Anthelmintic activity of Ethanolic extract of whole plant of Eupatorium Odoratum. L

Successive extracts from the Whole plant of Eupatorium Odoratum. L (Asteraceae) were investigated for their anthelmintic activity against Pheretima posthuma and three concentrations (10, 50 and 100 mg/ml) of each extracts were studied in activity, which involved the determination of time of paralysis and time of death of the worm. Ethanolic extract exhibited significant anthelmintic activity at highest concentration of 100 mg/ml. Piperazine citrate in 10 mg/ml concentration as that of extract was included as standard reference and 1% Gum acacia in normal saline as control. The anthelmintic activity of ethanloic extract was significant followed by hydroalcoholic extract of Eupatorium Odoratum.Keywords: Anthelmintic activity, Eupatorium Odoratum, Pheretima posithuma, Piperazine citrate

Molecular Diagnostics in the Evaluation of Thyroid Nodules: Current Use and Prospective Opportunities

Thyroid cancer is the most common endocrine malignancy with an estimated 43,800 new cases to be diagnosed in 2022 and representing the 7th most common cancer in women. While thyroid nodules are very common, being identified in over 60% of randomly selected adults, only 5-15% of thyroid nodules harbor thyroid malignancy. Therefore, it is incumbent upon physicians to detect and treat thyroid malignancies as is clinically appropriate and avoid unnecessary invasive procedures in patients with benign asymptomatic lesions. Over the last 15-20 years, rapid advances have been made in cytomolecular testing to aid in thyroid nodule management. Initially, indeterminate thyroid nodules, those with Bethesda III or IV cytology and approximately a 10-40% risk of malignancy, were studied to assess benignity or malignancy. More recently, next generation sequencing and micro-RNA technology platforms have refined the diagnostic capacity of thyroid nodule molecular testing and have introduced opportunities to glean prognostic information from both cytologically indeterminate and malignant thyroid nodules. Therefore, clinicians can move beyond determination of malignancy, and utilize contemporary molecular information to aid in decisions such as extent of surgery and post-therapy monitoring plans. Future opportunities include molecularly derived information about tumor behavior, neo-adjuvant treatment opportunities and response to thyroid cancer therapies

Public Attitudes Toward Psychiatric Hospitals: A Rural-Urban Comparative Public Survey in Odisha State, India

Background: Integration of psychiatric care with public health services and offering mental health care services to patients from lower socioeconomic status remains a global challenge. Scarcity of funds and professional workforce in psychiatric hospitals contribute to this situation. However, negative attitudes in the population are also a known impediment to patients seeking mental health services. This study aimed to assess the attitudes toward psychiatric hospitals among the urban and rural population in India. Subjects and Methods: The study was carried out amongst the general population in Odisha, India. The total sample (n = 988) includes 496 respondents from an urban-setting, and 492 respondents from rural parts of the district. Participants were selected by using simple random-sampling from the Asian Institute of Public Health (AIPH) data base. A standardized seven-item questionnaire was adopted, with responses indicated on a 5-point Likert-scale. Interviews were fully structured and conducted face-to-face. Results: Level of education (B = -0.192, ss = -0.320, p < 0.000) and urban-rural comparison (B = -0.272, ss = -0.189, p < 0.000) significantly influenced attitudes toward psychiatric hospitals. Gender, age, and religious beliefs did not show any significant effect on attitudes toward psychiatric hospitals. Individuals in rural areas and those with lower education levels showed more negative attitudes toward psychiatric hospitals. Conclusion: Negative attitudes toward psychiatric hospitals from those living in rural areas as well as those with lesser education may be reflective of the lack of availability, accessibility, affordability, and credibility of such mental health services. The Mental Health Care Act in India is a progressive legislation which might improve the situation of the provided services and, consequently, reduce negative attitudes in the years to come

The mechanism of H171T resistance reveals the importance of Nδ-protonated His171 for the binding of allosteric inhibitor BI-D to HIV-1 integrase

