Photochemical α-Aminonitrile Synthesis Using Zn-Phthalocyanines as Near-Infrared Photocatalysts.

While photochemical transformations with sunlight almost exclusively utilize the UV-vis part of the solar spectrum, the majority of the photons emitted by the sun have frequencies in the near-infrared region. Phthalocyanines show high structural similarity to the naturally occurring light-harvesting porphyrins, chlorins, and mainly bacteriochlorins and are also known for being efficient and affordable near-infrared light absorbers as well as triplet sensitizers for the production of singlet oxygen. Although having been neglected for a long time in synthetic organic chemistry due to their low solubility and high tendency toward aggregation, their unique photophysical properties and chemical robustness make phthalocyanines attractive photocatalysts for the application in near-infrared-light-driven synthesis strategies. Herein, we report a cheap, simple, and efficient photocatalytic protocol, which is easily scalable under continuous-flow conditions. Various phthalocyanines were studied as near-infrared photosensitizers in oxidative cyanations of tertiary amines to generate α-aminonitriles, a synthetically versatile compound class.

Hearing loss in individuals with osteogenesis imperfecta in North America: Results from a multicenter study.

Hearing loss (HL) is an extra-skeletal manifestation of the connective tissue disorder osteogenesis imperfecta (OI). Systematic evaluation of the prevalence and characteristics of HL in COL1A1/COL1A2-related OI will contribute to a better clinical management of individuals with OI. We collected and analyzed pure-tone audiometry data from 312 individuals with OI who were enrolled in the Linked Clinical Research Centers and the Brittle Bone Disorders Consortium. The prevalence, type, and severity of HL in COL1A1/COL1A2-related OI are reported. We show that the prevalence of HL in OI is 28% and increased with age in Type I OI but not in Types III and IV. Individuals with OI Types III and IV are at a higher risk to develop HL in the first decade of life when compared to OI Type I. We also show that the prevalence of SNHL is higher in females with OI compared to males. This study reveals new insights regarding prevalence of HL in OI including a lower general prevalence of HL in COL1A1/COL1A2-related OI than previously reported (28.3 vs. 65%) and high prevalence of SNHL in females. Our data support the need in early routine hearing evaluation in all types of OI that can be adjusted to the severity of the skeletal disease.

COVID-ABS: An agent-based model of COVID-19 epidemic to simulate health and economic effects of social distancing interventions.

The COVID-19 pandemic due to the SARS-CoV-2 coronavirus has directly impacted the public health and economy worldwide. To overcome this problem, countries have adopted different policies and non-pharmaceutical interventions for controlling the spread of the virus. This paper proposes the COVID-ABS, a new SEIR (Susceptible-Exposed-Infected-Recovered) agent-based model that aims to simulate the pandemic dynamics using a society of agents emulating people, business and government. Seven different scenarios of social distancing interventions were analyzed, with varying epidemiological and economic effects: (1) do nothing, (2) lockdown, (3) conditional lockdown, (4) vertical isolation, (5) partial isolation, (6) use of face masks, and (7) use of face masks together with 50% of adhesion to social isolation. In the impossibility of implementing scenarios with lockdown, which present the lowest number of deaths and highest impact on the economy, scenarios combining the use of face masks and partial isolation can be the more realistic for implementation in terms of social cooperation. The COVID-ABS model was implemented in Python programming language, with source code publicly available. The model can be easily extended to other societies by changing the input parameters, as well as allowing the creation of a multitude of other scenarios. Therefore, it is a useful tool to assist politicians and health authorities to plan their actions against the COVID-19 epidemic.

Photoarylation of Pyridines Using Aryldiazonium Salts and Visible Light: An EDA Approach.

