Background To date, it is not clarified whether patients with gastric polyps without any alarming symptoms for colorectal neoplasia need colonoscopy screening. The objective of this study is to prospectively determine the association between gastric polyps and colorectal neoplasia.Methods A multicenter prospective cross-sectional study was performed from July 2012 to December 2014. We compared patients with and without gastric polyps for prevalence of colorectal adenomas. The odds ratios (OR) were computed by logistic regression analysis after multivariable adjustments.Results Totally 1546 patients were included, with 770 patients in the gastric polyp group and 776 in the age- and sex- matched control group. Patients with gastric polyps had greater odds of having any colorectal adenoma  and advanced colorectal adenomas  than those without. The positive association between gastric polyps and colorectal adenomas remained significant in both women  and men . Patients over the age of 40 with gastric polyps had a higher prevalence of colorectal adenomas than those without .Conclusions The presence of gastric polyps is significantly associated with a higher prevalence of colorectal adenomas, especially advanced colorectal adenomas. Colonoscopy might be considered in patients with gastric polyps, of any gender, and over the age of 40. Colonoscopy is widely accepted as a primary tool in screening for colorectal cancer (CRC) and precancerous polyps 9 The combined analysis of five heterogeneous retrospective studies suggested that the prevalence of colorectal neoplasms was 1.15 to 1.31 times higher in patients with gastric polyps than those without, focusing mainly on fundic gland polyps (FGP) To date, available knowledge regarding this issue is limited and has been gathered in a meta-analysis.Therefore, the current evidence regarding the association between sporadic gastric polyps and colorectal neoplasia remains scarce, mainly based on restricted-sized retrospective studies. To address this issue, we conducted a large multicenter prospective cross-sectional study to investigate the potential relationship between the presence of gastric polyps and prevalence of colorectal adenomas.We performed a cross-sectional study (ChiCTR--OCC-12003010) by matching at-risk subjects (those with gastric polyps) and disease-free subjects (those without gastric polyps) and determining the likelihood that these patients had colorectal adenomas, including advanced colorectal adenomas. This multicenter study was conducted in the First Affiliated Hospital of Sun Yat-sen University, Shantou Central Hospital, and Meizhou People's Hospital. Consecutive subjects who underwent esophagogastroduodenoscopy (EGD) were prospectively enrolled between July 2012 and December 2014. Participants in the gastric polyp group had different types of polyps, detected by EGD and confirmed by pathology, including FGP, gastric hyperplastic polyps, adenomas, and inflammatory polyps. The control group comprised of sex- and age-matched participants without detection of gastric polyps by EGD during the same period, randomly selected using a one-to-one matching approach. Both groups of patients underwent total colonoscopy at the same day or within six months of the EGD procedure. Participants were included if they were between the ages of 18 and 74, and excluded according to the following criteria: 1) having a history of gastrointestinal tumors or colorectal polyps; 2) having a history of gastrointestinal surgery, including colorectal polypectomy; 3) having a history of inflammatory bowel disease, intestinal tuberculosis, or familial colorectal polyposis syndrome; 4) presenting with alarm symptoms of CRC, including hematochezia, positive fecal occult blood test, recent bowel habit changes, significant weight loss, or anemia; 5) failing to undergo colonoscopy within six months after EGD; 6) technically unsatisfactory colonoscopy owing to poor or inadequate bowel preparation or incomplete colonoscopy; and 7) with gastric polyps that were histologically confirmed as carcinoid tumors, lymphomas, fibromas, lipomas, leiomyomas, ectopic pancreatic tissues, or normal tissue.The study was conducted and reported according to the study protocol, conforming to the ethical guidelines of the 1975 Declaration of Helsinki, which was approved by Ethics Review Committees at each study center on 28 June, 2012. Written informed consents were obtained from participants upon their arrival at the study clinic and before the procedures.At each participating center, EGD and colonoscopy procedures were performed by experienced gastroscopists and colonoscopists respectively, who had performed at least 2000 gastroscopies, 1000 colonoscopies, and 200 polypectomies. Patients were prescribed two liters of polyethylene glycol oral lavage for bowel preparation 4 to 6 hours before the colonoscopy procedure. All polyps detected during EGD and colonoscopy were recorded, including the number, size, and location. Polyp size was estimated endoscopically using open biopsy forceps, or measured following specimen resection. Gastric polyps were classified according to their location in the fundus, body, antrum, cardia, or pylorus. The locations of colorectal polyps were categorized as right colon , left colon , or both right and left colon, as previously reported The primary outcome was the association between the presence of gastric polyps and the prevalence of colorectal adenomas. The secondary outcome was the prevalence of advanced colorectal adenomas among subjects with gastric polyps compared to those without. We also sought to determine whether these associations differed when patients were stratified by sex and age. Patients with advanced adenomas were classified as having at least one adenoma with at least one of the following characteristics: size of ≥10 mm in diameter, tubulovillous or villous components, or high-grade dysplasia Helicobacter pylori (H. pylori) infection was checked by urea breath tests or urease tests.Data regarding baseline characteristics of the participants were collected, including age, sex, body mass index (BMI), educational level, symptoms, family history of CRC, current smoking (≥1 cigarette per day for more than one year), alcohol consumption (at least 70 g per week), non-steroidal anti-inflammatory drugs (NSAIDS)/aspirin use (for at least three months) Symmetrically distributed continuous variables were presented as means with standard deviations, while categorical variables were presented as frequencies and percentages. To compare the baseline characteristics of participants in each group, we used the Pearson's chi-squared test for analysis of discrete variables and a t-test for continuous variables. We examined the association between gastric polyps and colorectal adenomas using binary logistic regression analysis. Adjusted odds ratios (OR) and their corresponding 95% confidence intervals (CI) were estimated by multivariable adjustments of baseline factors. In addition, we evaluated the relationship between gastric polyps and colorectal adenomas according to the number, size, location, and histopathology of both gastric polyps and colorectal adenomas, using both unadjusted and adjusted ORs and their corresponding 95% CIs. We also compared the presence of colorectal adenomas in patients with and without gastric polyps after stratifying by age and sex.Pre-specified subgroup analysis was performed based on baseline covariates. Whether the prevalence of colorectal adenoma differed in certain pre-specified subgroups was assessed by testing the interaction effect between gastric polyps and subgroups with the use of logistic models.All statistical analyses were performed using the Statistical Product and Service Solutions (SPSS) software, version 22.0 . All two-tailed tests were regarded as significant with a p value of less than 0.05. Figure 1. After excluding patients who failed to undergo colonoscopy within six months after EGD and patients with a technically unsatisfactory colonoscopy, 800 subjects with different types of gastric polyps, detected by EGD and confirmed by pathology, were enrolled according to the inclusion criteria. During the same time period, 800 sex- and age-matched gastric polyp-free control patients were enrolled. The indications for EGD included abdominal pain, gastroesophageal reflux, dyspepsia, upper gastrointestinal bleeding, and screening. After the application of strict exclusions, 1546 individuals were finally included, with 770 in the gastric polyp group and 776 in the gastric polyp-free control group.A detailed participant enrollment process is presented inTable 1. Subjects in these two groups did not differ significantly in age, sex, BMI, education level, positive CRC family history, hypertension, fasting hyperglycemia, steatosis, or potential use of chemopreventive agents, including NSAIDS and aspirin. However, significantly fewer subjects in the gastric polyp group were symptomatic , had current smoking, alcohol consumption, and positive H. pylori infection than those in the gastric polyp-free group. Lipid profiles differed significantly between the two groups, except for triglyceride levels.Baseline characteristics were compared between patients with and without gastric polyps and the results were shown in Table 2 presents the ORs of gastric polyps and baseline factors for colorectal adenomas as well as advanced colorectal adenomas. After multivariable adjustments, we found that subjects with gastric polyps had greater odds of having any colorectal adenoma  as well as advanced colorectal adenomas  compared with those in the control group. The adjusted ORs of gastric polyps for colorectal adenomas in the First Affiliated Hospital of Sun Yat-sen University, Shantou Central Hospital, and Meizhou People's Hospital were 3.56 , 2.35  and 2.65 , respectively.During the study period, we detected colorectal polyps in 506 participants by colonoscopy, including 198 of the 776 patients (25.5%) who did not have gastric polyps, and 308 of the 770 patients (40.0%) who did. Among the control group, we identified 133 subjects (17.1%) with any type of colorectal adenoma, of which 35 (4.5%) were classified as having advanced colorectal adenomas. In the gastric polyp group, 229 subjects (29.7%) had any type of colorectal adenoma, of which 77 (10.0%) had advanced colorectal adenomas. Table 3). Besides adenomas, we found no difference in the prevalence of colorectal hyperplastic polyps  between patients with and without gastric polyps. Furthermore, we found that the prevalence of CRC was 1.3% (10/776) in the gastric polyp group and 0.3% (2/770) in the control group, with an adjusted OR of 7.05  . However, we found no significant correlation between gastric