Feasibility and Acceptability of a Prospective Syphilis Sexual Network Study for Sexual Minority Men.

BACKGROUND: In preparation for a prospective syphilis network study of sexual minority men, we conducted a mixed-methods formative study with the following objectives: a) assess acceptability of respondent driven sampling (RDS), b) assess acceptability of study procedures, c) social network seed selection, and d) pilot an ecological momentary assessment (EMA) study to assess social networking, sexual and substance use behavior. METHODS: We conducted in-depth interviews with eight providers serving sexual minority men and five focus group discussions with 34 sexual minority men, prioritizing four target populations: young Black sexual minority men, 2) on PrEP, 3) living with HIV, 4) not engaged in care. The 4-week EMA pilot was conducted with 40 sexual minority men. EMA survey responses were analyzed to evaluate how different compensation levels influenced response rates. Brief exit surveys were used to assess EMA app acceptability. RESULTS: Primary themes identified through qualitative data collection: 1) importance of developing trust and maintaining confidentiality during proposed recruitment activities, 2) importance of compensating participants appropriately for study activities, and 3) cultural considerations for increasing visibility and participation of young Black sexual minority men. All EMA participants reported being "completely comfortable" reporting sexual behavior through the app. Most (78%) preferred the app to in-person interviews. Several participants identified technical issues with the app, including not receiving push notifications and spontaneous closure. CONCLUSIONS: This mixed-methods formative study allowed for adjustments to and tailoring of the planned network study, including recruitment protocols, compensation type and amount, and EMA survey wording and response items.

An Automated Text Messaging Intervention to Reduce Substance Use Self-Stigma (Project RESTART): Protocol for a Feasibility and Acceptability Pilot Study.

BACKGROUND: Stigma is a barrier to treatment and harm reduction seeking in people who use drugs. Most stigma reduction interventions offer psychotherapy or psychoeducation in group-based clinical settings, failing to reach people who are not in treatment. SMS text messaging is an effective and acceptable modality for delivering health information to people who use drugs and may be a suitable conduit for providing information and advice to understand and cope with stigma. OBJECTIVE: This paper presents the protocol for a study that aims to determine the feasibility, acceptability, and preliminary effectiveness of a 4-week automated SMS text message intervention to increase stigma resistance and reduce self-stigma in people who use drugs. METHODS: We designed a novel automated SMS text message intervention to address the four personal-level constructs of stigma resistance: (1) not believing stigma and catching and challenging stigmatizing thoughts, (2) empowering oneself through learning about substance use and one's recovery, (3) maintaining one's recovery and proving stigma wrong, and (4) developing a meaningful identity and purpose apart from one's substance use. Theory-based messages were developed and pilot-tested in qualitative elicitation interviews with 22 people who use drugs, resulting in a library of 56 messages. In a single-group, within-subjects, community-based pilot trial, we will enroll 30 participants in the Resisting Stigma and Revaluating Your Thoughts (RESTART) intervention. Participants will receive 2 daily SMS text messages for 4 weeks. Implementation feasibility will be assessed through recruitment, enrollment, retention, and message delivery statistics. User feasibility and acceptability will be assessed at follow-up using 23 survey items informed by the Theoretical Framework of Acceptability. Primary effectiveness outcomes are changes in self-stigma (Substance Abuse Self-Stigma Scale) and stigma resistance (Stigma Resistance Scale) from baseline to follow-up measured via a self-administered survey. Secondary outcomes are changes in hope (Adult Dispositional Hope Scale) and self-esteem (Rosenberg Self-Esteem Scale). Feasibility and acceptability will be assessed with descriptive statistics; effectiveness outcomes will be assessed with paired 2-tailed t tests, and group differences will be explored using ANOVA. Overall, 12 participants will also be selected to complete acceptability interviews. RESULTS: This pilot study was funded by the National Institute on Drug Abuse in April 2023 and received regulatory approval in January 2024 by the University of North Carolina-Chapel Hill Institutional Review Board. Recruitment and enrollment began in March 2024. Follow-up visits are expected to conclude by May 2024. Results will be disseminated in relevant peer-reviewed journals. CONCLUSIONS: To the best of our knowledge, this is the first study to address substance use stigma via a self-help SMS text messaging program. Results will add to the nascent literature on stigma reduction in people who use drugs. This protocol may interest researchers who are considering text messaging to address psychosocial needs in hard-to-reach populations. TRIAL REGISTRATION: ClinicalTrials.gov NCT06281548; https://clinicaltrials.gov/ct2/show/NCT06281548. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/59224.

