Mechanisms of bone development and repair.

Bone development occurs through a series of synchronous events that result in the formation of the body scaffold. The repair potential of bone and its surrounding microenvironment - including inflammatory, endothelial and Schwann cells - persists throughout adulthood, enabling restoration of tissue to its homeostatic functional state. The isolation of a single skeletal stem cell population through cell surface markers and the development of single-cell technologies are enabling precise elucidation of cellular activity and fate during bone repair by providing key insights into the mechanisms that maintain and regenerate bone during homeostasis and repair. Increased understanding of bone development, as well as normal and aberrant bone repair, has important therapeutic implications for the treatment of bone disease and ageing-related degeneration.

Single-route CNS prophylaxis for aggressive non-Hodgkin lymphomas: real-world outcomes from 21 US academic institutions.

Prophylaxis is commonly used to prevent central nervous sy stem (CNS) relapse in diffuse large B-cell lymphoma (DLBCL), with no clear standard of care. We retrospectively evaluated 1162 adult patients across 21 US academic centers with DLBCL or similar histologies who received single-route CNS prophylaxis as part of frontline therapy between 2013 and 2019. Prophylaxis was administered intrathecally(IT) in 894 (77%) and using systemic high-dose methotrexate (HD-MTX) in 236 (20%); 32 patients (3%) switched route due to toxicity and were assessed separately. By CNS-International Prognostic Index (IPI), 18% were considered low-risk, 51% moderate, and 30% high. Double-hit lymphoma (DHL) was confirmed in 243 of 866 evaluable patients (21%). Sixty-four patients (5.7%) had CNS relapse after median 7.1 months from diagnosis, including 15 of 64 (23%) within the first 6 months. There was no significant difference in CNS relapse between IT and HD-MTX recipients (5.4% vs 6.8%, P = .4), including after propensity score matching to account for differences between respective recipient groups. Weighting by CNS-IPI, expected vs observed CNS relapse rates were nearly identical (5.8% vs 5.7%). Testicular involvement was associated with high risk of CNS relapse (11.3%) despite most having lower CNS-IPI scores. DHL did not significantly predict for CNS relapse after single-route prophylaxis, including with adjustment for treatment regimen and other factors. This large study of CNS prophylaxis recipients with DLBCL found no significant difference in CNS relapse rates between routes of administration. Relapse rates among high-risk subgroups remain elevated, and reconsideration of prophylaxis strategies in DLBCL is of critical need.

Decoding the effect of photoperiodic cues in transducing kisspeptin-melatonin circuit during the pubertal onset in common carp.

This study unravels the intricate interplay between photoperiod, melatonin, and kisspeptin to orchestrate the pubertal onset of Common carp. Female fingerlings exposed to long days (LD) exhibited a hormonal crescendo, with upregulated hypothalamic-pituitary-ovarian (HPO) axis genes (kiss1, kiss1r, kiss2, gnrh2, gnrh3) and their downstream targets (lhr, fshr, ar1, esr1). However, the expression of the melatonin receptor (mtnr1a) diminished in LD, suggesting a potential inhibitory role. This hormonal symphony was further amplified by increased activity of key transcriptional regulators (gata1, gata2, cdx1, sp1, n-myc, hoxc8, plc, tac3, tacr3) and decreased expression of delayed puberty genes (mkrn1, dlk1). In contrast, short days (SD) muted this hormonal chorus, with decreased gnrh gene and regulator expression, elevated mtnr1a, and suppressed gonadal development. In in-vitro, estradiol mimicked the LD effect, boosting gnrh and regulator genes while dampening mtnr1a and melatonin-responsive genes. Conversely, melatonin acted as a conductor, downregulating gnrh and regulator genes and amplifying mtnr1a. Our findings illuminate the crucial roles of melatonin and kisspeptin as opposing forces in regulating pubertal timing. LD-induced melatonin suppression allows the kisspeptin symphony to flourish, triggering GnRH release and, ultimately, gonadal maturation. This delicate dance between photoperiod, melatonin, and kisspeptin orchestrates common carp's transition from juvenile to reproductive life.

