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Metal borides, a class of materials intensively used in industry as superconductors, magnetic materials, or hot cathodes, remain largely unexplored at the nanoscale mainly due to the difficulty in synthesizing single-phase nanocrystals. Recent works have shown that synthetic methods at lower temperatures (xB) could be a potential catalyst for a broad range of applications (hydrogenations, electrochemical hydrogen, and oxygen evolution reactions) under challenging conditions (such as high pH or high temperatures). Here, we report a novel solid-state method to synthesize NixB nanopowders (with a diameter of approximately 45 nm) and their conversion into colloidal suspensions (inks) through treatment of the nanocrystal surface. For the solid-state synthesis, we used commercially available salts and explored the reaction between the Ni and B sources while varying the synthetic parameters under mild and solvent-free reaction conditions. We show that pure phase Ni3B and Ni2B NCs can be obtained with high yield in the pure phase using as precursors NiCl2 and Ni, respectively. Through extensive mechanistic studies, we show that Ni nanoclusters (1-2 nm) are an intermediate in the boriding process, while the metal co-reactant lowers the decomposition temperature of NaBH4 (used as a reducing agent and B source). Size control can instead be exerted through reaction mediators, as seen from the differential nucleation and growth of Ni (clusters) or NixB NCs when employing L- (amine, phosphine) and X-type (carboxylate) mediators. Applying surface engineering methods to our NixB NCs, we stabilized them with inorganic (NOBF4) or organic (borane tert-butyl amine, oleylamine) ligands in the appropriate solvent (DMSO, hexane). With this method, we produce stable inks for further solution processing applications. Our results provide tools for further development of catalysts based on NixB NCs and pave the way for synthesizing other metal boride colloidal nanostructures.

Direct cortical stimulation of the mesial frontal premotor cortex, including the supplementary motor area (SMA), is challenging in humans. Limited access to these brain regions impedes understanding of human premotor cortex functional organization and somatotopy.To test whether seizure onset within the SMA was associated with functional remapping of mesial frontal premotor areas in a cohort of patients with epilepsy who underwent awake brain mapping after implantation of interhemispheric subdural electrodes.Stimulation trials from 646 interhemispheric subdural electrodes were analyzed and compared between patients who had seizure onset in the SMA (n = 13) vs patients who had seizure onset outside of the SMA (n = 12). 1:1 matching with replacement between SMA and non-SMA data sets was used to ensure similar spatial distribution of electrodes. Centroids and 95% confidence regions were computed for clustered head, trunk, upper extremity, lower extremity, and vision responses. A generalized linear mixed-effects model was used to test for significant differences in the resulting functional maps. Clinical, radiographic, and histopathologic data were reviewed.After analyzing direct cortical stimulation trials from interhemispheric electrodes, we found significant displacement of the head and trunk responses in SMA compared with non-SMA patients ( P.01 for both). These differences remained significant after accounting for structural lesions, preexisting motor deficits, and seizure outcome.The somatotopy of the mesial frontal premotor regions is significantly altered in patients who have SMA-onset seizures compared with patients who have seizure onset outside of the SMA, suggesting that functional remapping can occur in these brain regions.

Small-molecule inhibitors of PD-L1 are postulated to control immune evasion in tumors similar to antibodies that target the PD-L1/PD-1 immune checkpoint axis. However, the identity of targetable PD-L1 inducers is required to develop small-molecule PD-L1 inhibitors. In this study, using chromatin immunoprecipitation (ChIP) assay and siRNA, we demonstrate that vitamin D/VDR regulates PD-L1 expression in acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) cells. We have examined whether a VDR antagonist, MeTC7, can inhibit PD-L1. To ensure that MeTC7 inhibits VDR/PD-L1 without off-target effects, we examined competitive inhibition of VDR by MeTC7, utilizing ligand-dependent dimerization of VDR-RXR, RXR-RXR, and VDR-coactivators in a mammalian 2-hybrid (M2H) assay. MeTC7 inhibits VDR selectively, suppresses PD-L1 expression sparing PD-L2, and inhibits the cell viability, clonogenicity, and xenograft growth of AML cells. MeTC7 blocks AML/mesenchymal stem cells (MSCs) adhesion and increases the efferocytotic efficiency of THP-1 AML cells. Additionally, utilizing a syngeneic colorectal cancer model in which VDR/PD-L1 co-upregulation occurs in vivo under radiation therapy (RT), MeTC7 inhibits PD-L1 and enhances intra-tumoral CD8+T cells expressing lymphoid activation antigen-CD69. Taken together, MeTC7 is a promising small-molecule inhibitor of PD-L1 with clinical potential.

Major depressive disorder (MDD) continues to be one of the highest contributors to disease burden and years lived with disability in the world. Current existing treatments have been associated with intolerable side effects, long onset of action and suboptimal remission rates. Newer agents are being developed that will be reviewed here, such as glutamate and gamma-aminobutyric acid (GABA) and the reinvigorated testing of psychedelic drugs. This review will summarize the target mechanisms of the newer ADTs currently in development and available on the market.It briefly covers the existing agents for MDD and treatment-resistant depression (TRD) and the need for new agents with higher efficacy. Therapeutic agents currently in Phase II or later clinical trials are listed and discussed, based on a thorough review of the US National Institutes of Health clinicaltrials.gov index and a search of the Informa Pharmaprojects database. Compounds of interest are grouped into scientific rationale and include atypical antipsychotics, GABA positive allosteric modulators, glutamatergic agents, opioids, orexin 2 receptor antagonists, and psychedelics.New therapeutic agents currently in development are promising, with a more rapid onset of action and the ability to augment and treat TRD.