inflammatory polyps and the detection of advanced colorectal adenomas .Patients with gastric polyps had significantly higher prevalence of colorectal adenoma and advanced adenomas, when stratified by the number, distribution, size, histopathology of gastric polyps, and whether Table 5). For men, subjects with gastric polyps had higher prevalence of any colorectal adenoma  and advanced colorectal adenomas . However, the associations of gastric polyps with CRC were not significant in men , mainly due to limited cases of CRC. Furthermore, we found no significant association between gastric hyperplastic polyps and the prevalence of any colorectal adenoma type in men (Table 5).Women with gastric polyps had higher prevalence of any colorectal adenoma  as well as advanced colorectal adenomas  compared with those without gastric polyps. Such significant associations remained in any type of colorectal neoplasia when FGP and gastric hyperplastic polyps were analyzed separately (Table 6).Patients over the age of 40 with gastric polyps were associated with a higher prevalence of any adenoma  and advanced adenomas . The association remained significant in patients with FGP. In patients with gastric hyperplastic polyps over the age of 50, we detected a significantly higher rate of colorectal adenomas. In subjects under 40 years of age, no significant associations between gastric polyps and colorectal adenomas were detected . Subgroup analysis suggested no significant interactions in any of the 17 predefined subgroups .The increase in colorectal adenoma prevalence in patients with gastric polyps was accordant across all major subgroups based on baseline factors  and advanced colorectal adenomas (10.0%) were observed in patients with gastric polyps compared to the matched control group . Both men and women with gastric polyps had significantly higher prevalence of colorectal adenomas than those of control groups. Furthermore, Subjects over the age of 40 with gastric polyps were more likely to have both advanced and malignant colorectal adenomas.H. pylori infection rate in the gastric-polyp group at baseline. It is known that H. pylori infection are negatively associated with FGP H. pylori infection rate in the gastric-polyp group. Despite this, strong positive correlation between gastric polyps and colorectal adenomas still exists after adjusting the confounding effects of these factors.Although previous studies have shown that FGP The finding that higher prevalence of colorectal adenomas among patients with gastric polyps in this study are of clinical significance, because of the malignancy potential of colorectal adenomas Male gender is a recognized risk factor for colorectal neoplasia The risk of colorectal neoplasia increases with age H. Pylori infection and colonic neoplasia The association between gastric and colorectal neoplasia is well clarified in hereditary cancer syndromes, such as familial adenomatous polyposis (FAP) There were a few shortcomings of this study. First, colonoscopy was performed only within six months of EGD. Due to the prolonged formation and slow growing of polyps In summary, our results demonstrate that the presence of gastric polyps, regardless of their number, size, location, or pathology, is an independent risk factor for the detection of colorectal adenomas, particularly advanced adenomas. We recommend screening colonoscopy in patients of both sexes over the age of 40 with gastric polyps. Further studies are required to elucidate the initiation of de novo colorectal polyps among patients with gastric polyps, the cost effectiveness of such a colonoscopy screening approach, the application of our results to Western countries, and the clarification of the precise mechanism underlying the close relationship between gastric and colorectal polyps.Supplementary figures and tables.Click here for additional data file.


After adjustment for age and gender, the odds of having MetS was significantly higher for patients with WD GEP-NET grade G1 (OR 4.35 95%CI 1.30–14.53) and disseminated disease (OR 4.52 95%CI 1.44–14.15). GEP-NET primary tumor location or secretory syndrome did not influence the risk for MetS. None of the tumor characteristics evaluated were associated with body mass index, fasting plasma glucose category, or any of the individual MetS components. Patients with GEP-NET and MetS depicted a higher risk of presenting a lower tumor grade and disseminated disease. The positive association between MetS and GEP-NET characteristics further highlights the potential link between the two conditions.The association of well-differentiated gastro-entero-pancreatic neuroendocrine tumors (WD GEP-NETs) with metabolic syndrome (MetS), abdominal obesity, and fasting glucose abnormalities was recently described. The aim of this study was to evaluate whether the presence of MetS or any MetS individual component was also influenced by GEP-NET characteristics at diagnosis. A cohort of patients with WD GEP-NETs ( Gastro-entero-pancreatic neuroendocrine tumors (GEP-NETs) were previously a rare entity before the 6.5-fold increase in incidence observed over the past four decades . As a maOne of the most remarkable achievements of oncology in the 21st century was the finding that most cancers could be preventable diseases . The assThe aim of the current study was to evaluate whether the presence of MetS and individual MetS components at the time of WD GEP-NET diagnosis was associated with any specific tumor characteristics, such as grading, staging, primary tumor location, or hormonal hypersecretion, that were likely to influence the tumor biological behavior and disease prognosis.Patients with confirmed WD GEP-NETs were recruited from the Endocrine Tumors Clinic of a single large tertiary referral center for oncologic diseases (Portuguese Oncology Institute of Porto (IPO P)). The inclusion criteria included having a confirmed diagnosis of WD GEP-NETs by histopathology and/or PET-68Ga-DOTA-NOC. Patients excluded from the study were those who were younger than 18 years old when first diagnosed, as well as those harboring familial GEP-NETs, neuroendocrine carcinoma (NEC), and/or a type 1 gastric endocrine tumor (T1-GET), as these tumors are recognized as having a distinctive and well-established etiology and biological behavior .n = 159), those who did not fulfill the inclusion criteria or had insufficient data for analysis were excluded, while the remaining eligible patients were included in the study for statistical analysis (n = 136). Tumors were classified according to primary tumor location: gastrointestinal (GI-NET) or pancreatic (pNET); functioning or non-functioning (F or non-F); pathological WHO grading into G1  and G2  and disease extension  [68Ga-DOTA-NOC (n = 6). Patients with WD GEP-NETs metastatic tumors and carcinoid syndrome without any visible pancreatic or thoracic lesions on imaging studies were assumed as midgut primary tumor (n = 2). No insulinoma or rare functional pancreatic NET presenting with hyperglycemia, such as glucagonoma, VIPoma, or somatostatinoma, were included in this series [From the patients with confirmed WD GEP-NETs that consented to participate in the study (ysis n = 6. Tumorss series .Patients with WD GEP-NETs were assessed for body mass index (BMI) class , fastingData for analysis were collected during face-to-face patient interviews, to assess past medical history of T2DM, hypertension, dyslipidemia, ongoing medications, and family history of T2DM. Anthropometric parameters, such as height, weight, waist circumference (WC), and blood pressure (BP) were measured during the study visit. Additionally, biochemical data, including FPG and lipid profile, were evaluated after blood sampling in our institution for treatment-naïve patients, or retrospectively through data-files recollection of parameters before initiation of any treatment intervention at the referring healthcare institutions, whenever the patient was already under pharmacological treatment when first observed at our center.2), overweight (BMI 25–29.9 kg/m2), or obese (BMI ≥ 30 kg/m2) [Patients were classified into three categories according to BMI: normal weight (BMI < 25 kg/m0 kg/m2) . They we0 kg/m2) . MetS wa0 kg/m2) : WC ≥ 88This study was approved by the National Data Protection Committee (CNPD /4906/2015) and Institutional Ethics Review Board (IPOP/366/2013). All participants provided informed consent prior to study enrolment.t test or ANOVA, while medians were compared using the Mann–Whitney or Kruskal–Wallis tests.Statistical analysis was performed using IBM SPSS Statistics version 24.0 . Categorical and continuous variables were summarized using descriptive statistics . Proportions were compared using the Chi-square or Fisher’s exact test, as appropriate. Means were compared using Student’s A backward stepwise  method was used to obtain a multivariable logistic regression model, using the patient and tumor characteristics . A level of significance of 0.05 was adopted.n = 134) was divided into two groups, according to baseline characteristics and considering the absence (n = 57) or presence of MetS (n = 77) at the time of tumor diagnosis (p = 0.014), older (p < 0.001), and had a higher BMI at diagnosis (p < 0.001). When comparing the two patient groups, there was a homogeneous distribution in terms of primary tumor location (p = 0.652), presence of hormonal secretion syndrome (p = 0.187), and metastatic disease (p = 0.104). Grade 1 (G1) tumors were found to be more frequent in the MetS group; although, the difference was not statistically significant (p = 0.076) (The cohort of patients with WD GEP-NETs (iagnosis . Patient= 0.076) .p = 0.009) and increased with age (p < 0.001) (p = 0.010). In addition, G1 grade was found to be significantly associated with MetS , while the primary tumor location or hormonal secretory status of GEP-NETs did not influence the risk of MetS  . After a of MetS .No significant association was found between the primary tumor location of WD GEP-NETs, the presence of hormonal secretion syndrome, the tumor grading or disease extension, and the presence of any of the individual MetS components at diagnosis , or betwGEP-NETs are a group of heterogeneous neoplasms that may present considerable differences in what concerns primary tumor location, pattern of hormone secretion, proliferative behavior, and disease extension at diagnosis. Obesity, MetS, and T2DM were recognized as risk factors for several cancers ,9,18. ThThe incidence of GEP-NETs increased over the last four decades, disclosing a current prevalence of 6.4 cases/100,000 inhabitants . The ups+ T cells, which are key players in mediating immunity to tumors, for immune-mediator anticancer effects [The core pathological feature