Prevalence of Antimicrobial Resistance Among the Hydrogen Sulfide Producing Bacteria Isolated on XLD Agar from the Poultry Fecal Samples.

Poultry products remain as one of the most popular and extensively consumed foods in the world and the introduction of hydrogen sulfide (H2S) producing antibiotic resistant bacterial species into it is an emerging challenge. The current study has been designed to analyze the distribution of antibiotic resistance among the H2S producing bacteria isolated from the fecal samples of chickens from different poultry farms. Here, twenty bacterial isolates were selected based on their ability to produce H2S on XLD agar, and the16S rDNA sequencing was carried out for their molecular identification. The results showed the isolates as belong to Salmonella spp. and Citrobacter spp. and in the antibiotic susceptibility test (AST), three of the Salmonella strains were found to be resistant to antibiotics such as tetracycline, doxycycline, nalidixic acid, and amikacin. Also, fourteen Citrobacter strains showed resistance towards azithromycin, and furthermore, eleven of them were also resistant to streptomycin. Resistance towards tetracycline was observed among five of the Citrobacter strains, and seven were resistant to doxycycline. Further molecular screening by the PCR has showed three of the Salmonella strains along with eight Citrobacter isolates to have tetA gene along with four of the Citrobacter strains to have co-harbored blaTEM gene. The results on biofilm formation have also demonstrated three Salmonella strains along with nine Citrobacter strains to have the ability to form moderate biofilm. The study thus describes the occurrence of H2S producing multidrug-resistant bacteria in poultry feces, which might contribute towards the dissemination of antibiotic resistance genes to other microorganisms including human pathogens with likely risk to treat disease conditions.

A comparison of three thromboprophylaxis regimens in critically ill COVID-19 patients: An analysis of real-world data.

Introduction: Thrombotic complications of coronavirus disease 2019 (COVID-19) have received considerable attention. Although numerous conflicting findings have compared escalated thromboprophylaxis doses with a standard dose to prevent thrombosis, there is a paucity of literature comparing clinical outcomes in three different anticoagulation dosing regimens. Thus, we investigated the effectiveness and safety profiles of standard, intermediate, and high-anti-coagulation dosing strategies in COVID-19 critically ill patients. Methodology: This retrospective multicenter cohort study of intensive care unit (ICU) patients from the period of April 2020 to August 2021 in four Saudi Arabian centers. Inclusion criteria were age ≥ 18 years, diagnosis with severe or critical COVID-19 infection, and receiving prophylactic anticoagulant dose within 24-48 h of ICU admission. The primary endpoint was a composite of thrombotic events, with mortality rate and minor or major bleeding serving as secondary endpoints. We applied survival analyses with a matching weights procedure to control for confounding variables in the three arms. Results: A total of 811 patient records were reviewed, with 551 (standard-dose = 192, intermediate-dose = 180, and high-dose = 179) included in the analysis. After using weights matching, we found that the standard-dose group was not associated with an increase in the composite thrombotic events endpoint when compared to the intermediate-dose group {19.8 vs. 25%; adjusted hazard ratio (aHR) =1.46, [95% confidence of interval (CI), 0.94-2.26]} or when compared to high-dose group [19.8 vs. 24%; aHR = 1.22 (95% CI, 0.88-1.72)]. Also, there were no statistically significant differences in overall in-hospital mortality between the standard-dose and the intermediate-dose group [51 vs. 53.4%; aHR = 1.4 (95% CI, 0.88-2.33)] or standard-dose and high-dose group [51 vs. 61.1%; aHR = 1.3 (95% CI, 0.83-2.20)]. Moreover, the risk of major bleeding was comparable in all three groups [standard vs. intermediate: 4.8 vs. 2.8%; aHR = 0.8 (95% CI, 0.23-2.74); standard vs. high: 4.8 vs. 9%; aHR = 2.1 (95% CI, 0.79-5.80)]. However, intermediate-dose and high-dose were both associated with an increase in minor bleeding incidence with aHR = 2.9 (95% CI, 1.26-6.80) and aHR = 3.9 (95% CI, 1.73-8.76), respectively. Conclusion: Among COVID-19 patients admitted to the ICU, the three dosing regimens did not significantly affect the composite of thrombotic events and mortality. Compared with the standard-dose regimen, intermediate and high-dosing thromboprophylaxis were associated with a higher risk of minor but not major bleeding. Thus, these data recommend a standard dose as the preferred regimen.

