Protocolized Based Management of Cerebrospinal Fluid Drains in Thoracic Endovascular Aortic Aneurysm Repair Procedures.
Spinal cord ischemia (SCI) resulting in paraplegia is a devastating complication associated with thoracic endovascular aortic aneurysm repair (TEVAR) whose incidence has significantly declined over time. In this review, we present our experience with a multidisciplinary clinical protocol for cerebrospinal fluid (CSF) drain management in patients undergoing TEVAR. Furthermore, we aimed to characterize complications of CSF drain placement in a large, single center experience of patients who underwent TEVAR. This retrospective review is of patients undergoing TEVAR with and without CSF drain placement between January 2014 and December 2019 at a single institution. Patient demographics, hospital course, and drain-related complications were analyzed to assess the incidence of CSF drain-related complications. A total of 235 patients were included in this study, of which 85 received CSF drains. Eighty patients (94.1%) were placed by anesthesiologists, while 5 (5.9%) were placed under fluoroscopic guidance by interventional neurosurgery. The most common level of placement was L3-L4 in 38 (44.7%) cases followed by L4-L5 in 36 (42.4%) cases. The mean duration of CSF drain was 1.9 ± 1.4 days. Complications due to CSF drainage occurred in 5 (5.9%) patients and included partial retainment of catheter, subdural edema, epidural hematoma, headache, and bleeding near the drain site. The overall 30-day mortality rate was 5.5% and did not differ between those who received a CSF drain and those who did not (P = 0.856). The overall incidence of SCI resulting in paraplegia was 1.7% in the studied patients. A protocol-based CSF drainage program for spinal cord protection involves a multifaceted approach in identification and selection of patients meeting criteria for prophylactic drain placement, direct closed loop communication, and perioperative management by an experienced team. Despite the inherent advantages of CSF drain placement, it is not without complications, thus risk and benefit need to be weighed in context of the procedure and the patient with close communication and team approach.


Surgical treatment of lateral Hoffa fracture with a locking plate through the lateral approach.
The goal of this study is to determine the efficacy of the surgical treatment of lateral Hoffa fracture with a locking plate and cannulated or lag screws through the lateral approach. A total of 12 isolated lateral Hoffa fractures were identified during the study period (February 2005 to February 2010). All fractures were treated by open reduction through the lateral approach. Internal fixation was performed with a contoured locking plate and cannulated or lag screws introduced from the non-weight-bearing area of the cartilage surface of the lateral femoral condyle. Radiological and functional outcome analysis was performed using Knee Society scores. Bony union of Hoffa fracture was achieved in all patients. The articular surface of lateral femoral condyle was anatomically reduced. There was no loss of reduction and fixation. Functional outcome of knee measurements showed a continuous significant improvement over the follow-up period. Fixation with a locking plate and cannulated or lag screws for lateral Hoffa fracture seemed to be effective and reliable. The lateral approach had advantages for reduction and fixation of lateral Hoffa fracture during operation.


Observation of the A-X electronic transition of the 1-C3H7O2 and 2-C3H7O2 radicals using cavity ringdown spectroscopy.
Cavity ringdown spectra of the A-X electronic transition of the 1-propyl and 2-propyl peroxy radicals are reported. Spectroscopic assignments are facilitated by implementing several production mechanisms, either isomer-specific or not. Assignments of specific spectral lines to particular conformers of a given isomer are suggested. Observations on the temporal decay of the various species are reported.


Free radicals and anticancer drug resistance: oxygen free radicals in the mechanisms of drug cytotoxicity and resistance by certain tumors.
Certain anticancer agents form free radical intermediates during enzymatic activation. Recent studies have indicated that free radicals generated from adriamycin and mitomycin C may play a critical role in their toxicity to human tumor cells. Furthermore, it is becoming increasingly apparent that reduced drug activation and or enhanced detoxification of reactive oxygen species may be related to the resistance to these anticancer agents by certain tumor cell lines. The purposes of this review are to summarize the evidence pointing toward the significance of free radicals formation in drug toxicity and to evaluate the role of decreased free radical formation and enhanced free radical scavenging and detoxification in the development of anticancer drug resistance by a spectrum of tumor cell types. Studies failing to support the participation of oxyradicals in the cytotoxicity and resistance of adriamycin are also discussed.


Translation in Mitochondrial Ribosomes.
Mitochondrial protein synthesis is essential for the life of aerobic eukaryotes. Without it, oxidative phosphorylation cannot be coupled. Evolution has shaped a battery of factors and machinery that are key to production of just a handful of critical proteins. In this general concept chapter, we attempt to briefly summarize our current knowledge of the overall process in mitochondria from a variety of species, breaking this down to the four parts of translation: initiation, elongation, termination, and recycling. Where appropriate, we highlight differences between species and emphasize gaps in our understanding. Excitingly, with the current revolution in cryoelectron microscopy and mitochondrial genome editing, it is highly likely that many of these gaps will be resolved in the near future. However, the absence of a faithful in vitro reconstituted system to study mitochondrial translation is still problematic.


