Amchem Products, Inc. v. Windsor

Published in cooperation with the American Bar Association Section of Dispute Resolutio

Do soldiers seek more mental health care after deployment? Analysis of mental health consultations in the Netherlands Armed Forces following deployment to Afghanistan

Background: Military deployment to combat zones puts military personnel to a number of physical and mental challenges that may adversely affect mental health. Until now, few studies have been performed in Europe on mental health utilization after military deployment. Objective: We compared the incidence of mental health consultations with the Military Mental Health Service (MMHS) of military deployed to Afghanistan to that of non-deployed military personnel. Method: We assessed utilization of the MMHS by the full cohort of the Netherlands Armed Forces enlisted between 2008 and 2010 through linkage of mental health and human resource information systems. Results: The total population consisted of 50,508 military (18,233 deployed, 32,275 non-deployed), who accounted for 1,906 new consultations with the MMHS. The follow-up was limited to the first 2 years following deployment. We observed higher mental health care utilization in deployed vs. non-deployed military personnel; hazard ratio (HR), adjusted for sex, military branch and time in service, 1.84 [95% CI 1.61–2.11] in the first and 1.28 [1.09–1.49] in the second year after deployment. An increased risk of adjustment disorders (HR 2.59 [2.02–3.32] and 1.74 [1.30–2.32]) and of anxiety disorders (2.22 [1.52–3.25] and 2.28 [1.50–3.45]) including posttraumatic stress disorder (5.15 [2.55–10.40] and 5.28 [2.42–11.50]), but not of mood disorders (1.33 [0.90–1.97] and 1.11 [0.68–1.82]), was observed in deployed personnel in the first- and second-year post-deployment, respectively. Military personnel deployed in a unit with a higher risk of confrontation with potentially traumatic events had a higher HR (2.13 [1.84–2.47] and 1.40 [1.18–1.67]). Conclusions: Though absolute risk was low, in the first and second year following deployment to Afghanistan there was an 80 and 30% higher risk for mental health problems resulting in a consultation with the Dutch MMHS compared to military never deployed to Afghanistan. These observations underscore the need for an adequate mental health infrastructure for those returning from deployment

Synergistic effects of bombesin and epidermal growth factor on cancers.

Bombesin and gastrin-releasing peptide act as autocrine mitogens in various cancers. Bombesin antagonist RC-3095 inhibited growth in some cancers and slowed the progression of premalignant lesions, possibly by down-regulating epidermal growth factor (EGF) receptors. Since the EGF receptor mitogen response involves tyrosine kinase stimulation, we tested the hypotheses that bombesin stimulates, and RC-3095 inhibits, phosphorylation; EGF and bombesin promote the phosphorylation of the same substrates; and EGF and bombesin act synergistically on phosphorylation. Therefore, in vitro assays for phosphorylation were performed in the presence or absence of EGF, bombesin, RC-3095, and combinations in samples derived from tumor, tissue surrounding tumor, cell lines, and normal and transforming tissue derived from the 9,10-dimethyl-1,2-benzanthracene-induced squamous cell lesions of the hamster cheek pouch. Bombesin increased, and RC-3095 decreased, phosphorylation in these samples. In the human hepatoma sample and surrounding tissue, these ligands altered the phosphorylation of the same substrates affected by EGF. EGF and bombesin stimulated phosphorylation synergistically in the hamster samples and the hepatoma. Bombesin-induced phosphorylation was greater in tissue surrounding the hepatoma, whereas RC-3095 was more effective in inhibiting phosphorylation in the hepatoma itself. This cancer, therefore, could be endogenously stimulated by gastrin-releasing peptide. These observations support the hypothesis that bombesin stimulates growth of tissues and tumors by amplifying the phosphorylation response to EGF. The growth inhibitory response to RC-3095, or other bombesin analogues, of individual tumors may be prognosed by in vitro phosphorylation assays using the samples from the patient's tumor

Periodontal dysbiosis associates with reduced CSF Aβ42 in cognitively normal elderly

Introduction: Periodontal disease is a chronic, inflammatory bacterial dysbiosis that is associated with both Alzheimer's disease (AD) and Down syndrome. / Methods: A total of 48 elderly cognitively normal subjects were evaluated for differences in subgingival periodontal bacteria (assayed by 16S rRNA sequencing) between cerebrospinal fluid (CSF) biomarker groups of amyloid and neurofibrillary pathology. A dysbiotic index (DI) was defined at the genus level as the abundance ratio of known periodontal bacteria to healthy bacteria. Analysis of variance/analysis of covariance (ANOVA/ANCOVA), linear discriminant effect‐size analyses (LEfSe) were used to determine the bacterial genera and species differences between the CSF biomarker groups. / Results: At genera and species levels, higher subgingival periodontal dysbiosis was associated with reduced CSF amyloid beta (Aβ)42 (P = 0.02 and 0.01) but not with P‐tau. / Discussion: We show a selective relationship between periodontal disease bacterial dysbiosis and CSF biomarkers of amyloidosis, but not for tau. Further modeling is needed to establish the direct link between oral bacteria and Aβ

The Mitochondrial Ca(2+) Uniporter: Structure, Function, and Pharmacology.