A metal-free methodology for the photoarylation of pyridines, in water, is described giving 2 and 4-arylated-pyridines in yields up to 96%. The scope of the aryldiazonium salts is presented showing important results depending on the nature and position of the substituent group in the diazonium salt, that is, electron-donating or electron-withdrawing in the ortho, meta, or para positions. Further heteroaromatics were also successfully photoarylated. Mechanistic studies and comparison between our methodology and similar metal-catalyzed procedures are presented, suggesting the occurrence of a visible-light EDA complex which generates the aryl radical with no need for an additional photocatalyst.

Organocatalyzed Asymmetric Vinylogous Addition of Oxazole-2(3H)-thiones to α,ß-Unsaturated Ketones: An Additive-Free Approach for Diversification of Heterocyclic Scaffold.

A straightforward organocatalyzed asymmetric addition of oxazole-2(3H)-thiones to α,ß-unsaturated ketones is described. This additive-free Michael reaction in the presence of chiral cinchonine-derived primary amines as catalysts has proven to be highly effective for a wide range of cyclic and acyclic enones, leading to the Michael adducts in very good yields and excellent enantioselectivities. The absolute configuration (R) of compound 5j was unambiguously assigned by X-ray diffraction analysis. Furthermore, experimental and theoretical studies were performed and a mechanism is presented and discussed for this novel reaction.

Limited Dissolved Phosphorus Runoff Losses from Layered Double Hydroxide and Struvite Fertilizers in a Rainfall Simulation Study.

The enrichment of P in surface waters has been linked to P runoff from agricultural fields amended with fertilizers. Novel slow-release mineral fertilizers, such as struvite and P-exchanged layered double hydroxides (LDHs), have received increasing attention for P recycling from waste streams, and these fertilizers may potentially reduce the risk of runoff losses. Here, a rainfall simulation experiment was performed to evaluate P runoff associated with the application of recycled slow-release fertilizers relative to that of a soluble fertilizer. Monoammonium phosphate (MAP), struvite, and LDH granular fertilizers were broadcasted at equal total P doses on soil packed in trays (5% slope) and covered with perennial ryegrass ( L.). Four rainfall simulation events of 30 min were performed at 1, 5, 15, and 30 d after the fertilizer application. Runoff water from the trays was collected, filtered, and analyzed for dissolved P. For the MAP treatment, P runoff losses were high in the first two rain events and leveled off in later rain events. In total, 42% of the applied P in the MAP treatment was lost due to runoff. In the slow-release fertilizer treatments, P runoff losses were limited to 1.9 (struvite) and 2.4% (LDH) of the applied doses and were more similar over the different rain events. The use of these novel P fertilizer forms could be beneficial in areas with a high risk of surface water eutrophication and a history of intensive fertilization.

Vertebral Anomalies in Microtia Patients at a Tertiary Pediatric Care Center.

OBJECTIVE: Microtia is a congenital condition known to be associated with vertebral anomalies and congenital syndromes, most prominently hemifacial microsomia. There is controversy, however, on whether to screen with spinal imaging. Additionally, microtia ear reconstruction utilizes rib harvesting that could potentially worsen pre-existing vertebral and rib anomalies, specifically scoliosis. We report on the prevalence and characteristics of vertebral anomalies among microtia patients at a tertiary pediatric center. STUDY DESIGN: Retrospective case review with literature review. SETTING: Tertiary pediatric referral center. METHODS: A review of 425 children with microtia was conducted, characterized as either syndromic or nonsyndromic. Data included demographics, spinal imaging performed, indications, anomalies detected, and microtia repair. RESULTS: Among 425 microtia patients, 24.5% were syndromic with an average age of 9.7 years. Only 18.4% of all patients had spinal imaging performed (50% syndromic vs 8.1% nonsyndromic). Overall, 10.6% had a vertebral anomaly with a 57.7% detection rate (67.3% syndromic vs 38.5% nonsyndromic). The most common anomaly was scoliosis, with a prevalence of 7.8%. Fusion defects and rib deformities were the next most prominent. Microtia repair, most commonly with an autologous rib graft, was performed in 21.6% of the cohort. However, only 19.2% had spinal imaging and 16.7% with a vertebral anomaly. CONCLUSION: Children with microtia are at a greater risk of vertebral abnormalities. Scoliosis prevalence in isolated microtia is comparable to the general population (2%-3%) but greatly increased with genetic syndromes. Screening for vertebral anomalies should be considered when planning microtia reconstructions, especially in the syndromic population.

