispensed under NSO from 70% of Massachusetts retail pharmacies, we examined relationships between community-level demographics, rurality, measures of treatment for opioid use disorder, and overdose deaths with naloxone dispensed under NSO per ZIP Code-quarter from 2014 until 2018. We used a multi-variable zero-inflated negative binomial model, assessing odds of any naloxone dispensed under NSO, as well as a multi-variable negative binomial model assessing quantities of naloxone dispensed under NSO., Results: From 2014-2018, quantities of naloxone dispensed under NSO and the number of pharmacies dispensing any naloxone under NSO increased over time. However, communities with greater percentages of people with Hispanic ethnicity (aOR 0.91, 95% CI 0.86-0.96 per 5% increase), and rural communities compared to urban communities (aOR 0.81, 95% CI 0.73-0.90) were less likely to dispense any naloxone by NSO. Communities with more individuals treated with buprenorphine dispensed more naloxone under NSO, as did communities with more opioid-related overdose deaths., Conclusion: Naloxone dispensing has substantially increased, in part driven by standing orders. A lower likelihood of naloxone being dispensed under NSO in communities with larger Hispanic populations and in more rural communities suggests the need for more equitable access to, and uptake of, lifesaving medications like naloxone., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Transient receptor potential, melastatin-like 7 (Trpm7) is a combined ion channel and kinase implicated in the differentiation or function of many cell types. Early lethality in mice and frogs depleted of the corresponding gene impedes investigation of the functions of this protein particularly during later stages of development. By contrast, zebrafish trpm7 mutant larvae undergo early morphogenesis normally and thus do not have this limitation. The mutant larvae are characterized by multiple defects including melanocyte cell death, transient paralysis, and an ion imbalance that leads to the development of kidney stones. Here we report a requirement for Trpm7 in differentiation or function of dopaminergic neurons in vivo. First, trpm7 mutant larvae are hypomotile and fail to make a dopamine-dependent developmental transition in swim-bout length. Both of these deficits are partially rescued by the application of levodopa or dopamine. Second, histological analysis reveals that in trpm7 mutants a significant fraction of dopaminergic neurons lack expression of tyrosine hydroxylase, the rate-limiting enzyme in dopamine synthesis. Third, trpm7 mutants are unusually sensitive to the neurotoxin 1-methyl-4-phenylpyridinium, an oxidative stressor, and their motility is partially rescued by application of the iron chelator deferoxamine, an anti-oxidant. Finally, in SH-SY5Y cells, which model aspects of human dopaminergic neurons, forced expression of a channel-dead variant of TRPM7 causes cell death. In summary, a forward genetic screen in zebrafish has revealed that both melanocytes and dopaminergic neurons depend on the ion channel Trpm7. The mechanistic underpinning of this dependence requires further investigation., (© 2013 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Up to 3% of patients undergoing heart surgery suffer from an intraabdominal complication (IAC). These complications carry a high mortality besides adding to the morbidity and cost. This review was undertaken to see if a subset of patients with increased risk of IAC could be identified., Methods: Medical records of 7,731 consecutive patients undergoing heart surgery in a single center were screened for identification of postoperative IAC. One hundred and twenty (120) cases were found. One hundred and six (106) cases were compared with the same number of matched controls., Results: Significant predictors of the development of IAC were increased cardiopulmonary bypass times (> 99 minutes), peripheral vascular disease, chronic steroid use, and low left ventricular ejection fraction. Patients on postoperative antiplatelet therapy or warfarin had a lower risk of IAC. Significant predictors of mortality in IAC were increased cardiopulmonary bypass times (> or = 120 minutes.), use of inotropes, cerebral vascular disease, and incremental age., Conclusions: A subset of patients can be identified who are at higher risk for IAC and an associated adverse outcome. Patients who have prolonged cardiopulmonary bypass, have a low left ventricular ejection fraction, are on steroids, and suffer from other vascular disease should be observed carefully for development of IAC. Postoperative anticlotting strategies may be helpful. Early diagnosis and intervention are essential for improving outcomes in cases of IAC.

Centrin - higher plants - MTOCs - microtubules nucleation In most eukaryotic cells, the Ca(2+)-binding protein centrin is associated with structured microtubule-organizing centers (MTOCs) such as centrosomes. In these cells, centrin either forms centrosome-associated contractile fibers, or is involved in centrosome biogenesis. Our aim was to investigate the functions of centrin in higher plant cells which do not contain centrosome-like MTOCs. We have cloned two tobacco BY-2 centrin cDNAs and we show that higher plant centrins define a phylogenetic group of proteins distinct from centrosome-associated centrins. In addition, tobacco centrins were found primarily associated with microsomes and did not colocalize with gamma-tubulin, a known MTOC marker. While the overall level of centrin did not vary during the cell cycle, centrin was prominently detected at the cell plate during telophase. Our results suggest that in tobacco, the major portion of centrin is not MTOC-associated and could be involved in the formation of the cell plate during cytokinesis.

