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Co3C magnetic nanoparticles have been synthesized using supercritical conditions of ethanol. The phase structure of the samples has shown two phases of orthorhombic Co3C and Co structures. The morphology of the prepared nanoparticles reveals a spherical-like shape. Tailoring the synthesis parameters has led to controlling the magnetic properties depending on the ratio of Co3C:Co in the samples. The magnetic properties of the samples have been measured, revealing ferromagnetic behavior. The data yield coercivity (HC) was of 600–950 Oe and saturation magnetization (MS) of 20–38 emu/g. The results present alternative approach to nucleate Co3C magnetic nanoparticles. The synthesis method will be optimized in the future to produce a pure Co3C phase structure.

Naviculocuneiform (NC) joint arthrodesis is an effective procedure to treat pain and provide stability to the medial column. Various forms of fixation have been described for NC arthrodesis. Despite this, the available literature is scant and questions remain regarding nonunion rate and contributory factors. A systematic review of the literature was undertaken to determine the rate of nonunion for NC joint arthrodesis. Seven studies involving 139 NC joint arthrodeses met inclusion criteria. The nonunion rate was 6.5% at a weighted mean follow-up of 73.2 months. There is insufficient evidence to provide a practice guideline based on the current literature. Adequately powered prospective clinical trials comparing well-matched patient groups with long-term follow-up are required to limit systematic error and enhance external validity. Specific outcomes measures should include union, functional assessment, complications, and cost-benefit analysis.

Background: Given findings that generally support the benefits of information and communication technology (ICT) for older adults’ psychosocial adjustment, one might surmise that lonely older adults, who have a stronger need for psychological support, would reap more psychosocial benefits from ICT use. However, scant research has examined this view, much less the likelihood that ICT use might worsen the psychological well-being of lonely older adults, as has been shown to be the case in younger adults. Objective: To examine whether the association between ICT use and psychological adjustment (i.e., psychological distress and sense of community [SOC]) among older adults depends on their loneliness levels. Methods: A representative sample of 738 Hong Kong SAR Chinese older adults aged 60 years or older (56% female) was interviewed in 2017 on loneliness, frequency of ICT use (i.e., Internet and smart devices), psychological distress (6-item Kessler scale; K6), and SOC. Results: Regression analyses showed that loneliness significantly moderated the relationship between ICT use frequency and psychological adjustment (psychological distress and SOC); more frequent ICT use was associated with more psychological distress and less SOC, with higher levels of loneliness. Conclusion: These findings suggest that ICT use may be a mixed blessing for older adults, i.e., using more ICT might predict worse psychological adjustment among lonelier older adults. Efforts that promote ICT use among older adults should take their loneliness levels into account.

Social distancing protocols during the COVID-19 pandemic have resulted in a rapid expansion of telemedicine. It has allowed patients to save time and money on clinic visits, and physicians to communicate with patients who live remotely. Telemedicine has also been valuable in plastic surgery during initial consultations, transfers, and follow up visits. However, given the often-sensitive nature of plastic surgery, the professionalism and expectations of telemedicine have to be reviewed. A comprehensive literature search of the MEDLINE, PubMed, Google Scholar, EMBASE, and Cochrane Central Register of Controlled Trials was conducted for studies published through October 2020 with multiple search terms related to telemedicine and its use in plastic surgery. Data on the effectiveness, challenges, and professionalism of telemedicine were collected. Our review suggests that telemedicine can be an effective mode of communication in many realms of plastic surgery, including cleft care and craniofacial deformities. However, many plastic surgeons are unfamiliar with the existing platforms, and there are no clear guidelines on the most optimal platforms. Physicians have to recognize that patients might have low digital health literacy or may not even possess digital device for telemedicine. There also needs to be an overall improvement in patient education. Given that telemedicine use will continue to increase after the COVID-19 pandemic, regulations on Health Insurance Portability and Accountability Act-compliant platforms and specific guidelines on telemedicine visits, such as undressing, chaperones, privacy matters, need to be established while maintaining a professional relationship between the patient and the physician.