Phosphatase and tensin homolog (PTEN) is a major negative regulator of the phosphatidylinositol-3-kinase (PI3K)/Akt/mechanistic target of rapamycin (mTOR) pathway. Loss-of-function mutations inPTENhave been found in a subset of patients with macrocephaly and autism spectrum disorder (ASD). PTEN loss in neurons leads to somal hypertrophy, aberrant migration, dendritic overgrowth, increased spine density, and hyperactivity of neuronal circuits. These neuronal overgrowth phenotypes are present onPtenknock-out (KO) and reconstitution with autism-associated point mutations. The mechanism underlying dendritic overgrowth inPtendeficient neurons is unclear. In this study, we examined howPtenloss impacts microtubule (MT) dynamics in both sexes using retroviral infection and transfection strategies to manipulate PTEN expression and tag the plus-end MT binding protein, end-binding protein 3 (EB3). We foundPtenKO neurons sprout more new processes over time compared with wild-type (WT) neurons. We also found an increase in MT polymerization rate inPtenKO dendritic growth cones. Reducing MT polymerization rate to the WT level was sufficient to reduce dendritic overgrowth inPtenKO neuronsin vitroandin vivo. Finally, we found that rescue of dendritic overgrowth via inhibition of MT polymerization was sufficient to improve the performance ofPtenKO mice in a spatial memory task. Taken together, our data suggests that one factor underlying PTEN loss dependent dendritic overgrowth is increased MT polymerization. This opens the possibility for an intersectional approach targeting MT polymerization and mTOR with low doses of inhibitors to achieve therapeutic gains with minimal side effects in pathologies associated with loss of neuronal PTEN function.SIGNIFICANCE STATEMENTLoss ofPtenfunction because of genetic deletion or expression of mutations associated with autism spectrum disorder (ASD), results in overgrowth of neurons including increased total dendritic length and branching. We have discovered that this overgrowth is accompanied by increased rate of microtubule (MT) polymerization. The increased polymerization rate is insensitive to acute inhibition of mechanistic target of rapamycin (mTOR)C1 or protein synthesis. Direct pharmacological inhibition of MT polymerization can slow the polymerization rate inPtenknock-out (KO) neurons to rates seen in wild-type (WT) neurons. Correction of the MT polymerization rate rescues increased total dendritic arborization and spatial memory. Our studies suggest that phosphatase and tensin homolog (PTEN) inhibits dendritic growth through parallel regulation of protein synthesis and cytoskeletal polymerization.

Background: Despite advances in surgery and pharmacotherapy, there remains significant residual ischemic risk after coronary artery bypass grafting surgery. Methods: In REDUCE-IT (Reduction of Cardiovascular Events With Icosapent Ethyl–Intervention Trial), a multicenter, placebo-controlled, double-blind trial, statin-treated patients with controlled low-density lipoprotein cholesterol and mild to moderate hypertriglyceridemia were randomized to 4 g daily of icosapent ethyl or placebo. They experienced a 25% reduction in risk of a primary efficacy end point (composite of cardiovascular death, myocardial infarction, stroke, coronary revascularization, or hospitalization for unstable angina) and a 26% reduction in risk of a key secondary efficacy end point (composite of cardiovascular death, myocardial infarction, or stroke) when compared with placebo. The current analysis reports on the subgroup of patients from the trial with a history of coronary artery bypass grafting. Results: Of the 8179 patients randomized in REDUCE-IT, a total of 1837 (22.5%) had a history of coronary artery bypass grafting, with 897 patients randomized to icosapent ethyl and 940 to placebo. Baseline characteristics were similar between treatment groups. Randomization to icosapent ethyl was associated with a significant reduction in the primary end point (hazard ratio [HR], 0.76 [95% CI, 0.63–0.92]; P =0.004), in the key secondary end point (HR, 0.69 [95% CI, 0.56–0.87]; P =0.001), and in total (first plus subsequent or recurrent) ischemic events (rate ratio, 0.64 [95% CI, 0.50–0.81]; P =0.0002) compared with placebo. This yielded an absolute risk reduction of 6.2% (95% CI, 2.3%–10.2%) in first events, with a number needed to treat of 16 (95% CI, 10–44) during a median follow-up time of 4.8 years. Safety findings were similar to the overall study: beyond an increased rate of atrial fibrillation/flutter requiring hospitalization for at least 24 hours (5.0% vs 3.1%; P =0.03) and a nonsignificant increase in bleeding, occurrences of adverse events were comparable between groups. Conclusions: In REDUCE-IT patients with a history of coronary artery bypass grafting, treatment with icosapent ethyl was associated with significant reductions in first and recurrent ischemic events. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT01492361.

Background Contralateral C7 (CC7) nerve transfer has successfully restored hand function in patients with spastic hemiplegia from chronic central nervous system injuries. However, little is known about the morphology and anatomy of the donor C7 nerve root in patients undergoing this procedure. This study quantified intraoperative measurements of donor C7 nerve roots during CC7 transfer surgery for spastic hemiplegia in patients treated at a high-volume center to describe observed anatomical variations for successful direct anastomosis. Methods A database of images from 21 patients (2 females, 19 males) undergoing CC7 surgery was searched for photographic data that contained a standard ruler measuring donor C7 nerve root length after surgical sectioning and before transfer. Two independent observers analyzed these images and recorded C7 nerve root diameter, length, and branch lengths. Results Mean (SD) values of donor C7 nerve measurements were length, 53.5 (8.0) mm; diameter, 5.1 (0.9) mm; branch length following surgical sectioning, 18.3 (6.3) mm. Right-sided donor C7 nerve roots yielded significantly longer branches compared with left-sided donor C7 nerve roots (P = 0.01). Other patient factors such as age, sex, or laterality of brain injury did not influence intraoperative anatomy. Conclusions We report detailed intraoperative measurements of the donor C7 root during CC7 nerve transfer for spastic hemiplegia. These findings describe existing variation in surgical C7 nerve root anatomy in patients undergoing this procedure and may serve as a general reference for the expected donor C7 length in successful direct anastomosis.

