bluuebunny/crossref_metadata_2025 huggingface dataset:
Lysosomal abnormalities during benzo(a)pyrene‐induced experimental lung carcinogenesis – defensive role of capsaicin
Authors: Anandakumar P. , Kamaraj S. , Jagan S. , Ramakrishnan G. , Devaki T.
Published: January 2009

The objective of the present study was to investigate whether lysosome is a target in benzo(a)pyrene‐induced, oxidative stress‐mediated lung cancer in Swiss albino mice and the plausible role of the phytochemical substance capsaicin in mitigating lysosomal damage. Oxidative stress was assessed based on the level of carbonyl content. The activities of lysosomal proteases like cathepsin‐D, cathepsin‐B, β‐d‐glucosidase, β‐d‐galactosidase, β‐d‐glucuronidase, β‐d‐N‐acetylglucosaminidase and acid phosphatase were assessed to evaluate lysosomal function. Administration of benzo(a)pyrene (50 mg/kg body weight) to mice induced a increase in the activities of lysosomal enzymes and oxidative stress was evident by the increase in carbonyl content. Treatment with capsaicin (10 mg/kg body weight) decreased carbonyl content and restored the activities of lysosomal enzymes to near normalcy. Transmission electron microscopic study of lysosomes further showed the defensive action of capsaicin against the lysosomal damage caused in benzo(a)pyrene‐induced lung cancer. From the present study, it can be concluded that lysosomal damage is an indispensable event in benzo(a)pyrene‐induced lung cancer, and capsaicin was able to effectively prevent it, which proves the chemoprotective effect of capsaicin against benzo(a)pyrene‐induced experimental lung carcinogenesis.
Time to Send the Preemie Home? Additional Maturity at Discharge and Subsequent Health Care Costs and Outcomes
Authors: Silber Jeffrey H. , Lorch Scott A. , Rosenbaum Paul R. , Medoff‐Cooper Barbara , Bakewell‐Sachs Susan , Millman Andrea , Mi Lanyu , Even‐Shoshan Orit , Escobar Gabriel J.
Published: January 2009

Objective.To determine whether longer stays of premature infants allowing for increased physical maturity result in subsequent postdischarge cost savings that help counterbalance increased inpatient costs.

Data Sources.One thousand four hundred and two premature infants born in the Northern California Kaiser Permanente Medical Care Program between 1998 and 2002.

Study Design/Methods.Using multivariate matching with a time‐dependent propensity score we matched 701 “Early” babies to 701 “Late” babies (developmentally similar at the time the earlier baby was sent home but who were discharged on average 3 days later) and assessed subsequent costs and clinical outcomes.

Principal Findings.Late babies accrued inpatient costs after the Early baby was already home, yet costs after discharge through 6 months were virtually identical across groups, as were clinical outcomes. Overall, after the Early baby went home, the Late–Early cost difference was $5,016 (p<.0001). A sensitivity analysis suggests our conclusions would not easily be altered by failure to match on some unmeasured covariate.

Conclusions.In a large integrated health care system, if a baby is ready for discharge (as defined by the typical criteria), staying longer increased inpatient costs but did not reduce postdischarge costs nor improve postdischarge clinical outcomes.
Use of Prolonged Travel to Improve Pediatric Risk‐Adjustment Models
Authors: Lorch Scott A. , Silber Jeffrey H. , Even‐Shoshan Orit , Millman Andrea
Published: January 2009

Objective. To determine whether travel variables could explain previously reported differences in lengths of stay (LOS), readmission, or death at children's hospitals versus other hospital types.

Data Source. Hospital discharge data from Pennsylvania between 1996 and 1998.

Study Design. A population cohort of children aged 1–17 years with one of 19 common pediatric conditions was created (N=51,855). Regression models were constructed to determine difference for LOS, readmission, or death between children's hospitals and other types of hospitals after including five types of additional illness severity variables to a traditional risk‐adjustment model.

Principal Findings. With the traditional risk‐adjustment model, children traveling longer to children's or rural hospitals had longer adjusted LOS and higher readmission rates. Inclusion of either a geocoded travel time variable or a nongeocoded travel distance variable provided the largest reduction in adjusted LOS, adjusted readmission rates, and adjusted mortality rates for children's hospitals and rural hospitals compared with other types of hospitals.

Conclusions. Adding a travel variable to traditional severity adjustment models may improve the assessment of an individual hospital's pediatric care by reducing systematic differences between different types of hospitals.
Incidence and risk factors for development of malignant neoplasia after feline renal transplantation and cyclosporine‐based immunosuppression
Authors: Schmiedt C. W. , Grimes J. A. , Holzman G. , McAnulty J. F.
Published: January 2009

The objective of this retrospective study is to report and analyse the incidence of and risk factors for post‐transplant malignant neoplasia (PTMN) in feline renal transplant recipients (cases, n = 45) and compare incidence to a population of cats that did not receive a transplant (controls, n = 79). Information from the medical records of cases regarding signalment, blood work and concomitant disease, post operative cyclosporine concentrations, survival time (ST), and whether PTMN developed, the type of PTMN, time to occurrence (TTO), and ST after diagnosis was gathered. PTMN occurred in 11 of 45 (24%) cases, of which, four were lymphoma. Median TTO of all PTMN was 1020 days. Median TTO of lymphoma was 454 days. Median ST after diagnosis of PTMN was 15 days. No risk factors were identified. Compared with control cats, cases had more than six times higher odds of developing PTMN compared with control cats (P < 0.01).
Fish Responses to Experimental Fragmentation of Seagrass Habitat
Authors: MACREADIE PETER I. , HINDELL JEREMY S. , JENKINS GREGORY P. , CONNOLLY ROD M. , KEOUGH MICHAEL J.
Published: January 2009

