Synthesis and Regioselective Functionalization of Tetrafluorobenzo-[α]-Fused BOPYPY Dyes.

The synthesis of a new bis-BF2 tetrafluorobenzo-[α]-fused BOPYPY dye from 4,5,6,7-tetrafluoroisoindole and 2-hydrazinopyrazine is reported. The regioselectivity of nucleophilic substitution reactions at the periphery of the tetrafluorinated BOPYPY and its α-bromo derivative were investigated using N-, O-, S-, and C-based nucleophiles. Among the aromatic fluorine atoms, the F2 atom is consistently regioselectively substituted, except when the α-position contains a thiophenol group; in this case, F4 is substituted instead due to stabilizing π-π-stacking between the two aromatic groups. The α-bromo BOPYPY derivative also reacts under Stille cross-coupling reaction conditions to produce the corresponding α-substituted product. The spectroscopic properties of these new fluorinated BOPYPYs were investigated and compared with nonfluorinated analogs.

5- and 10-oxocorroles from ß-octaalkylcorroles.

The reaction of Zn ions with ß-octaalkylcorroles leads to the air oxidation of the macrocycle, with the formation of a mixture of 5- and 10-oxocorroles. Spectroscopic characterization confirms the antiaromatic character of these macrocycles. A simple synthetic protocol opens the way for more detailed studies of oxocorrole chemistry.

Palladium Complexes of N-Methylcorroles.

Alkylation of one of the inner-core nitrogen atoms is one possible approach to obtain dianionic corrole ligands, suitable for the coordination of divalent metal ions, such as PdII . Inner-core N-methylation can be obtained by treating the corrole with CH3 I, but the reaction conditions should be optimized to limit the formation of the dimethylated derivative. Two regioisomers, the N-21 and the N-22 methyl derivatives are obtained from the reaction, with the first product achieved in a higher amount. Structural characterization of the reaction products evidenced the distortion induced by the introduction of the methyl groups; the N-methylcorroles are chiral compounds, and the enantiomers were separated by chromatography, with their absolute configuration assigned by ECD computation. Palladium insertion was achieved in the case of monosubstituted corroles, but not with the dimethylated macrocycle; X-ray characterization of the complexes showed the distortion of the macrocycles. The Pd complexes do not show luminescence emission, but are able to produce singlet oxygen upon irradiation. The PdII complexes were also inserted in human serum albumin (HSA) and dispersed in water; in this case, the protein protects the corroles from photobleaching, and a switch from the type II to the type I mechanism in reactive oxygen species (ROS) production is observed.

Multi-Functional Boron-Delivery Agents for Boron Neutron Capture Therapy of Cancers.

Boron neutron capture therapy (BNCT) is a binary cancer treatment that involves the irradiation of 10B-containing tumors with low-energy neutrons (thermal or epithermal). The alpha particles and recoiling Li nuclei that are produced in the 10B-capture nuclear reaction are high-linear-energy transfer particles that destroy boron-loaded tumor cells; therefore, BNCT has the potential to be a localized therapeutic modality. Two boron-delivery agents have been used in clinical trials of BNCT in patients with malignant brain tumors, cutaneous melanoma, or recurrent tumors of the head and neck region, demonstrating the potential of BNCT in the treatment of difficult cancers. A variety of potentially highly effective boron-delivery agents have been synthesized in the past four decades and tested in cells and animal models. These include boron-containing nucleosides, peptides, proteins, polyamines, porphyrins, liposomes, monoclonal antibodies, and nanoparticles of various types. The most promising agents are multi-functional boronated molecules and nanoparticles functionalized with tumor cell-targeting moieties that increase their tumor selectivity and contain a radiolabel or fluorophore to allow quantification of 10B-biodistribution and treatment planning. This review discusses multi-functional boron agents reported in the last decade, but their full potential can only be ascertained after their evaluation in BNCT clinical trials.

Paul A. Castelfranco (1921-2021): a scientist par excellence, a man of lasting faith, and ever a humanist.

