Broad Groups Research Articles

2269 Preventing frailty crises: improving the care of frail patients in an acute hospital Ward setting

Abstract Introduction Frailty is common in hospitalised older patients and hospitalisation can lead to negative outcomes. Our study aimed to provide insights into current decision-making processes on treatment, care and discharge by clinical teams. Methods We conducted a prospective cohort study in frail older patients ≥65 years old admitted to acute medical and surgical wards. Clinical Frailty Scale ≥5 was used to identify frail patients and process mapping was undertaken to identify common themes, trajectories and potentially modifiable factors. We followed patient journeys from admission to discharge and examined factors contributing to longer hospitalisation. We documented existing processes, environmental, system and clinical factors influencing patient care. Comprehensive geriatric assessments identified underlying geriatric syndromes and where gaps in management were identified, we recommended frailty interventions. Results Fifteen patients provided informed consent, of whom 73% were female and average age 80 years, ranging 69–95 years. 67% were frail (CFS 5–6) and 33% were severely frail (CFS 7–9). Most patients were sarcopenic with a SARC-F score of ≥4 and had functional and gait impairment. 60% were underweight (BMI <22). Process mapping revealed gaps in frailty-focused care and included delayed transfer to acute wards, delayed investigations, and multiple unidentified geriatric syndromes which were prevalent in this cohort. Patients fell into three broad groups, short (1–6 days), intermediate (7–14 days), or long (>14 days) length of stay and delays in discharge-planning were common, mean of 4.17 days, as were delays in identification of a caregiver. Recommendations for community support services were provided to >50% patients. Conclusion Our study shows that mapping the frail patient’s journey can identify gaps in existing processes and opportunities for improvement and collaboration. Integrating geriatric care into general wards could improve patient outcomes. We aim to use this work to guide frailty-attuned care for hospitalised older patients.

Flavin-catalyzed, TBHP-promoted oxidation of (het)aryl alkane to ketone

A protocol of flavin-catalyzed, TBHP-promoted aerobic oxidation of (het)aryl alkane to ketones has been developed and the products were provided in moderate-to-excellent yields with broad functional group tolerance. Flavin was first employed as a catalyst to oxidize (het)aryl alkane to ketones. The methodology were applied to the synthesis of many biologically active, pharmaceutical molecules and natural products. Mechanistic investigation reveals that a radical pathway may be involved in the transformation.

Synthesis of Sulfilimines via Visible-Light-Mediated Triplet Energy Transfer to Sulfonyl Azides.

Sulfilimines and their derivatives have garnered considerable interest in both synthetic and medicinal chemistry. Photochemical nitrene transfer to sulfides is known as a conventional synthetic approach to sulfilimines. However, the existing methods have a limited substrate scope stemming from the incompatibility of singlet nitrene intermediates with nucleophilic functional groups. Herein, we report the synthesis of N-sulfonyl sulfilimines via visible-light-mediated energy transfer to sulfonyl azides, uncovering the previously overlooked reactivity of triplet nitrenes with sulfides. This reaction features broad functional group tolerance, water compatibility, and amenability to the late-stage functionalization of drugs. Thus, this work represents an important example of energy transfer chemistry that overcomes challenges in traditional synthetic methods.

Transition-Metal-Free C-Diarylations to Reach All-Carbon Quaternary Centers.

Herein, we disclose a convenient protocol for the α-diarylation of carbon nucleophiles to yield heavily functionalized quaternary products. Diaryliodonium salts are utilized to transfer both aryl groups under transition-metal-free conditions, which enables an atom-efficient and high-yielding method with broad functional group tolerance. The methodology is amenable to a wide variety of carbon nucleophiles and can be utilized in late-stage functionalization of complex arenes. Furthermore, it is compatible with a new class of zwitterionic iodonium reagents, which gives access to phenols with an ortho-quaternary center. The diarylated products bear an ortho-iodo substituent that can be utilized in further transformations, including the formation of novel, functionalized six-membered cyclic iodonium salts.

