[Thinking about family carers in terms of their experiential knowledge]. / Penser le proche aidant au regard de son savoir expérientiel.

Despite well-established recommendations and psycho-education programmes, the health of family carers is most often impaired, which means that the support they provide is seen only in terms of burden. A phenomenological approach based on strength-based care shows that they develop skills and strategies for the well-being of their loved one, and are nurtured by a sense of hope that enables them to acquire experiential knowledge.

Globally deployed sorghum aphid resistance gene RMES1 is vulnerable to biotype shifts but is bolstered by RMES2.

Durable host plant resistance (HPR) to insect pests is critical for sustainable agriculture. Natural variation exists for aphid HPR in sorghum (Sorghum bicolor), but the genetic architecture and phenotype have not been clarified and characterized for most sources. In order to assess the current threat of a sorghum aphid (Melanaphis sorghi) biotype shift, we characterized the phenotype of Resistance to Melanaphis sorghi 1 (RMES1) and additional HPR architecture in globally admixed populations selected under severe sorghum aphid infestation in Haiti. We found RMES1 reduces sorghum aphid fecundity but not bird cherry-oat aphid (Rhopalosiphum padi) fecundity, suggesting a discriminant HPR response typical of gene-for-gene interaction. A second resistant gene, Resistance to Melanaphis sorghi 2 (RMES2), was more frequent than RMES1 resistant alleles in landraces and historic breeding lines. RMES2 contributes early and mid-season aphid resistance in a segregating F2 population; however, RMES1 was only significant with mid-season fitness. In a fixed population with high sorghum aphid resistance, RMES1 and RMES2 were selected for demonstrating a lack of severe antagonistic pleiotropy. Associations with resistance colocated with cyanogenic glucoside biosynthesis genes support additional HPR sources. Globally, therefore, an HPR source vulnerable to biotype shift via selection pressure (RMES1) is bolstered by a second common source of resistance in breeding programs (RMES2), which may be staving off a biotype shift and is critical for sustainable sorghum production.

Presentations of Cutaneous Disease in Various Skin Pigmentations: Acne Vulgaris - Comedonal Acne.

Description Acne vulgaris is a common inflammatory skin condition of the pilosebaceous unit in adolescents and young adults and is primarily characterized by the presence of open and closed comedones. In patients of various skin pigmentations, skin-colored comedones may be difficult to appreciate and lead to incorrect or delayed diagnosis of acne. To aid in the identification of acne vulgaris in patients of various skin pigmentations, we present comedonal acne in different skin types and commonly encountered differential diagnoses. With its significant volume and burden of disease, acne vulgaris should be correctly identified in various skin pigmentations by primary care clinicians for the initiation of appropriate management.

Response Assessment in Brain Metastases Managed by Stereotactic Radiosurgery: A Reappraisal of the RANO-BM Criteria.

BACKGROUND: Brain metastases (BM) are increasingly being treated using stereotactic radiosurgery (SRS). Standardized response criteria are necessary to improve research and treatment protocols. This study's goal was to validate the RANO-BM criteria thresholds for tumor progression in a cohort of patients with brain metastases managed using SRS. METHODS: We performed a retrospective analysis of patients treated at least twice with SRS for brain metastases. Local progression, as defined by RANO-BM criteria, was compared to our multidisciplinary tumor board's treatment recommendation. A ROC curve was generated using varying diameter thresholds to assess the sensitivity and specificity of current RANO-BM criteria. RESULTS: 249 metastases in 67 patients were included in the analysis. RANO-BM criteria current progression thresholds yielded a sensitivity of 38%, a specificity of 95%, a positive predictive value of 71%, and a negative predictive value of 84% relative to our tumor board's treatment recommendation. Modified RANO-BM criteria using absolute diameter differences of 2.5 mm yielded a sensitivity of 83%, a specificity of 87%, a positive predictive value of 67% and a negative predictive value of 94%. CONCLUSIONS: Current RANO-BM criteria unreliably identifies clinically relevant tumor progression. The use of absolute diameter differences thresholds appears superior in our BM cohort.

