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1.  Prevalence and Subtype Identification of Blastocystis sp. in Healthy Individuals in the Tunis Area, Tunisia 
Blastocystis sp. is currently the most common eukaryotic parasite found in humans. Despite its potential public health impact, epidemiological data regarding its prevalence and molecular subtype (ST) distribution in Maghreb are rarely reported. Therefore, the aim of this study was to determine the prevalence of the parasite in a cohort of healthy food handler Tunisian individuals and to acquire the first molecular data regarding the distribution of Blastocystis sp. STs in this country. Therefore, 524 fecal samples were collected, and 68 of them (13%) were identified as positive for the parasite by direct-light microscopy of smears. Seventeen samples of 100 negative by microscopy were also shown to be positive by real-time quantitative polymerase chain reaction. Among all the positive samples, 61 Blastocystis isolates were subtyped using partial small subunit ribosomal RNA gene analysis. ST3 was the most abundant (51%) followed by ST1 (30%), ST2 (16%), and ST4 and ST7 (both 1.6%).
PMCID: PMC5239694  PMID: 27920396
2.  Voluntary vs. compulsory student evaluation of clerkships: effect on validity and potential bias 
Students evaluations of their learning experiences can provide a useful source of information about clerkship effectiveness in undergraduate medical education. However, low response rates in clerkship evaluation surveys remain an important limitation. This study examined the impact of increasing response rates using a compulsory approach on validity evidence.
Data included 192 responses obtained voluntarily from 49 third-year students in 2014–2015, and 171 responses obtained compulsorily from 49 students in the first six months of the consecutive year at one medical school in Lebanon. Evidence supporting internal structure and response process validity was compared between the two administration modalities. The authors also tested for potential bias introduced by the use of the compulsory approach by examining students’ responses to a sham item that was added to the last survey administration.
Response rates increased from 56% in the voluntary group to 100% in the compulsory group (P < 0.001). Students in both groups provided comparable clerkship rating except for one clerkship that received higher rating in the voluntary group (P = 0.02). Respondents in the voluntary group had higher academic performance compared to the compulsory group but this difference diminished when whole class grades were compared. Reliability of ratings was adequately high and comparable between the two consecutive years. Testing for non-response bias in the voluntary group showed that females were more frequent responders in two clerkships. Testing for authority-induced bias revealed that students might complete the evaluation randomly without attention to content.
While increasing response rates is often a policy requirement aimed to improve the credibility of ratings, using authority to enforce responses may not increase reliability and can raise concerns over the meaningfulness of the evaluation. Administrators are urged to consider not only response rates, but also representativeness and quality of responses in administering evaluation surveys.
Electronic supplementary material
The online version of this article (10.1186/s12909-017-1116-8) contains supplementary material, which is available to authorized users.
PMCID: PMC5756350  PMID: 29304800
Clerkship; Evaluation; Rating; Authority; Bias
3.  Anoctamin 6 Contributes to Cl− Secretion in Accessory Cholera Enterotoxin (Ace)-stimulated Diarrhea 
The Journal of Biological Chemistry  2016;291(52):26816-26836.
Accessory cholera enterotoxin (Ace) of Vibrio cholerae has been shown to contribute to diarrhea. However, the signaling mechanism and specific type of Cl− channel activated by Ace are still unknown. We have shown here that the recombinant Ace protein induced ICl of apical plasma membrane, which was inhibited by classical CaCC blockers. Surprisingly, an Ace-elicited rise of current was neither affected by ANO1 (TMEM16A)-specific inhibitor T16A(inh)-AO1(TAO1) nor by the cystic fibrosis transmembrane conductance regulator (CFTR) blocker, CFTR inh-172. Ace stimulated whole-cell current in Caco-2 cells. However, the apical ICl was attenuated by knockdown of ANO6 (TMEM16F). This impaired phenotype was restored by re-expression of ANO6 in Caco-2 cells. Whole-cell patch clamp recordings of ANO currents in HEK293 cells transiently expressing mouse ANO1-mCherry or ANO6-GFP confirmed that Ace induced Cl− secretion. Application of Ace produced ANO6 but not the ANO1 currents. Ace was not able to induce a [Ca2+]i rise in Caco-2 cells, but cellular abundance of phosphatidylinositol 4,5-bisphosphate (PIP2) increased. Identification of the PIP2-binding motif at the N-terminal sequence among human and mouse ANO6 variants along with binding of PIP2 directly to ANO6 in HEK293 cells indicate likely PIP2 regulation of ANO6. The biophysical and pharmacological properties of Ace stimulated Cl− current along with intestinal fluid accumulation, and binding of PIP2 to the proximal KR motif of channel proteins, whose mutagenesis correlates with altered binding of PIP2, is comparable with ANO6 stimulation. We conclude that ANO6 is predominantly expressed in intestinal epithelia, where it contributes secretory diarrhea by Ace stimulation in a calcium-independent mechanism of RhoA-ROCK-PIP2 signaling.
