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Establishing and maintaining social relationships is a critical developmental milestone for adolescents and young adults and can be disrupted by childhood adversities. Adverse and positive childhood experiences (ACEs and PCEs, respectively) represent independent, yet critical, domains that support the exploration of positive and adverse childhood experiences (PACEs) as pathways to social connection. Recent research has examined the impact of COVID-19 on child development. The current study expands on existing research by examining the effects that PACEs clusters and high school enrollment during COVID-19 had on social connectedness. Young adults (N = 211; M age  = 20.97 years, SD = 2.14) completed an online survey examining social functioning and childhood experiences. Two measures comprised PACEs: Benevolent Childhood Experiences (BCEs) scale and Adverse Childhood Experiences questionnaire. An adapted Berkman-Syme Social Network Index measured social connection. High school enrollment during COVID-19 was determined by graduation year. Cluster analyses identified three PACEs profiles: (1) high BCEs/low ACEs (74.9%), (2) moderate BCEs/high ACEs (14.7%), and (3) low BCEs/moderate ACEs (10.4%). Regression analyses showed that High Risk/High Protection (β = -3.326, p = .001) and Moderate Risk/Moderate Protection (β = -4.845, p < .001) profiles had significantly fewer social connections than the Low Risk/High Protection profile. High school enrollment at the COVID-19 onset did not predict social connection (β = 0.067, p = .305). Implications include clinicians considering PACEs when forming a holistic view of clients and integrating positive contexts into adversity research., (Copyright © 2024 Elsevier Inc. All rights reserved.)

The overwhelming majority of research on the role of gonadal hormones in behavioral development has focused on perinatal, pubertal, or adult life stages. The juvenile period has been overlooked because it is thought to be a time of gonadal quiescence. In the present study, we tested whether prepubertal gonadectomy impacts the behavior of male and female juvenile hamsters on the Light/Dark Box, Novel Object, and Social Approach tests (Experiment 1) and compared these findings to those obtained after adult gonadectomy (Experiment 2). Prepubertal ovariectomy increased exploration (i.e. time spent in the light zone of the Light/Dark Box) and novel object investigation of juveniles indicating an inhibitory role for the juvenile ovary; social approach was unaffected. In contrast, adult ovariectomy and castration (both prepubertal and adult) had no effect on any behavioral measure. Experiment 3 tested whether rearing hamsters in a short day length (SD), which delays puberty in this species, extends the interval of juvenile ovarian inhibition on exploration and novelty seeking. We also tested whether provision of estradiol reverses the effects of prepubertal ovariectomy. Hormonal manipulations and behavioral tests of Experiment 3 were conducted at ages when long day-reared hamsters are adult (as in Experiment 2), but SD-reared hamsters remain reproductively immature. Ovariectomy again increased exploration in the SD-reared juveniles despite the older age of surgery and testing. Estradiol treatment had no effect. These findings reveal a novel role for the juvenile ovary in exploration and novelty seeking that is unlikely to be mediated exclusively by estradiol., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Dysregulated arousal often accompanies neurodevelopmental disorders such as attention deficit hyperactivity disorder and autism spectrum disorder. Recently, we have found that adolescent homozygous Brattleboro (Hom) rats, which contain a mutation in the arginine vasopressin (AVP) gene, exhibit lower behavioral arousal than their heterozygous (Het) littermates in the open field test. This hypoaroused phenotype could be due to loss of AVP in magnocellular cells that supply AVP to the peripheral circulation and project to limbic structures or parvocellular cells that regulate the stress axis and other central targets. Alternatively, hypoarousal could be a side effect of diabetes insipidus - polydipsia and polyuria seen in Hom rats due to loss of AVP facilitation of water reabsorption in the kidney. We developed a viral-rescue approach to "cure" magnocellular AVP cells of their Brattleboro mutation. Infusion of a recombinant adeno-associated virus (rAAV) containing a functional Avp gene and promoter (rAAV-AVP) rescued AVP within magnocellular cells and fiber projections of the paraventricular nucleus of the hypothalamus (PVN) of male and female adolescent Hom rats. Furthermore, water intake was markedly reduced, ameliorating the symptoms of diabetes insipidus. In contrast, open field activity was unaffected. These findings indicate that the hyporaoused phenotype of adolescent Hom rats is not due to the loss of AVP function in magnocellular cells or a side effect of diabetes insipidus, but favors the hypothesis that central, parvocellular AVP mechanisms underlie the regulation of arousal during adolescence.