T-cell prolymphocytic leukemia: Epidemiology and survival trends in the era of novel treatments.

Survival remains poor for T-cell prolymphocytic leukemia, though treatment in recent years, associated with access to novel therapies, and management at academic medical centers is associated with improved outcomes. There remains a critical need to improve the available treatment options for this population, and access to specialized academic medical centers, comprehensive supportive care, clinical trials, and early palliative care remains essential for T-PLL patients.

Phase Transitions Involving Channel Hydrates of a New Pharmaceutical Compound.

INTRODUCTION: Hydrates are often used as pharmaceutical active pharmaceutical ingredients (API), especially when anhydrates may not be feasible likely due to physicochemical properties concerns. Pharmaceutical hydrates, whereas water is present as crystal adduct, are feasible for drug products as they do not pose any safety concern. Hydrates can impart many different advantages; therefore, they are quite common and preferred solid forms for numerous pharmaceutical materials on market. However, hydrates may involve various phase transitions, which may impact the stability and processability of drug substance. METHODS: Phase transitions, which include temperature-induced dehydration and moisture-facilitated rehydration are investigated by different solid-state analytical techniques such as powder x-ray diffraction, thermogravimetric analysis, differential scanning calorimetry, polarized light microscopy, and single-crystal x-ray diffraction. RESULTS: This research investigation focuses on the different phase transition behaviors of a newly discovered pharmaceutical compound with three channel hydrates, two of which confirmed by single-crystal analysis. The retention or rearrangement of crystal structures over the transitions are studied. Hydrate 3 exhibits a characteristic feature of channel hydrate that involves symmetric lattice relaxation. Unlike hydrate 3, hydrate 2 results in a potentially new unit cell upon dehydration due to asymmetric lattice relaxation, which converted back to Hydrate 2 in presence of water, a very unique behavior for a channel hydrate, rarely observed, which entails novelty of this research work. CONCLUSION: The relationship among crystal forms of different hydrates of this new compound is thus established. The current investigation is a vital part of drug product risk assessment for hydrates to avoid any challenges during manufacturing operations and/or stability studies. This investigation was successfully applied in the present study and can be expanded to other newly discovered APIs in future.

Anconeus Muscle Transfer to Correct or Prevent Wrist Radial Deviation in Radial and Posterior Interosseous Nerve Injuries.

PURPOSE: Wrist radial deviation is a possible complication of tendon transfer for restoration of wrist extension in cases of radial nerve paralysis. In posterior interosseous nerve (PIN) injury, this is because of the imbalance caused by the intact extensor carpi radialis longus and paralysis of the extensor carpi ulnaris (ECU). This deformity may also occur following transfer of the pronator teres (PT) to the extensor carpi radialis brevis (ECRB) for radial nerve palsy. To address wrist radial deviation, we propose transferring the anconeus muscle, extended by the intermuscular septum between the ECU and the flexor carpi ulnaris (FCU), to the ECU tendon. METHODS: Through an incision over the ulna, the intermuscular septum between the ECU and FCU is harvested at the level of the periosteum and left attached to the anconeus proximally. The anconeus muscle is then released from the ulna, and the intramuscular septum extension is sutured to the ECU tendon under maximal tension. Anconeus muscle transfer was performed on two patients to correct chronic wrist radial deviation following PT to ECRB tendon transfer for radial nerve injury, as well as on two patients with PIN paralysis. In four patients, transfer was performed in addition to standard tendon transfers for radial nerve paralysis to prevent radial wrist deviation deformity. RESULTS: Wrist radial deviation was corrected or prevented in all but one patient at an average follow-up of 10 months. Patients with PIN lesions and those who had anconeus transfer concomitantly with radial nerve tendon transfers were capable of active ulnar deviation. No patient experienced elbow extension weakness, pain, or instability. CONCLUSIONS: Anconeus muscle transfer extended by intermuscular septum presents a viable alternative for addressing radial deviation of the wrist in cases of PIN nerve lesions or following PT to ECRB tendon transfer in radial nerve paralysis. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic V.

Design of Experiments-Driven Optimization of Spray Drying for Amorphous Clotrimazole Nanosuspension.