PI3Kδ activation, IL6 over-expression, and CD37 loss cause resistance to the targeting of CD37-positive lymphomas with the antibody-drug conjugate naratuximab emtansine.

Purpose: The transmembrane protein CD37 is expressed almost exclusively in lymphoid tissues, with the highest abundance in mature B cells. CD37-directed antibody- and, more recently, cellular-based approaches have shown preclinical and promising early clinical activity. Naratuximab emtansine (Debio 1562, IMGN529) is an antibodydrug conjugate (ADC) that incorporates an anti-CD37 monoclonal antibody conjugated to the maytansinoid DM1 as payload. Naratuximab emtansine has shown activity as a single agent and in combination with the anti-CD20 monoclonal antibody rituximab in B cell lymphoma patients. Experimental Design: We assessed the activity of naratuximab emtansine using in vitro models of lymphomas, correlated its activity with CD37 expression levels, characterized two resistance mechanisms to the ADC, and identified combination partners providing synergy. Results: The anti-tumor activity of naratuximab emtansine was tested in 54 lymphoma cell lines alongside its free payload. The median IC 50 of naratuximab emtansine was 780 pM, and the activity, primarily cytotoxic, was more potent in B than in T cell lymphoma cell lines. In the subgroup of cell lines derived from B cell lymphoma, there was some correlation between sensitivity to DM1 and sensitivity to naratuximab emtansine (r=0.28, P = 0.06). After prolonged exposure to the ADC, one diffuse large B cell lymphoma (DLBCL) cell line developed resistance to the ADC due to the biallelic loss of the CD37 gene. After CD37 loss, we also observed upregulation of IL6 (IL-6) and other transcripts from MYD88/IL6-signaling. Recombinant IL6 led to resistance to naratuximab emtansine, while the anti-IL6 antibody tocilizumab improved the cytotoxic activity of the ADC in CD37-positive cells. In a second model, resistance was sustained by an activating mutation in the PIK3CD gene, associated with increased sensitivity to PI3K δ inhibition and a switch from functional dependence on the anti-apoptotic protein MCL1 to reliance on BCL2. The addition of idelalisib or venetoclax to naratuximab emtansine overcame resistance to the ADC in the resistant derivative while also improving the cytotoxic activity of the ADC in the parental cells. Conclusions: Targeting B cell lymphoma with the CD37 targeting ADC naratuximab emtansine showed vigorous anti-tumor activity as a single agent, which was also observed in models bearing genetic lesions associated with inferior outcomes, such as MYC translocations and TP53 inactivation or resistance to R-CHOP. Resistance DLBCL models identified active combinations of naratuximab emtansine with drugs targeting IL6, PI3K δ , and BCL2. Despite notable progress in recent decades, we still face challenges in achieving a cure for a substantial number of lymphoma patients (1,2). A pertinent example is diffuse large B cell lymphoma (DLBCL), the most prevalent type of lymphoma (3). More than half of DLBCL patients can achieve remission, but around 40% of them experience refractory disease or relapse following an initial positive response (3). Regrettably, the prognosis for many of these cases remains unsatisfactory despite introducing the most recent antibody-based or cellular therapies (3,4), underscoring the importance of innovating new therapeutic strategies and gaining insights into the mechanisms of therapy resistance. CD37 is a transmembrane glycoprotein belonging to the tetraspanin family, primarily expressed on the surface of immune cells, principally in mature B cells but also, at lower levels, in T cells, macrophages/monocytes, granulocytes and dendritic cells (5) (6-8). CD37 plays a crucial role in various immune functions, including B cell activation, proliferation, and signaling, although its precise role still needs to be fully elucidated. CD37 interacts with multiple molecules, including SYK, LYN, CD19, CD22, PI3K δ , PI3K γ , and different integrins, among others (6-8). In mice, the lack of CD37 is paired with reduced T cell-dependent antibody-secreting cells and memory B cells, apparently due to the loss of CD37-mediated clustering of α 4 ß 1 integrins (VLA-4) on germinal center B cells and decreased downstream activation of PI3K/AKT signaling and cell survival (5). Reflecting the expression pattern observed in normal lymphocytes, CD37 exhibits elevated expression in all mature B-cell lymphoid neoplasms, including most lymphoma subtypes, and absence in early progenitor cells or terminally differentiated plasma cells (6,8-14). In DLBCL, CD37 expression has been reported between 40% and 90% of cases across multiple studies performed using different antibodies (10,14-16). CD37-directed antibody- and, more recently, cellular-based approaches have shown preclinical (7,10-14,17-23) and early promising clinical activity (24-32). Among the CD37-targeting agents, naratuximab emtansine (Debio 1562, IMGN529) is an antibody-drug conjugate (ADC) that incorporates the anti-CD37 humanized IgG1 monoclonal antibody K7153A conjugated to the maytansinoid DM1, as payload, via the thioether linker, N-succinimidyl-4-(N-maleimidomethyl)cyclohexane-1-carboxylate (SMCC) (10). Based on the initial in vitro and in vivo evidence of anti-tumor activity in lymphoma and chronic lymphocytic leukemia (CLL) (7,10), naratuximab emtansine entered the clinical evaluation as a single agent. The phase 1 study exploring naratuximab emtansine enrolled 39 patients with relapsed/refractory B cell lymphoma (27). The overall response rate (ORR) was 13% across all patients and 22% in DLBCL patients, including the only observed complete remission (CR) (27). In preliminary results of a phase 2 trial exploring the combination of naratuximab emtansine with the anti-CD20 monoclonal antibody rituximab (18), based on positive preclinical data (18), the ORR was 45% in 76 patients with DLBCL with 24 CRs (32%), 57% in 14 patients with follicular lymphoma (five CR), 50% in four MCL patients (2 CR) (31). Here, we studied the pattern of activity of naratuximab emtansine across a large panel of cell lines derived from DLBCL and other lymphoma subtypes and characterized two resistance mechanisms to the ADC.