The Scandinavian Total Ankle Replacement (STAR, DJO, Dallas, TX) is a three-part, mobile-bearing ankle implant that has been approved by the Food and Drug Administration for implantation in the United States. Due to the prevalent usage and length of time that the STAR implant has been available, it is one of the most reviewed and researched TAR prostheses. The three-piece design of the STAR prosthesis consists of a flat metallic tibial component with two dorsal dowels, a cylindrical metallic talar component with a small central ridge and a central component composed of high-density polyethylene gliding core. As we become more sophisticated with our techniques and implants, we may find that certain indications are evolving. Currently, implantation of the STAR may be used for the treatment of end-stage ankle arthritis in adult patients. Contraindications include active ankle infection, neuropathic joint, significant areas of avascular osteonecrosis of the talus or distal tibia, complete paralysis of the operative limb, inadequate soft tissue coverage, vascular insufficiency, severe deformity that cannot be corrected, and skeletal immaturity. In this chapter, we provide an in-depth description of the procedure technique including surgical pearls from the authors. To date, a number of studies have reviewed the long-term results and 15-year survivorship of the STAR. Additional long-term studies are needed to further understand the survivability of this implant.

Karnataka, a state in south India, reported its first case of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection on March 8, 2020, more than a month after the first case was reported in India. We used a combination of contact tracing and genomic epidemiology to trace the spread of SARS-CoV-2 in the state up until May 21, 2020 (1578 cases). We obtained 91 genomes of SARS-CoV-2 which clustered into seven lineages (Pangolin lineages—A, B, B.1, B.1.80, B.1.1, B.4, and B.6). The lineages in Karnataka were known to be circulating in China, Southeast Asia, Iran, Europe and other parts of India and are likely to have been imported into the state both by international and domestic travel. Our sequences grouped into 17 contact clusters and 24 cases with no known contacts. We found 14 of the 17 contact clusters had a single lineage of the virus, consistent with multiple introductions and most (12/17) were contained within a single district, reflecting local spread. In most of the 17 clusters, the index case (12/17) and spreaders (11/17) were symptomatic. Of the 91 sequences, 47 belonged to the B.6 lineage, including eleven of 24 cases with no known contact, indicating ongoing transmission of this lineage in the state. Genomic epidemiology of SARS-CoV-2 in Karnataka suggests multiple introductions of the virus followed by local transmission in parallel with ongoing viral evolution. This is the first study from India combining genomic data with epidemiological information emphasizing the need for an integrated approach to outbreak response.

Karnataka, a state in south India, reported its first case of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) on March 8, 2020, more than a month after the first case was reported in India. We used a combination of contact tracing and genomic epidemiology to trace the spread of SARS-CoV-2 in the state up until May 21, 2020 (1578 cases). We obtained 47 full genomes of SARS-CoV-2 which clustered into six lineages (Pangolin lineages-A, B, B.1, B.1.1, B.4, and B.6). The lineages in Karnataka were known to be circulating in China, Southeast Asia, Iran, Europe and other parts of India and are likely to have been imported into the state both by international and domestic travel. Our sequences grouped into 12 contact clusters and 11 cases with no known contacts. We found nine of the 12 contact clusters had a single lineage of the virus, consistent with multiple introductions and most (8/12) were contained within a single district, consistent with local spread. In most of the twelve clusters, the index case (9/12) and spreaders (8/12) were symptomatic. Of the 47 sequences, 31 belonged to the B/B.6 lineage, including seven of eleven cases with no known contact, this is consistent with the ongoing transmission of this lineage in the state. Genomic epidemiology of SARS-CoV-2 in Karnataka is consistent with multiple introductions of the virus followed by local transmission in parallel with ongoing viral evolution. This is the first study from India combining genomic data with epidemiological information emphasizing the need for an integrated approach to outbreak response.

