Variations in subpectoral biceps tenodesis locations do not impact clinical outcomes.

Background: Biceps tenodesis is a common treatment for pathologies involving the long head of the biceps brachii. Given variations in surgical approach, focus has been placed on the location of the tenodesis to maintain appropriate length-tension relationship. The purpose of this study is to assess for variations in the tunnel placement in subpectoral biceps tenodesis procedures and correlation of tunnel position with patient-reported outcomes. Methods: This is a retrospective case series of outcomes as a function of tunnel location with open subpectoralis biceps tenodesis. The location of the biceps tenodesis tunnel was measured on postoperative Grashey radiographs. Correlation between the tenodesis tunnel and postoperative American Shoulder and Elbow Surgeons (ASES) score and Visual Analog Scale (VAS) was assessed. Results: 31 patients were included in the study with an average follow-up of 17 months. The overall tunnel position from the superior edge of the greater tuberosity ranged from 4.20 cm to 12.61 cm, with an average of 7.46 cm. Final ASES score and VAS were 84.5 and 1.2, respectively. There was only weak correlation between both ASES score and tunnel position (r = -0.12) and VAS and tunnel position (r = -0.23). Discussion: Subpectoralis biceps tenodesis continues to be a viable treatment option for biceps and superior labral pathology. There remains no consensus on tenodesis location, and this study found no significant difference between tunnel location and patient-reported outcomes. Therefore, it is likely that a range of tenodesis locations exists in which favorable clinical results are achieved, explaining the numerous recommendations on tunnel placement.

Tumor integrin targeted theranostic iron oxide nanoparticles for delivery of caffeic acid phenethyl ester: preparation, characterization, and anti-myeloma activities.

Multiple myeloma (MM) is characterized by the accumulation of malignant plasma cells preferentially in the bone marrow. Currently, emerging chemotherapy drugs with improved biosafety profiles, such as immunomodulatory agents and protease inhibitors, have been used in clinics to treat MM in both initial therapy or maintenance therapy post autologous hematopoietic stem cell transplantation (ASCT). We previously discovered that caffeic acid phenethyl ester (CAPE), a water-insoluble natural compound, inhibited the growth of MM cells by inducing oxidative stress. As part of our continuous effort to pursue a less toxic yet more effective therapeutic approach for MM, the objective of this study is to investigate the potential of CAPE for in vivo applications by using magnetic resonance imaging (MRI)-capable superparamagnetic iron oxide nanoparticles (IONP) as carriers. Cyclo (Arg-Gly-Asp-D-Phe-Cys) (RGD) is conjugated to IONP (RGD-IONP/CAPE) to target the overexpressed αvß3 integrin on MM cells for receptor-mediated internalization and intracellular delivery of CAPE. A stable loading of CAPE on IONP can be achieved with a loading efficiency of 48.7% ± 3.3% (wt%). The drug-release studies indicate RGD-IONP/CAPE is stable at physiological (pH 7.4) and basic pH (pH 9.5) and subject to release of CAPE at acidic pH (pH 5.5) mimicking the tumor and lysosomal condition. RGD-IONP/CAPE causes cytotoxicity specific to human MM RPMI8226, U266, and NCI-H929 cells, but not to normal peripheral blood mononuclear cells (PBMCs), with IC50s of 7.97 ± 1.39, 16.75 ± 1.62, and 24.38 ± 1.71 µM after 72-h treatment, respectively. Apoptosis assays indicate RGD-IONP/CAPE induces apoptosis of RPMI8226 cells through a caspase-9 mediated intrinsic pathway, the same as applying CAPE alone. The apoptogenic effect of RGD-IONP/CAPE was also confirmed on the RPMI8226 cells co-cultured with human bone marrow stromal cells HS-5 in a Transwell model to mimic the MM microenvironment in the bone marrow. In conclusion, we demonstrate that water-insoluble CAPE can be loaded to RGD-IONP to greatly improve the biocompatibility and significantly inhibit the growth of MM cells in vitro through the induction of apoptosis. This study paves the way for investigating the MRI-trackable delivery of CAPE for MM treatment in animal models in the future.

FlaxPack: Tailored Natural Fiber Reinforced (NFRP) Compliant Folding Corrugation for Reversibly Deployable Bending-Active Curved Structures.