Diffusely infiltrating gliomas are associated with high morbidity and mortality due to the infiltrative nature of tumor spread. They are morphologically complex tumors, with a high degree of proteomic variability across both the tumor itself and its heterogenous microenvironment. The malignant potential of these tumors is enhanced by the dysregulation of proteins involved in several key pathways, including processes that maintain cellular stability and preserve the structural integrity of the microenvironment. Although there have been numerous bulk and single-cell glioma analyses, there is a relative paucity of spatial stratification of these proteomic data. Understanding differences in spatial distribution of tumorigenic factors and immune cell populations between the intrinsic tumor, invasive edge, and microenvironment offers valuable insight into the mechanisms underlying tumor proliferation and propagation. Digital spatial profiling (DSP) represents a powerful technology that can form the foundation for these important multilayer analyses. DSP is a method that efficiently quantifies protein expression within user-specified spatial regions in a tissue specimen. DSP is ideal for studying the differential expression of multiple proteins within and across regions of distinction, enabling multiple levels of quantitative and qualitative analysis. The DSP protocol is systematic and user-friendly, allowing for customized spatial analysis of proteomic data. In this experiment, tissue microarrays are constructed from archived glioblastoma core biopsies. Next, a panel of antibodies is selected, targeting proteins of interest within the sample. The antibodies, which are preconjugated to UV-photocleavable DNA oligonucleotides, are then incubated with the tissue sample overnight. Under fluorescence microscopy visualization of the antibodies, regions of interest (ROIs) within which to quantify protein expression are defined with the samples. UV light is then directed at each ROI, cleaving the DNA oligonucleotides. The oligonucleotides are microaspirated and counted within each ROI, quantifying the corresponding protein on a spatial basis.

Objective: The efficacy of deep brain stimulation (DBS) depends on accurate placement of electrodes. Although stereotactic frames enable co-registration of image-based surgical planning and the operative field, the accuracy of electrode placement can be degraded by intra-operative brain shift. In this study, we adapted a biomechanical model to estimate whole brain displacements from which we deformed preoperative CT (preCT) to generate an updated CT (uCT) that compensates for brain shift. Methods: We drove the deformation model using displacement data derived from deformation in the frontal cortical surface that occurred during the DBS intervention. We evaluated 15 patients, retrospectively, who underwent bilateral DBS surgery, and assessed the accuracy of uCT in terms of target registration error (TRE) relative to a CT acquired post-placement (postCT). We further divided subjects into large (Group L) and small (Group S) deformation groups based on a TRE threshold of 1.6mm. Anterior commissure (AC), posterior commissure (PC) and pineal gland (PG) were identified on preCT and postCT and used to quantify TREs in preCT and uCT. Results: In the group of large brain deformation, average TREs for uCT were 1.11 ± 0.13 and 1.07 ± 0.38 mm at AC and PC, respectively, compared to 1.85 ± 0.17 and 0.92 ± 0.52 mm for preCT. The model updating approach improved AC localization but did not alter TREs at PC. Conclusion: This preliminary study suggests that our image updating method may compensate for brain shift around surgical targets of importance during DBS surgery, although further investigation is warranted before conclusive evidence will be available. Significance: With further development and evaluation, our model-based image updating method using intraoperative sparse data may compensate for brain shift in DBS surgery efficiently, and have utility in updating targeting coordinates.

The New England Neurosurgical Society (NENS) was founded in 1951 under the leadership of its first President (Dr. William Beecher Scoville) and Secretary-Treasurer (Dr. Henry Thomas Ballantine). The purpose of creating the NENS was to unite local neurosurgeons in the New England area; it was one of the first regional neurosurgical societies in America. Although regional neurosurgical societies are important supplements to national organizations, they have often been overshadowed in the available literature. Now in its 70th year, the NENS continues to serve as a platform to represent the needs of New England neurosurgeons, foster connections and networks with colleagues, and provide research and educational opportunities for trainees. Additionally, regional societies enable discussion of issues uniquely relevant to the region, improve referral patterns, and allow for easier attendance with geographic proximity. In this paper, the authors describe the history of the NENS and provide a roadmap for its future. The first section portrays the founders who led the first meetings and establishment of the NENS. The second section describes the early years of the NENS and profiles key leaders. The third section discusses subsequent neurosurgeons who steered the NENS and partnerships with other societies. In the fourth section, the modern era of the NENS and its current activities are highlighted.

Intraoperative nerve monitoring (IONM) is a tool used during thyroid surgery to assist in the identification of the recurrent laryngeal nerve (RLN). Multiple IONM systems that exist for thyroidectomy require intubation with an endotracheal tube. Given that one of the advantages of thermal ablation procedures, such as radiofrequency ablation, is that they can be done safely without the use of general anesthesia, nerve monitoring systems that utilize cutaneous surface electrodes have been developed, though are not widely available in the United States. This article will review the use of IONM for RFA including the cutaneous surface electrode system.