Background Life Goals Programme (LGP) was developed as a psychological intervention for bipolar disorder, with its structured 6-session psychoeducation phase (Phase 1) targeting understanding of the disorder, medication adherence, early warning signs, and coping with symptoms and triggers. The present study tested the efficacy of Phase 1 of the LGP on symptom recovery and moment-by-moment mood stability, as well as medication adherence and quality of life. Methods Adults with bipolar disorder were randomly allocated to the LGP condition (six weekly group sessions) or the waitlist condition (six weeks of standard care, followed by the same LGP intervention). Participants were assessed before and after treatment, and at 6-month follow up. Waitlist participants were additionally assessed at baseline. Assessment included a clinical interview (SCID, MADRS, YMRS, and HAM-A), self-reported questionnaires, and 6-day experience sampling assessment on a mobile device. Results 64 out-patients with bipolar disorder (44 Bipolar I and 20 Bipolar II subtypes) participated in this study. LGP was well received and attended. Following LGP, there were significant improvements in knowledge about illness and level of anxiety, which were of large effect sizes and sustained at 6-month follow-up. Experience sampling assessment revealed small but significant improvements in moment-by-moment mood stability. Improvement in medication adherence was significant at 6 months and was of a moderate-to-large effect size. Changes in anxiety and mood stability were significantly greater following LGP than standard care. Limitations Our results warrant further testing against active control. Conclusions There was a robust improvement in emotional regulation following the 6-week LGP.

Ankle fractures are common orthopedic injuries. Although operative indications and subsequent stabilization of these fractures have not significantly changed, postoperative protocols remain highly variable. Effects of early weight bearing (EWB) on fracture characteristics in operatively stabilized bimalleolar and bimalleolar equivalent ankle fractures remain poorly publicized. This study seeks to clarify postoperative fracture union rates, rates of hardware loosening or failure, and radiographic medial clear space changes when comparing EWB to late weight bearing (LWB) following open reduction and internal fixation (ORIF). A total of 95 patients with either bimalleolar (66%) or bimalleolar equivalent (34%) fractures who underwent ORIF were retrospectively reviewed. Weight bearing was allowed at three weeks in the EWB group and when signs of radiographic union were noted in the LWB group. Postoperatively, patients were evaluated at regular intervals for fracture union, signs of implant failure, and evidence of medial clear space widening radiographically. There were 38 patients (40%) in the EWB group and 57 patients (60%) comprising the LWB cohort. There were no significant demographic differences between groups. The EWB group on average began to weight bear at 3.1 + 1.4 weeks postoperatively, whereas the LWB group began at 7.2 + 2.1 weeks postoperatively (p0.1 at all time intervals) were not notably different between groups. No differences in medial clear space were detected at any postoperative interval between groups (p>0.1 at all time intervals). This study suggests that EWB at three weeks postoperatively does not increase markers of radiographic failure compared to six weeks of non-weight bearing (NWB), which has been regarded as the gold standard of treatment to allow for healing; this may represent an improvement to rehabilitation protocols after bimalleolar ankle ORIF of unstable ankle fractures.

Introduction: There is an ongoing debate about whether negative affect are consequences or triggers of paranoid thinking. It has also been suggested that aberrant salience is central to the development of delusions. This study modelled the moment-to-moment relationships between negative affect, aberrant salience, and paranoia in acute inpatients with psychosis.Methods: Participants with active paranoid delusions were assessed using clinical rating scales and experience sampling method (ESM) over 14 days. ESM data were analysed using time-lagged multilevel regression modelling.Results: Both negative affect and aberrant salience predicted an increase in paranoia at the next time point. Conversely, the level of paranoia did not predict subsequent changes in negative affect or aberrant salience. Negative affect predicted an increase in aberrant salience at the next time point, and vice versa.Conclusions: Negative affect and aberrant salience appear to drive and exacerbate paranoia, rather than being merely the sequelae of the symptom. Our results suggest both direct and indirect (via aberrant salience) pathways from negative affect to paranoia.