As the use of Natural Fiber Reinforced Polymers (NFRPs) become increasingly popular in the built environment, steps in established workflows, including molding and transportation, continue to impose constraints on what is possible in the material's fabrication process. This research builds on previous studies of moldless fiber composites using tailored fiber placement (TFP) as a fabrication method. By integrating compliant folding mechanisms into the flat preform to give shape to the final desired geometry this research replaces all dependencies on molds and formworks during the resin curing process with programmed formal deformations. The desired geometry is digitally simulated from its two-dimensional state into its resultant three-dimensional state and then subsequently structurally analyzed. The flat pack components are material efficient and can be transported flat to the site for their final assembly into their programmed geometry. This form is locked into its bent active state through the use of a simple drawstring that can later be removed to revert the form back into its flat state. This method is demonstrated through the digital fabrication of a stool where flat-packed elements can be deployed into elegant solutions that embody structure, material, and form simultaneously.

Off-label: The results of adjunctive bone morphogenetic protein for challenging femur fractures; a review of two cases.

Background: Although bone morphogenetic proteins (BMPs) are used as an adjunct to promote healing, they may have unintended effects such as heterotopic ossification (HO). The literature is limited regarding the effect of using off-label BMPs for femur fractures. Case presentation: We report two outcomes after off-label use of BMPs for the treatment of femur fractures and propose a possible explanation for the difference. Conclusions: BMPs are critical osteoinductive factors in injured bone and muscle that facilitate bony healing. However, it may be important to recognize the potentially negative effects of adding BMP to bone graft material in certain cases to stimulate bone repair. We hope this case series helps surgeons consider the risks and benefits of using BMP for femur fractures, and therefore to decide with caution when BMP is indicated.

Nonintrusive thermal-wave sensor for operando quantification of degradation in commercial batteries.

Monitoring real-world battery degradation is crucial for the widespread application of batteries in different scenarios. However, acquiring quantitative degradation information in operating commercial cells is challenging due to the complex, embedded, and/or qualitative nature of most existing sensing techniques. This process is essentially limited by the type of signals used for detection. Here, we report the use of effective battery thermal conductivity (keff) as a quantitative indicator of battery degradation by leveraging the strong dependence of keff on battery-structure changes. A measurement scheme based on attachable thermal-wave sensors is developed for non-embedded detection and quantitative assessment. A proof-of-concept study of battery degradation during fast charging demonstrates that the amount of lithium plating and electrolyte consumption associated with the side reactions on the graphite anode and deposited lithium can be quantitatively distinguished using our method. Therefore, this work opens the door to the quantitative evaluation of battery degradation using simple non-embedded thermal-wave sensors.

Cytotoxic and Apoptotic Effects of Pinostilbene and Bortezomib Combination Treatment on Human Multiple Myeloma Cells.

Multiple myeloma (MM) is a cancer of plasma cells in the bone marrow characterized by bone lesions, hypercalcemia, anemia, and renal failure. Bortezomib (BTZ), a common treatment for MM, is a proteasome inhibitor that induces apoptosis in MM cells. However, high doses of BTZ can be very toxic, signifying a need for a synergistic drug combination to improve treatment efficacy. Resveratrol (RES), a phenolic compound found in grapes, has been shown to inhibit MM cell growth. We sought to identify a synergistic combination of BTZ with a RES derivative and analyze the effects on reducing viability and inducing apoptosis in human MM cells. BTZ as well as RES and its derivatives pinostilbene (PIN) and piceatannol (PIC) decreased MM cell viability in a dose- and time-dependent manner and increased expression of cleaved proapoptotic proteins poly(ADP-ribose) polymerase 1 (PARP1) and caspase-3 in a dose-dependent manner. The combination of 5 nM BTZ and 5 µM PIN was identified to have synergistic cytotoxic effects in MM RPMI 8226 cells. MM RPMI 8226 cells treated with this combination for 24 h showed increased cleaved PARP1 and caspase-3 expression and higher percentages of apoptotic cells versus cells treated with the individual compounds alone. The treatment also showed increased apoptosis induction in MM RPMI 8226 cells co-cultured with human bone marrow stromal HS-5 cells in a Transwell model used to mimic the bone marrow microenvironment. Expression of oxidative stress defense proteins (catalase, thioredoxin, and superoxide dismutase) in RPMI 8226 cells were reduced after 24 h treatment, and cytotoxic effects of the treatment were ameliorated by antioxidant N-acetylcysteine (NAC), suggesting the treatment impacts antioxidant levels in RPMI 8226 cells. Our results suggest that this combination of BTZ and PIN decreases MM cell viability synergistically by inducing apoptosis and oxidative stress in MM cells.

Extreme fast charging of commercial Li-ion batteries via combined thermal switching and self-heating approaches.