Medical Students' Views of the Future in a Rapidly Changing World.

BACKGROUND AND OBJECTIVES: Physicians have long been considered valued members of a solid US health care system. Significant changes in medical education, health care, and society at-large suggest that current medical students may face a different future. To help guide educators and policy makers, we set out to understand medical students' perceptions of the future of health care and their place in it. METHODS: In year one of a longitudinal study, we conducted in-depth interviews of Case Western Reserve University medical students. A multidisciplinary team performed iterative thematic analyses and sampling until reaching saturation on major themes. RESULTS: Eleven medical student participants described social and health care issues as major influences on their professional futures. Concerns included health care system failings, unsustainable costs, climate change, demographic shifts, disinformation, and public distrust in health care. Students looked forward to team practice and using technology, data, and artificial intelligence in care delivery. They hoped for greater access and equity in health care, with a focus on prevention and social, behavioral, and environmental drivers of health. Most students expected to be employed rather than in private practice and sought time/flexibility for professional and personal interests. Paying off medical school debt and advocating for patients and change were priorities. Many saw primary care as important, but fewer envisioned it as their career path of choice. CONCLUSIONS: Medical students envision a future shaped by health care systems and social issues. These findings can inform those helping students prepare for uncertainty and rapid change in their careers, their lives, and the lives of their patients.

Developing Leaders in Surgical Residency: A Curriculum for Success.

OBJECTIVE: As surgical residents continue in their training, they are expected to not only take part in more complicated procedures, but to also serve as leaders in their respective care teams. While surgical skills are intensively taught in surgical residency programs, leadership is often learned informally, to the detriment of residents. Our curriculum was developed and implemented to provide foundational knowledge for surgical residents as they take on senior roles so that they may successfully act as leaders. This educational workshop was effective and efficient and can be applied at other residency programs that seek to improve the leadership skills of their residents. DESIGN: Implementation of a 3-day program focused on leadership, surgical skills, and career development to provide rising PGY-4 surgical residents with the abilities necessary for successful training. SETTING: This program was implemented at the University of Minnesota General Surgery residency program. PARTICIPANTS: Rising PGY-4 general surgery residents. RESULTS: The program consisted of a 3-day workshop which all rising PGY-4 residents participating in before transitioning into their respective roles. The program was led by the general surgery faculty. CONCLUSIONS: Curricula focused on developing leadership skills in residents can be effectively applied in a time-efficient manner that can benefit the residents as they move into official leadership roles on the care team.

Caffeine Abstinence in Habituated Users: Cardiovascular Responses to Exercise With Blood Flow Restriction.

CONTEXT: Blood flow restriction resistance exercise studies often require caffeine abstinence to avoid cardiovascular effects that could change the blood flow restriction stimulus. However, effects may be attenuated for habituated users. OBJECTIVE: To compare cardiovascular responses to blood flow restriction resistance exercise when habituated users consume or abstain from caffeine. DESIGN: Thirty participants completed a 3-visit within-subject study beginning with familiarization and caffeine intake questionnaire. METHODS: Visits 2 and 3 consisted of blood flow restriction resistance exercise (3 sets bicep curls to failure, 30% 1-repetition max, 40% arterial occlusion pressure [AOP]), following participants' normal caffeine consumption (CAFF) or abstaining (ABS). AOP, systolic (SBP) and diastolic (DBP) blood pressure, and heart rate were measured preexercise and postexercise. Prevalues and preexercise to postexercise change scores for SBP, DBP, AOP (all millimeters of mercury), heart rate (in beats per minute), and repetitions were compared between conditions. Results are represented as mean (SD). RESULTS: Preexercise AOP was similar for CAFF (137.8 [14.4]) and ABS (137.1 [14.9], BF10 = 0.2), although pre-SBP was higher for CAFF (115.4 [9.8]) than ABS (112.3 [9.4], BF10 = 1.9). Pre-DBP was similar between conditions. The exercise-induced change in AOP was greater for CAFF (18.4 [11.2]) than ABS (13.2 [14.9]), though evidence was anecdotal (BF10 = 0.7). Exercise-induced changes in SBP, DBP, and heart rate were similar between conditions (all BF10 ≤ 0.40). More repetitions were completed for CAFF (63 [26]) than ABS (57 [17], BF10 = 2.1). CONCLUSIONS: The findings of this study suggest that for habituated users, maintaining daily caffeine habits will not have substantial effects on common cardiovascular variables relevant to blood flow restriction.