Ten new species and notes on the genus Psoralea L. (Psoraleeae, Fabaceae) from South Africa

Background and aims – Following detailed phylogenetic and biogeographic studies of the tribe Psoraleeae, the genus Psoralea L. was shown to have been derived out of Otholobium C.H.Stirt. As Psoralea has nomenclatural priority, Otholobium has been subsumed into Psoralea, whereby two broad subgeneric groups are aligned with the previous descriptions of the separate genera, but some problems of placement of a few species remain unresolved. Work is ongoing to study and describe the nearly 20 undescribed species that will have to be considered before sectional groups can be established. In this paper we describe ten new species, including several putative taxa already recognized in regional floras, based on historic specimens and more recent field collections. Material and methods – Standard practices of herbarium and field taxonomy have been applied to study herbarium material available at B, BLFU, BM, BOL, BR, E, GRA, J, JRAU, K, KEI, L, LE, LINN, M, MO, NBG, NH, NU, NY, OXF, P, PRA, PRC, PRE, PRU, S, SAM, SCHG, SRGH, TCD, Z, ZT, and US. Additional material was provided from fieldwork by the authors and collaborators. Key results – Ten new species of Psoralea from southern Africa are described: Psoralea crista C.H.Stirt. & Muasya, P. fulva C.H.Stirt. & Muasya, P. luteovirens C.H.Stirt. & Muasya, P. nubicola C.H.Stirt. & Muasya, P. oreopola C.H.Stirt., P. pallescens C.H.Stirt. & Muasya, P. papillosa C.H.Stirt. & Muasya, P. prompta C.H.Stirt. & Muasya, P. schutteae C.H.Stirt. & Muasya, and P. vlokii C.H.Stirt. & Muasya. Conclusion – The newly described species, all restricted to South Africa, increases the number of Psoralea species to 129. These species arise from expanded fieldwork into previously under-collected areas, as well as from better refinement in species delimitations in the leafless ‘aphylla’ and pinnately-leaved species complexes.

Regio‐ and enantioselective nickel-alkyl catalyzed hydroalkylation of alkynes

The migratory insertion of metal-hydride into alkene has allowed regioselective access to organometallics, readily participating in subsequent functionalization as one conventional pathway of hydroalkylation, whereas analogous process with feedstock alkyne is drastically less explored. Among few examples, the regioselectivity of metal-hydride insertion is mostly governed by electronic bias of alkynes. To alter the regioselectivity and drastically expand the intermediate pools that we can access, one aspirational design is through alternative nickel-alkyl insertion, providing opposite regioselectivity induced by steric demand. Leveraging in situ formed nickel-alkyl species, we herein report the regio- and enantioselective hydroalkylation of alkynes with broad functional group tolerance, excellent regio- and enantioselectivity, enabling efficient route to diverse valuable chiral allylic amines motifs. Preliminary mechanistic studies indicate the aminoalkyl radical species can participate in metal-capture and lead to formation of nickel-alkyl, of which the migratory insertion is key to reverse regioselectivity observed in metal-hydride insertion.

A high-density linkage map reveals broad- and fine-scale sex differences in recombination in the hihi (stitchbird; Notiomystis cincta)

Recombination, the process of DNA exchange between homologous chromosomes during meiosis, plays a major role in genomic diversity and evolutionary change. Variation in recombination rate is widespread despite recombination often being essential for progression of meiosis. One such variation is heterochiasmy, where recombination rates differ between sexes. Heterochiasmy has been observed across broad taxonomic groups, yet it remains an evolutionary enigma. We used Lep-MAP3, a pedigree-based software that is efficient in handling large datasets, to generate linkage maps for the hihi or stitchbird (Notiomystis cincta), utilising information from >36 K SNPs and 36 families. We constructed 29 linkage maps, including for the previously unscaffolded Z chromosome. The hihi is an endangered passerine endemic to Aotearoa New Zealand that is sexually dimorphic and exhibits high levels of sexual conflict, including sperm competition. Patterns in recombination in the hihi are consistent with those in other birds, including higher recombination rates in micro-chromosomes. Heterochiasmy in the hihi is male-biased, in line with predictions of the Haldane-Huxley rule, with the male linkage map being 15% longer. Micro-chromosomes exhibit heterochiasmy to a greater extent, contrary to that reported in other birds. At the intra-chromosomal level, heterochiasmy is higher nearer to chromosome ends and in gene-rich regions. Regions of extreme heterochiasmy are enriched for genes implicated in cell structure. This study adds an important contribution in assessing evolutionary theories of heterochiasmy and provides a framework for future studies investigating fine-scale heterochiasmy.

