Investigating the health disparities in the association between lifestyle behaviors and the risk of head and neck cancer.

Many studies have reported a positive association between lower socioeconomic status (SES) and higher head and neck cancer (HNC) risk. Fewer studies have examined the impact of SES on the association between alcohol or cigarette use and HNC risk. The current case-control study (1104 HNC cases and 1363 controls) investigated the influence of education, a SES indicator, on the association between HNC and the use of alcohol, cigarettes, or betel quids in Taiwan, a country with universal health care. Our results showed a larger increase in HNC risk associated with alcohol among those with lower educational level (odds ratio [OR] = 2.07; 95% confidence interval [CI], 1.53-2.80) than those with higher educational level (OR = 1.38; 95% CI, 1.04-1.85) (heterogeneity-P = .03). Educational level had an influence on the association between alcohol use and HNC risk among those with genetic susceptibility (ALDH2-deficient) to the carcinogenic effect of alcohol. The association between cigarette or betel quid use and HNC risk was similar between the high and low educational groups. National policies and social interventions have led to the decline in the prevalence of cigarette and betel quid users in Taiwan. In contrast, due to the lack of adequate alcohol control policies, alcohol consumption in Taiwan has continued to rise. A higher impact of alcohol on HNC risk among lower SES individuals even with universal health care could be the result of insufficient alcohol control policies in Taiwan.

Ethnomedical uses and pharmacological activities of most prevalent species of genus Piper in Panama: A review.

ETHNOPHARMACOLOGICAL RELEVANCE: Piperaceae is the fifth largest family of plants in Panama. This review focuses on the ethnomedical uses of the most prevalent Panamanian species and biological activities of their extracts and/or constituents both in Panama and worldwide. Many species have a plethora of ethnomedical uses such as antibacterial, antifungal, anti-inflammatory, anticancer, antidiabetic, anti-Helicobacter pylori, antiulcer, antiprotozoal, estrogenic, insecticidal, local anesthetic, diuretic, and for women's health conditions. AIM OF THE REVIEW: The aim of this review is to compile all ethnomedical uses of most prevalent species of Piper in Panama, and their extracts or phytoconstituents worldwide, through a complete literature search, so that it may allow selection of potential unexplored Piper species for future research and development of phytotherapeuticals for important ailments. METHODOLOGY: This review conducted a thorough search in books and databases such as Google Scholar, PubMed, Sci-Finder, Scopus, ACS publications, Science Direct, and Reaxys (Elsevier), until October of 2017. The information provided in this review is based on peer-reviewed papers only in English. The key words used to search were: "Piper", "Piperaceae", "Panama", "Pharmacological activity", "Chemistry," "Toxicity," and "Clinical studies". Scientific names of the plants were validated through www.tropicos.org. Potential full-texts of eligible papers, irrespective of database, were identified. Study selection and data extraction were conducted by one author (AIS) and confirmed by others (MPG, ADA). The extracted data were summarized in tabular form and a narrative description was used to provide a summary of updated information. RESULTS: The ethnomedical uses of most prevalent 23 Panamanian species of Piper both in Panama as well in the world are provided. Of these species only Piper arboreum, Piper auritum, Piper cordulatum, Piper hispidum, Piper dariense, Piper multiplinervium and Piper umbellatum have ethnomedical uses in Panama. Some of the uses are by native Amerindians of Panama. These include ailments such as liver pains, common colds, skin infections, insecticidal, as a bath to alleviate colds, snakebites, different types of pains, skin ailments, wound healing, rheumatism, women's health, antipyretic, and anti-inflammatory. Other Panamanian species are widely used in many countries of the world. Of all the Piper species, P. aduncum has the most ethnomedical uses. Panamanian uses are different from the ones in other countries. A total of 61 compounds present in Piper species reported in this review have shown a variety of biological activities in vitro. These compounds belong to different chemical types, such as chromenes, amides, alkaloids, benzopyrans, benzoates, essential oils, pyrrolidines, flavokaines, chalcones, methylenedioxy propiophenones, cinnamates, monoterpenes, sesquiterpenes, phenols, among others. From this review it is evident that extracts and pure compounds isolated from Piper species have shown a wide array of mainly in vitro activity and some ethnomedical uses may be correlated with their activities reported. CONCLUSIONS: Plants of this genus have provided bioactive species, both from crude extracts and pure compounds thus substantiating their efficacy in traditional medicine. In vivo and toxicological studies are still limited, but the results of different activities of Piper reported point out the great potential of these species for obtaining bioactive principles that may be useful in treating diseases. However, a thorough investigation of Piper species relating to chemistry, in vivo pharmacological activities, with emphasis on their mechanism of action, safety and efficacy and toxicity is warranted.