Tocilizumab effectiveness in mechanically ventilated COVID-19 patients (T-MVC-19 Study): a multicenter real-world evidence.

BACKGROUND: This study aimed to evaluate the effectiveness of tocilizumab in mechanically ventilated patients with coronavirus disease 2019 (COVID-19). RESEARCH DESIGN AND METHODS: This retrospective multicenter study included adults (≥18 years) diagnosed with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) by real-time polymerase chain reaction (RT-PCR) from nasopharyngeal swab, and requiring invasive mechanical ventilation during admission. Survival analyses with inverse propensity score treatment weighting (IPTW) and propensity score matching (PSM) were conducted. To account for immortal bias, we used Cox proportional modeling with time-dependent covariance. Competing risk analysis was performed for the extubation endpoint. RESULTS: A total of 556 (tocilizumab = 193, control = 363) patients were included. Males constituted the majority of the participants (69.2% in tocilizumab arm,74.1% in control arm). Tocilizumab was not associated with a reduction in mortality with hazard ratio [(HR) = 0.82,95% confidence interval (95%CI): 0.62-1.10] in the Inverse propensity score weighting (IPTW) analysis and (HR = 0.86,95% CI: 0.64-1.16) in the PSM analysis. However, tocilizumab was associated with an increased rate of extubation (33.6%) compared to the control arm (11.9%); subdistributional hazards (SHR) = 3.1, 95% CI: 1.86-5.16). CONCLUSIONS: Although tocilizumab was not found to be effective in reducing mortality, extubation rate while on mechanical ventilation was higher among tocilizumab treated group.

Validity of Using Accreditation Phantom in Quality Control of Digital Tomosynthesis.

AIM: This study was undertaken to compare the two image-quality phantoms commonly used in full-field digital mammography (FFDM) and digital breast tomosynthesis (DBT) imaging. METHODS: Mammography units with two targets and three filters resulting in three possible target/filter combinations and two kVp values which are widely used (28 and 32) were used for the comparison. The automatic exposure control system was used in combination with the selected kVp. The CIRS 15 mammographic accreditation phantom (MAP) and CIRS 20 (BR3D) breast imaging phantom were used with the three target/filter combinations and two kVp values. A total of 24 images were acquired and evaluated. Image score was determined as the smallest sized object detectable. The data were analyzed by using Mann-Whitney test. RESULTS: There were significant (p<0.001) differences between the detectability of fibers present in the two phantoms, but there were no differences in the detectability of specks. CONCLUSION: The finding in FFDM and DBT showed there were significant differences between the two phantoms (p<0.02) in fibers and specks visibility. The CIRS 20 phantom provided greater visibility of smaller structures, while the MAP was more suitable for assessing image quality of both FFDM and DBT imaging systems.

In vitro evaluation of anti-Alzheimer effects of dry ginger (Zingiber officinale Roscoe) extract.

As the disease modifying therapies against Alzheimer's disease (AD) continue to exist as a major challenge of this century, the search for newer drug leads with lesser side effects is on the rise. A large number of plant extracts and phytocompounds are being actively pursued for their anti-Alzheimer effects. In the present study, the antioxidant activity, cholinesterase inhibition, anti-amyloidogenic potential and neuroprotective properties of methanolic extract of dry ginger (GE) have been evaluated. The extract contained 18 +/- 0.6 mg/g gallic acid equivalents of total phenolic content and 4.18 +/- 0.69 mg quercetin equivalents/g of dry material. GE expressed high antioxidant activity with an IC50 value of 70 +/- 0.304 microg/mL in DPPH assay and 845.4 +/- 56.62 microM Fe(II) equivalents/g dry weight in FRAP assay respectively. In Ellman's assay for the cholinesterase inhibitory activity, GE had an IC50 value of 41 +/- 1.2 microg/mL and 52 +/- 2 microg/mL for inhibition of acetyl- and butyrylcholinesterase respectively. Also, GE increased the cell survival against amyloid beta (Abeta) induced toxicity in primary adult rat hippocampal cell culture. Aggregation experiments with the thioflavin T binding studies showed that GE effectively prevented the formation of Abeta oligomers and dissociated the preformed oligomers. These findings suggest that methanolic GE influences multiple therapeutic molecular targets of AD and can be considered as an effective nontoxic neutraceutical supplement for AD.

