Physical Therapy Management for a 16-year old Female Following Arthroscopic Plica Resection and Partial Synovectomy: A Case Report

Background and Purpose. Synovial plica is a common abnormality found primarily in the knee joint. Plicae can become irritated and inflamed with repeated motions causing pain and limited range of motion. Conservative management of symptoms is often the first method of treatment. However, surgical excision is considered if symptoms still persist. Case Description. The patient is a 16-year-old female referred to physical therapy (PT) for post-arthroscopic management of a left plica resection and partial synovectomy. The patient presented with limited strength, range of motion and increased pain, congruent with her post-operative condition. The patient was seen by PT 2 times per week for 7 weeks. Intervention. Physical therapy management focused on implementing blood flow restriction training (BFR) along with neuromuscular reeducation (NMR), stretching, and gait training to improve her overall functional status and return to prior level of function. Outcomes. The patient’s Focus on Therapeutic Outcome Measure (FOTO) score improved from a 62/100 to a 84/100, visual analog scale (VAS) from a 3/10 to a 0/10, and improved strength from a 3/5 to 5/5 in the left lower extremity. The patients left knee range of motion was also normalized to \u3e120 degrees of flexion and 0 degrees of extension. Discussion. This case report outlines how a combination of BFR training, NMR, stretching, and gait training can improve the functional status of a patient post- arthroscopic plica resection. Limited literature is available on post-operative management for patient who had undergone arthroscopic knee surgery for a plica resection. More research is needed to define the appropriate PT treatment methods for those with a similar post-operative condition

The Cost of Confusion: The Paradox of Trademarked Pharmaceuticals

The United States spends nearly $1,000 per person annually on drugs—forty percent more than the next highest spender, Canada, and more than twice the amount France and Germany spend. Although myriad factors contribute to high drug spending in the United States, intellectual property law plays a crucial and well-documented role in inhibiting access to cheaper, generic medications. Yet, for the most part, the discussion of the relationship between intellectual property law and drug spending has centered on patent protection. Recently, however, a few researchers have turned their attention to a different avenue of exclusivity—trademark law. New studies suggest that pharmaceutical trademarks are diminishing the ability of physicians and consumers to accurately understand the relationship between generic and brand name medications. This Article synthesizes and relies on that research to demonstrate that trademarks in the pharmaceutical industry are at odds with the theoretical foundations of trademark law. The conventional justification for trademark protection is two pronged: trademarks not only minimize consumer confusion but also ensure manufacturers maintain consistent product quality. Relying on pharmaceutical case studies and behavioral research, this Article contends that pharmaceutical trademarks and trade dress are performing the opposite functions. Instead of reducing consumer confusion and enhancing market efficiency, pharmaceutical trademarks are actually confusing patients into believing that trademarked and generic drugs are distinct medications, leading to wasteful spending and even substantial morbidity. Accordingly, this Article encourages policymakers to reexamine the utility of trademarks in the pharmaceutical industry and ultimately suggests that such trademarked names should be replaced with a different type of mark—one that serves to distinguish a drug’s manufacturer without differentiating the drug itself from identical generics. Such an approach has the potential to not only save millions of dollars, but also improve patient outcomes

Developmental Basis of Pronephric Defects in Xenopus Body Plan Phenotypes

AbstractWe have used monoclonal antibodies that recognize the pronephric tubules or pronephric duct to explore the induction of the embryonic kidney in developing Xenopus embryos. Morphogenesis of the pronephros was examined in UV-ventralized and lithium-dorsalized embryos. We find that the pronephric tubules are present in all but the strongest UV-induced phenotypes, but absent from relatively moderate lithium phenotypes. Interestingly the pronephric duct, which develops from the ventroposterior portion of the pronephric anlage, is missing from more of the mild UV phenotypes than are pronephric tubules. The loss of the capacity to form pronephroi in UV-ventralized embryos is caused by the loss of tissues capable of inducing the pronephric mesoderm, as marginal zone explants from ventralized embryos are still competent to respond to pronephric-inductive signals. Explant recombination experiments indicate that the tissue responsible for both the loss of pronephroi in UV-ventralized embryos and the induction of pronephroi during normal development is the anterior somites. The absence of pronephroi in relatively mild lithium phenotypes has a developmental basis different from that of the UV phenotype, as explants from lithium-treated embryos are effective inducers of pronephroi in recombinants with competent mesoderm, even though they themselves do not form pronephroi in isolation. Together these data indicate that dorsal tissues, especially the anterior somites, are responsible for the establishment of the intermediate mesoderm and the induction of the embryonic kidneys and that even mild dorsalization destroys the capacity to form cells competent to receive this signal