PMCID: PMC5207189  PMID: 27799301
epithelial cell; epithelial cell adhesion molecule (EpCAM); intestinal epithelium; ion channel; membrane; pathogenesis; phosphatidylinositol; signaling
4.  High association of Cryptosporidium spp. infection with colon adenocarcinoma in Lebanese patients 
PLoS ONE  2017;12(12):e0189422.
The association between Cryptosporidium and human colon cancer has been reported in different populations. However, this association has not been well studied. In order to add new strong arguments for a probable link between cryptosporidiosis and colon human cancer, the aim of this study was to determine prevalence and to identify species of Cryptosporidium among Lebanese patients.
Methodology and principal findings
Overall, 218 digestive biopsies were collected in Tripoli, Lebanon, from three groups of patients: (i) patients with recently diagnosed colon intraepithelial neoplasia/adenocarcinoma before any treatment (n = 72); (ii) patients with recently diagnosed stomach intraepithelial neoplasia/adenocarcinoma before any treatment (n = 21); and (iii) patients without digestive intraepithelial neoplasia/adenocarcinoma but with persistent digestive symptoms (n = 125). DNA extraction was performed from paraffin-embedded tissue. The presence of the parasite in tissues was confirmed by PCR, microscopic observation and immunofluorescence analysis. We identified a high rate (21%) of Cryptosporidium presence in biopsies from Lebanese patients with recently diagnosed colonic neoplasia/adenocarcinoma before any treatment. This prevalence was significantly higher compared to 7% of Cryptosporidium prevalence among patients without colon neoplasia but with persistent gastrointestinal symptoms (OR: 4, CI: 1.65–9.6, P = 0.001). When the comparison was done against normal biopsies, the risk of infection increased 11-fold in the group of patients with colon adenocarcinoma (OR: 11.315, CI: 1.44–89.02, P = 0.003).
This is the first study performed in Lebanon reporting the prevalence of Cryptosporidium among patients with digestive cancer. These results show that Cryptosporidium is strongly associated with human colon cancer being maybe a potential etiological agent of this disease.
PMCID: PMC5736188  PMID: 29261714
5.  Is hematoxylin-eosin staining in rectal mucosal and submucosal biopsies still useful for the diagnosis of Hirschsprung disease? 
Diagnostic Pathology  2017;12:84.
Hematoxylin-eosin (HE) staining of a full-thickness rectal wall fragment is classically used for the diagnosis of Hirschsprung disease (HD). However, this technique requires large fragments for a better diagnosis. Additionally, the histochemical and immunohistochemical methods of staining small fragments of rectal mucosal and submucosal biopsies are not available in all centers. Therefore, the possibility of diagnosing HD through HE staining in these biopsies could be a valuable alternative for centers that do not have more specific techniques. The objectives of the current investigation were to evaluate the concordance of the results obtained by HE staining and the calretinin method with acetylcholinesterase (AChE) activity in fragments of mucosa and submucosa in the diagnosis of HD.
For this study, 50 cases from our laboratory were selected. The tissue material was embedded in paraffin. Sixty levels of each fragment were utilized for HE, and the other 3 levels were used for calretinin. These slides were analyzed under the microscope, photographed and classified as either positive for HD when no ganglion cells were found with nerve trunks present or as negative when ganglion cells were found. The results from reading the slides were compared with those of AChE.
Of the 50 cases evaluated by the HE technique, only 5 contradicted the diagnosis based on AChE, with a Kappa value of 0.800 and an accuracy of 90%. In the comparison between calretinin and AChE, 8 cases were discordant, with a Kappa value of 0.676 and an accuracy of 84%.
The concordance of results from AChE and HE methods was satisfactory, allowing for the potential use of the HE method for fragments of mucosa and submucosa as a valid alternative in the diagnosis of HD. The immunohistochemical technique of calretinin did not show good agreement with the AChE activity in our study.
PMCID: PMC5719668  PMID: 29212517
Hirschsprung’s disease; Rectal biopsy; Acetylcholinesterase, Hematoxylin-eosin; Calretinin
6.  Favorable impact of allogeneic stem cell transplantation in patients with therapy-related myelodysplasia regardless of TP53 mutational status 
Haematologica  2017;102(12):2030-2038.