Crohn’s disease exacerbations can often be associated with bacterial infections causing gastroenteritis. We report a child who experienced exacerbation of his Crohn’s disease associated with a positive stool culture forEdwardsiella tarda (E. tarda). Endoscopy showed features of moderate inflammation similar to exacerbation of Crohn’s disease. The patient was treated simultaneously with intravenous steroids and antibiotics, and his symptoms resolved. This case report highlights the importance of clinicians being able to promptly recognize and treat concurrent bacterial infections in Crohn’s disease exacerbations.

Background The primary analysis of the STAT study demonstrated the feasibility, efficacy, and safety of using DTG/3TC as a first-line regimen in a test-and-treat setting through 24 weeks, with therapy adjustments for baseline resistance or hepatitis B virus (HBV) co-infection. Here we present secondary analyses through Week 48 of virologic outcomes in participants by baseline viral load (VL). Methods STAT is a single-arm study of treatment-naive adults with HIV-1 infection who initiated DTG/3TC ≤ 14 days after HIV-1 diagnosis without availability of screening/baseline laboratory results. If baseline testing indicated DTG or 3TC resistance, HBV co-infection, or creatinine clearance < 30 mL/min/1.73 m2, then antiretroviral therapy (ART) was potentially adjusted and participants remained on study. Efficacy analyses included proportion of participants with HIV-1 RNA < 50 c/mL regardless of ART regimen at Week 48, among all participants (ITT-E missing = failure analysis) and among participants with available HIV-1 RNA data at Week 48 (observed analysis). Results Of 131 enrolled, DTG/3TC treatment was adjusted in 10 participants, and of those with available data (n=7), all (100%) achieved HIV-1 RNA < 50 c/mL at Week 48. At Week 48, 82% (107/131) of all participants (Figure 1) and 97% (107/110) of those with available data (Figure 2) achieved HIV-1 RNA < 50 c/mL. Of participants with baseline VL ≥ 500,000 c/mL, 89% (17/19) achieved HIV-1 RNA < 50 c/mL at Week 48; the remaining 2 withdrew from study. Of participants with baseline VL ≥ 1,000,000 c/mL, 90% (9/10) achieved HIV-1 RNA < 50 c/mL at Week 48 (Table); the remaining participant withdrew consent. Of the 17 participants with baseline VL ≥ 500,000 c/mL with available data through Week 48, 76% (13/17) achieved virologic suppression by Week 24. One participant with baseline VL ≥ 500,000 c/mL switched from DTG/3TC before the Week 48 assessment. Of the 9 participants with baseline VL ≥ 1,000,000 c/mL with available data through Week 48, most participants (8/9; 89%) were suppressed by Week 24. Figure 1. Virologic outcomes at Week 48, overall and by baseline VL and CD4+ cell count: ITT-E missing = failure analysis. Figure 2. Virologic outcomes at Week 48, overall and by baseline VL and CD4+ cell count: observed analysis. Table. Viral Load by Study Visit Among Participants with Baseline HIV-1 RNA ≥1,000,000 c/mL Conclusion These data provide evidence for the efficacy and feasibility of using DTG/3TC as a first-line regimen in a test-and-treat setting, including among participants with very high baseline VL. Disclosures Charlotte-Paige M. Rolle, MD MPH, Gilead Sciences (Grant/Research Support, Scientific Research Study Investigator, Speaker’s Bureau)Janssen Infectious Disease (Scientific Research Study Investigator, Advisor or Review Panel member)ViiV Healthcare (Grant/Research Support, Scientific Research Study Investigator, Advisor or Review Panel member, Speaker's Bureau) Tulika Singh, MD MS AAHIVS, Gilead (Grant/Research Support, Advisor or Review Panel member)ViiV (Grant/Research Support, Advisor or Review Panel member, Speaker's Bureau) Moti Ramgopal, MD FIDSA, Abbvie (Scientific Research Study Investigator, Speaker's Bureau)Gilead (Consultant, Scientific Research Study Investigator, Speaker's Bureau)Janssen (Consultant, Scientific Research Study Investigator, Research Grant or Support, Speaker's Bureau)Merck (Consultant, Scientific Research Study Investigator)ViiV (Consultant, Scientific Research Study Investigator, Speaker's Bureau) Dushyantha Jayaweera, MD, mrcog(uk), face, Gilead (Research Grant or Support)Janssen (Research Grant or Support)viiv (Research Grant or Support) Peter Leone, MD, viiv healthcare (Employee) Jessica Matthews, BS, ViiV Healthcare (Employee) Michael Cupo, Ph.D., GlaxoSmithKline (Employee) Mark Underwood, PhD, GlaxoSmithKline (Shareholder)ViiV Healthcare (Employee) Kostas Angelis, PhD, GSK (Employee, Shareholder) Brian Wynne, MD, ViiV Healthcare (Employee, Shareholder, I have shares in GSK, the part owner of ViiV) Deanna Merrill, PharmD, MBA, AAHIVP, GlaxoSmithKline (Shareholder)ViiV Healthcare (Employee) Christopher T. Nguyen, MD, ViiV Healthcare (Employee) Jean A. van Wyk, MB,ChB, GlaxoSmithKline (Shareholder)ViiV Healthcare (Employee) Andrew Zolopa, MD, GlaxoSmithKline (Shareholder)ViiV Healthcare (Employee)