CAPSTONE: Recovery & Operations of a Tumbling Small Satellite in Deep Space

The Cislunar Autonomous Positioning System Technology Operations and Navigation Experiment (CAPSTONE) satellite, deployed in July 2022, experienced a thruster anomaly in September 2022 during its Ballistic Lunar Transfer (BLT) into the Earth-Moon L2 Near Rectilinear Halo Orbit (NRHO). CAPSTONE\u27s primary mission objective to achieve and maintain NRHO serves to validate the cislunar CONOPS contemplated for NASA\u27s Lunar Gateway. Terran Orbital designed and built CAPSTONE, and serves as the operator of the on-orbit spacecraft. Advanced Space owns and operates the CAPSTONE payload and its software on behalf of NASA, as well as performs mission navigation and maneuver design. This 12U+ lunar nanosatellite contains a pump-fed hydrazine propulsion system from Stellar Exploration, enabling all orbital maneuvers and momentum management for the mission. The CAPSTONE mission is funded by the NASA Space Technology Mission Directorate (STMD) through the Small Spacecraft Technology program, and by the Human Exploration and Operations Mission Directorate (HEOMD) through the Advanced Exploration Systems program. This paper will examine the timeline, innovation, and steps taken by the spacecraft team to recover the vehicle from the thruster anomaly and the resulting high-rate tumble. The high-rate tumble was induced by a valve which became stuck open at the conclusion of Trajectory Correction Maneuver 3 (TCM-3). The timeline discussion includes initial autonomous fault recovery, the evolution of the state of the vehicle, and the recovery actions taken by a small, agile engineering team. The off-nominal attitude and thermal state was determined from a limited data set, requiring the largest assets in NASA\u27s Deep Space Network (DSN) to support communications with the vehicle. Once a determination was made that the hydrazine propellant was freezing, an assessment was made on the minimum amount of heat required to thaw propellant without placing the spacecraft in a power-negative state. The integrated spacecraft team performed root cause analysis and incrementally tested the propulsion system to recommission it in the face of an anomalous thruster valve. The recommissioning approach eventually lead to the development of a new propulsive state machine and Guidance Navigation and Control (GNC) thruster controller for detumbling. After recovering 3-axis attitude control, power and thermal stability, and establishing nominal communications, significant development and testing was required to ensure the vehicle could operate in the presence of a continued thruster anomaly. This effort enabled CAPSTONE to execute future propulsive maneuvers with an open thruster valve. The resultant updates were tested on Terran Orbital\u27s Hardware-in-the-Loop (HITL) platform in partnership with Stellar Exploration. A comparison of GNC subsystem requirements will be presented pre-and post-anomaly, based on the resulting capability and restrictions of the propulsion system to meet mission objectives. Ultimately, the spacecraft was successfully recovered from body rates exceeding 120 deg/s, allowing the CAPSTONE spacecraft to continue its mission, including successful insertion into NRHO in November 2022. An examination of the lessons learned for future deep space small satellite missions is also discussed herein

Sellar Remodeling after Surgery for Nonfunctioning Pituitary Adenoma: Intercarotid Distance as a Predictor of Recurrence

Introduction  As they grow, pituitary adenoma can remodel the sella turcica and alter anatomical relationships with adjacent structures. The intercarotid distance (ICD) at the level of the sella is a measure of sella width. The purpose of this study was to (1) assess how ICD changes after transsphenoidal surgery and (2) explore whether the extent of ICD change is associated with tumor recurrence. Methods  A retrospective analysis of preoperative and postoperative coronal magnetic resonance imaging (MRI) scans was carried out by two independent assessors on patients who underwent transsphenoidal surgery for nonfunctioning pituitary macroadenomas. Preoperative tumor volume and any change in ICD following surgery were recorded and compared between groups. Logistic regression models of recurrence were generated. Results  In 36 of 42 patients, ICD fell after surgery (mean = 1.8 mm) and six cases were static. At time of follow-up (mean = 77 months), 25 had not required further intervention and 17 had undergone second surgery or radiosurgery. In patients in whom no further intervention has yet been necessary, the postoperative reduction in ICD was significantly smaller than in those who required repeat intervention (1.1 vs. 2.7 mm respectively, p  < 0.01). ICD decrease was weakly correlated with tumor volume ( r  = 0.35). ICD decrease was a significant predictor of recurrence (odds ratio [OR] = 3.15; 95% confidence interval [CI]: 1.44–6.87), largely independent of tumor volume. Conclusion  For most patients, ICD falls following surgical excision of a nonfunctioning pituitary macroadenoma. A greater reduction in ICD postsurgery appears to predict recurrence. Change in ICD shows promise as a radiographic tool for prognosticating clinical course after surgery

