Pavement ant extract is a chemotaxis repellent for C. elegans.

Ant behavior relies on a collection of natural products, from following trail pheromones during foraging to warding off potential predators. How nervous systems sense these compounds to initiate a behavioral response remains unclear. Here, we used Caenorhabditis elegans chemotaxis assays to investigate how ant compounds are detected by heterospecific nervous systems. We found that C. elegans avoid extracts of the pavement ant ( Tetramorium immigrans ) and either osm-9 or tax-4 ion channels are required for this response. These experiments were conducted in an undergraduate laboratory course, demonstrating that new insights into interspecies interactions can be generated through genuine research experiences in a classroom setting.

Conservation and Targets of miR-71: A Systematic Review and Meta-Analysis.

MicroRNAs (miRNAs) perform a pivotal role in the regulation of gene expression across the animal kingdom. As negative regulators of gene expression, miRNAs have been shown to function in the genetic pathways that control many biological processes and have been implicated in roles in human disease. First identified as an aging-associated gene in C. elegans, miR-71, a miRNA, has a demonstrated capability of regulating processes in numerous different invertebrates, including platyhelminths, mollusks, and insects. In these organisms, miR-71 has been shown to affect a diverse range of pathways, including aging, development, and immune response. However, the exact mechanisms by which miR-71 regulates these pathways are not completely understood. In this paper, we review the identified functions of miR-71 across multiple organisms, including identified gene targets, pathways, and the conditions which affect regulatory action. Additionally, the degree of conservation of miR-71 in the evaluated organisms and the conservation of their predicted binding sites in target 3' UTRs was measured. These studies may provide an insight on the patterns, interactions, and conditions in which miR-71 is able to exert genotypic and phenotypic influence.

Primary Repair of Upper Extremity Peripheral Nerve Injuries: An NSQIP Analysis From 2010 to 2016.

BACKGROUND: To identify the rate of 30-day complications after primary repair of upper extremity peripheral nerve injuries, associated diagnoses, and postoperative complication rate. METHODS: The American College of Surgeons National Surgical Quality Improvement Program database was reviewed from 2010 to 2016. Current Procedural Terminology codes consistent with primary nerve repair of the upper extremity were identified and included in the analysis. Patient demographics, comorbidities, type of procedure (elective/emergent), wound class, operative time, and 30-day complications were recorded. Patients with isolated upper extremity nerve injuries (isolated) were compared with those with peripheral nerve injuries in addition to bone, tendon, or soft tissue injuries (multiple). RESULTS: In all, 785 patients were identified as having upper extremity nerve repairs (0.16%). Of them, 64% were men and 36% were women; the average patient age was 40 years. The most common indication for surgery was injury to the digits (54% of cases). Thirty-day adverse events occurred in 3% of all cases. Isolated nerve injury occurred in 43% of patients, whereas 57% had additional injuries. The multiple injury group had a significantly higher complication rate compared with the isolated group (1% vs 4.5%) (P = .007). Repair of tendon at forearm or wrist was the most common concurrent procedure performed. CONCLUSIONS: Thirty-day complications among upper extremity peripheral nerve injuries are low, accounting for 3% of cases. Return to the operating room accounted for nearly half of all complications. Patients in the multiple injury group accounted for more than half of these and had a significantly higher complication rate compared with patients with isolated nerve injuries.

Dickkopf-1 Can Lead to Immune Evasion in Metastatic Castration-Resistant Prostate Cancer.