Abstract:  Understanding the consequences of habitat fragmentation has come mostly from comparisons of patchy and continuous habitats. Because fragmentation is a process, it is most accurately studied by actively fragmenting large patches into multiple smaller patches. We fragmented artificial seagrass habitats and evaluated the impacts of fragmentation on fish abundance and species richness over time (1 day, 1 week, 1 month). Fish assemblages were compared among 4 treatments: control (single, continuous 9‐m2 patches); fragmented (single, continuous 9‐m2 patches fragmented to 4 discrete 1‐m2 patches); prefragmented/patchy (4 discrete 1‐m2 patches with the same arrangement as fragmented); and disturbance control (fragmented then immediately restored to continuous 9‐m2 patches). Patchy seagrass had lower species richness than actively fragmented seagrass (up to 39% fewer species after 1 week), but species richness in fragmented treatments was similar to controls. Total fish abundance did not vary among treatments and therefore was unaffected by fragmentation, patchiness, or disturbance caused during fragmentation. Patterns in species richness and abundance were consistent 1 day, 1 week, and 1 month after fragmentation. The expected decrease in fish abundance from reduced total seagrass area in fragmented and patchy seagrass appeared to be offset by greater fish density per unit area of seagrass. If fish prefer to live at edges, then the effects of seagrass habitat loss on fish abundance may have been offset by the increase (25%) in seagrass perimeter in fragmented and patchy treatments. Possibly there is some threshold of seagrass patch connectivity below which fish abundances cannot be maintained. The immediate responses of fish to experimental habitat fragmentation provided insights beyond those possible from comparisons of continuous and historically patchy habitat.
Inflammatory Neuropathy Consortium: Report of a meeting held on 4–6 July 2008, Bâtiment Babinski, Hôpital de la Salpêtrière, Paris, France
Authors: Hughes Richard A. C. , Cornblath David R.
Published: January 2009

Abstract  The Inflammatory Neuropathy Consortium held its first scientific meeting in Paris on 4–6 July 2008. The consortium is a special interest group of the Peripheral Nerve Society. The meeting included 10 plenary lectures and over 60 abstracts. A meeting summary is provided.
What’s new in chronic inflammatory demyelinating polyradiculoneuropathy in 2007–2008?
Authors: Van Schaik Ivo N.
Published: January 2009

Abstract  Chronic inflammatory demyelinating polyradiculoneuropathy (CIDP)–related research has made progress in the field of pathogenesis, genetics, and treatment. The number of circulating CD4+ CD25+ T‐regulatory cells was shown to be reduced in CIDP patients. Increased frequency of genotype GA13‐16 of the SH2D2A gene encoding for a T‐cell‐specific adapter protein in CIDP patients may result in a defective control and elimination of autoreactive T cells. IVIg treatment has been shown to increase numbers and function of peripheral CD4+ CD25+ T‐regulatory cell in a mouse model. These findings shed new light on the understanding of why peripheral tolerance is breached in CIDP patients and why the disease becomes chronic and adds another possible mechanism of action of intravenous immunoglobulin to the already long list. Long‐term effectiveness of IVIg has now been proven. Subcutaneous immunoglobulin could be an alternative for IVIg, but this has to be explored further in well‐designed trials. Autologous stem cell transplantation has been tried in refractory patients, but larger trials are necessary to assess safety and effect of this treatment.
What’s new in multifocal motor neuropathy in 2007–2008?
Authors: Nobile‐Orazio Eduardo
Published: January 2009

Abstract  Several articles on multifocal motor neuropathy (MMN) have appeared in 2007 and 2008, broadening the boundaries of this neuropathy and improving its diagnosis. A number of retrospective studies confirmed the prolonged efficacy of high‐dose intravenous immunoglobulins (IVIg) in this neuropathy. The efficacy of other immune therapies was not however, confirmed in other studies in MMN including a randomized controlled trial on mycophenolate mofetil as adjunctive therapy to IVIg. These negative results and the lack of new other studies on the cause of MMN should lead to some reconsideration on its pathogenesis.
Role of a pre‐existing neuropathy on the course of bortezomib‐induced peripheral neurotoxicity
Authors: Lanzani Francesca , Mattavelli Laura , Frigeni Barbara , Rossini Fausto , Cammarota Sara , Petrò Daniela , Jann Stefano , Cavaletti Guido
Published: January 2009

Abstract  We investigated a series of bortezomib‐treated patients and correlated the course of bortezomib‐induced peripheral neurotoxicity with the presence or absence of peripheral neuropathy at baseline. Forty‐eight patients were examined with the total neuropathy score reduced version (TNSr), visual analogue score (VAS) for pain, and nerve conduction studies at baseline and after two and four cycles of chemotherapy. Twenty‐three patients had a baseline TNSr = 0–2, and 25 patients had a baseline TNSr >2 (median = 6, range 3–13). The course of bortezomib‐induced peripheral neurotoxicity was generally more severe in those patients with the highest baseline TNSr. However, among those subjects with a normal baseline TNSr, two patients developed a clinically relevant peripheral neuropathy with a marked increase in TNSr as early as after two cycles of bortezomib treatment (TNSr = 10 and 15, respectively), while after four cycles, three other patients with normal baseline TNSr had a TNSr of 11, 12, and 13. VAS reporting confirmed that painful neuropathy is frequent after bortezomib administration. Our results indicate that the course of bortezomib‐induced peripheral neurotoxicity can be severe in subjects with normal neurological examination at baseline, and therefore, careful monitoring during treatment is suggested in these patients.
Characteristics of bortezomib‐ and thalidomide‐induced peripheral neuropathy
Authors: Chaudhry Vinay , Cornblath David R. , Polydefkis Michael , Ferguson Anna , Borrello Ivan
Published: January 2009