Cefiderocol heteroresistance associated with mutations in TonB-dependent receptor genes in Pseudomonas aeruginosa of clinical origin.

The siderophore-cephalosporin cefiderocol (FDC) presents a promising treatment option for carbapenem-resistant (CR) P. aeruginosa (PA). FDC circumvents traditional porin and efflux-mediated resistance by utilizing TonB-dependent receptors (TBDRs) to access the periplasmic space. Emerging FDC resistance has been associated with loss of function mutations within TBDR genes or the regulatory genes controlling TBDR expression. Further, difficulties with antimicrobial susceptibility testing (AST) and unexpected negative clinical treatment outcomes have prompted concerns for heteroresistance, where a single lineage isolate contains resistant subpopulations not detectable by standard AST. This study aimed to evaluate the prevalence of TBDR mutations among clinical isolates of P. aeruginosa and the phenotypic effect on FDC susceptibility and heteroresistance. We evaluated the sequence of pirR, pirS, pirA, piuA, or piuD from 498 unique isolates collected before the introduction of FDC from four clinical sites in Portland, OR (1), Houston, TX (2), and Santiago, Chile (1). At some clinical sites, TBDR mutations were seen in up to 25% of isolates, and insertion, deletion, or frameshift mutations were predicted to impair protein function were seen in 3% of all isolates (n = 15). Using population analysis profile testing, we found that P. aeruginosa with major TBDR mutations were enriched for a heteroresistant phenotype and undergo a shift in the susceptibility distribution of the population as compared to susceptible strains with wild-type TBDR genes. Our results indicate that mutations in TBDR genes predate the clinical introduction of FDC, and these mutations may predispose to the emergence of FDC resistance.

Long-term Outcomes of Liver Transplantation for Inborn Errors of Metabolism in Children.

BACKGROUND: Liver transplantation for inborn errors of metabolism is increasingly common and has historically had positive outcomes. However, this therapeutic modality is not without risks, and patient post-transplant quality of life should be part of the consideration. METHODS: This retrospective, observational cohort study included all pediatric patients receiving liver transplant from 2010 through 2020 at a single center. Recipients were split into 2 groups based on metabolic or non-metabolic indications for liver transplant. Ten-year patient survival and graft survival were analyzed. The PedsQL Transplant Module and RAND 36-Item Health Survey 1.0 were administered prospectively to those recipients with metabolic indications. RESULTS: Ten-year patient survival was statistically significantly higher in the metabolic group than in the non-metabolic (p < .05), and there was no difference in 10-year graft survival between groups. Of the 12 patients in the metabolic group who completed the PedsQL Transplant Module or RAND 36-Item Health Survey 1.0, the median score was 88, similar to the score seen in healthy children. CONCLUSIONS: Liver transplantation for inborn errors of metabolism provides excellent long-term outcomes in terms of patient and graft survival, while maintaining a high quality of life.

Prevalence of the Cefazolin Inoculum Effect (CzIE) in Nasal Colonizing Methicillin-Susceptible Staphylococcus aureus in Patients from Intensive Care Units in Colombia and Use of a Modified Rapid Nitrocefin Test for Detection.