Monopolar Cautery Use in Pediatric Cochlear Implant Users.

OBJECTIVES: To determine the incidence and impact of monopolar cautery use in a cohort of pediatric cochlear implant (CI) users. STUDY DESIGN: Case series from a retrospective chart review and a systematic review of the literature. SETTING: Tertiary academic referral center. METHODS: CI patient charts from 2012 to 2021 were reviewed from a single pediatric hospital system to determine if monopolar cautery was used during a subsequent surgical procedure. In addition, a systematic review of the literature was performed to identify additional, relevant patients. Postoperative CI function was the primary outcome measure. RESULTS: In total, 190 patients underwent a surgical procedure following cochlear implantation in a single pediatric hospital system. Fifteen patients (7.9%) and 17 distinct surgical procedures were identified in which monopolar cautery was used. Seven of these 17 cases (41.2%) involved the head and neck, and 10 were performed below the clavicles. No patients experienced a device failure or a decline in CI performance following surgery. A systematic review identified an additional 4 patients who underwent a surgery that used monopolar cautery following cochlear implantation, and no change in CI function was identified. CONCLUSIONS: The present study adds additional support to the notion that monopolar cautery does not necessarily injure CI functionality. While the most risk adverse strategy when planning a surgical procedure for a CI patient is to avoid monopolar cautery use altogether, the use of cautery should not immediately be associated with implant dysfunction.

Synthesis of the Brivaracetam Employing Asymmetric Photocatalysis and Continuous Flow Conditions.

An original total synthesis of the antiepileptic drug brivaracetam (BRV) is reported. The key step in the synthesis consists of an enantioselective photochemical Giese addition, promoted by visible-light and the chiral bifunctional photocatalyst Δ-RhS. Continuous flow conditions were employed to improve the efficiency and allow an easy scale-up of the enantioselective photochemical reaction step. The intermediate obtained from the photochemical step was converted into BRV by two different pathways, followed by one alkylation and amidation, thus giving the desired active pharmaceutical ingredients (API) in 44% overall yield, 9:1 diastereoisomeric ratio (dr) and >99:1 enantiomeric ratio (er).

Biomimetic Design of a Tendon-Driven Myoelectric Soft Hand Exoskeleton for Upper-Limb Rehabilitation.

Degenerative diseases and injuries that compromise hand movement reduce individual autonomy and tend to cause financial and psychological problems to their family nucleus. To mitigate these limitations, over the past decade, hand exoskeletons have been designed to rehabilitate or enhance impaired hand movements. Although promising, these devices still have limitations, such as weight and cost. Moreover, the movements performed are not kinematically compatible with the joints, thereby reducing the achievements of the rehabilitation process. This article presents the biomimetic design of a soft hand exoskeleton actuated using artificial tendons designed to achieve low weight, volume, and cost, and to improve kinematic compatibility with the joints, comfort, and the sensitivity of the hand by allowing direct contact between the hand palm and objects. We employed two twisted string actuators and Bowden cables to move the artificial tendons and perform the grasping and opening of the hand. With this configuration, the heavy part of the system was reallocated to a test bench, allowing for a lightweight set of just 232 g attached to the arm. The system was triggered by the myoelectric signals of the biceps captured from the user's skin to encourage the active participation of the user in the process. The device was evaluated by five healthy subjects who were asked to simulate a paralyzed hand, and manipulate different types of objects and perform grip strength. The results showed that the system was able to identify the intention of movement of the user with an accuracy of 90%, and the orthosis was able to enhance the ability of handling objects with gripping force up to 1.86 kgf.