Abstract  Dose‐limiting peripheral neuropathy (PN) is frequently reported with the use of thalidomide and bortezomib, novel proteasome inhibitors. While these two agents have significant activity in multiple myeloma (MM), the combination and the associated PN have not been fully examined in untreated patients. The objective of this study was to report the baseline prevalence and occurrence of PN in newly diagnosed MM patients treated with bortezomib and thalidomide. Twenty‐seven patients (11 men and 16 women) with previously untreated MM were prospectively monitored for PN. Total neuropathy score reduced (TNSr) was calculated at baseline and after every two cycles of bortezomib treatment. The median cumulative dose of bortezomib was 35.6 mg/m2 (median 8 cycles) and of thalidomide was 16.8 g. Only three subjects showed mild PN at baseline (whole group median TNSr 0). At the end of treatment, PN developed in 26 patients (median TNSr 8). PN was of mild to moderate severity (TNSr grade 1 = 11, grade 2 = 10, grade 3 = 5, and grade 4 = 0). Nerve conduction studies showed axonal physiology in all except three subjects in whom demyelinating physiology was noted. The median TNSr was 17 in the demyelinating group and 9 in the axonal group. There was no significant correlation of TNSr with cumulative bortezomib or thalidomide dose. At follow‐up, 80% of patients had become asymptomatic after discontinuation of the chemotherapy. We conclude that bortezomib and thalidomide combination chemotherapy induces a reversible length‐dependent sensory>motor, predominantly axonal, large‐fiber>small‐fiber polyneuropathy. In a subset, a more severe demyelinating polyneuropathy may develop.
Short‐ and intermediate‐term efficacy of buprenorphine TDS in chronic painful neuropathies
Authors: Penza Paola , Campanella Angela , Martini Alfredo , Melli Giorgia , Lombardi Raffaella , Camozzi Francesca , Devigili Grazia , Lauria Giuseppe
Published: January 2009

Abstract  Buprenorphine is a potent opioid available as a transdermal delivery system (TDS) formulation. This open‐label study investigated its safety, tolerability, and efficacy in 30 patients with chronic painful neuropathy. Subjects with visual analogue scale (VAS) score ≥5 under stable analgesic treatment were entered. The starting dosage of 35 μg/h was increased up to 70.0 μg/h in case of unsatisfactory pain control as assessed by fortnightly visits. The primary endpoint was the number of patients achieving at least 30% pain relief at day 42 visit. Treatment was safe over the study period. Nine patients dropped out for side effects, mostly nausea and daily sleepiness. Buprenorphine TDS was well tolerated in 21 patients. Thirteen patients achieved >30% of pain relief at day 42 visit. Five patients needed to increase the dosage to 52.5 μg/h. Eight patients did not meet the primary outcome, but none allowed increasing the dosage to 70 μg/h, and four patients withdrew consent to continue the study before day 42 visit because of a ‘fear to become addicted,’ although 40% had obtained VAS reduction. In our study, which needs to be confirmed by a controlled trial, buprenorphine TDS induced clinically meaningful pain relief in about 40% of patients with chronic painful neuropathy, suggesting its use as a third‐line treatment.
Inhibition of inducible nitric oxide synthase reduces an acute peripheral motor neuropathy produced by dermal burn injury in mice
Authors: Higashimori Haruki , Whetzel Thomas P. , Carlsen Richard C.
Published: January 2009

Abstract  The systemic inflammatory response produced by a full‐thickness dermal burn injury is associated with a peripheral motor neuropathy. We previously reported that a 20% body surface area (BSA) full‐thickness dermal burn in C57BL6 mice produced structural and functional deficits in motor axons at a distance from the burn site. The etiology of the neuropathy, however, is not well characterized. Burn injury leads to an increase in production of a number of proinflammatory mediators, including nitric oxide (NO). We tested the hypothesis that dermal burn‐induced motor neuropathy is mediated by increased production of NO. NO synthase (NOS) activity was inhibited following a 20% BSA full‐thickness burn by injection of non‐specific NOS inhibitor, nitro‐l‐arginine methyl ester or inducible NOS (iNOS) inhibitors, l‐N6‐(1‐iminoethyl) lysine, and aminoguanidine. NOS inhibitors also prevented the reduction in ventral roots mean axon caliber and the decrease in a motor nerve conduction velocity (MCV) following burn. iNOS knockout mice prevented MCV decrease in the first 3 days post‐burn, but iNOS knockout MCV was significantly reduced at 7–14 days post‐burn. These results suggest that an increase in NO production generated by systemic inflammatory response pathways after burn injury contributes to the development of structural and functional deficits in peripheral motor axons.
Diabetes mellitus exacerbates motor and sensory impairment in CMT1A
Authors: Sheth Soham , Francies Kevin , Siskind Carly E. , Feely Shawna M. E. , Lewis Richard A. , Shy Michael E.
Published: January 2009