The cefazolin inoculum effect (CzIE) has been associated with poor clinical outcomes in patients with MSSA infections. We aimed to investigate the point prevalence of the CzIE among nasal colonizing MSSA isolates from ICU patients in a multicenter study in Colombia (2019-2023). Patients underwent nasal swabs to assess for S. aureus colonization on admission to the ICU and some individuals had follow-up swabs. We performed cefazolin MIC by broth-microdilution using standard and high-inoculum and developed a modified nitrocefin-based rapid test to detect the CzIE. Whole genome sequencing was carried out to characterize BlaZ types and allotypes, phylogenomics and Agr-typing. All swabs were subjected to 16S-rRNA metabarcoding sequencing to evaluate microbiome characteristics associated with the CzIE. A total of 352 patients were included; 46/352 (13%) patients were colonized with S. aureus; 22% (10/46) and 78% (36/46) with MRSA and MSSA, respectively. Among 36 patients that contributed with 43 MSSA colonizing isolates, 21/36 (58%) had MSSA exhibiting the CzIE. BlaZ type A and BlaZ-2 were the predominant type and allotype in 56% and 52%, respectively. MSSA belonging to CC30 were highly associated with the CzIE and SNP analyses supported transmission of MSSA exhibiting the CzIE among some patients of the same unit. The modified nitrocefin rapid test had 100%, 94.4% and 97.7% sensitivity, specificity and accuracy, respectively. We found a high prevalence point prevalence of the CzIE in MSSA colonizing the nares of critically-ill patients in Colombia. A modified rapid test was highly accurate in detecting the CzIE in this patient population.

Comparing the acute responses between a manual and automated blood flow restriction system.

The purpose of this study was to compare acute responses between manual and automated blood flow restriction (BFR) systems. Methods: A total of 33 individuals completed this study. On visit 1, arterial occlusion pressure (AOP, mm Hg), cardiovascular responses, and discomfort (RPE-D) were measured with each BFR system at rest. On visit 2, unilateral bicep curls were completed [30% one-repetition maximum; 50% AOP] with one system per arm. Muscle thickness (MT, cm) and maximal force (N) were assessed before (pre), immediately (post-0), 5 min (post-5), and 10 min (post-10) post-exercise. Ratings of perceived exertion (RPE-E) and ratings of perceived discomfort (RPE-D) were assessed throughout the exercise. AOP and repetitions were compared with Bayesian paired t-tests. Other outcomes were compared with Bayesian RMANOVAs. BF10 represents the likelihood of the best model vs. the null. The results are presented as mean ± SD. Results: Supine cardiovascular responses and RPE-D were similar for manual and automated (all BF10 ≤ 0.2). Supine AOP for manual (157 ± 20) was higher than that of automated (142 ± 17; BF10 = 44496.0), but similar while standing (manual: 141 ± 17; automated: 141 ± 22; BF10 = 0.2). MT (time, BF10 = 6.047e + 40) increased from Pre (3.9 ± 0.7) to Post-0 (4.4 ± 0.8; BF10 = 2.969e + 28), with Post-0 higher than Post-5 (4.3 ± 0.8) and Post-10 (4.3 ± 0.8; both BF10 ≥ 275.2). Force (time, BF10 = 1.246e + 29) decreased from Pre (234.5 ± 79.2) to Post-0 (149.8 ± 52.3; BF10 = 2.720e + 22) and increased from Post-0 to Post-5 (193.3 ± 72.7; BF10 = 1.744e + 13), with Post-5 to Post-10 (194.0 ± 70.6; BF10 = 0.2) being similar. RPE-E increased over sets. RPE-D was lower for manual than automated. Repetitions per set were higher for manual (Set 1: 37 ± 18; Set 4: 9 ± 5) than automated (Set 1: 30 ± 7; Set 4: 7 ± 3; all BF10 ≥ 9.7). Conclusion: Under the same relative pressure, responses are mostly similar between BFR systems, although a manual system led to lower exercise discomfort and more repetitions.

