The global distribution of oral and maxillofacial surgeons: a mixed-methods study.

Despite its role in treating the most dominant non-communicable diseases worldwide, the global workforce of oral and maxillofacial (OM) surgeons is not well-characterized. To address the current deficit in understanding of the global OM surgeon workforce and to elevate oral and maxillofacial surgery (OMS) in the global health discourse, we join other surgical specialties in evaluating global surgical capacity with a descriptive analysis of the distribution of OM surgeons worldwide. A mixed-methods study was implemented using a combination of literature review, in-country contacts, internet searches, and survey data. The survey was distributed globally from January to June 2022. Data regarding OM surgeon workforce estimates were obtained for 104 of 195 United Nations-recognized countries (53.3%). Among countries with available estimates, the median global workforce density was 0.518 OM surgeons per 100,000 population. Twenty-eight countries (26.9%) were reported to have two or fewer OM surgeons. The median OM surgeon workforce density for low-income countries was 0.015 surgeons per 100,000 population, compared to 1.087 surgeons per 100,000 population in high-income countries. low and middle-income countries countries have the least workforce density as well as the least data coverage. More work is needed to better understand the capacity of the global OM surgeon workforce and access to OMS care.

Identification and characterization of androgen receptor associated coregulators in prostate cancer cells.

The androgen receptor (AR) is a member of the nuclear receptor (NR) superfamily that mediates the effects of androgens on target tissues. Over the last decade, it has become apparent that NRs require accessory factors for optimal activation of target gene expression. Numerous NR coregulators have been identified, with diverse structures and potential mechanisms of coregulation, creating an increasingly complicated picture of NR action. Due to the expanding complexity of the coregulator field, this review will focus on the AR ligand-binding domain (LBD) and N-terminal interacting proteins identified by our lab. The LBD-interacting proteins ARA70, ARA55 and ARA54 were first characterized and ARA70 was found to have a relatively higher specificity for the AR in human prostate cancer DU145 cells. Characterization of the functional relationship between the AR and these coregulators indicated that ARA70 and ARA55 could enhance the androgenic effects of 17beta-estradiol (E2) and hydroxyflutamide (HF), an antiandrogen commonly used in the treatment of prostate cancer. ARA160, an AR N-terminal interacting protein also known as TATA element modulatory factor (TMF), was subsequently shown to cooperate with ARA70 in enhancing AR activity. Another AR N-terminal interacting protein, ARA24, interacted with the poly-Q tract, a region within the N-terminus of the AR linked to Kennedy's disease (X-linked spinal and bulbar muscular atrophy). More recently, our lab has identified ARA267, a SET domain containing protein, and supervillin, an F-actin binding protein, as AR coregulators. Collectively, the data from these studies indicate that these coregulators are necessary for optimal AR transactivation. Interruption of the interaction between AR and these proteins may serve as a new therapeutic target in the treatment of prostate cancer.

Identification of 3',5'-cyclic adenosine monophosphate response element and other cis-acting elements in the human androgen receptor gene promoter.

Androgen and androgen receptor (AR) play an important role in sexual differentiation and prostate proliferation. To investigate AR gene transcriptional regulation, a 2.3-kilobase AR gene promoter region was isolated, sequenced, and characterized. Chloramphenicol acetyltransferase (CAT) assay and sequence homology search of AR gene promoter among human, rat, and mouse revealed some potential cis-acting elements, including a GC box, a suppressor region, and a purine-rich element. Deletion analysis and gel retardation assay using a 50-base pair (bp) double-strand purine-rich element showed that this purine-rich element can bind to specific proteins in nuclear extract of LNCaP and HeLa cells and may be essential for AR gene transcription. Furthermore, to investigate the effect of cAMP on AR gene transcription, we treated LNCaP and HeLa cells with 10 mM (Bu)2cAMP after transfection with CAT gene reporter plasmids linked to the AR gene promoter. This treatment induced several folds of CAT activity in LNCaP cells only, and the induction was further confirmed at AR mRNA level by Northern blot analysis and reverse transcription-polymerase chain reaction assay. Deletion analysis of the AR gene promoter showed that a region between 530 bp and 380 bp upstream of AR gene transcription initiation site, which includes one potential cAMP response element (CRE), is responsible for cAMP induction. Gel retardation analysis using this CRE (AR/CRE1) showed that AR/CRE1 can bind to specific proteins in nuclear extract of LNCaP cells, which appears to form a different binding complex compared to somatostatin/CRE.