The mass adoption of electric vehicles is hindered by the inadequate extreme fast charging (XFC) performance (i.e., less than 15 min charging time to reach 80% state of charge) of commercial high-specific-energy (i.e., >200 Wh/kg) lithium-ion batteries (LIBs). Here, to enable the XFC of commercial LIBs, we propose the regulation of the battery's self-generated heat via active thermal switching. We demonstrate that retaining the heat during XFC with the switch OFF boosts the cell's kinetics while dissipating the heat after XFC with the switch ON reduces detrimental reactions in the battery. Without modifying cell materials or structures, the proposed XFC approach enables reliable battery operation by applying <15 min of charge and 1 h of discharge. These results are almost identical regarding operativity for the same battery type tested applying a 1 h of charge and 1 h of discharge, thus, meeting the XFC targets set by the United States Department of Energy. Finally, we also demonstrate the feasibility of integrating the XFC approach in a commercial battery thermal management system.

Unraveling Li growth kinetics in solid electrolytes due to electron beam charging.

Revealing the local structure of solid electrolytes (SEs) with electron microscopy is critical for the fundamental understanding of the performance of solid-state batteries (SSBs). However, the intrinsic structural information in the SSB can be misleading if the sample's interactions with the electron beams are not fully understood. In this work, we systematically investigate the effect of electron beams on Al-doped lithium lanthanum zirconium oxide (LLZO) under different imaging conditions. Li metal is observed to grow directly on the clean surface of LLZO. The Li metal growth kinetics and the morphology obtained are found to be heavily influenced by the temperature, accelerating voltage, and electron beam intensity. We prove that the lithium growth is due to the LLZO delithiation activated by a positive charging effect under electron beam emission. Our results deepen the understanding of the electron beam impact on SEs and provide guidance for battery material characterization using electron microscopy.

HSF1 Pathway Inhibitor Clinical Candidate (CCT361814/NXP800) Developed from a Phenotypic Screen as a Potential Treatment for Refractory Ovarian Cancer and Other Malignancies.

CCT251236 1, a potent chemical probe, was previously developed from a cell-based phenotypic high-throughput screen (HTS) to discover inhibitors of transcription mediated by HSF1, a transcription factor that supports malignancy. Owing to its activity against models of refractory human ovarian cancer, 1 was progressed into lead optimization. The reduction of P-glycoprotein efflux became a focus of early compound optimization; central ring halogen substitution was demonstrated by matched molecular pair analysis to be an effective strategy to mitigate this liability. Further multiparameter optimization led to the design of the clinical candidate, CCT361814/NXP800 22, a potent and orally bioavailable fluorobisamide, which caused tumor regression in a human ovarian adenocarcinoma xenograft model with on-pathway biomarker modulation and a clean in vitro safety profile. Following its favorable dose prediction to human, 22 has now progressed to phase 1 clinical trial as a potential future treatment for refractory ovarian cancer and other malignancies.

Using Thermal Interface Resistance for Noninvasive Operando Mapping of Buried Interfacial Lithium Morphology in Solid-State Batteries.

The lithium metal-solid-state electrolyte interface plays a critical role in the performance of solid-state batteries. However, operando characterization of the buried interface morphology in solid-state cells is particularly difficult because of the lack of direct optical access. Destructive techniques that require isolating the interface inadvertently modify the interface and cannot be used for operando monitoring. In this work, we introduce the concept of thermal wave sensing using modified 3ω sensors that are attached to the outside of the lithium metal-solid-state cells to noninvasively probe the morphology of the lithium metal-electrolyte interface. We show that the thermal interface resistance measured by the 3ω sensors relates directly to the physical morphology of the interface and demonstrates that 3ω thermal wave sensing can be used for noninvasive operando monitoring the morphology evolution of the lithium metal-solid-state electrolyte interface.

Discovery of a Potent and Orally Bioavailable Zwitterionic Series of Selective Estrogen Receptor Degrader-Antagonists.

Herein, we report the optimization of a meta-substituted series of selective estrogen receptor degrader (SERD) antagonists for the treatment of ER+ breast cancer. Structure-based design together with the use of modeling and NMR to favor the bioactive conformation led to a highly potent series of basic SERDs with promising physicochemical properties. Issues with hERG activity resulted in a strategy of zwitterion formation and ultimately in the identification of 38. This compound was shown to be a highly potent SERD capable of effectively degrading ERα in both MCF-7 and CAMA-1 cell lines. The low lipophilicity and zwitterionic nature led to a SERD with a clean secondary pharmacology profile and no hERG activity. Favorable physicochemical properties resulted in good oral bioavailability in preclinical species and potent in vivo activity in a mouse xenograft model.