We present here the life and the work of Paul A. Castelfranco (1921-2021), a very special person who was not only a top chemist of chlorophyll biosynthesis, but also made major contributions on fatty acid oxidation, acetate metabolism and cellular organization. He led an extraordinary and exemplary life as a human being. We present here both his personal life as well as his scientific life, which is followed by reminiscences by William Breidenbach, Kevin Smith, Alan Stemler, Ann Castelfranco, and John Castelfranco. As the subtitle of this Tribute implies, till the end Paul was a scientist par excellence, an intellectual with unlimited curiosity, a humanist, and a man of enduring religious faith. We all miss him dearly.

Amino Acid Derivatives of Chlorin-e6-A Review.

Details of the structural elucidation of the clinically useful photodynamic therapy sensitizer NPe6 (15) are presented. NPe6, also designated as Laserphyrin, Talaporfin, and LS-11, is a second-generation photosensitizer derived from chlorophyll-a, currently used in Japan for the treatment of human lung, esophageal, and brain cancers. After the initial misidentification of the structure of this chlorin-e6 aspartic acid conjugate as (13), NMR and other synthetic procedures described herein arrived at the correct structure (15), confirmed using single crystal X-ray crystallography. Interesting new features of chlorin-e6 chemistry (including the intramolecular formation of an anhydride (24)) are reported, allowing chemists to regioselectively conjugate amino acids to each available carboxylic acid on positions 131 (formic), 152 (acetic), and 173 (propionic) of chlorin e6 (14). Cellular investigations of several amino acid conjugates of chlorin-e6 revealed that the 131-aspartylchlorin-e6 derivative is more phototoxic than its 152- and 173-regioisomers, in part due to its nearly linear molecular conformation.

High Interest in Pursuing Trauma-Informed Care in Nursing Home Social Services Directors.

This study explored nursing home social services directors' interest in pursuing trauma-informed care (TIC) training, and individual and organizational characteristics associated with their interest. Data from the 2019 National Nursing Home Social Services Directors Survey, a national cross-sectional survey, were used. Measures sought information on participants' interest in TIC training, sociodemographic characteristics, and characteristics of employing nursing homes. Descriptive statistics and multivariate binary logistic regression analyses were used. Of the 924 respondents, 880 (95.2%) were included in the analysis. Most (71.7%) expressed high interest in TIC training. Younger age, fewer years of nursing home social services experience, being degreed and licensed in social work, and being a person of color were associated with greater odds of high interest in TIC training. Neither nursing home ownership nor social services staffing ratio was significantly associated with interest in TIC training. As policy requires TIC in nursing homes, these findings present a first step towards understanding implementation.

An exploration of factors related to service utilization in emerging adults: Loneliness and psychosocial supports.

Objective: To examine the relationships between loneliness and psychosocial supports, emerging adult service utilization, and barriers to utilization. Participants: 18 to 29-year-old students enrolled in a large Midwestern University (n = 292). Methods: Online surveys were administered to all participants involving information on loneliness, social supports, basic need satisfactions, community/university service utilization, and barriers to service use. Logistic and linear regressions, analysis of variance were conducted. Results: Emerging adults were found to have a greater likelihood of service utilization when higher in social support from friends and less likely to utilize services when high in relatedness and competence need satisfaction, specifically in regard to community services. Group differences in greater barriers to service utilization were found among the highest levels of loneliness and the lowest levels of need satisfaction. Conclusion: Overall, this study indicates psychosocial supports and loneliness are related to service utilization in a nuanced manner.

Investigations on the Synthesis, Reactivity, and Properties of Perfluoro-α-Benzo-Fused BOPHY Fluorophores.

The synthesis and reactivity of 3,8-dibromo-dodecafluoro-benzo-fused BOPHY 2 are reported, via SN Ar with O-, N- S- and C-nucleophiles, and in Pd(0)-catalyzed cross-coupling reactions (Suzuki and Stille). The resulting perfluoro-BOPHY derivatives were investigated for their reactivity in the presence of various nucleophiles. BOPHY 3 displays reversible color change and fluorescence quenching in the presence of bases (Et3 N, DBU), whereas BOPHY 7 reacts preferentially at the α-pyrrolic positions, and BOPHY 8 undergoes regioselective fluorine substitution in the presence of thiols. The structural and electronic features of the fluorinated BOPHYs were studied by TD-DFT computations. In addition, their spectroscopic and cellular properties were investigated; BOPHY 10 shows the most red-shifted absorption/emission (λmax 659/699 nm) and 7 the highest fluorescence (Φf =0.95), while all compounds studied showed low cytotoxicity toward human HEp2 cells and were efficiently internalized.

