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Abstract Introduction Brodalumab is a human interleukin-17 receptor A antagonist indicated for the treatment of moderate-to-severe plaque psoriasis in adult patients who are candidates for systemic therapy or phototherapy and have failed to respond or have lost response to other systemic therapies. Although the US prescribing information for brodalumab includes a boxed warning regarding suicidal ideation and behavior, no causal association has been demonstrated. Here, we summarize 5 years of pharmacovigilance data, from August 15, 2017, through August 14, 2022, reported to Ortho Dermatologics by US patients and healthcare providers. Methods Prevalence of the most common adverse events (AEs) listed in the brodalumab package insert (incidence ≥ 1%) and AEs of special interest are described. Brodalumab exposure was estimated as the time from the first to last prescription-dispensing authorization dates. Data were collected from 4744 patients in the USA, with an estimated exposure of 5815 patient-years. Results Over 5 years, 11 cases of adjudicated major adverse cardiovascular events were reported (0.23 events/100 patients), a rate lower than that experienced by patients in the international Psoriasis Longitudinal Assessment and Registry. There were 106 serious infections. No serious fungal infections were reported. There were 40 confirmed and 2 suspected COVID-19 cases, with no new COVID-19-related deaths. Of 49 reported malignancies among 42 patients, 3 were deemed possibly related to brodalumab. No completed suicides and no new suicidal attempts were reported. Conclusion Five-year pharmacovigilance data are consistent with the established safety profile reported in long-term clinical trials and previous pharmacovigilance reports, with no new safety signals.

Growers rely on broad-spectrum agrochemicals to manage one of the most economically important fruit tree diseases, huanglongbing (HLB, citrus greening disease), presumptively caused by the gram-negative bacterium ‘Candidatus Liberibacter asiaticus’ (CLas). Although genetic resistance would be an attractive alternative to chemical management, this option is not yet available for HLB. Here, we tested whether a single chain variable fragment (scFv) antibody targeting the predicted CLas outer membrane transporter NodT can inhibit CLas growth or HLB disease development when expressed in ‘Duncan’ grapefruit (Citrus × paradisi). CLas NodT is similar to TolC and could be involved in Type I secretion and virulence. The scFv antibody was expressed in grapefruit trees as a C-terminal translational fusion to the Flowering Locus T protein of Poncirus trifoliata (FT-scFv) to promote expression in the phloem. Wild-type and FT-scFv-expressing transgenic lines were challenged with CLas using three inoculation approaches: psyllid-mediated inoculation, vegetative graft inoculation, and natural exposure in grove-like conditions. With the first two approaches, HLB symptom expression and CLas bacterial titers in FT-scFv grapefruit lines were not significantly different from wild-type controls. In the grove trial, one FT-scFv line exhibited a slight, but significant, reduction in canopy chlorosis compared to wild-type controls. Wild-type and FT-scFv lines were similar in all other metrics. We conclude that the expression of anti-NodT FT-scFv antibody in grapefruit did not decrease HLB susceptibility. Although our approach was unsuccessful, we hope that documenting our results will be useful for those seeking to develop HLB-resistant citrus germplasm in the future. [Figure: see text] Copyright © 2023 The Author(s). This is an open access article distributed under the CC BY-NC-ND 4.0 International license.

Florida citrus production from 1980-2021 was examined and modeled to determine the impacts associated with weather events and disease introductions.  Specifically, the study examined the effects of North Atlantic hurricanes, freezes events and two disease introductions -- Asiatic citrus canker (ACC), and Huanglongbing (HLB) -- on productions levels and on the structure of the Florida citrus industry.  The models estimated quantified the effects on production associated with the weather events and disease introductions.  Using the deterministic model generated, forecasts were generated to identify future implications of HLB on Florida citrus production.  Theses generated forecasts were compared to actual production levels and the USDA Crop forecast to test and validate the model.  Whereas testing indicated a significant structural change in the Florida citrus industry resulting from adverse weather events and disease introductions, published economic impact studies were examined and reviewed to gage the resulting reduction in total economic impact.