Synergic vascular photodynamic activity by methylene blue-curcumin supramolecular assembly.

A supramolecular assembly was obtained by combining methylene blue (MB) with a natural plant extract, curcumin (Curc), in a stoichiometric ratio of 1:4 in aqueous solution (90% PBS + 10% ethanol) at room temperature. The MB-Curc supramolecular assembly was evidenced by absorption and fluorescence spectroscopies, and the stoichiometry and bonding constant were obtained using Cielens model. Its stability and photostability were evaluated by chromatographic analysis and UV-Vis absorption. The MB-Curc avoids the aggregation of both isolated compounds and efficiently produces singlet oxygen (ΦΔ= 0.52 ± 0.03). Its potential for photodynamic antiangiogenic treatments was evaluated through the vascular effect observed in chicken chorioallantoic membrane (CAM) assay. The results showed intense damage in CAM vascular network by MB-Curc after irradiation, which is higher than the effect of isolated compounds, indicating a synergistic vascular effect. This combination can be essential to prevent cancer revascularization after photodynamic application and improve the efficacy of this approach. The characteristics exhibited by MB-Curc make it a potential candidate for use in cancer treatments through photodynamic antiangiogenic therapy.

Fabrication of 3D Models for Microtia Reconstruction Using Smartphone-Based Technology.

OBJECTIVE: Microtia reconstruction is technically challenging due to the intricate contours of the ear. It is common practice to use a two-dimensional tracing of the patient's normal ear as a template for the reconstruction of the affected side. Recent advances in three-dimensional (3D) surface scanning and printing have expanded the ability to create surgical models preoperatively. This study aims to describe a simple and affordable process to fabricate patient-specific 3D ear models for use in the operating room. STUDY DESIGN: Applied basic research on a novel 3D optical scanning and fabrication pathway for microtia reconstruction. SETTING: Tertiary care university hospital. METHODS: Optical surface scanning of the patient's normal ear was completed using a smartphone with facial recognition capability. The Heges application used the phone's camera to capture the 3D image. The 3D model was digitally isolated and mirrored using the Meshmixer software and printed with a 3D printer (MonopriceTM Select Mini V2) using polylactic acid filaments. RESULTS: The 3D model of the ear served as a helpful intraoperative reference and an adjunct to the traditional 2D template. Collectively, time for imaging acquisition, editing, and fabrication was approximately 3.5 hours. The upfront cost was around $210, and the recurring cost was approximately $0.35 per ear model. CONCLUSION: A novel, low-cost approach to fabricate customized 3D models of the ear is introduced. It is feasible to create individualized 3D models using currently available consumer technology. The low barrier to entry raises the possibility for clinicians to incorporate 3D printing into various clinical applications.

Dual role of benzophenone enables a fast and scalable C-4 selective alkylation of pyridines in flow.

The efficient C-4 selective modification of pyridines is a major challenge for the synthetic community. Current strategies are plagued with at least one drawback regarding functional group-tolerant electronic activation of the heteroarene, mild generation of the required alkyl radicals, regioselectivity, safety and/or scalability. Herein, we describe a fast, safe and scalable flow process which allows preparation of said C-4 alkylated pyridines. The process involves a photochemical hydrogen atom transfer (HAT) event to generate the carbon-centered radicals needed to alkylate the C-2 blocked pyridine. In a two-step streamlined flow process, this light-mediated alkylation step is combined with a nearly instantaneous inline removal of the blocking group. Notably, cheap benzophenone plays a dual role in the pyridine alkylation mechanism by activating the hydrocarbon feedstock reagents via a HAT mechanism, and by acting as a benign, terminal oxidant. The key role of benzophenone in the operative reaction mechanism has also been revealed through a combination of experimental and computational studies.

Bone conduction hearing device adherence in relationship to age in pediatric unilateral congenital aural atresia.