This study employed a Quality by Design (QbD) approach to spray dry amorphousclotrimazole nanosuspension (CLT-NS) consisting of Soluplus® and microcrystallinecellulose. Using the Box-Behnken Design, a systematic evaluation was conducted toanalyze the impact of inlet temperature, % aspiration, and feed rate on the criticalquality attributes (CQAs) of the clotrimazole spray-dried nanosuspension (CLT-SDNS). In this study, regression analysis and ANOVA were employed to detect significantfactors and interactions, enabling the development of a predictive model for the spraydrying process. Following optimization, the CLT-SD-NS underwent analysis using Xraypowder diffraction (XRPD), Fourier transform infrared spectroscopy (FTIR), Dynamic Scanning Calorimetry (DSC), and in vitro dissolution studies. The resultsshowed significant variables, including inlet temperature, feed rate, and aspiration rate,affecting yield, redispersibility index (RDI), and moisture content of the final product. The models created for critical quality attributes (CQAs) showed statistical significanceat a p-value of 0.05. XRPD and DSC confirmed the amorphous state of CLT in theCLT-SD-NS, and FTIR indicated no interactions between CLT and excipients. In vitrodissolution studies showed improved dissolution rates for the CLT-SD-NS (3.12-foldincrease in DI water and 5.88-fold increase at pH 7.2 dissolution media), attributed torapidly redispersing nanosized amorphous CLT particles. The well-designed studyutilizing the Design of Experiments (DoE) methodology.

A comprehensive SEER registry analysis of elderly patients with classical Hodgkin lymphoma based on treatment era and race.

We conducted a Surveillance, Epidemiology, and End Results Program (SEER-18) registry analysis of classical Hodgkin lymphoma (cHL) patients more than 60 years old and compared outcomes of those diagnosed between 2006 and 2010 (cohort 1) to those identified between 2011 and 2015 (cohort 2) based on treatment era and race. Cohort 1 had a median overall survival (OS) of 4 years and cohort 2 had a median OS of 4.75 years [hazard ratio (HR): 0.92 (0.85-1.00); p = 0.052]. Non-Hispanic blacks (NHBs) had a similar 5-year OS compared to non-Hispanic whites (NHWs) of 48.6% vs. 50.2% (HR: 0.95 [0.79-1.15]; p > 0.99); on the contrary, Hispanics had worse 5-year OS of 41.8% vs. 48.6% (HR: 1.24 [1.09-1.41]; p < 0.001). NHW was the only race that had improvement in 5-year OS in 2011-2015 compared to 2006-2010 (51% vs. 46.5%, p = 0.002). In the multivariable analysis, older age, male gender, stage III-IV, unmarried status, Hispanic race, lack of chemotherapy, and diagnosis in 2006-2010 were associated with worse OS. Lymphoma was the most common cause of death in 60% of patients. In conclusion, elderly cHL patients diagnosed after 2010 had improved OS by nine months that was most prevalent in NHWs, and disparity in OS existed between NHWs and Hispanics throughout the study period.

Effect of cumulative dose of brentuximab vedotin maintenance in relapsed/refractory classical Hodgkin lymphoma after autologous stem cell transplant: an analysis of real-world outcomes.

Sixteen cycles of Brentuximab vedotin (BV) after autologous stem cell transplant (ASCT) in high-risk relapsed/refractory classical Hodgkin lymphoma demonstrated an improved 2-year progression-free survival (PFS) over placebo. However, most patients are unable to complete all 16 cycles at full dose due to toxicity. This retrospective, multicenter study investigated the effect of cumulative maintenance BV dose on 2-year PFS. Data were collected from patients who received at least one cycle of BV maintenance after ASCT with one of the following high-risk features: primary refractory disease (PRD), extra-nodal disease (END), or relapse <12 months (RL<12) from the end of frontline therapy. Cohort 1 had patients with >75% of the planned total cumulative dose, cohort 2 with 51-75% of dose, and cohort 3 with ≤50% of dose. The primary outcome was 2-year PFS. A total of 118 patients were included. Fifty percent had PRD, 29% had RL<12, and 39% had END. Forty-four percent of patients had prior exposure to BV and 65% were in complete remission before ASCT. Only 14% of patients received the full planned BV dose. Sixty-one percent of patients discontinued maintenance early and majority of those (72%) were due to toxicity. The 2-year PFS for the entire population was 80.7%. The 2-year PFS was 89.2% for cohort 1 (n=39), 86.2% for cohort 2 (n=33), and 77.9% for cohort 3 (n=46) (P=0.70). These data are reassuring for patients who require dose reductions or discontinuation to manage toxicity.