'We have goals but [it is difficult]'. Barriers to antiretroviral therapy adherence among women using alcohol and other drugs living with HIV in South Africa.

BACKGROUND: Women living with HIV who misuse alcohol and live in economically disadvantaged settings in South Africa experience a multitude of contextual barriers as they navigate the HIV care continuum. The Women's Health CoOp (WHC), a brief, woman-focused, behavioural, evidence-based intervention, has been shown to be effective in reducing heavy drinking and improving HIV-related outcomes among this key population. However, these women face other broader socioecological barriers to antiretroviral therapy (ART) adherence. METHODS: The WHC was implemented in a modified, stepped-wedge implementation science trial in public health clinics and substance use treatment programmes in Cape Town, South Africa. A qualitative substudy was conducted to explore barriers to HIV treatment adherence among women enrolled in this trial. Eight focus group discussions were conducted with 69 participants 6 months after completion of the WHC workshops. Focus groups were audio-recorded (with consent), transcribed verbatim and analysed using a thematic approach. RESULTS: The mean age of the participants was 33 years and the mean self-reported number of drinks per day was 13. The main contextual factors influencing participants' ART adherence were intrapersonal-level factors (substance use, financial constraints, food insecurity; community-level factors (anticipated and enacted stigma, community violence) and institutional-level factors (patient-provider relationships, health facility barriers, environmental stigma). CONCLUSION: Comprehensive interventions addressing the contextual barriers and unique challenges faced by women who misuse alcohol in low-resource settings that intersect with HIV treatment nonadherence should be implemented in tandem with successful biobehavioural HIV interventions for long-term effectiveness and sustainability. PATIENT OR PUBLIC CONTRIBUTION: Our South African community collaborative board has been involved throughout this study; participants and clinic staff voices have been essential in our interpretation of these findings.

Syntheses and Investigations of Conformationally Restricted, Linker-Free α-Amino Acid-BODIPYs via Boron Functionalization.

A series of α-amino acid-BODIPY derivatives were synthesized using commercially available N-Boc-l-amino acids, via boron functionalization under mild conditions. The mono-linear, mono-spiro, and di-amino acid-BODIPY derivatives were obtained using an excess of basic (histidine, lysine, and arginine), acidic (aspartic acid), polar (tyrosine, serine), and nonpolar (methionine) amino acid residues, in yields that ranged from 37 to 66%. The conformationally restricted mono-spiro- and di-amino acid-BODIPYs display strong absorptions in the visible spectral region with high molar extinction coefficients and significantly enhanced fluorescence quantum yields compared with the parent BF2-BODIPY. Cellular uptake and cytotoxicity studies using the human HEp2 cell line show that both the presence of an N,O-bidentate spiro-ring and basic amino acids (His and Arg) increase cytotoxicity and enhance cellular uptake. Among the series of BODIPYs tested, the spiro-Arg- and spiro-His-BODIPYs were found to be the most cytotoxic (IC50 ∼ 22 µM), while the spiro-His-BODIPY was the most efficiently internalized, localizing preferentially in the cell lysosomes, ER, and mitochondria.

Dementia Care Involvement and Training Needs of Social Services Directors in U.S. Nursing Homes.

This study describes social services directors' involvement in dementia care in U.S. nursing homes, focusing on interest in and needs for dementia care training. Respondents were 924 social service directors from U.S. nursing homes. We found that 87% of social service departments engaged in cognitive assessment; 59% of social services directors were strongly interested in dementia care training, and 23% would need up to 10 hours of preparation time or would not be able to train staff on dementia-related care. Multinomial logistic regression analysis (n = 836) revealed that, in comparison to having no interest in dementia training, age, years of experience in nursing homes, outside mental health contracting, barriers to staffing, and hours needed to prepare dementia training predicted varying interest in dementia care training. These findings demonstrate social services directors' active involvement in dementia care and need for training.

