Genomic Microevolution of Vibrio cholerae O1, Lake Tanganyika Basin, Africa.

Africa's Lake Tanganyika basin is a cholera hotspot. During 2001-2020, Vibrio cholerae O1 isolates obtained from the Democratic Republic of the Congo side of the lake belonged to 2 of the 5 clades of the AFR10 sublineage. One clade became predominant after acquiring a parC mutation that decreased susceptibility to ciprofloxacin.

Vessel effects in organic chemical reactions; a century-old, overlooked phenomenon.

One of the most intriguing aspects of synthetic chemistry is the interplay of numerous dependent and independent variables en route to achieve a successful, high-yielding chemical transformation. The experienced synthetic chemist will probe many of these variables during reaction development and optimization, which will routinely involve investigation of reaction temperature, solvent, stoichiometry, concentration, time, choice of catalyst, addition sequence or quenching conditions just to name some commonly addressed variables. Remarkably, little attention is typically given to the choice of reaction vessel material as the surface of common laboratory borosilicate glassware is, incorrectly, assumed to be chemically inert. When reviewing the scientific literature, careful consideration of the vessel material is typically only given during the use of well-known glass-etching reagents such as HF, which is typically only handled in HF-resistant, polyfluorinated polymer vessels. However, there are examples of chemical transformations that do not involve such reagents but are still clearly influenced by the choice of reaction vessel material. In the following review, we wish to condense the most significant examples of vessel effects during chemical transformations as well as observations of container-dependent stability of certain molecules. While the primary focus is on synthetic organic chemistry, relevant examples from inorganic chemistry, polymerization reactions, atmospheric chemistry and prebiotic chemistry are also covered.

Self-Shielding Gyroscopic Radiosurgery-A First Clinical Experience, Case Series, and Dosimetric Comparison.

BACKGROUND: Self-shielding gyroscopic radiosurgery (GRS) represents a technical innovation in the field of stereotactic radiosurgery. GRS does not require a radiation vault and is optimized for radiosurgical treatments. Reports on its usage are limited. We describe the first clinical experience of GRS at our institution to assess the application of GRS in the treatment of cranial tumors. Moreover, we perform a dosimetric comparison to robotic radiosurgery (RRS) with vestibular schwannoma (VS) GRS patients. METHODS: Patients who were treated with GRS between July and November 2021 were included. Patient, tumor, and dosimetric characteristics were retrospectively summarized and analyzed. RESULTS: Forty-one patients with 48 intracranial tumors were included. Tumor entities mostly comprised VS, brain metastases, and meningiomas. The median prescription dose and isodose line were 13.5 Gy and 50.0% for benign neoplasia versus 20 Gy and 60.0% for malignant tumors, respectively. The mean planning target volume was 1.5 cubic centimeters. All patients received a single-fraction treatment without encountering any technical setup difficulties. Treatment plan comparisons with RRS revealed comparable plan characteristics, dose gradients, and organs at risk doses. Significant differences were detected concerning the new conformity index and number of monitor units per treatment (both P < 0.01). CONCLUSIONS: This case series provides more evidence on the usage of self-shielding GRS in the management of cranial tumors. Dosimetric comparisons for VS cases revealed mostly equivalent dosimetric characteristics to RRS. Further clinical and physical analyses for GRS are underway.

Single-isocenter stereotactic radiosurgery for multiple brain metastases: Impact of patient misalignments on target coverage in non-coplanar treatments.