Abstract The Philippines as a tropical country is home to several indigenous berries that offer enough supply of health-promoting bioactive compounds like vitamin C. Vitamin C is an important micronutrient in the human diet that is usually supplied by fruits and vegetables. The amount of this vitamin in different products varies depending on the species, variety, maturity, processing, and other conditions. In this study, the vitamin C contents of selected Philippine indigenous berries such as bignay and lipote were evaluated as affected by fruit maturity and processing treatment. Fruits of two bignay (Antidesma bunius (Linn.) Spreng), varieties, ‘Common’ and ‘Kalabaw’, as well as of lipote (Syzygium polycephaloides (C. B. Rob.) Merr.), at three maturity stages (unripe, half-ripe, and fully ripe) were acquired in Laguna, Philippines. Samples were subjected to two processing treatments: blanched (90 ± 5 °C, 2 minutes) and steamed (105 ± 5 °C, 5 minutes), while control samples did not undergo processing treatment. The flesh and seeds were separated, lyophilized, extracted, and subjected to quantification of vitamin C using reversed-phase high performance liquid chromatography. Results showed that the vitamin C levels of both fruits were significantly affected by maturity, processing, and their interaction (P

Bignay (Antidesma bunius L. Spreng) is an indigenous fruit in the Philippines known for its bioactive compounds and is commonly preserved by conventional freezing. Processing can be done to improve its storage condition and convert it into functional ingredients. This study aimed to determine the effect of freeze-drying, oven drying (50°C), spray drying, and juice concentrating on the dietary fiber composition, phenolic compounds, and antioxidant activity of Bignay. Results showed that oven drying increased the total dietary fiber of Bignay by 29% while freeze drying resulted to an increase in total phenolics, total flavonoids, and total anthocyanin by 69%, 55%, and 66%, respectively, with an increase in antioxidant activity in terms of DPPH, FRAP, and ABTS by 57%, 15% and 31%, respectively. Spray drying was found to be the most detrimental method while juice concentration gave little to no significant effects. Epicatechin, catechin, and gallic acid were the main phenolic compounds quantified in the processed Bignay. The study recommends that freeze-drying is the best method followed by oven drying, concentration, and spray drying.

Abstract Bignay pomace is a processing byproduct that can be a source of bioactive compounds. However, a suitable dehydration method should be considered to efficiently valorize this waste material into high-value food ingredient and maximize its health-promoting properties. Bignay pomace was subjected to convection oven-drying and freeze-drying to investigate the effect of these pre-processing techniques on the physicochemical, bioactives, and antioxidant properties of the samples. Both drying methods significantly (p

Millions of Americans lack access to high-speed broadband, which is important for connectivity in the modern world. For me, as a Member of the House Committee on Energy and Commerce, closing this digital divide is a top priority. In this Essay, I discuss how a streamlined permitting process, as outlined by my American Broadband Deployment Act, can promote investment and innovation while also connecting more Americans with this vital service. [ABSTRACT FROM AUTHOR]

Purpose: Light affects a variety of non-image forming processes, such as circadian rhythm entrainment and the pupillary light reflex, which are mediated by intrinsically photosensitive retinal ganglion cells (ipRGCs). The purpose of this study was to assess the effects of long- and short-wavelength ambient lighting on activity patterns and pupil responses in rhesus monkeys.Methods: Infant rhesus monkeys were reared under either broadband “white” light (n = 14), long-wavelength “red” light (n = 20; 630 nm), or short-wavelength “blue” light (n = 21; 465 nm) on a 12-h light/dark cycle starting at 24.1 ± 2.6 days of age. Activity was measured for the first 4 months of the experimental period using a Fitbit activity tracking device and quantified as average step counts during the daytime (lights-on) and nighttime (lights-off) periods. Pupil responses to 1 s red (651 nm) and blue (456 nm) stimuli were measured after approximately 8 months. Pupil metrics included maximum constriction and the 6 s post-illumination pupil response (PIPR).Results: Activity during the lights-on period increased with age during the first 10 weeks (p < 0.001 for all) and was not significantly different for monkeys reared in white, red, or blue light (p = 0.07). Activity during the 12-h lights-off period was significantly greater for monkeys reared in blue light compared to those in white light (p = 0.02), but not compared to those in red light (p = 0.08). However, blue light reared monkeys exhibited significantly lower activity compared to both white and red light reared monkeys during the first hour of the lights-off period (p = 0.01 for both) and greater activity during the final hour of the lights-off period (p < 0.001 for both). Maximum pupil constriction and the 6 s PIPR to 1 s red and blue stimuli were not significantly different between groups (p > 0.05 for all).Conclusion: Findings suggest that long-term exposure to 12-h narrowband blue light results in greater disruption in nighttime behavioral patterns compared to narrowband red light. Normal pupil responses measured later in the rearing period suggest that ipRGCs adapt after long-term exposure to narrowband lighting.