Enabled to Stand: A Single-subject Research Design Study Exploring Pediatric Power Wheelchair Standing Device Use.

PURPOSE: To investigate the influence of powered wheelchair standing device (PWSD) use on changes in activity/participation in children with neurodevelopmental conditions. METHODS: A mixed methods A-B-A single-subject research design was replicated with participants. The target behavior was parental perceptions of changes in children's performance of activity/participation goals measured via the Canadian Occupational Performance Measure (COPM). Secondary outcome measures included the COPM with children, an interview, and a 3-measure implementation survey. COPM data related to the target behavior were analyzed using the split-middle celeration line method. RESULTS: Four child-parent dyads participated in the study. All participants achieved statistically and clinically significant increases in COPM performance ratings for the 5 parent-identified activity/participation goals. CONCLUSIONS: For the participant dyads in this study, use of the PWSD appeared to positively influence parental perceptions of improvements in their child's performance of activity/participation goals.

Campylobacter devanensis sp. nov., Campylobacter porcelli sp. nov., and Campylobacter vicugnae sp. nov., three novel Campylobacter lanienae-like species recovered from swine, small ruminants, and camelids.

In a previous study characterizing Campylobacter strains deficient in selenium metabolism, 50 strains were found to be similar to, but distinct from, the selenonegative species Campylobacter lanienae. Initial characterization based on multilocus sequence typing and the phylogeny of a set of 20 core genes determined that these strains form three putative taxa within the selenonegative cluster. A polyphasic study was undertaken here to further clarify their taxonomic position within the genus. The 50 selenonegative strains underwent phylogenetic analyses based on the sequences of the 16S rRNA gene and an expanded set of 330 core genes. Standard phenotypic testing was also performed. All strains were microaerobic and anaerobic, Gram-negative, spiral or curved cells with some displaying coccoid morphologies. Strains were motile, oxidase, catalase, and alkaline phosphatase positive, urease negative, and reduced nitrate. Strains within each clade had unique phenotypic profiles that distinguished them from other members of the genus. Core genome phylogeny clearly placed the 50 strains into three clades. Pairwise average nucleotide identity and digital DNA-DNA hybridization values were all below the recommended cut-offs for species delineation with respect to C. lanienae and other related Campylobacter species. The data presented here clearly show that these strains represent three novel species within the genus, for which the names Campylobacter devanensis sp. nov. (type strain RM3662T=LMG 33097T=NCTC 15074T), Campylobacter porcelli sp. nov. (type strain RM6137T=LMG 33098T=CCUG 77054T=NCTC 15075T) and Campylobacter vicugnae sp. nov. (type strain RM12175T=LMG 33099T=CCUG 77055T=NCTC 15076T) are proposed.

Scaling up a brief alcohol intervention to prevent HIV infection in Vietnam: a cluster randomized, implementation trial.

BACKGROUND: Evidence-based interventions (EBIs) often address normative behaviors. If a behavior is also common among clinicians, they may be skeptical about the necessity or effectiveness of an EBI. Alternatively, clinicians' attitudes and behaviors may be misaligned, or they may lack the knowledge and self-efficacy to deliver the EBI. Several EBIs address unhealthy alcohol use, a common and often culturally acceptable behavior. But unhealthy alcohol use may be particularly harmful to people with HIV (PWH). Here, we present an implementation trial using an experiential implementation strategy to address clinicians' knowledge, attitudes, and behaviors. Clinicians receive the experiential intervention before they begin delivering an evidence-based brief alcohol intervention (BAI) to PWH with unhealthy alcohol use. METHODS: Design: In this hybrid type 3 implementation-effectiveness cluster randomized controlled trial, ART clinics (n = 30) will be randomized 1:1 to facilitation, a flexible strategy to address implementation barriers, or facilitation plus the experiential brief alcohol intervention (EBAI). In the EBAI arm, clinicians, irrespective of their alcohol use, will be offered the BAI as experiential learning. EBAI will address clinicians' alcohol-related attitudes and behaviors and increase their knowledge and confidence to deliver the BAI. PARTICIPANTS: ART clinic staff will be enrolled and assessed at pre-BAI training, post-BAI training, 3, 12, and 24 months. All PWH at the ART clinics who screen positive for unhealthy alcohol use will be offered the BAI. A subset of PWH (n = 810) will be enrolled and assessed at baseline, 3, and 12 months. OUTCOMES: We will compare implementation outcomes (acceptability, fidelity, penetration, costs, and sustainability) and effectiveness outcomes (viral suppression and alcohol use) between the two arms. We will assess the impact of site-level characteristics on scaling-up the BAI. We will also evaluate how experiencing the BAI affected clinical staff's alcohol use and clinic-level alcohol expectations in the EBAI arm. DISCUSSION: This trial contributes to implementation science by testing a novel strategy to implement a behavior change intervention in a setting in which clinicians themselves may engage in the behavior. Experiential learning may be useful to address normative and difficult to change lifestyle behaviors that contribute to chronic diseases. TRIAL REGISTRATION: NCT06358885 (04/10/2024), https://clinicaltrials.gov/study/NCT06358885 .