There is a lack of consensus in the literature regarding optimal treatment methods for Lisfranc injuries, and recent literature has emphasized the need to compare open reduction and internal fixation (ORIF) with primary arthrodesis (PA). The purpose of the current study is to compare reoperation and complication rates between ORIF and PA following Lisfranc injury in a private, outpatient, orthopaedic practice. A retrospective chart review was performed on patients undergoing operative intervention for Lisfranc injury between January 2009 and September 2015. A total of 196 patients met the inclusion criteria (130 ORIF, 66 PA), with a mean follow-up of 61.3 and 81.7 weeks, respectively. The ORIF group had a higher reoperation rate than the PA group, due to hardware removal. When hardware removals were excluded, the reoperation rate was similar. Postsurgical complications were compared between the 2 groups with no significant difference. In conclusion, ORIF and PA had similar complication rates. When hardware removals were excluded, the reoperation rates were similar, although hardware removals were more common in the ORIF group compared with the PA group. Levels of Evidence: Level III

Background: Research suggests that diabetes mellitus (DM) has a negative impact on employment and workplace injury, but there is little data within the Canadian context. Objective: To determine if DM has an impact on various occupational health outcomes using the Canadian Community Health Survey (CCHS). Methods: CCHS data between 2001 and 2014 were used to assess the relationships between DM and various occupational health outcomes. The final sample size for the 14-year study period was 505 606, which represented 159 432 239 employed Canadians aged 15–75 years during this period. Results: We found significant associations between people with diabetes and their type of occupation (business, finance, administration: 2009, p=0.002; 2010, p=0.002; trades, transportation, equipment: 2008, p=0.025; 2011, p=0.002; primary industry, processing, manufacturing, utility: 2013, p=0.018), reasons for missing work (looking for work: 2001, p=0.024; school or education: 2003, p=0.04; family responsibilities: 2014, p=0.015; other reasons: 2001, p

