The externalizing and internalizing pathways to marijuana use initiation: Examining the synergistic effects of impulsiveness and sensation seeking.

Adolescent marijuana use has become increasingly more problematic compared with the past; thus, understanding developmental processes that increase the liability of marijuana use is essential. Two developmental pathways to adolescent substance use have been proposed: an externalizing pathway that emphasizes the expression of aggressive and delinquent behavior, and an internalizing pathway that emphasizes the role of depressive symptoms and negative affect. In this study, we aimed to examine the synergistic role of impulsiveness and sensation seeking in the two risk pathways to determine whether both high and low levels of the traits are risk factors for marijuana use. Our study included 343 adolescents (52% were girls, 78% identified as Hispanic) that oversampled high-risk youth (78% had a family history of substance use disorder), assessed biannually between the ages of 13-16 years old. Moderated mediation analyses revealed that high levels of sensation seeking indirectly predicted marijuana use through higher mean levels of externalizing behavior. The positive relationship between sensation seeking and externalizing behavior was only significant at high levels of impulsiveness. Conversely, low levels of sensation seeking indirectly predicted marijuana use through higher mean levels of internalizing behavior. The negative relationship between sensation seeking and internalizing behavior was only significant at low levels of impulsiveness. Collectively, these results demonstrate that high and low levels of both impulsiveness and sensation seeking confer increased risk of marijuana use, albeit through different mechanisms. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

The Development of Externalizing and Internalizing Behaviors Among Youth With or Without a Family History of Substance Use Disorder: The Indirect Effects of Early-Life Stress and Impulsivity.

Youth with a family history of substance use disorder (FH+) are more prone to have externalizing and internalizing problems compared to youth without a family history of substance use disorder (FH-), increasing the likelihood of later maladjustment. However, mechanisms for this association remain understudied. In this longitudinal study, we examined if FH+ youth are more likely to experience early-life stressors (ELS), which in turn would increase impulsivity and the expression of externalizing and internalizing behaviors. Data were collected from youth and a parent (n = 386) during a baseline assessment (age 10-12 years) and every six months when the youth was 13-16 years old. In support of the primary hypothesis, FH+ youth reported higher levels of externalizing and internalizing behaviors through ELS to impulsivity providing a developmental pathway through which FH+ youth are more prone to externalizing and internalizing problems.

Absorbed dose determination in kilovoltage X-ray synchrotron radiation using alanine dosimeters.

Alanine dosimeters from the National Physical Laboratory (NPL) in the UK were irradiated using kilovoltage synchrotron radiation at the imaging and medical beam line (IMBL) at the Australian Synchrotron. A 20 × 20 mm2 area was irradiated by scanning the phantom containing the alanine through the 1 mm × 20 mm beam at a constant velocity. The polychromatic beam had an average energy of 95 keV and nominal absorbed dose to water rate of 250 Gy/s. The absorbed dose to water in the solid water phantom was first determined using a PTW Model 31014 PinPoint ionization chamber traceable to a graphite calorimeter. The alanine was read out at NPL using correction factors determined for 60Co, traceable to NPL standards, and a published energy correction was applied to correct for the effect of the synchrotron beam quality. The ratio of the doses determined by alanine at NPL and those determined at the synchrotron was 0.975 (standard uncertainty 0.042) when alanine energy correction factors published by Waldeland et al. (Waldeland E, Hole E O, Sagstuen E and Malinen E, Med. Phys. 2010, 37, 3569) were used, and 0.996 (standard uncertainty 0.031) when factors by Anton et al. (Anton M, Büermann L., Phys Med Biol. 2015 60 6113-29) were used. The results provide additional verification of the IMBL dosimetry.

Methamphetamine, smoking, and gestational hypertension affect norepinephrine levels in umbilical cord tissues.