PURPOSE: Metastatic castration-resistant prostate cancer (mCRPC) with low androgen receptor (AR) and without neuroendocrine signaling, termed double-negative prostate cancer (DNPC), is increasingly prevalent in patients treated with AR signaling inhibitors and is in need of new biomarkers and therapeutic targets. METHODS: Candidate genes enriched in DNPC were determined using differential gene expression analysis of discovery and validation cohorts of mCRPC biopsies. Laboratory studies were carried out in human mCRPC organoid cultures, prostate cancer (PCa) cell lines, and mouse xenograft models. Epigenetic studies were carried out in a rapid autopsy cohort. RESULTS: Dickkopf-1 (DKK1) expression is increased in DNPC relative to prostate-specific antigen (PSA)-expressing mCRPC in the Stand Up to Cancer/Prostate Cancer Foundation discovery cohort (11.2 v 0.28 reads per kilobase per million mapped reads; q < 0.05; n = 117) and in the University of Washington/Fred Hutchinson Cancer Research Center cohort (9.2 v 0.99 fragments per kilobase of transcript per million mapped reads; P < .0001). DKK1 expression can be regulated by activated Wnt signaling in vitro and correlates with activating canonical Wnt signaling mutations and low PSA mRNA in mCRPC biopsies (P < .05). DKK1 hypomethylation was associated with increased DKK1 mRNA expression (Pearson r = -0.66; P < .0001) in a rapid autopsy cohort (n = 7). DKK1-high mCRPC biopsies are infiltrated with significantly higher numbers of quiescent natural killer (NK) cells (P < .005) and lower numbers of activated NK cells (P < .0005). Growth inhibition of the human PCa model PC3 by the anti-DKK1 monoclonal antibody DKN-01 depends on the presence of NK cells in a severe combined immunodeficient xenograft mouse model. CONCLUSION: These results support DKK1 as a contributor to the immunosuppressive tumor microenvironment of DNPC. These data have provided the rationale for a clinical trial targeting DKK1 in mCRPC (ClinicalTrials.gov identifier: NCT03837353).

Novel destabilizing Dynactin variant (DCTN1 p.Tyr78His) in patient with Perry syndrome.

INTRODUCTION: Perry syndrome, also recognized as Perry disease, is a rare autosomal dominant disorder characterized by midlife-onset atypical parkinsonism, apathy or depression, respiratory failure and weight loss caused by a mutation in the Dynactin (DCTN1) gene. CASE DESCRIPTION: A fifty-six years-old adopted male presented with atypical parkinsonism with bradykinesia and postural instability, apathy, weight loss, and recurrent respiratory failure due to central hypoventilation requiring tracheostomy. METHODS AND RESULTS: Clinical workup revealed a novel DCTN1 p.Tyr78His variant. Using bioinformatic protein structure modeling, we compare our patient's variant to known DCTN1 mutations and predict protein stability of each variant at the CAP-Gly domain of p150Glued. All eight variants causing Perry syndrome, as well as Tyr78His, are located at site expected to interact with MAPRE1 tail and are predicted to be destabilizing. Variants causing atypical parkinsonism with incomplete Perry syndrome phenotype (K56R and K68E) are not significantly destabilizing in silico. CONCLUSION: We propose p.Tyr78His as the ninth pathogenic DCTN1 variant causing Perry syndrome. Bioinformatic protein modeling may provide additional window to understand and interpret DCTN1 variants, as we observed non-destabilizing variants to have different phenotype than destabilizing variants.

Gastrostomy tube placement increases the risk of ventriculoperitoneal shunt infection: a multiinstitutional study.

OBJECTIVEGastrostomy tube placement can temporarily seed the peritoneal cavity with bacteria and thus theoretically increases the risk of shunt infection when the two procedures are performed contemporaneously. The authors hypothesized that gastrostomy tube placement would not increase the risk of ventriculoperitoneal shunt infection. The object of this study was to test this hypothesis by utilizing a large patient cohort combined from multiple institutions.METHODSA retrospective study of all adult patients admitted to five institutions with a diagnosis of aneurysmal subarachnoid hemorrhage between January 2005 and January 2015 was performed. The primary outcome of interest was ventriculoperitoneal shunt infection. Variables, including gastrostomy tube placement, were tested for their association with this outcome. Standard statistical methods were utilized.RESULTSThe overall cohort consisted of 432 patients, 47% of whom had undergone placement of a gastrostomy tube. The overall shunt infection rate was 9%. The only variable that predicted shunt infection was gastrostomy tube placement (p = 0.03, OR 2.09, 95% CI 1.07-4.08), which remained significant in the multivariate analysis (p = 0.04, OR 2.03, 95% CI 1.04-3.97). The greatest proportion of shunts that became infected had been placed more than 2 weeks (25%) and 1-2 weeks (18%) prior to gastrostomy tube placement, but the temporal relationship between shunt and gastrostomy was not a significant predictor of shunt infection.CONCLUSIONSGastrostomy tube placement significantly increases the risk of ventriculoperitoneal shunt infection.