Background Black Americans are disproportionately impacted by HIV. The BRAAVE 2020 study, evaluated the safety and efficacy of switching to the guidelines-recommended single-tablet regimen bictegravir, emtricitabine, tenofovir alafenamide (B/F/TAF) in Black adults through week (W) 48. Methods Adults with HIV who self-identified as Black or African American and were virologically suppressed on 2 NRTIs plus a 3rd agent were randomized (2:1) to switch to open-label B/F/TAF once daily or stay on their baseline regimen (SBR). Prior virologic failure was allowed except failure on an INSTI. Prior resistance to NNRTIs, PIs and/or NRTIs was permitted except K65R/E/N, ≥3 thymidine analog mutations or T69-insertions. Primary INSTI-resistance was excluded. SBR participants switched to B/F/TAF at W24. Efficacy was assessed at the W24 (1○ endpoint, noninferiority margin 6%) and at W48 as the proportion with HIV-1 RNA ≥ 50 c/mL by FDA Snapshot and by changes in CD4 count. Safety was assessed by adverse events (AE) and lab results. Results 495 were randomized and treated (B/F/TAF n=330, SBR n=165): 32% cis women, 2% transgender women, median age 49 y (range 18-79), 10% had pre-existing M184V/I mutation (Table 1), and 62% lived in the US South. At W24, 1% (2/328) on B/F/TAF vs 2% (3/165) on SBR had HIV-1 RNA ≥50 c/mL (difference -1.2%; 95% CI -4.8% to 0.9%) demonstrating noninferiority of B/F/TAF; 2 with pre-existing primary INSTI resistance were excluded from analysis. 163 assigned to SBR completed W24 and switched to B/F/TAF (SBR to B/F/TAF). At W48 1% (3/328) originally randomized to B/F/TAF and 0 SBR to B/F/TAF had HIV-1 RNA ≥ 50 c/mL (Table 2). The presence of baseline NRTI resistance did not affect the efficacy of B/F/TAF. No treatment emergent resistance was detected. The mean (SD) changes in CD4 were +7 cells/mm3 (189) for B/F/TAF and -8 cells/mm3 (159) for SBR to B/F/TAF. Median (IQR) weight increased 0.9 kg (-1.5, 4.1) and 0.6 kg (-1.0, 3.1) for B/F/TAF and SBR to B/F/TAF groups, respectively. Study drug-related AEs occurred in 10% of participants while on B/F/TAF; most were grade 1. Table 1. Table 2. Conclusion Switching to B/F/TAF was highly effective for Black adults regardless of baseline regimen or pre-existing NRTI resistance and was associated with few treatment related AEs or discontinuations. Disclosures Debbie Hagins, MD, Gilead Sciences Inc. (Consultant, Grant/Research Support, Scientific Research Study Investigator, Advisor or Review Panel member)Janssen (Grant/Research Support)Merck (Consultant, Grant/Research Support, Advisor or Review Panel member)Viiv Healthcare (Consultant, Grant/Research Support, Advisor or Review Panel member) Princy Kumar, MD, Gilead Sciences Inc. (Scientific Research Study Investigator) Michael Saag, MD, Gilead Sciences Inc. (Consultant, Grant/Research Support, Scientific Research Study Investigator)Merck (Consultant, Grant/Research Support)Proteus (Grant/Research Support)Viiv Healthcare (Consultant, Grant/Research Support) Anson K. Wurapa, MD, Gilead Sciences Inc. (Grant/Research Support, Scientific Research Study Investigator, Advisor or Review Panel member)GlaxoSmithKline (Grant/Research Support)Janssen (Grant/Research Support, Advisor or Review Panel member)Pfizer (Grant/Research Support) Indira Brar, MD, Gilead (Speaker’s Bureau)janssen (Speaker’s Bureau)ViiV (Speaker’s Bureau) Daniel Berger, MD, Gilead Sciences Inc. (Scientific Research Study Investigator) Olayemi Osiyemi, M.D, GlaxoSmithKline (Advisor or Review Panel member, Speaker’s Bureau)ViiV Healthcare (Advisor or Review Panel member, Speaker’s Bureau) Corrilynn Hileman, MD, Gilead Sciences Inc. (Consultant, Scientific Research Study Investigator) Moti Ramgopal, MD FACP FIDSA, AbbVie (Speaker’s Bureau)Allergan (Speaker’s Bureau)Gilead Sciences Inc. (Consultant, Scientific Research Study Investigator, Speaker’s Bureau)Janssen (Speaker’s Bureau)Merck (Consultant)Viiv Healthcare (Consultant) Cheryl McDonald, MD, Gilead Sciences Inc. (Grant/Research Support, Scientific Research Study Investigator, Speaker’s Bureau)Janssen (Grant/Research Support)Merck (Grant/Research Support, Speaker’s Bureau)Viiv Healthcare (Grant/Research Support) Christiana Blair, MS, Gilead Sciences (Employee, Shareholder) Kristen Andreatta, MSc, Gilead Sciences (Employee, Shareholder) Sean E. Collins, MD, MS, Gilead Sciences (Employee) Diana M. Brainard, MD, Gilead Sciences (Employee) Hal Martin, MD, MPH, Gilead Sciences Inc. (Employee, Shareholder)