Therapy-related myelodysplastic syndrome is a long-term complication of cancer treatment in patients receiving cytotoxic therapy, characterized by high-risk genetics and poor outcomes. Allogeneic hematopoietic cell transplantation is the only potential cure for this disease, but the prognostic impact of pre-transplant genetics and clinical features has not yet been fully characterized. We report here the genetic and clinical characteristics and outcomes of a relatively large cohort of patients with therapy-related myelodysplastic syndrome (n=67) who underwent allogeneic transplantation, comparing these patients to similarly treated patients with de novo disease (n=199). The 5-year overall survival was not different between patients with therapy-related and de novo disease (49.9% versus 53.9%; P=0.61) despite a higher proportion of individuals with an Intermediate-2/High International Prognostic Scoring System classification (59.7% versus 43.7%; P=0.003) and high-risk karyotypes (61.2% versus 30.7%; P<0.01) among the patients with therapy-related disease. In mutational analysis, TP53 alteration was the most common abnormality in patients with therapy-related disease (n=18: 30%). Interestingly, the presence of mutations in TP53 or in any other of the high-risk genes (EZH2, ETV6, RUNX1, ASXL1: n=29: 48%) did not significantly affect either overall survival or relapse-free survival. Allogeneic stem-cell transplantation is, therefore, a curative treatment for patients with therapy-related myelodysplastic syndrome, conferring a similar long-term survival to that of patients with de novo disease despite higher-risk features. While TP53 alteration was the most common mutation in therapy-related myelodysplastic syndrome, the finding was not detrimental in our case-series.
PMCID: PMC5709102  PMID: 28971906
7.  Assessment of the Mental Foramen Location in a Sample of Fully Dentate Lebanese Adults Using Cone-beam Computed Tomography Technology 
Acta Informatica Medica  2017;25(4):259-262.
The literature reports that the location of mental foramen shows differences among races. The aim of this study was to assess the mental foramen position in a sample of Lebanese population using cone-beam computed tomography (CBCT) technology.
Materials and methods:
In this study, we investigated CBCT images of 50 fully dentate Lebanese adults (23 males and 27 females). We assessed the horizontal position of the mental foramen in relation with the mandibular premolars in both right and left sides and the vertical position by measuring the distance from the upper border of the foramen to the inferior border of the body of the mandible. The data obtained were statistically analyzed using Chi-square test, and two-sided t-test. Statistical significance was set at p < 0.05.
In our sample, the mental foramen was mostly found in line with the second mandibular premolar in both sides and the mean distance from the superior border of the foramen to the inferior border of the body of the mandible was 13.0120 ± 0.98487 mm on the right and 13.0728 ± 0.96029 mm on the left.
Within the limits of this study, we concluded that in our sample of Lebanese population, there was substantial variability in the mental foramen location.
PMCID: PMC5723193
Cone-beam computed tomography; Lebanese population; mental foramen
8.  Oral lesions associated with human immunodeficiency virus in 75 adult patients: a clinical study 
The objective of this study was to investigate the presence of oral lesions in human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS) patients in a descriptive cross-sectional study, and to establish their presence according to levels of CD4+ cells (including the CD4+/CD8+ cell ratio).
Materials and Methods
A total of 75 patients infected with HIV were included. Oral lesions were observed and classified using World Health Organization classification guidelines. Potential correlations between the presence and severity of oral lesions and CD4+ cells, including the CD4+/CD8+ cell ratio, were studied.
The most frequent oral lesion detected was oral pseudomembranous candidiasis (80.0%), followed by periodontal disease (40.0%), herpetic lesions (16.0%), hairy leukoplakia (16.0%), gingivitis (20.0%), oral ulceration (12.0%), Kaposi's sarcoma (8.0%), and non-Hodgkin's lymphoma (4.0%). The CD4+ count was <200 cells/mm3 in 45 cases (60.0%), between 200–500 cells/mm3 in 18 cases (24.0%), and >500 cells/mm3 in 12 cases (16.0%). The mean CD4+ count was 182.18 cells/mm3. The mean ratio of CD4+/CD8+ cells was 0.26. All patients showed at least one oral manifestation.
There was no correlation between the CD4+/CD8+ cell ratio and the presence of oral lesions. The severity of the lesions was more pronounced when the CD4+ cell count was less than 200 cells/mm3.
PMCID: PMC5756795
Acquired immunodeficiency syndrome; CD4+; HIV; Oral lesions
9.  Nanostructured carbon electrode modified with N-doped graphene quantum dots–chitosan nanocomposite: a sensitive electrochemical dopamine sensor 
Royal Society Open Science  2017;4(11):171199.
A highly selective and sensitive dopamine electrochemical sensor based on nitrogen-doped graphene quantum dots–chitosan nanocomposite-modified nanostructured screen printed carbon electrode is presented, for the first time. Graphene quantum dots were prepared via microwave-assisted hydrothermal reaction of glucose, and nitrogen doping was realized by introducing ammonia in the reaction mixture. Chitosan incorporation played a significant role towards the selectivity of the prepared sensor by hindering the ascorbic acid interference and enlarging the peak potential separation between dopamine and uric acid. The proposed sensor's performance was shown to be superior to several recently reported investigations. The as-prepared CS/N,GQDs@SPCE exhibited a high sensitivity (i.e. ca. 418 µA mM cm−2), a wide linear range i.e. (1–100 µM) and (100–200 µM) with excellent correlations (i.e. R2 = 0.999 and R2 = 1.000, respectively) and very low limit of detection (LOD = 0.145 µM) and limit of quantification (LOQ = 0.482 µM) based on S/N = 3 and 10, respectively. The applicability of the prepared sensor for real sample analysis was tested by the determination of dopamine in human urine in pH 7.0 PBS showing an approximately 100% recovery with RSD < 2% inferring both the practicability and reliability of CS/N,GQDs@SPCE. The proposed sensor is endowed with high reproducibility (i.e. RSD = ca. 3.61%), excellent repeatability (i.e. ca. 0.91% current change) and a long-term stability (i.e. ca. 94.5% retained activity).