Absolute Configuration Determination of Chiral API Molecules by MicroED Analysis of Cocrystal Powders Formed Based on Cocrystal Propensity Prediction Calculations.

Establishing the absolute configuration of chiral active pharmaceutical ingredients (APIs) is of great importance. Single crystal X-ray diffraction (scXRD) has traditionally been the method of choice for such analysis, but scXRD requires the growth of large crystals, which can be challenging. Here, we present a method for determining absolute configuration that does not rely on the growth of large crystals. By examining microcrystals formed with chiral probes (small chiral compounds such as amino acids), absolute configuration can be unambiguously determined by microcrystal electron diffraction (MicroED). Our streamlined method employs three steps: (1) virtual screening to identify promising chiral probes, (2) experimental cocrystal screening and (3) structure determination by MicroED and absolute configuration assignment. We successfully applied this method to analyze two chiral API molecules currently on the market for which scXRD was not used to determine absolute configuration.

Influence of racial and ethnic identity on overall survival in patients with chronic lymphocytic leukemia.

Overall survival for chronic lymphocytic leukemia (CLL) patients by race; propensity score matched by age, Charlson-Deyo comorbidity score, insurance, and income and education level of zip code of residence.

Checkpoint inhibitor-based salvage regimens prior to autologous stem cell transplant improve event-free survival in relapsed/refractory classic Hodgkin lymphoma.

Clinical trials of novel salvage therapies have encouraging outcomes for relapsed/refractory transplant-eligible classic Hodgkin lymphoma (R/R cHL) but comparison with conventional chemotherapy is lacking. Herein, we report the final analysis of a multicenter retrospective cohort of R/R cHL assessing outcomes by type of salvage therapy before autologous stem cell transplant (ASCT). R/R cHL patients who underwent ASCT at 14 institutions across the United States were included. Outcomes were compared among patients receiving conventional chemotherapy, brentuximab vedotin (BV) + chemotherapy, BV alone, and a checkpoint inhibitor (CPI)-based regimens before ASCT. Study endpoints included event-free survival (EFS), progression-free survival (PFS), and overall survival (OS). All endpoints are defined from relapse. Of 936 patients, 728 received conventional chemotherapy, 73 received BV + chemotherapy, 70 received BV alone, and 65 received CPI-based regimens prior to ASCT. When adjusted for time to relapse, pre-ASCT response and use of BV maintenance, patients receiving CPI-based regimens had superior 2-year EFS compared to conventional chemotherapy, BV + chemotherapy, and BV alone (79.7, 49.6, 62.3, and 36.9%, respectively, p < .0001). Among 649 patients transplanted after 1 line of salvage therapy, CPI-based regimens were associated with superior 2-year PFS compared to conventional chemotherapy (98% vs. 68.8%, hazard ratio: 0.1, 95% confidence interval: 0.03-0.5, p < .0001). OS did not differ by pre-ASCT salvage regimen. In this large multicenter retrospective study, CPI-based regimens improved EFS and PFS compared to other salvage regimens independent of pre-ASCT response. These data support earlier sequencing of CPI-based regimens in R/R cHL in the pre-ASCT setting.

Computational and Experimental Screening Approaches to Aripiprazole Salt Crystallization.