Affinity optimization of monoclonal antibodies (mAbs) is essential for developing drug candidates with the highest likelihood of clinical success; however, a quantitative approach for setting affinity requirements is often lacking. In this study, we computationally analyzed the in vivo mAb-target binding kinetics to delineate general principles for defining optimal equilibrium dissociation constant (\( {K}_D^{opt} \)) of mAbs against soluble and membrane-bound targets. Our analysis shows that in general \( {K}_D^{opt} \) to achieve 90% coverage for a soluble target is one tenth of its baseline concentration (\( {K}_D^{opt}=0.1\times {S}_0 \)), and is independent of the dosing interval, target turnover rate or the presence of competing ligands. For membrane-bound internalizing targets, it is equal to the ratio of internalization rate of mAb-target complex and association rate constant (\( {K}_D^{opt}=\raisebox{1ex}{${k}_{elDM}$}\!\left/ \!\raisebox{-1ex}{${k}_{on}$}\right. \)). In cases where soluble and membrane-bound forms of the target co-exist, \( {K}_D^{opt} \) lies within a range determined by the internalization rate (\( {k}_{elDM} \)) of the mAb-membrane target complex and the ratio of baseline concentrations of soluble and membrane-bound forms (\( \raisebox{1ex}{${S}_0$}\!\left/ \!\raisebox{-1ex}{${M}_0$}\right. \)). Finally, to demonstrate practical application of these general rules, we collected target expression and turnover data to project \( {K}_D^{opt} \) for a number of marketed mAbs against soluble (TNFα, RANKL, and VEGF) and membrane-bound targets (CD20, EGFR, and HER2).

The article offers a brief history of pitted keratolysis (PK), research regarding PK etiology, evaluation of PK, and current treatment modalities. The main objective of this article focuses on the current literature on PK, its presentation and symptomatology, prevalence, and available therapeutic options. We present a case report and review on PK of a patient treated with an over the counter antiperspirant, topical erythromycin, oral erythromycin, and proper education on hygiene, with complete resolution and without recurrence after a follow up of greater than 12 months.

There is an increase in interest in the relationships between loneliness and psychosis. The notion of psychosis continuum implies that psychotic experiences extend from clinical populations with psychotic disorders to non-clinical populations. This meta-analytic review aimed to examine the respective associations of loneliness with positive and negative psychotic experiences along the psychosis continuum. A systematic database search was conducted and a total of 30 studies were included in the first meta-analysis and 15 studies were included in the second meta-analysis. There was a medium association between loneliness and positive psychotic experiences (r = 0.302, p r = 0.448, p r = 0.347, p