Clinical Features and Genomic Epidemiology of Bloodstream Infections due to Enterococcal Species Other Than Enterococcus faecalis or E. faecium in Patients With Cancer.

Background: Non-Enterococcus faecium, non-E. faecalis (NFF) enterococci are a heterogeneous group of clinically pathogenic enterococci that include species with intrinsic low-level vancomycin resistance. Patients with cancer are at increased risk for bacteremia with NFF enterococci, but their clinical and molecular epidemiology have not been extensively described. Methods: We conducted a retrospective review of all patients (n = 70) with NFF bacteremia from 2016 to 2022 at a major cancer center. The main outcomes assessed were 30-day mortality, microbiological failure (positive blood cultures for ≥4 days), and recurrence of bacteremia (positive blood culture <14 days after clearance). Whole-genome sequencing was performed on all available NFF (n = 65). Results: Patients with hematological malignancies made up 56% of the cohort (77% had leukemia). The majority of solid malignancies (87%) were gastrointestinal in origin. The majority of infections (83%) originated from an intra-abdominal source. The most common NFF species were E. gallinarum (50%) and E. casseliflavus (30%). Most (61%) patients received combination therapy. Bacteremia recurred in 4.3% of patients, there was a 30-day mortality of 23%, and 4.3% had microbiological failure. E. gallinarum and E. casseliflavus isolates were genetically diverse with no spatiotemporal clustering to suggest a single strain. Frequencies of ampicillin resistance (4.3%) and daptomycin resistance (1.9%) were low. Patients with hematologic malignancy had infections with NFF enterococci that harbored more resistance genes than patients with solid malignancy (P = .005). Conclusions: NFF bacteremia is caused by a heterogeneous population of isolates and is associated with significant mortality. Hematological malignancy is an important risk factor for infection with NFF resistant to multiple antibiotics.

Lateral canthal reconstruction for the treatment of macroblepharon/diamond eye conformation in dogs.

PURPOSE: To introduce a novel surgical technique for treatment of macroblepharon and diamond eye conformation in dogs. METHODS: Lateral canthal reconstruction was used in dogs with prominent eyelid malformations resulting in ocular surface disease. Lateral canthus was resected and new lateral canthus was created using a two-layer closure. This technique was performed either alone or in combination with additional procedure(s). Additionally, this technique was used to resect lateral canthal dermoid. RESULTS: One hundred and fifty-three eyes of 85 dogs were included in the study. Procedure was done for macroblepharon and/or lateral canthal entropion (149 eyes of 81 dogs) or for lateral canthal dermoid (four eyes of four dogs). Procedure was done either alone (n = 68 eyes) or in combination with additional procedure (n = 85 eyes). Favorable cosmetic outcome and client satisfaction was achieved in all dogs. Good to excellent functional outcome was recorded in all but 6 eyes of 4 dogs, which required additional surgery. Most common complications included slight undercorrection or overcorrection. CONCLUSIONS: Lateral canthal reconstruction is a simple yet effective surgical procedure for macroblepharon and/or lateral canthal entropion. If done early, it prevents development of secondary eyelid malformation ("pagoda defect") in giant breed dogs. If done after severe eyelid malformation has developed, combining this technique with concurrent pagoda resection is recommended to achieve ideal eyelid conformation. None.