Altered Long- and Short-Range Functional Connectivity in Patients with Betel Quid Dependence: A Resting-State Functional MRI Study.

OBJECTIVE: Addiction is a chronic relapsing brain disease. Brain structural abnormalities may constitute an abnormal neural network that underlies the risk of drug dependence. We hypothesized that individuals with Betel Quid Dependence (BQD) have functional connectivity alterations that can be described by long- and short-range functional connectivity density(FCD) maps. METHODS: We tested this hypothesis using functional magnetic resonance imaging (fMRI) data from subjects of the Han ethnic group in Hainan, China. Here, we examined BQD individuals (n = 33) and age-, sex-, and education-matched healthy controls (HCs) (n = 32) in a rs-fMRI study to observe FCD alterations associated with the severity of BQD. RESULTS: Compared with HCs, long-range FCD was decreased in the right anterior cingulate cortex (ACC) and increased in the left cerebellum posterior lobe (CPL) and bilateral inferior parietal lobule (IPL) in the BQD group. Short-range FCD was reduced in the right ACC and left dorsolateral prefrontal cortex (dlPFC), and increased in the left CPL. The short-range FCD alteration in the right ACC displayed a negative correlation with the Betel Quid Dependence Scale (BQDS) (r=-0.432, P=0.012), and the long-range FCD alteration of left IPL showed a positive correlation with the duration of BQD(r=0.519, P=0.002) in BQD individuals. CONCLUSIONS: fMRI revealed differences in long- and short- range FCD in BQD individuals, and these alterations might be due to BQ chewing, BQ dependency, or risk factors for developing BQD.

The Role of Physical Activity in Harm Reduction among Betel Quid Chewers from a Prospective Cohort of 419,378 Individuals.

OBJECTIVE: To assess the benefits of regular exercise in reducing harms associated with betel quid (BQ) chewing. METHODS: The study cohort, 419,378 individuals, participated in a medical screening program between 1994 and 2008, with 38,324 male and 1,495 female chewers, who consumed 5-15 quids of BQ a day. Physical activity of each individual, based on "MET-hour/week", was classified as "inactive" or "active", where activity started from a daily 15 minutes/day or more of brisk walking (≥3.75 MET-hour/week). Hazard ratios for mortality and remaining years in life expectancy were calculated. RESULTS: Nearly one fifth (18.7%) of men, but only 0.7% of women were chewers. Chewers had a 10-fold increase in oral cancer risk; and a 2-3-fold increase in mortality from lung, esophagus and liver cancer, cardiovascular disease, and diabetes, with doubling of all-cause mortality. More than half of chewers were physically inactive (59%). Physical activity was beneficial for chewers, with a reduction of all-cause mortality by 19%. Inactive chewers had their lifespan shortened by 6.3 years, compared to non-chewers, but being active, chewers improved their health by gaining 2.5 years. The improvement, however, fell short of offsetting the harms from chewing. CONCLUSIONS: Chewers had serious health consequences, but being physically active, chewers could mitigate some of these adverse effects, and extend life expectancy by 2.5 years and reduce mortality by one fifth. Encouraging exercise, in addition to quitting chewing, remains the best advice for 1.5 million chewers in Taiwan.

Betel quid dependence is associated with functional connectivity changes of the anterior cingulate cortex: a resting-state fMRI study.