BACKGROUND Juvenile psammomatoid ossifying fibroma (JPOF) is an uncommon benign fibro-osseous lesion that only rarely presents in the calvaria. OBSERVATIONS The authors reported a case of JPOF in the left parietal bone of a 20-year-old patient and reviewed the 27 other cases of JPOF occurring in the calvaria as reported in the literature. LESSONS JPOF rarely presents in the calvaria, and because diagnosis is a histopathologic one, clinicians should consider this entity when presented with a lytic, expansile mass on imaging. Little is known about the molecular mechanisms driving development of JPOF. MDM2 amplification may play a role, although this was not seen in the case presented herein.

Spinal epidural abscess (SEA) is an uncommon yet serious infection, associated with significant morbidity and mortality. Patients diagnosed with SEA often require surgical interventions or critical care services that are not available at community hospitals and are therefore transferred to tertiary care centers. Little is known about the effects of interhospital transfer on acute outcomes for patients with SEA.To study the effects of interhospital transfer on acute outcomes for patients with SEA.Cross sectional analysis using the 2009 to 2017 National Inpatient Sample (NIS).Using the 2009 to 2017 NIS, we identified cases of SEA using ICD, Ninth, or Tenth Revision diagnosis codes 324.1G06.1.Our primary endpoint was in hospital mortality.The association between interhospital transfer and inpatient mortality was assessed using multivariable logistic regression to adjust for potential covariates. Patient and hospital factors associated with interhospital transfer were assessed in a secondary analysis.A total of 21.5% of patient with SEA were treated after transfer from another hospital. After adjusting for covariates, those who presented after transfer had higher odds of death during hospitalization (OR: 1.51, 95% CI 1.27-1.78, p.001). Transferred patients were significantly more likely to live in rural communities (11.4 % vs. 5.3 % for nontransferred patients).Interhospital transfer, which occurred more frequently in patients from rural hospitals, was associated with death even after controlling for disease severity. Addressing healthcare delivery disparities across the US, including across the rural-urban spectrum, will require better understanding of the observed increased mortality of interhospital transfer as a preventable source of in-hospital mortality for SEA.

Background The soluble prorenin receptor (sPRR), a member of the renin-angiotensin system (RAS), is elevated in plasma of patients with preeclampsia, hypertension, chronic kidney disease (CKD), and type 2 diabetes. Our goal was to examine the relationship between sPRR and RAS activation to define whether sexual dimorphisms in sPRR might explain sex disparities in renal outcomes in patients with type 2 diabetes. Methods Two hundred sixty-nine participants were included in the study (mean age, 48 ± 16 years; 42% men, 58% women), including 173 controls and 96 subjects with type 2 diabetes. In plasma and urine, we measured sPRR, plasma renin activity (PRA), and prorenin. In the urine, we also measured angiotensinogen along with other biomarkers of renal dysfunction. Results Plasma sPRR and PRA were significantly higher in women with type 2 diabetes compared to men. In these women, plasma sPRR was positively correlated with PRA, age, and body mass index (BMI). In contrast, in men the sPRR in urine but not in plasma positively correlated with eGFR in urine, but negatively correlated with urine renin activity, plasma glucose, age, and BMI. Conclusions In patients with type 2 diabetes, sPRR contributes to RAS stimulation in a sex-dependent fashion. In diabetic women, increased plasma sPRR parallels the activation of systemic RAS; while in diabetic men, decreased sPRR in urine matches intrarenal RAS stimulation. sPRR might be a potential indicator of intrarenal RAS activation and renal dysfunction in men and women with type 2 diabetes.

Background Melatonin is a potent oxygen scavenger and is capable of altering blood flow in various vascular beds. Aims We aimed to determine the effect of melatonin on ovarian vascular indices during ovarian stimulation for in vitro fertilisation (IVF). Materials and methods This is a pilot double-blind placebo-controlled randomised trial. Sixty-nine women (mean age 35.8 ± 4.3 years) undergoing their first cycle of IVF were randomised to receive either placebo, 2, 4 or 8 mg of melatonin, twice a day. Each participant underwent a transvaginal ultrasound at days 6-10 assessing follicular number and size. The vascularisation index (VI), flow index (FI) and vascularisation-flow index (VFI) were measured. These indices were then correlated with embryological outcomes. Informed consent was obtained from participants. This trial was registered with the Australia New Zealand Clinical Trials Registry (ACTRN12613001317785). Results The number of follicles did not differ between groups (P = 0.4). There were no differences in the VI (P = 0.4), FI (P = 0.1) or VFI (P = 0.3) in the right ovary or the FI (P = 0.3) or VFI (P = 0.3) in the left ovary between groups. When comparing placebo to any dose of melatonin, there were no differences in any measured parameter. While there was correlation between the number of follicles on ultrasound and all measured embryological outcomes, there was no correlation between ovarian vascular indices and these important clinical outcomes. Conclusions Melatonin does not appear to change ovarian vascular indices during ovarian stimulation. In addition, such vascular indices cannot predict the number or quality of oocytes or embryos obtained in an IVF cycle. These findings require confirmation in future larger studies.

Neurogenic thoracic outlet syndrome (nTOS) describes a set of disorders related to symptomatic compression of the brachial plexus as it passes through the thoracic outlet into the arm. In children, nTOS is a rare and frequently delayed diagnosis due to the difficulty of communicating symptoms with adults and healthcare providers and decreased prevalence of the syndrome compared to adult nTOS. Additionally, nTOS is an uncommon variant of pediatric thoracic outlet syndrome, which is predominantly arterial or vascular in nature. In this chapter we review the presentation, associated radiographic and exam findings, and management for pediatric nTOS. We summarize the outcomes for pediatric nTOS reported in the literature to date, and also present our institutional experience managing these challenging and uncommon patients.