that characterizes MetS is hyperinsulinism. In turn, hyperinsulinism leads to the subsequent activation of the insulin-IGF1 axis that has been theoretically proposed to support the relevance of MetS for WD GEP-NET biology . Consequ effects . Indeed, effects .Our study aimed to evaluate the association of the four main characteristics of WD GEP-NETs, namely primary tumor location, presence of hypersecretion syndrome, WHO grade, and stage, with the occurrence of MetS. We were able to demonstrate, for the first time, that patients with WD GEP-NETs and MetS, independent of age or gender, are more likely to have lower-grade tumors or present advanced-stage disease at diagnosis. In fact, despite the fact that patients with MetS were more likely to be older, in parallel to what is observed in the general background population, this parameter was not shown to influence WD GEP-NET characteristics . MoreoveOne of the main strengths of this study is that it enrolled a reasonably large patient cohort for what is considered a relatively rare disease, along with consistent data retrieval, since all clinical and anthropometrical parameters were assessed by a single clinical researcher. However, some limitations must also be acknowledged. First, this study was conducted in a single center; therefore, and despite the sample size, these results require further validation, ideally in multicenter prospective studies. In addition, since our study was conducted in an end-of-line tertiary center, a small proportion of patients with WD GEP-NETs were already under pharmacological treatment for the disease when referred and first evaluated at our center. For these cases, clinical parameters were obtained retrospectively to minimize any possible bias for statistical analysis concerning data before treatment initiation. Last, but not least, other potential confounding factors, such as family history of cancer, cigarette smoking, alcohol consumption, dietary habits, physical activity, occupation, and socioeconomic status, were not evaluated in this study; therefore, we are unable to estimate whether these could have had any impact on the study results.Overall, our data emphasize the unmet need to further explore the mechanisms underlying the association of obesity, abdominal obesity, and the metabolic abnormalities that characterize MetS with GEP-NETs, as such an exploration could not only improve the knowledge of the causes for the recently increased burden of these tumors, but it could also open a field of work that might lead to the disclosure of novel and more effective preventive and treatment avenues, as already described for other types of cancer.In conclusion, this study demonstrates, for the first time, a positive association of MetS with WD GEP-NETs disease extension and tumor grade. Our results demonstrate that patients with WD GEP-NETs and MetS are more likely to have tumors with better differentiation and disseminated disease at diagnosis, independent of primary tumor location and hormonal status. Our findings suggest that further research on the mechanisms underlying the metabolic abnormalities associated with WD-GEP-NETs is warranted, as these underlying mechanisms could potentially harbor the keys for novel and more effective preventive and treatment interventions.


The positive control leupeptin showed effects on cathepsin L at a 20-fold lower concentration compared to the respective LC50 (0.4 mM) of the zebrafish embryo assay (FET). The observed effects on the enzyme activity of the four other xenobiotics were not or just slightly more sensitive (factor of 1.5 to 3), but the differences did not reach statistical significance. Results of this study indicate that the analysed cathepsins are not susceptible to toxins other than the known peptide-like inhibitors. However, specific cathepsin inhibitors might be identified using the zebrafish embryo. Cathepsins have been proposed as biomarkers of chemical exposure in the zebrafish embryo model but it is unclear whether they can also be used to detect sublethal stress. The present study evaluates three cathepsin types as candidate biomarkers in zebrafish embryos. In addition to other functions, cathepsins are also involved in yolk lysosomal processes for the internal nutrition of embryos of oviparous animals until external feeding starts. The baseline enzyme activity of cathepsin types H, C and L during the embryonic development of zebrafish in the first 96 h post fertilisation was studied. Secondly, the effect of leupeptin, a known cathepsin inhibitor, and four embryotoxic xenobiotic compounds with different modes of action —an inhibitor of ATP synthesis; and tebuconazole—a sterol biosynthesis inhibitor) on  Danio rerio, Hamilton-Buchanan 1822), an established ecotoxicological and toxicological model organism. Zebrafish embryos are applied in the ‘fish embryo acute toxicity test’ (FET) Danio rerribed in . Within ribed in , as described in , with a rding to  using anDanio rerio embryos (FET) 33], deteMany authors have suggested the indicative potential of embryonic cathepsins in the monitoring of disturbances in embryonic development. The present study tested this hypothesis by analysing three embryonic cathepsins as biomarkers for xenobiotic stress in zebrafish embryos. The experiments with four xenobiotics and one specific and known cathepsin inhibitor show that the measured cathepsins do not seem to exhibit the sensitivity attribute requested for candidate biomarkers . In addi


Mammals live and thrive in environments presenting ongoing threats from parasites in the form of biting flies, ticks and intestinal worms and from pathogens as wound contaminants and agents of infectious disease. Several strategies have evolved that enable animals to deal with parasites and pathogens, including eliminating away from the sleeping–resting areas, use of an array of grooming techniques, use of saliva in licking, and consuming medicinal plant-based compounds. These strategies all are species-specific and reflect the particular environment that the animal inhabits.This article is part of the Theo Murphy meeting issue ‘Evolution of pathogen and parasite avoidance behaviours’. With the prevalence of medicine in the everyday lives of humans and their domesticated animals, it is a challenge to imagine how animals, and even prehistoric humans, living in nature with no access to vaccinations, antibiotics, worm treatments, wound medicine and the like, survive, and even thrive, as they do. The theme of this paper is to portray a sampling of behavioural adaptations that have evolved in various species and contexts to reveal how mammals do as well as they do in nature using evolved behavioural strategies to avoid and reduce infection by parasites and pathogens.A discourse on how animals stay healthy in nature could cover a wide variety of vertebrate species, and even some non-vertebrate species, given recent research. However, staying with mammals illustrates the broad range of parasite–pathogen avoidance strategies in a group of animals with which readers are familiar. In addition, several of the avoidance strategies have been studied in greater detail in domestic mammals than is possible in the wild mammalian counterparts, lending a wider perspective to the mammals living in nature. Some aspects of this paper have been presented previously ,2. This One overriding concept that comes through is that animals living in nature are nowhere as free of parasites and pathogens as we might expect from looking at domestic animals. For external parasites such as fleas and ticks, and for intestinal parasites such as roundworms and tapeworms, there is a manageable parasite load in most cases that presumably does not impact fitness in a major way. Almost all defensive behaviours are carried out at some costs, such as reduced vigilance for predators or loss of feeding time; hence, having a manageable parasite load is adaptive in nature, representing a balance between parasite load and other physiological demands. This perspective is different from that in modern medicine, where administration of drugs and treatments carries no implications for reduced predator avoidance or food accessibility.The evolution of avoidance and removal strategies for pathogens and parasites implies that the strategies evolved when there were survival and fitness pay-offs. The particular environment where an animal lives may present a particular parasite/pathogen threat that does not occur in other environments. Thus, for the widespread African antelope, the impala, discussed below, which typically inhabits the interface between wooded areas and grasslands as a defence against predators, ticks are very prevalent, and tick removal by tooth combing is very prominent. Some small rodents and felids, on the other hand, spend most of their time in dens and nearby rest areas where there is less risk from ticks but where fleas multiply by jumping back and forth between the den and rest area and the hosts’ pelage. Small felids have an evolved flea removal system, relying on systematic grooming with the tongue flea-combing morphology. For the dusky-footed wood rat, which typically finds a secure nest in a clump of sticks at the base of a bay leaf tree, fleas are also a major threat. However, the wood rats have evolved a different flea control strategy, that of bringing in fresh aromatic bay leaves that repel adult fleas and kill flea larvae that manage to hatch from ova.2.Biting flies can be more than just an annoyance. Several studies have revealed the considerable costs of flying parasites. Tabanid flies, common in Asia, East Africa and the USA, offer a good example. A study on horses found that on a typical day a horse may be bitten by about 4000 tabanid flies, accounting for a loss of as much as 0.5 l of blood . In addiper capita encounter with flies is diluted, the so-called encounter-dilution effect [One common means of avoiding such flies is grouping, where the n effect . Ungulatn effect –7.While on most of the body elephants have fly-resistant thick skin that large tabanids cannot penetrate, they have thinner skin on the belly, in the axillae and behind the ears, and the flies target those sites. As mentioned, flies can remove considerable blood and be costly to the animal. While the trunk would be hopeless at swatting flies, Asian elephants have evolved a way of avoiding the biting flies with a fly switch consisting of a tree branch that allows the elephant to repel flies from the belly, axillae and around the ears . In an e3.Ungulates are particularly vulnerable to ticks as they graze in grasslands. Engorging pregnant female ticks can remove considerable blood. Studies on growing cattle, for example, have revealed that a single