Polarization modulation infrared reflectance absorption spectroscopy (PM-IRRAS) and infrared reflectance absorption spectroscopy (IRRAS) have been used to characterize the formation of a self-assembled monolayer of N-(3-dihydroxyborylphenyl)-11-mercaptoundecanamide) (abbreviated PBA) on a gold surface and the subsequent binding of various sugars to the PBA adlayer through the phenylboronic acid moiety to form a phenylboronate ester. Vibrationally resonant sum frequency generation (VR-SFG) spectroscopy confirmed the ordering of the substituted phenyl groups of the PBA adlayer on the gold surface. Solution FTIR spectra and density functional theory were used to confirm the identity of the observed vibrational modes on the gold surface of PBA with and without bound sugar. The detection of the binding of glucose on the gold surface was confirmed in part by the presence of a C-O stretching mode of glucose and the observed O-H stretching mode of glucose that is shifted in position relative to the O-H stretching mode of boronic acid. An IR marker mode was also observed at 1734 cm(-1) upon the binding of glucose. Additionally, changes in the peak profile of the B-O stretching band were observed upon binding, confirming formation of a phenylboronate ester on the gold surface. The binding of mannose and lactose were also detected primarily through the IR marker mode at approximately 1736 to 1742 cm(-1) depending on the identity of the bound sugar.

An 18-year-old student presented with a two-year history of daytime sleepiness and noisy breathing during sleep. Both he and his brother, aged 25 years, had Scheie's syndrome, a mucopolysaccharidosis characterised by small stature, micrognathia, corneal clouding, hepatosplenomegaly, raised urinary mucopolysaccharides, and undetectable levels of oa-L-iduronidase assayed in cultured fibroblasts. Both brothers had sleep apnoea (apnoea index, 59 and 35 respectively) during which there was a significant fall in heart rate and arterial oxygen saturation. One brother had EEG changes suggestive of cerebral hypoxia and the other had ventricular extrasystoles at the end of several episodes. Tracheostomy in the younger brother produced a dramatic symptomatic improvement and reduced the number and severity of apnoeic episodes (post-tracheostomy apnoea index 2.4).

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The purpose was to determine the association of milk California Mastitis Test (CMT), somatic cell concentration (SCC), and milk differential cell count results on day 3 postcalving with subsequent lactation production and health events. On d 3 postcalving, the CMT was performed and quarter milk samples were collected from 130 dairy cows. Quarter SCC and milk differential cell counts were determined. Microbiology on duplicate quarter milk samples was used to determine the presence of intramammary infection by major or minor pathogens. Production measures obtained using Dairy Herd Improvement Association testing were 150-d standardized and summit milks. Milk culture results on a cow basis included 82 (63.1%) samples with no growth, 31 (23.9%) with major pathogens, and 17 (13.1%) with minor pathogens. Milk culture results comparing cows with no growth to those with any growth (major or minor pathogens) were not associated with statistically significant differences in milk production. Milk culture results comparing cows with major pathogens to those with no growth and minor pathogens combined were associated with statistically significant differences in 150 d milk. Milk production did not differ for cows with CMT results above and below a cut-off of trace, and for SCC results above and below cut-offs of 200,000, 300,000, and 400,000/mL, respectively. Statistically significant differences in milk production were found for cows above and below cut-offs for percentage neutrophils in milk and for absolute neutrophil counts. Associations were found for milk production and number of quarters (0, 1, 2, or 3 and 4 combined) above respective cut-offs for SCC, percentage neutrophils in milk, and absolute numbers of neutrophils in milk, but not for CMT. Milk production differed for cows experiencing any health event versus those with no health event. The most commonly recorded health event was clinical mastitis. Statistically significant associations were detected between health events and milk culture results, SCC, neutrophil percentage, and neutrophil absolute counts. Results of the present investigation indicate that milk monitoring on d 3 of lactation using milk neutrophil percentage or neutrophil absolute counts may be useful as an indication of subsequent milk production.