Excessive interfacility transfer to a tertiary care facility of minimally injured patients for subspecialty evaluation leads to overuse of resources and is referred to as secondary overtriage (SO). Little is known regarding the epidemiology of SO in rural settings, particularly for patients with a mild head injury who may be safely managed without admission to level I trauma centers.In order to determine the rate of SO for neurosurgical patients with Glasgow Coma Scale (GCS) of 13-15 referred to a rural level 1 trauma center, we conducted a retrospective chart review of 224 patients evaluated for potential transfer to Dartmouth-Hitchcock Medical Center from January 1, 2014 through December 31, 2014. SO was defined as any admission where a patient was transferred from an outside facility, had a length of stay shorter than 48 h, did not require neurosurgical intervention, and was alive at the time of discharge.Of the 224 patients evaluated, 163 patients were transferred. Of the 163 patients included in this study, 43 (26.4%) met criteria for SO, 59 (36.2%) patients met criteria for intervention, and 61 (37.2%) patients met criteria for observation.Approximately a quarter of the total patients who are transferred to a rural level I trauma center for neurosurgical evaluation are minimally injured, do not require neurosurgical intervention, and are discharged within 48 h of presentation. Management at their referring facility with remote neurosurgical consultation is likely safe in this population. Understanding the rate of SO in neurosurgical patients and risk factors present in this group can better guide future transfer policies at rural medical centers.

Introduction Although testosterone therapy (TTh) is the standard practice in otherwise healthy hypogonadal men, this therapy has historically been contraindicated in men with a history of prostate cancer. Recent evidence suggests that there is minimal or no prostate cancer growth in the setting of TTh administration in men definitively treated for non-metastatic prostate cancer. Objective To review the evidence supporting the safety and efficacy of TTh in patients previously treated for localized prostate cancer. Methods A literature review of the PubMed database was performed to identify studies evaluating the safety and efficacy of TTh in patients with a history of prostate cancer. Search terms included Testosterone Therapy, Testosterone Replacement Therapy and Radical Prostatectomy, Radiotherapy, External Beam Radiation Therapy, EBRT, Brachytherapy; Prostate Cancer and Hypogonadism, Low Testosterone; Bipolar Androgen Therapy. Results Available literature provides evidence for the safe application of TTh in patients previously treated for prostate cancer with either radical prostatectomy or radiotherapy. Furthermore, there exists evidence that severely hypogonadal levels of testosterone may lead to worse oncological outcomes. More recent research has begun to elucidate the effectiveness of bipolar androgen deprivation therapy in the treatment of prostate cancer. This mechanism of action increases the level of evidence indicating that the traditional management of maintaining testosterone levels at low levels may no longer be standard of care. TTh likely has a role in improved erectile function and other quality-of-life concerns in patients developing testosterone deficiency after being treated for prostate cancer. Conclusions TTh should be offered to select hypogonadal patients who have a history of definitively treated prostate cancer. Adequately designed randomized controlled trials are necessary to confirm the safety and efficacy of TTh in this population. Natale C, Carlos C, Hong J, et al. Testosterone Replacement Therapy After Prostate Cancer Treatment: A Review of Literature. Sex Med Rev 2021;9:393–405.

Low cross-link density thermally reversible networks were successfully synthesized from jatropha and sunflower oils. The oils were epoxidized and subsequently reacted with furfurylamine to attach furan groups onto the triglycerides, preferably at the epoxide sites rather than at the ester ones. Under the same reaction conditions, the modified jatropha oil retained the triglyceride structure more efficiently than its sunflower-based counterpart, i.e., the ester aminolysis reaction was less relevant for the jatropha oil. These furan-modified oils were then reacted with mixtures of aliphatic and aromatic bismaleimides, viz. 1,12-bismaleimido dodecane and 1,1&prime, (methylenedi-4,1-phenylene)bismaleimide, resulting in a series of polymers with Tg ranging between 3.6 and 19.8 &deg, C. Changes in the chemical structure and mechanical properties during recurrent thermal cycles suggested that the Diels&ndash, Alder and retro-Diels&ndash, Alder reactions occurred. However, the reversibility was reduced over the thermal cycles due to several possible causes. There are indications that the maleimide groups were homopolymerized and the Diels&ndash, Alder adducts were aromatized, leading to irreversibly cross-linked polymers. Two of the polymers were successfully applied as adhesives without modifications. This result demonstrates one of the potential applications of these polymers.

Acylhydrazones formation has been widely applied in materials science and biolabeling. However, their sluggish condensation rate under neutral conditions limits its application. Herein, indolines with electron-donating groups are reported as a new catalyst scaffold, which can catalyze acylhydrazone, hydrazone, and oxime formation via an iminium ion intermediate. This new type of catalyst showed up to 15-fold rate enhancement over the traditional aniline-catalyzed reaction at neutral conditions. The identified indoline catalyst was successfully applied in hydrogel formation.

A novel freeze-cast porous chitosan conduit for peripheral nerve repair with highly-aligned, double layered porosity, which provides the ideal mechanical and chemical properties was designed, manufactured, and assessed in vivo. Efficacies of the conduit and the control inverted nerve autograft were evaluated in bridging 10-mm Lewis rat sciatic nerve gap at 12 weeks post-implantation. Biocompatibility and regenerative efficacy of the porous chitosan conduit were evaluated through the histomorphometric analysis of longitudinal and transverse sections. The porous chitosan conduit was found to have promising regenerative characteristics, promoting the desired neovascularization, and axonal ingrowth and alignment through a combination of structural, mechanical and chemical cues.