Lewis Acid-Mediated Isothiocyanation and Chlorination of Quinoxalin-2(1H)-ones under Visible Light Conditions.

Lewis acid-mediated selective C3-isothiocyanation of quinoxalin-2(1H)-ones using N-thiocyanatosaccharin as an isothiocyanate source under visible light conditions at room temperature is described. Under similar conditions with N-chlorosaccharin, the C3-chlorination of quinoxalin-2(1H)-ones achieved a 2 h time frame. Good to an excellent yield of products was obtained in both cases with broad functional group tolerance. Control experiments suggest that the reaction proceeds through a radical mechanism. The present procedure demonstrates the applicability at gram-scale reactions and highlights the subsequent conversion of isothiocyanates into representative thiourea derivatives, and one of the chloro derivatives transformed to glycogen phosphorylase inhibitors.

AB082. Navigating barriers to epilepsy surgery: a national survey of patient and neurologist perspectives.

Potential barriers to epilepsy surgery can be divided into two broad groups: reluctance of patients/caregivers and deficient knowledge of neurologists. Pakistan, in particular, faces an epilepsy surgery treatment gap of 70-94%. This study aimed to assess the knowledge and practice of neurologists and the knowledge of the patients diagnosed with epilepsy to identify the barriers to adequate provision of this modality in Pakistan. We conducted a cross-sectional study comprising two surveys. Records of patients diagnosed with epilepsy at our hospital during 2.5 years were retrieved from the Neurophysiology database. The second form was designed for neurologists working in Pakistan. The questionnaires were disseminated via email to neurologists and phone calls to patients. In the patients' survey, we obtained 194 responses from caregivers. The median age of patients was 10 years [interquartile range (IQR): 6-14 years]. We found that 74.2% (n=144) of patients were unaware of surgical options in medically refractory epilepsy (MRE). Therefore, most did not comment on it due to the limited information. Forty-eight patients (24.8%) reported more than 1 seizure per month, and 29 (60.4%) were unaware of the surgical treatment. Seizures were disabling in 88% (n=171) of patients. Patients taking more AEDs were significantly more likely to be aware of surgical options (P=0.001). In the survey from neurologists, only 6.6% (n=4) always discussed epilepsy surgery with MRE patients. Around half of the neurologists, 44.3% (n=27), had never referred a patient for epilepsy surgery. However, 95.1% (n=58) were aware of the under-utilization of epilepsy surgery, and 67.2% (n=41) believed that epilepsy surgery is under-recommended. Almost all neurologists (n=60; 98.4%) believe that comprehensive epilepsy treatment centers are required in the country. In our survey, we found a lack of awareness in both patients and neurologists to be a major barrier. This contrasts the literature from developed or high-income countries, where physician awareness seems adequate, and stigmas associated with surgery seem to be the major barrier. Multifaceted approaches catered to local concerns are necessary to address these hindrances.

1,3-Hydro-di/monofluoromethylation of N,N'-Cyclic Azomethine Imines with HCF2SO2Na/H2CFSO2Na via Photocatalytic Radical Addition.

