Characterizing Hydroxyl Radical Formation from the Light-Driven Fe(II)-Peracetic Acid Reaction, a Key Process for Aerosol-Cloud Chemistry.

The reaction of peracetic acid (PAA) and Fe(II) has recently gained attention due to its utility in wastewater treatment and its role in cloud chemistry. Aerosol-cloud interactions, partly mediated by aqueous hydroxyl radical (OH) chemistry, represent one of the largest uncertainties in the climate system. Ambiguities remain regarding the sources of OH in the cloud droplets. Our research group recently proposed that the dark and light-driven reaction of Fe(II) with peracids may be a key contributor to OH formation, producing a large burst of OH when aerosol particles take up water as they grow to become cloud droplets, in which reactants are consumed within 2 min. In this work, we quantify the OH production from the reaction of Fe(II) and PAA across a range of physical and chemical conditions. We show a strong dependence of OH formation on ultraviolet (UV) wavelength, with maximum OH formation at λ = 304 ± 5 nm, and demonstrate that the OH burst phenomenon is unique to Fe(II) and peracids. Using kinetics modeling and density functional theory calculations, we suggest the reaction proceeds through the formation of an [Fe(II)-(PAA)2(H2O)2] complex, followed by the formation of a Fe(IV) complex, which can also be photoactivated to produce additional OH. Determining the characteristics of OH production from this reaction advances our knowledge of the sources of OH in cloudwater and provides a framework to optimize this reaction for OH output for wastewater treatment purposes.

The Feasibility of Translaminar Screws in the Subaxial Cervical Spine: Computed Tomography and Cadaveric Validation.

BACKGROUND: The use of translaminar screws may serve as a viable salvage method for complicated cases. To our understanding, the study of the feasibility of translaminar screw insertion in the actual entire subaxial cervical spine has not been carried out yet. The purpose of this study was to report the feasibility of translaminar screw insertion in the entire subaxial cervical spine. METHODS: Eighteen cadaveric spines were harvested from C3 to C7 and 1-mm computed tomography (CT) scans and three-dimensional reconstructions were created to exclude any bony anomaly. Thirty anatomically intact segments were collected (C3, 2; C4, 3; C5, 3; C6, 8; and C7, 14), and randomly arranged. Twenty-one segments were physically separated at each vertebral level (group S), while 9 segments were not separated from the vertebral column and left in situ (group N-S). CT measurement of lamina thickness was done for both group S and group N-S, and manual measurement of various length and angle was done for group S only. Using the trajectory proposed by the previous studies, translaminar screws were placed at each level. Screw diameter was the same or 0.5 mm larger than the proposed diameter based on CT measurement. Post-insertion CT was performed. Cortical breakage was checked either visually or by CT. RESULTS: When 1° and 2° screws of the same size were used, medial cortex breakage was found 13% and 33% of the time, respectively. C7 was relatively safer than the other levels. With larger-sized screws, medial cortex breakage was found in 47% and 46% of 1° and 2° screws, respectively. There were no facet injuries due to the screws in group N-S. CONCLUSIONS: Translaminar screw insertion in the subaxial cervical spine is feasible only when the lamina is thick enough to avoid any breakage that could lead to further complications. The authors do not recommend inserting translaminar screws in the subaxial cervical spine except in some salvage cases in the presence of a thick lamina.

Prion protein lowering is a disease-modifying therapy across prion disease stages, strains and endpoints.

Lowering of prion protein (PrP) expression in the brain is a genetically validated therapeutic hypothesis in prion disease. We recently showed that antisense oligonucleotide (ASO)-mediated PrP suppression extends survival and delays disease onset in intracerebrally prion-infected mice in both prophylactic and delayed dosing paradigms. Here, we examine the efficacy of this therapeutic approach across diverse paradigms, varying the dose and dosing regimen, prion strain, treatment timepoint, and examining symptomatic, survival, and biomarker readouts. We recapitulate our previous findings with additional PrP-targeting ASOs, and demonstrate therapeutic benefit against four additional prion strains. We demonstrate that <25% PrP suppression is sufficient to extend survival and delay symptoms in a prophylactic paradigm. Rise in both neuroinflammation and neuronal injury markers can be reversed by a single dose of PrP-lowering ASO administered after the detection of pathological change. Chronic ASO-mediated suppression of PrP beginning at any time up to early signs of neuropathology confers benefit similar to constitutive heterozygous PrP knockout. Remarkably, even after emergence of frank symptoms including weight loss, a single treatment prolongs survival by months in a subset of animals. These results support ASO-mediated PrP lowering, and PrP-lowering therapeutics in general, as a promising path forward against prion disease.