engorging tick can reduce the annualized weight gain of a growing calf by 3 kg ,11.For most ungulates, the first attempt at avoiding ticks is to swipe the tongue or lower incisors across the shoulders and trunk as the ticks crawl up legs and across the shoulders on the way to the head and neck or hindquarters, where they cannot be removed by oral grooming. Grooming has been especially studied in antelope of eastern and southern Africa. During grooming bouts, antelope swipe the lateral incisors across the shoulders, abdomen and flanks, presumably catching most of the traversing ticks . These lMuch of the grooming seen in antelope and other ungulates is referred to as programmed grooming, in which bouts of oral grooming are delivered to the body regularly, driven by an envisioned underlying central mechanism . This meThe environmental threat of tick exposure can influence the programmed grooming rate. For example, the dwarf antelope, steinbok, inhabits areas flush with vegetation and ticks. Another dwarf antelope of similar size, the klipspringer, inhabits rocky outcroppings that support few ticks. One would predict that the steinbok would have evolved a faster-paced programmed grooming rate than would have klipspringers. This was tested in a tick-free zoological environment where members of the two antelope species lived in adjacent enclosures. Klipspringers delivered oral grooming bouts at just 11% of the hourly rate of the steinbok ,17.The programmed grooming rate is also influenced by testosterone. In breeding male impala, vigilance over the females appears to reduce grooming time to about one-fourth that of the females. Correspondingly, males were found to carry about six times the tick load of females . Two relIn response to the ongoing threat from ticks reaching the head and neck area, where impala cannot remove them by self-grooming, impala have evolved a reciprocal allogrooming system of exchanging grooming bouts with another impala in a tit-for-tat manner that is unique among antelope. One impala approaches another in the group, often not related, and directs a bout of grooming episodes to the head or neck of the other. The partner typically reciprocates with an equivalent bout of grooming . This tiThe evolved innate basis of this reciprocal allogrooming system is evident in observations of newborn impala fawns where they can be observed in a tick-free zoological setting. These fawns exchanged bouts of grooming episodes with their dam or other females, and attempted to reciprocally allogroom with other fawns in the first week after birth. Even orphaned impala fawns raised with gazelles  repeatedly tried to initiate reciprocal grooming with the gazelles even though the gazelles never returned any grooming .Non-human primates, such as baboons and rhesus monkeys, have been studied extensively with regard to allogrooming, or social grooming, and the role in maintaining affiliative relationships. It has been estimated that some non-human primates invest at least one-fifth of their time in grooming . HoweverThis research on baboons may provoke other studies on various species of primates where social grooming is prominent. In nature, self-grooming and social grooming are the main ways of avoiding detrimental tick infestation in primates as in other frequently grooming species. For primates, it appears as though social grooming can have health consequences, adding an important dimension to the dynamics and stability of group social structure.Ectoparasites other than ticks can be removed by grooming in primates, and infestation with lice has been looked at recently. Theoretically, social grooming may provide a way that lice are transmitted between partners, increasing infestation, or grooming may remove lice, reducing the infestation. Investigators studying louse infestation and sociality in female Japanese macaques found that females interacting the most with grooming partners had fewer lice than those interacting with fewer partners . PresumaThe grooming picture for primates gets a bit more complicated with a recent study on intestinal parasites in vervet monkeys in South Africa, where investigators found a correlation between group size and degree of hookworm infection . The invThere are a couple of non-grooming approaches to the control of ticks that are relevant to the discussion on tick control in ungulates. One is a unique adaptation of impala for removing feeding ticks that make it to the ears that are not even accessible to a grooming partner. Impala will quite noticeably accommodate the foraging of oxpeckers on their heads, around their ears, and even hold quite still while oxpeckers forage inside their ears . Ungulat4.Turn next to the household pet that is regularly seen grooming its pelage—the domestic cat. Grooming in the cat is arguably a guide to what one would expect in a wild small cat species. Oral grooming typically occurs in bouts directed in a rostral–caudal direction, and appears to be centrally programmed, as is oral grooming in antelope . The maiIn an experiment in a flea-ridden environment with over 30 cats, Elizabethan collars were placed on nine cats to prevent oral grooming and flea counts three weeks later were compared with flea counts on nine control cats wearing no collars. The collared cats had double the number of fleas on the control cats .in vitro studies to get precise results. One in vitro experiment with adult fleas showed that a measured amount of bay leaf extract was as effective as the traditional N,N-diethyl m-toluamide (DEET) in repelling fleas [in vitro experiment with flea larvae, torn bay leaves killed 75% of the larvae, compared with almost none by control plants [Dusky-footed wood rats make nests in above-ground clumps of branches, usually in a grove of bay trees where they are safe from predators. However, the nest is also an ideal habitat for fleas, where they can feed on the wood rat, hop off and lay eggs, which develop into larvae that then easily re-infect the mammalian host. Wood rats have the unique behaviour of placing fresh bay leaves in the nest area. Investigators wondered if the aromatic bay leaves may be providing a way to avoid what could be an overwhelming flea infestation. This avoidance hypothesis was tested in ng fleas . In anotl plants . This nel plants ,34.5.Very important for mammals living in nature is control of intestinal parasites. Virtually all wild mammals carry some intestinal parasites and they generally manage a modest intestinal parasite load with no evident effects. Parasitic round-worms (helminths) expel ova in faeces, which within a few days (depending upon moisture) hatch into mobile larvae that shortly become infective to new hosts.For herbivorous ungulates, intestinal parasites are very important because infective larvae are consumed as they crawl up on blades of grass, or other plants, and are eaten by the foraging ungulate. Something has been learned about the immune system and gastrointestinal parasites in domestic ungulates ,36, and A study involving three wild antelope species  in Kenya, serves to illustrate the potential value of defecating in restricted areas or middens and avoiding foraging near the middens. The study confirmed that counts of parasite larvae were greater in the vicinity of the middens than in areas with no faecal droppings or just one clump of faeces. In dik-diks, where foraging behaviour was observed, the animals selectively avoided areas near concentrations of faeces .The generality of defecating in certain areas and avoiding the clumps of faeces in foraging is illustrated in a very different environment by reindeer which use dunging areas and avoid these areas in foraging . For botA question that arises in investigations of ungulate faecal avoidance in grazing is the degree to which the animals might sense a level of intestinal parasite infestation in guidance foraging behaviour. A detailed study on cattle given experimental doses of an intestinal parasite where the animals with the heaviest parasite load were the most cautious in foraging away from faeces supports this perspective . The catHowever, in a wild ungulate, the Alpine ibex, that also consistently avoids grazing near faeces , the invThe faecal avoidance behaviour is considered a balance between meeting nutritional demands and the degree of risk of acquiring parasites from nearby faeces. The foraging behaviour of the bushbuck in Uganda appeared, initially, to not reflect this balance because bushbucks forage right over faecal-contaminated areas. Upon close examination, it was noted that they do not forage close to the ground level, where parasite larvae would be found, but rather on the stems of grass and other plants at a level above that where the parasite larvae could be picked up .As a final example of herbivores avoiding faecal-borne parasites, a study in Australia on the common eastern grey kangaroo revealed that these animals carry an intestinal parasite load, but manage to keep the load at a tolerable level by avoiding faecal-contaminated forage. While the animals preferred the taller forage with a higher nutrient level, they would not trade a higher parasite risk if the preferred forage was in a contaminated area .The avoidance of faeces and faecal-borne intestinal parasites extends to wild carnivores which also carry an intestinal parasite load. The species-specific roundworms re-infect hosts through larvae that crawl out of the faeces where they can attach to the hair coat of hosts and are groomed off and consumed. Surveys of scats of wolves and wild felids reveal that virtually all carnivores have intestinal parasites –46. One Of course, newborn canids and felids have almost no mobility and cannot eliminate away from the den. They would be at risk of making a faecal mess in the den and re-infesting themselves with intestinal parasites, were it not for their mother's vigilance in quickly consuming their faecal deposits . This maOne might think that species that are primarily arboreal, such as monkeys, would not face the challenges of avoiding faeces because they generally defecate in trees as they move around. However, if the faeces drop on areas to be foraged upon or handled, there is a risk of parasite reinfection. Addressing this risk are observations on the red howling monkey, where it was revealed that they selectively defecate in areas free of underlying branches or vegetation. This selective defecation behaviour, of course, decreases the likelihood of contaminating potential food sources, an observation consistent with the low intestinal parasite load of the monkeys .Mandrills live in dense equatorial rainforests and face intense pressures from intestinal parasites. This is a species that enjoys a good deal of