The radical 1,3-hydro-di/monofluoromethylation of N,N'-cyclic azomethine imines with HCF2SO2Na/H2CFSO2Na via photoredox catalysis is described. This reaction exhibits broad functional group compatibility, providing the desired products in good yields. However, CF3SO2Na failed to produce the trifluoromethyl product. DFT calculations revealed that the transition state activation energy for radical trifluoromethylation was significantly higher and the isotropic charge repulsion makes it difficult for the CF3 radical to transfer electrons.

Effects of replacing fishmeal with Spirulina platensis powder on the Zig-zag eel (Mastacembelus armatus): Growth performance, flesh quality, digestibility, and gut microbial composition

Protein demand from aquaculture exacerbates environmental pressures. Zig-zag eel (Mastacembelus armatus, MA) is a new aquaculture species in southern China and has great potential for future promotion. In this study, we used Spirulina platensis powder (SPP) to replace 0–20 % of fishmeal in the feed, respectively. A 10-week aquaculture experiment was conducted on 600 MAs with five groups of F0 (0 %), F1 (5 %), F2 (10 %), F3 (15 %), and F4 (20 %) set up with equal nitrogen (approximately 50.00 % crude protein) and equal fat (about 5.50 % crude fat) feeds. The experimental results showed that replacing fishmeal with different proportions of SPP significantly reduced FCR (p < 0.05), increased WGR and SGR (p < 0.05), and reduced the feeding cost, with the best performance in F2. Polynomial analysis combining WGR and SGR showed that the optimum percentage of substitution was 10.93 % and 11.09 % in MA diets, respectively. The addition of SPP significantly reduced the levels of EPA and DHA content (p < 0.05), significantly increased the proportion of C14:0, C16:1, C20:5n3, and C22:6n3 (p < 0.05), and a high proportion of SPP addition significantly decreased saturated fatty acid content (p < 0.05). The length of intestinal villi and the secretion levels of Chymotrypsin and Pepsin were significantly increased (p < 0.05), and the secretion level of Lipase was significantly decreased (p < 0.05) in the experimental group. A low percentage of SPP increased microbial diversity in MA’s gut. Functional pathways related to metabolic functions were the most obvious broad groups with the most significant changes in relative abundance in the experimental group, and Plesiomonas and Aeromonas may be the key microorganisms involved in regulating the digestion and metabolism of SPP in the gut of MA.

Highly Enantioselective Hydrogenation of Unsymmetrical Benzophenones via Iridium-f-phamidol Catalysis.

A sequence of f-phamidol-based tetradentate phosphine ligands have been developed and successfully used in iridium-catalyzed enantioselective hydrogenation of benzophenones to deliver chiral benzhydrols in almost quantitative yields and with excellent enantioselectivities (up to >99% yield and up to >99% ee). Moreover, the catalytic system shows a broad substrate scope and functional group tolerance. The synthetic utilities of this methodology have been showcased by gram-scale experiments and the formal synthesis of levocetirizine.

Rh-Catalyzed Carbonylative Cyclization of Propargylic Alcohols with Aryl Boronic Acids.

2(3H)-Furanones are tremendously important not only because of their wide occurrence in bioactive compounds but also due to their versatility in organic synthesis. Here, a straightforward approach to 2(3H)-furanones from readily available tertiary propargylic alcohols with arylboronic acids in the presence of CO using rhodium as a catalyst has been established. The method exhibits a broad substrate scope tolerating useful functional groups with a moderate to high stereoselectivity.

What are the perceived unmet needs for patient care, education, and research among genitourinary cancer nurses in Australia? A mixed method study