Abstract  Charcot‐Marie‐Tooth disease type 1A (CMT1A) is caused by a duplication of PMP22 on chromosome 17 and is the most commonly inherited demyelinating neuropathy. Diabetes frequently causes predominantly sensory neuropathy. Whether diabetes exacerbates CMT1A is unknown. We identified 10 patients with CMT1A and diabetes and compared their impairment with 48 age‐matched control patients with CMT1A alone. Comparisons were made with the Charcot‐Marie‐Tooth disease (CMT) neuropathy score (CMTNS) and by electrophysiology. The CMTNS was significantly higher in patients with diabetes (20.25 ± 2.35) compared with controls (15.19 ± 0.69; p = 0.01). Values were particularly higher for motor signs and symptoms. Seven of the 10 diabetic patients had CMTNS >20 (severe CMT), while only 7 of the 48 age‐matched controls had scores >20. There was a trend for CMT1A patients with diabetes to have low compound muscle action potentials and sensory nerve action potentials, although nerve conduction velocities were not slower in diabetic patients compared with controls. Diabetes was associated with more severe motor and sensory impairment in patients with CMT1A.
Effects of Acute Alcohol Intoxication and Paroxetine on Aggression in Men
Authors: McCloskey Michael S. , Berman Mitchell E. , Echevarria David J. , Coccaro Emil F.
Published: January 2009

Background:  The purpose of this study was to examine the role of the serotonin (5‐HT) system in alcohol‐related aggression.

Methods:  Specifically, we experimentally examined the effects of 5‐HT augmentation on alcohol‐related aggression in men (n = 56). After consuming either alcohol (mean blood alcohol concentration of 0.10%) or a placebo (no alcohol) drink, and taking either 20 mg of paroxetine (Paxil®) or a placebo pill, participants were provided the opportunity to administer electric shock to a (faux) opponent during a task disguised as a reaction‐time game. Aggression was defined as the intensity of shock chosen and the frequency with which an extreme (clearly painful) shock was chosen. We predicted that 5‐HT augmentation would be associated with lower aggressive behavior overall, and also reduce the aggression facilitating effects of acute alcohol intoxication.

Results:  The results indicated that alcohol intoxication increased aggression, particularly under low provocation. Paroxetine decreased aggression, particularly during high provocation. These effects, however, occurred independently of each other.

Conclusions:  The effect of alcohol on extreme aggression was moderated by previous aggression history, with more aggressive individuals showing greater alcohol‐related increases in extreme aggression.
Dietary Zinc Supplementation Throughout Pregnancy Protects Against Fetal Dysmorphology and Improves Postnatal Survival After Prenatal Ethanol Exposure in Mice
Authors: Summers Brooke L. , Rofe Allan M. , Coyle Peter
Published: January 2009

Background:  We have previously demonstrated that ethanol teratogenicity is associated with metallothionein‐induced fetal zinc (Zn) deficiency, and that maternal subcutaneous Zn treatment given with ethanol in early pregnancy prevents fetal abnormalities and spatial memory impairments in mice. Here we investigated whether dietary Zn supplementation throughout pregnancy can also prevent ethanol‐related dysmorphology.

Methods:  Pregnant mice were injected with saline or 25% ethanol (0.015 ml/g intraperitoneally at 0 and 4 hours) on gestational day (GD) 8 and fed either a control (35 mg Zn/kg) or a Zn‐supplemented diet (200 mg Zn/kg) from GD 0 to 18. Fetuses from the saline, saline + Zn, ethanol and ethanol + Zn groups were assessed for external birth abnormalities on GD 18. In a separate cohort of mice, postnatal growth and survival of offspring from these treatment groups were examined from birth until postnatal day 60.

Results:  Fetuses from dams treated with ethanol alone in early pregnancy had a significantly greater incidence of physical abnormalities (26%) compared to those from the saline (10%), saline + Zn (9%), or ethanol + Zn (12%) groups. The incidence of abnormalities in ethanol + Zn‐supplemented fetuses was not different from saline‐treated fetuses. While ethanol exposure did not affect the number of fetal resorptions or pre‐ or postnatal weight, there were more stillbirths with ethanol alone, and cumulative postnatal mortality was significantly higher in offspring exposed to ethanol alone (35% deaths) compared to all other treatment groups (13.5 to 20.5% deaths). Mice supplemented with Zn throughout pregnancy had higher plasma Zn concentrations than those in un‐supplemented groups.

Conclusions:  These findings demonstrate that dietary Zn supplementation throughout pregnancy ameliorates dysmorphology and postnatal mortality caused by ethanol exposure in early pregnancy.
Long‐Term Behavioral Changes in Response to Early Developmental Exposure to Ethanol in Zebrafish
Authors: Fernandes Yohaan , Gerlai Robert
Published: January 2009

Background:  Zebrafish is becoming an important research tool for the analysis of brain function and behavior. It has been proposed to model human alcoholism as well as fetal alcohol syndrome. Previous studies investigating the consequences of exposure to ethanol during early development of zebrafish employed robust dosing regimens (high ethanol concentration and long exposure) that may model a rare situation in the human clinic. These studies found major structural abnormalities developing in the exposed fish.

Methods:  Here we hope to avoid such gross changes and administer only low doses of ethanol (0.00, 0.25, 0.50, 0.75, 1.00 vol/vol %) at 24‐hour postfertilization and for only a short period of time (for 2 hours). We analyze the behavior of exposed fish at adult stage using computerized stimulus presentation and automated videotracking response quantification.

Results:  Despite the short ethanol exposure period and the modest concentrations, significant behavioral alterations were found: fish exposed to higher doses of ethanol swam at an increased distance from a computer‐animated zebrafish shoal while their activity levels did not change.