OBJECTIVE: It is generally acknowledged that drug dependence is connected with abnormal functional organization in the individual's brain. The present study aimed to identify the anterior cingulate cortex (ACC) abnormality with the cerebral networks involved in betel quid dependence (BQD) by resting-state functional connectivity (rsFC) using functional magnetic resonance imaging (fMRI). METHODS: With fMRI data measured from 33 resting-state BQD individuals and 32 non-addicted and age-, sex-, education-matched healthy controls, we inquired into the BQD-related changes in FC between the regions of ACC with the whole brain involved in BQD individuals using a region of interest vised method, and to identify the relation of the alteration with the severity of BQD and duration. RESULTS: Compared to controls, the BQD group showed increased connectivity from ACC to the regions of the reward network (brainstem including midbrain regions such as the ventral tegmental area and pons, caudate, thalamus) and cerebellum. Decreased connectivity was observed in the BQD group in regions from ACC to the default mode network (medial prefrontal cortex and precuneus) and para Hippocampal/hypothalamus. Specifically, the BQD scale was positively correlated with increased FC of right ACC to left thalamus and left ACC to pons; the durations were negatively correlated with FC of right ACC to left precuneus. CONCLUSION: These disturbances in rsFC from ACC to the reward network and DMN revealed by fMRI may have a key function in providing insights into the neurological pathophysiology underlying BQD-associated executive dysfunction and disinhibition. These findings may contribute to our better understanding of the mechanisms underlying BQD.

A review of the literature and latest advances in research of Piper sarmentosum.

CONTEXT: Piper sarmentosum Roxb. (Piperaceae) is a traditional medicinal as well as a culinary plant in South East Asian countries, whereby aerial parts of the plant are consumed as a vegetable in various forms and the whole plant or parts are used as folk remedies, alone or in combination with other herbs, to treat various ailments. The plant has extensively been investigated in a broad range of studies to provide scientific evidence for folklore claims or to find new therapeutic uses; however, heretofore, a summary of the data are not available. OBJECTIVE: In order to describe nutritional and therapeutic potential of P. sarmentosum and summarize scientific evidence that supports traditional claims, a literature review and latest advances in research of the plant are given herein. MATERIALS AND METHODS: The literature has been retrieved from a number of databases such as Google Scholar, PubMed, Medline, Science Direct and SciFinder. The articles related to synthetic work, ecology and agriculture have been excluded. RESULTS AND DISCUSSION: The review has not only revealed a number of pharmacological activities supporting the traditional claims but indicates new prospects for the plant. Antiangiogenic activity and toxicity studies suggest the usage of the plant in treating diseases involving neo-vascularization. The available efficacy, safety, pharmacokinetic and stability data urge clinical studies on extracts of the plant. CONCLUSION: The present review may be helpful to future researchers intending to investigate the plant and natural pharmaceutical industry for preparing evidence-based formulations.

Necrosis cutánea profunda por la aplicación local de hojas de Piper auritum Kunth (caisimón de anís) / Deep cutaneous necrosis caused by the local application of Piper aurifum Kunth (caisimón de anis) leaves

Introducción: Piper auritum Kunth (caisimón de anís) es una de las plantas más utilizadas tradicionalmente en Cuba por sus propiedades antiinflamatorias, analgésicas y cicatrizantes. Objetivos: reportar un caso clínico que sufrió una reacción adversa por automedicación de hojas de Piper auritum. Métodos: se revisó la literatura y la historia clínica de una paciente femenina atendida en el servicio del Hospital Universitario Dr Miguel Enríquez, Servicio de Cirugía Plástica y Caumatología. Resultados: se presentó el caso de una paciente que sufrió lesiones por quemaduras hipodérmicas y sus consecuencias al aplicar hojas de P auritum de forma incorrecta sobre la piel de las mamas, que necesitaron autoinjertos de piel laminar de espesor parcial medio con resultados satisfactorios. Conclusiones: es importante la orientación por personal especializado para el uso de las plantas medicinales