Serious Mental Illness in Nursing Homes: Roles and Perceived Competence of Social Services Directors.

Providing nursing home psychosocial care to persons with serious mental illnesses (SMI) requires understanding of comorbidities and attention to resident rights, needs and preferences. This quantitative study reports how 924 social service directors (SSDs) taking part in the National Nursing Home Social Service Director survey identified their roles and competence, stratified by the percentage of residents with SMI. More than 70% of SSDs, across all categories of homes, reported the social services department was "always" involved in conducting depression screening, biopsychosocial assessments and PASRR planning. SSDs in homes with lower concentrations of residents with SMI reported less involvement in anxiety screening. Those employed in homes with higher concentrations of residents with SMI reported lower involvement conducting staff interventions for resident aggression or making referrals. More than one-fifth of SSDs lacked confidence in their ability to compare/contrast dementia, depression, and delirium or to develop care plans for residents with SMI. SSDs' perceived competence in developing care plans for residents with SMI was associated with education and involvement in care planning. About one-quarter of social services directors reported not being prepared to train a colleague on how to develop care plans for residents with SMI. Training in SMI could enhance psychosocial care.

About a Third of Nursing Home Social Services Directors Have Earned a Social Work Degree and License.

Nursing home (NH) residents have high psychosocial needs related to illness, disability, and changing life circumstances. The staff member with the most expertise in addressing psychosocial needs is the social worker. However, federal regulations indicate that only NHs with 120+ beds need hire a social services staff member and that a "qualified social worker" need not have a social work degree. Therefore, two-thirds of NHs are not required to employ a social services staff member and none are required to hire a degreed social worker. This is in stark contrast to NASW professional standards. Reporting findings from this nationally representative sample of 924 social services directors, we describe the NH social services workforce and document that most NHs do hire social services staff, although 42% of social services directors are not social work educated. 37% of NHs have a degreed and licensed social worker at the helm of social services. The odds of hiring a degreed and licensed social workers are higher for larger NHs, especially if not-for-profit and not part of a chain. NH residents deserve psychosocial care planned by staff with such expertise. Quality of psychosocial care impacts quality of life.

Flipped Classroom in Podiatric Medical Education.

BACKGROUND: The purpose of this study was to evaluate student learning outcomes in a flipped classroom versus a traditional classroom in a podiatric medical school. To date no published reports in podiatric medical schools have used the flipped classroom for the entirety of a medical school course. METHODS: Students from the class of 2017 completed the Emergency Medicine and Trauma course using traditional classroom lectures, and the class of 2018 used a flipped classroom approach. Each class took two assessments that contained 99 identical questions and completed a postcourse evaluation that contained student comments. A multivariate analysis of covariance was conducted to determine whether student performances were significantly affected by the differences in the teaching method. Student evaluation comments were analyzed using textual data analysis to determine the sentiments that students expressed regarding their exposure to the teaching method. RESULTS: The multivariate analysis of covariance results revealed that students scored slightly lower on assessments during the flipped classroom delivery compared with the traditional classroom delivery, when adjusted for Medical College Admission Test scores and grade point average, but not significantly (P = .4340). Similarly, the sentiment analysis of student comments indicated that the average positive sentiment score for the flipped classroom delivery was higher but was not significant (P = .08914). CONCLUSIONS: The analysis showed there was not a statistically significant change in examination scores based on teaching method. Sentiment analysis revealed that student sentiments were more positive with the flipped classroom group compared with the traditional lecture group, although not statistically significantly.

Identifying Risk and Resilience Factors Associated With the Likelihood of Seeking Mental Health Care Among U.S. Army Soldiers-in-Training.