PMCID: PMC5717679
electrochemical sensor; graphene quantum dots; chitosan; screen printed carbon electrode; dopamine
10.  A Relationship between the aldosterone - mineralocorticoid receptor pathway and alcohol drinking: preliminary translational findings across rats, monkeys and humans 
Molecular psychiatry  2017;10.1038/mp.2017.97.
Aldosterone regulates electrolyte and fluid homeostasis through binding to the mineralocorticoid receptors (MR). Previous work provides evidence for a role of aldosterone in alcohol use disorders (AUD). We tested the hypothesis that high functional activity of the mineralocorticoid endocrine pathway contributes to vulnerability for AUD. In Study 1, we investigated the relationship between plasma aldosterone levels, ethanol self-administration, and the expression of CYP11B2 and mineralocorticoid receptor (NR3C2) genes in the prefrontal cortex area (PFC) and central nucleus of the amygdala (CeA) in monkeys. Aldosterone significantly increased after 6 and 12-month ethanol self-administration. NR3C2 expression in the CeA was negatively correlated to average ethanol intake during the 12 months. In Study 2, we measured Nr3c2 mRNA levels in the PFC and CeA of dependent and nondependent rats and the correlates with ethanol drinking during acute withdrawal. Low Nr3c2 expression levels in the CeA were significantly associated with increased anxiety-like behavior and compulsive-like drinking in dependent rats. In Study 3, the relationship between plasma aldosterone levels, alcohol drinking and craving was investigated in alcohol-dependent patients. Non-abstinent patients had significantly higher aldosterone levels than abstinent patients. Aldosterone levels positively correlated with the number of drinks consumed, craving and anxiety scores. These findings support a relationship between ethanol drinking and the aldosterone/MR pathway in three different species.
PMCID: PMC5668213  PMID: 28461696
aldosterone; mineralocorticoid receptor; alcohol use disorders; monkeys; rats; alcoholic patients; alcohol craving; animal models; principal component analysis
11.  Adenomatoid Odontogenic Tumor Associated with an Impacted Maxillary Lateral Incisor: A Case Report with Five-Year Follow-Up 
Case Reports in Dentistry  2017;2017:1709492.
Adenomatoid odontogenic tumor (AOT), a benign (hamartomatous) lesion of odontogenic origin, is an uncommon tumor which affects mainly females in the second decade. This lesion is most commonly associated with an impacted maxillary canine. This paper reported a case of AOT, in a 16-year-old female, associated with an impacted maxillary left lateral incisor. The evolution of this tumor was followed over 36 months and 24 months after excision.
PMCID: PMC5682065
12.  Ureteropelvic Junction Obstruction and Parathyroid Adenoma: Coincidence or Link? 
Case Reports in Nephrology  2017;2017:9852912.
Congenital ureteropelvic junction obstruction (UPJO) is the most common cause of upper urinary tract obstruction in children. It is generally diagnosed in the routine work-up during antenatal period and is characterized by spontaneous recovery. It can be associated with urolithiasis; hence further investigation should be carried out. We report the case of a 15-year-old boy, who is known to have right UPJO, presented with right renal colic and discovered to have bilateral kidney stones. Further studies showed primary hyperparathyroidism and genetic analysis revealed a CDC73 mutation (initially HRPT2). We believe that association of UPJO and PHPT is a rare coincidence that can be linked. Careful work-up of children with UPJO and urolithiasis is recommended to exclude an underlying metabolic disease. Surgical correction can be evitable as treatment of the primary cause can lead to complete dissolution of kidney stones and improvement of the medical condition.
PMCID: PMC5664328
13.  Unusual cause of upper gastrointestinal bleed, when OGD could be fatal 
BMJ Case Reports  2015;2015:bcr2015210804.
A 57-year-old man presented with chest pain, dyspnoea and coffee grounds emesis. He was haemodynamically stable without significant drop in haemoglobin. He suddenly developed cardiac arrest with wide complex tachycardia and became comatose. CT scan of the head revealed pneumocephalus and multiple infarcts. Given the recent history of radiofrequency ablation for atrial fibrillation, atrio-oesophageal fistula (AOF) was suspected. CT angiography of the thorax showed a 5 mm diverticulum on the posterior wall of the left atrium, also raising suspicion for AOF. The patient was taken to the operating room. An AOF was found and repaired. He did not have any further gastrointestinal bleeding. There was no neurological recovery at day 11 and life support was withdrawn per his family's request. This case highlights the importance of obtaining history of recent cardiac procedures in patients presenting with an upper gastrointestinal bleed. An oesophagogastroduodenoscopy in this patient could have been instantaneously deadly.