Frameless single-isocenter non-coplanar stereotactic radiosurgery (SRS) for patients with multiple brain metastases is a treatment at high geometrical complexity. The goal of this study is to analyze the dosimetric impact of non-coplanar image guidance with stereoscopic X-ray imaging. Such an analysis is meant to provide insights on the adequacy of safety margins, and to evaluate the benefit of imaging at non-coplanar configurations. The ExacTrac® (ET) system (Brainlab AG, Munich, Germany) was used for stereoscopic X-ray imaging in frameless single-isocenter non-coplanar SRS for multiple brain metastases. Sub-millimeter precision was found for the ET-based pre-treatment setup, whereas a degradation was noted for non-coplanar treatment angles. Misalignments without intra-fractional positioning corrections were reconstructed in 6 degrees of freedom (DoF) to resemble the situation without non-coplanar image guidance. Dose recalculation in 20 SRS patients with applied positioning corrections did not reveal any significant differences in D98% for 75 planning target volumes (PTVs) and gross tumor volumes (GTVs). For recalculation without applied positioning corrections, significant differences (p<0.05) were reported in D98% for both PTVs and GTVs, with stronger effects for small PTV volumes. A worst-case analysis at increasing translational and rotational misalignment revealed that dosimetric changes are a complex function of the combination thereof. This study highlighted the important role of positioning correction with ET at non-coplanar configurations in frameless single-isocenter non-coplanar SRS for patients with multiple brain metastases. Uncorrected patient misalignments at non-coplanar couch angles were linked to a significant loss of PTV coverage, with effects varying according to the combination of single DoF and PTV geometrical properties.

Stereoselective O-Glycosylations by Pyrylium Salt Organocatalysis.

Despite many years of invention, the field of carbohydrate chemistry remains rather inaccessible to non-specialists, which limits the scientific impact and reach of the discoveries made in the field. Aiming to increase the availability of stereoselective glycosylation chemistry for non-specialists, we have discovered that several commercially available pyrylium salts catalyze stereoselective O-glycosylations of a wide range of phenols and alkyl alcohols. This catalytic reaction utilizes trichloroacetimidates, an easily accessible and synthetically proven electrophile, takes place under air and only initiates when all three reagents are mixed, which should provide better reproducibility by non-specialists. The reaction exhibits varying degrees of stereospecificity, resulting in ß-selective glycosylations from α-trichloroacetimidates, whilst an α-selective glycosylation proceeds from ß-trichloroacetimidates. A mechanistic study revealed that the reaction likely proceeds via an SN 2-like substitution on the protonated electrophile.

Verbal memory in children with temporal lobe epilepsy: Exploring task-specificity.

RATIONALE: This study explored the applicability of the adult model of task-specificity of memory to children with temporal lobe epilepsy (TLE). METHOD: Retrospective clinical audit; 38 children and adolescents (6-16 years) with lesional TLE (n = 22 mesial; n = 16 lateral) treated at tertiary pediatric hospitals completed two types of verbal memory paradigms: arbitrary associative (Verbal Paired Associates - Hard Pairs) and semantically related (Verbal Paired Associates - Easy Pairs; Stories). RESULTS: Children with mesial TLE performed more poorly than their lateral TLE counterparts on both types of memory paradigms: arbitrary associative and semantically related (Stories only). Groups with left and right TLE performed comparably on all verbal memory measures. CONCLUSIONS: Our findings suggest that the adult model of task-specificity may not be completely applicable to children with TLE. Consideration of the developmental context is critical in research and clinical work with pediatric populations.

Self-promoted and stereospecific formation of N-glycosides.

A stereoselective and self-promoted glycosylation for the synthesis of various N-glycosides and glycosyl sulfonamides from trichloroacetimidates is presented. No additional catalysts or promoters are needed in what is essentially a two-component reaction. When α-glucosyl trichloroacetimidates are employed, the reaction resulted in the stereospecific formation of the corresponding ß-N-glucosides in high yields at ambient conditions. On the other hand, when equatorial glucosyl donors were used, the stereospecificity decreased and resulted in a mixture of anomers. By NMR-studies, it was concluded that this decrease in stereospecificity was due to an, until now, unpresented anomerization of the trichloroacetimidate under the very mildly acidic conditions. The mechanism and kinetics of the glycosylations have been studied by NMR-experiments, which gave an insight into the activation of trichloroacetimidates, suggesting an SNi-like mechanism involving ion pairs. The scope of glycosyl donors and sulfonamides was found to be very broad including popular N-protective groups and common glycosyl donors of various reactivity. Peracetylated GlcNAc trichloroacetimidate could be used without the need for any promotors or additives and a tyrosine side chain was glycosylated as an N-glycosyl carbamate. The N-carbamates and the N-sulfonyl groups functioned as orthogonal protective groups of the N-glycoside and hence allowed further N-functionalization without risking mutarotation of the N-glycoside. The N-glycosylation was also performed on a gram scale, without a drop in stereoselectivity nor yield.

