Actinomyces israelii (AI) is a Gram-positive, rod-shaped bacterium that lives commensally on and within humans as a typical colonizer within the gastrointestinal tract, including the mouth. As an ...opportunistic pathogen, infection often results from tissue injury or breach of the mucosal barrier (ie, during various dental or GI procedures, aspiration, or specific pathologies such as diverticulitis). Symptoms generally present slowly as a non-tender, indurated mass that evolves into multiple abscesses, fistulae, or draining sinus tracts without regard for anatomical barriers, including fascial planes or lymphatic drainage. However, it may also present as an acute suppurative infection with pain and rapid progression to abscess formation.
Malaria incidence has reached staggering numbers in Venezuela. Commonly, Bolívar State accounted for approximately 70% of the country cases every year. Most cases cluster in the Sifontes ...municipality, a region characterized by an extractive economy, including gold mining. An increase in migration to Sifontes, driven by gold mining, fueled a malaria spillover to the rest of the country and the region. Here samples collected in 2018 were compared with a previous study of 2003/2004 to describe changes in the parasites population structures and the frequency of point mutations linked to anti-malarial drugs.
A total of 88 Plasmodium falciparum and 94 Plasmodium vivax isolates were collected in 2018 and compared with samples from 2003/2004 (106 P. falciparum and 104 P. vivax). For P. falciparum, mutations linked to drug resistance (Pfdhfr, Pfdhps, and Pfcrt) and the Pfk13 gene associated with artemisinin delayed parasite clearance, were analysed. To estimate the multiplicity of infection (MOI), and perform P. falciparum and P. vivax population genetic analyses, the parasites were genotyped by using eight standardized microsatellite loci.
The P. falciparum parasites are still harbouring drug-resistant mutations in Pfdhfr, Pfdhps, and Pfcrt. However, there was a decrease in the frequency of highly resistant Pfdhps alleles. Mutations associated with artemisinin delayed parasite clearance in the Pfk13 gene were not found. Consistent with the increase in transmission, polyclonal infections raised from 1.9% in 2003/2004 to 39% in 2018 in P. falciparum and from 16.3 to 68% in P. vivax. There is also a decrease in linkage disequilibrium. Bayesian clustering yields two populations linked to the time of sampling, showing that the parasite populations temporarily changed. However, the samples from 2003/2004 and 2018 have several alleles per locus in common without sharing multi-locus genotypes.
The frequency of mutations linked with drug resistance in P. falciparum shows only changes in Pfdhps. Observations presented here are consistent with an increase in transmission from the previously circulating parasites. Following populations longitudinally, using molecular surveillance, provides valuable information in cases such as Venezuela with a fluid malaria situation that is affecting the regional goals toward elimination.
Mutations in the
(
) gene are linked to delayed parasite clearance in response to artemisinin-based combination therapies (ACTs) in Southeast Asia. To explore the evolutionary rate and constraints ...acting on this gene,
orthologs from species sharing a recent common ancestor with
and
were analyzed. These comparative studies were followed by genetic polymorphism analyses within
using 982 complete
sequences from public databases and new data obtained by next-generation sequencing from African and Haitian isolates. Although
orthologs evolve at heterogeneous rates, the gene was conserved across the genus, with only synonymous substitutions being found at residues where mutations linked to the delayed parasite clearance phenotype have been reported. This suggests that those residues were under constraint from undergoing nonsynonymous changes during evolution of the genus. No fixed nonsynonymous differences were found between
and its orthologs in closely related species found in African apes. This indicates that all nonsynonymous substitutions currently found in
are younger than the time of divergence between
and its closely related species. At the population level, no mutations linked to delayed parasite clearance were found in our samples from Africa and Haiti. However, there is a high number of single
mutations segregating in
populations, and two predominant alleles are distributed worldwide. This pattern is discussed in terms of how changes in the efficacy of natural selection, affected by population expansion, may have allowed for the emergence of mutations tolerant to ACTs.