PMCID: PMC4600810  PMID: 26438675
14.  Bereavement support for family caregivers: The gap between guidelines and practice in palliative care 
PLoS ONE  2017;12(10):e0184750.
Standards for bereavement care propose that support should be matched to risk and need. However, studies in many countries demonstrate that palliative care services continue to adopt a generic approach in offering support to bereaved families.
To identify patterns of bereavement support in palliative care services based upon the experience of bereaved people from a population based survey and in relation to clinical practice guidelines.
An anonymous postal survey collected information from clients of six funeral providers in four Australian states (2014–15), 6 to 24 months after the death of their family member or friend, with 1,139 responding. Responses from 506 bereaved relatives of people who had terminal illnesses were analysed. Of these, 298 had used palliative care services and 208 had not.
More people with cancer (64%) had received palliative care in comparison to other illnesses such as heart disease, dementia and organ failure (4–10%). The support for family caregivers before and after their relative’s death was not considered optimal. Only 39.4% of the bereaved reported being specifically asked about their emotional/ psychological distress pre-bereavement, and just half of the bereaved perceived they had enough support from palliative care services. Half of the bereaved had a follow up contact from the service at 3–6 weeks, and a quarter had a follow-up at 6 months. Their qualitative feedback underlined the limited helpfulness of the blanket approach to bereavement support, which was often described as “not personal” or “generic”, or “just standard practice”.
Timeliness and consistency of relationship is crucial to building rapport and trust in the service’s ability to help at post-bereavement as well as a focus on the specific rather than the generic needs of the bereaved. In light of these limitations, palliative care services might do better investing their efforts principally in assessing and supporting family caregivers during the pre-bereavement period and developing community capacity and referral pathways for bereavement care. Our findings suggest that bereavement support in Australian palliative care services has only a tenuous relationship with guidelines and assessment tools, a conclusion also drawn in studies from other countries, emphasizing the international implications of our study.
PMCID: PMC5627900  PMID: 28977013
15.  Reduction of intracerebral hemorrhage in hemodialysis patients after reducing aspirin use: A quality-assurance observational study 
PLoS ONE  2017;12(10):e0185847.
There is so far no international consensus concerning the prescription of antithrombotic agents in hemodialysis patients. It is not clear yet why they cause more bleeding in some patients and are beneficial in others. We therefore tried to find out what triggers bleeding in this population. This is an observational before-and-after study that included all patients undergoing hemodialysis in our center between 2005 and 2015. We divided the study into two phases: phase one (125 patients) where aspirin was used without restrictions and phase two (110 patients) where aspirin was avoided in severe hypertension and primary prevention. We aimed to assess the differential occurrence of intracerebral hemorrhage between the two phases and the cardiovascular mortality of patients whether on aspirin or not. Bleeding events occurred in 12.8% of patients in phase one and 13.6% in phase two (p = 0.85). Seven out of 125 patients (6%) in phase one experienced intracerebral hemorrhage and none in phase two. Intracerebral hemorrhage was significantly increased in those with the combination of aspirin and severe hypertension (p = 0.003). Aspirin and acenocoumadin were significantly associated with total bleeding (OR = 3.81 and 4.85 with p = 0.005 and 0.001 respectively). Cardiovascular mortality did not differ between phase one and two whether patients were on aspirin or not (p = 0.45 and 0.31 respectively). Minimizing aspirin use in hemodialysis patients with severe hypertension reduced intracerebral bleeding without a significant difference in cardiovascular mortality.
PMCID: PMC5624631  PMID: 28968454
16.  What pelvic radiation disease symptoms are experienced by patients receiving external beam radiotherapy and a high-dose-rate brachytherapy boost for prostate cancer? 
Research describing proctitis or pelvic radiation disease symptoms of prostate cancer patients one year after external beam radiotherapy (EBRT) plus high-dose-rate (HDR) brachytherapy is limited. This study aimed to assess prostate cancer patients’ pelvic radiation disease symptoms from baseline to 12 months post-radiotherapy.
Material and methods
Men with prostate cancer referred for EBRT and HDR brachytherapy were recruited. Patients’ age, diagnosis, staging, PSA, past medical history, and treatment were recorded. Pelvic radiation disease symptoms were assessed via the Phase III EORTC proctitis module. Patients completed questionnaires before radiotherapy (baseline) and at one, three, six, and 12 months afterwards. To assess acute toxicity, symptoms one month after radiotherapy were compared with baseline. To assess post-treatment recovery, symptoms at three, six, and 12 months post radiotherapy were compared with one month. Symptom changes over time were assessed with linear mixed effect models.