ObjectiveSpecialist genitourinary (GU) nurses provide care to a broad and diverse group of patients diagnosed with kidney, bladder, prostate, testicular, adrenal, and penile cancer. The purpose of this study was to identify GU cancer nurse perspectives of perceived unmet needs in service provision, specific educational and research priorities. MethodsA concurrent mixed methods study design incorporated quantitative and qualitative data collection from the GU Cancer nurses workforce in Australia. Quantitative data collected using an electronic survey instrument and were analysed using descriptive statistics. Qualitative data collected through semi-structured interviews and coded for thematic analysis. Ethical approval was gained. ResultsFifty responses were received from the electronic survey. 39/50 (78%) were female and 35 (70%) were metropolitan based. The highest domains of perceived unmet needs related to psychological/emotional needs – 17/23 (74%), intimacy needs – 15/23 (65%) and informational needs – 13/23 (57%). The themes from the qualitative interviews identified: (1) Patient needs – lack of tumour specific contact for cancer patients, fragmented delivery of cancer care, perception of better access to supportive care for public patients, lack of access to supportive care screening tools for needs assessment. (2) Educational needs – lack of GU specific cancer educational resources/learning opportunities and barriers to accessing educational opportunities. (3) Research priorities – impact on carers/partners, specific needs of different GU cancers, future focus on genetic testing/counselling, interventions for financial toxicity and development of models of care for geriatric GU patients. ConclusionsSpecialist GU cancer nurses support a broad group of patients. Given the prominence of addressing unmet cancer care needs among people with GU cancers in this study, cancer nursing as a discipline alongside the multidisciplinary team, requires innovative solutions to overcome fragmented care which is often highly complex, and develop individualised and integrated care across the cancer care continuum. We encourage clinicians, researchers, policy makers, people affected by cancer, and their care networks, to continue to drive innovation by (1) Embedding an integrated approach to cancer nursing, (2) Implementation of shared care, (3) Implementation of patient navigation, (4) Embracing emerging technologies, (5) Future focus on education, and (6) Future focus on nurse-led research.

Ways to think about vasculitic neuropathy.

Vasculitis as a pathomechanism for neuropathy can be isolated to the peripheral nervous system, a part of a systemic autoimmune condition or a component of another syndrome. This review aims to discuss the broad range of diagnoses in which vasculitic neuropathy can be encountered, highlight the progress in imaging techniques in identifying vasculitis, and the new drugs developed for other autoimmune diseases that may be applied to neurological conditions. Advances in imaging modalities, ultrasound, MRI and FDG-PET scanning for neuromuscular applications has redefined many aspects of vasculitic neuropathies. The benefit of dividing vasculitides by vessel size is becoming less absolute as diagnostic approaches advance. MRI and FDG-PET are widely used in diagnosis, defining extent of involvement of disease and monitoring. In neuralgic amyotrophy, the identification of hourglass-like constrictions on imaging has changed the treatment paradigm to include surgical interventions. These diagnostic approaches are supported by new immunomodulating and immunosuppression techniques. Vasculitic neuropathies are a broad group of conditions with a range of causes and associations. Increased use of imaging techniques impacts our traditional definitions and classifications. The growth in treatment options for other autoimmune conditions are likely to infiltrate the neurological landscape.

Forensic Characterization, Genomic Variability and Ancestry Analysis of Six Populations from Odisha Using mtDNA SNPs and Autosomal STRs.

Located on India's eastern coast, Odisha is known for its diverse tribes and castes. In the early days of genome sequencing technology, researchers primarily studied the Austroasiatic communities inhabiting this region to reconstruct the ancient origins and dispersal of this broad linguistic group. However, current research has shifted towards identifying population and individual-specific genome variation for forensic applications. This study aims to analyze the forensic efficiency and ancestry of six populations from Odisha. We assessed the SF mtDNA-SNP60™ PCR Amplification Kit by comparing it with PowerPlex® Fusion 6C System, a widely used autosomal STR (aSTR) kit, in an Indian cohort. Although the mtDNA SNP kit showed low discriminating power for individuals of a diverse population, it could identify deep lineage divergence. Also, we utilized mitochondrial and autosomal variation information to analyze the ancestry of six endogamous ethnic groups in Odisha. We observe two extremities-populations with higher West Asian affinity and those with East Asian affinity. This observation is in congruence with the existing information of their tribal and non-tribal affiliation. When compared with neighbouring populations from Central and Eastern India, multivariate analysis showed that the Brahmins clustered separately or with the Gopala, Kaibarta appeared as an intermediate, Pana and Kandha clustered with the Gonds, and Savara with the Munda tribes. Our findings indicate significant deep lineage stratification in the ethnic populations of Odisha and a gene flow from West and East Asia. The artefacts of unique deep lineage in such a diverse population will help in improving forensic identification. In addition, we conclude that the SF mtDNA-SNP60 PCR Amplification Kit may be used only as a supplementary tool for forensic analysis.