INTRODUCTION: The screening of multicomponent crystal system (MCC) is a key method for improving physicochemical properties of active pharmaceutical ingredients (APIs). The challenges associated with experimental salt screening include a large number of potential counterions and solvent systems and tendency to undergo disproportionation to produce free form during crystallization. These challenges may be mitigated by a combination of experimental and computational approaches to salt screening. The goal of this study is to evaluate performance of the counterion screening methods and propose and validate novel approaches to virtual solvent screening for MCC crystallization. METHODS: The actual performance of the ΔpKa > 3 rule for counterion selection was validated using multiple screenings reports. Novel computational models for virtual solvent screening to avoid MCC incongruent crystallization were proposed. Using the ΔpKa rule, 10 acid counterions were selected for experimental aripiprazole (APZ) salt screening using 10 organic solvents. The experimental results were used to validate the proposed novel virtual solvent screen models. RESULTS: Experimental APZ salt screening resulted in a total of eight MCCs which included glucuronate, mesylate, oxalate, tartrate, salicylate and mandelate. The new model to virtually screen solvents provided a general agreement with APZ experimental findings in terms of selecting the optimal solvent for MCC crystallization. CONCLUSION: The rational selection of counterions and organic solvents for MCC crystallization was presented using combined novel computational model as well as experimental studies. The current virtual solvent screen model was successfully implemented and validated which can be easily applied to newly discovered APIs.

Capacity Building, Knowledge Enhancement, and Consultative Processes for Development of a Digital Tool (Ni-kshay SETU) to Support the Management of Patients with Tuberculosis: Exploratory Qualitative Study.

BACKGROUND: Achieving the target for eliminating tuberculosis (TB) in India by 2025, 5 years ahead of the global target, critically depends on strengthening the capacity of human resources as one of the key components of the health system. Due to the rapid updates of standards and protocols, the human resources for TB health care suffer from a lack of understanding of recent updates and acquiring necessary knowledge. OBJECTIVE: Despite an increasing focus on the digital revolution in health care, there is no such platform available to deliver the key updates in national TB control programs with easy access. Thus, the aim of this study was to explore the development and evolution of a mobile health tool for capacity building of the Indian health system's workforce to better manage patients with TB. METHODS: This study involved two phases. The first phase was based on a qualitative investigation, including personal interviews to understand the basic requirements of staff working in the management of patients with TB, followed by participatory consultative meetings with stakeholders to validate and develop the content for the mobile health app. Qualitative information was collected from the Purbi Singhbhum and Ranchi districts of Jharkhand and Gandhinagar, and from the Surat districts of Gujarat State. In the second phase, a participatory design process was undertaken as part of the content creation and validation exercises. RESULTS: The first phase collected information from 126 health care staff, with a mean age of 38.4 (SD 8.9) years and average work experience of 8.9 years. The assessment revealed that more than two-thirds of participants needed further training and lacked knowledge of the most current updates to TB program guidelines. The consultative process determined the need for a digital solution in easily accessible formats and ready reckoner content to deliver practical solutions to address operational issues for implementation of the program. Ultimately, the digital platform named Ni-kshay SETU (Support to End Tuberculosis) was developed to support the knowledge enhancement of health care workers. CONCLUSIONS: The development of staff capacity is vital to the success or failure of any program or intervention. Having up-to-date information provides confidence to health care staff when interacting with patients in the community and aids in making quick judgments when handling case scenarios. Ni-kshay SETU represents a novel digital capacity-building platform for enhancing human resource skills in achieving the goal of TB elimination.

Long-Term Donor-Site Morbidity Following Entire Sural Nerve Harvest for Grafting.

PURPOSE: The sural nerve is the autologous nerve used most commonly for grafting. However, recent studies indicate a high rate of complications and complaints after sural nerve removal. In this prospective study, we evaluated donor-site morbidity following full-length sural nerve harvesting on long-term follow-up. METHODS: Fifty-one legs from 43 patients who underwent complete sural nerve harvesting for brachial plexus reconstruction were included in the study. After an average of 5 years, with a minimum postoperative follow-up of 12 months, sensory deficits in the leg and foot were analyzed using 2.0-g monofilaments. Regions of sensory deficit were marked with a skin marker and photographed. Over these regions of decreased sensation, we tested nociception using an eyebrow tweezer. Patients were also asked about pain, cold intolerance, pruritis, difficulties walking, and foot swelling. RESULTS: Regions most affected (84% of patients) were over the calcaneus and cuboid. However, in these regions, nociception was preserved. Regions of decreased sensation extended to the calf region in 11 of 51 legs. In 13 patients, we also observed regions of decreased sensation on the proximal leg. In five feet, the sensation was entirely preserved. No patient had any complaints about pain, cold intolerance, itchiness, difficulties walking, or foot swelling. CONCLUSION: Decreased sensation with nociception preserved was most common along the lateral side of the foot over the calcaneus and cuboid. Removing the entire sural nerve produced no long-term complaints of pain. Sural nerve use appears safe. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic II.