OBJECTIVENeurogenic thoracic outlet syndrome (nTOS) is an uncommon compression syndrome of the brachial plexus that presents with pain, sensory changes, and motor weakness in the affected limb. The authors reviewed the clinical presentations and outcomes in their series of pediatric patients with surgically treated nTOS over a 6-year period.METHODSCases of nTOS in patients age 18 years or younger were extracted for analysis from a prospective database of peripheral nerve operations. Baseline patient characteristics, imaging and neurophysiological data, operative findings, and outcomes and complications were assessed.RESULTSTwelve patients with 14 cases of nTOS surgically treated between April 2010 and December 2016 were identified. One-third of the patients were male, and 2 male patients underwent staged, bilateral procedures. Disabling pain (both local and radiating) was the most common presenting symptom (100%), followed by numbness (35.7%), then tingling (28.6%). The mean duration of symptoms prior to surgery was 15.8 ± 6.6 months (mean ± SD). Sports-related onset of symptoms was seen in 78.6% of cases. Imaging revealed cervical ribs in 4 cases, prominent C-7 transverse processes in 4 cases, abnormal first thoracic ribs in 2 cases, and absence of bony anomalies in 4 cases. Neurophysiological testing results were normal in 85.7% of cases. Conservative management failed in all patients, with 5 patients reporting minimal improvement in symptoms with physical therapy. With a mean follow-up after surgery of 22 ± 18.3 months (mean ± SD), pain relief was excellent (> 90%) in 8 cases (57.1%), and good (improved > 50%) in 6 cases (42.9%). On univariate analysis, patients who reported excellent pain resolution following surgery at long-term follow-up were found to be significantly younger, and to have suffered a shorter duration of preoperative symptoms than patients who had worse outcomes. Lack of significant trauma or previous surgery to the affected arm was also associated with excellent outcomes. There were 4 minor complications in 3 patients within 30 days of surgery: 1 patient developed a small pneumothorax that resolved spontaneously; 1 patient suffered a transient increase in pain requiring consultation, followed by hiccups for a period of 3 hours that resolved spontaneously; and 1 patient fell at home, with transient increased pain in the surgically treated extremity. There were no new neurological deficits, wound infections, deep vein thromboses, or readmissions.CONCLUSIONPediatric nTOS commonly presents with disabling pain and is more frequently associated with bony anomalies compared with adult nTOS. In carefully selected patients, surgical decompression of the brachial plexus results in excellent pain relief, which is more likely to be seen in younger patients who present for early surgical evaluation.

Background Meralgia paresthetica, a pain syndrome that is caused by injury to the lateral femoral cutaneous nerve, is a well-documented complication after anterior hip arthroplasty (THA). Traditional treatment of this peripheral nerve entrapment syndrome can be complicated in patients who have had THA via an anterior approach owing to the presence of scar in the postoperative bed. Case Description In a 70-year-old man, we performed a novel laparoscopic-assisted intra-abdominal approach to treat meralgia paresthetica in the setting of previous anterior THA. Conclusions Minimally invasive intra-abdominal treatment of meralgia paresthetica following anterior THA results in durable pain relief. This approach is a helpful alternative to traditional techniques of decompression or section of the lateral femoral cutaneous nerve below the inguinal ligament.

Patients with autologous stem cell transplantation (ASCT) have a variable period of immune deficiency in the post-transplant period. Guidelines recommend revaccination of patients after ASCT as standard care. The response to vaccination may affect the outcome of the transplant patients. We aim to evaluate the vaccination response after ASCT. All myeloma and lymphoma patients with ASCT who had vaccination and measured vaccination response, were included in the study. We retrospectively evaluated 73 ASCT patients, 55 with multiple myeloma (MM) and 18 with lymphoma between 2013 and 2018. The current ASCT protocol for active immunization includes three doses of pneumococcal conjugate vaccine (PCV13) from 6-12 months after ASCT, followed by a 23-valent polysaccharide pneumococcal vaccine (PPSV23). Haemophilus Influenza B (HiB), hepatitis B, and TDAP/TD vaccines are administered within one year after initiation of vaccination. The responses to these vaccines were investigated by checking antibody titers at a minimum of two months after completion of vaccination. Both MM and lymphoma groups had similar pre-vaccination immunologic parameters, including IgG levels, absolute CD4+, and CD4+CD45RA+ cell counts (Table 1). Diphtheria and tetanus had 89% response rate to the vaccination in all patients (Table 2). Only half of the patients (47%) responded to hepatitis B vaccine. The response was higher but not statistically significant in the lymphoma group compared to the MM group (57 % versus 43.9 % P: NS). More than 80% of the patients had a response to H. Influenza vaccine. All patients had a 59% response to pneumococcal vaccination. We then analyzed the pneumococcal responses according to serotype. PCV13 includes vaccine against 13 serotypes of S. pneumonia (1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 19A, 19F, 18C, and 23F). PPSV23 contains additional 11 serotypes (2, 8, 9N, 10A, 11A, 12F, 15B, 17F, 20, 22F, 33F). 76 % of MM patients responded to PCV13 serotypes, while only 41 % responded to PPSV23 specific serotypes (p: In conclusion, ASCT patients respond well to most vaccinations except for Hepatitis B and PPSV23. Further studies may need to explore pathophysiology of vaccine failure. Strategies to enhance immune reconstitution may augment the immune response and improve the outcome of the patients with ASCT. Disclosures Alpdogan: Seattle Genetics: Research Funding. Binder:Sanofi: Consultancy; Janssen: Membership on an entity's Board of Directors or advisory committees. Kasner:Jazz Pharmaceuticals: Membership on an entity's Board of Directors or advisory committees, Research Funding; Otsuka Pharmaceutical: Research Funding. Martinez-Outschoorn:Otsuka Pharmaceutical: Research Funding. Palmisiano:AbbVie: Research Funding; Genentech: Research Funding. Porcu:Viracta Therapeutics: Membership on an entity's Board of Directors or advisory committees; Celgene: Research Funding; Cell Medica: Research Funding; Daiichi: Consultancy, Honoraria; Galderma: Research Funding; Innate Pharma: Membership on an entity's Board of Directors or advisory committees, Research Funding; Kiowa Kirin: Research Funding; Kura Oncology: Research Funding; Miragen: Research Funding; Verastem: Consultancy. Flomenberg:Tevogen: Consultancy, Honoraria.