Digital healthcare equity in primary care: implementing an integrated digital health navigator.

The 21st Century Cures Act and the rise of telemedicine led to renewed focus on patient portals. However, portal use disparities persist and are in part driven by limited digital literacy. To address digital disparities in primary care, we implemented an integrated digital health navigator program supporting portal use among patients with type II diabetes. During our pilot, we were able to enroll 121 (30.9%) patients onto the portal. Of newly enrolled or trained patients, 75 (62.0%) were Black, 13 (10.7%) were White, 23 (19.0%) were Hispanic/Latinx, 4 (3.3%) were Asian, 3 (2.5%) were of another race or ethnicity, and 3 (2.5%) had missing data. Our overall portal enrollment for clinic patients with type II diabetes increased for Hispanic/Latinx patients from 30% to 42% and Black patients from 49% to 61%. We used the Consolidated Framework for Implementation Research to understand key implementation components. Using our approach, other clinics can implement an integrated digital health navigator to support patient portal use.

Impact of Kidney Failure Risk Prediction Clinical Decision Support on Monitoring and Referral in Primary Care Management of CKD: A Randomized Pragmatic Clinical Trial.

Rationale & Objective: To design and implement clinical decision support incorporating a validated risk prediction estimate of kidney failure in primary care clinics and to evaluate the impact on stage-appropriate monitoring and referral. Study Design: Block-randomized, pragmatic clinical trial. Setting & Participants: Ten primary care clinics in the greater Boston area. Patients with stage 3-5 chronic kidney disease (CKD) were included. Patients were randomized within each primary care physician panel through a block randomization approach. The trial occurred between December 4, 2015, and December 3, 2016. Intervention: Point-of-care noninterruptive clinical decision support that delivered the 5-year kidney failure risk equation as well as recommendations for stage-appropriate monitoring and referral to nephrology. Outcomes: The primary outcome was as follows: Urine and serum laboratory monitoring test findings measured at one timepoint 6 months after the initial primary care visit and analyzed only in patients who had not undergone the recommended monitoring test in the preceding 12 months. The secondary outcome was nephrology referral in patients with a calculated kidney failure risk equation value of >10% measured at one timepoint 6 months after the initial primary care visit. Results: The clinical decision support application requested and processed 569,533 Continuity of Care Documents during the study period. Of these, 41,842 (7.3%) documents led to a diagnosis of stage 3, 4, or 5 CKD by the clinical decision support application. A total of 5,590 patients with stage 3, 4, or 5 CKD were randomized and included in the study. The link to the clinical decision support application was clicked 122 times by 57 primary care physicians. There was no association between the clinical decision support intervention and the primary outcome. There was a small but statistically significant difference in nephrology referral, with a higher rate of referral in the control arm. Limitations: Contamination within provider and clinic may have attenuated the impact of the intervention and may have biased the result toward null. Conclusions: The noninterruptive design of the clinical decision support was selected to prevent cognitive overload; however, the design led to a very low rate of use and ultimately did not improve stage-appropriate monitoring. Funding: Research reported in this publication was supported by the National Institute of Diabetes and Digestive and Kidney Diseases of the National Institutes of Health under award K23DK097187. Trial Registration: ClinicalTrials.gov Identifier: NCT02990897.