BACKGROUND: These studies were undertaken to determine methamphetamine (METH) and smoking effects on umbilical vascular dynamics and pregnancy outcomes. MATERIALS AND METHODS: Umbilical cords (54) were collected prospectively at birth, washed of blood, and stored at -80°C. Cords were thawed and lysates prepared, then catecholamine levels quantified with enzyme-linked immunosorbent assay (ELISA). RESULTS: Catecholamine levels in umbilical cords were not associated with maternal or gestational age, gravidity, parity, neonatal or placental weight. Neither smoking nor METH affected dopamine or epinephrine. However, smoking (two-fold) and METH (four-fold) decreased norepinephrine and together a 60-fold reduction occurred (p = 0.025). Cesarean section and hypertension were both associated with lower norepinephrine levels (p < 0.001) regardless of drug status. In normotensive pregnancies, smoking and METH significantly decreased norepinephrine levels (two-fold and 3.5-fold each, respectively) with a 40-fold decrease for METH/smoking together. DISCUSSION: Depletion of norephinephrine by METH and smoking likely contributes to pregnancy complications, including the higher incidence of respiratory distress and postpartum hemorrhage in cesarean section.

High spatial resolution dosimetric response maps for radiotherapy ionization chambers measured using kilovoltage synchrotron radiation.

Small circular beams of synchrotron radiation (0.1 mm and 0.4 mm in diameter) were used to irradiate ionization chambers of the types commonly used in radiotherapy. By scanning the chamber through the beam and measuring the ionization current, a spatial map of the dosimetric response of the chamber was recorded. The technique is able to distinguish contributions to the large-field ionization current from the chamber walls, central electrode and chamber stem. Scans were recorded for the NE 2571 Farmer chamber, the PTW 30013, IBA FC65-G Farmer-type chambers, the NE 2611A and IBA CC13 thimble chambers, the PTW 31006 and 31014 pinpoint chambers, the PTW Roos and Advanced Markus plane-parallel chambers, and the PTW 23342 thin-window soft x-ray chamber. In all cases, large contributions to the response arise from areas where the incident beam grazes the cavity surfaces. Quantitative as well as qualitative information about the relative chamber response was extracted from the maps, including the relative contribution of the central electrode. Line scans using monochromatic beams show the effect of the photon energy on the chamber response. For Farmer-type chambers, a simple Monte Carlo model was in good agreement with the measured response.

Agreement of umbilical cord drug and cotinine levels with maternal self-report of drug use and smoking during pregnancy.

OBJECTIVE: We undertook this study to assess the agreement between fetal umbilical cord drug levels and maternal self-report. STUDY DESIGN: Cord samples were collected from 103 placentas after delivery as a subproject of the larger Pacific Research Center for Early Human Development (PRCEHD) study. These cord samples were then processed to obtain cord lysates and enzyme-linked immunosorbent assay (ELISA) performed for cotinine and illicit drugs. Levels of each of these substances were compared with clinical information. RESULT: We found fair agreement between self-reported smoking and cotinine levels (κ = 0.26 (0.07 to 0.5)) as well as slight agreement with current drug use and positive drug levels (κ = 0.19 (-0.05 to 0.4)). Compared with maternal self-report, sensitivity of cotinine levels was 27% and specificity was 98%. Sensitivity of positive cord illicit drug levels was 32% and specificity was 85%. CONCLUSION: Umbilical cords provide another independent measure of maternal drug use and are readily available. To our knowledge, this is the first study to measure cotinine levels in the umbilical cord tissue.

Transforming growth factor beta(2) lowers the incidence of incisional hernias.

BACKGROUND: Approximately 200,000 incisional hernias are repaired annually in the United States. The high incidence (11-20%) and recurrence rate (24-54%) for incisional hernias have not changed appreciably in 75 years. Mechanical advances in suture material, incision orientation, and closure technique have failed to eliminate this common surgical complication. A biological approach to acute wound failure may offer a new strategy. METHODS: A rodent incisional hernia model was used. Seventy rats underwent 5-cm midline celiotomies and were closed with fine, fast-absorbing sutures to induce intentional acute wound failure. Group 1 received no other treatment. The midline fascia in groups 2 and 3 was injected immediately prior to incision with 100 microl of vehicle alone or vehicle containing 1 microg of transforming growth factor beta(2) (TGF-beta(2)). Necropsy was performed on Postoperative Day 28 and the wounds were examined for herniation. RESULTS: Incisional hernias developed in 88% (35/40) and 79% (11/14) of untreated incisions and those treated with vehicle alone. No hernias formed in the TGF-beta(2)-treated incisions (0/16, P < 0.05). Standard histology and immunohistochemistry demonstrated enhanced macrophage, lymphocyte, and fibroblast chemotaxis and increased collagen I and III production in TGF-beta(2) treated incisions. CONCLUSIONS: Treatment of abdominal wall fascial incisions with TGF-beta(2) prevented the development of incisional hernias in this rat model. TGF-beta(2) stimulated fascial macrophage and fibroblast chemotaxis as well as acute wound collagen production. A biological approach such as this may reduce the incidence of incisional hernia formation in humans.