social grooming which undoubtedly helps control ectoparasites as well as having a social function. But mandrills avoid grooming others if they are infected with one of the intestinal protozoan parasites that could be picked up in grooming. When the infected mandrills at the study site were treated for the parasites, they were then groomed more often. Apparently, the parasites change the body odour which group mates sense .6.In contrast to parasites, of which animals living in nature are expected to harbour a load without apparent impact, with pathogenic bacteria or viruses a small dose can lead to a major illness, and accordingly behavioural defences differ from those used with parasites. The immune system is particularly relevant, so the steady state is an immune system activated by gradual exposure to common pathogens in the environment. The pathogens are typically species-specific and animals pick up pathogens in a variety of ways, most notably by being exposed to conspecifics that are sick with a bacterium or virus. For social animals growing up within a group, such as wolves and lions, rejection of non-group conspecifics is an adaptive behaviour from the standpoint of avoidance of pathogenic infections from strangers ,2.7.In vitro experiments found saliva of dogs to be bactericidal to the common wound contaminants, Escherichia coli and Streptococcus canis [Aside from exposure to pathogens causing systemic illness from strangers, the environment can harbour opportunistic pathogens that hang around and infect vulnerable animals. For carnivores a main way of dealing with the threat of infections that come about from invasion by surface pathogens is licking behaviour and the protective substances in saliva—‘the medicine cabinet in the mouth’. The range of bactericidal substances in saliva, as studied in dogs and humans, include lysozyme, lactoferrin, leucocytes, lactoperoxidase and immunoglobins ,52. For us canis . Saliva us canis ,55.The first job for canid and felid mothers that have just given birth is to expose the mammary area and nipples to the newborn so that they can begin nursing and get their first meal of antibody-rich colostrum. However, the lactating mother has, most likely, been exposing her nipples to environmental bacteria from the den floor and adjacent rest areas. The newborn is particularly vulnerable to environmental bacteria as intestinal epithelium is permeable to bacteria for the first 48–72 h . The evoMycoplasma pulmonis and Pasteurella pneumotropica. In vitro experiments reveal rat saliva is effective in killing both of these pathogens [Another application for antibacterial saliva in carnivores, rodents and other animals that can easily lick their penises is the apparent prevention of sexually transmissible diseases. Post-copulatory penis licking in rats is so consistent it almost looks compulsory . Two patathogens . The ant8.Finding adequate food, when relying on regularly capturing prey, is a challenge for a carnivore, whether social or not. Animals may be attracted to scavenge upon dead animals that they could run across. Generally, the fresher the dead carcass, the more appealing and valuable it would be as a food source. Even if the dead animal had died of a pathogenic disease, the animal feeding upon it is not likely to contract the disease—assuming the dead animal is of a difference species—because, in most instances, pathogens are species-specific.But what about a carnivore running across a freshly dead conspecific? This would appear to be an ideal food source because the animal would be consuming a meal exactly matching the nutritional resources of their own body. But the dead conspecific may have died from an infectious disease that the animal consuming it could contract. The protective behaviour addressing this pathogen risk is referred to as the cannibalism taboo. Carnivores will virtually never feed on the carcass of a recently dead conspecific . But wha9.Herbal medicine, as practised in traditional human cultures, and long before modern medicines existed, has been extensively studied. Several, or even most, modern medicines have an origin in ancient herbal remedies that, at least sometimes, removed parasites or pathogens and avoided major infections. The plant-derived medicinal substances, referred to as secondary plant compounds, are effective in protecting the plant from foraging insects, parasites and pathogens. It may be simply a coincidence that they have the medicinal effects for animals .Vernonia amygdalina plant, which is known to have antimicrobial effects [Brachyteles arachnoides) revealed that the diet of this primate includes plant species with demonstrated medicinal properties and that these were used in a medicinal way by humans in areas surrounding the park [The most convincing example of the use of herbal medicine for pathogens in mammals was an observation of a sick chimpanzee that was seen extracting, and chewing upon, the bitter pith of a  effects . Follow-the park .Information on the specific constituents of plant parts that convey the therapeutic effects has come from work on animal models in the laboratory. Various medicinal herbs have been shown to have one or more of the following properties: anti-inflammatory, antimicrobial, immunomodulatory, analgesic . The antThe constituents mentioned are rarely found alone. Usually, an anti-inflammatory constituent would be found along with an antimicrobial or immunomodulatory constituent. Thus, the medicinal plant part is broad spectrum. The secondary plant compounds with medicinal effects usually have a bitter or astringent taste, which apparently protects the plant from being grazed upon by herbivores.V. amygdalina, is bitter tasting, indicating that the sick individual was experiencing illness and possibly sought out the ‘bitter pill’.For primates, including humans, the bitter plant part will not be sought out as food. But it is hypothesized that when ill, there is a lowering of the threshold for bitter, and even an evolved predisposition to seek out a bitter-tasting plant part that has some probability of being effective for the animal's illness . The theManniophyton fulvum) with the effect of purging of intestinal parasites. Wild chimpanzees eat leaves from a variety of plants that pass through the intestinal tract whole. In some instances, the plant material increases intestinal motility that, which then purges the intestinal tract of nematodes. Sometimes in scats the leaves are even seen wrapped around worms that have been expelled. There can be seasonal differences in the risk of nematode infections in chimpanzees, and when one particular nematode increased in the study site in Tanzania, the swallowing of whole leaves increased, indicating that the animal sensed an increased parasite burden [A different angle of animal herbal medicine is the use of the ‘pharmacy in the woods' for anthelminthics to expel intestinal parasites from the intestinal tract. Studies on chimpanzees  as well e burden .The most common use of plants as protection from intestinal parasites is seen in canids and felids  commonlyJust as humans cannot feel worms in their intestines, dogs and cats (and their wild ancestors and relatives) presumably cannot feel, or otherwise know, whether or not they are infected with worms, aside from a vague stuffed feeling. The evolution of regular plant-eating by canids and felids is arguably an adaptive ongoing strategy for maintaining the intestinal parasite infection at a low to moderate level.In veterinary clinical practice, the traditional explanation for plant-eating in dogs and cats is that there is a dietary deficiency or that plant-eating is a way of inducing vomiting. In two broad-ranging Web-based surveys of thousands of dog and cat owners, it was found that the great majority of dogs and cats appeared normal before and after eating plants and did not vomit ,73 figu. An impoThe use of medicinal compounds in plants can also extend to ungulates as they graze on plants. Observations have been made on domestic ungulates that were reported to self-medicate on plants in association with an apparent ailment. One report interviewed pastoralists in Uganda about consumption of known medicinal plants, using the specific criteria for self-medication: (i) the animal had an obvious ailment; (ii) the animal was consuming a plant or plant part that it rarely did when healthy; (iii) there was subsequent improvement in the animal's signs related to the ailment and (iv) the animal no longer continued the self-medication . This stA review of several ruminant self-medication studies raises several relevant questions. How do they experience malaise during a parasitic infection? How do they experience relief after consuming an anti-parasitic plant? How do they identify medicinally active plants? When they get sick do they preferentially forage on anything that tastes or smells unpleasant, such having as a bitter taste? Do they learn from other animals? Do they learn by trial and error? Does the unpleasant taste of medicinal foliage become more acceptable to a sick animal ?10.In surveying the broad picture of how animals stay healthy and thrive in nature several points come to mind. Animals are generally not free of parasites either on the body surface or in the intestinal tract, but the parasite load is manageable by the strategies discussed. The avoidance behaviours are specific to the most important threats of the specific animal species. The strategies for controlling both parasites and pathogens in mammals living in nature include: avoiding external parasites, such as flies by fly switching; removing ticks, fleas and lice by grooming; using nest fumigation to repel and kill fleas; defecating in certain areas, and avoiding faeces in foraging; practising den sanitation to avoid intestinal parasites; showing the cannibalism taboo to avoid systemic infections from dead conspecifics; using the medicine cabinet in the mouth to remove surface pathogens; and using the pharmacy in the woods to get plant parts with medicinal properties, including natural worm-purging anthelminthics. Although mammals are emphasized in this paper, behavioural strategies have been identified in other vertebrate and invertebrate species that illustrate the variety of strategies used by animals living in nature to control the risk of infection from parasites and pathogens. Given the focus in modern society on human and veterinary medicine, and the never-ending search for ways to control pathogens and parasites that have rapidly evolved resistance to our defensive antibiotics and other treatments, we might profit from learning more about how animals do so well in nature without access to modern medicine, and stay healthy and thrive.