Conclusions:  Although the interpretation of and the mechanisms underlying this finding will require further investigation, the results suggest that zebrafish will be an appropriate model organism for the analysis of the effects of moderate to mild prenatal ethanol exposure.
Alcohol Stimulates Ciliary Motility of Isolated Airway Axonemes Through a Nitric Oxide, Cyclase, and Cyclic Nucleotide‐Dependent Kinase Mechanism
Authors: Sisson Joseph H. , Pavlik Jacqueline A. , Wyatt Todd A.
Published: January 2009

Background:  Lung mucociliary clearance provides the first line of defense from lung infections and is impaired in individuals who consume heavy amounts of alcohol. Previous studies have demonstrated that this alcohol‐induced ciliary dysfunction occurs through impairment of nitric oxide (NO) and cyclic nucleotide‐dependent kinase‐signaling pathways in lung airway ciliated epithelial cells. Recent studies have established that all key elements of this alcohol‐driven signaling pathway co‐localize to the apical surface of the ciliated cells with the basal bodies. These findings led us to hypothesize that alcohol activates the cilia stimulation pathway at the organelle level. To test this hypothesis we performed experiments exposing isolated demembranated cilia (isolated axonemes) to alcohol and studied the effect of alcohol‐stimulated ciliary motility on the pathways involved with isolated axoneme activation.

Methods:  Isolated demembranated cilia were prepared from bovine trachea and activated with adenosine triphosphate. Ciliary beat frequency, NO production, adenylyl and guanylyl cyclase activities, cAMP‐ and cGMP‐dependent kinase activities were measured following exposure to biologically relevant concentrations of alcohol.

Results:  Alcohol rapidly stimulated axoneme beating 40% above baseline at very low concentrations of alcohol (1 to 10 mM). This activation was specific to ethanol, required the synthesis of NO, the activation of soluble adenylyl cyclase (sAC), and the activation of both cAMP‐ and cGMP‐dependent kinases (PKA and PKG), all of which were present in the isolated organelle preparation.

Conclusions:  Alcohol rapidly and sequentially activates the eNOS→NO→GC→cGMP→PKG and sAC→cAMP→ PKA dual signaling pathways in isolated airway axonemes. These findings indicate a direct effect of alcohol on airway cilia organelle function and fully recapitulate the alcohol‐driven activation of cilia known to exist in vivo and in intact lung ciliated cells in vitro following brief moderate alcohol exposure. Furthermore, these findings indicate that airway cilia are exquisitely sensitive to the effects of alcohol and substantiate a key role for alcohol in the alterations of mucociliary clearance associated with even low levels of alcohol intake. We speculate that this same axoneme‐based alcohol activation pathway is down regulated following long‐term high alcohol exposure and that the isolated axoneme preparation provides an excellent model for studying the mechanism of alcohol‐mediated cilia dysfunction.
Adverse Drinking‐Related Consequences Among Lower Income, Racial, and Ethnic Minority Drinkers: Cross‐Sectional Results
Authors: Vilamovska Anna‐Marie , Brown Taylor Didra , Bluthenthal Ricky N.
Published: January 2009

Objective:  To examine factors associated with adverse consequences of alcohol consumption among a community sample of drinkers in a low‐income, racial, and ethnic minority community.

Methods:  A sample of 329 drinkers was recruited from 17 randomly selected off‐sell alcohol outlets in South Los Angeles. Respondents were interviewed by trained research personnel on their demographic characteristics, income, drinking patterns and preferences, and alcohol‐related adverse consequences (using the Drinkers Inventory of Consequences—DrInC), among other items. We developed logistic regression models predicting high scores on DrInC total score and subscales (impulse control, interpersonal, intrapersonal, physical, and social responsibility).

Results:  In this sample, we found drinking patterns—bingeing, drinking outdoors, drinking in the morning—to be significantly associated with total DrInC scores and some subscales. Malt liquor beverage (MLB) use was significantly associated with total DrInC score and interpersonal and social responsibility subscales. Previous alcohol treatment predicted all but 1 DrInC subscale and total score.

Conclusions:  A diverse array of factors predicted high DrInC total and subscale scores. More research on the association between MLB use and consequences is required. In addition, studies with community samples are likely to further enrich our understanding of the interactions between drinking patterns and preferences, settings, and negative consequences.
A double‐blind, placebo‐controlled trial of rosiglitazone for clozapine‐induced glucose metabolism impairment in patients with Schizophrenia
Authors: Henderson D. C. , Fan X. , Sharma B. , Copeland P. M. , Borba C. P. , Boxill R. , Freudenreich O. , Cather C. , Eden Evins A. , Goff D. C.
Published: January 2009

Objective:  The primary purpose of this 8‐week double‐blind, placebo‐controlled trial of rosiglitazone 4 mg/day was to examine its effect on insulin sensitivity index (SI) and glucose utilization (SG) in clozapine‐treated subjects with schizophrenia with insulin resistance.

Method:  Eighteen subjects were randomized and accessed with a Frequently Sampled Intravenous Glucose Tolerance Test (FSIVGTT) at baseline and at week 8 to estimate SG and SI.

Results:  Controlling for the baseline, comparing the rosiglitazone group with placebo group, there was a non‐significant improvement in SG (0.016 ± 0.006–0.018 ± 0.008, effect size = 0.23, P = 0.05) with a trend of improvement in SI in the rosiglitazone group (4.6 ± 2.8–7.8 ± 6.7, effect size = 0.18, P = 0.08). There was a significant reduction in small low‐density lipoprotein cholesterol (LDL‐C) particle number (987 ± 443–694 ± 415, effect size = 0.30, P = 0.04).

Conclusion:  Rosiglitazone may have a role in addressing insulin resistance and lipid abnormalities associated with clozapine.
Which comes first: atypical antipsychotic treatment or cardiometabolic risk?
Authors: Stahl S. M. , Mignon L. , Meyer J. M.
Published: January 2009

Objective:  To provide an overview for practicing clinicians on the pharmacological basis of cardiometabolic risk induced by antipsychotic drugs in patients with serious mental illness, to propose hypotheses to explain these risks and to give tips for managing cardiometabolic risk during antipsychotic treatment.