Effectiveness of an intervention to overcome influenza vaccine hesitancy in specialty clinic patients.

BACKGROUND: Individuals on immunosuppressive therapies experience greater morbidity and mortality due to vaccine-preventable illnesses, but there are low rates of adherence to immunization guidelines within this population. OBJECTIVE: To determine the effectiveness of clinician-led education, patient-centered dialogue, and immediately available immunization on influenza vaccination uptake in patients taking immunosuppressive therapies. METHOD: We used a controlled before-and-after quasi-experimental design to evaluate our quality improvement intervention occurring from September 2019 to March 2020, with follow-up through July 2020. The study included 2 dermatology practices wherein nursing staff offered influenza vaccination during patient rooming (standard care). Within each practice, clinicians either implemented the intervention or provided only standard care. Patients received the intervention or standard care depending on the clinician they visited. Patients seen at the 2 clinics during the intervention period were included in analyses if they were taking or newly prescribed immunosuppressant medication at the time of their visit. We examined influenza immunization status for 3 flu seasons: 2017-2018 (preintervention), 2018-2019 (preintervention), and 2019-2020 (intervention). INTERVENTION: Immunosuppressed patients initially declining an influenza vaccine were provided dermatologist-led education on the benefits of immunization. Dermatologists explored and addressed individual patients' immunization concerns. Influenza vaccination was then offered immediately postdialogue. RESULTS: Analyses included 201 dermatology patients who were prescribed or currently taking immunosuppressive medication (intervention group [72.6%], comparison group [27.4%]). During the intervention period, 91.1% of the intervention group received influenza vaccination compared to 56.4% of the comparison group. Vaccination trends from 2018-2019 (preintervention) to 2019-2020 (intervention) differed significantly between groups (χ2 = 22.92, P < .001), with greater improvement in the intervention group. In 2019-2020, influenza vaccination was more likely in the intervention group relative to the comparison group (odds ratio: 16.22, 95% confidence interval: 5.55-47.38). In the subset of patients that had never received an influenza vaccine, influenza immunization in 2019-2020 was more common in the intervention group (75.8%, 25/33) relative to the comparison group (13.3%, 2/15, P < .001). CONCLUSION: The intervention successfully addressed vaccine hesitancy and improved influenza immunization rates in an immunosuppressed population receiving care from a specialty clinic. Implementing a similar model across specialty clinics may improve vaccination rates for influenza, coronavirus disease 2019, and other vaccine-preventable illnesses in other populations.

The recent evolutionary rescue of a staple crop depended on over half a century of global germplasm exchange.

Rapid environmental change can lead to population extinction or evolutionary rescue. The global staple crop sorghum (Sorghum bicolor) has recently been threatened by a global outbreak of an aggressive new biotype of sugarcane aphid (SCA; Melanaphis sacchari). We characterized genomic signatures of adaptation in a Haitian breeding population that had rapidly adapted to SCA infestation, conducting evolutionary population genomics analyses on 296 Haitian lines versus 767 global accessions. Genome scans and geographic analyses suggest that SCA adaptation has been conferred by a globally rare East African allele of RMES1, which spread to breeding programs in Africa, Asia, and the Americas. De novo genome sequencing revealed potential causative variants at RMES1. Markers developed from the RMES1 sweep predicted resistance in eight independent commercial and public breeding programs. These findings demonstrate the value of evolutionary genomics to develop adaptive trait technology and highlight the benefits of global germplasm exchange to facilitate evolutionary rescue.