OBJECTIVE: To characterize the adherence of bone conduction hearing devices (BCHDs) for hearing management in children with unilateral congenital aural atresia (UCAA) in relation to the age of offer and fitting. BCHD Soft Bands help predict amplification benefits before surgery can be performed beginning around five years when both hearing and parental compliance reach stability. We hypothesized device compliance might decrease with age of fitting from lack of early acclimatization. METHODS: Retrospective case series of patients less than five years old at a tertiary pediatric center's microtia clinic database, born between 2014 and 2018 with UCAA. Adherence was assessed through electronic health record note documentation at less than 1 year, 1-2 years, and greater than 2 years from fitting. The ages at offer and fitting, along with the time from offer to fitting, were recorded. RESULTS: One hundred and eight patients with UCAA were identified, including 46 patients fit with a BCHD used for further analysis. Adherence rates at 1 year, 1-2 years, and greater than 2 years were 47.8%, 30%, and 43.5%, respectively. However, there was no significant association between age offered, age fit, or time from offer to fit and adherence at all time points. Also, there was no significant difference between ages at the time of BCHD offer for those who chose not to proceed with fitting (20.9 months) compared to the age of offer in patients that were subsequently fit (13.9 months). CONCLUSION: BCHD adherence in patients less than five years old may not be affected by the age offered or fit. The time between offer and fitting was also not associated with usage. BCHDs should be offered to UCAA patients regardless of age. Further investigation in this younger age group would help expand these findings.

Screening fertilizers for their phosphorus runoff risk using laboratory methods.

Losses of phosphorus (P) from fertilized fields may result in degradation of water quality. Various initiatives are under evaluation to minimize water contamination, including the adoption of less soluble or coated P fertilizer formulations aiming to mitigate losses of P in runoff. Field-based rainfall simulators are traditionally used to evaluate P runoff, but using these is time consuming, labor intensive, and costly given the complex apparatus and analyses involved. We hypothesized that laboratory-based methods could be useful to evaluate the risk of P runoff from fertilizers. In order to identify a rapid, inexpensive, and efficient screening process, we compared two laboratory-scale measurements, one in water (based on electrical conductivity measurements) and one in soil (based on visualization of P diffusion in soil), with runoff results from field-, glasshouse-, and laboratory-based rainfall simulators, using coated soluble phosphate fertilizers. The laboratory-based methods assessing the P release rate in water and in soil correlated closely (r ≥ .96) with the losses of P obtained in the three rainfall simulators regardless of the type of coating or solubility of the fertilizer. The faster and inexpensive electrical conductivity and diffusion visualization methodologies were useful to rank the fertilizers by P release to runoff. Hence, these tools may be useful for screening fertilizer formulations with respect to their runoff risk.

Recrudescence of Toxoplasma gondii infection in chronically infected rats (Rattus norvegicus).

The kinetics of Toxoplasma gondii infection reactivation in the brain and muscles was analyzed in this study to determine the preferred tissue by the parasite during immunosuppression. Two groups of Wistar rats (G1 and G2) were inoculated with 10(4) bradyzoites of BTU10 strain (genotype I), p.o., and other two groups (G3 and G4) were inoculated with 0.9% saline solution. G2 and G4 were immunosuppressed with dexamethasone (DXM) and hydrocortisone sodium succinate (HSS). The presence of antibodies was researched in all groups through modified agglutination test (MAT) on days 0 and 21 p.i., and brain and muscle tissues of the rats were bioassayed in mice. G2 rats died at approximately 19.2days after drug treatment, while G1 rats survived. The reactivation was initially observed in G1 brain and G2 muscles. Thus, the initial reactivation in muscles after immunosuppression allows doctors to save precious time to control the evolution of reactivated infection, preventing brain damage to the host.

Direct C-H photoarylation of diazines using aryldiazonium salts and visible-light.