The author attempts, for the first time, a chronological account of the different plant migrations, which have resulted in the present flora characteristic of the mountainous regions of the southern Appalachians. It studies the groups of flora and plant migrations that appear to have participated in the evolution of the modern flora of the southern Appalachians, and which are the following: 1) The ancient Paleozoic tlora, composed mainly of Pteridophytes and Pteridosperms, was modified, during the Appalachian Revolution, by the extermination and evolution of forms, to the primitive Mesozoic vegetation. 2) The almost flat Appalachian region was invaded in the early Cretaceous times by the new development and rapid spread of Angiosperms, which were then tropical in their distribution. 3) At the end of the Mesozoic era, the uprising caused the migration of these tropical forms towards the coastal plains that had recently emerged, leaving however numerous colonies, vestiges in the Appalachians. 4) The new high mountains were occupied by the arctotertiary forests, which were then circumboreal in extension, but are now limited to small geographically widely separated regions. 5) In the last Cenozoic era, the climates that became colder, caused the segregation of the originally homogeneous arctoterciary flora, in a coniferous forest in the north and a perishable forest in the south. 6) The Pleistocene glaciation caused migration to the southern mountains in many ways from the north. 7) The retreat of the ice allowed the migration of the coniferous forests to the north, reoccupying their original area, but leaving an extensive residue in the higher and colder southern Appalachian regions. Note that the individual work of many botanists will be required to fill in the gaps and supply evidence to modify the hypothesis discussed here.

Sugarcane and energy cane (Saccharum spp. hybrids) are ideal for plant-based production of recombinant proteins because their high resource-use efficiency, rapid growth and efficient photosynthesis enable extensive biomass production and protein accumulation at a cost-effective scale. Here, we aimed to develop these species as efficient platforms to produce recombinant Galanthus nivalis L. (snowdrop) agglutinin (GNA), a monocot-bulb mannose-specific lectin with potent antiviral, antifungal and antitumor activities. Initially, GNA levels of 0.04% and 0.3% total soluble protein (TSP) (0.3 and 3.8 mg kg–1 tissue) were recovered from the culms and leaves, respectively, of sugarcane lines expressing recombinant GNA under the control of the constitutive maize ubiquitin 1 (Ubi) promoter. Co-expression of recombinant GNA from stacked multiple promoters (pUbi and culm-regulated promoters from sugarcane dirigent5-1 and Sugarcane bacilliform virus) on separate expression vectors increased GNA yields up to 42.3-fold (1.8% TSP or 12.7 mg kg–1 tissue) and 7.7-fold (2.3% TSP or 29.3 mg kg–1 tissue) in sugarcane and energy cane lines, respectively. Moreover, inducing promoter activity in the leaves of GNA transgenic lines with stress-regulated hormones increased GNA accumulation to 2.7% TSP (37.2 mg kg–1 tissue). Purification by mannose-agarose affinity chromatography yielded a functional sugarcane recombinant GNA with binding substrate specificity similar to that of native snowdrop-bulb GNA, as shown by enzyme-linked lectin and mannose-binding inhibition assays. The size and molecular weight of recombinant GNA were identical to those of native GNA, as determined by size-exclusion chromatography and MALDI-TOF mass spectrometry. This work demonstrates the feasibility of producing recombinant GNA at high levels in Saccharum species, with the long-term goal of using it as a broad-spectrum antiviral carrier molecule for hemopurifiers and in related therapeutic applications.