Background: Auditory impairment post stroke is common and may be due to both peripheral hearing loss and or central auditory processing disorder (CAPD). When auditory impairment remains untreated, it may impact on patient communication and rehabilitation after stroke. Offering a comprehensive audiological assessment to all stroke patients would be both costly and time-consuming. A brief hearing screening is thus required.Objective: The aim of this study was to determine whether a two-tiered hearing screening approach, with use of a handheld hearing screener and two validated hearing questionnaires could be used as a hearing screening for peripheral hearing loss and CAPD in stroke survivors. The sensitivity and specificity of the screening method was analyzed.Methods: This was a prospective study conducted in a tertiary neurology hospital. Forty-two consecutive stroke patients were recruited and tested within 3–12 months post-onset of their stroke. Three screening tools for the identification of hearing impairment were evaluated in this study: A handheld hearing screener for determination of peripheral audiometric hearing loss and two validated questionnaires (The Amsterdam Inventory Auditory for Disability (AIAD) and the Hearing Handicap Inventory for Elderly (HHIE) questionnaires) for determination of peripheral hearing loss and/or CAPD.Results: The hearing screener had a sensitivity of 92. 59% detecting a hearing loss and specificity of 100%. The greatest test accuracy in identifying a central auditory processing type hearing impairment in stroke patients was found when the handheld hearing screener and the AIAD questionnaire were combined.Conclusion: This study is a first step toward addressing the complex auditory needs of stroke survivors in a systematic manner, with the ultimate aim to support their communication needs and long-term recovery and wellbeing.Registration: Project Identification number 11/0469 and REC ref 11/LO/1675. Stroke can affect all levels of the auditory pathway from the hearing organ to the cortex and manifest with deficits in audiometric thresholds and/or more complex central auditory processing disorder (CAPD) with perceptual difficulties in speech, sound recognition, and localization –3. HowevOffering a comprehensive audiological assessment to all stroke patients would be both costly and time-consuming. A preliminary brief screening assessment to reliably identify perceived auditory difficulties among stroke survivors is thus required. To date, only four studies have attempted to screen hearing in a stroke population , 12–14. Handheld hearing screeners are used to identify the possibility of an individual presenting with peripheral hearing loss who requires full audiological assessment . In addiThe primary purpose of this study was to determine whether a two-tiered screening approach, with use of a handheld hearing screener and two validated hearing questionnaires at the 3-month follow up post discharge from a stroke unit could be used as a hearing screening strategy to facilitate early identification and appropriate referral of auditory impaired stroke patients.This was a study of diagnostic accuracy using sensitivity and specificity. The study was a prospective study where the data collection was planned before the index test and reference standard were performed.The Ethics Committee of the National Hospital for Neurology and Neurosurgery (NHNN) approved the Hearing Evaluation and Auditory Rehabilitation after Stroke (HEARS) study (Project Identification number 11/0469 and REC ref 11/LO/1675). We obtained written informed consent from all the stroke participants. Fifty consecutive stroke patients were recruited and tested at the department of Neuro-otology, NHNN Queen Square London, within 3–12 months post-onset stroke, since auditory impairments are stable at that point . BecauseThe screening tests were completed for each subject in a random order during a single visit, before the administration of the full audiological assessment which aimed to identify and categorize the patient's auditory profile into one of the following: (1) normal, (2) peripheral hearing loss (cochlea to auditory nerve), (3) CAPD (brainstem to cortex and beyond) , 21, andBelow we describe the definition and diagnostic criteria for each category.Threshold assessment was made at 250, 500, 1,000, 2,000, 4,000, 6,000, and 8,000 Hz, and a pure-tone audiometry (PTA) average was calculated. The severity of hearing loss was determined using the British Society of Audiology audiometric descriptors . Also, hThe peripheral hearing loss  was defined as (a) “cochlear type” hearing loss: abnormal pure-tone average, reduced or absent Transient-evoke otoacoustic emission (TEOAEs), present and normal acoustic reflex threshold (ART), and normal auditory brainstem response (ABR) or normal interwave interval ABR ; “neuralThe definition of CAPD adopted by this study was according to the technical report of the American Speech-Language-Hearing Association (ASHA) Working Group (2005) , “deficiThe electrophysiological/electroacoustic test abnormality was not attributable to the presence of hearing loss (see ABR and ART criteria).A semantic test abnormality in the QSTAC without abnormalities in the perceptual spectral and/or apperceptive tests of the same battery was not considered to be evidence of disordered auditory processing.For the purpose of this study, if CAPD and/or an isolated brainstem type ABR and ART test abnormality was detected in the presence of peripheral hearing loss, we defined the pattern as a combination  type auditory impairment.Three screening tools for the identification of hearing impairment were evaluated in this study:Handheld hearing screener  for determination of peripheral audiometric hearing loss.Two validated self-reported hearing questionnaires for determination of hearing disability.– The modified Amsterdam Inventory Auditory for Disability (AIAD) questionnaire : The AIA– The Hearing Handicap Inventory for Elderly (HHIE) questionnaire : The HHIThe screening tests were performed at the department of neuro-otology (NHNN), in a quiet but not soundproofed test room situated next to the outpatient clinic rooms. This room was free of visual and auditory distractions and similar to the clinic rooms of the NHNN stroke follow-up clinic, with the same levels of ambient noise level that did not exceed 50 dBA and was most commonly around 41–42 dBA, as measured with a sound level meter .All the screening tests  were completed for each subject in a randomized order during a single visit before the administration of the full audiological assessment.For the handheld hearing screener test the participants were asked to respond according to the British Society of Audiology recommended procedure for PTA . This teThe AIAD and HHIE questionnaires, that were administered to the stroke patients as self-reported questionnaires, took under 10 min per questionnaire for completion.For the handheld hearing screener, the pure-tone audiogram was established as the “gold standard” according to the ASHA “guidelines for audiologic screening” .the best available method of categorizing participants as having or not having the target condition). All patients received the same set of audiological tests that are described below in brief  the criteria of Ventry and Weinstein study ; patientAIAD questionnaire: Hearing disability was defined by the criteria of Meijer et al. . Pass waCombined handheld hearing screener and AIAD questionnaire for identifying CAPD: For those with CAPD, auditory disability was defined according to the criteria of departmental normative data for CAPD in conjunction with Bamiou's studies in CAPD and stroke patients , 32: FaiPatients were tested in a sound-treated booth with standard clinical procedures including PTA (to determine hearing thresholds), tympanometry and acoustic reflexes threshold to determine middle ear or auditory nerve to lower brainstem problems), transient-evoked otoacoustic emissions (to assess cochlear function), auditory-evoked brainstem responses (to assess auditory nerve & brainstem). A non-verbal auditory processing test battery was used to assess temporal resolution [Gaps-in-noise]  and earlTo evaluate the accuracy of the screening tools for the diagnosis of hearing impairment, calculations of sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were performed using the “gold standard” described in Methods. Sensitivities were calculated as the proportions of persons with hearing impairment correctly identified by the tests, while specificities were calculated as the proportions of persons without hearing impairment correctly identified by the tests. PPV is the probability that subjects with a positive screening test truly have the disease, and NPV is the probability that subjects with a negative screening test truly do not have the disease.n = 84 ears). The age ranged from 23 to 80 years old with an average of 58.19 years old (SD = 15.06). Days since stroke ranged between 92 and 360 days . The stroke was haemorrhagic in six and ischemic in 36. See Data from 42 stroke patients were obtained for all screening protocols  and specificity (100%) in detecting a mild or greater hearing loss in stroke patients, similar to previous studies on non-neurological populations , 34. SucThe HHIE yielded low sensitivity (44%) and NPV (23%) but optimal specificity and PPV (100%) for the detection of peripheral hearing loss. Low sensitivity and low NPV indicate that stroke patients tend to under report hearing disability. Several studies show that the HHIE questionnaire is effective for identification of moderate to severe hearing loss , 36–38 rThe AIAD questionnaire gave similar results to the HHIE when used to screen for peripheral hearing loss after stroke. For a cut-off value of >64 , the AIAThe poor sensitivity for detection of peripheral hearing loss of both AIAD and HHIE questionnaires could be attributed to the fact that these measure self-reported auditory disability, which may arise due to impairment at any level of the auditory pathway. In addition, PTA results do not entirely correspond with self-reported hearing loss .To this end, and toward the detection of central auditory deficits corresponding to self-reported auditory difficulties, combined use of the handheld hearing screener and AIAD, gave the