Experimental and molecular dynamics studies of an ultra-fast sequential hydrogen plasma process for fabricating phosphorene-based sensors.

Low concentration phosphorene-based sensors have been fabricated using a facile and ultra-fast process which is based on an exfoliation-free sequential hydrogen plasma treatment to convert the amorphous phosphorus thin film into mono- or few-layered phosphorene sheets. These sheets have been realized directly on silicon substrates followed by the fabrication of field-effect transistors showing the low leakage current and reasonable mobility for the nano-sensors. Being capable of covering the whole surface of the silicon substrate, red phosphorus (RP) coated substrate has been employed to achieve large area phosphorene sheets. Unlike the available techniques including mechanical exfoliation, there is no need for any exfoliation and/or transfer step which is significant progress in shortening the device fabrication procedure. These phosphorene sheets have been examined using transmission electron microscopy (TEM), Scanning electron microscopy (SEM), Raman spectroscopy and atomic-force microscopy (AFM). Electrical output in different states of the crystallization as well as its correlation with the test parameters have been also extensively used to examine the evolution of the phosphorene sheets. By utilizing the fabricated devices, the sensitivity of the phosphorene based-field effect transistors to the soluble L-Cysteine in low concentrations has been studied by measuring the FET response to the different concentrations. At a gate voltage of - 2.5 V, the range of 0.07 to 0.60 mg/ml of the L-Cysteine has been distinguishably detected presenting a gate-controlled sensor for a low-concentration solution. A reactive molecular dynamics simulation has been also performed to track the details of this plasma-based crystallization. The obtained results showed that the imparted energy from hydrogen plasma resulted in a phase transition from a system containing red phosphorus atoms to the crystal one. Interestingly and according to the simulation results, there is a directional preference of crystal growth as the crystalline domains are being formed and RP atoms are more likely to re-locate in armchair than in zigzag direction.

Progastrin production transitions from Bmi1+/Prox1+ to Lgr5high cells during early intestinal tumorigenesis.

Progastrin is an unprocessed soluble peptide precursor with a well-described tumor-promoting role in colorectal cancer. It is expressed at small levels in the healthy intestinal mucosa, and its expression is enhanced at early stages of intestinal tumor development, with high levels of this peptide in hyperplastic intestinal polyps being associated with poor neoplasm-free survival in patients. Yet, the precise type of progastrin-producing cells in the healthy intestinal mucosa and in early adenomas remains unclear. Here, we used a combination of immunostaining, RNAscope labelling and retrospective analysis of single cell RNAseq results to demonstrate that progastrin is produced within intestinal crypts by a subset of Bmi1+/Prox1+/LGR5low endocrine cells, previously shown to act as replacement stem cells in case of mucosal injury. In contrast, our findings indicate that intestinal stem cells, specified by expression of the Wnt signaling target LGR5, become the main source of progastrin production in early mouse and human intestinal adenomas. Collectively our results suggest that the previously identified feed-forward mechanisms between progastrin and Wnt signaling is a hallmark of early neoplastic transformation in mouse and human colonic adenomas.

Global prevalence of latent toxoplasmosis in pregnant women: a systematic review and meta-analysis.

BACKGROUND: Toxoplasma gondii infection, if acquired as an acute infection during pregnancy, can have substantial adverse effects on mothers, fetuses and newborns. Latent toxoplasmosis also causes a variety of pathologies and has been linked to adverse effects on pregnancy. OBJECTIVE: Here, we present results of a comprehensive systematic review and meta-analysis of the global prevalence of latent toxoplasmosis in pregnant women. DATA SOURCE: We searched PubMed, EMBASE, Web of Science, SciELO and Scopus databases for relevant studies that were published between 1 January 1988 and 20 July 2019. STUDY ELIGIBILITY CRITERIA: All population-based, cross-sectional and longitudinal studies reporting the prevalence of latent toxoplasmosis in healthy pregnant women were considered for inclusion. PARTICIPANTS: Pregnant women who were tested for prevalence of latent toxoplasmosis. INTERVENTIONS: There were no interventions. METHOD: We used a random effects model to calculate pooled prevalence estimates with 95% confidence intervals (CIs). We grouped prevalence data according to the geographic regions defined by the World Health Organization (WHO). Multiple subgroup and meta-regression analyses were performed. RESULTS: In total, 311 studies with 320 relevant data sets representing 1 148 677 pregnant women from 91 countries were eligible for inclusion in the meta-analysis. The global prevalence of latent toxoplasmosis in pregnant women was estimated at 33.8% (95% CI, 31.8-35.9%; 345 870/1 148 677). South America had the highest pooled prevalence (56.2%; 50.5-62.8%) of latent toxoplasmosis in pregnant women, whereas the Western Pacific region had the lowest prevalence (11.8%; 8.1-16.0%). A significantly higher prevalence of latent toxoplasmosis was associated with countries with low income and low human development indices (p < 0.001). CONCLUSION: Our results indicate a high level of latent toxoplasmosis in pregnant women, especially in some low- and middle-income countries of Africa and South America, although the local prevalence varied markedly. These results suggest a need for improved prevention and control efforts to reduce the health risks to women and newborns.

