Inhibition of Aminoglycoside Acetyltransferase Resistance Enzymes by Metal Salts

Aminoglycosides (AGs) are clinically relevant antibiotics used to treat infections caused by both Gram-negative and Gram-positive bacteria, as well as Mycobacteria. As with all current antibacterial agents, resistance to AGs is an increasing problem. The most common mechanism of resistance to AGs is the presence of AG-modifying enzymes (AMEs) in bacterial cells, with AG acetyltransferases (AACs) being the most prevalent. Recently, it was discovered that Zn2+ metal ions displayed an inhibitory effect on the resistance enzyme AAC(6\u27)-Ib in Acinetobacter baumannii and Escherichia coli. In this study, we explore a wide array of metal salts (Mg2+, Cr3+, Cr6+, Mn2+, Co2+, Ni2+, Cu2+, Zn2+, Cd2+, and Au3+ with different counter ions) and their inhibitory effect on a large repertoire of AACs [AAC(2\u27)-Ic, AAC(3)-Ia, AAC(3)-Ib, AAC(3)-IV, AAC(6\u27)-Ib\u27, AAC(6\u27)-Ie, AAC(6\u27)-IId, and Eis]. In addition, we determine the MIC values for amikacin and tobramycin in combination with a zinc pyrithione complex in clinical isolates of various bacterial strains (two strains of A. baumannii, three of Enterobacter cloacae, and four of Klebsiella pneumoniae) and one representative of each species purchased from the American Type Culture Collection

Conscientious objection to provision of legal abortion care

Despite advances in scientific evidence, technologies, and human rights rationale for providing safe abortion, a broad range of cultural, regulatory, and health system barriers that deter access to abortion continues to exist in many countries. When conscientious objection to provision of abortion becomes one of these barriers, it can create risks to women’s health and the enjoyment of their human rights. To eliminate this barrier, states should implement regulations for healthcare providers on how to invoke conscientious objection without jeopardizing women’s access to safe, legal abortion services, especially with regard to timely referral for care and in emergency cases when referral is not possible. In addition, states should take all necessary measures to ensure that all women and adolescents have the means to prevent unintended pregnancies and to obtain safe abortion

Costs of alternative treatments for incomplete abortion

Unsafely performed abortion is one of the five leading causes of maternal deaths worldwide. Many women who have undergone unsafe abortions enter the healthcare system to seek help for the resulting complications, including incomplete abortion. This human and financial cost of this health problem is tremendous, especially in the developing world. This study examined the potential for reducing costs to healthcare systems by changing the standard method of treatment for incomplete abortion. Vacuum aspiration (VA) has been shown to be safer than dilation and curettage (D&C) for uterine evacuation; the World Health Organization includes VA as an essential service at the first referral level. The technique most commonly used for treating first-trimester incomplete abortion in developing countries, however, is D&C. This study examined the hypothesis that use of manual vacuum aspiration (MVA) - a variation of VA - would be less costly than D&C and thus advantageous to healthcare systems with limited resources. The purpose of the study was to identify and, where possible, to explain the factors that contributed to cost differences between MVA and D&C for treatment of first-trimester incomplete abortion. To achieve this objective, researchers observed patient management and documented resource use at hospital sites in Ecuador, Kenya, and Mexico. In most cases, treatment with MVA required a shorter patient stay and fewer hospital resources than D&C, as the two techniques were practiced at the various study sites. The policy decision to adopt MVA, supported by procurement of instruments and incorporation of training in its use, is the chief prerequisite for achieving these improvements. But the full advantages of MVA are realized only if it is introduced in conjunction with certain changes in patient-management practices, such as offering outpatient treatment of incomplete abortion. Further, decentralizing MVA services can maximize the benefits of the technique, facilitating (hospitals'and) healthcare systems'efforts to decrease the cost of delivery service and improve the quality of care.Health Monitoring&Evaluation,Gender and Health,Health Systems Development&Reform,Information Technology,Business Environment

Non-adiabatic corrections to elastic scattering of halo nuclei

We derive the formalism for the leading order corrections to the adiabatic approximation to the scattering of composite projectiles. Assuming a two-body projectile of core plus loosely-bound valence particle and a model (the core recoil model) in which the interaction of the valence particle and the target can be neglected, we derive the non-adiabatic correction terms both exactly, using a partial wave analysis, and using the eikonal approximation. Along with the expected energy dependence of the corrections, there is also a strong dependence on the valence-to-core mass ratio and on the strength of the imaginary potential for the core-target interaction, which relates to absorption of the core in its scattering by the target. The strength and diffuseness of the core-target potential also determine the size of the corrections. The first order non-adiabatic corrections were found to be smaller than qualitative estimates would expect. The large absorption associated with the core-target interaction in such halo nuclei as Be11 kills off most of the non-adiabatic corrections. We give an improved estimate for the range of validity of the adiabatic approximation when the valence-target interaction is neglected, which includes the effect of core absorption. Some consideration was given to the validity of the eikonal approximation in our calculations.Comment: 14 pages with 10 figures, REVTeX4, AMS-LaTeX v2.13, submitted to Phys. Rev.