Antisense oligonucleotides extend survival of prion-infected mice.

Prion disease is a fatal, incurable neurodegenerative disease of humans and other mammals caused by conversion of cellular prion protein (PrP; PrPC) into a self-propagating neurotoxic conformer (prions; PrPSc). Strong genetic proofs of concept support lowering PrP expression as a therapeutic strategy. Antisense oligonucleotides (ASOs) can provide a practical route to lowering one target mRNA in the brain, but their development for prion disease has been hindered by three unresolved questions from prior work: uncertainty about mechanism of action, unclear potential for efficacy against established prion infection, and poor tolerability of drug delivery by osmotic pumps. Here we test antisense oligonucleotides (ASOs) delivered by bolus intracerebroventricular injection to intracerebrally prion-infected wild-type mice. Prophylactic treatments given every 2-3 months extended survival times 61-98%, and a single injection at 120 days post-infection, near the onset of clinical signs, extended survival 55% (87 days). In contrast, a non-targeting control ASO was ineffective. Thus, PrP lowering is the mechanism of action of ASOs effective against prion disease in vivo, and infrequent, or even single, bolus injections of ASOs can slow prion neuropathogenesis and markedly extend survival, even when initiated near clinical signs. These findings should empower development of PrP-lowering therapy for prion disease.

Anatomy of Lamina in the Subaxial Cervical Spine With the Special Reference to Translaminar Screws: CT and Cadaveric Analysis With Screw Trajectory Simulation.

STUDY DESIGN: A cadaveric study. SUMMARY OF BACKGROUND DATA: Translaminar screws were initially developed for C2 fixation. Since then, their usage has expanded to include the subaxial cervical spine, and thoracic and lumbar spine. To the best of our knowledge, special anatomy for inserting translaminar screws in the subaxial cervical spine has not been studied. OBJECTIVE: To report the special anatomy for inserting translaminar screws in the subaxial cervical spine. METHODS: A total of 18 cadaveric spines were harvested from C3 to C7 and 1 mm computed tomography (CT) scans and 3D reconstructions were obtained. Bilateral translaminar screw entry points and trajectories were simulated at each level from C3 to C7 utilizing Kodak Carestream/Pacs Ver 10.2. Constructs were selected to achieve maximal bony purchase with 1 screw, designated the "primary screw." The contralateral screw, designated the "secondary screw," was selected to achieve the optimal allowable diameter possible while avoiding a simulated cortical breach, which was not always necessarily the "best purchase" diameter. Initial screw diameters selected were 3.5 mm; however, in the event that a narrower portion was encountered, then a 3.0 mm diameter screw was utilized instead. The crossing area of both screws were calculated geometrically. Maximal thickness of the lamina was considered in determining the diameter of screws. Whenever possible, 3.5 mm screws were selected in both lamina (3.5/3.5 mm); however, if a 3.5 mm screw was utilized as the primary screw, but the permissible range (P) for the secondary screw was <3.5 mm, then a hybrid construct was utilized (3.5/3.0 mm). In cases where P was <3 mm, then both screws were studied at 3 mm (3.0/3.0 mm). Screw diameters that optimized trajectory and bony purchase, while remaining within the permissible range, were analyzed, tabulated, and recorded. On CT, along the trajectory of the screws, the image was cut and measured in terms of screw length, the narrowest portion of the lamina, vertical angle, and horizontal angle in both primary and secondary screws. On the individually separated cervical spine segments in cadavers (11 of 18), we performed caliper measurements on the same portions that were measured on CT. It could not be exactly the same portions, however, due to the 3-dimensional characteristics of the specimens. RESULTS: For C3, only 1 specimen allowed 2 screws (3/3 mm), while the remaining specimens permitted a unilateral primary screw (3.5 or 3 mm) only. For C4, 37% of specimens allowed 2 screws (3.5/3 mm or 3/3 mm), but the rest allowed only a unilateral primary screw (3.5 or 3 mm). For C5, 58% allowed 2 screws (3.5/3.5, 3.5/3, or 3/3 mm). For C6, 89% of specimen allowed 2 screws (3.5/3.5, 3.5/3, or 3/3 mm). For C7, all levels allowed 2 screws (3.5/3.5, 3.5/3, 4/4, 4/3, 4.5/3, 4.5/3.5, or 4/3.5 mm). On CT, the average lengths of the 1- and 2-degree screws were 26.14 and 24.01 mm, respectively. The average vertical and horizontal angles were 22.26 and 40.66 degrees for the 1-degree screw, and 3.45 and 45.59 degrees for the 2-degree screw. On cadavers, the average lengths of the 1- and the 2-degree screws were 22.58 and 23.44 mm, respectively. The average vertical and horizontal angles were 23.67 and 54.44 degrees for the 1-degree screw, and 2.28 and 54.89 degrees for the 2-degree screw. CONCLUSIONS: This is a report of the anatomy of the lamina in the subaxial cervical spine with the special reference to translaminar screws. It was analyzed with CT and cadaveric spines along with simulated screw trajectories. For the 1-degree translaminar screw, the entry point is the distance of the diameter of desired screw superior to the inferior margin of lamina-spinous process junction. The trajectory should be targeted toward the most superomedial corner of lateral mass. For the 2-degree translaminar screw, the entry point is the distance of the diameter of desired screw below the superior margin of lamina-spinous process junction, and the target is the most superolateral corner of lateral mass, which is typically horizontal. Further studies are needed to assess the feasibility of translaminar screw insertion in the actual subaxial cervical spine.