Ethene Dimerization on Zeolite-Hosted Ni Ions: Reversible Mobilization of the Active Site.

The active site in ethene oligomerization catalyzed by Ni-zeolites is proposed to be a mobile Ni(II) complex, based on density functional theory-based molecular dynamics (DFT-MD) simulations corroborated by continuous-flow experiments on Ni-SSZ-24 zeolite. The results of the simulations at operating conditions show that ethene molecules reversibly mobilize the active site as they exchange with the zeolite as ligands on Ni during reaction. Microkinetic modeling was conducted on the basis of free-energy profiles derived with DFT-MD for oligomerization on these mobile [(ethene)2-Ni-alkyl]+ species. The model reproduces the experimentally observed high selectivity to dimerization and indicates that the mechanism is consistent with the observed second-order rate dependence on ethene pressure.

Hepatitis C virus infection among people who inject drugs in Bangkok, Thailand, 2005–2010

Background Approximately 1% of adults in Thailand are infected with hepatitis C virus (HCV). Newdirect-acting antiviral agents achieve sustained virologic responses in >95% of HCV-infected patientsand are becoming available in countries around the world. To prepare for new HCV treatment optionsin Thailand, this study characterized HCV infections among people who inject drugs (PWID) inBangkok.Methods The Bangkok Tenofovir Study (BTS) was a pre-exposure prophylaxis trial conducted amongPWID, 2005–2013. Blood specimens were randomly selected from PWID screened for the BTS, to testfor anti-HCV antibody and HCV RNA. The HVR1 region was amplified by polymerase chain reaction,using multiplex primer sets with unique identifier sequences; amplification products were pooled in setsof 25; and consensus sequencing was performed to characterize individual HCV genotypes.Results The median age of 3679 participants tested for anti-HCV antibody was 31 years, 3016(82.0%) were male and 447 (12.2%) were HIV infected. The prevalence of anti-HCV antibody was44.3%. The adjusted odds of testing positive for anti-HCV antibody were higher in men (adjustedodds ratio [aOR] 3.2, 95% confidence interval [CI] 2.4–4.3), those aged 40 years or older (aOR 2.7,95% CI 2.1–3.5), those who had more than a primary school education (aOR 1.7, 95% CI 1.4–2.1),and those who tested HIV positive (aOR 5.2, 95% CI 3.7–7.4). HCV RNA was detected in 644(81.3%) of the 792 anti-HCV antibody-positive specimens, yielding an HCV RNA-positive prevalenceof 36.0% (95% CI 33.8–38.2). Among a random sample of 249 of the 644 specimens, 218 could becharacterized, and the most common HCV subtypes were 1a (30.3%), 1b (12.8%), 3a (35.8%), 3b(6.9%) and 6n (8.7%).Conclusion The prevalence of anti-HCV antibody among PWID was 44.3% and more than one third(36.0%) were HCV RNA positive. Genotypes 1, 3 and 6 accounted for all typable infections. As thegovernment of Thailand considers introduction of direct-acting antiviral medications for people withhepatitis C, it will be important to ensure that the medications target these subtypes.

Catalytic Glycosylations in Oligosaccharide Synthesis.

Catalytic glycosylation has been a central reaction in carbohydrate chemistry since its introduction by Fischer 125 years ago, but it is only in the past three to four decades that catalytic methods for synthesizing oligosaccharides have appeared. Despite the development of numerous elegant and ingenious catalytic glycosylation methods, only a few are in general use. This review covers all methods of catalytic glycosylation with the focus on the development and application in oligosaccharide synthesis and provide an overview of the scope and limitations of these. The review also includes relevant mechanistic studies of catalytic glycosylations. The future of catalytic glycosylation chemistry is discussed, including specific, upcoming methods and possible directions for the field of research in general.

Pipamperone and delirium: a preliminary evaluation of its effectiveness in the management of delirium and its subtypes.