In this study, direct C-H photoarylation of pyrazine with aryldiazonium salts under visible-light irradiation (blue-LEDs) is described, and additional examples including photoarylations of pyrimidine and pyridazine are also covered. The corresponding aryl-diazines were prepared in yields up to 84% only by mixing and irradiating the reaction with no need for an additional photocatalyst. We demonstrate the efficacy of this protocol by the scope with electron-donor, -neutral, and -withdrawing groups attached at the ortho, meta, and para positions of the aryldiazonium salts; the results are better than those reported for ruthenium-complex mediated photoarylations. Additionally, we demonstrate the robustness of this methodology with a 5 mmol scaled-up experiment. Mechanistic studies were carried out giving support to the proposal of a photocatalyzed approach by an electron donor-acceptor (EDA) complex, also highlighting the crucial role that solvents play in the formation of the EDA complex.

Acquisition limitations of bone conduction hearing devices in children with unilateral microtia and atresia.

OBJECTIVE: To characterize the use of bone conduction hearing devices (BCHD) for hearing management in children with unilateral congenital aural atresia (CAA) at a tertiary pediatric center's microtia clinic while assessing challenges in acquisition. BCHD generally provides better audiologic outcomes than atresiaplasty in pediatric CAA. BCHD is formally recommended for only bilateral CAA, although literature has begun to show benefit in unilateral CAA. METHODS: A retrospective case series of patients born between 2014 and 2018 with unilateral microtia at an urban tertiary care children's hospital collected information on demographics, CAA laterality, hearing loss (HL) severity, management, and acquisition. Statistical analysis aided characterization of BCHD use. RESULTS: 131 patients (65% males) were included with a mean age of 3.5 years. 108 (82%) patients with unilateral microtia were used for further analysis, and right sided microtia was most common (67.6%). Of patients with auditory brain response (ABR) testing available, 70% demonstrated conductive HL, 16% mixed HL, 1% sensorineural HL, 6% no HL secondary to grade 1 microtia, and 7% were pending evaluation. Overall, 46 (42.6%) patients with unilateral microtia obtained a BCHD. 68.7% of those offered a BCHD after ABR opted for acquisition. The average length of time from offer to fit was about 6 months. CONCLUSION: Even with thorough consultation and follow up, less than half of the patients with unilateral CAA received a BCHD. Missed initial ABR appointments that lead to BCHD recommendation seem to be the greatest limiting factor, while demographics did not play a confounding role. Family education and future research on obstacles preventing BCHD use in unilateral CAA will help standardize management and improve hearing within this critical auditory period.

Author Correction: Improving the efficacy of selenium fertilizers for wheat biofortification.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

A Systematic Review of Cochlear Implant Outcomes in Prelingually-deafened, Late-implanted Patients.

OBJECTIVE: To analyze outcomes of cochlear implantation (CI) in prelingually-deafened, late-implanted patients. DATA SOURCES: A search of MEDLINE and EMBASE was performed in February 2018 using SCOPUS for the intersection of "cochlear implant," "prelingual," "deaf," and "delay." REVIEW METHODS: Two independent reviewers screened all abstracts and titles for relevance, with conflicts resolved by either the primary or senior author. All articles passing this screen were subjected to a full-text review, during which the primary and senior author each examined manuscripts for inclusion and exclusion criteria. The Cochrane Risk of Bias Assessment Tool was used to assess potential sources of systematic error, and postoperative clinical outcomes were collected at the latest clinical follow-up. RESULTS: Twenty-eight articles were yielded in the final systematic review, accounting for 542 patients. For open-set sentence scores, 10 studies representing 240 patients showed an overall estimated improvement of 44.6% (95% CI: 38.0-51.2%). In terms of quality of life, studies generally showed improvement when looking at specific emotional, social, or hearing-specific domains, but not in global measures. Nonuser rates ranged from 0 to 9.5%. CONCLUSION: Despite performance that is generally poorer than what is generally seen in "traditional" candidates, prelingually-deafened, late-implanted (PL-LI) CI users can experience benefit in terms of both QOL and audiometric scores. The wide range of performance that is reported in the literature highlights the importance of careful patient counseling.