INTRODUCTION: The Department of Defense aims to maintain mission readiness of its service members. Therefore, it is important to understand factors associated with treatment seeking in order to identify areas of prevention and intervention early in a soldier's career that can promote positive functioning and increase their likelihood of seeking mental health care when necessary. METHOD: Using a theory of planned behavior lens, this study identified potential barriers (risk) and facilitators (resilience) to treatment seeking among 24,717 soldiers-in-training who participated in the New Soldiers Study component of the "Army Study to Assess Risk and Resilience in Servicemembers" (Army STARRS). Approval for this study was granted by the University of Iowa IRB # 201706739. Hierarchal linear regression modeling and independent samples t-tests were used to examine associations between demographics and study variables, intersections of risk and resilience, and to explore differences in the likelihood of seeking help based on mental health diagnoses. RESULTS: A four-stage hierarchical linear regression was conducted, using likelihood of help-seeking as the dependent variable, to identify the most salient factors related to help-seeking. "Step one" of the analysis revealed soldiers-in-training who identified as female, Hispanic or Other ethnicity, and married, divorced, or separated reported a greater likelihood of seeking help. "Step two" of the analysis indicated soldiers-in-training with a history of sexual trauma, experience of impaired parenting, and clinical levels of mental health symptomatology (anxiety, depression, PTSD) reported a greater likelihood of seeking help. Inversely, soldiers-in-training with a history of emotional trauma and parental absence/separation reported a lower likelihood of seeking help. "Step three" of the analysis demonstrated soldiers-in-training with a prior history of seeking help and larger social networks had a greater likelihood of seeking help. "Step four" of the analysis revealed several interactive effects between risk and resilience factors. Specifically, soldiers-in-training who reported greater depressive symptomatology in combination with prior history of treatment seeking reported a greater likelihood of help seeking, whereas soldiers-in-training who reported prior sexual trauma and PTSD in combination with large social networks reported a lower likelihood of seeking help. Finally, a greater percentage of soldiers-in-training with clinical levels of anxiety, depression, and PTSD indicated they would likely seek help in comparison to soldiers-in-training without clinical symptoms. CONCLUSION: Findings suggest few soldiers-in-training are likely to seek help when experiencing a problem. General efforts to encourage help-seeking when needed are warranted with particular focus on subsets of soldiers-in-training (eg, men, those with a history of some adverse childhood experiences). Strengths of this study include the examination of a large sample of soldiers-in-training to identify possible leverage points for early intervention or prevention prior to entering stressful military operating environments. Limitations of this study include the examination of only one military branch and exclusion of soldiers not "in-training." Future studies could consider replicating the current study using a sample of military personnel longitudinally to track behavioral trends as well as looking at military populations outside of basic combat training.

ß-Arylethynyl substituted silver corrole complexes.

Silver corrolates are attractive compounds from both practical and theoretical points of view. Indeed, they play a key role in peripheral functionalization reactions occurring at the macrocycle, enabling high-yield and regioselective group insertions useful to further elaborate the molecular skeleton. In parallel, the Janus innocent or noninnocent behavior of the corrole ligand in these complexes makes their description particularly challenging. Herein, we report properties for a series of silver 3,17-disubstituted triarylcorrole complexes with various functionalities (halogens or different phenylethynyl units) that deeply affect the electron density in the macrocyclic ligand, with obvious repercussions on the observed spectral characteristics. The compounds were obtained in yields of 54-92% by applying the Stille coupling reaction with the appropriate tributylethynyl stannane. Among the complexes prepared was a derivative bearing two terminal acetylenic units which opens the way to "click" reactions for new corrole-based architectures. This corrole was structurally characterized by single crystal X-ray crystallography. The addition of substituted ethynyl groups resulted in red-shifts of the electronic absorption spectra, the largest of which was observed for the compound with two ß-NO2-Ph-C[triple bond, length as m-dash]C substituents. The remarkable influence of the NO2 groups on the electron density of this macrocycle was further demonstrated by electrochemical measurements, where an easier reduction of this complex derivative was observed as compared to the others. DFT calculations showed full delocalization over the entire p-nitrophenylethynyl unit of 5, largely affecting orbital distributions and the corresponding electronic absorptions. Although a variation of the ß-substituents dramatically modifies the Soret- and Q-band positions towards lower energies for all the examined complexes, the saddling of the macrocycle resulting from functionalization is only moderate. The collected results suggest the description of these compounds as AgIII-corrolate3-, a metallocorrole with an innocent macrocyclic ligand.

Synthesis and Investigation of Linker-Free BODIPY-Gly Conjugates Substituted at the Boron Atom.