ESKAPE pathogens: antimicrobial resistance, epidemiology, clinical impact and therapeutics.

The rise of antibiotic resistance and a dwindling antimicrobial pipeline have been recognized as emerging threats to public health. The ESKAPE pathogens - Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa and Enterobacter spp. - were initially identified as critical multidrug-resistant bacteria for which effective therapies were rapidly needed. Now, entering the third decade of the twenty-first century, and despite the introduction of several new antibiotics and antibiotic adjuvants, such as novel ß-lactamase inhibitors, these organisms continue to represent major therapeutic challenges. These bacteria share several key biological features, including adaptations for survival in the modern health-care setting, diverse methods for acquiring resistance determinants and the dissemination of successful high-risk clones around the world. With the advent of next-generation sequencing, novel tools to track and combat the spread of these organisms have rapidly evolved, as well as renewed interest in non-traditional antibiotic approaches. In this Review, we explore the current epidemiology and clinical impact of this important group of bacterial pathogens and discuss relevant mechanisms of resistance to recently introduced antibiotics that affect their use in clinical settings. Furthermore, we discuss emerging therapeutic strategies needed for effective patient care in the era of widespread antimicrobial resistance.

Biology in the 21st century: Natural selection is cognitive selection.

Natural selection has a formal definition as the natural process that results in the survival and reproductive success of individuals or groups best adjusted to their environment, leading to the perpetuation of those genetic qualities best suited to that organism's environmental niche. Within conventional Neo-Darwinism, the largest source of those variations that can be selected is presumed to be secondary to random genetic mutations. As these arise, natural selection sustains adaptive traits in the context of a 'struggle for existence'. Consequently, in the 20th century, natural selection was generally portrayed as the primary evolutionary driver. The 21st century offers a comprehensive alternative to Neo-Darwinian dogma within Cognition-Based Evolution. The substantial differences between these respective evolutionary frameworks have been most recently articulated in a revision of Crick's Central Dogma, a former centerpiece of Neo-Darwinism. The argument is now advanced that the concept of natural selection should also be comprehensively reappraised. Cognitive selection is presented as a more precise term better suited to 21st century biology. Since cognition began with life's origin, natural selection represents cognitive selection.

Creation and characterization of novel rat model for recessive dystrophic epidermolysis bullosa: Frameshift mutation of the Col7a1 gene leads to severe blistered phenotype.

Recessive dystrophic epidermolysis bullosa is a rare genodermatosis caused by a mutation of the Col7a1 gene. The Col7a1 gene codes for collagen type VII protein, a major component of anchoring fibrils. Mutations of the Col7a1 gene can cause aberrant collagen type VII formation, causing an associated lack or absence of anchoring fibrils. This presents clinically as chronic blistering, scarring, and fibrosis, often leading to the development of cutaneous squamous cell carcinoma. Patients also experience persistent pain and pruritus. Pain management and supportive bandaging remain the primary treatment options. The pathology of recessive dystrophic epidermolysis bullosa was first described in the 1980s, and there has since been a multitude of encouraging treatment options developed. However, in vivo research has been hindered by inadequate models of the disease. The various mouse models in existence possess longevity and surface area constraints, or do not adequately model a normal human disease state. In this paper, we describe a novel rat model of recessive dystrophic epidermolysis bullosa that offers an alternative to previous murine models. An 8-base pair deletion was induced in the Col7a1 gene of Lewis rats, which was subsequently found to cause a premature stop codon downstream. Homozygous mutants presented with a fragile and chronically blistered phenotype postnatally. Further histological analysis revealed subepidermal clefting and the absence of anchoring fibrils. The generation of this novel model offers researchers an easily maintained organism that possesses a larger surface area for experimental topical and transfused therapies to be tested, which may provide great utility in the future study of this debilitating disease.