Regulation of breast cancer stem cell activity by signaling through the Notch4 receptor

The Notch receptor signalling pathway plays an important role in breast development, regulation of stem cells and differentiation of luminal progenitor cells. The pathway also plays a significant role in breast cancer development and progression. However, which of the Notch receptors that regulate breast cancer stem cells is unknown. We assessed stem cell activity in breast cancer cell lines and nine primary human tumour samples. In vitro and in vivo breast cancer stem cell activity was enriched using selection of anoikis resistant cells or cells expressing the membrane phenotype ESA(+)/CD44(+)/CD24(low). We compared the activation of Notch receptors in the breast cancer stem cell-enriched population to luminally differentiated cells and studied the effects of pathway inhibition, both in vitro and in vivo. We find that Notch4 signalling activity is 8-fold higher in the breast cancer stem cell-enriched cells compared to the differentiated cells while Notch1 activation is 4-fold lower in breast cancer stem cells. Furthermore, pharmacological or genetic Notch inhibition markedly reduced breast cancer stem cell activity in vitro, and significantly reduced tumour formation in vivo. Importantly, cells with Notch4 knock-down using specific shRNA formed fewer mammosphere colonies than Notch1 knock-down cells. In vivo Notch1 knock-down, like pharmacological inhibition, reduced the number and size of tumours but Notch4 knock-down suppressed tumour initiation completely. Our findings indicate that Notch4-targeted therapies will be more effective than targeting Notch1 in suppressing breast cancer recurrence initiated by breast cancer stem cells

Assessment of the reproducibility and inter-site transferability of the murine direct splenocyte mycobacterial growth inhibition assay (MGIA)

Tuberculosis (TB) vaccine candidates must be tested for safety and efficacy using preclinical challenge models prior to advancement to human trials, because of the lack of a validated immune correlate or biomarker of protection. New, unbiased tools are urgently needed to expedite the selection of vaccine candidates at an early stage of development and reduce the number of animals experimentally infected with virulent Mycobacterium tuberculosis (M.tb). In recent years, there has been a concerted effort to develop standardised functional ex vivo mycobacterial growth inhibition assays (MGIAs) as a potential surrogate read-out of vaccine efficacy. We have previously described a direct MGIA for use with mouse splenocytes. In the current study, we set out to systematically compare co-culture conditions for the murine direct splenocyte MGIA with respect to both intra-assay repeatability and inter-site reproducibility. Common sample sets were shared between laboratory sites and reproducibility and sensitivity to detect a BCG-vaccine induced response were assessed. Co-culturing 5×106 splenocytes in 48-well plates resulted in improved reproducibility and superior sensitivity to detect a vaccine response compared with standing or rotating sealed 2ml screw-cap tubes. As the difference between naïve and BCG vaccinated mice was not consistently detected across both sample sets at both sites, we sought to further improve assay sensitivity by altering the multiplicity of infection (MOI). Cell viability at the end of the co-culture period was improved when splenocyte input number was reduced, with the highest viability for the condition of 3×106 splenocytes in 48-well plates. This cell input was also associated with the greatest sensitivity to detect a BCG vaccine-mediated MGIA response using an M.tb inoculum. Based on our findings, we recommend optimal co-culture conditions in a move towards aligning direct MGIA protocols and generating a cross-species consensus for early evaluation of TB vaccine candidates and biomarker studies