Among mammalian soft tissues, articular cartilage is particularly interesting because it can endure a lifetime of daily mechanical loading despite having minimal regenerative capacity. This remarkable resilience may be due to the depth-dependent mechanical properties, which have been shown to localize strain and energy dissipation. This paradigm proposes that these properties arise from the depth-dependent collagen fiber orientation. Nevertheless, this structure-function relationship has not yet been quantified. Here, we use confocal elastography, quantitative polarized light microscopy, and Fourier-transform infrared imaging to make same-sample measurements of the depth-dependent shear modulus, collagen fiber organization, and extracellular matrix concentration in neonatal bovine articular cartilage. We find weak correlations between the shear modulus |G(∗)| and both the collagen fiber orientation and polarization. We find a much stronger correlation between |G(∗)| and the concentration of collagen fibers. Interestingly, very small changes in collagen volume fraction vc lead to orders-of-magnitude changes in the modulus with |G(∗)| scaling as (vc - v0)(ξ). Such dependencies are observed in the rheology of other biopolymer networks whose structure exhibits rigidity percolation phase transitions. Along these lines, we propose that the collagen network in articular cartilage is near a percolation threshold that gives rise to these large mechanical variations and localization of strain at the tissue's surface., (Copyright © 2014 Biophysical Society. Published by Elsevier Inc. All rights reserved.)

There are few appropriate single-copy genetic tools for most Burkholderia species, and the high level of antibiotic resistance in this genus further complicates the development of genetic tools. In addition, the utilization of resistance genes for clinically important antibiotics is prohibited for the bioterrorism agents Burkholderia pseudomallei and Burkholderia mallei, necessitating the development of additional nonantibiotic-based genetic tools. Three single-copy systems devoid of antibiotic selection based on two nonantibiotic selectable markers, tellurite resistance (Tel(r)) and Escherichia coli aspartate-semialdehyde dehydrogenase (asd(Ec)), were developed to facilitate genetic manipulation in Burkholderia species. These systems include one mariner transposon, a mini-Tn7-derived site-specific transposon, and six FRT reporter fusion vectors based on the lacZ, gfp, and luxCDABE reporter genes. Initially, we showed that the random mariner transposon pBT20-Deltabla-Tel(r)-FRT efficiently transposed within Burkholderia cenocepacia, Burkholderia thailandensis, B. pseudomallei, and B. mallei. We then utilized the mini-Tn7-Tel(r)-based transposon vector (mini-Tn7-Tel(r)-betBA) and a transposase-containing helper plasmid (pTNS3-asd(Ec)) to complement the B. thailandensis DeltabetBA mutation. Next, one of the FRT-lacZ fusion vectors (pFRT1-lacZ-Tel(r)) was integrated by Flp (encoded on a helper plasmid, pCD13SK-Flp-oriT-asd(Ec)) to construct the B. thailandensis DeltabetBA::FRT-lacZ-Tel(r) reporter fusion strain. The betBA operon was shown to be induced in the presence of choline and under osmotic stress conditions by performing beta-galactosidase assays on the B. thailandensis DeltabetBA::FRT-lacZ-Tel(r) fusion strain. Finally, we engineered B. thailandensis DeltabetBA::FRT-gfp-Tel(r) and DeltabetBA::FRT-lux-Tel(r) fusion strains by utilizing fusion vectors pFRT1-gfp-Tel(r) and pFRT1-lux-Tel(r), respectively. The induction of the betBA operon by choline and osmotic stress was confirmed by performing fluorescent microscopy and bioluminescent imaging analyses.

Allelic replacement in the Burkholderia genus has been problematic due to the lack of appropriate counter-selectable and selectable markers. The counter-selectable marker sacB, commonly used in gram-negative bacteria, is nonselective on sucrose in many Burkholderia species. In addition, the use of antibiotic resistance markers of clinical importance for the selection of desirable genetic traits is prohibited in the United States for two potential bioterrorism agents, Burkholderia mallei and Burkholderia pseudomallei. Here, we engineered a mutated counter-selectable marker based on the B. pseudomallei PheS (the alpha-subunit of phenylalanyl tRNA synthase) protein and tested its effectiveness in three different Burkholderia species. The mutant PheS protein effectively killed 100% of the bacteria in the presence of 0.1% p-chlorophenylalanine. We assembled the mutant pheS on several allelic replacement vectors, in addition to constructing selectable markers based on tellurite (Tel(r)) and trimethoprim (Tp(r)) resistance that are excisable by flanking unique FLP recombination target (FRT) sequences. As a proof of concept, we utilized one of these gene replacement vectors (pBAKA) and the Tel(r)-FRT cassette to produce a chromosomal mutation in the Burkholderia thailandensis betBA operon, which codes for betaine aldehyde dehydrogenase and choline dehydrogenase. Chromosomal resistance markers could be excised by the introduction of pFLP-AB5 (Tp(r)), which is one of two constructed flp-containing plasmids, pFLP-AB4 (Tel(r)) and pFLP-AB5 (Tp(r)). These flp-containing plasmids harbor the mutant pheS gene and allow self curing on media that contain p-chlorophenylalanine after Flp-FRT excision. The characterization of the Delta betBA::Tel(r)-FRT and Delta betBA::FRT mutants indicated a defect in growth with choline as a sole carbon source, while these mutants grew as well as the wild type with succinate and glucose as alternative carbon sources.