Reproductive genetics laboratory may impact euploid blastocyst and live birth rates: a comparison of 4 national laboratories' PGT-A results from vitrified donor oocytes.

OBJECTIVE: To evaluate potential variation in the euploid blastocyst rate and live birth rate (LBR) per single frozen euploid blastocyst transfer, among 4 unique United States reproductive genetics laboratories. Analyses were limited to blastocysts derived from vitrified donor oocytes, to minimize variation in oocyte quality. DESIGN: Retrospective cohort study from 2016 to 2020. SETTING: Donor Egg Bank Database. PATIENT(S): Patients undergoing in vitro fertilization with donor oocytes. We excluded patients with uterine factor, male factor, or surgically extracted sperm. Only healthy women <34 years old were accepted as oocyte donors. INTERVENTION(S): Next generation sequencing platforms for chromosomal analysis MAIN OUTCOME MEASURE(S): Euploid blastocyst rate and LBR per euploid transfer. Secondary outcomes included the rate of aneuploidy, mosaic calls, biochemical pregnancy loss, and miscarriage rate. RESULT(S): A total of 2,633 embryos were included. Four laboratories had >200 embryos tested. Euploid blastocyst rate was significantly higher in laboratory A (73.6%) vs. B (63.3%), C (60.9%), and D (52.3%). Mosaic rate was significantly lower for Laboratories B (2.8%) and C (5.5%) vs. Laboratories A (9.9%) and D (11.5). The LBR was significantly higher in laboratory A (58.73%) vs. laboratory D (47.3%). There were no significant differences in the implantation or miscarriage rate among laboratories. CONCLUSION(S): In this large study, controlling for oocyte quality, some preimplantation genetic testing for aneuploidy (PGT-A) laboratories report a significantly higher euploid blastocyst rate with concurrent higher LBR. This type of comparison is important as it provides insight into the role of the PGT-A process in outcomes. Further research is needed to evaluate the differences in laboratory techniques and bioinformatic algorithms accounting for variable outcomes across PGT-A laboratories.

Surgically Treated Femoral Neck Stress Fractures Are Likely to Result in Military Separation During Basic Combat Training.

BACKGROUND: Femoral neck stress fractures are a common condition affecting military service members, most noticeably during basic combat training. Previous studies have investigated the risk factors for femoral neck stress fracture development in basic trainees and outcomes associated with treatment; however, few studies have focused on operatively treated femoral neck stress fracture in the military trainee. Doing so would be important not only for the military, but also providers caring for athletes, such as distance runners, who have a heightened risk for femoral neck stress fracture development. QUESTIONS/PURPOSES: (1) What proportion of US Army trainees completing basic combat training at Fort Jackson, SC, USA, who undergo surgery for femoral neck stress fracture during basic training subsequently leave military service because of the injury? (2) What factors are related to the patient or the fracture are associated with a higher likelihood of military separation? (3) What factors on the initial MRI are associated with progression of the stress fracture extent? METHODS: A retrospective study of a longitudinally maintained database of stress injuries involving basic combat trainees from a single military post was reviewed over a 3-year period. Inclusion criteria included basic trainees undergoing surgery for a femoral neck stress fracture between January 2018 and June 2020 with a minimum of 1-year follow-up. Surgery was indicated for service members with complete and tension-sided femoral neck stress fractures and those with high risk compression-sided stress fractures, generally representing fractures involving more than 50% of the femoral neck width. Over the study period, 57 service members (51% [29 of 57] women with a mean age of 24 years) underwent surgery for a femoral neck stress fracture, and all 57 had a minimum of 1-year follow-up. Identified service members underwent independent data collection including injury and radiographic parameters based on chart and imaging review. Documented fracture line progression on repeat imaging was present in 39% of service members, with a mean fracture line progression of 55% of the femoral neck width. Service members were subdivided based upon the ability to return to military service at 1 year. Univariate analysis was performed using patient and injury variables to identify factors associated with the ability to return to military service. RESULTS: Overall, 58% (33 of 57) of service members who had a femoral neck stress fracture treated surgically underwent military separation. A higher proportion of service members who demonstrated fracture line progression leading to surgical treatment remained in the military (58% [14 of 24] versus 30% [10 of 33]; odds ratio 0.3 [95% confidence interval (CI) 0.1 to 0.9]; p = 0.03). With the numbers available, we found no other patient- or fracture-related variables associated with military separation, although we suspect we may have been underpowered on some of these comparisons, in particular gender (61% [20 of 33] of individuals separated after surgery for this injury were women compared with 38% [9 of 24] who were retained; OR 2.6 [95% CI 0.9 to 7.56]; p = 0.09). The extent of osseous edema on T1-weighted imaging in association with a hip effusion demonstrated a significant positive correlation with final fracture percentage (r = 0.62; p = 0.003). CONCLUSION: Military service members with a femoral neck stress fracture initially managed nonoperatively but with progression of the fracture line requiring surgical intervention were more likely to return to military duties and complete basic combat training, suggesting that early diagnosis of femoral neck stress fractures may be associated with better functional recovery after surgical treatment. Additionally, the extent of the osseous edema on initial MRI T1-weighted imaging sequences may help predict the final extent of femoral neck stress fractures on repeat imaging. Further investigations should incorporate patient-reported outcomes and further explore factors associated with fracture progression and the inability to return to active duty or sport. LEVEL OF EVIDENCE: Level III, therapeutic study.