Time to improve informed consent for dialysis: an international perspective

The literature reveals that current nephrology practice in obtaining informed consent for dialysis falls short of ethical and legal requirements. Meeting these requirements represents a significant challenge, especially because the benefits and risks of dialysis have shifted significantly with the growing number of older, comorbid patients. The importance of informed consent for dialysis is heightened by several concerns, including: (1) the proportion of predialysis patients and patients on dialysis who lack capacity in decision making and (2) whether older, comorbid, and frail patients understand their poor prognosis and the full implications to their independence and functional status of being on dialysis. This article outlines the ethical and legal requirements for a valid informed consent to dialysis: (1) the patient was competent, (2) the consent was made voluntarily, and (3) the patient was given sufficient information in an understandable manner to make the decision. It then considers the application of these requirements to practice across different countries. In the process of informed consent, the law requires a discussion by the physician of the material risks associated with dialysis and alternative options. We argue that, legally and ethically, this discussion should include both the anticipated trajectory of the illness and the effect on the life of the patient with particular regard to the outcomes most important to the individual. In addition, a discussion should occur about the option of a conservative, nondialysis pathway. These requirements ensure that the ethical principle of respect for patient autonomy is honored in the context of dialysis. Nephrologists need to be open to, comfortable with, and skillful in communicating this information. From these clear, open, ethically, and legally valid consent discussions, a significant dividend will hopefully flow for patients, families, and nephrologists alike

A method for extracting electronic patient record data from practice management software systems used in veterinary practice

BackgroundData extracted from electronic patient records (EPRs) within practice management software systems are increasingly used in veterinary research. The use of real patient data gives the potential to generate research that can readily be applied to clinical practice. The use of veterinary EPRs for research in the United Kingdom is hindered by the number of different Practice Management System (PMS) providers used by practices, as obtaining and combining data from different systems electronically can be problematic. The use of extensible mark up language (XML) to extract clinical data for research would potentially resolve the compatibility issues between systems. The aim of this study was to establish and validate a method for the extraction of small animal patient records from a veterinary PMS that could potentially be used across multiple systems. An XML schema was designed to extract clinical information from EPRs. The schema was tested and validated in a test system, and was then tested in a real small animal practice where data was extracted for 16 weeks. A 10 % sample of the extracted records was then compared to paper copies provided by the practice.ResultsAll 21 fields encoded by the XML schema, from all of the records in the test system, were extracted with 100 % accuracy. Over the 18 week data collection period 4946 records, from 1279 patients, were extracted from the small animal practice. The 10 % printed records checked and compared with the XML extracted records demonstrated all required data was present. No unrequired, sensitive information e.g. costs or services/products or personal client information was extracted.ConclusionsThis is the first time a method for data extraction from EPRs in veterinary practice using an XML schema has been reported in the United Kingdom. This is an efficient and accurate way of extracting data which could be applied to all PMSs nationally and internationally

Capturing health and eating status through a nutritional perception screening questionnaire (NPSQ9) in a randomised internet-based personalised nutrition intervention : the Food4Me study

BACKGROUND: National guidelines emphasize healthy eating to promote wellbeing and prevention of non-communicable diseases. The perceived healthiness of food is determined by many factors affecting food intake. A positive perception of healthy eating has been shown to be associated with greater diet quality. Internet-based methodologies allow contact with large populations. Our present study aims to design and evaluate a short nutritional perception questionnaire, to be used as a screening tool for assessing nutritional status, and to predict an optimal level of personalisation in nutritional advice delivered via the Internet. METHODS: Data from all participants who were screened and then enrolled into the Food4Me proof-of-principle study (n = 2369) were used to determine the optimal items for inclusion in a novel screening tool, the Nutritional Perception Screening Questionnaire-9 (NPSQ9). Exploratory and confirmatory factor analyses were performed on anthropometric and biochemical data and on dietary indices acquired from participants who had completed the Food4Me dietary intervention (n = 1153). Baseline and intervention data were analysed using linear regression and linear mixed regression, respectively. RESULTS: A final model with 9 NPSQ items was validated against the dietary intervention data. NPSQ9 scores were inversely associated with BMI (β = -0.181, p < 0.001) and waist circumference (Β = -0.155, p < 0.001), and positively associated with total carotenoids (β = 0.198, p < 0.001), omega-3 fatty acid index (β = 0.155, p < 0.001), Healthy Eating Index (HEI) (β = 0.299, p < 0.001) and Mediterranean Diet Score (MDS) (β = 0. 279, p < 0.001). Findings from the longitudinal intervention study showed a greater reduction in BMI and improved dietary indices among participants with lower NPSQ9 scores. CONCLUSIONS: Healthy eating perceptions and dietary habits captured by the NPSQ9 score, based on nine questionnaire items, were associated with reduced body weight and improved diet quality. Likewise, participants with a lower score achieved greater health improvements than those with higher scores, in response to personalised advice, suggesting that NPSQ9 may be used for early evaluation of nutritional status and to tailor nutritional advice. TRIAL REGISTRATION: NCT01530139 .Peer reviewedFinal Published versio