Base of the Third Metacarpal as a Palpable and Reliable Landmark for Identifying the Median Nerve's Thenar Branch.

PURPOSE: The objective of this study was to investigate whether the base of the third metacarpal can predict the location of the thenar branch (TB) of the median nerve and the accuracy of palpating the base of the third metacarpal. METHODS: In 15 patients with ulnar nerve lesions around the elbow, we transferred the opponens motor branch to repair the deep terminal division of the ulnar nerve (DTDUN). Before surgery, we located the TB by palpating the base of the third metacarpal volarly. During surgery, we placed three needles at the following places: one at the entrance of the TB into the abductor pollicis brevis, another at the point where the TB contacted the thenar muscles, and third at the DTDUN's trajectory over the third metacarpal. We obtained fluoroscopic images and measured distances between the needles and structures with image software. We also examined the relationship between the TB, DTDUN, and the volar tubercle of the base of the third metacarpal in cadaver hands. Finally, we invited 22 surgeons to palpate the base of the third metacarpal on volunteer hands and verified their accuracy using fluoroscopy. RESULTS: During surgery, after dissection and palpation of the TB, under fluoroscopy, we confirmed that the palpable bone prominence was the base of the third metacarpal. In cadaver dissections, we observed the TB crossing the volar tubercle of the base of the third metacarpal superficially from proximal to distal and from ulnar to radial. The DTDUN was, on average, 14 mm distal to the base of the third metacarpal distal limit. In total, 19 of the 22 surgeons correctly identified the base of the third metacarpal and consequently the trajectory of the TB. CONCLUSIONS: The palpable base of the third metacarpal can be used to determine the trajectory of both the TB and DTDUN. TYPE OF STUDY/LEVEL OF EVIDENCE: Diagnostic II.

When intravenous vancomycin prophylaxis is needed in shoulder arthroplasty, incomplete administration is associated with increased infectious complications.

BACKGROUND: Vancomycin is often used as antimicrobial prophylaxis for shoulder arthroplasty (SA) either when first generation cephalosporins are contraindicated or colonization with resistant bacteria is anticipated. In general, vancomycin necessitates longer infusion times to mitigate potential side effects. When infusion is started too close to the time of the incision, administration may not be complete during surgery. This study evaluated whether incomplete administration of intravenous vancomycin prior to SA affects the rate of infectious complications. METHODS: Between 2000 and 2019, all primary SA types (hemiarthroplasty, anatomic total SA, reverse SA) performed at a single institution for elective and trauma indications using intravenous vancomycin as the primary antibiotic prophylaxis and a minimum follow-up of 2 yr were identified. The time between the initiation of vancomycin and skin incision was calculated. Complete administration was defined as at least 30 min of infusion prior to incision. Demographic characteristics and infectious complications including survival free of prosthetic joint infection (PJI) were generated. Multivariable analyses were conducted to evaluate the association between vancomycin timing and the development of PJI. RESULTS: A total of 461 primary SAs were included. Infusion was incomplete (< 30 minutes preoperatively) for 163 [35.4%] SA and complete (> 30 minutes preoperatively) for 298 [64.6%] SAs. The incomplete group demonstrated higher rates of any infectious complication (8% vs. 2.3%; P = .005), PJI (5.5% vs. 1%; P = .004), and reoperation inclusive of revision due to infectious complications (4.9% vs. 1%; P = .009). Survivorship free of PJI was worse in SA with incomplete compared to those with complete vancomycin administration. Survival rates for incomplete and complete administration were 97.6% and 99.3% at 1 mo, 95.7% and 99.0% at 2 yr, 95.1% and 99.0% at 5 yr, and 93.9% and 99.0% at 20 yr, respectively (P = .006). Multivariable analyses confirmed that incomplete vancomycin administration was an independent risk factor for PJI compared with complete administration (hazard ratio, 4.22 [95% confidence interval, 1.12-15.90]; P = .033), even when other independent predictors of PJI (age, male sex, prior surgery, methicillin-resistant Staphylococcus aureus colonization, and follow-up) were considered. CONCLUSIONS: When vancomycin is the primary prophylactic agent used at the time of primary SA, incomplete administration (infusion to incision time under 30 min) seems to adversely increase the rates of infectious complications and PJI. Prophylaxis protocols should ensure that complete vancomycin administration is achieved to minimize infection after SA.