An efficient synthesis of boron-functionalized cyclic BODIPY-Gly conjugates, using commercially available N-protected glycine amino acids and a BF2-BODIPY moiety as starting materials, is reported. The existence of two conformers (up and down) is revealed through comprehensive DFT calculations and 1H and 11B NMR analyses. The experimental and computational results indicate that all BODIPYs are stable in aqueous solutions at neutral pH and that Fmoc-BODIPY (4) is more stable than Ac-BODIPY (6) in the presence of trifluoroacetic acid (TFA). In part due to their enhanced rigidity, all BODIPY-Gly conjugates display increased fluorescence quantum yields (0.6 < Φ < 0.9) relative to the corresponding BF2-BODIPY, making them excellent candidates for fluorescence imaging applications.

Early results of displaced femoral neck fragility fractures treated with supercapsular percutaneous-assisted total hip arthroplasty.

BACKGROUND: Total hip arthroplasty (THA) is the preferred treatment for displaced femoral neck fractures in select patients, although dislocation remains a concern. In some studies, the supercapsular percutaneously assisted (SuperPATH) approach has demonstrated early mobilization, short hospital stay, and low dislocation rates in primary THA, but there are little data on its use for fractures. This study describes the perioperative outcomes and early dislocation rate of SuperPATH THA for displaced femoral neck fragility fractures. METHODS: A retrospective review was performed of previous ambulatory patients with a displaced femoral neck fragility fracture treated with THA using the SuperPATH approach. Demographic data, time to ambulation, length of stay, and in-hospital complications during the hospital stay and follow-up period were recorded. Phone interviews were conducted to check for dislocations 1 year after surgery. RESULTS: Thirty-seven consecutive patients were included with an average age of 75.0 years. Hospital stay averaged 5.5 days, and patients were discharged on average postoperative day 3.6. About 83.8% of patients were ambulatory by postoperative day 1, and 94.6% ambulatory before discharge. Twenty-seven percent of patients were discharged home, 46% to inpatient rehabilitation, 24% to skilled nursing facility, and 1 patient to hospice. At follow-up, there was no symptomatic heterotopic ossification and no infections. Thirty-two patients were available for telephone interviews at 1 year, with no dislocations reported. CONCLUSIONS: In this small cohort, the SuperPATH approach for THA appears to be safe and effective for use in femoral neck fragility fractures, resulting in early ambulation and a low dislocation rate.

Single-stage revision anterior cruciate ligament reconstruction using bone grafting for posterior or widening tibial tunnels restores stability of the knee and improves clinical outcomes.

PURPOSE: Revision ACL surgery may be complicated by tunnel malposition and/or tunnel widening and often requires a staged treatment approach that includes bone grafting, a period of several months to allow bone graft incorporation and then definitive revision ACL reconstruction. The purpose of this study was to evaluate the results of a single-staged ACL revision reconstruction technique using a cylindrical dowel bone graft for patients who have existing posteriorly placed and/or widened tibial tunnels in the tibia at a minimum of 2 years follow-up. METHODS: Between 2010 and 2014, patients undergoing single-stage revision ACL reconstruction with the described technique were prospectively enrolled and evaluated. At a minimum of 24 months, patients were evaluated by physical examination, multiple clinical outcome instruments including KOOS, Tegner and Lysholm, and preoperative and postoperative MRIs. RESULTS: At a mean of 35.1 months, 18 consecutive patients had no revision surgery and no subjective knee instability. There were statistically significant improvements in the Tegner (median 2, interquartile range 2.25; p < 0.01), Lysholm (20.0 ± 15.0; p < 0.01), KOOS symptoms scale (12.9 ± 11.8; p < 0.01), KOOS pain scale (15.4 ± 18.7; p < 0.01), KOOS ADL scale (13.5 ± 19.0; p < 0.01), KOOS sports scale (32.8 ± 26.4; p < 0.01), and KOOS QoL scale (18.1 ± 16.9; p < 0.01). Postoperative MRI demonstrated statistically significant anteriorization of the tibial tunnel and a statistically significant decrease in tunnel widening. CONCLUSION: Revision ACL reconstruction utilizing a single-staged tibial tunnel grafting technique resulted in improved knee pain, function, and stability at a minimum of 24-month follow-up. LEVEL OF EVIDENCE: IV.