Ammonia Capture in Rhodium(II)-Based Metal-Organic Polyhedra via Synergistic Coordinative and H-Bonding Interactions.

Ammonia (NH3) is among the world's most widely produced bulk chemicals, given its extensive use in diverse sectors such as agriculture; however, it poses environmental and health risks at low concentrations. Therefore, there is a need for developing new technologies and materials to capture and store ammonia safely. Herein, we report for the first time the use of metal-organic polyhedra (MOPs) as ammonia adsorbents. We evaluated three different rhodium-based MOPs: [Rh2(bdc)2]12 (where bdc is 1,3-benzene dicarboxylate); one functionalized with hydroxyl groups at its outer surface [Rh2(OH-bdc)2]12 (where OH-bdc is 5-hydroxy-1,3-benzene dicarboxylate); and one decorated with aliphatic alkoxide chains at its outer surface [Rh2(C12O-bdc)2]12 (where C12O-bdc is 5-dodecoxybenzene-1,3-benzene dicarboxylate). Ammonia-adsorption experiments revealed that all three Rh-MOPs strongly interact with ammonia, with uptake capacities exceeding 10 mmol/gMOP. Furthermore, computational and experimental data showed that the mechanism of the interaction between Rh-MOPs and ammonia proceeds through a first step of coordination of NH3 to the axial site of the Rh(II) paddlewheel cluster, which triggers the adsorption of additional NH3 molecules through H-bonding interaction. This unique mechanism creates H-bonded clusters of NH3 on each Rh(II) axial site, which accounts for the high NH3 uptake capacity of Rh-MOPs. Rh-MOPs can be regenerated through their immersion in acidic water, and upon activation, their ammonia uptake can be recovered for at least three cycles. Our findings demonstrate that MOPs can be used as porous hosts to capture corrosive molecules like ammonia, and that their surface functionalization can enhance the ammonia uptake performance.

Expanding legal treatment options for medical marijuana in the State of Louisiana.

Background: The use of cannabis for 'medical' purposes has expanded throughout the USA. Despite the limited peer-reviewed medical research, medical marijuana therapy has been to treat chronic pain, stimulate appetite, treat nausea, and ameliorate muscle spasticity. Challenge: In the state of Louisiana, this potential treatment is strictly controlled. The ability of the individual patient to receive this therapy is limited since any prescribing provider had to be both licensed by the state medical board and registered with the board to prescribe medical marijuana. Medical cannabis could be used only for limited medical disorders. The 'Medical Marijuana' HB819 bill authorizes the recommendation of medical marijuana for additional conditions and allows any state-licensed physician to recommend/prescribe medical marijuana. Alternative options: The government may consider working with the state medical board to lessen its regulation allowing a collaborative effort to formalize protocols for safe prescribing of medical marijuana. A more liberal option would be to make it available to the consumer over the counter, while a state tracking mechanism is set in place to limit the amount purchased. Conclusions: Two stakeholders pertaining to this new legislation to focus on are the Louisiana State government and healthcare providers. This law probably has the biggest impact on healthcare providers and their relationship to patients. This legislation may allow providers to have more 'freedom in medical marijuana treatment plans'. These benefits would be monitored using such criteria as cost, access to care, as well as patient and healthcare provider satisfaction.

Identification of plasmepsin inhibitors as selective anti-malarial agents using ligand based drug design.

We describe the application of ligand based virtual screening technologies towards the discovery of novel plasmepsin (PM) inhibitors, a family of malarial parasitic aspartyl proteases. Pharmacophore queries were used to screen vendor libraries in search of active and selective compounds. The virtual hits were biologically assessed for activity and selectivity using whole cell Plasmodium falciparum parasites and on target in PM II, PM IV and the closely related human homologue, Cathepsin D assays. Here we report the virtual screening highlights, structures of the hits and their demonstrated biological activity.

Validation and field testing of library-independent microbial source tracking methods in the Gulf of Mexico.

Water quality is frequently impacted by microbial pollution from human and animal feces. Microbial source tracking (MST) can identify dominant pollution sources and improve assessment of health risk compared to indicator bacteria alone. This study aims to standardize and validate MST methods across laboratories in coastal Gulf of Mexico states. Three laboratories evaluated library-independent MST methods for human sewage detection via conventional PCR: (1) human-associated Bacteroidales, (2) human polyomaviruses (HPyVs), and (3) Methanobrevibacter smithii. All methods detected targets in human sewage seeded into buffer, freshwater or marine water (100% sensitivity). The limit of detection (LOD) for human sewage was lowest for the Bacteroidales assay (10(-5)-10(-6) dilution). LODs for HPyVs and M. smithii assays were similar to each other (10(-3)-10(-4)), but were higher than Bacteroidales. The HPyVs assay was 100% specific, showing no cross-reactivity to dog, cow, cat, bird, or wild animal feces among >300 samples from three Gulf Coast regions. The human Bacteroidales assay was 96% specific, but cross-reacted with 10% of dog and some chicken samples. The M. smithii assay was 98% specific with limited cross-reactivity with cow, dog and seagull samples. An experts' workshop concluded that all methods showed sufficient accuracy and reliability to move forward. SOPs will be distributed to collaborating laboratories for further inter-laboratory comparison, and field validation will occur in year 2.