Modulational Instability in Equations of KdV Type

It is a matter of experience that nonlinear waves in dispersive media, propagating primarily in one direction, may appear periodic in small space and time scales, but their characteristics --- amplitude, phase, wave number, etc. --- slowly vary in large space and time scales. In the 1970's, Whitham developed an asymptotic (WKB) method to study the effects of small "modulations" on nonlinear periodic wave trains. Since then, there has been a great deal of work aiming at rigorously justifying the predictions from Whitham's formal theory. We discuss recent advances in the mathematical understanding of the dynamics, in particular, the instability of slowly modulated wave trains for nonlinear dispersive equations of KdV type.Comment: 40 pages. To appear in upcoming title in Lecture Notes in Physic

Monkey hybrid stem cells develop cellular features of Huntington's disease

<p>Abstract</p> <p>Background</p> <p>Pluripotent stem cells that are capable of differentiating into different cell types and develop robust hallmark cellular features are useful tools for clarifying the impact of developmental events on neurodegenerative diseases such as Huntington's disease. Additionally, a Huntington's cell model that develops robust pathological features of Huntington's disease would be valuable for drug discovery research.</p> <p>Results</p> <p>To test this hypothesis, a pluripotent Huntington's disease monkey hybrid cell line (TrES1) was established from a tetraploid Huntington's disease monkey blastocyst generated by the fusion of transgenic Huntington's monkey skin fibroblast and a wild-type non-transgenic monkey oocyte. The TrES1 developed key Huntington's disease cellular pathological features that paralleled neural development. It expressed mutant huntingtin and stem cell markers, was capable of differentiating to neural cells, and developed teratoma in severely compromised immune deficient (SCID) mice. Interestingly, the expression of mutant htt, the accumulation of oligomeric mutant htt and the formation of intranuclear inclusions paralleled neural development <it>in vitro </it>, and even mutant htt was ubiquitously expressed. This suggests the development of Huntington's disease cellular features is influenced by neural developmental events.</p> <p>Conclusions</p> <p>Huntington's disease cellular features is influenced by neural developmental events. These results are the first to demonstrate that a pluripotent stem cell line is able to mimic Huntington's disease progression that parallels neural development, which could be a useful cell model for investigating the developmental impact on Huntington's disease pathogenesis.</p

Inspiring and Aspiring Educators: An Intersection of Historic and Current Education Landscapes

The book Inspiring and Aspiring Educators: An Intersection of Historic and Current Education Landscapes is a collection of graduate student writings from the 2021 summer Education Doctorate Residency at Winona State University.https://openriver.winona.edu/educationeddbooks/1002/thumbnail.jp

Colorectal Cancer with Residual Polyp of Origin: A Model of Malignant Transformation

AbstractThe majority of colorectal cancers (CRCs) arise from adenomatous polyps. In this study, we sought to present the underrecognized CRC with the residual polyp of origin (CRC RPO+) as an entity to be utilized as a model to study colorectal carcinogenesis. We identified all subjects with biopsy-proven CRC RPO+ that were evaluated over 10 years at Mayo Clinic, Rochester, MN, and compared their clinical and pathologic characteristics to CRC without remnant polyps (CRC RPO−). Overall survival and disease-free survival overlap with an equivalent hazard ratio between CRC RPO+ and RPO− cases when age, stage, and grade are adjusted. The somatic genomic profile obtained by whole genome sequencing and the gene expression profiles by RNA-seq for CRC RPO+ tumors were compared with that of age -and gender-matched CRC RPO− evaluated by The Cancer Genome Atlas. CRC RPO+ cases were more commonly found with lower-grade, earlier-stage disease than CRC RPO−. However, within the same disease stage and grade, their clinical course is very similar to that of CRC RPO−. The mutation frequencies of commonly mutated genes in CRC are similar between CRC RPO+ and RPO− cases. Likewise, gene expression patterns are indistinguishable between the RPO+ and RPO− cases. We have confirmed that CRC RPO+ is clinically and biologically similar to CRC RPO− and may be utilized as a model of the adenoma to carcinoma transition

Shifts in the Fecal Microbiota Associated with Adenomatous Polyps

BACKGROUND: Adenomatous polyps are the most common precursor to colorectal cancer, the second leading cause of cancer-related death in the United States. We sought to learn more about early events of carcinogenesis by investigating shifts in the gut microbiota of patients with adenomas. METHODS: We analyzed 16S rRNA gene sequences from the fecal microbiota of patients with adenomas (n = 233) and without (n = 547). RESULTS: Multiple taxa were significantly more abundant in patients with adenomas, including Bilophila, Desulfovibrio, proinflammatory bacteria in the genus Mogibacterium, and multiple Bacteroidetes species. Patients without adenomas had greater abundances of Veillonella, Firmicutes (Order Clostridia), and Actinobacteria (family Bifidobacteriales). Our findings were consistent with previously reported shifts in the gut microbiota of colorectal cancer patients. Importantly, the altered adenoma profile is predicted to increase primary and secondary bile acid production, as well as starch, sucrose, lipid, and phenylpropanoid metabolism. CONCLUSIONS: These data hint that increased sugar, protein, and lipid metabolism along with increased bile acid production could promote a colonic environment that supports the growth of bile-tolerant microbes such as Bilophilia and Desulfovibrio In turn, these microbes may produce genotoxic or inflammatory metabolites such as H2S and secondary bile acids, which could play a role in catalyzing adenoma development and eventually colorectal cancer. IMPACT: This study suggests a plausible biological mechanism to explain the links between shifts in the microbiota and colorectal cancer. This represents a first step toward resolving the complex interactions that shape the adenoma-carcinoma sequence of colorectal cancer and may facilitate personalized therapeutics focused on the microbiota