Methoxychlor (MXC) and vinclozolin (VIN) are well-recognized endocrine disrupting chemicals known to alter epigenetic regulations and transgenerational inheritance; however, non-endocrine disruption ...endpoints are also important. Thus, we determined the effects of MXC and VIN on the dysregulation of gap junctional intercellular communication (GJIC) and activation of mitogen-activated protein kinases (MAPKs) in WB-F344 rat liver epithelial cells. Both chemicals induced a rapid dysregulation of GJIC at non-cytotoxic doses, with 30 min EC50 values for GJIC inhibition being 10 µM for MXC and 126 µM for VIN. MXC inhibited GJIC for at least 24 h, while VIN effects were transient and GJIC recovered after 4 h. VIN induced rapid hyperphosphorylation and internalization of gap junction protein connexin43, and both chemicals also activated MAPK ERK1/2 and p38. Effects on GJIC were not prevented by MEK1/2 inhibitor, but by an inhibitor of phosphatidylcholine-specific phospholipase C (PC-PLC), resveratrol, and in the case of VIN, also, by a p38 inhibitor. Estrogen (ER) and androgen receptor (AR) modulators (estradiol, ICI 182,780, HPTE, testosterone, flutamide, VIN M2) did not attenuate MXC or VIN effects on GJIC. Our data also indicate that the effects were elicited by the parental compounds of MXC and VIN. Our study provides new evidence that MXC and VIN dysregulate GJIC via mechanisms involving rapid activation of PC-PLC occurring independently of ER- or AR-dependent genomic signaling. Such alterations of rapid intercellular and intracellular signaling events involved in regulations of gene expression, tissue development, function and homeostasis, could also contribute to transgenerational epigenetic effects of endocrine disruptors.
Urinary incontinence in children is an underdiagnosed symptom in India with a prevalence of 7%. An appropriate diagnosis and early intervention can help prevent the progression of the disorder. Here ...we present a case reportof an 8-year-old girl referred for physiotherapy with the chief complaint of urinary incontinence. She had a wide bladder neck along with leaking urine and a small bladder capacity. She was managed conservatively with medications and comprehensive physiotherapeutic assessment and management that included a combination of electrotherapy, pelvic floor training, balance and postural exercises and other interventions that gave a positive outcome in terms of eliminating the dribbling episodes and improvement in her quality of life.
This research aims to provide long term streamflow forecast models using multiple climate indices as the predictors with the help of an advanced evolutionary method, Gene Expression Programming (GEP) ...to solve the developed symbolic regression problems as it is found to be superior than other traditional methods. Being a transparent model, GEP is able to provide the relationship between input (climate indices) and output (streamflow) variables with mathematical expressions which help the users to understand the underlying hydrological process between the climate mode and streamflow without having much knowledge about the used software. Two stations of New South Wales (NSW) are chosen based on their longer data record and fewer missing values. Several preliminary researches including single and multiple correlation analyses reveal PDO (Pacific Decadal Oscillation), IPO (Inter Decadal Pacific Oscillation), IOD (Indian Ocean Dipole) and ENSO (El Nino Southern Oscillation) are few among the influential indices on the study region. The resultant models appear to be more efficient with up to 50% higher Pearson correlation (r) values than that of the simple MLR technique adapted in one of our previous studies. Furthermore, the statistical performance analyses including Root Mean Square Error (RMSE), Mean Absolute Error (MAE), Willmott index of agreement (d) and Nash-Sutcliffe efficiency (NSE) ensure high predictability of the developed models. The similar correlation values (r) generated from calibration and validation periods which ranges between 0.74 and 0.91 increase the reliability of the resultant models for predicting seasonal streamflow up to three months in advance.
Wilson’s disease is an autosomal recessive genetic disorder affecting copper transport leading to hepatic and/or neuropsychiatric manifestations. Changes in pregnancy can mimic certain clinical ...features of chronic liver disease such as spider naevi, and constraints for the use of various investigation for diagnosis pose a challenge to physicians. A high index of suspicion, multi-disciplinary team approach, use of correct non-invasive testing including viral serology, autoantibodies and copper studies and ultrasonography help to diagnose most of the pre-existing, de novo or pregnancy-specific hepatological conditions. We report a case of Wilson’s disease diagnosed during pregnancy and discuss the challenges in diagnosis and treatment in pregnancy.
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