Unhealthy eating habits and physical inactivity along with lack of access to quality healthcare contribute to the marked health disparities in chronic diseases among African-Americans. Faith-based public health conferences offer a potential opportunity to improve health literacy and change health behaviors through health promotion within this population, thereby reducing health disparities. This study examined the self-reported health behaviors and preventive healthcare utilization patterns of 77 participants at a predominantly African-American faith-based public health conference, Healthy Churches 2020. A self-administered questionnaire was distributed to a sample of attendees to assess their health behaviors (diet and physical activity), preventive healthcare utilization (annual healthcare provider visits), and health-promoting activities at their places of worship. The results indicate that attendees of a faith-based public health conference have adequate preventive healthcare utilization, but suboptimal healthy behaviors. Our findings support the need for ongoing health-promoting activities with an emphasis on diet and physical activity among this population.

Research is needed to examine the impact of sleep problems on older adults in IRFs, including work that focuses on intervention trials to identify successful treatments for these problems and translate those approaches into practice.

The inhalation route is a relatively novel drug delivery route for biotherapeutics and, as a result, there is a paucity of published data and experience within the toxicology/pathology community. In recent years, findings arising in toxicology studies with inhaled biologics have provoked concern and regulatory challenges due, in part, to the lack of understanding of the expected pathology, mechanisms, and adversity induced by this mode of delivery. In this manuscript, the authors describe 12 case studies, comprising 18 toxicology studies, using a range of inhaled biotherapeutics (monoclonal antibodies, fragment antigen-binding antibodies, domain antibodies, therapeutic proteins/peptides, and an oligonucleotide) in rodents, nonhuman primates (NHPs), and the rabbit in subacute (1 week) to chronic (26 weeks) toxicology studies. Analysis of the data revealed that many of these molecules were associated with a characteristic pattern of toxicity with high levels of immunogenicity. Microscopic changes in the airways consisted of a predominantly lymphoid perivascular/peribronchiolar (PV/PB) mononuclear inflammatory cell (MIC) infiltrate, whereas changes in the terminal airways/alveoli were characterized by simple (“uncomplicated”) increases in macrophages or inflammatory cell infiltrates ranging from mixed inflammatory cell infiltration to inflammation. The PV/PB MIC changes were considered most likely secondary to immunogenicity, whereas simple increases in alveolar macrophages were most likely secondary to clearance mechanisms. Alveolar inflammatory cell infiltrates and inflammation were likely induced by immune modulation or stimulation through pharmacologic effects on target biology or type III hypersensitivity (immune complex disease). Finally, a group of experts provide introductory thoughts regarding the adversity of inhaled biotherapeutics and the basis for reasonable differences of opinion that might arise between toxicologists, pathologists, and regulators.

Inhibitors of phosphodiesterase 4 (PDE4) are potent anti-inflammatory agents, inhibiting the production of inflammatory mediators through the elevation of intracellular cAMP concentrations. We studied the activity of a novel PDE4 inhibitor, CHF6001, both in vitro in human cells and in vivo, using bioluminescence imaging (BLI) in mice lung inflammation. Mice transiently transfected with the luciferase gene under the control of an NF-κB responsive element (NF-κB-luc) have been used to assess the in vivo anti-inflammatory activity of CHF6001 in lipopolysaccharide (LPS)-induced lung inflammation. BLI as well as inflammatory cells and the concentrations of pro-inflammatory cytokines were monitored in bronchoalveolar lavage fluids (BALF) while testing in vitro its ability to affect the production of leukotriene B4 (LTB4), measured by LC/MS/MS, by LPS/LPS/N-formyl--methionyl--leucyl-phenylalanine (fMLP)-activated human blood. CHF6001 inhibited the production of LTB4 in LPS/fMLP-activated human blood at sub-nanomolar concentrations. LPS-induced an increase of BLI signal in NF-κB-luc mice, and CHF6001 administered by dry powder inhalation decreased in parallel luciferase signal, cell airway infiltration, and pro-inflammatory cytokine concentrations in BALF. The results obtained provide in vitro and in vivo evidence of the anti-inflammatory activity of the potent PDE4 inhibitor CHF6001, showing that with a topical administration that closely mimics inhalation in humans, it efficiently disrupts the NF-κB activation associated with LPS challenge, an effect that may be relevant for the prevention of exacerbation episodes in chronic obstructive pulmonary disease subjects.