Echinococcus granulosus genotypes in Iran: a systematic review.

Cystic echinococcosis (CE) caused by Echinococcus granulosus sensu lato (s.l.) is a significant zoonosis, especially in developing countries of the Middle East, with many studies focusing on CE genotypes in Iran. We performed a systematic review to determine the exact status of E. granulosus genotypes in the country. We explored English (Pubmed, Scopus, ISI Web of Science and Science Direct) and Persian (Magiran, Iran Medex and Scientific Information Database) databases along with Google Scholar. Our review included 73 studies published prior to the end of 2015. In total, 2952 animal (intermediate and definitive) hosts were examined, and the prevalent genotypes comprised G1 (92.75%) and G6 (4.53%) in sheep, cattle, camels, goats and buffaloes; G3 (2.43%) in five herbivore hosts and dogs; G7 (0.2%) in sheep and goats; and G2 (0.06%) in dogs. G1 was mostly dominant in West Azerbaijan, whereas G3 and G6 were identified most frequently in the provinces of Isfahan and Fars, respectively. Regarding human CE infection, 340 cases were reported from Iran, with the identified genotypes G1 (n = 320), G6 (n = 13) and G3 (n = 7). Most CE-infected humans originated from Isfahan province (168 cases), whereas the lowest number of infected persons was noted in Kerman province (two cases). The information obtained from this systematic review is central to better understanding the biological and epidemiological characteristics of E. granulosus s.l. genotypes in Iran, leading to more comprehensive control strategies.

Seroprevalence and molecular evaluation of Toxoplasma gondii in Schizophrenic patients hospitalized in Sistan and Baluchestan province, Southeast of Iran.

Over one-third of the world's population are seropositive for Toxoplasma gondii. One of the important traits of T. gondii is its ability to alter and manipulating the behavior and personality of its intermediate host. The current study was aimed to determine the prevalence of acute and chronic toxoplasmosis in those persons suffer from schizophrenia using serological and molecular techniques. In this cross-sectional study, blood samples were taken from 118 Schizophrenia patients hospitalized in Sistan and Baluchestan province, southeast of Iran. IgM and IgG anti-Toxoplasma antibodies were measured using enzyme-linked immunosorbent assay (ELISA). Furthermore, the presence of parasite was evaluated using nested-PCR B1 gene. Among 118 schizophrenic patients, 48 (40.67%), 4 (3.37%) and 14 (11.86%) were tested seropositive only for IgG, only for IgM and for both of IgG/IgM. So that, total prevalence was 66/118 (55.91%). All samples were also examined using nested-PCR and T. gondii DNA was found in 41 (34.74%) samples. Our study showed high seroprevalence of toxoplasmosis in southeast of Iran.

Seroprevalence and molecular detection of Toxoplasma gondii in healthy blood donors in southwest Iran.

BACKGROUND: Toxoplasmosis is a cosmopolitan parasitic disease caused by Toxoplasma gondii (T. gondii). Blood transfusion is a probable route of T. gondii transmission. Due to lack of information about seroprevalence of T. gondii in healthy blood donors, this study was aimed to determine the chronic and acute infection using serological and molecular methods. MATERIAL AND METHODS: In this cross-sectional investigation, 380 samples were collected from donated bloods. Anti-Toxoplasma IgG and IgM antibodies were examined using enzyme-linked immunosorbent assay (ELISA). Also, all IgG positive samples were tested by IgG avidity test. Eventually, to detection of active infection, DNA was extracted from IgM positive and low IgG avidity samples and then tested using nested-polymerase chain reaction (PCR). RESULTS: Among 380 blood donors, 131 (34.47%) were positive for only anti-T. gondii IgG, 2 (0.5%) were positive for only anti-T. gondii IgM, and 11 (2.9%) were positive for both IgG and IgM antibodies. Then, 142 samples (131 IgG + and 11 IgG +IgM +) were evaluated using IgG avidity test. Of these, 115 (81%) had high avidity IgG indicates past infection; 16 (11.26%) had low avidity IgG representing recent infection, and 11 (7.74%) were equivocal. With nested PCR, 20 samples of 50 seropositive samples were diagnosed positive. CONCLUSION: Detected active infection using nested-PCR draws attention to the possibility of T. gondii infection via blood transfusion which emphasizes the importance of parasite DNA screening before donation of blood in high risk groups such as: multi-transfused persons, immunosuppressed patient, and pregnant women.