A Tardy Ulnar Palsy with an Anomalous Course of Ulnar Nerve.

Variations are inherent feature of the intricate brachial plexus. They can be at the level of origin, the course, or the innervation pattern of each peripheral nerve. Knowledge of the various described variations can be worthwhile during the routine hand surgery procedures. We present a case of an elderly patient with anomalous intramuscular course of the ulnar nerve presenting with ulnar neuropathy at the elbow. Level of Evidence: IV.

A handheld electronic device with the potential to detect lung cancer biomarkers from exhaled breath.

Lung cancer is the leading cause of cancer death in the United States. It has the lowest 5-year survival rate among the most common cancers and therefore, early diagnosis is critical to improve the survival rate. In this paper, a new handheld electronic device is proposed to detect nine lung cancer biomarkers in the exhaled breath. An electrochemical gas sensor was produced through deposition of a thin layer of graphene and Prussian blue on a chromium-modified silicon substrate. Selective binding of the analyte was formed by molecular imprinting polymer (MIP). Subsequent polymerization and removal of the analyte yielded a layer of a conductive polymer on top of the sensor containing molecularly imprinted cavities selective for the target molecule. The sensors were tested over 1-20 parts per trillion (ppt) level of concentration while the sensor resistance has been monitored as the sensors react to the analyte by resistance change. Pentane sensor was also tested for selectivity. A printed circuit board was designed to measure the resistance of each sensor and send the data to a developed application in smartphone through Bluetooth. This handheld device has the potential to be used as a diagnostic method in the near future.

Modeling of Adhesion in Tablet Compression at the Molecular Level Using Thermal Analysis and Molecular Simulations.

The molecular basis of adhesion leading to sticking was investigated by exploring the correlation between thermal analysis and molecular simulations. It is hypothesized that intermolecular interactions between a drug molecule and a punch face are the first step in the adhesion process and the rank order of adhesion during tablet compression should correspond to the rank order of the energies of these interactions. In the present study, the sticking propensity was investigated using ibuprofen, flurbiprofen, and ketoprofen as model substances. At the intermolecular level, a thermal analysis model was proposed as an experimental technique to estimate the work of adhesion between ibuprofen, flurbiprofen, and ketoprofen in a DSC aluminum pan. The linear relationship was established between the enthalpy of vaporization and sample mass to demonstrate the accuracy of the instruments used. The threshold mass for ibuprofen, flurbiprofen, and ketoprofen was determined to be 107, 112, and 222 µg, respectively, after three replicate measurements consistent with the experimental results. Ketoprofen showed a 2-fold higher threshold mass compared to ibuprofen and flurbiprofen, which predicts that ketoprofen should have the highest sticking propensity. Computationally, the rank order of the work of adhesion between ibuprofen, flurbiprofen, and ketoprofen with the metal surface was simulated to be -75.91, 44.75, and -96.91 kcal/mol, respectively, using Materials Studio. The rank order of the interaction between the drug molecule and the iron superlattice decreases in the order ketoprofen > ibuprofen > flurbiprofen. The results indicate that the thermal model can be successfully implemented to assess the sticking propensity of a drug at the molecular level. Also, a new molecular simulation script was successfully applied to determine the interaction energy of the drug molecule upon contact with iron.