Two hundred and sixty-six patients were recruited. Mean scores were below 2 at all time-points. The proportion of patients experiencing symptoms were also calculated. Linear mixed effect models showed that time-point, age, and T-stage were associated with some pelvic radiation disease symptoms.
Patients receiving EBRT plus HDR brachytherapy to the prostate experienced mild pelvic radiation disease symptoms. Determining the proportion of patients with symptoms provided the most meaningful data.
PMCID: PMC5705828
brachytherapy; proctitis; prostate cancer; radiation therapy; signs and symptoms
17.  Predictive value of brain 18F-FDG PET/CT in macrophagic myofasciitis? 
Medicine  2017;96(39):e8134.
Although several functional studies have demonstrated that positron emission tomography/computed tomography with 18F-fluorodeoxyglucose (18F-FDG PET/CT) appears to be efficient to identify a cerebral substrate in patients with known macrophagic myofasciitis (MMF), the predictive value of this imaging technique for MMF remains unclear.
Patient concerns:
We presented data and images of a 46-year-old woman.
The patient was referred to our center for suspected MMF due to diffuse arthromyalgias and cognitive disorder (involving an impairment of visual selective attention and a weakness in executive functions revealed by neuropsychological assessment) which occurred few years after last vaccine injections.
After a first negative deltoid muscle biopsy, a brain 18F-FDG PET/CT was performed and revealed the known spatial pattern of a cerebral glucose hypometabolism involving occipital cortex, medial temporal areas, and cerebellum.
Given the clinical suspicion of MMF and brain 18F-FDG PET/CT findings, a 2nd deltoid muscle biopsy was performed and confirmed the diagnosis of MMF with typical histopathological features.
This case highlights the predictive value of brain 18F-FDG PET/CT as a noninvasive imaging tool for MMF diagnosis, even when muscle biopsy result comes back negative.
PMCID: PMC5626290  PMID: 28953647
aluminum hydroxide; brain imaging; 18F-FDG; macrophagic myofasciitis; PET/CT
18.  Temporal dynamics and Leishmania infantum infection prevalence of Phlebotomus perniciosus (Diptera, Phlebotominae) in highly endemic areas of visceral leishmaniasis in Tunisia 
PLoS ONE  2017;12(9):e0184700.
Phlebotomus perniciosus is one of the major vectors of Leishmania infantum in the Mediterranean basin. The aim of this work was (i) to provide information about abundance and temporal dynamics of this Larroussius species in a hot spot area of visceral leishmaniasis in Tunisia, (ii) to detect L. infantum DNA in wild caught female sandflies and (iii) to measure Phlebotomus perniciosus infection rate throughout the active season. Sandflies were collected monthly during one year using CDC miniature light-traps in house and in animal shelters. Male specimens were identified at species level according to morphological characters. Female specimens were conserved individually for molecular study. Leishmania infection was tested by kinetoplast DNA real-time PCR and ITS-1 PCR-sequencing. Subsequent sandfly species identification of infected specimens was done by mitochondrial cytochrome b sequencing. In one year period, overall 4,441 specimens (2230 males and 2211 females) were collected. Sandfly activity started in end-April and ended in early-November. Mean sandfly density in house was significantly lower than in animal shelters (51 ± 50 versus 504 ± 460 sandflies /CDC night, p<0.05). However, a higher proportion of females was found in house (58.4% versus 49.2%, p<0.001). Based on species identification of male specimens, Phlebotomus perniciosus was the dominant species (56% of the whole male sandfly fauna, p<0.0001). It showed two peaks of density in the active season, a sharp one in early May and a higher long lasting one from end-July to end-September. DNA was extracted from 190 female specimens randomly sampled and corresponding to 96 specimens from house and 94 from animal shelters. Twenty four female sandfly were infected by Leishmania infantum. All infected specimens were recognized as Phlebotomus perniciosus. Leishmania infantum infection rate in female sandflies was 2.3 fold higher in house than in animal shelters (17.7% versus 7.4%, p<0.05). In house, estimated number of infected specimens was the highest at the end of the active season. Abundance, dynamics of density and Leishmania infantum infection prevalence of Phlebotomus perniciosus in Tunisian hot spot of visceral leishmaniasis highlight the major role of this Phlebotominae species in L. infantum transmission.
PMCID: PMC5608219  PMID: 28934263
19.  Oxidative stress and prostatic diseases 
Molecular and Clinical Oncology  2017;7(5):723-728.
Prostatic diseases are a common health problem among males in Western countries, and include chronic prostatic diseases, which have an unclear pathogenesis and few treatment options. In vitro and in vivo studies describe oxidative stress as a major pathway involved in the occurrence of benign prostatic hyperplasia, prostatic cancer and chronic prostatitis. Thus, the oxidative stress cascade is a potential target for the treatment of prostatic diseases. This paper presents a systematic review of the available data concerning the association between oxidative stress and the most common chronic prostatic diseases, and describes the available treatment options that act upon this pathway.