Background Amyloidosis cardiomyopathy is a systemic disease with high risk of disability and death. Patient-reported outcomes (PROs) are validated tools that measure health-related quality of life (HRQoL) and provide prognostic information in patients with heart failure. However, data on HRQoL profile and prognostic value of PROs in patients with cardiac amyloidosis are limited. Methodology This is an observational study of patients with transthyretin amyloidosis (ATTR) and light chain amyloidosis (AL) who completed Kansas City Cardiomyopathy Questionnaire (KCCQ-12) at the time of clinic visit. We examined KCCQ-12 scores and their relationship to HF hospitalization or death in both amyloidosis groups. Results A total of 81 patients were included in the study, 48 with ATTR and 33 with AL with a mean age of 78±7 years and 65±10 years, respectively. KCCQ-12 results were similar in both groups and showed significant HRQoL limitation - median summary score of 38 (IQR 24-60) for ATTR and 51 (IQR 31-73) for AL, p = 0.128. Compared to AL, patients with ATTR had more impairment in the physical limitation domain (Table). Over a median follow-up of 343 days, HF hospitalization or death occurred in 23 (48%) patients with ATTR and 17 (51%) patients with AL. KCCQ score was associated with the risk of HF hospitalization or death with a correlation ratio of 0.9 for ATTR (p=0.025) and 1.0 for AL (p=0.03). ROC AUC for KCCQ-12 ability to predict HF hospitalization or death was 0.7 (95% CI, 0.54-0.84, p = 0.026) for ATTR and 0.8 (95% CI, 0.62-0.95, p = 0.006) for AL. In ATTR, the rate of HF hospitalization or death increased proportionally with decreasing KCCQ-12 scores while in patients with AL high events rates were seen for KCCQ-12 scores 60 or lower. (Figure). Conclusions Patients with ATTR and AL amyloidosis cardiomyopathy suffer from poor HRQoL and high burden of events. Our study shows that KCCQ provides important prognostic information in these patients. Routine KCCQ assessments could be used to identify high-risk patients in need of close monitoring.

Objective Arrested hydrocephalus is stable ventriculomegaly without evidence of neurologic deterioration or symptoms. Management of arrested hydrocephalus in asymptomatic adults is controversial, with little clinical data. This case highlights the potential for decompensation in adults with arrested hydrocephalus and reviews the literature regarding pathophysiology and management of this clinical entity. Patients and methods A 39 year-old gentleman with arrested hydrocephalus incidentally found during work-up for new-onset seizure and managed conservatively for ten years presented with increasing headache, memory loss, gait instability and urinary and fecal incontinence. Stable massive triventriculomegaly was documented on serial brain imaging, and ophthalmologic exam revealed no papilledema. Results The patient underwent endoscopic third ventriculostomy with immediate post-operative improvement of headache, resolution of incontinence, and cessation of seizures. At 15 months after surgery, neuropsychiatric testing demonstrated improvement in visuomotor skills, problem solving, verbal fluency and cognitive flexibility compared to his pre-operative baseline. At 18 months after surgery he remained seizure free with full continence and significant improvement in headaches. Conclusion Early recognition of arrested hydrocephalus and its potential for decompensation may prompt surgical treatment and prevent neurologic deterioration.

A highly multiplexed superresolution imaging strategy with single-molecule accuracy enabled by fluorescent nanodiamonds called madSTORM affords the ability to define spatial relationships among constituent molecules within structures. It makes it possible to probe the molecular topology of complex signaling cascades and other heterogeneous networks., Investigation of heterogeneous cellular structures using single-molecule localization microscopy has been limited by poorly defined localization accuracy and inadequate multiplexing capacity. Using fluorescent nanodiamonds as fiducial markers, we define and achieve localization precision required for single-molecule accuracy in dSTORM images. Coupled with this advance, our new multiplexing strategy, madSTORM, allows accurate targeting of multiple molecules using sequential binding and elution of fluorescent antibodies. madSTORM is used on an activated T-cell to localize 25 epitopes, 14 of which are on components of the same multimolecular T-cell receptor complex. We obtain an average localization precision of 2.6 nm, alignment error of 2.0 nm, and