Prospective Genomic Profiling of Prostate Cancer Across Disease States Reveals Germline and Somatic Alterations That May Affect Clinical Decision Making.

PURPOSE: A long natural history and a predominant osseous pattern of metastatic spread are impediments to the adoption of precision medicine in patients with prostate cancer. To establish the feasibility of clinical genomic profiling in the disease, we performed targeted deep sequencing of tumor and normal DNA from patients with locoregional, metastatic non-castrate, and metastatic castration-resistant prostate cancer (CRPC). METHODS: Patients consented to genomic analysis of their tumor and germline DNA. A hybridization capture-based clinical assay was employed to identify single nucleotide variations, small insertions and deletions, copy number alterations and structural rearrangements in over 300 cancer-related genes in tumors and matched normal blood. RESULTS: We successfully sequenced 504 tumors from 451 patients with prostate cancer. Potentially actionable alterations were identified in DNA damage repair (DDR), PI3K, and MAP kinase pathways. 27% of patients harbored a germline or a somatic alteration in a DDR gene that may predict for response to PARP inhibition. Profiling of matched tumors from individual patients revealed that somatic TP53 and BRCA2 alterations arose early in tumors from patients who eventually developed metastatic disease. In contrast, comparative analysis across disease states revealed that APC alterations were enriched in metastatic tumors, while ATM alterations were specifically enriched in CRPC. CONCLUSION: Through genomic profiling of prostate tumors representing the disease clinical spectrum, we identified a high frequency of potentially actionable alterations and possible drivers of disease initiation, metastasis and castration-resistance. Our findings support the routine use of tumor and germline DNA profiling for patients with advanced prostate cancer, for the purpose of guiding enrollment in targeted clinical trials and counseling families at increased risk of malignancy.

Achieving 0.2% relative expanded uncertainty in ion chromatography analysis using a high-performance methodology.

A high-performance (HP) technique that was originally developed for inductively coupled plasma optical emission spectrometry (ICP-OES) has been successfully translated to ion chromatography (IC) to enable analyses with extremely low uncertainty. As an example application of the HP-IC methodology, analyses of several National Institute of Standards and Technology (NIST) Standard Reference Materials (SRMs) in the SRM 3180 series of anion standard solutions are reported. The relative expanded uncertainty values expressed at 95% confidence for these analyses range from 0.087% to 0.27% and average 0.18%. Strong correlation between analyte and internal standard anion peak heights or peak areas, as well as the use of a unique drift-correction approach, is shown to be important for attaining such low uncertainty.

The role of orthophosphate and dissolved oxygen in the performance of arsenic-iron removal plants in Bangladesh.

Arsenic iron removal plants (AIRPs) are used in some locations in Bangladesh to remove arsenic from groundwater to provide access to safer drinking water. In this study, the influence of orthophosphate in influent water on the performance of 21 (of 105) AIRPs installed in the Manikganj District was evaluated. The degree of aeration was also estimated, and the role of dissolved oxygen in AIRP performance is discussed. AIRP installations were done by a local non-governmental organization (The Society for People's Action in Change and Equity) with financial assistance from the Australian High Commission, Dhaka under the Direct Aid Program of the Australian Government. The presence of orthophosphate in the influent did not influence arsenic removal efficiency in the tested AIRPs, likely due to the high iron concentrations at all sites. The high iron provides adequate surface area for both orthophosphate and arsenic to be removed. Orthophosphate co-precipitated with iron oxides much more quickly than arsenic, in one cleaning cycle study, and is expected to play a more significant role in interfering with arsenic removal at sites with much lower iron concentrations. The aeration trays studied are estimated to introduce at least 2.4-3.7 mg/L of dissolved oxygen. In normal operation, sufficient oxygen is introduced through the aeration tray to fully oxidize all influent iron. The AIRPs studied show promise for use in areas of Bangladesh with high natural iron, where users are concerned with arsenic, iron, or both, in their drinking water.