PMCID: PMC5700279
oxidative stress; reactive oxygen species; prostate; prostate cancer; benign prostatic hyperplasia
20.  Epidemiological features and pathological study of avian leukosis in turkeys’ flocks 
Veterinary World  2017;10(9):1135-1138.
The purpose of this study was focused on the identification of tumor diseases in turkeys on the basis of a detailed description of epidemiological features, clinical signs, lesions, and histopathological changes.
Materials and Methods:
Outbreak of a tumor disease in turkeys was investigated in various regions of Eastern Algeria. Four turkeys’ flocks aged from 17 weeks were affected, resulting to mortality often over 10%, on a period of 15 days. The main epidemiological characters, clinical signs, and lesions were observed throughout all the course of the disease. Serum samples were collected from affected turkeys in each flock to detect p27 antigen in enzyme-linked immunosorbent assay (ELISA) test to diagnose avian leukosis virus (ALV). Portions of sciatic nerves and livers are taken from dead turkeys for microscopic examination.
The disease was characterized by clinical signs such as anorexia, weakness, and diarrhea. Necropsy of the dead birds showed hepatomegaly and gross splenomegaly with neoplastic nodules or gray foci and diffuse infiltration in the myocardium and lungs. ALV antigen test using ELISA confirmed the presence of virus leukosis. Histopathological sections of the liver had proliferations of lymphoblastoid cells and absence of any modifications or lymphocytic infiltration in peripheral nerves.
The present study confirms that this disease condition is caused by lymphoid leukosis.
PMCID: PMC5639114
enzyme-linked immunosorbent assay; epidemiological features; histopathology; lesions; leukosis; turkeys
21.  Assessment of Hygiene Habits in Acrylic Denture Wearers: a Cross-sectional Study 
Materia Socio-Medica  2017;29(3):216-218.
To assess the denture hygiene habits in a population of Lebanese denture wearers.
Materials and Methods:
One hundred and thirty-two (132) patients [71 women (53.8%) and 61 men (46.2%)] wearing their acrylic dentures for more than two years were included in this study. The hygiene methods related to their dentures were evaluated and the data obtained were analyzed statistically using the IBM® SPSS® statistics 20.0 (USA) statistical package.
Regardless of the cleaning technique, the big majority of our participants [123 out of 132 (93.1%)] cleaned their dentures daily. The two mostly used denture cleaning techniques were rinsing with tap water (34.1%) and brushing with toothpaste (31.8%). Nearly half of our patients (45.5%) soaked their dentures during the night; most of them with cleansing tablets dissolved in water (28.8%).
Within the limitations of our study, it was concluded that in a sample of Lebanese population surveyed about denture hygiene habits, the daily frequency of denture cleaning is satisfactory, but the techniques and products used were self-estimated and, consequently, not sufficient.
PMCID: PMC5644200
denture hygiene; habits; Lebanese; population
22.  Cerebral 18F-FDG PET in macrophagic myofasciitis: An individual SVM-based approach 
PLoS ONE  2017;12(7):e0181152.
Macrophagic myofasciitis (MMF) is an emerging condition with highly specific myopathological alterations. A peculiar spatial pattern of a cerebral glucose hypometabolism involving occipito-temporal cortex and cerebellum have been reported in patients with MMF; however, the full pattern is not systematically present in routine interpretation of scans, and with varying degrees of severity depending on the cognitive profile of patients. Aim was to generate and evaluate a support vector machine (SVM) procedure to classify patients between healthy or MMF 18F-FDG brain profiles.
18F-FDG PET brain images of 119 patients with MMF and 64 healthy subjects were retrospectively analyzed. The whole-population was divided into two groups; a training set (100 MMF, 44 healthy subjects) and a testing set (19 MMF, 20 healthy subjects). Dimensionality reduction was performed using a t-map from statistical parametric mapping (SPM) and a SVM with a linear kernel was trained on the training set. To evaluate the performance of the SVM classifier, values of sensitivity (Se), specificity (Sp), positive predictive value (PPV), negative predictive value (NPV) and accuracy (Acc) were calculated.
The SPM12 analysis on the training set exhibited the already reported hypometabolism pattern involving occipito-temporal and fronto-parietal cortices, limbic system and cerebellum. The SVM procedure, based on the t-test mask generated from the training set, correctly classified MMF patients of the testing set with following Se, Sp, PPV, NPV and Acc: 89%, 85%, 85%, 89%, and 87%.
We developed an original and individual approach including a SVM to classify patients between healthy or MMF metabolic brain profiles using 18F-FDG-PET. Machine learning algorithms are promising for computer-aided diagnosis but will need further validation in prospective cohorts.