Method:  A MEDLINE search using terms for atypical antipsychotics (including individual drug names), metabolic, cardiovascular, weight gain and insulin resistance, cross‐referenced with schizophrenia was performed on articles published between 1990 and May 2008.

Results:  Strong evidence exists for significant cardiometabolic risk differences among several antipsychotic agents. Histamine H1 and serotonin 5HT2C antagonism are associated with risk of weight gain, but receptor targets for dyslipidemia and insulin resistance have not yet been identified. Convincing data indicate that hypertriglyceridemia and insulin resistance may occur in the absence of weight gain with certain antipsychotics.

Conclusion:  Although lifestyle and genetics may contribute independent risks of cardiometabolic dysfunction in schizophrenia and other serious mental illness, antipsychotic treatment also represents an important contributor to risk of cardiometabolic dysfunction, particularly for certain drugs and for vulnerable patients. Mental health professionals must learn to recognize the clinical signposts indicating antipsychotic‐related cardiometabolic problems to forestall progression to type II diabetes, cardiovascular events and premature death.
Predictors of response to Systems Training for Emotional Predictability and Problem Solving (STEPPS) for borderline personality disorder: an exploratory study
Authors: Black D. W. , Allen J. , St. John D. , Pfohl B. , McCormick B. , Blum N.
Published: January 2009

Objective:  Few predictors of treatment outcome or early discontinuation have been identified in persons with borderline personality disorder (BPD).

Aim:  The aim of the study was to examine the relationship between baseline clinical variables and treatment response and early discontinuation in a randomized controlled trial of System Training for Emotional Predictability and Problem Solving, a new cognitive group treatment.

Method:  Improvement was rated using the Zanarini Rating Scale for BPD, the Clinical Global Impression Scale, the Global Assessment Scale and the Beck Depression Inventory. Subjects were assessed during the 20 week trial and a 1‐year follow‐up.

Results:  Higher baseline severity was associated with greater improvement in global functioning and BPD‐related symptoms. Higher impulsivity was predictive of early discontinuation. Optimal improvement was associated with attending ≥15 sessions.

Conclusion:  Subjects likely to improve have the more severe BPD symptoms at baseline, while high levels of impulsivity are associated with early discontinuation.
Atypical depression is associated with suicide attempt in bipolar disorder
Authors: Sánchez‐Gistau V. , Colom F. , Mané A. , Romero S. , Sugranyes G. , Vieta E.
Published: January 2009

Objective:  There is a dearth of research focusing on factors associated with suicide attempts. High rates of atypical depression have been reported in studies including unipolar and bipolar II patients. In this study, the association between suicide attempt and atypical depression, in addition to other major risk factors, was evaluated in 390 bipolar I and II out‐patients.

Method:  Variables were defined according to DSM‐IV criteria, and assessed with a Structured Interview for DSM‐IV (axis I and II). History of suicide attempt was obtained through interviews with patients and relatives. Attempters and non‐attempters were compared using univariate and multivariate analysis.

Results:  Attempters showed significantly higher rates of atypical depression, family history of completed suicide, depression at index episode and cluster B personality disorder.

Conclusion:  Our results highlight the relevance of atypical depression in bipolar disorder. A more accurate identification of potential attempters may contribute to the development of effective preventive treatment strategies.
Molecular pathways involved in hair follicle tumor formation: all about mammalian target of rapamycin?
Authors: Van Steensel Maurice A. M. , Van Geel Michel , Badeloe Sadhanna , Poblete‐Gutiérrez Pamela , Frank Jorge
Published: January 2009

Abstract:  Hair follicle tumors show a broad range of phenotypic variability and diverse histopathological characteristics. To date, different genes and signalling cascades have been implicated in the development and growth of these tumors including the sonic hedgehog, nuclear factor kappa‐B and wingless pathway. While the former three have received ample attention, little is known about the possible role of mammalian target of rapamycin (mTOR) in trichofollicular tumorigenesis. Here, we delineate how mTOR can link the various signalling pathways, thereby proposing a unifying model for hair follicle tumor formation.
Fish feeding in changing habitats: effects of invasive macrophyte control and habitat complexity
Authors: Kovalenko K. , Dibble E. D. , Fugi R.
Published: January 2009

Abstract –  Many freshwater lakes have been invaded by non‐native aquatic plants. Although managing the invasions is necessary to restore native macrophytes, little is known about the effects of invasive macrophyte eradication on fish foraging. This study was designed to determine whether fish feeding was affected by large‐scale changes in plant composition after selective control of invasive Eurasian watermilfoil, Myriophyllum spicatum, and whether feeding was correlated with habitat complexity or abundance of invasive plants on a smaller scale. Popnets were used to collect plants, invertebrates and fishes in the littoral zone of four Minnesota lakes twice a year for 4 years. The degree of stomach fullness in fishes was not correlated with the proportion of invasive plants or habitat complexity. Bluegills, the most abundant fish species, exhibited high selectivity for Diptera and their preferences varied little in different plant habitats. Changes in niche width of bluegills were not consistent with invasive plant control. Overall, invasive macrophyte control with timely restoration of the native plant community did not affect the characteristics of fish feeding we investigated. This study also contributes to our understanding of fish–macroinvertebrate interactions as a function of habitat complexity.
REVIEW ARTICLE: Control of Interferon‐Tau Expression During Early Pregnancy in Ruminants
Authors: Ealy Alan D. , Yang Qi En
Published: January 2009

Problem  A type I interferon (IFN), termed IFN‐tau (τ), is responsible for the establishment and maintenance of early pregnancy in cattle and sheep. The control of IFNτ gene (IFNT) expression is not completely understood.