In vitro screening for anti-cholinesterase and antioxidant activity of methanolic extracts of ayurvedic medicinal plants used for cognitive disorders.

Inhibition of Acetylcholinesterase (AChE) is still considered as the main therapeutic strategy against Alzheimer's disease (AD). Many plant derived phytochemicals have shown AChE inhibitory activity in addition to the currently approved drugs for AD. In the present study, methanolic extracts of 20 plants used in Indian Ayurvedic system of medicine for improving cognitive function were screened for acetylcholinesterase inhibitory activity by Ellman's microplate colorimetric method. Out of 20 extracts, Emblica officinalis, Nardostachys jatamansi, Nelumbo nucifera, Punica granatum and Raulfia Serpentina showed IC50 values <100 µg/ml for acetylcholinesterase inhibitory activity. Antioxidant activities of these plants were assessed by DPPH scavenging assay. Among the extracts used, antioxidant activity was highest for Terminalia chebula and Emblica officinalis with IC50 values <10 µg/ml. Considering the complex multifactorial etiology of AD, these plant extracts will be safer and better candidates for the future disease modifying therapies against this devastating disease.

Reducing excess radiation from portal imaging of pediatric brain tumors.

Previously we have shown that our routine portal imaging (PI) of the craniofacial region in pediatric brain tumor patients contributed an additional 2%-3% of the prescribed dose and up to 200 cGy to the planning target volume (PTV) and nearby organs at risk (OARs). The purpose of this study is to quantify the reduction in dose to PTV and OARs from portal imaging (PI) of the craniofacial region of pediatric patients treated after the implementation of changes in our portal imaging practices. Twenty consecutive pediatric patients were retrospectively studied since the implementation of changes to our portal imaging procedure. Each received portal imaging of treatment fields and orthogonal setup fields to the craniofacial region. PI modifications included a reduction in the field size of setup orthogonal fields without loss of radiographic information needed for treatment verification. In addition, treatment fields were imaged using a single exposure, rather than double exposure. Dose-volume histograms were generated to quantify the dose to the target and critical structures through PI acquisition. These results were compared with our previous cohort of 20 patients who were treated using the former portal imaging practices. The mean additional target dose from portal imaging following the new guidelines was 1.5% of the prescribed dose compared to 2.5% prior to the new portal image practices (p < 0.001). With the new portal imaging practices, the percentage decrease in portal imaging dose to the brainstem, optic structures, cochlea, hypothalamus, temporal lobes, thyroid, and eyes were 25%, 35%, 35%, 51%, 45%, 80%, and 55%, respectively. Reductions in portal imaging doses were significant in all OARs with exception of the brainstem, which showed a trend towards significance. Changes to portal imaging practices can reduce the radiation dose contribution from portal imaging to surrounding OARs by up to 80%. This may have implications on both late toxicity and second cancer development in pediatric brain tumors.

Vemurafenib and radiation therapy in melanoma brain metastases.

Brain metastases in malignant melanoma carries a poor prognosis with minimal response to any therapy. The purpose of this pilot analysis was to find the effectiveness of vemurafenib, an oral BRAF inhibitor, and radiation therapy in V600 mutated melanoma with brain metastases. BRAF mutation status of the melanoma patients was determined by real-time PCR assay. Retrospective analysis was performed on twelve patients who had the mutation and were treated with either stereotactic radiosurgery or whole brain radiation therapy prior to or along with vemurafenib at a dose of 960 mg orally twice a day. Clinical and radiological responses, development of new brain metastases, overall survival and toxicity were assessed. Improvement in neurological symptoms was seen in 7/11 (64 %) following therapy. Radiographic responses were noted in 36/48 (75 %) of index lesions with 23 (48 %) complete responses and 13 (27 %) partial responses. Six month local control, freedom from new brain metastases and overall survival were 75, 57 and 92 %. Four patients had intra-tumoral bleed prior to therapy and two patients developed steroid dependence. One patient experienced radiation necrosis. This retrospective study suggests that melanoma patients with brain metastases harboring BRAF mutation appear to be a distinct sub-group with a favorable response to vemurafenib and radiation therapy and acceptable morbidity.

Ipilimumab in melanoma with limited brain metastases treated with stereotactic radiosurgery.