best results with a sensitivity of 50% and a high specificity of 89%, PPV of 80%, and NPV of 67%. Similar to the HHIE results for peripheral hearing loss, a significant proportion of stroke patients with a central auditory impairment failed to report it. However, the high specificity showed the ability of the auditory questionnaires to correctly identify patients without central auditory impairments. Their use will potentially limit the number of unnecessary referrals for further central auditory evaluations.The results of our study, albeit preliminary, are promising, in that the handheld hearing screener use yielded reliable information about patients requiring detailed assessment for peripheral hearing loss. Furthermore, the addition of the AIAD self-report measure identified a further proportion of patients in need of further central auditory evaluation, who might not routinely receive such assessment otherwise.This protocol may provide useful information for the rehabilitation team to help identify patients with high levels of perceived deficits and disability who need additional investigation and input on a case-by-case basis. In Clinical implication of the present study is noteworthy. The National Institute for Health and Care Excellence in the UK recommends performing a full medical assessment of the person with stroke including functional ability and communication. However, hearing assessment is not featured in this guideline. Uncorrected hearing loss may affect outcome of speech and language assessment and related therapies , and impThe findings of this preliminary study will require corroboration and development in further pragmatic studies involving larger cohorts, within stroke units and possibly including those with severe aphasia and/or cognitive impairments. However, this study is a first step toward addressing the complex auditory needs of stroke survivors in a systematic manner, with the ultimate aim to support their communication needs, long-term recovery and wellbeing, and thus possibly delay onset of post stroke dementia .To our knowledge, this is the first study to assess the efficacy of a low-cost hearing screening program in the stroke population for both peripheral hearing loss and central auditory impairments. Of the three tools used, the handheld hearing screener had the highest sensitivity (93%) and specificity (100%) in detecting a mild or greater hearing loss in stroke patients, similar to previous studies on non-neurological populations , 34. SucThe raw data supporting the conclusions of this manuscript will be made available by the authors, without undue reservation, to any qualified researcher.NK, DV, NU, DW, and D-EB contributed to the design, results analysis, interpretation, and write-up of the paper. NK and NU conducted the tests. The paper was drafted, finalized and revised by NK and D-EB, and approved by all authors.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


Recent findings have suggested an association between pubic hair grooming and self-reported history of sexually transmitted infection (STI), specifically gonococcal infection (GC), chlamydial infection (CT), or human immunodeficiency virus (HIV). We evaluated the association between self-reported extreme grooming and laboratory-confirmed prevalence of GC/CT. Between April 2017 and April 2018, we enrolled English-speaking, adult, female students at a large, Midwestern university who presented on-campus for STI testing. Participants completed a questionnaire on demographics and sexual and grooming behaviors, which was linked to their GC/CT test results based on nucleic acid amplification testing. We defined extreme grooming as removal of all pubic hair either at least weekly in the past 12 months or ≥6 times in the past 30 days. We used two separate logistic regression models to determine whether odds of GC/CT varied by extreme groomer status for either time interval. In the study sample of 214 women, prevalence of GC/CT was 9.8%. Nearly all participants (98.1%) reported ever grooming; 53.6% were extreme groomers in the past year and 18% in the past month. Extreme grooming was not associated with prevalent GC/CT in the past year  or in the past month . Pubic hair grooming was common among female university students attending for STI testing. Findings do not support pubic hair grooming as an STI risk factor in this population. Sexually transmitted infections (STIs) are prevalent in the U.S. and can have lifelong consequences if untreated . GonococA recent analysis suggested a possible association between pubic hair grooming and self-reported history of STI, specifically a combined outcome of GC, CT, or human immunodeficiency virus (HIV) –7. PubicOur study objective was to evaluate the association between self-reported extreme grooming and laboratory-confirmed prevalence of GC/CT among female university students presenting at one of two walk-in STI testing sites on the campus of a large, Midwestern university from April 2017 to April 2018. Eligible study participants were female, at least 18 years of age, spoke and read English, and presented for GC/CT testing. Using an electronic tablet with REDCap , particiextreme grooming within the past 12 months. Extreme grooming was defined as responding either “Weekly” or “Daily” to the question, “In the past 12 months, which best describes how often you have removed all of your pubic hair?” Non-extreme groomers were defined as participants who responded “Monthly,” “Less than 12 times,” or “Never.” As a sensitivity analysis, we used an alternative dichotomous variable for extreme grooming in the past 30 days based on responding either “11+ times” or “6–10 times” to “In the past 30 days, how often have you removed all of your pubic hair?” Non-extreme groomers for this measure were those who responded "2–5 times,” “1 time,” or “Never.”Our main exposure was a binary yes/no variable for Urine samples for GC/CT testing were collected at study sites by trained test counselors affiliated with the university and were sent to a nearby health department for processing and testing using the Aptima Combo 2® assay . We linked STI test results with questionnaire records using unique participant study identification numbers. We created a binary variable to describe whether a participant tested positive for GC/CT (either or both infections vs. neither).Possible correlates of both pubic hair grooming and STI were identified based on existing literature ,4,7,8,13st through 5th or greater). We created three categories for race: white, Black, and other, including Asian, American Indian, Native Hawaiian, more than one race, and those who selected “other” race. The sample size was insufficient to stratify race into more distinct categories. We used SAS  to conduct all analyses.We calculated descriptive statistics for all demographic variables , sexual activity and grooming. We used separate logistic regression models to determine whether GC/CT status varied by extreme groomer status 1) within the past 12 months or 2) within the past 30 days. We used manual backward selection by adding all variables identified as potential confounders from the DAG   and those for whom we were unable to link questionnaire and STI test results (n = 18). The inability to link data could have resulted from participants providing different names to study staff and STI testing staff or from participants leaving the site before giving a specimen for STI testing. Finally, we excluded participants with testing encounter dates that differed from their questionnaire date (n = 4) and those who failed to complete the questionnaire (n = 3). The final analysis population consisted of the remaining 214 participants.In a sensitivity analysis, we used exact chi-squared tests for categorical variables and Wilcoxon rank-sum tests for continuous variables to compare demographic characteristics and sexual behaviors of participants with STI data versus those who were excluded from the analysis for missing STI data . Only onMost women in the analysis population were white (75.2%), single (72.0%), and reported a parental or guardian income of $60,000 or greater 81.4%; . The meaAmong those who reported ever grooming, 112 (53.6%) were extreme groomers within the past year, defined as removal of all pubic hair weekly or daily within the past 12 months. Thirty-eight (18.0%) participants were extreme groomers within the past month, defined as removal of all pubic hair 6 or more times within the past 30 days. Most respondents reporting using a non-electric blade razor to groom most often (82.9%), either with soap (41.7%) or with shaving cream (41.2%). Nearly two-thirds (63.3%) had ever had a grooming injury, and the mean number of lifetime grooming injuries was 4.9 (SD = 3.8).In both unadjusted and adjusted models, we found no evidence of difference in the odds of GC/CT between women who were extreme groomers within the past year compared to those who were not extreme groomers  = 0.6, 95% CI = 0.3–2.0, respectively; We found no evidence of an association between extreme pubic hair grooming (in the past 12 months or the past 30 days) and prevalent GC or CT infection among a convenience sample of female, mostly white, single, university students presenting for STI testing at a large Midwestern university. In contrast, three previous studies have suggested a link between these practices and prevalent STI. First, a case series of 30 individuals presenting with new cases of sexually transmitted molluscum contagiousum virus at a dermatology office in France showed that 93% of infected individuals practiced pubic hair grooming  . HoweverMost recently, a large web survey of men and women 18–65 years of age found that 74% of study participants reported ever having groomed their pubic hair [Our analysis is an important contribution to the scant literature about this topic for several reasons. First, we used laboratory-confirmed GC/CT to measure STI status rather than rely on respondent reporting. Self-reported history of CT infection has been shown to be have only moderate agreement with serologically-confirmed infection . Our anaIn summary, ever pubic hair grooming was almost universal 98.1%) in our sample, which is consistent with previous estimates of grooming prevalence among college-aged individuals [8.1% in oS1 Table(DOCX)Click here for additional data file.