Introduction: Piper aurifum Kunth (caisimón de anis) is one of the most used plants traditionally in Cuba because of its anti-inflammatory, analgesic and healing properties. Objectives: to report a clinical case suffering from an adverse reaction caused by self-medication with Piper aurifum leaves. Methods: the medical literature and the medical history of a female patient, who was seen at Dr Miguel Enríquez university hospital plastic surgery and burn treatment service, were reviewed. Results: the case of a patient who suffered lesions from hypodermic burns caused by the wrong application of P aurifum leaves on the breast skin was presented. It was necessary to use laminar skin autografts of average partial thickness to cure the lesions, with satisfactory results. Conclusions: it is important that specialists provide appropriate instructions about the use of medicinal plants

Betel quid extract promotes oral cancer cell migration by activating a muscarinic M4 receptor-mediated signaling cascade involving SFKs and ERK1/2.

Betel quid (BQ) is a widely accepted etiological factor for oral squamous cell carcinoma (OSCC) in Southeast Asia, but how BQ chewing leads to oral carcinogenesis remains to be elucidated. We have previously demonstrated that the activation of Src family kinases (SFKs) is critical for BQ-induced oral cancer cell motility. Here we investigate whether this biological effect is mediated by specific membrane receptors in oral cancer cells. We found that BQ-induced activation of extracellular signal-regulated kinase 1/2 (ERK1/2) and cell migration could be inhibited by atropine, suggesting the involvement of the muscarinic receptor family. The enhanced activities of ERK1/2 and cell migration were significantly counteracted by PD102807, the selective antagonist of muscarinic M4 receptor. Moreover, cold BQ extract effectively competed with a known ligand, [(3)H]-N-methyl scopolamine, for binding to muscarinic M4 receptor in vitro, thereby implying that BQ could activate motility-promoting signaling pathways through direct interaction with the receptor. The requirement of muscarinic M4 receptor for BQ-induced oral cancer cell migration was demonstrated by knockdown of the receptor using RNA interference (RNAi). Remarkably, ectopic expression of muscarinic M4 receptor in two oral cancer cell lines, Ca9-22 and SCC-9, further augmented BQ-induced cell migration by 83% and 99%, respectively. Finally, we verified that BQ-induced oral cancer cell migration was mediated through a muscarinic M4 receptor-->SFKs-->ERK1/2 signaling pathway. Thus, our findings have identified a novel signaling cascade mediating BQ-induced oral cancer cell motility, which could be a therapeutic target for BQ-related oral malignancies.

Risk of betel quid chewing on the development of liver cirrhosis: a community-based case-control study.

PURPOSE: The role of betel quid on the development of liver cirrhosis is unclear; we thus designed a community-based case-control study to evaluate the association between betel quid chewing and liver cirrhosis. METHODS: A total of 42 cases of liver cirrhosis and 165 matched controls were included for analysis. Questionnaires were administered to obtain histories of betel quid chewing, alcohol consumption, smoking, and family history of liver disease. Hepatitis B surface antigen and anti-hepatitis C antibody were also determined by immunoassay. RESULTS: Individuals with more betel quid chewing (more than 55 quid-years vs. less than 55 quid-years and never-chewers, matched odds ratio [OR(m)] = 2.2; 95% confidence interval [CI]: 1.0-5.0) had higher risks for liver cirrhosis. The combined effects on liver cirrhosis by betel quid chewing and the number of other risk factors, including hepatitis B virus (HBV) infection, smoking, and alcohol drinking, were also observed. When individuals with less betel quid chewing (less than 55 quid-years and never-chewers) and with no other risk factors used as a reference, betel quid chewers expressing greater betel quid chewing (more than 55 quid-years) and more risk factors of HBV infection, cigarette smoking, and habitual alcohol drinking expressed a greater risk of liver cirrhosis (OR(m) = 70.8; 95% CI: 4.0-1260.1). CONCLUSIONS: Our results suggest that betel quid chewing may play an important role in the development of hepatic cirrhosis. Larger study and cohort studies would be necessary to provide further evidence regarding this finding.