Presentations of Cutaneous Disease in Various Skin Pigmentations: Inverse Psoriasis.

Description Inverse psoriasis is a clinical variant of psoriasis involving flexural or intertriginous areas of the body. Inverse psoriasis may be present in 3 to 36% of psoriasis patients. Lesions are clinically characterized as smooth, well-demarcated, erythematous plaques (raised, >1 cm) without the typical silvery scales of classic psoriasis. Differential diagnosis includes tinea infection, candidiasis, seborrheic dermatitis, or bacterial streptococcal infection. The clinical images in this review focus on identifying inverse psoriasis along the full spectrum of skin tones.

Presentations of Cutaneous Disease in Various Skin Pigmentations: Cutaneous Abscesses.

Description Cutaneous abscesses are collections of pus resulting from skin and soft tissue bacterial infections. They clinically exhibit the four cardinal inflammatory signs of pain, warmth, swelling, and erythema. In patients with darkly pigmented skin, classically-associated erythema may be challenging to appreciate and can lead to missed or delayed diagnosis. We compare abscess presentations in different skin types. Recognition of varying presentations of cutaneous abscesses in diverse skin colors will help clinicians utilize additional clues to identify and diagnose this entity correctly.

Acyclovir-Resistant Anogenital Herpes Simplex Virus in an HIV Patient With Pseudoepitheliomatous Hyperplasia Resembling Squamous Cell Carcinoma.

Background: Herpes simplex virus (HSV) is a common infection. However, it may present atypically when patients are immunocompromised, such as with slowly expanding, long-lasting ulcerative or hypertrophic lesions. The histopathologic finding of pseudoepitheliomatous hyperplasia (PEH) can occur in a variety of situations where there is chronic inflammation and can be seen in patients with chronic HSV. Atypical presentations of HSV, particularly hypertrophic lesions with histopathologic findings of PEH, can be misinterpreted as squamous cell carcinoma, create difficulty in diagnosis and hinder appropriate treatment. Case Description: We report a case of a 59-year-old female with a past medical history of human immunodeficiency virus (HIV), who presented at a dermatology clinic with multiple exophytic ulcerations of varying sizes in the perianal region. The patient was diagnosed with HSV and was started on valacyclovir. Over a several-year period, the patient had multiple recurrences of her HSV lesions with persistent vulvodynia despite prophylactic treatment with valacyclovir. Specimens were collected for culture and sensitivities, which revealed acyclovir resistance. The patient's lesions were biopsied due to concern for possible malignancy. Biopsies revealed prominent PEH. The patient had improvement of her HSV with saucerization, topical imiquimod, and increased doses of prophylactic valacyclovir. Conclusion: Atypical, chronic presentations of HSV are common in immunocompromised patients. Hypertrophic HSV is the least common clinical presentation and can be mistaken for squamous cell carcinoma, creating difficulty in diagnosis. Due to concerns for malignancy, our patient's lesions were biopsied, which revealed prominent PEH. While PEH is benign, it can be misdiagnosed as squamous cell carcinoma on histopathology, particularly when there is clinical suspicion for malignancy. In these cases, the clinician needs to alert the pathologist to the immunosuppressed status of the patient. Detailed evaluation for infectious causes, such as HSV, can avoid misinterpretation and potential surgical and oncological overtreatment.

Oral enzymatic detoxification system: Insights obtained from proteome analysis to understand its potential impact on aroma metabolization.