Streamlined Electrochemical Dihalogenation (F, Cl, and Br) of gem‐Difluoroalkenes Using Hydrogen Halides as Reagents

AbstractWe established a straightforward electrochemical dihalogenation (F, Cl, and Br) process for gem‐difluoroalkenes. This reaction exhibits a broad functional group tolerance and has been effectively utilized in the construction of complex molecules. The subsequent synthetic transformations of the products have highlighted the adaptable nature of the dihalogenated compounds, demonstrating their potential application in drug discovery and the investigation of innovative materials. The effective utilization of the dihalogenated product for 18F‐labeling represents a novel approach in generating highly potent 18F‐labeled tracers.

TBAB-catalyzed assisted C-C/C-N bond formations: An efficient approach to dihydrobenzo[b][1,8]naphthyridin derivatives via metal free Cascade annulation

An eco-friendly, metal-free approach for synthesizing dihydrobenzo[b][1,8]naphthyridine derivatives has been established. This method employs ortho-chloroquinolin-α,β-unsaturated ketones as dipolarophiles and acyclic enaminones as amphiphilic nucleophiles, enabling a formal [3 + 3] annulation reaction under phase-transfer catalysis to offed the targeted products. It boasts transition-metal-free conditions, broad functional group compatibility, and straightforward operational procedures.

Clinical and Imaging Follow-Up for High-Risk Cutaneous Melanoma: Current Evidence and Guidelines.

The most recent (eighth) edition of the American Joint Committee on Cancer (AJCC) staging system divides invasive cutaneous melanoma into two broad groups: "low-risk" (stage IA-IIA) and "high-risk" (stage IIB-IV). While surveillance imaging for high-risk melanoma patients makes intuitive sense, supporting data are limited in that they are mostly respective and used varying methods, schedules, and endpoints. As a result, there is a lack of uniformity across different dermatologic and oncologic organizations regarding recommendations for follow-up, especially regarding imaging. That said, the bulk of retrospective and prospective data support imaging follow-up for high-risk patients. Currently, it seems that either positron emission tomography (PET) or whole-body computerized tomography (CT) are reasonable options for follow-up, with brain magnetic resonance imaging (MRI) preferred for the detection of brain metastases in patients who can undergo it. The current era of effective systemic therapies (ESTs), which can improve disease-free survival (DFS) and overall survival (OS) beyond lead-time bias, has emphasized the role of imaging in detecting various patterns of EST response and treatment relapse, as well as the importance of radiologic tumor burden.

Regioselective hydroamination of unactivated olefins with diazirines as a diversifiable nitrogen source

Nitrogen-containing compounds, such as amines, hydrazines, and heterocycles, play an indispensable role in medicine, agriculture, and materials. Alkylated derivatives of these compounds, especially in sterically congested environments, remain a challenge to prepare. Here we report a versatile method for the regioselective hydroamination of readily available unactivated olefins with diazirines. Over fifty examples are reported, including the protecting group-free amination of fourteen different natural products. A broad functional group tolerance includes alcohols, ketones, aldehydes, and epoxides. The proximate products of these reactions are diaziridines, which, under mild conditions, are converted to primary amines, hydrazines, and heterocycles. Five target- and diversity-oriented syntheses of pharmaceutical compounds are shown, along with the preparation of a bis-15N diazirine validated in the late-stage isotopic labeling of an RNA splicing modulator candidate. In this work, we report using diazirine (1) as an electrophilic nitrogen source in a regioselective hydroamination reaction, and the diversification of the resulting diaziridines.