INTRODUCTION: Delirium has been recognised as an underdiagnosed and undermanaged syndrome with substantial prevalence rates and potentially deleterious consequences in the medically ill population. Despite its frequent administration in the management of delirium, the effectiveness of pipamperone has not yet been evaluated. METHODS: In this retrospective, descriptive cohort study of 192 patients, pipamperone as monotherapy and as an adjunct to haloperidol, haloperidol alone, or atypical antipsychotics were compared with respect to their effectiveness in the management of delirium and its subtypes over the course of 20 days. RESULTS: In this elderly patient population, pipamperone alone and as an adjunct to haloperidol was as effective as haloperidol or atypical antipsychotics in the management of delirium. Management with low-dose pipamperone monotherapy achieved delirium resolution in 70% of patients, over a mean of 6.4 (2-20) days. With pipamperone as an adjunct to haloperidol, delirium resolved in 59% of patients, over a mean of 7.4 (2-20) days. When haloperidol or atypical antipsychotics (risperidone, olanzapine or quetiapine) were used, the delirium resolution rates were 72 and 67%, over a mean of 5.2 (2-11) and 6.4 (2-20) days, respectively. The addition of pipamperone to haloperidol decreased the requirement for lorazepam. Pipamperone proved to be equally effective in all delirium subtypes - hypoactive, hyperactive and mixed. Nonetheless, potential bias could not be excluded in this observational design. CONCLUSION: From these initial results, low-dose pipamperone was as effective as haloperidol or atypical antipsychotics in the management of delirium and its subtypes, and was benzodiazepine-sparing when used as an adjunct to haloperidol.

Specific ion effects on the particle size distributions of cell culture-derived influenza A virus particles within the Hofmeister series.

Virus particle (VP) aggregation can have serious implications on clinical safety and efficacy of virus-based therapeutics. Typically, VP are suspended in buffers to establish defined product properties. Salts used to achieve these properties show specific effects in chemical and biological systems in a reoccurring trend known as Hofmeister series (HS). Hofmeister series effects are ubiquitous and can affect colloidal particle systems. In this study, influences of different ions (anions: SO4 2-, HPO4 2-, Cl-, Br-, NO3 -, I-; cations: K+, Na+, Li+, Mg2+, Ca2+) on particle size distributions of cell culture-derived influenza VP were investigated. For the experimental setup, influenza virus A/Puerto Rico/8/34 (H1N1) VP produced in adherent and suspension Madin Darby canine kidney cells were used. Inactivated and concentrated virus harvests were dialyzed against buffers containing the ions of interest, followed by differential centrifugal sedimentation to measure particle size distributions. VP from both cell lines showed no aggregation over a wide range of buffers containing different salts in concentrations ≥60 mM. However, when dialyzed to low salt or Ca2+ buffers, VP produced in adherent cells showed increased aggregation compared to VP produced in suspension cells. Additionally, changes in VP diameters depending on specific ion concentrations were observed that partially reflected the HS trend.

Comparison of Influenza Virus Particle Purification Using Magnetic Sulfated Cellulose Particles with an Established Centrifugation Method for Analytics.

A method for the purification of influenza virus particles using novel magnetic sulfated cellulose particles is presented and compared to an established centrifugation method for analytics. Therefore, purified influenza A virus particles from adherent and suspension MDCK host cell lines were characterized on the protein level with mass spectrometry to compare the viral and residual host cell proteins. Both methods allowed one to identify all 10 influenza A virus proteins, including low-abundance proteins like the matrix protein 2 and nonstructural protein 1, with a similar impurity level of host cell proteins. Compared to the centrifugation method, use of the novel magnetic sulfated cellulose particles reduced the influenza A virus particle purification time from 3.5 h to 30 min before mass spectrometry analysis.

Magnetically guided recellularization of decellularized stented porcine pericardium-derived aortic valve for TAVI.