Mitochondrial Ca(2+) uptake is crucial for an array of cellular functions while an imbalance can elicit cell death. In this chapter, we briefly reviewed the various modes of mitochondrial Ca(2+) uptake and our current understanding of mitochondrial Ca(2+) homeostasis in regards to cell physiology and pathophysiology. Further, this chapter focuses on the molecular identities, intracellular regulators as well as the pharmacology of mitochondrial Ca(2+) uniporter complex

Can bile duct injuries be prevented? "A new technique in laparoscopic cholecystectomy"

BACKGROUND: Over the last decade, laparoscopic cholecystectomy has gained worldwide acceptance and considered to be as "gold standard" in the surgical management of symptomatic cholecystolithiasis. However, the incidence of bile duct injury in laparoscopic cholecystectomy is still two times greater compared to classic open surgery. The development of bile duct injury may result in biliary cirrhosis and increase in mortality rates. The mostly blamed causitive factor is the misidentification of the anatomy, especially by a surgeon who is at the beginning of his learning curve. Biliary tree injuries may be decreased by direct coloration of the cystic duct, ductus choledochus and even the gall bladder. METHODS: gall bladder fundus was punctured by Veress needle and all the bile was aspirated. The same amount of fifty percent methylene blue diluted by saline solution was injected into the gall bladder for coloration of biliary tree. The dissection of Calot triangle was much more safely performed after obtention of coloration of the gall bladder, cystic duct and choledocus. RESULTS: Between October 2003 and December 2004, overall 46 patients (of which 9 males) with a mean age of 47 (between 24 and 74) underwent laparoscopic cholecystectomy with methylene blue injection technique. The diagnosis of chronic cholecystitis (the thickness of the gall bladder wall was normal) confirmed by pre-operative abdominal ultrasonography in all patients. The diameters of the stones were greater than 1 centimeter in 32 patients and calcula of various sizes being smaller than 1 cm. were documented in 13 cases. One patient was operated for gall bladder polyp (our first case). Successful coloration of the gall bladder, cystic duct and ductus choledochus was possible in 43 patients, whereas only the gall bladder and proximal cystic duct were visualised in 3 cases. In these cases, ductus choledochus visibility was not possible. None of the patients developed bile duct injury. CONCLUSION: The number of bile duct injuries related to anatomic misidentification can be decreased and even vanished by using intraoperative methylene blue injection technique into the gall bladder fundus intraoperatively

Culture(s) of control: Political dynamics in cannabis policy in England & Wales and the Netherlands

© 2016, © The Author(s) 2016. This paper draws upon an empirical comparative study of policy-making in England & Wales and the Netherlands. Recent changes in cannabis policy prima facie indicate some convergence towards a toughening of approaches, thereby suggesting commonalities in control cultures. However, analysis of findings illuminate significant differences in the policy process between these jurisdictions which contribute towards continued divergence towards small-scale supply and consumption of cannabis. It is argued that this can be understood and explained through an understanding of differences in both political institutions and cultures, and in organizational responsibilities and relations of power. Consequentially, this further supports the notion that comparative research and theorizing needs to take account of mechanisms and features which lead to variegated control cultures

Bid can mediate a pro-apoptotic response to etoposide and ionizing radiation without cleavage in its unstructured loop and in the absence of p53

BH3-only protein Bid is a key player in death receptor-induced apoptosis, because it provides the link with the mitochondrial route for caspase activation. In this pathway, Bid is activated upon cleavage by caspase-8. Its BH3 domain-containing carboxy-terminal fragment subsequently provokes mitochondrial outer membrane permeabilization by Bak/Bax activation. Bid has also been implicated in the apoptotic response to ionizing radiation (IR) and the topoisomerase inhibitor etoposide, anti-cancer regimens that cause double-strand (ds)DNA breaks. We confirm the existence of this pathway and show that it is p53-independent. However, the degree of Bid participation in the apoptotic response to dsDNA breaks depends on the nature of cell transformation. We used Bid-deficient mouse embryonic fibroblast (MEF) lines that were reconstituted with Bid to control the cellular background and demonstrated that the Bid-dependent apoptotic pathway induced by IR and etoposide operates in MEFs that are transformed by SV40, but is not evident in E1A/Ras-transformed MEFs. The Bid-dependent apoptotic response in p53-deficient SV40-transformed MEFs contributed to clonogenic execution of the cells, implying relevance for treatment outcome. In these cells, Bid acted in a conventional manner in that it required its BH3 domain to mediate apoptosis in response to IR and etoposide, and triggered apoptotic execution by indirect activation of Bak/Bax, mitochondrial permeabilization and caspase-9 activation. However, the mechanism of Bid activation was unconventional, because elimination of all known or suspected cleavage sites for caspases or other proteolytic enzymes and even complete elimination of its unstructured cleavage loop left Bid's pro-apoptotic role in the response to IR and etoposide unaffected