In vitro fertilization and andrology laboratories in 2030.

The in vitro fertilization and andrology laboratories are at the center of assisted reproductive technologies and the place where technicians and embryologists manipulate gametes and preimplantation-stage embryos with the goal of achieving the best embryo for transfer. Through the years, these laboratories have seen developments in technique, technology, and testing. The goal of this Views and Interviews series is to bring together the thought leaders in the field and envision what the laboratories will look like in the next 10 years.

In vitro fertilization and andrology laboratory in 2030: expert visions.

The aim of this article is to gather 9 thought leaders and their team members to present their ideas about the future of in vitro fertilization and the andrology laboratory. Although we have seen much progress and innovation in the laboratory over the years, there is still much to come, and this article looks at what these leaders think will be important in the future development of technology and processes in the laboratory.

Operative vs. Nonoperative Treatment of Isolated Humeral Shaft Fractures: A Prospective Cohort Study.

The purpose was to compare plate and screw fixation (open reduction internal fixation [ORIF]) and functional bracing (FB) of isolated humeral shaft fractures with treatment and patient-based outcomes. We performed a prospective trial of ORIF v. FB at 12 centers. Surgeons counseled patients on treatment options and a patient centered decision was made. We enrolled 179 patients, of which 6-month data was analyzed for 102 (39 female; 63 male). Forty-five were treated with ORIF and 57 with FB. We found no difference in the disability of the arm, shoulder and hand (DASH) score, visual analogue score (VAS) or elbow range of motion (ROM) at 6 months. However, 11% of the FB group developed nonunion. Complications in the ORIF group included a 2% infection and nonunion rate and 13% iatrogenic radial nerve dysfunction (RND). ORIF can be expected to result in higher union rates with the inherent risks of infection and RND. Finally, at 6 months, both groups demonstrated higher DASH scores than population norms, indicating a lack of full recovery. (Journal of Surgical Orthopaedic Advances 30(2):067-072, 2021).

Is There a Critical Radiographic Angle That Portends Poor Functional Outcome Scores in Nonoperative Treatment of Isolated Humeral Shaft Fractures?

Our purpose was to evaluate radiographic alignment of nonoperatively treated humerus fractures and determine if there is a critical angle associated with worse outcomes. All patients with humeral shaft fractures that were prospectively followed as part of a larger multicenter trial were reviewed. These patients were selected for nonoperative management based on shared decision making. There were 80 patients that healed with adequate data. The receiver operating characteristic (ROC) had best fit with a sagittal radiographic angle of 10° (AUC: 0.731) and coronal angle of 15° (AUC: 0.580) at 1-year follow-up. We found increased or worse disabilities of the arm, shoulder and hand (DASH) scores with > 10° sagittal alignment or > 15° of coronal alignment. Poor DASH scores were observed at angles lower than previously accepted for nonoperative treatment. These findings are useful in decision making and patient guidance. (Journal of Surgical Orthopaedic Advances 30(2):073-077, 2021).

Addition of Fluorine and a Late-Stage Functionalization (LSF) of the Oral SERD AZD9833.

Herein we describe our efforts using a late stage functionalization together with more traditional synthetic approaches to generate fluorinated analogues of the clinical candidate AZD9833. The effects of the addition of fluorine on the lipophilicity, permeability, and metabolism are discussed. Many of these changes were tolerated in terms of pharmacology and resulted in high quality molecules which reached advanced stages of profiling in the testing cascade.