Method of study  This article will provide an overview of recent progress made in understanding the dynamic expression pattern of IFNT during pre‐ and peri‐attachment conceptus development.

Results  Several ubiquitous transcriptional regulators (Ets2 and AP1) and at least two trophectoderm factors (Cdx2 and Dlx3) control IFNT transcription during early pregnancy. Co‐activators (CBP/p300) are also involved in this process. At least two uterine‐derived factors (GM‐CSF and FGF2) stimulate IFN‐τ production in bovine trophectoderm, and multiple signaling pathways are functionally linked with IFNT expression.

Conclusion  Although understanding the regulation of IFNT expression is far from complete, considerable progress has been made in uncovering how uterine‐derived factors and key placental‐specific transcriptional regulators control IFNT expression.
ORIGINAL ARTICLE: Changes in the Subpopulation of CD25+ CD4+ and FOXP3+ Regulatory T Cells in Decidua with Respect to the Progression of Labor at Term and the Lack of Analogical Changes in the Subpopulation of Suppressive B7‐H4+ Macrophages – A Preliminary Report
Authors: Galazka Krystyna , Wicherek Lukasz , Pitynski Kazimierz , Kijowski Jacek , Zajac Kszysztof , Bednarek Wieslawa , Dutsch‐Wicherek Magdalena , Rytlewski Krzysztof , Kalinka Jaroslaw , Basta Antoni , Majka Marcin
Published: January 2009

Problem  The initiation of labor is accompanied by alterations in the level of maternal immune tolerance toward fetal antigens. It is a complex molecular response leading to a brief activation of the maternal immune system with an accompanying capacity to restrict this same activation. The aim of our study was to evaluate the subpopulation of regulatory T cells (Tregs) and B7‐H4 macrophages in the decidua basalis during cesarean sections performed on patients in various stages of labor.

Method of study  The decidual tissue samples evaluated in our study were obtained from 23 pregnant women who underwent cesarean sections at term. Moreover, the patients were divided into three subgroups according to the progression of labor at the time of the cesarean. The presence of Treg cells and B7‐H4 positive macrophages were analysed by fluorescence‐activated cell sorter.

Results  The percentages of FOXP3+ cells in the subpopulation of CD25+ CD4+ T lymphocytes found in the deciduas of patients decreased with the successive stages of labor, while the percentages of B7‐H4 positive cells in the macrophage subpopulation remained almost constant.

Conclusion  These changes in the Treg cell subpopulation in the decidua would seem to be related to a brief activation of the maternal immune system as labor begins and lack of analogical changes in the subpopulation of decidual suppressive B7‐H4+ macrophages that enable the restriction of this same activation as labor progresses.
ORIGINAL ARTICLE: In situ Reconstruction of Humoral Immune Response Against Sperm: Comparison of SCID and NOD/SCID Mouse Models
Authors: Grygielska Beata , Kamieniczna Marzena , Wiland Ewa , Kurpisz Maciej
Published: January 2009

Problem  Comparison of two types of immunocompromised mouse strains (SCID and NOD/SCID) for production of human antisperm antibodies (AsA).

Method of study  Human peripheral blood lymphocytes (PBL) were grafted to mouse peritoneal cavity and sensitized with natively glycosylated and N‐deglycosylated sperm extracts.

Results and conclusion  NOD/SCID mice inoculated with hu‐PBLs exhibited higher AsA titres with a tendency for greater sperm agglutination than human AsA raised in SCID mouse model. A comparison between ‘native’ and deglycosylated sperm extracts revealed higher agglutination titres by sera induced with the latter ones. Inhibitory effect of human polyclonal AsA in sperm penetration assay, however, produced opposite results to that for agglutination. Western immunoblotting was used to evaluate reactive sperm antigens prior to and after in situ sensitization showing multiple bands different from positive reactions brought by original sera of in vivo primed AsA‐positive males. It seems that in situ generated AsA recognized sperm entities different from those revealed by blood donor’s sera samples.
ORIGINAL ARTICLE: Lipopolysaccharide Alters the Vaginal Electrical Resistance in Cycling and Pregnant Mice
Authors: Agrawal Varkha , Jaiswal Mukesh K. , Chaturvedi Madan M. , Tiwari Dinesh C. , Jaiswal Yogesh K.
Published: January 2009

Problem  Lipopolysaccharide (LPS) has been postulated to exert harmful biologic effects during pregnancy. The objective of present investigation is to measure the vaginal electrical resistance (VER) in LPS‐treated normal cycling and pregnant female mice.

Method of study  Minimum dose (MD) of LPS (250 μg/kg body weight) was injected in pregnant female mice through i.p. route on day 0.5 of pregnancy. VER was measured during different phases of reproductive cycle in female mice, which were pre‐exposed to LPS and in untreated cycling female mice. VER was also measured in control pregnant female mice (saline‐treated mice) through whole pregnancy and LPS‐treated female mice in early stages of pregnancy.

Results  Vaginal electrical resistance was significantly higher during proestrous or early estrous stage as compared with any other stages of reproductive cycle in mouse. One peak of VER was observed during peri‐implantation period of pregnancy in control female mice. The significant differences in the pattern of VER were found between LPS‐treated and control female mice during peri‐implantation period of pregnancy, and between cycling female mice, which were pre‐exposed to LPS and untreated cycling female mice during proestrus.