Effect of 2% Chlorhexidine Gluconate-Impregnated Cloth on Surgical Site Infections in Vascular Surgery.

BACKGROUND: Surgical site infections (SSIs) are a significant burden to patients and health care systems. This retrospective study evaluates the observed rates of SSI after our institution implemented chlorhexidine gluconate-impregnated (CHG) cloth as a preoperative antiseptic preparation in elective vascular surgery. METHODS: Between March 2011 and January 2012, we reviewed 250 patients who underwent elective vascular surgery who used the CHG cloth preoperatively. Their rate of SSIs was compared with 252 control patients who received the CHG shower preoperatively during the preintervention period. Urgent and emergent cases were excluded. The primary outcome measured was SSI within 30 days of index operation. RESULTS: There was no baseline difference in mean age, gender distribution, smoking status, diabetes, chronic obstructive pulmonary disease, and the number of patients with body mass index >40 between the cohorts. There was no difference in the overall rate (5.6% vs. 5.6%, P = 1.00) and type of SSIs between the 2 groups, but the control group trended toward deeper infections (4 deep incisional and 2 organ space vs. none and 1, respectively). The control group also had more dirty or infected wound categories (10 vs. 21.4%, P < 0.01) and more perioperative antibiotic errors and hypothermia (P < 0.02). CONCLUSIONS: There was no observed difference in SSI rates before and after implementation of the CHG as the preoperative method of skin decontamination in our retrospective case-control cohorts.

The insertion technique of translaminar screws in the thoracic spine: computed tomography and cadaveric validation.