The oral cavity is an entry path into the body, enabling the intake of nutrients but also leading to the ingestion of harmful substances. Thus, saliva and oral tissues contain enzyme systems that enable the early neutralization of xenobiotics as soon as they enter the body. Based on recently published oral proteomic data from several research groups, this review identifies and compiles the primary detoxification enzymes (also known as xenobiotic-metabolizing enzymes) present in saliva and the oral epithelium. The functions and the metabolic activity of these enzymes are presented. Then, the activity of these enzymes in saliva, which is an extracellular fluid, is discussed with regard to the salivary parameters. The next part of the review presents research evidencing oral metabolization of aroma compounds and the putative involved enzymes. The last part discusses the potential role of these enzymatic reactions on the perception of aroma compounds in light of recent pieces of evidence of in vivo oral metabolization of aroma compounds affecting their release in mouth and their perception. Thus, this review highlights different enzymes appearing as relevant to explain aroma metabolism in the oral cavity. It also points out that further works are needed to unravel the effect of the oral enzymatic detoxification system on the perception of food flavor in the context of the consumption of complex food matrices, while considering the impact of food oral processing. Thus, it constitutes a basis to explore these biochemical mechanisms and their impact on flavor perception.

A sorghum practical haplotype graph facilitates genome-wide imputation and cost-effective genomic prediction.

Successful management and utilization of increasingly large genomic datasets is essential for breeding programs to accelerate cultivar development. To help with this, we developed a Sorghum bicolor Practical Haplotype Graph (PHG) pangenome database that stores haplotypes and variant information. We developed two PHGs in sorghum that were used to identify genome-wide variants for 24 founders of the Chibas sorghum breeding program from 0.01x sequence coverage. The PHG called single nucleotide polymorphisms (SNPs) with 5.9% error at 0.01x coverage-only 3% higher than PHG error when calling SNPs from 8x coverage sequence. Additionally, 207 progenies from the Chibas genomic selection (GS) training population were sequenced and processed through the PHG. Missing genotypes were imputed from PHG parental haplotypes and used for genomic prediction. Mean prediction accuracies with PHG SNP calls range from .57-.73 and are similar to prediction accuracies obtained with genotyping-by-sequencing or targeted amplicon sequencing (rhAmpSeq) markers. This study demonstrates the use of a sorghum PHG to impute SNPs from low-coverage sequence data and shows that the PHG can unify genotype calls across multiple sequencing platforms. By reducing input sequence requirements, the PHG can decrease the cost of genotyping, make GS more feasible, and facilitate larger breeding populations. Our results demonstrate that the PHG is a useful research and breeding tool that maintains variant information from a diverse group of taxa, stores sequence data in a condensed but readily accessible format, unifies genotypes across genotyping platforms, and provides a cost-effective option for genomic selection.

Successful Management of Glioblastoma Chemotherapy-Associated Dysgeusia with Gabapentin.

Dysgeusia is a frequent, yet underreported side effect of chemotherapy for cancer. We report here the first use of gabapentin in two glioblastoma patients who developed dysgeusia following intra-arterial administration of carboplatin or oral administration of lomustine, respectively. Treatment initiation was followed by resolution of taste alteration within weeks. Both patients reported significant improvement in their quality of life and regained weight, allowing further chemotherapy cycles. We hypothesized that in these two cases, chemotherapy impeded gustatory cells turnover and function, resulting in a gustatory "deafferentation-like" syndrome which was successfully addressed by the medication.

Cutaneous leishmaniasis in a 65-year-old North Texas male, treated with cryotherapy: A case report.

We report a case of a 65-year-old male seen in a North Texas dermatology clinic with three erythematous nodules possessing central ulceration and scaling on the left lateral shoulder, present for months. Head, ears, lips, oral mucosa, and other body surfaces did not reveal similar lesions, and review of systems was negative. Shave biopsy was performed and histopathological findings demonstrated granulomatous inflammation in the dermis and parasitized histiocytes containing peripherally located amastigotes. Leishmaniasis was diagnosed and patient was educated on the disease while communication with the Centers for Disease Control and Prevention was initiated. The patient declined systemic medications from infectious disease specialists and, 3 weeks later, returned for follow-up treatment with cryotherapy.

Collisional mechanism of ligand release by Bombyxmori JHBP, a member of the TULIP / Takeout family of lipid transporters.