Fascial incisions heal faster than skin: a new model of abdominal wall repair.

BACKGROUND: Optimal healing of the fascial layer is a necessary component of complete abdominal wall repair. The majority of acute wound healing studies have focused on the dermis. We designed a model of abdominal wall repair that, to our knowledge, for the first time simultaneously characterizes differences in the wound healing trajectories of the fascia and skin. METHODS: Full-thickness dermal flaps were raised on the ventral abdominal walls of rats, and midline fascial celiotomies were completed. The dimensions of the flap were developed so as to have no detrimental effect on skin healing. The dermal flaps were replaced so that the fascial incisions would heal separately from the overlying skin incisions. Animals were killed 7, 14, and 21 days after operation and fascial and dermal wounds were harvested and tested for breaking strength. Fascial and dermal wounds were also compared histologically for inflammatory response, fibroplasia, and collagen staining. RESULTS: Fascial wound breaking strength exceeded dermal wound breaking strength at all time points (9.16 +/- 2.17 vs 3.51 +/- 0.49 N at 7 days, P <.05). Fascial wounds also developed greater fibroblast cellularity and greater collagen staining 7 days after the incision. There was no difference in wound inflammatory response. CONCLUSIONS: Fascial incisions regain breaking strength faster than simultaneous dermal incisions. The mechanism for this appears to involve increased fascial fibroplasia and collagen production after acute injury.

Abdominal wall repair is delayed during hepatic regeneration.

BACKGROUND: Abdominal wall wound failure remains a common surgical problem. The signals that activate normal fibroplastic repair versus regeneration pathways are unknown. Transforming growth factor beta levels rise during incisional healing but fall during hepatic regeneration. Changes in the injured host cytokine milieu may therefore differentially effect abdominal wall repair versus hepatic regeneration. MATERIALS AND METHODS: Forty-eight rats were divided into four groups (n = 12). Groups 1-3 underwent sham celiotomy, 70% hepatectomy, or 80% enterectomy with anastamosis. Incisions from Group 4 were treated with either 1 microg of transforming growth factor beta(2) (TGF-beta(2)) or vehicle following hepatectomy. Isolated fascial and dermal incisions were harvested and tested for breaking strength on POD 7. Serum (TGF-beta(2)) and hepatocyte growth factor (HGF) levels were measured by ELISA. RESULTS: Recovery of incisional wound breaking strength was delayed following hepatectomy but not enterectomy (P<0.002). The inhibitory effect was observed in both the fascia and the dermis of the abdominal wall. TGF-beta(2) levels were depressed in hepatectomy animals on POD 7, while at the same time HGF levels were elevated. Exogenous TGF-beta(2) shifted the healing trajectory of deficient wounds back toward a control pattern. CONCLUSION: Abdominal wall fascial and dermal healing is delayed during hepatic regeneration. Elevated HGF and depressed TGF-beta(2) suggest a host mechanism that prioritizes hepatic parenchymal regeneration over fibroplastic repair (scar). Observations such as these are needed as therapeutic wound healing enters the clinical realm.

Effects of intrapartum administration of invert sugar and D5LR on neonatal blood glucose levels.

OBJECTIVE: To compare the effects of D5LR and invert sugar administered intrapartum on neonatal blood glucose concentrations. STUDY DESIGN: This is a prospective, randomized, double-blind study. A total of 32 insulin-requiring diabetic patients were randomized to receive either intravenous 10% invert sugar or lactated Ringer's solution with 5% dextrose (D5LR). Regular insulin was given intravenously with an infusion pump to maintain the plasma glucose concentration between 60 and 90 mg/dl. Neonatal blood glucoses were measured at 30 minutes after birth, four times every hour, and thereafter as indicated. Student's t-test was used for continuous variables and Fisher's exact test was used for categorical data. RESULTS: There were no differences in neonatal blood glucose levels, incidence of neonatal hypoglycemia, or length of neonatal hospital stay between the two groups. CONCLUSION: Intrapartum administration of invert sugar is not associated with better neonatal homeostasis of glucose compared with using D5LR. Thus, given the expense of invert sugar, D5LR appears to be preferable for intrapartum control of maternal blood glucose.