Vitamin A, Vitamin E or beta-carotene status and hepatitis B-related hepatocellular carcinoma.

A case-control study was carried out in 59 patients with newly diagnosed hepatocellular carcinoma and 101 control subjects, who were all male hepatitis B carriers. The odds ratios of hepatocellular carcinoma occurring among hepatitis B carriers in the lowest quartile and those highest quartile of dietary and serum status were 5.3 (1.9 to 15.0) and 86.9 (20.0 to 377.2), respectively. The odds ratios for hepatitis B carriers in the lowest quartile and those in the highest quartile of dietary and serum beta-carotene status were 1.7 (0.7 to 4.1) and 5.0 (1.9 to 13.2). Vitamin E status did not differ in case patients and control subjects. Low education level, heavy consumption of alcohol, and smoking status were also associated with increased odds of hepatocellular carcinoma. Serum retinol, positively associated with dietary retinol, demonstrated an independent effect on hepatocellular carcinoma. This effect may reflect changes in the physiologic condition of the patients at the time of entering the hospital.

Photosensitization of mitochondrial adenosine-triphosphatase and adenylate kinase by hematoporphyrin derivative in vitro.

Mitochondrial ATPase and adenylate kinase activity of hepatoma cells were inhibited by hematoporphyrin derivative (HPD) followed by photoirradiation. Inhibition of ATPase activity was a dose- and time-related event. Malonaldehyde (MDA) content of mitochondrial membranes was markedly increased by HPD plus light. The content of mouse liver microsomal cytochrome P-450 was greatly increased after intraperitoneal injection of HPD for 4 days (5 mg/kg/day). The liver weight, and levels of liver microsomal G-6-phosphatase, MDA and triglyceride (TG) showed no difference in treated vs. control animals. The data presented here demonstrate that mitochondria may be a sensitive site of action of HPD photosensitization, and inactivation of ATPase and adenylate kinase may be an important contributing factor to tumor cell damage and death.

Emergency hysterectomy for obstetric hemorrhage.

From 1978 to 1982, 70 cases of emergency hysterectomy for obstetric hemorrhage were performed at Los Angeles County/University of Southern California Women's Hospital. Sixty hysterectomies followed cesarean section, and ten were performed for hemorrhage after vaginal delivery. The most common indication for hysterectomy was atony (43%) followed by placenta accreta (30%), uterine rupture (13%), extension of a low transverse incision (10%), and leiomyomata preventing uterine closure and hemostasis (4%). Hysterectomies performed for atony had a significant association with the following factors when compared to hysterectomies performed for other indications: 1) amnionitis, 2) cesarean section for labor arrest, 3) oxytocin augmentation of labor, 4) MgSO4 infusion, and 5) fetal weight. Fifty-seven percent of hysterectomies performed for placenta accreta were associated with a previous cesarean section. During the study period, 53% of all patients presenting at term with both a placenta previa and one or more previous cesarean sections, subsequently underwent hysterectomy for placenta accreta. Even with a broad inclusion of risk factors, only 74% of patients developing a hemorrhagic complication leading to hysterectomy can be identified before delivery.

Possible effects of normetabolites on the subjective and reinforcing characteristics of opioids in animals and man.

When an opioid capable of forming active metabolites is administered, the total pharmacology is the result of interactions of the opioid and such metabolites, especially normetabolites. Normetabolites may affect the morphine-like characteristics of certain opioids and thus influence their reinforcement in animals and man. Most opioids, when administered in single doses, are positively reinforcing in addicts. Oral administration, as compared with parenteral, facilitates the formation of normetabolites. When chronically administered, many opioids, including acetylmethadol, meperidine, morphine, codeine, propoxyphene, and levorphanol, show evidence of a longer half-life for their normetabolites. Normetabolites may have aversive characteristics and thus impair positive reinforcement of the parent drug in animals and man. For example, addicts do not like chronic oral morphine or chronic oral codeine. Conversely, methadone, the normetabolites of which are inactive, is well accepted during chronic oral administration. Drugs which inhibit N-demethylation will increase the agonist potency of opioids having inactive normetabolites (e.g., methadone) but will decrease the agonist potency of opioids having more potent normetabolites than the parent (e.g., acetylmethadol). The divergent responses of addicts to single doses of opiates as compared with chronic doses indicate that chronic addiction tests in man are needed befored relative abuse liability can be predicted.