Integration of ligand and structure-based virtual screening for the identification of the first dual targeting agent for heat shock protein 90 (Hsp90) and tubulin.

We describe the discovery of a novel indazole-based scaffold that represents the "first-in-class" dual Hsp90/tubulin binding compound. Individual known ligands for both targets shared similar 3',4',5'-trimethoxyphenyl cores, and from this it was hypothesized that application of an integrated ligand and structure-based virtual screening (VS) workflow could yield a single scaffold with dual binding affinity. Following validation of the VS protocol, we successfully identified a novel dual inhibitor, sourced from a commercial screening collection of 160 000 compounds.

Postoperative malignant hyperthermia: an analysis of cases from the North American Malignant Hyperthermia Registry.

BACKGROUND: The initial presentation of malignant hyperthermia (MH) may begin in the postoperative period. However, the maximal latency period between the end of anesthesia care and the onset of postoperative MH is unknown. The authors hypothesized that this latency period is short and is not manifested by hyperthermia as the initial presenting sign. The authors sought to test this hypothesis and to describe the clinical characteristics of postoperative MH by analysis of suspected cases in the North American Malignant Hyperthermia Registry. METHODS: Of 528 possible or suspected cases of MH in the North American Malignant Hyperthermia Registry, the authors identified 64 possible reports of postoperative MH. The records were reviewed in detail by the authors, each of whom assigned a qualitative score of "likely," "not likely," "not enough information available," or "not applicable" (where MH was not the final definitive diagnosis). Postoperative MH was confirmed after a consensus meeting of the three senior authors who reviewed in detail all possible "likely" cases. RESULTS: The authors identified postoperative MH in 10 subjects. All received volatile agents and 5 also received succinylcholine. All demonstrated signs characteristic of acute MH, including generalized rigidity, hypercapnia and/or tachypnea, tachycardia, and hyperthermia. No subject demonstrated hyperthermia as the presenting sign. The latency period between the anesthesia finish time and the onset of a sign indicative of acute MH ranged from 0 to 40 min. CONCLUSIONS: Postoperative MH is uncommon, occurring in 10 of 528 suspected MH cases (1.9%) reported to the North American Malignant Hyperthermia Registry. Postoperative MH began shortly after completion of the anesthetic care. Hyperthermia was not a presenting sign of MH.

Preparation of the cardiac patient for noncardiac surgery.

Approximately 20 to 40 percent of patients at high risk of cardiac-related morbidity develop myocardial ischemia perioperatively. The preferred approach to diagnostic evaluation depends on the interactions of patient-specific risk factors, surgery-specific risk factors, and exercise capacity. Stress testing should be reserved for patients at moderate to high risk undergoing moderate- or high-risk surgery and those who have poor exercise capacity. Further cardiovascular studies should be limited to patients who are at high risk, have poor exercise tolerance, or have known poor ventricular function. Medical therapy using beta blockers, statins, and alpha agonists may be effective in high-risk patients. The evidence appears to be the strongest for beta blockers, especially in high-risk patients with proven ischemia on stress testing who are undergoing vascular surgery. Many questions remain unanswered, including the optimal role of statins and alpha agonists, whether or not these therapies are as effective in patients with subclinical coronary artery disease or left ventricular dysfunction, and the optimal timing and dosing regimens of these medications.

Final myocardial blush grade predicts troponin I elevation in unstable angina patients undergoing percutaneous intervention.

BACKGROUND: Improved myocardial blush grade is associated with better MACE outcomes in acute myocardial infarction patients but there are no data on myocardial blush grade (MBG) assessment in unstable angina (UA) patients treated with coronary intervention. We sought to evaluate the use of angiographic MBG assessment in a cohort of UA patients treated with angioplasty. METHODS: Three hundred and seventy-two consecutive UA patients (mean age 68+/-1 years) treated with PCI were included. No patients had a pre-procedural troponin I (TnI) elevation. Final MBG was recorded for the territory subserving the PCI treated culprit lesion in each patient and graded 0 (no blush), 1 (minimal blush), 2 (moderate blush) and 3 (normal blush). TnI (normal range <0.1 microg/L) was measured 24h post-procedure. Patients who did not have a TnI elevation (i.e. <0.1 microg/L) were ascribed a value of 0.1 microg/L. Patients were followed up (mean 962+/-83 days) by postal questionnaire. RESULTS: Baseline risk factors were comparable between final MBG groups. There was no significant difference in mortality rate between groups. Post-procedural troponin I elevations were 0.34+/-0.12, 0.68+/-0.26, 0.14+/-0.01 and 0.11+/-0.01 for MBG groups 0, 1, 2 and 3 (p<0.001). Patients with minimal MBG underwent proportionately more target vessel revascularisation (p<0.05). CONCLUSIONS: Improved blush grade in UA patients undergoing PCI is associated with lower post-procedural TnI elevation. Identification of UA patients with poor final MBG may allow a window of opportunity for the administration of adjuvant therapies to improve microvascular perfusion in the future.