Hearing loss is a major health problem and is associated with several negative outcomes such as difficulties in communicating and poor quality of life. The aim of this study was to conduct a systematic literature review to evaluate the impact of different types of hearing rehabilitation after hearing loss and their impact on quality of life.A systematic literature search was conducted on Pubmed which retrieved 549 articles. Of these, 29 articles regarding cochlear implants, bone anchored hearing devices and traditional amplification hearing aids have been systematically reviewed. The search was limited to articles published from 1960/01/01 to 2017/05/22, included human participants and available in English.The main finding was that hearing rehabilitation is beneficial in all types of hearing loss and treatment regarding quality of life. However, bone-anchored hearing devices and cochlear implants were shown to produce greater improvements in terms of quality of life than conventional hearing aids.From these findings, we concluded that hearing rehabilitation does have a positive impact on quality of life after hearing loss. Hearing loss is a major health problem that often goes un-noticed or untreated. It is associated with an array of problems, such as poor quality of life, negative outcomes with socialisation, independence, interpersonal relationships, socialisation and communications. Figures show that approximately 10 million people in the UK are affected by hearing loss [There are three main types of hearing loss: conductive, sensorineural and mixed. Sensorineural hearing loss (SNHL) is a result of damage to the cochlear or vestibulocochlear nerve . There aIn simplistic terms, a hearing aid is an electronic device that is worn behind or in the ear that works by making sounds louder for individuals with hearing loss to hear better. This is done via three basic components: a microphone, an amplifier and a speaker. Sound is received through the microphone, which converts it into electrical signals; these electrical signals are transported to the amplifier which is responsible for increasing the power of the signals which are projected through the speaker .” (BAHA) is a type of hearing aid that requires surgical implantation. During surgery, a small vibrator is plugged on to a titanium screw (fixture) that is implanted behind the ear. These two components convert sound into a vibration via the screw, which then stimulates the cochlea through an alternative conduction pathway [The “bone anchored hearing aid pathway . The BAH pathway . A cochl pathway .Hearing loss is a debilitating condition, and as with any disability patients often undergo rehabilitation. American Speech–Language–Hearing Association define hearing rehabilitation as a process where those who suffer with hearing loss are provided treatment and training to help improve their impairment. This is done by helping patients adjust to hearing loss, exploring suitable hearing aids and other devices, and helping them to converse and communicate .Hearing loss can lead to secondary problems such as learning disabilities, social isolation, lack of independence, depression and possible early dementia which all effect quality of life. Valente et al.  have welThis systematic review aims to investigate the different types of hearing rehabilitation and whether the rehabilitation improves quality of life, as well as audiological improvements.The literature search was divided into different domains and the following search criteria was implemented on Pubmed:  AND  AND (rehabilitation OR treatment OR hearing aid OR bone conduction). These terms were to be included in the title or the abstract. Articles were only included if they were in full text, published from 1960/01/01 to 2017/05/22, included human participants and the publication was available in English.The search retrieved 549 articles, which were carefully narrowed down to 45. The majority of these articles were excluded after reading title and abstract as they had no relevance to the research question. Of the 45 articles which had their full-text read, 29 were included in the results. The main reason for exclusion at this stage was due to different outcome measures than quality of life such as hearing improvement solely see Fig. .A cochlear implant is an alternative electronic device that is used in profound hearing loss when a conventional amplification hearing aid had little or no benefit or cannot be used. Aimoni et al.  conducteCosetti et al.  conducteNecula et al.  looked aFrancis et al.  proposedCochlear implantation is a surgical procedure, and with any surgery comes concern and worry about complications. Estomba et al.  conducteThe BAHA plays a role in an array of psychological and personal benefits, such as quality of life, comfort, practicality, cosmetic appearances, anxiety and depression improvements, more social interactions and less social isolation. Arunachalam et al.  used theFurther research by Hol et al.  was condIn addition, De Wolf et al.  conducteGillett et al.  receivedIt is important to understand the long-term effects of the BAHA device on quality of life. Newman et al.  performeCarr et al.  highlighA conventional amplification hearing aid is one of the most frequent devices used to rehabilitate hearing loss. Stewart et al.  conductep ≤ 0.0001); communication function (p ≤ 0.0001); cognitive function (p = 0.008); depression (p = 0.03) [However, Murlow et al.  highligh = 0.03) . These rp ≤ 0.000) [Similarly, Lotfi et al.  conducte≤ 0.000) . These rA more recent study by Niemensivu et al.  conducteChen et al.  investigSchneider et al.  investigFrom the results it is evident that hearing rehabilitation impacts quality of life in an array of different ways. When considering cochlear implants, several different measures have revealed how the device is beneficial in terms of treating hearing loss and improving quality of life. Furthermore, research highlights how the minimalistic surgery has few risks and several benefits that are long lasting .Regarding the research investigating the BAHA, the results are similar to that of the cochlear implant. Quality of life is consistently improved throughout a large range of different research methodologies which highlights how reliable and consistent the BAHA is. It has been shown to improve and prevent social isolation and learning difficulties in children later in life . FurtherWhile the research on conventional hearing aids has not been as profound as the other research in terms of quality of life improvement, it does play an important role preserving hearing abilities . As wellIn summary, there is a large body of research into the impact of hearing loss rehabilitation and quality of life. The majority of it states that the results of hearing rehabilitation are largely positive. A hearing device is no longer just available to improve auditory health, instead increased knowledge and awareness has opened our eyes in our understanding to hearing loss, in the sense that there are many different areas of our lives that can be affected from hearing loss. Therefore, successful hearing rehabilitation can have a profound impact on quality of life.


Objectives: Children with hearing loss listen and learn in environments with noise and reverberation, but perform more poorly in noise and reverberation than children with normal hearing. Even with amplification, individual differences in speech recognition are observed among children with hearing loss. Few studies have examined the factors that support speech understanding in noise and reverberation for this population. This study applied the theoretical framework of the Ease of Language Understanding (ELU) model to examine the influence of auditory, cognitive, and linguistic factors on speech recognition in noise and reverberation for children with hearing loss.Design: Fifty-six children with hearing loss and 50 age-matched children with normal hearing who were 7–10 years-old participated in this study. Aided sentence recognition was measured using an adaptive procedure to determine the signal-to-noise ratio for 50% correct (SNR50) recognition in steady-state speech-shaped noise. SNR50 was also measured with noise plus a simulation of 600 ms reverberation time. Receptive vocabulary, auditory attention, and visuospatial working memory were measured. Aided speech audibility indexed by the Speech Intelligibility Index was measured through the hearing aids of children with hearing loss.Results: Children with hearing loss had poorer aided speech recognition in noise and reverberation than children with typical hearing. Children with higher receptive vocabulary and working memory skills had better speech recognition in noise and noise plus reverberation than peers with poorer skills in these domains. Children with hearing loss with higher aided audibility had better speech recognition in noise and reverberation than peers with poorer audibility. Better audibility was also associated with stronger language skills.Conclusions: Children with hearing loss are at considerable risk for poor speech understanding in noise and in conditions with noise and reverberation. Consistent with the predictions of the ELU model, children with stronger vocabulary and working memory abilities performed better than peers with poorer skills in these domains. Better aided speech audibility was associated with better recognition in noise and noise plus reverberation conditions for children with hearing loss. Speech audibility had direct effects on speech recognition in noise and reverberation and cumulative effects on speech recognition in noise through a positive association with language development over time. Children spend a considerable amount of time listening in environments with suboptimal acoustics, including high levels of background noise and reverberation  amplification compared to linear amplification on a sentence recognition task . Three research questions were examined:Does listening in noise and reverberation present additional challenges to children with hearing loss compared to peers with normal hearing? Based on previous research, we predicted greater difficulty listening in noise and reverberation for children with hearing loss than peers with normal hearing.Consistent with the ELU model, do linguistic and cognitive abilities predict individual differences in speech recognition in noise and reverberation for children with normal hearing and children with hearing loss? We predicted that our results would be consistent with the ELU model in that children with stronger working memory, language, and auditory attention skills would have better speech recognition in noise and reverberation than children with poorer skills in these domains.Does aided speech audibility have a direct relationship with speech recognition in noise and reverberation or is the relationship mediated by the child's language skills? Based on previous research, we anticipated that the relationship between audibility and aided speech recognition in noise and reverberation would include direct and mediated paths.n = 50) and children with mild-to-severe hearing loss (n = 56) participated in the experiment. Children were recruited from research centers at Boys Town National Research Hospital  and the University of Iowa  and the surrounding areas as part of a longitudinal study of developmental outcomes for children with bilateral mild-to-severe hearing loss. Children with normal hearing  for each ear, and the PTA for the better-ear was used to represent degree of hearing loss in the statistical analyses.3 coupler on the Verifit system to simulate the output of the hearing aid in the child's ear canal. The proximity of each child's fitting to Desired Sensation Level . The Verifit calculated the aided Speech Intelligibility Index  are reported for simplicity with the exception of the subject type (NH vs. HL) interaction with reverberation, which was specifically hypothesized. The effects of aided audibility on language, working memory, and SNR50 in reverberation were also assessed for children with hearing loss with linear regression using a mediation analysis approach. The normality of each model's residuals was assessed to identify potential violations of statistical assumptions. To control for Type I error rate for statistical tests involving multiple comparisons, the p-values were adjusted using the False Discovery Rate procedure  of 600 ms reduced SNR50 for both groups by an additional 5 dB. Although children with hearing loss performed more poorly than peers with normal hearing, the performance difference between groups was similar for both noise and noise plus reverberation conditions. The finding of poorer performance for children with hearing loss is consistent with the previous literature (Finitzo-Hieber and Tillman, As predicted by the ELU model (Rönnberg et al., Our previous research has also demonstrated that children with better aided speech audibility have better speech recognition under degraded conditions because of the direct effects of audibility on speech recognition (McCreery et al., Despite the fact that this study was one of the first to examine the auditory, cognitive, and linguistic factors that predict speech recognition in noise and reverberation for children who wear hearing aids, there are several limitations that could be addressed in future research on this topic. The reverberation simulation used in this study was implemented to be completed with minimal equipment requirements so that children could be tested at multiple sites. More sophisticated methods of reverberation simulation have been developed and used in recent studies with adults with hearing loss Zahorik,  and chilThe current study was conducted as part of a longitudinal study of children with mild to severe hearing loss, and therefore, did not include children with cochlear implants. Children with cochlear implants are likely to have significant challenges in noise and reverberation (Neuman et al., The datasets generated for this study are available on request to the corresponding author.The studies involving human participants were reviewed and approved by Boys Town National Research Hospital Institutional Review Board. Written informed consent to participate in this study was provided by the participants' legal guardian/next of kin. All children completed written assent or consent to participate in the study.RM, EW, MS, MB, and DL planned the proposed experiment. EW, MS, and MB were involved in data collection. RM wrote the first draft of the article. RM, EW, MS, MB, and DL edited and approved the final version of the article.DL is a member of the Phonak Pediatric Advisory Board, but this work was not supported or affected by her involvement. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.