Prevalence of cystic echinococcosis in Iran: a systematic review and meta-analysis.

As a significant zoonosis, cystic echinococcosis (CE) is endemic in some parts of the world, such as the Middle East. There are studies on the prevalence of this infection in animal and human reservoirs in Iran; hence, we conducted this meta-analysis to elucidate the prevalence of CE in Iran. English (PubMed, Scopus, Web of Science, Science Direct and Google Scholar) and Persian (Magiran, Iran Medex, Iran Doc and SID) databases were explored. In the case of definitive, animal and human intermediate hosts, 37, 90 and 33 studies, respectively, have been included in the current review from January 1990 to December 2015. According to outcomes of the heterogeneity test, either Der Simonian and Laird's random-effects method or Mantel-Haenszel's fixed-effects method were employed to pool the estimations. The pooled prevalence of Echinococcus granulosus infection in definitive hosts was calculated as 23.6% (95% confidence interval (CI) = 17.6-30.1%). The weighted prevalence of animal and human hydatidosis was calculated as 15.6% (95% CI = 14.2-17.1%) and 4.2% (95% CI = 3.0-5.5%), respectively. Meanwhile, most cases of human hydatidosis were in southern Iran, with a prevalence of 5.8% (3.2-9.2%). In terms of human hydatidosis, more infections were found in rural regions, and mostly in female individuals. Egger's regression test revealed publication bias, with a remarkable impact on total prevalence of the infection in animal intermediate hosts (P < 0.001), while it was not significant in human hosts (P = 0.4) and definitive hosts (P = 0.3). According to the weighted estimated prevalence of cystic echinococcosis and its financial burden, implementing appropriate control programmes should be compulsory to decrease the burden of the disease in Iran.

Celiac disease hidden by cryptogenic hypertransaminasemia mistaken for fatty liver.

A variety of signs and symptoms have been reported in regards to the typical and atypical presentations of CD. It is now well recognised that its onset may occur at any age and that atypical forms of CD are much more prevalent than its classic form (1).In this case, where the patient presented with high BMI and evidence of grade I of fatty liver disease, CD was suspected due to mildly abnormal bloating, cryptogenic hypertransaminasemia, abnormal LFT and poor response to fatty liver treatment. This presentation type is not uncommon; diagnosis was confirmed by the presence of subtotal villous atrophy in the biopsy specimen, positive specific antibody screening (AGA, tTG and EMA antibodies), negative antibody screening and normalization of liver enzymes on a gluten-free diet (Tab. 2, Ref. 13).

Ion-pair strategy for enabling amifostine oral absorption: rat in situ and in vivo experiments.

This study shows the effect of ion pair formation on intestinal absorption and oral bioavailability of amifostine. Amifostine is a prodrug used as a highly potent and selective radiotherapy and chemotherapy protectant but due to its low lipophilicity and charge at physiological pH range, its trans epithelial transport and its potential for oral drug delivery is very low. Ion pair formation with negatively charged counter ions was evaluated by in situ rat perfusion studies as a possible strategy to enhance intestinal absorption of amifostine. Succinic acid, phthalic acid and benzoic acid were used as counter ions. Rat intestinal perfusion studies confirmed a statistically significant increase in amifostine permeability in the presence of the counter ions in the order of succinic>phthalic>benzoic. Rat pharmacokinetic studies in vivo were performed to calculate oral absolute bioavailability of amifostine alone and with ion pairs in order to confirm the in situ perfusion results and the applicability of the ion pair approach. Intravenous and intraduodenal administrations were done in rats using a permanent jugular vein cannulation technique and a duodenal cannulation method to avoid drug degradation in stomach. In vivo oral bioavailability studies demonstrated a 20-30-fold increase in amifostine bioavailability with succinic acid depending on counter ion ratio and 10-fold increase with phthalic acid as ion pair. In summary ion pair strategy with succinic acid could enable amifostine oral administration on enteric coated formulations.