Background: Allosteric HIV-1 integrase (IN) inhibitors (ALLINIs) are an important new class of anti-HIV-1 agents. ALLINIs bind at the IN catalytic core domain (CCD) dimer interface occupying the principal binding pocket of its cellular cofactor LEDGF/p75. Consequently, ALLINIs inhibit HIV-1 IN interaction with LEDGF/p75 as well as promote aberrant IN multimerization. Selection of viral strains emerging under the inhibitor pressure has revealed mutations at the IN dimer interface near the inhibitor binding site. Results: We have investigated the effects of one of the most prevalent substitutions, H171T IN, selected under increasing pressure of ALLINI BI-D. Virus containing the H171T IN substitution exhibited an ~68-fold resistance to BI-D treatment in infected cells. These results correlated with ~84-fold reduced affinity for BI-D binding to recombinant H171T IN CCD protein compared to its wild type (WT) counterpart. However, the H171T IN substitution only modestly affected IN-LEDGF/p75 binding and allowed HIV-1 containing this substitution to replicate at near WT levels. The x-ray crystal structures of BI-D binding to WT and H171T IN CCD dimers coupled with binding free energy calculations revealed the importance of the Nδ- protonated imidazole group of His171 for hydrogen bonding to the BI-D tert-butoxy ether oxygen and establishing electrostatic interactions with the inhibitor carboxylic acid, whereas these interactions were compromised upon substitution to Thr171. Conclusions: Our findings reveal a distinct mechanism of resistance for the H171T IN mutation to ALLINI BI-D and indicate a previously undescribed role of the His171 side chain for binding the inhibitor. Electronic supplementary material The online version of this article (doi:10.1186/s12977-014-0100-1) contains supplementary material, which is available to authorized users

Elevated APOBEC mutational signatures implicate chronic injury in etiology of an aggressive head-and-neck squamous cell carcinoma: a case report.

BACKGROUND: Aggressive squamous cell carcinomas (SCCs) present frequently in the context of chronic skin injury occurring in patients with the congenital blistering disease recessive dystrophic epidermolysis bullosa. Recently, these cancers were shown to harbor mutation signatures associated with endogenous deaminases of the active polynucleotide cytosine deaminase family, collectively termed APOBEC, and clock-like COSMIC [Catalogue of Somatic Mutations in Cancer] signatures, which are associated with normal aging and might result from cumulative DNA replication errors. We present a case of a nasal septal SCC arising in the context of recurrent injury, but also modest past tobacco use. Our genetic analysis of this tumor reveals unusually high APOBEC and clock-like but low tobacco-related COSMIC signatures, suggesting that chronic injury may have played a primary role in somatic mutation. This case report demonstrates how signature-based analyses may implicate key roles for certain mutagenic forces in individual malignancies such as head-and-neck SCC, with multiple etiological origins. CASE PRESENTATION: We report the case of a 43-year-old male former smoker who presented with congestion and swelling following a traumatic nasal fracture. During surgery, the mucosa surrounding the right nasal valve appeared abnormal, and biopsies revealed invasive keratinizing SCC. Frozen section biopsies revealed multiple areas to be positive for SCC. Gene sequencing showed loss of PTEN (exons 2-8), CDKN2A/B and TP53 (exons 8-9), MYC amplification, and BLM S338*. Exome sequencing data also revealed that 36% of mutations matched an APOBEC mutational signature (COSMIC signatures 2 and 13) and 53% of mutations matched the clock-like mutation signature (COSMIC signature 5). These proportions place this tumor in the 90th percentile bearing each signature, independently, in a reference data set combining cutaneous and The Cancer Genome Atlas (TCGA) head and neck SCC data. In contrast, few mutations harbored a tobacco-related COSMIC signature 4, representing about the 10th percentile in our reference SCC data set. The patient was treated with partial rhinectomy with local flap reconstruction, bilateral neck dissection, and adjuvant radiation therapy; the patient remains disease-free to date. CONCLUSION: Based on comparative mutational signature analysis, we propose that the history of tobacco use and traumatic injury may have collaborated in activating APOBEC enzymes and the clock-like mutational process, ultimately leading to cancer formation. Clinical awareness of the relationship between epithelial injury and tumorigenesis should enhance earlier detection of this particularly aggressive type of cancer

Use of hydroxyethyl starch in leukocytapheresis procedures does not increase renal toxicity

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/134412/1/trf13795.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/134412/2/trf13795_am.pd

Malodorous consequences: What comprises negligence in anosmia litigation?