Multi-level corpectomies and reconstruction via a single posterolateral approach.

The surgical treatment of ventral spinal canal compression has traditionally required either an anterior or combined anterior-posterior decompression and stabilization. These types of approaches carry a significant morbidity and may not be appropriate for all patients. We report our experience with multi-level corpectomies and reconstruction performed via a single, posterolateral approach. A retrospective review was performed of six consecutive patients at a single institution who were treated for ventral multi-level spinal cord compression via a single posterolateral approach. All six patients underwent reconstruction and stabilization with an expandable cage and posterior fixation. Five patients had metastatic cancer with spinal cord compression and one patient had osteomyelitis with a ventral epidural abscess and vertebral body collapse. All patients underwent 2-level corpectomies. Pre-operative and post-operative neurologic function and stabilization construct integrity were analyzed. All patients had successful decompression and stabilization and there were no hardware complications. Three peri-operative complications were encountered: post-operative pleural effusion needing thoracostomy drainage, transient leg paresis that resolved at 2months and a post-operative wound infection needing operative debridement. At last follow-up all patients had improvement or stabilization of their neurological function. Long-term follow-up was limited by the progression of metastatic disease and death in all the patients with cancer. This study demonstrates that symptomatic improvement can be achieved in select patients requiring multi-level corpectomies when using a single posterolateral approach with expandable cage reconstruction and posterior stabilization.

Heat-assisted argon electrospray interface for low-flow rate liquid sample introduction in plasma spectrometry.

A heated (approximately 90 degrees C) laminar flow interface has been designed to assist in the development of an argon electrospray sample introduction system for low-flow rate applications using inductively coupled plasma (ICP) spectrometry. Previously, the stability and robustness of the ICP were compromised by the entrainment of air, N2, or gas mixtures (e.g., Ar-N2) from the electrospray source. Also, more concentrated organic solvents (e.g., 50% (v/v) methanol-water), typically introduced by electrospray, could generate carbon deposits that obstruct the entrance lens to an ICP optical emission spectrometer (ICP-OES) or the sampler/skimmer cone interface in an ICP mass spectrometer (ICP-MS), decreasing analyte sensitivity. With the new interface design, a stable spray of 5% (v/v) methanol-water in a pure argon environment is achieved, eliminating the aforementioned problems. The turbulence and the consequent droplet loss caused by high gas velocity around the electrospray capillary are mitigated by the use of a laminar-flow gas with the aid of a flow diffuser. The argon electrospray interface is successfully installed on an ICP-OES and an ICP-MS for the first time.

Potential primary measurement tool for the quantification of DNA.

An automated sample introduction system, utilizing a demountable direct injection high-efficiency nebulizer (d-DIHEN), is successfully incorporated for the first time with an inductively coupled plasma optical emission spectrometer (ICP-OES) for the measurement of the phosphorus content in acid-digested nucleotides and deoxyribonucleic acid (DNA). With this experimental setup, the solution uptake rate and volume are reduced from 170 to 30 microL min(-1) and from 10 to 2.4 mL, respectively, thereby reducing the required DNA sample mass for solutions containing 3 microg g(-1) P from 300 to 72 microg of DNA, in comparison to previous analyses in our laboratory using a glass concentric nebulizer with cyclonic spray chamber arrangement. The use of direct injection also improves P (I) 213.617 nm sensitivity by a factor of 4 on average. A high-performance (HP) methodology in combination with the previous sample introduction system and ICP-OES provides simultaneous, time-correlated internal standardization and drift correction resulting in relative expanded uncertainties (% U) for the P mass fractions in the range of 0.1-0.4 (95% confidence level) for most of the thymidine 5'-monophosphate (TMP), calf thymus DNA (CTDNA), and plasmid DNA (PLDNA) analyses. The d-DIHEN with HP-ICP-OES methodology allows for the quantification of DNA mass at P mass fractions as low as 0.5 microg g(-1), further reducing the required DNA mass to 12 microg, with small uncertainty (< or = 0.4%). This successful approach will aid in the development and certification of nucleic acid certified reference materials (CRMs), particularly for these samples that are typically limited in volume.