The anti-cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) monoclonal antibody ipilimumab has been shown to improve survival in patients with metastatic non-CNS melanoma. The purpose of this study was to investigate the efficacy of CTLA-4 inhibitors in the treatment of metastatic melanoma with limited brain metastases treated with stereotactic radiosurgery (SRS). Between January 2008 and June 2011, 58 patients with limited brain metastases from melanoma were treated with SRS with a median dose of 20 Gy delivered to the 50% isodose line (range, 15-20 Gy). In 25 patients, ipilimumab was administered intravenously at a dose of 3 mg/kg over 90 min every 3 weeks for a median of four doses (range, 1-8). Local control (LC), freedom from new brain metastases, and overall survival (OS) were assessed from the date of the SRS procedure. The median LC, freedom from new brain metastases, and OS for the entire group were 8.7, 4.3, and 5.9 months, respectively. The cause of death was CNS progression in all but eight patients. Six-month LC, freedom from new brain metastases, and OS were 65, 35, and 56%, respectively, for those who received ipilimumab and 63, 47, and 46% for those who did not (P=NS). Intracranial hemorrhage was noted in seven patients who received ipilimumab compared with 10 patients who received SRS alone (P=NS). In this retrospective study, administration of ipilimumab neither increased toxicity nor improved intracerebral disease control in patients with limited brain metastases who received SRS.

Involved field radiation therapy after surgical resection of solitary brain metastases--mature results.

BACKGROUND: Whole brain radiation therapy (WBRT) reduces local recurrence in patients after surgical resection of brain metastases without improving overall survival. Involved field radiation therapy (IFRT) has been used at our center to avoid delayed neurotoxicity associated with WBRT in well-selected patients with surgically resected single brain metastases. The purpose of this study was to evaluate the long-term outcomes of these patients. METHODS: Thirty-three consecutive patients with single brain metastases from a known primary tumor were treated with gross total resection followed by IFRT between 2006 and 2011. The postoperative surgical bed was treated to 40.05 Gy in 15 fractions of 2.67 Gy with conformal radiation therapy. Patients received serial MRIs and neurological exams in follow-up. Surgery, WBRT, or stereotactic radiosurgery was performed as salvage treatment when necessary. RESULTS: The median follow-up was 16 months (range: 2-65 months). Local control, distant brain recurrence-free survival, and overall survival at 12 and 24 months were 90.3% and 85.8%, 60.7% and 51.4%, and 65.6% and 61.5%, respectively. Overall, 5 (15%) patients developed recurrence at the resection cavity, and 13 (39%) patients experienced recurrence at a new intracranial site. Two patients received WBRT, 8 stereotactic radiosurgery, 2 surgery, and 2 both chemotherapy and IFRT as salvage. Four patients died from CNS disease progression. CONCLUSION: For patients with newly diagnosed single brain metastases treated with surgical resection, postoperative IFRT to the resection cavity achieves reasonable rates of local control and is an excellent alternative to WBRT.

Antiangiogenic therapy in the management of brain tumors: a clinical overview.

Central to the process of brain tumor development is angiogenesis, which involves a host of molecules and receptors. In recent years, antiangiogenic therapies have been developed and tested for their effectiveness against these tumors. Among them are inhibitors against vascular endothelial growth factor and its receptors, as well as inhibitors targeting the platelet-derived growth factor family, integrins, and histone deacetylase. While many have been shown to be effective with limited toxicity, some tumors are able to adopt escape mechanisms. Further research is needed in the development of effective multi-targeted agents to reduce these effects.

Design and development of non-fibrillar amyloid beta as a potential Alzheimer vaccine.

Alzheimer's disease (AD) is the most common cause of dementia affecting the elderly. Treatment for effective cure of this complex neurodegenerative disease does not yet exist. In AD, otherwise soluble, monomeric form of amyloid beta (Abeta) peptide converts into toxic, fibrillar form rich in beta-sheet content. Several immunological approaches that prevent this conversion of Abeta into pathological form or that accelerate its clearance are being actively pursued worldwide. As part of these attempts, we report here, the design and characterization of a non-amyloidogenic homologue of Abeta (Abeta-KEK). We demonstrate that this peptide is helical in nature and retains the immunoneutralizing epitopes of native Abeta. More importantly, Fab fragments of the polyclonal anti-Abeta-KEK antibodies interfere with formation of Abeta fibrils as well as dissociate the preformed Abeta aggregates in vitro. These results suggest that non-amyloidogenic Abeta-KEK may serve as a safer alternative vaccine for Alzheimer's disease.