Where there's smoke there must be ire! Nicotine addiction treatment: a review.

Tobacco use in the United States has decreased by almost 50 percent since 1965, although the decline over the past few years has stalled. In the high school student population the smoking rates have not only plateaued over the past several years but have even increased. This paper will discuss the pathophysiology of tobacco addiction and treatment options for smoking cessation.

Management of Maxillofacial Gunshot Injuries With Emphasis on Damage Control Surgery During the Yemen Civil War. Review of 173 Victims From a Level 1 Trauma Hospital in Najran, Kingdom of Saudi Arabia.

Study Design: Studies on the concept of Damage Control Surgery (DCS) in the management of firearm injuries to the oral and maxillofacial region are still scarce, hence the basis for the current study. Objectives: The objectives of the current study is to share our experience in the management of maxillofacial gunshot injuries with emphasis on DCS and early definitive surgery. Methods: This was a retrospective study of combatant Yemeni patients with maxillofacial injuries who were transferred across the border from Yemen to Najran, Kingdom of Saudi Arabia. Demographics and etiology of injuries were stored. Paths of entry and exit of the projectiles were also noted. Also recorded were types of gunshot injury and treatment protocols adopted. Data was stored and analyzed using IBM SPSS Statistics for Windows Version 25 (Armonk, NY: IBM Corp). Results: A total of 408 victims, all males, were seen during the study period with 173 (42.4%) males sustaining gunshot injuries to the maxillofacial region. Their ages ranged from 21 to 56 years with mean ± SD (27.5 ± 7.6) years. One hundred and twenty-one (70.0%) victims had extraoral bullet entry, while 53 (30.0%) victims had intraoral entry route. Ocular injuries, consisting of 25 (14.5%) cases of ruptured globe and 6 (3.5%) cases of corneal injuries, were the most commonly associated injuries. A total of 78 (45.1%) hemodynamically unstable victims had DCS as the adopted treatment protocol while early definitive surgery was carried out in 47(27.2%) hemodynamically stable victims. ORIF was the treatment modality used for the fractures in 132 (76.3%) of the victims. Conclusions: We observed that 42.4% of the war victims sustained gunshot injuries. DCS with ORIF was the main treatment protocol adopted in the management of the hemodynamically unstable patients.

Acute lymphoid and gastrointestinal toxicity induced by selective p38alpha map kinase and map kinase-activated protein kinase-2 (MK2) inhibitors in the dog.

Exposure to moderately selective p38alpha mitogen-activated protein kinase (MAPK) inhibitors in the Beagle dog results in an acute toxicity consisting of mild clinical signs (decreased activity, diarrhea, and fever), lymphoid necrosis and depletion in the gut-associated lymphoid tissue (GALT), mesenteric lymph nodes and spleen, and linear colonic and cecal mucosal hemorrhages. Lymphocyte apoptosis and necrosis in the GALT is the earliest and most prominent histopathologic change observed, followed temporally by neutrophilic infiltration and acute inflammation of the lymph nodes and spleen and multifocal mucosal epithelial necrosis and linear hemorrhages in the colon and cecum. These effects are not observed in the mouse, rat, or cynomolgus monkey. To further characterize the acute toxicity in the dog, a series of in vivo, in vitro, and immunohistochemical studies were conducted to determine the relationship between the lymphoid and gastrointestinal (GI) toxicity and p38 MAPK inhibition. Results of these studies demonstrate a direct correlation between p38alpha MAPK inhibition and the acute lymphoid and gastrointestinal toxicity in the dog. Similar effects were observed following exposure to inhibitors of MAPK-activated protein kinase-2 (MK2), further implicating the role of p38alpha MAPK signaling pathway inhibition in these effects. Based on these findings, the authors conclude that p38alpha MAPK inhibition results in acute lymphoid and GI toxicity in the dog and is unique among the species evaluated in these studies.

Partial mGlu5 Negative Allosteric Modulators Attenuate Cocaine-Mediated Behaviors and Lack Psychotomimetic-Like Effects.

Cocaine abuse remains a public health concern for which pharmacotherapies are largely ineffective. Comorbidities between cocaine abuse, depression, and anxiety support the development of novel treatments targeting multiple symptom clusters. Selective negative allosteric modulators (NAMs) targeting the metabotropic glutamate receptor 5 (mGlu5) subtype are currently in clinical trials for the treatment of multiple neuropsychiatric disorders and have shown promise in preclinical models of substance abuse. However, complete blockade or inverse agonist activity by some full mGlu5 NAM chemotypes demonstrated adverse effects, including psychosis in humans and psychotomimetic-like effects in animals, suggesting a narrow therapeutic window. Development of partial mGlu5 NAMs, characterized by their submaximal but saturable levels of blockade, may represent a novel approach to broaden the therapeutic window. To understand potential therapeutic vs adverse effects in preclinical behavioral assays, we examined the partial mGlu5 NAMs, M-5MPEP and Br-5MPEPy, in comparison with the full mGlu5 NAM MTEP across models of addiction and psychotomimetic-like activity. M-5MPEP, Br-5MPEPy, and MTEP dose-dependently decreased cocaine self-administration and attenuated the discriminative stimulus effects of cocaine. M-5MPEP and Br-5MPEPy also demonstrated antidepressant- and anxiolytic-like activity. Dose-dependent effects of partial and full mGlu5 NAMs in these assays corresponded with increasing in vivo mGlu5 occupancy, demonstrating an orderly occupancy-to-efficacy relationship. PCP-induced hyperlocomotion was potentiated by MTEP, but not by M-5MPEP and Br-5MPEPy. Further, MTEP, but not M-5MPEP, potentiated the discriminative-stimulus effects of PCP. The present data suggest that partial mGlu5 NAM activity is sufficient to produce therapeutic effects similar to full mGlu5 NAMs, but with a broader therapeutic index.