Since the inception of the first surgical training system by Sir William Stewart Halsted, resident surgical skill development has been promulgated in teaching hospitals. Currently, the Council on Podiatric Medical Education does not mandate the availability of a cadaver lab as a residency curriculum requirement. The purpose of the present study is to assess the structure of the cadaver lab and availability in the current podiatric surgical training programs. A survey was sent electronically to 229 American Association of Colleges of Podiatric Medicine–approved residency programs, excluding OhioHealth, across all residency programs. A total of 173 (6.9%) residents from 74 (32.3%) residency programs completed the survey. This survey analyzed the characteristics and perception of the current state of cadaver lab in podiatric residency. The most reported type of cadaver labs available were medical company sponsored and hospital sponsored. Other hands-on training, including inanimate simulators (n = 24) and animal models (n = 5), was also reported. Overall, 87.9% of the surveyed residents found that cadaver lab is either extremely beneficial (57.8%) or somewhat beneficial (30.1%). The most important factors perceived in a successful cadaver lab were faculty instruction (n = 78), accessibility of lab (n = 46), and availability of instrumentation/hardware (n = 26). This qualitative survey is the first study to address the uniformity, perception, and potential value of the cadaver lab in a podiatric surgical residency.

Clinical development of biotherapeutics for combination therapy requires monitoring the concentrations of both drugs in biological samples. Traditionally, two assays are required to measure drug levels one at a time, which poses challenges in sample management, data reporting, and cost. The Meso Scale Discovery (MSD®) U-PLEX™ platform provides a simple and flexible way to create custom multiplex ligand binding assays (LBAs). We developed and fully validated a two-plex assay on the U-PLEX platform where two therapeutic monoclonal antibodies (mAbs) in Merck's pipeline, which we call MK-A and MK-B in this manuscript, can be measured simultaneously in one sample. Our results demonstrated that the multiplexed pharmacokinetic (PK) assay has performances, including accuracy, precision, and cross-reactivity, that meet requirements in regulatory guidance. Furthermore, results of MK-A from the multiplex assay are comparable to results from a previously validated MK-A single-plex assay with 80% of samples tested in both assays having concentration differences < 30% relative to the mean of the two measurements. The multiplex assay was used to support a phase I MK-A/MK-B combination therapy clinical study and generated results consistent with historical MK-A monotherapy PK data. The ability to measure both biotherapeutics in a multiplexed assay is beneficial in that it improves consistency and efficiency while reduces sample volume and cost. With the number of combination therapies increasing in development, multiplexed assays can potentially have wide applications in biologics bioanalysis.

Background: Current treatment for HIV-infected individuals with renal failure on haemodialysis frequently requires complex regimens with multiple pills. A daily single-tablet regimen of coformulated elvitegravir, cobicistat, emtricitabine, and tenofovir alafenamide is approved in Europe, the USA, and in other regions for use in HIV-1-infected individuals with mild-to-moderate chronic kidney disease (creatinine clearance 30–69 mL/min). We aimed to assess the safety, efficacy, and pharmacokinetics of this regimen in HIV-infected adults with end-stage renal disease on chronic haemodialysis. Methods: We did an open-label, single-arm, multicentre, phase 3b trial at 26 outpatient clinics in Austria, France, Germany, and the USA. Participants were HIV-1-infected adults with end-stage renal disease (creatinine clearance

Understanding pharmacological target coverage is fundamental in drug discovery and development as it helps establish a sequence of research activities, from laboratory objectives to clinical doses. To this end, we evaluated the impact of tissue target concentration data on the level of confidence in tissue coverage predictions using a site of action (SoA) model for antibodies. By fitting the model to increasing amounts of synthetic tissue data and comparing the uncertainty in SoA coverage predictions, we confirmed that, in general, uncertainty decreases with longitudinal tissue data. Furthermore, a global sensitivity analysis showed that coverage is sensitive to experimentally identifiable parameters, such as baseline target concentration in plasma and target turnover half‐life and fixing them reduces uncertainty in coverage predictions. Overall, our computational analysis indicates that measurement of baseline tissue target concentration reduces the uncertainty in coverage predictions and identifies target‐related parameters that greatly impact the confidence in coverage predictions.