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/106718/1/alr21257.pd

Multi-Institutional Study Validates Safety of Intraoperative Cesium-131 Brachytherapy for Treatment of Recurrent Head and Neck Cancer

Introduction: Surgery is the primary treatment for resectable, non-metastatic recurrent head and neck squamous cell carcinoma (HNSCC). We explore the safety and oncologic benefit of intraoperative Cesium-131 (Cs-131) brachytherapy combined with salvage local and/or regional surgical resection. Methods and materials: Findings were reported from a single arm multi-institutional prospective phase 1/2 trial involving surgery plus Cs-131 (surgery + Cs-131) treatment. The results of two retrospective cohorts-surgery alone and surgery plus intensity modulated radiation therapy (surgery + ReIMRT)-were also described. Included patients had recurrent HNSCC and radiation history. Safety, tumor re-occurrence, and survival were evaluated. Results: Forty-nine patients were enrolled in the surgery + Cs-131 prospective study. Grade 1 to 3 adverse events (AEs) occurred in 18 patients (37%), and grade 4 AEs occurred in 2 patients. Postoperative percutaneous endoscopic gastrostomy (PEG) tubes were needed in 10 surgery + Cs-131 patients (20%), and wound and vascular complications were observed in 12 patients (24%). No cases of osteoradionecrosis were reported in the surgery + Cs-131 cohort. We found a 49% 2-year disease-free survival at the site of treatment with a substantial number of patients (31%) developing metastatic disease, which led to a 31% overall survival at 5 years. Conclusions: Among patients with local/regional recurrent HNSCC status-post radiation, surgery + Cs-131 demonstrated acceptable safety with compelling oncologic outcomes, as compared to historic control cohorts. Clinical trial registration: ClinicalTrials.gov, identifiers NCT02794675 and NCT02467738

Fine mapping and sequence analysis reveal a promising candidate gene encoding a novel NB-ARC domain derived from wild rice (Oryza officinalis) that confers bacterial blight resistance

Bacterial blight disease of rice caused by Xanthomonas oryzae pv. oryzae (Xoo) is one of the most serious constraints in rice production. The most sustainable strategy to combat the disease is the deployment of host plant resistance. Earlier, we identified an introgression line, IR 75084-15-3-B-B, derived from Oryza officinalis possessing broad-spectrum resistance against Xoo. In order to understand the inheritance of resistance in the O. officinalis accession and identify genomic region(s) associated with resistance, a recombinant inbred line (RIL) mapping population was developed from the cross Samba Mahsuri (susceptible to bacterial blight) × IR 75084-15-3-B-B (resistant to bacterial blight). The F2 population derived from the cross segregated in a phenotypic ratio of 3: 1 (resistant susceptible) implying that resistance in IR 75084-15-3-B-B is controlled by a single dominant gene/quantitative trait locus (QTL). In the F7 generation, a set of 47 homozygous resistant lines and 47 homozygous susceptible lines was used to study the association between phenotypic data obtained through screening with Xoo and genotypic data obtained through analysis of 7K rice single-nucleotide polymorphism (SNP) chip. Through composite interval mapping, a major locus was detected in the midst of two flanking SNP markers, viz., Chr11.27817978 and Chr11.27994133, on chromosome 11L with a logarithm of the odds (LOD) score of 10.21 and 35.93% of phenotypic variation, and the locus has been named Xa48t. In silico search in the genomic region between the two markers flanking Xa48t identified 10 putatively expressed genes located in the region of interest. The quantitative expression and DNA sequence analysis of these genes from contrasting parents identified the Os11g0687900 encoding an NB-ARC domain-containing protein as the most promising gene associated with resistance. Interestingly, a 16-bp insertion was noticed in the untranslated region (UTR) of the gene in the resistant parent, IR 75084-15-3-B-B, which was absent in Samba Mahsuri. The association of Os11g0687900 with resistance phenotype was further established by sequence-based DNA marker analysis in the RIL population. A co-segregating PCR-based INDEL marker, Marker_Xa48, has been developed for use in the marker-assisted breeding of Xa48t

Evaluation of sesamum gum as an excipient in matrix tablets

In developing countries modern medicines are often beyond the affordability of the majority of the population. This is due to the reliance on expensive imported raw materials despite the abundance of natural resources which could provide an equivalent or even an improved function. The aim of this study was to investigate the potential of sesamum gum (SG) extracted from the leaves of Sesamum radiatum (readily cultivated in sub-Saharan Africa) as a matrix former. Directly compressed matrix tablets were prepared from the extract and compared with similar matrices of HPMC (K4M) using theophylline as a model water soluble drug. The compaction, swelling, erosion and drug release from the matrices were studied in deionized water, 0.1 N HCl (pH 1.2) and phosphate buffer (pH 6.8) using USP apparatus II. The data from the swelling, erosion and drug release studies were also fitted into the respective mathematical models. Results showed that the matrices underwent a combination of swelling and erosion, with the swelling action being controlled by the rate of hydration in the medium. SG also controlled the release of theophylline similar to the HPMC and therefore may have use as an alternative excipient in regions where Sesamum radiatum can be easily cultivated