The aim of this work on rat hepatic P450 2E1 activity was to seek the most suitable experimental model to study the role of cytochrome P450 2E1 in the metabolism of industrial chemicals. Two sets of experiments were devoted to selecting the age and sex of animals and to estimating the response of male and female rats to different inducers. In the first set, the effect of three inducers (fasting; ethanol; acetone) was studied in male rats aged 5, 7 and 9 weeks. In the second set, the effect of different inducers, namely beta-naphthoflavone (BNF), phenobarbital (PB), ethanol, acetone and pyridine, on PNP and chlorzoxazone (CLZO) hydroxylase activities was studied in 7 week old male and female rats. The results demonstrate firstly that microsomal p-nitrophenol (PNP) hydroxylase activity significantly decreases in control male rats in inverse function of age, and secondly that induction by ethanol decreases with age. The PNP hydroxylase activity level of controls and the significant increases in PNP hydroxylase activity observed in 7 week old male rats show that this is the most suitable age for the second set of experiments. In this second set, it was shown that P450 1A (induced by BNF) is involved in CLZO hydroxylase activity only. PB increased the hydroxylase activities in male and female rats by about 1.5 and 1.7 times those of the controls, respectively. The effects of P450 2E1 inducers in function of sex show that male rats exhibited more significant increases in PNP and CLZO hydroxylase activities than female. The specificity of these two substrates is discussed. Neither of these two reactions was specifically catalysed by P450 2E1, but PNP may be considered as the most specific and the least sensitive substrate. In addition, the linear relationship observed between the two substrates (PNP and CLZO) showed a good correlation between their activities (r = 0.90, P < 0.001). In conclusion, these results suggest the use of the 7 week old male rat as the experimental model to study the role of cytochrome P450 2E1 in the hepatotoxicity of low molecular weight industrial chemicals.

Compelling evidence supports the idea that actin filaments play an active role in the cytokinetic process of higher plant cells. However, the mechanisms that control the growth of the cell plate and its stabilization remain so far unknown. We show that a novel population of short actin filaments continuously assembles in the phragmoplast at the growing cell plate. Microinjection of rhodamine-phalloidin during these final stages of telophase revealed the dynamic assembly and organization of these actin filaments during vesicle fusion. Comparable data were obtained in endosperm syncytia during the development of the cell plate between non sister nuclei, i.e. independently of the formation of the mitotic phragmoplast. Concomitantly, plant polypeptides sharing epitopes with human vinculin are revealed within the forming cell plate, suggesting their recruitment during cytokinesis-associated actin assembly. These vinculin-like antigens may participate in membrane/F-actin anchorage protein complexes. Our data, in addition to the identification of plant integrin homologues reported by several authors, suggest the existence of a cell wall/extracellular matrix/plasma membrane/actin cytoskeleton continuum. Such an architecture may control cell-cell interactions during cell plate formation and may contribute to the establishment of polarity in higher plants.

In this study, we investigated the effect of plant microtubule-associated proteins (MAPs) on microtubule nucleation and growth in vitro. Since it has recently been demonstrated that plant nuclear surface acts as a microtubule-organizing center (MTOC), we tested the effects of plant MAPs using a nucleus-mediated microtubule nucleation assay. Nuclei were isolated from interphase tobacco BY-2 cells, and MAPs were isolated from tobacco BY-2 cells at different stages of the cell cycle. The effects of tobacco MAPs on microtubule nucleation at mammalian centrosomes were also analyzed. Under our experimental conditions, both interphase and mitotic tobacco MAPs promoted microtubule assembly around tobacco nuclei and at mammalian centrosomes below the critical tubulin concentration for spontaneous assembly. Interphase tobacco MAPs increase the mean length of nucleated microtubules in proportion to its molar ratio to tubulin. In contrast, mitotic tobacco MAPs do not induce nucleus- and centrosome-mediated nucleation of microtubules in a dose-dependent manner. Both MAP-fractions possessed microtubule bundling activity. The implications of these plant MAP properties on microtubule nucleation in living cells are discussed.

Compelling evidence has recently been obtained for the idea that the nuclear surface of higher plant cells has a microtubule-nucleating function under cell cycle dependent control. Whatever the final organization of microtubules, they all seem to originate in the nuclear periphery. The spatial distribution of microtubules is a secondary process involving actin and microtubule-associated proteins, and other morphogenetic controls. How microtubules are nucleated and/or reorganized at the spindle poles during mitosis remains unknown.

The molecular architecture of tubulin from higher plant remains unknown. In this report we have made an attempt to identify higher plant tubulin domains using total and limited proteolysis of Haemanthus endosperm tubulin. The tubulin was previously purified and characterized (Picquot and Lambert 1988). The amino acid composition revealed a high content of basic residues, such as arginine and lysine. Tubulin domains were probed by tryptic and chymotryptic cleavage and analyzed by immunoblotting using specific monoclonal antibodies against alpha or beta subunits. These data shed light on specific properties of the higher plant tubulin.