Juvenile hormones (JHs) regulate important processes in insects, such as postembryonic development and reproduction. In the hemolymph of Lepidoptera, these lipophilic sesquiterpenic hormones are transported from their site of synthesis to target tissues by high affinity carriers, the juvenile hormone binding proteins (JHBPs). Lepidopteran JHBPs belong to a recently uncovered, yet very ancient family of proteins sharing a common lipid fold (TULIP domain) and involved in shuttling various lipid ligands. One important, but poorly understood aspect of JHs action, is the mechanism of hormone transfer to or through the plasma membranes of target cells. Since many membrane-active peptides and proteins, such as the pore-forming bacterial toxins, are activated by low pH or interaction with phospholipid membranes, we have examined the effect of these factors on JH binding by JHBPs. The affinity of Bombyx mori and Manduca sexta JHBPs for JH III was determined by the DCC assay, equilibrium dialysis, and isothermal titration calorimetry, and found to be greatly reduced at low pH, in agreement with previous observations. Loss of binding was accompanied by changes in fluorescence and near-UV CD spectra, indicating significant changes in protein structure in the environment of aromatic residues. The apparent dissociation rate constant (koff) of the JHBP-JH III complex was greater at acidic pH, suggesting that low pH favors ligand release by opening of the binding pocket. The affinity of recombinant B. mori JHBP (rBmJHBP) was also decreased in the presence of anionic phospholipid vesicles. Measurements of steady-state fluorescence anisotropy with the lipophilic probe TMA-DPH demonstrated that rBmJHBP specifically interacts with anionic membranes. These results suggest the existence of a collisional mechanism for ligand release that may be important for delivery of JHs to the target cells, and could be relevant to the function of related members of this emerging family of lipid-transport proteins.

Repeat stereotactic radiosurgery for the management of locally recurrent brain metastases.

PURPOSE: Stereotactic radiosurgery (SRS) is a well-established treatment option for brain metastases (BM). Repeat SRS for progressive BM is an increasingly used paradigm, although little data is available to support this practice. The goal of this study was to assess the safety and efficacy of a second SRS procedure on a previously treated BM. METHODS: We performed a retrospective metastasis-level analysis of patients who underwent two SRS procedures on the same lesion and for whom at least 6 months of radiological follow-up was available. The data collected included patient characteristics, clinical symptoms at time of treatment, SRS parameters, radiological response per RANO-BM criteria, clinical evolution and survival. RESULTS: Seventy-five BM in 56 patients were included in the analysis. Most frequent primary histologies were non-small-cell lung cancer (59%) and breast cancer (19%). At the second SRS, median treatment volume was 1.19 cc (range 0.07-20.6) treated with a median margin dose of 18 Gy (range 12-20) at the 50% isodose line (range 30-80%). Median follow-up was 11 months. Progression per RANO-BM criteria occurred in 31%, yielding actuarial local control at 1, 2, and 5 years of 68%, 54% and 54% respectively. At last follow-up, 10 patients (18%) had improved relative to the initial presentation, while 21 (38%) were stable and 25 (44%) were deteriorated. Radiation-induced edema and radionecrosis occurred in 8.3% and 5% respectively. The median survival from the diagnosis of BM was 30 months. CONCLUSION: Repeat SRS is a safe and effective novel therapeutic approach to consider in carefully selected patients.

Sarecycline: a narrow spectrum tetracycline for the treatment of moderate-to-severe acne vulgaris.

Sarecycline is a novel, narrow-spectrum, once-daily tetracycline-derived oral antibiotic that is FDA-approved in the US to be taken with or without food for moderate-to-severe acne vulgaris for ages 9 years of age and older. Sarecycline possesses anti-inflammatory properties and potent activity against Gram-positive bacteria, including activity against multiple strains of Cutibacterium acnes, while exhibiting minimal activity against enteric aerobic Gram-negative bacteria. Unlike many acne studies, sarecycline was investigated for chest and back acne. Significant reduction in inflammatory lesions was seen at week 12 at 1.5 mg/kg/day of sarecycline, with statistically significant improvement seen as early as week 3. No reports of phototoxicity, dizziness, pseudotumor cerebri or lupus but 1.2% nausea and 1.2% vaginal candidiasis was reported in the pivotal Phase III studies.