Mathematical modelling of the transport of hydroxypropyl-ß-cyclodextrin inclusion complexes of ranitidine hydrochloride and furosemide loaded chitosan nanoparticles across a Caco-2 cell monolayer.

Chitosan nanoparticles (CS-NPs) have been used to enhance the permeability of furosemide and ranitidine hydrochloride (ranitidine HCl) which were selected as candidates for two different biopharmaceutical drug classes having low permeability across Caco-2 cell monolayers. Drugs loaded CS-NPs were prepared by ionic gelation of CS and pentasodium tripolyphosphate (TPP) which added to the drugs inclusion complexes with hydroxypropyl-ß-cyclodextrin (HP-ßCD). The stability constants for furosemide/HP-ßCD and ranitidine HCl/HP-ßCD were calculated as 335 M(-1) and 410 M(-1), whereas the association efficiencies (AE%) of the drugs/HP-ßCD inclusion complexes with CS-NPs were determined to be 23.0 and 19.5%, respectively. Zetasizer and scanning electron microscopy (SEM) were used to characterise drugs/HP-ßCD-NPs size and morphology. Transport of both nano and non-nano formulations of drugs/HP-ßCD complexes across a Caco-2 cell monolayer was assessed and fitted to mathematical models. Furosemide/HP-ßCD-NPs demonstrated transport kinetics best suited for the Higuchi model, whereas other drug formulations demonstrated power law transportation behaviour. Permeability experiments revealed that furosemide/HP-ßCD and ranitidine HCl/HP-ßCD nano formulations greatly induce the opening of tight junctions and enhance drug transition through Caco-2 monolayers.

Computer-aided manufacturing of implants for the repair of large cranial defects: an improvement of the stereolithography technique.

The objective of this study is to demonstrate the utility of geometric modeling in cranioplasty; in other words, to use geometric modeling to generate a prototype that will be used as the base structure of a composite prosthesis for covering cranial defects. This geometric model is easy to manipulate and can be modified. To achieve this goal, the top surface of a cranial bone flap is digitized using a portable coordinate measurement machine. Intentionally, a sub-surface of the bone flap, representing the skull defect, was not digitized. A geometric model of the bone flap is generated that includes the undigitized region. With the technique described in this paper the authors generated the geometric model of the undigitized region (the skull defect). The geometric model of the bone flap is further manipulated and a series of conical cavities are introduced. Prototypes of the geometric models are manufactured using stereolithography. The clinical implications of this technique are discussed.

Stereolithography: application to neurosurgery

Computer-aided design (CAD) and computer-aided manufacturing (CAM) by stereolithography are already being widely used in industry for the design and manufacture of new parts and have already shown accuracy in reproducing the desired model. The only shortcoming of this technique is that it can only make one model at a time, a "prototype." It cannot be used for mass production. It is precisely this property, namely making a prototype, that makes it so attractive in reconstructive surgery and implantation of prostheses, where each "part" has to be adapted to the unique anatomy of the patient. It was not until the early nineties that reports of the application of stereolithography to reconstructive surgery appeared in the literature, and even now they are scarce. However, it is a very promising technique, and we think that it is important for physicians to familiarize themselves with this concept.

Third ventriculostomy, phase-contrast cine MRI and endoscopic techniques.

Endoscopic third ventriculostomy has become an increasingly popular procedure. This is mainly due to the improvement of the endoscopes. The progress in imaging techniques and Phase-Contrast Cine MRI in particular offers a reliable method of pre-and post-operative assessment of the patients. Two endoscopes, NeuroPEN and Channel Neuroendoscope (Medtronic PS Medical, CA, USA) have been evaluated in our center for third ventriculostomy. These instruments are light, have a good maneuverability and are disposable. The illumination and the quality of the image are excellent. We have performed Phase-Contrast Cine MRI pre-operatively and post-operatively for our patients. It offers a good assessment of the patency of the ventriculostomy and the fluid dynamics of the CSF pathways. Endoscopic third ventriculostomy is the technique of choice for the treatment of obstructive hydrocephalus. This is mainly due to two points: The progress in the endoscopic instrumentation (namely the reduction in size of endoscopes and introduction of disposable models), and the establishment of Phase-Contrast Cine MRI as the gold standard method for the pre- and post-operative evaluation of the CSF dynamics. However, to date, no technique can show the patency of the subarachnoid space, which is the most important predictive factor of surgical outcome.