BACKGROUND CONTEXT: Translaminar screws can be a good salvage technique in some cases of severe deformities, infection, tumor, osteoporosis, and revision cases with altered anatomy. To our knowledge, the insertion technique for translaminar screws in the thoracic spine has not been studied. PURPOSE: To suggest a safe insertion technique of translaminar screws in the thoracic spine. STUDY DESIGN: A cadaveric study. METHODS: Fifteen cadaveric spines were harvested from T1 to T12, and 1-mm computed tomography (CT) scans and three-dimensional reconstructions were obtained to rule out any bony anomaly. Eleven of the cadaveric spines were separated at each level from T1 to T12 (Group S) and four were not separated (Group N-S). Translaminar screws were inserted into every level along the trajectories proposed by the previous studies. The screw diameter was determined based on the reference article. For T1-T6, the screw diameter selected was 4 mm, and for T7-T12, a 3.5-mm diameter screw was used instead. The entry point for the 1° screw was at a distance equal to the diameter of the desired screw above the inferior margin of the spinolaminar junction. To create the trajectory, a drill guide was inserted at the entry point and directed toward the middle portion of the base of the transverse process of the contralateral side and was followed carefully to not break the inner/outer cortex of the lamina. The length of the drilled hole, representing the trajectory of the screw made by the drill guide, was measured, and the 1° screws were inserted according to the length measured. The entry point for the 2° screw was at a distance equal to the diameter of the screw below the superior margin of the base of the spinous process and lamina junction. The drill guide was pointed toward the inferior angle of the contralateral junction of the rib and the vertebra along the slope of the contralateral lamina. The 2° screw was inserted in the same manner as previously described. The 2° screw diameter was downsized if there was not enough space because of the 1° screw. For each vertebra from the 11 separated cadaveric spines, inner or outer cortex breakage was checked visually. For the remaining four nonseparated spines, CT scans were used to find any inner or outer cortex breakage. RESULTS: Thirty-three vertebral levels were abandoned from Group S because of altered anatomy (eg, fusion, fracture during separation, anatomical anomaly of having only 11 thoracic spine segments). Out of 147 vertebral levels, there was no vertebra that did not allow screw insertion. No specimen required using smaller diameter 2° screw because of blockage of the 1° screw. There was no cortical breakage by the screws in Group S. In Group N-S, CT scan showed four inner cortex breakages and three outer cortex breakages, all of which were slight cortical breakages. There were no facet injuries due to the screws in Group N-S. There was no blockage of the ribs during screw placement in all specimens, and the drill guide could lean against the rib for guidance because the angle of the rib and the opposite lamina tended to be the same. CONCLUSIONS: Translaminar screws can be inserted relatively safely in the thoracic spine. For the 1° translaminar screw, the entry point is at a distance equal to the diameter of the desired screw superior to the inferior margin of the lamina-spinous process junction. The trajectory should be targeted toward the center of the base of the contralateral transverse process. For the 2° translaminar screw, the entry point is at a distance equal to the diameter of the desired screw below the superior margin of lamina-spinous process junction, and the target is the inferior angle of the junction of the rib and vertebra on the contralateral side.

Activation of brainstem neurons by underwater diving in the rat.

The mammalian diving response is a powerful autonomic adjustment to underwater submersion greatly affecting heart rate, arterial blood pressure, and ventilation. The bradycardia is mediated by the parasympathetic nervous system, arterial blood pressure is mediated via the sympathetic system and still other circuits mediate the respiratory changes. In the present study we investigate the cardiorespiratory responses and the brainstem neurons activated by voluntary diving of trained rats, and, compare them to control and swimming animals which did not dive. We show that the bradycardia and increase in arterial blood pressure induced by diving were significantly different than that induced by swimming. Neuronal activation was calculated after immunohistochemical processing of brainstem sections for Fos protein. Labeled neurons were counted in the caudal pressor area, the medullary dorsal horn, subnuclei of the nucleus tractus solitarii (NTS), the nucleus raphe pallidus (RPa), the rostroventrolateral medulla, the A5 area, the nucleus locus coeruleus, the Kölliker-Fuse area, and the external lateral and superior lateral subnuclei of the parabrachial nucleus. All these areas showed significant increases in Fos labeling when data from voluntary diving rats were compared to control rats and all but the commissural subnucleus of the NTS, A5 area, and RPa were significantly different from swimming rats. These data provide a substrate for more precise experiments to determine the role of these nuclei in the reflex circuits driving the diving response.

Expression of the coxsackie adenovirus receptor in normal prostate and in primary and metastatic prostate carcinoma: potential relevance to gene therapy.

Adenovirus-based gene therapy may provide an alternative mode of treatment for prostate cancer, especially for late-stage and androgen-independent disease for which there is currently no effective treatment. Efficient adenovirus infection of target cells depends upon the presence of the coxsackie adenovirus cell surface receptor, CAR, which is the primary receptor for group C adenoviruses and is important for the attachment of adenovirus to the cell membrane. To evaluate the potential efficacy of adenoviral therapy for prostate cancer, we evaluated CAR expression in normal prostate tissue and in prostate carcinoma of increasing Gleason grades in paraffin-embedded, archival tissues using a polyclonal antibody raised against human CAR. Immunohistochemical analysis of benign prostate epithelia demonstrated intense luminal and lateral cell membrane staining. There was a statistically significant difference in CAR membrane expression with respect to Gleason score. In addition, metastatic prostate specimens demonstrated strong membrane staining for CAR. Adenovirus therapy may, therefore, provide an alternate modality in the treatment of prostate cancer and may be especially efficacious in the treatment of metastatic disease.