Application of somatic stem cells for growth, proliferation, and differentiation in a three-dimensional pattern is an important aspect in tissue engineering. Here, we report on our bioreactor, which we applied for magnetically guided recellularization of nitinol-stented valve. Human-derived unrestricted somatic stem cells were cultured in medium in our pulsatile dynamic bioreactor for 4-6 days. Stented valves were prepared by decellularization of porcine pericardium and construction of stented tissue-engineered valves (n = 8). A magnetic field was created around the bioreactor to prevent the loss of cells. In the control group, no magnetic device was used (n = 4). Morphological characterization was assessed by immunohistochemical staining of paraffin sections and electron microscopy. The bioreactor enabled the preservation of physiologic culture conditions with aerobic cell metabolism and physiological pH values. Histological analysis showed homogeneous seeding of the pericardium with progenitor cells in the recellularized samples, whereas no cell seeding could be observed in the nonmagnetic group. Our magnetically guided multifunctional bioreactor allows for an efficient three-dimensional culturing of somatic stem cells on decellularized organ-specific matrix.

Oncogenetic tree modeling of human hepatocarcinogenesis.

Classical comparative genomic hybridization (CGH) has been used to identify recurrent genomic alterations in human HCC. As hepatocarcinogenesis is considered as a stepwise process, we applied oncogenetic tree modeling on all available classical CGH data to determine occurrence of genetic alterations over time. Nine losses (1p, 4q, 6q, 8p, 9p, 13q, 16p, 16q and 17p) and ten gains (1q, 5p, 6p, 7p, 7q, 8q, 17q, 20p, 20q and Xq) of genomic information were used to build the oncogenetic tree model. Whereas gains of 1q and 8q together with losses of 8p formed a cluster that represents early etiology-independent alterations, the associations of gains at 6q and 17q as well as losses of 6p and 9p were observed during tumor progression. HBV-induced HCCs had significantly more chromosomal aberrations compared to HBV-negative tumors. Losses of 1p, 4q and 13q were associated with HBV-induced HCCs, whereas virus-negative HCCs showed an association of gains at 5p, 7, 20q and Xq. Using five aberrations that were significantly associated with tumor dedifferentiation a robust progression model of stepwise human hepatocarcinogensis (gain 1q → gain 8q → loss 4q → loss 16q → loss 13q) was developed. In silico analysis revealed that protumorigenic candidate genes have been identified for each recurrently altered hotspot. Thus, oncogenic candidate genes that are coded on chromosome arms 1q and 8q are promising targets for the prevention of malignant transformation and the development of biomarkers for the early diagnosis of human HCC that may significantly improve the treatment options and thus prognosis of HCC patients.

Prospective validation of protocol for occult penetrating cardiac injury

OBJECTIVE: Preliminary studies done at the Philippine General Hospital have documented the reliability of pericardial ultrasound in the diagnosis of occult penetrating cardiac injury. This study sought to validate a protocol formulated from these studies in a larger trauma patient population at a high-volume center. METHODS: Over a 2-year period, all hemodynamically stable patients with penetrating injury to the precordial area were managed according to the occult penetrating cardiac injury protocol. Patients with a negative result on pericardial ultrasound were admitted for 24-hour observation. Those with minimal fluid or equivocal findings underwent a subxiphoid pericardiotomy. Patients with moderate to large amounts of fluid on ultrasound, as well as those with positive results on subxiphoid pericardiotomy, underwent definitive surgery. Demographic data, wounding patterns, and clinical course were studied. RESULTS: Three hundred forty patients were analyzed. Majority (91%) had negative ultrasound results, and where either discharged after 24-hour observation, or were treated for other associated injuries. None developed signs or symptoms of cardiac tamponade on follow-up. Twenty-six patients (8%) had either minimal fluid or equivocal findings. These underwent subxiphoid pericardiotomy, of which 10 had positive cardiac injury while nine had serous fluid. Three had moderate amount of fluid on ultrasound and underwent immediate thoracotomy; all had significant cardiac injury. There were no late complications noted. CONCLUSION: Our data provides further validation that subxiphoid pericardial ultrasound is effective as an initial tool in ruling out cardiac injury. Because of a significant number of false positives in Filipino patients, those with minimal fluid should undergo subxiphoid pericardiotomy. The finding of moderate fluid is an indication for definitive surgery.