PMCID: PMC5509294  PMID: 28704562
23.  High Dephosphorylated-Uncarboxylated MGP in Hemodialysis patients: risk factors and response to vitamin K2, A pre-post intervention clinical trial 
BMC Nephrology  2017;18:191.
Vascular calcifications are highly prevalent in hemodialysis patients. Dephosphorylated-uncarboxylated MGP (dp-ucMGP) was found to increase in vitamin K-deficient patients and may be associated with vascular calcifications. Supplementation of hemodialysis patients with vitamin K2 (menaquinone-7) has been studied in Europe with a maximum 61% drop of dp-ucMGP levels. The aim of this study is to assess first the drop of dp-ucMGP in an Eastern Mediterranean cohort after vitamin K2 treatment and second the correlation between baseline dp-ucMGP and vascular calcification score.
This is a prospective, pre-post intervention clinical trial involving 50 hemodialysis patients who received daily 360 μg of menaquinone-7 for 4 weeks. At baseline they were assessed for plasma dp-ucMGP levels and vascular calcification scores (AC-24) as well as for other demographic, clinical and biological variables. Dp-ucMGP levels were measured a second time at 4 weeks.
At baseline, dp-ucMGP levels were extremely elevated with a median of 3179.15 (1825.25; 4339.50) pM and correlated significantly with AC-24 (Spearman’s rho = 0.43, P = 0.002). Using a bivariate regression analysis, the association between dp-ucMGP levels and AC-24 was most significant when comparing dp-ucMGP levels less than 1000 to those more than 1000 pM (P = 0.02). Dp-ucMGP levels higher than 5000 pM were significantly associated with females, patients with recent fracture and patients with lower serum albumin (respectively P = 0.02, 0.004 and 0.046).
The average drop of dp-ucMGP at 4 weeks of treatment was found to be 86% with diabetics having the lowest drop rate (P = 0.01).
Vitamin K deficiency, as assessed by high dp-ucMGP levels, is profound in hemodialysis patients from the Eastern Mediterranean region and it is significantly correlated with vascular calcifications. Daily 360 μg of menaquinone-7, given for 4 weeks, effectively reduces dp-ucMGP in this population. Future studies are needed to assess the changes in vascular calcifications in hemodialysis patients treated with vitamin K2 over a longer follow-up period.
Trial registration
The clinical trial was registered on (Identification number NCT02876354, on August 11, 2016).
PMCID: PMC5463325
Dephosphorylated Uncarboxylated matrix Gla protein; Pre-post intervention clinical trial; Hemodialysis; Menaquinone-7; Vascular calcifications; Vitamin K2
24.  Language assessment of children with severe liver disease in a public service in Brazil 
Clinics  2017;72(6):351-357.
The aim of this research was to compare language development (expressive and receptive skills) in children awaiting liver transplantation with that of children who have already undergone the surgical procedure.
An observational, descriptive, cross-sectional study was conducted with 76 children divided into groups, as follows: 31 children who were candidates for liver transplantation (Group 1; G1), 45 children who had already undergone liver transplantation (Group 2; G2), and a control group (CG) of 60 healthy, normally developing children. Health status information was gathered, and the Test of Early Language Development (TELD)-3 was used to assess language skills. Family household monthly income data were also gathered using a specific questionnaire.
G1 had poorer language performance compared with G2 and the CG. G2 had lower language performance when compared with the CG. However, when considering the TELD-3 standard scores, G2 had scores within normal limits. The regression analysis indicated age as a risk factor for language deficits in Group 1 and family income as a risk factor for language deficits in G2.
The results suggested that children with chronic liver disease have delays in language development. Transplanted children have linguistic performance within normal limits, but their scores tended to be lower than the CG.
PMCID: PMC5463267
Child Language; Language Development; Language Development Disorders; Liver Transplantation; Language Tests
25.  Amyotrophic lateral sclerosis: improving care with a multidisciplinary approach 
Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease, leading to death within an average of 2–3 years. A cure is yet to be found, and a single disease-modifying treatment has had a modest effect in slowing disease progression. Specialized multidisciplinary ALS care has been shown to extend survival and improve patients’ quality of life, by providing coordinated interprofessional care that seeks to address the complex needs of this patient group. This review examines the nature of specialized multidisciplinary care in ALS and draws on a broad range of evidence that has shaped current practice. The authors explain how multidisciplinary ALS care is delivered. The existing models of care, the role of palliative care within multidisciplinary ALS care, and the costs of formal and informal care are examined. Critical issues of ALS care are then discussed in the context of the support rendered by multidisciplinary-based care. The authors situate the patient and family as key stakeholders and decision makers in the multidisciplinary care network. Finally, the current challenges to the delivery of coordinated interprofessional care in ALS are explored, and the future of coordinated interprofessional care for people with ALS and their family caregivers is considered.
PMCID: PMC5446964
quality of life; interdisciplinary; interprofessional; palliative care; care coordination; motor neuron disease

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