Initiating the inflammatory phase of incisional healing prior to tissue injury.

BACKGROUND: The time required for incisional healing accounts for the majority of postoperative pain and convalescence. Impaired healing prolongs the process further. If a method for accelerating acute incisional wound healing could be developed, patients would benefit from decreased wound failure and an earlier return to their premorbid condition. MATERIALS AND METHODS: In a rat dermal model, cytokine or vehicle infiltration prior to incision was performed using a single dose or four daily doses preincision. Planned incision sites were primed with the proinflammatory cytokine granulocyte-macrophage colony-stimulating factor (GM-CSF) or platelet-derived growth factor BB (PDGF-BB) in an effort to activate the inflammatory phase of healing prior to wounding. At the time of incision closure, one half of the incisions were treated with transforming growth factor beta(2) (TGF-beta(2)). Incisional sites were biopsied and stained with hematoxylin and eosin and immunohistochemistry for inflammatory cells and fibroblast populations and breaking strength was measured. RESULTS: Priming skin with GM-CSF or PDGF-BB mimicked the early inflammatory phase of wound healing. Macrophage staining (EB1) and fibroblast staining (vimentin) were significantly increased prior to incision. Inflammatory priming as well as priming coupled with TGF-beta(2) at the time of the incision closure synergistically improved breaking strength. CONCLUSION: This study demonstrates that sequential therapy consisting of priming of tissue with an inflammatory cytokine followed by application of a proliferative cytokine at the time of incision closure nearly doubles the breaking strength of an acute wound. By manipulating the inflammatory and early proliferative phases of wound healing with tissue growth factors, it may be possible to accelerate acute wound repair and shift the wound healing trajectory to the left.

Use of the wound healing trajectory as an outcome determinant for acute wound healing.

Accurate and clinically practical methods for measuring the progress of acute wound healing is necessary before interventions designed to optimize and even accelerate acute wound healing can be applied. Complete wound closure rates and operative wound closure severity are irrelevant to most acute wounds since most are closed at the time of primary tissue repair and remain closed throughout healing. Analogous to chronic wound closure, the rate of increase of incision tensile strength progressively decreases as time passes and 100% unwounded tissue strength is never achieved making the endpoint definition of "healed" vague. Conceptualizing acute wound healing in terms of its design elements with reintegration into a final outcome lends itself to the description of acute wound healing as a mathematical trajectory. Frequently such an equation is a rate expressing the change in an acute healing parameter, most often tensile strength, over time. Such an approach also normalizes misinterpretations in analysis or errors in theory developed by measuring healing parameters at fixed points in time. Distributions of fractional strength gain times (e.g., 85% normal strength) can be determined using statistical methodology similar that used for failure time of survival analysis. Preclinical studies show that acute wound healing trajectories can be shifted to the left from a "normal" or "impaired" curve to an accelerated or more "ideal" curve. A useful method for measuring acute wound healing outcomes is therefore required before the basic science of acute wound healing is inevitably applied to the problem of acute surgical wounds.

The effect of TGF-beta2 in various vehicles on incisional wound healing.

BACKGROUND: The isoforms of transforming growth factor beta (TGF-beta) have been shown to be deficient in models of impaired wound healing. Exogenous application of the growth factor to enhance healing as been investigated. TGF-beta1 has been shown to enhance incisional wound strength, but to be dependent on the vehicle used to carry the cytokine. Because TGF-beta2 has shown safety in human trials of chronic wound healing, this study evaluates TGF-beta2 in acute incisional healing using a variety of vehicles. METHODS: Using an acute incisional wound model in healthy rats, rhTGF-beta2 was suspended in various vehicles including fibrin sealant (normal commercial concentration), fibrin sealant (dilute concentration), phosphate buffered saline/serum albumin, and a carboxymethycellulose gel. A single dose of the agent was instilled into the incisions at the time of wound closure and breaking strength analyses and histology performed periodically from days 3-14. RESULTS: TGF-beta2 enhanced the gain of incisional strength in all vehicles during the first two weeks of healing. This was most noticeable by day three with the carboxymethycellulose gel, but by day 7 with the other vehicles. Like reports with TGF-beta1, TGF-beta2 accelerated the gain of wound strength by about three days by day 11. Normal density fibrin sealant delayed incisional healing; whereas, the other vehicles without TGF-beta2 had no significant effect. CONCLUSIONS: The use of TGF-beta2 appears to be of value in increasing incisional wound strength in the first 14 days post-wounding in healthy rats and this effect is demonstrated in a variety of vehicles. These data support the hypothesis that the "normal" incisional wound healing curve can he shifted to the left. Shortening the time for gain of incisional wound strength may have potential clinical use.