Effects of sildenafil on nigrostriatal dopamine neurons in a murine model of Parkinson's disease.

The objective of this study was to determine if the phosphodiesterase 5 (PDE-5) inhibitor, sildenafil, could be used as a neuroprotective agent in a chronic 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) murine model of Parkinson's disease. The underlying hypothesis of these studies is that blockade of PDE-5 catabolism of cGMP will attenuate the loss of nigrostriatal dopamine (NSDA) neurons following chronic neurotoxin exposure. Chronic MPTP-treated mice were administered sildenafil using three different regimens. Animals were: 1) treated with sildenafil and then exposed to chronic MPTP; 2) treated concurrently with sildenafil and MPTP; and 3) first exposed to MPTP and subsequently treated with sildenafil. End points of neurotoxicity included dopamine (DA) and tyrosine hydroxylase (TH) concentrations in NSDA axon terminals in the striatum, and stereological cell counts of TH immunoreactive neurons in the substantia nigra. Results reveal that sildenafil did not prevent neurotoxicity produced by chronic MPTP exposure regardless of the treatment paradigms employed. On the other hand, sildenafil did not produce any deleterious effect on NSDA neuron function nor did it potentiate the neurotoxic effects of MPTP. These results suggest that sildenafil would not accelerate DA cell loss when used as a treatment for erectile dysfunction in men diagnosed with Parkinson's disease.

Minimally invasive image-guided direct repair of bilateral L-5 pars interarticularis defects.

Lower back pain from spondylolysis historically has been treated with a variety of options ranging from conservative care to open fusion. The authors describe the novel technique of minimally invasive bilateral pars interarticularis screw placement by utilizing intraoperative 3D imaging and frameless navigation in a 17-year-old male athlete. This technique is a modification of the open technique first described in 1970 by Buck and has the advantages of minimal dissection requirements with improved screw trajectory visualization. The patient's postoperative course is discussed, followed by a brief literature review of pars interarticularis defect treatment.

Autophagic death of adult hippocampal neural stem cells following insulin withdrawal.

Novel therapeutic approaches using stem cell transplantation to treat neurodegenerative diseases have yielded promising results. However, survival of stem cells after transplantation has been very poor in animal models, and considerable efforts have been directed at increasing the viability of engrafted stem cells. Therefore, understanding the mechanisms that regulate survival and death of neural stem cells is critical to the development of stem cell-based therapies. Hippocampal neural (HCN) stem cells derived from the adult rat brain undergo cell death following insulin withdrawal, which is associated with downregulation of antiapoptotic Bcl-2 family members. To understand the type of cell death in HCN cells following insulin withdrawal, apoptosis markers were assessed. Of note, DNA fragmentation or caspase-3 activation was not observed, but rather dying cells displayed features of autophagy, including increased expression of Beclin 1 and the type II form of light chain 3. Electron micrographs showed the dramatically increased formation of autophagic vacuoles with cytoplasmic contents. Staurosporine induced robust activation of caspase-3 and nucleosomal DNA fragmentation, suggesting that the machinery of apoptosis is intact in HCN cells despite the apparent absence of apoptosis following insulin withdrawal. Autophagic cell death was suppressed by knockdown of autophagy-related gene 7, whereas promotion of autophagy by rapamycin increased cell death. Taken together, these data demonstrate that HCN cells undergo a caspase-independent, autophagic cell death following insulin withdrawal. Understanding the mechanisms governing autophagy of adult neural stem cells may provide novel strategies to improve the survival rate of transplanted stem cells for treatment of neurodegenerative diseases. Disclosure of potential conflicts of interest is found at the end of this article.