The concept of liquid metal membranes for hydrogen separation, based on gallium or indium, was recently introduced as an alternative to conventional palladium-based membranes. The potential of this class of gas separation materials was mainly attributed to the promise of higher hydrogen diffusivity. The postulated improvements are only beneficial to the flux if diffusion through the membrane is the rate-determining step in the permeation sequence. Whilst this is a valid assumption for hydrogen transport through palladium-based membranes, the relatively low adsorption energy of hydrogen on both liquid metals suggests that other phenomena may be relevant. In the current study, a microkinetic modeling approach is used to enable simulations based on a five-step permeation mechanism. The calculation results show that for the liquid metal membranes, the flux is limited by the dissociative adsorption over a large temperature range, and that the membrane flux is expected to be orders of magnitude lower compared to the membrane flux through pure palladium membranes. Even when accounting for the lower cost of the liquid metals compared to palladium, the latter still outperforms both gallium and indium in all realistic scenarios, in part due to the practical difficulties associated with making liquid metal thin films.

BackgroundHuman cytomegalovirus (HCMV) is a betaherpesvirus that causes severe disease in situations where the immune system is immature or compromised. HCMV immediate early (IE) gene expression is stimulated by the virion phosphoprotein pp71, encoded by open reading frame (ORF) UL82, and this transactivation activity is important for the efficient initiation of viral replication. It is currently recognized that pp71 acts to overcome cellular intrinsic defences that otherwise block viral IE gene expression, and that interactions of pp71 with the cell proteins Daxx and ATRX are important for this function. A further property of pp71 is the ability to enable prolonged gene expression from quiescent herpes simplex virus type 1 (HSV-1) genomes. Non-human primate cytomegaloviruses encode homologs of pp71, but there is currently no published information that addresses their effects on gene expression and modes of action.ResultsThe UL82 homolog encoded by simian cytomegalovirus (SCMV), strain Colburn, was identified and cloned. This ORF, named S82, was cloned into an HSV-1 vector, as were those from baboon, rhesus monkey and chimpanzee cytomegaloviruses. The use of an HSV-1 vector enabled expression of the UL82 homologs in a range of cell types, and permitted investigation of their abilities to direct prolonged gene expression from quiescent genomes. The results show that all UL82 homologs activate gene expression, and that neither host cell type nor promoter target sequence has major effects on these activities. Surprisingly, the UL82 proteins specified by non-human primate cytomegaloviruses, unlike pp71, did not direct long term expression from quiescent HSV-1 genomes. In addition, significant differences were observed in the intranuclear localization of the UL82 homologs, and in their effects on Daxx. Strikingly, S82 mediated the release of Daxx from nuclear domain 10 substructures much more rapidly than pp71 or the other proteins tested. All UL82 homologs stimulated the early release of ATRX from nuclear domain 10.ConclusionAll of the UL82 homolog proteins analysed activated gene expression, but surprising differences in other aspects of their properties were revealed. The results provide new information on early events in infection with cytomegaloviruses.

The Three Man Thermal Team (T.T.T.) is a technique developed within the Fairfax County Virginia Integrated Deer Management Plan in cooperation with the Fairfax County Police Department’s Special Weapons and Tactics (SWAT) unit for control of overabundant white-tailed deer populations within a suburban/urban setting. The technique utilizes a combination of specialized equipment including a hand-held thermal imager, a laser pointer, a 6-million-candlepower MaxaBeam™ searchlight with focusable beam, and a suppressed rifle. T.T.T. allows targeted animals to be located in total darkness. With the use of a night vision or thermal scope in lieu of the light, the entire operation can be conducted in darkness. While this technique was specifically designed for deer, it can be easily adapted for other species.