Conclusion  The presented results demonstrate, for the first time, that LPS exposure during pregnancy may be determined by measuring VER in mothers without any adverse effect on ongoing pregnancy and may help in refining the assisted reproduction techniques.
ORIGINAL ARTICLE: Glycation Endproducts, Soluble Receptor for Advanced Glycation Endproducts and Cytokines in Diabetic and Non‐diabetic Pregnancies
Authors: Pertyńska‐Marczewska Magdalena , Głowacka Ewa , Sobczak Małgorzata , Cypryk Katarzyna , Wilczyński Jan
Published: January 2009

Problem  Cytokines, advanced glycation end products (AGEs), and their receptor RAGE have been recently suggested to play a role in human pregnancy. In this study, we sought to determine the alterations of plasma AGEs, soluble RAGE (sRAGE), and proinflammatory cytokines in normal pregnancies and those complicated with type 1 diabetes mellitus.

Method of study  These parameters were measured in samples from healthy non‐pregnant (C), diabetic non‐pregnant (D), healthy pregnant (HP), and pregnant diabetic (DP) women.

Results  In the first trimester, DP showed lower sRAGE and higher AGEs compared to HP. In the DP group, significant negative correlations were seen between TNF‐α and lipopolysaccharide (LPS)‐stimulated ΙL‐6 in the first trimester and sRAGE in the third trimester. LPS‐stimulated IL‐12 was positively correlated with levels of AGEs in the third trimester.

Conclusion  We detected several differences in the levels of AGEs, sRAGE, and proinflammatory cytokines between euglycemic and diabetic pregnancies.
Hepatosplenic T‐cell lymphomas and therapy with TNF‐α‐blocking biologics: a risk for psoriasis patients?
Authors: Beyer Marc , Steinhoff Matthias , Anagnostopoulos Ioannis , Assaf Chalid , Sterry Wolfram
Published: January 2009

Tumor necrosis factor (TNF)‐α antagonists have considerably improved the therapeutic approach to chronic inflammatory disorders including psoriasis vulgaris. Recently, some cases of highly aggressive hepatosplenic T‐cell lymphoma (HSTCL) have developed in patients with inflammatory bowel diseases (IBD) being treated with infliximab or adalimumab. Analysis of the published data suggests that the emergence of HSTCL is favored by the combination of purine analogues and infliximab or adalimumab in the therapy of a granulomatous inflammation involving Vδ1+γδ T cells. Because psoriasis vulgaris is different from IBD in regard to the type of inflammation, the concomitant therapies used and the tissue‐specific subsets of γδ T cells, the use of infliximab or adali‐mumab in psoriasis may not necessarily be associated with an increase in the risk of HSTCL.
Encapsulated lipomas of the tongue in benign symmetric lipomatosis
Authors: Ettl Tobias , Gaumann Andreas , Ehrenberg Ramin , Reichert Torsten E. , Driemel Oliver
Published: January 2009

Benign symmetric lipomatosis (Madelung disease) is a rare disorder of unknown etiology characterized by diffuse growth of unencapsulated lipomas predominantly in the head, neck and shoulder region. Involvement of the tongue has been previously described in only five cases. A 49‐year‐old man with alcoholic liver cirrhosis presented with an 11‐year history of benign symmetric lipomatosis complaining of increasing dysphagia, dysarthria and hoarseness. Clinical intraoral examination revealed asymmetric, globular, firm, circumscribed masses on both borders of the tongue. During surgery, the masses seemed encapsulated from surrounding muscles and could easily be extirpated. However, “satellite fat cells” became obvious, which might give rise to the development of new lipomas.
Establishment of the gut microbiota in Western infants
Authors: Adlerberth I , Wold AE
Published: January 2009

In adult individuals, the intestinal microbiota comprises several hundred, mostly anaerobic, bacterial species. This complex ecosystem is formed through the successive establishment of different bacteria in infancy and early childhood. Facultative and aerotolerant bacteria establish first, followed by more and more strict anaerobes. The bacteria derive from different sources and the colonization pattern is influenced by delivery mode and environmental factors. Commensal microbes provide the major drive for maturation of the immune system. Increased hygiene appears to have changed the gut flora of Western infants, which may affect the risk of developing immune mediated diseases.

Conclusion: It is clear that the process of infant colonization needs to be studied further, since composition of the microbiota may impact on child health.
Body temperature measurement in VLBW infants by continuous skin measurement is a good or even better alternative than continuous rectal measurement
Authors: Van Der Spek RDG , Van Lingen RA , Van Zoeren‐Grobben D
Published: January 2009

Background: An inadequate body temperature in preterm infants influences morbidity and mortality. Continuous rectal measurement is a reliable method to measure body temperature but might have adverse effects and is even contra‐indicated in case of low platelets or necrotising enterocolitis. A save and non‐invasive method to measure body temperature is the transcutaneous ‘zero heat flow’ method.

Aim: We hypothesised that for monitoring body temperature in very low birth weight (VLBW) infants, central measurement of temperature by way of the zero heat flow principle is just as reliable as rectal temperature.

Methods: Twenty‐six infants, birth weight between 520 g and 1250 g, gestational age 25.28–32.28 weeks were provided with an insulated continuous skin probe with ‘zero heat flow’ and a continuous rectal probe. Both measurements were registered every hour over a period of 48 h. The sample size was calculated to detect a difference of less than or equal to 0.20°C.

Results: 1205 of the 1248 temperature measurements were analysed. At any moment, skin temperature was higher or equal when compared to rectal temperature. Mean skin temperature was 0.13°C (SD 0.33) higher than mean rectal temperature (t‐test, p < 0.001). Correlation between rectal and skin temperature was 0.82 (p ≤ 0.05).

Conclusion: In VLBW infants, temperature measurement by ‘zero heat flow’ method is just as reliable as by rectal method.