Introduction Retained reservoirs can be a complex problem for clinicians who manage patients with inflatable penile prostheses (IPPs). Although the general safety of retained reservoirs is well documented, data on the long-term outcomes of these foreign bodies is scarce. In recent years, complications associated with retained reservoirs and the subsequent management of these cases have become more recognized. Aim To review, analyze, and summarize the concept of retained reservoirs and their associated complications with retained reservoirs and to provide a guide for management of complicated retained reservoir patients. Methods We performed a systematic review of the PubMed database on retained reservoir-related complications and perioperative management. Main Outcome Measures We reviewed all publications that detailed complications associated specifically with retained penile prosthesis reservoirs and analyzed perioperative strategies used by providers. Any publication outlining IPP reservoir–related complication(s) stemming from a reservoir that was part of a functioning IPP was excluded. Results Although the risk is low, serious complications can and do arise from retained reservoirs. To properly manage these patients, clinicians must have knowledge of the prosthetic history and maintain a low threshold for obtaining cross-sectional imaging. By using methodical perioperative planning, the need for reintervention in patients with complications can be reduced, and improved surgical outcomes can be achieved. Conclusions The management of retained reservoirs and their complications can be a clinical challenge for prosthetics providers. As such, more data regarding long-term outcomes and management strategies of retained reservoirs are required to better serve this subset of patients with prostheses. Reddy AG, Tsambarlis PN, Akula KP, et al. Retained Reservoirs of Inflatable Penile Prosthesis: A Systematic Review of Literature. Sex Med Rev 2020;8:355–363.

The potential to image subsurface fluorescent contrast agents at high spatial resolution has facilitated growing interest in short-wave infrared (SWIR) imaging for biomedical applications. The early but growing literature showing improvements in resolution in small animal models suggests this is indeed the case, yet to date, images from larger animal models that more closely recapitulate humans have not been reported. We report the first imaging of SWIR fluorescence in a large animal model. Specifically, we imaged the vascular kinetics of an indocyanine green (ICG) bolus injection during open craniotomy of a mini-pig using a custom SWIR imaging instrument and a clinical-grade surgical microscope that images ICG in the near-infrared-I (NIR-I) window. Fluorescence images in the SWIR were observed to have higher spatial and contrast resolutions throughout the dynamic sequence, particularly in the smallest vessels. Additionally, vessels beneath a surface pool of blood were readily visualized in the SWIR images yet were obscured in the NIR-I channel. These first-in-large-animal observations represent an important translational step and suggest that SWIR imaging may provide higher spatial and contrast resolution images that are robust to the influence of blood.

Elderly subjects are predisposed to intrarenal renin-angiotensin system (RAS) activation, which increases the risk for hypertension, kidney injury, and chronic kidney disease (CKD). The prorenin re...

Depression may occur in up to 30% of individuals with cutaneous lupus erythematosus (CLE), many of whom may also have systemic manifestations. Chronic cutaneous lupus erythematosus (CCLE) conditions are less likely to present systemic involvement than acute and subacute conditions but more often cause permanent scarring and dyspigmentation. However, little is known about depression in those who have CCLE confined to the skin (primary CCLE). As African Americans are at high risk for primary CCLE and depression, we aimed to investigate the prevalence of and explore the risk factors for depression in a population-based cohort of predominantly Black patients with primary CCLE. This was a cross-sectional analysis of a cohort of individuals with a documented diagnosis of primary CCLE, established in metropolitan Atlanta, GA, USA. Participants were recruited from the Centers for Disease Control and Prevention (CDC) population-based Georgia Lupus Registry, multicenter dermatology clinics, community practices, and self-referrals. The Patient-Reported Outcomes Measurement Information System (PROMIS) was used to measure the primary outcome: depressive symptoms. Stand-alone questions were used to assess sociodemographics and healthcare utilization. Emotional, informational, and instrumental support were measured with PROMIS short forms, interpersonal processes of care with the IPC-29 survey, and skin-related quality of life with the Skindex-29+ tool. Of 106 patients, 92 (86.8%) were female, 91 (85.8%) were Black, 45 (42.9%) were unemployed or disabled, and 28 (26.4%) reported moderate to severe depressive symptoms. Depression severity was lower in patients who were aged ≥ 60 years, were married, or had graduated from college. Univariate analysis showed that being employed (odds ratio [OR] 0.24; 95% confidence interval [CI] 0.10–0.61), insured (OR 0.23; 95% CI 0.09–0.60), reporting higher instrumental, informational, and emotional support (OR 0.75; 95% CI 0.60–0.94; OR 0.62; 95% CI 0.49–0.78; and OR 0.48; 95% CI 0.35–0.65, respectively), visiting a primary care physician in the last year (OR 0.16; 95% CI 0.04–0.61) and reporting better physician–patient interactions (OR 0.56; 95% CI 0.37–0.87) were negatively associated with depression. Patient’s perception of staff disrespect (OR 2.30; 95% CI 1.19–4.47) and worse skin-related quality of life (OR 1.04; 95% CI 1.02–1.06) rendered higher risk. In multivariate analysis, only perception of staff disrespect (OR 2.35; 95% CI 1.06–5.17) and lower emotional support (OR 0.48; 95% CI 0.35–0.66) remained associated with depression. Over one-quarter of a predominantly Black population-based cohort of individuals with primary CCLE reported moderate to severe depression, a rate three to five times higher than described previously in the general population from the same metropolitan Atlanta area. Our findings suggest that, while patient’s perception of discrimination in the healthcare setting may play a role as a determinant of depression, social support may be protective. In addition to routine mental health screening and depression treatment, interventions directed at providing emotional support and improving office staff interpersonal interactions may contribute to reduce the risk of depression in patients with CCLE.