The authors have previously reported on the laboratory development of the Acrobot Navigation System for accurate computer-assisted hip resurfacing surgery. This paper describes the findings of using the system in the clinical setting and including the improvements that have been made to expedite the procedure. The aim of the present system is to allow accurate planning of the procedure and precise placement of the prosthesis in accordance with the plan, with a zero intraoperative time penalty in comparison to the standard non-navigated technique. At present the navigation system is undergoing final clinical evaluation prior to a clinical study designed to demonstrate the accuracy of outcome compared with the conventional technique. While full results are not yet available, this paper describes the techniques that will be used to evaluate accuracy by comparing pre-operative computed tomography (CT)-based plans with post-operative CT scans. Example qualitative clinical results are included based on visual comparison of the plan with post-operative X-rays.

A brief history of robotic systems in knee arthroplasty is provided. The place of autonomous robots is then discussed and compared to more recent 'hands-on' robotic systems that can be more cost effective. The case is made for robotic systems to have a clear justification, with improved benefits compared to those from cheaper navigation systems. A number of more recent, smaller, robot systems for knee arthroplasty are also described. A specific example is given of an active constraint medical robot, the ACROBOT system, used in a prospective randomized controlled trial of unicondylar robotic knee arthroplasty in which the robot was compared to conventional surgery. The results of the trial are presented together with a discussion of the need for measures of accuracy to be introduced so that the efficacy of the robotic surgery can be immediately identified, rather than have to wait for a number of years before long-term clinical improvements can be demonstrated.

Surgeons need to be able to measure angles and distances in three dimensions in the planning and assessment of knee replacement. Computed tomography (CT) offers the accuracy needed but involves greater radiation exposure to patients than traditional long-leg standing radiographs, which give very little information outside the plane of the image. There is considerable variation in CT radiation doses between research centres, scanning protocols and individual scanners, and ethics committees are rightly demanding more consistency in this area. By refining the CT scanning protocol we have reduced the effective radiation dose received by the patient down to the equivalent of one long-leg standing radiograph. Because of this, it will be more acceptable to obtain the three-dimensional data set produced by CT scanning. Surgeons will be able to document the impact of implant position on outcome with greater precision.

Hip resurfacing is an alternative to total hip replacement (THR) and is particularly suitable for the younger, more active patient. However, it is a more demanding procedure. This paper describes a system that enables the surgeon to plan the surgery preoperatively with optimally sized and placed components, and then transfer this plan to an intraoperative system that registers computer models to the real patient and tracks surgical tools, allowing the surgeon to ensure that the bone is resected correctly and that the components are fitted in accordance with the plan. The paper describes a series of instruments used with the system which are locked to the bone. These instruments serve the dual purpose of soft tissue retraction and bone immobilization. The system will shortly be the subject of laboratory and clinical evaluation. Registration, a cornerstone of the tracked instrument system, has been tested, and accuracy measures are provided. Experimental results for the remainder of the system will be provided after clinical trials.

A generic framework for a computer-assisted system for both soft tissue endoscopic surgery and surgical training is being researched and developed. The concept demonstrator is a specific system for transurethral prostatic resection (TURP). The main novelty of the research is that it is not confined to an in vitro trainer system. An in vivo monitoring version of the system, for use in the operating theater, is also being researched. This paper presents the framework's structure and design using the United Modeling Language. It also discusses and justifies the underlying information technologies chosen to implement this approach. Object-oriented concepts and well-proven mathematical tools have been adopted as the foundation of this research and development. The rationale for having chosen such tools is presented. The objectives are to arrive at a system which is modular, general, and reusable.