In vivo characterization of keratinocyte growth factor-2 as a potential wound healing agent.

Human keratinocyte growth factor-2 exerts a proliferative effect on epithelial cells and mediates keratinocyte migration. It has also been shown to increase both deposition of granulation tissue and collagen and maturation of collagen. Because these properties should affect the healing trajectory of wounds, this study set out to investigate the effects of keratinocyte growth factor-2 on the healing of three different types of wounds. Human meshed skin grafts explanted to athymic "nude" rats, surgical incisions in Sprague-Dawley rats, and acute excisional rat wounds inoculated with Escherichia coli were used. Two concentrations of recombinant human keratinocyte growth factor-2 were compared to a vehicle control and keratinocyte growth factor-1. Keratinocyte growth factor-2 significantly accelerated the rate of epithelialization in the meshed skin graft model and effected a modestly more rapid gain in breaking strength of surgical incisions than keratinocyte growth factor-1 or the vehicle control treatment. Neither keratinocyte growth factors accelerated wound closure by contraction of the excisional wounds. Based on these data, keratinocyte growth factor-2 may be useful in accelerating healing in wounds healing mainly by the process of epithelialization such as venous stasis ulcers, partial thickness burn wounds, and skin graft donor sites. It might also accelerate the gain in incisional wound strength in acute surgical or traumatic wounds.

Minoxidil and wound contraction.

Minoxidil has been proposed as a potential topical inhibitor of wound contraction and proliferative scarring. Suggestions for this application are derived from in vitro investigations demonstrating inhibition of various fibroblastic functions. The purpose of this study was to attempt to establish in vivo support of these effects using an established animal model of wound contraction. Standardized cutaneous wounds were created on the dorsum of Sprague-Dawley rats, which were divided equally into six treatment groups. Wounds were treated daily after tracing their unhealed areas. On complete closure of the wounds, analyses of the contraction rates and tensile strength were performed for comparison among groups. Minoxidil did not demonstrate significant inhibition of wound contraction rates relative to either an inert vehicle, an active vehicle, or no treatment. Contrarily, as previously demonstrated in this animal model, silver sulfadiazine did demonstrate significant inhibition of wound contraction rates relative to both vehicles. No significant difference in tensile strength was demonstrated among groups. These observations do not support the proposed use of minoxidil as an "antifibrotic" agent.

Performance of the polypropylene fiber tailstring on the Copper 7 intrauterine device.

New and used polypropylene tailstrings from the Copper 7 (Cu-7) intrauterine device were examined by a combination of analytical techniques. Optical microscopy, scanning acoustic and electron microscopy, x-ray diffraction, energy dispersive x-ray analysis, and chemical etching were employed to elucidate both the surface and interior morphology of new Cu-7 tailstrings. Tailstrings removed from women following varying periods of use were investigated with optical microscopy, scanning and transmission electron microscopy. In addition, a subset of the used tailstrings were cultured to identify the types of microorganisms associated with them. Our findings show that unused Cu-7 tailstrings are in various stages of degradation owing to a combination of factors which include the high-draw ratio employed during manufacturing, the method of packaging, and the use of a particulate colourant. Furthermore, it is evident that used Cu-7 tailstrings undergo major deterioration while in situ because of the unfavorable interactions between the highly drawn polypropylene and the physiological environment. These results indicate that the polypropylene tailstrings as manufactured for use with the Cu-7 IUD fail to meet accepted design criteria for biomedical implants.