Age over 80 years is not associated with increased hemorrhagic transformation after stroke thrombolysis.
Thrombolysis trials have recruited few patients aged ≥80 years, which has led to uncertainty about the likely risk-to-benefit profile in the elderly. Leukoaraiosis (LA) has been associated with hemorrhagic transformation (HT) and increases with advanced age. We tested whether there were any independent associations between age, LA and HT. Consecutive patients treated with intravenous (IV) tissue plasminogen activator (tPA) were identified from a prospective database. LA on baseline CT scans was assessed by two independent raters using the modified Van Swieten Score (mVSS) (maximum score 8, severe >4). HT was assessed on routine 24 hour to 48 hour CT /MRI scans using the European Cooperative Acute Stroke Study criteria for hemorrhagic infarct (HI) or parenchymal hematoma (PH) and judged symptomatic by the treating neurologist as per Safe Implementation of Thrombolysis in Stroke criteria. There were 206 patients treated with IV tPA (mean age: 71.0 years; range: 24-92 years), of whom 65/206 (32%) were aged ≥80 years. Overall, HT occurred in 41/206 patients (20%), HI in 31, PH1 in four (one symptomatic) and PH2 in six (three symptomatic). Age was not associated with HT (any HT: odds ratio [OR]=1.01; 95% confidence interval [CI]=0.5-2.08; p=0.99; PH: OR=0.53; 95% CI=0.12-2.3; p=0.51). There was one patient with PH1 and one patient with PH2 in 65 patients ≥80 years, both asymptomatic. LA was present in 112/208 (54%), and severe in 16.5%. LA increased with age (p<0.001) but was not associated with PH (any LA: OR=0.83; 95% CI=0.25-2.8; p=0.99; severe LA: OR=0.54, 95% CI=0.09-3.5; p=0.99). Age ≥80 years or LA did not increase the risk of HT (including PH) after thrombolysis, although LA increased with age. Neither factor should exclude otherwise eligible patients from tPA treatment.


The birth of yeast peroxisomes.
This contribution describes the phenotypic differences of yeast peroxisome-deficient mutants (pex mutants). In some cases different phenotypes were reported for yeast mutants deleted in the same PEX gene. These differences are most likely related to the marker proteins and methods used to detect peroxisomal remnants. This is especially evident for pex3 and pex19 mutants, where the localization of receptor docking proteins (Pex13, Pex14) resulted in the identification of peroxisomal membrane remnants, which do not contain other peroxisomal membrane proteins, such as the ring proteins Pex2, Pex10 and Pex12. These structures in pex3 and pex19 cells are the template for peroxisome formation upon introduction of the missing gene. Taken together, these data suggest that in all yeast pex mutants analyzed so far peroxisomes are not formed de novo but use membrane remnant structures as a template for peroxisome formation upon reintroduction of the missing gene. The relevance of this model for peroxisomal membrane protein and lipid sorting to peroxisomes is discussed.


Own and Others' Prior Experiences Influence Children's Imitation of Causal Acts.
Young children learn from others' examples, and they do so selectively. We examine whether the efficacy of prior experiences influences children's imitation. Thirty-six-month-olds had initial experience on a causal learning task either by performing the task themselves or by watching an adult perform it. The nature of the experience was manipulated such that the actor had either an easy or a difficult experience completing the task. Next, a second adult demonstrated an innovative technique for completing it. Children who had a difficult first-person experience, and those who had witnessed another person having difficulty, were significantly more likely to adopt and imitate the adult's innovation than those who had or witnessed an easy experience. Children who observed another were also more likely to imitate than were those who had the initial experience themselves. Imitation is influenced by prior experience, both when it is obtained through one's own hands-on motor manipulation and when it derives from observing the acts of others.


Association Between the Percentage of US Drug Sales Subject to Inflation Penalties and the Extent of Drug Price Increases.
Policy makers have proposed levying penalties for drug price increases that are higher than the rate of inflation for drugs covered in the US Medicare program, but research is lacking regarding the ways in which manufacturers might respond to those penalties. An understanding of manufacturers' responses to existing inflation penalties could inform such policy discussions. To estimate the association of existing inflation penalties in the US 340B Drug Pricing Program with manufacturer pricing behavior in the Medicare Part D program and associated changes in Medicare pharmacy expenditures. This study included a pooled cross-sectional time-series analysis of price changes for Medicare Part D drugs used annually by more than 5000 beneficiaries between January 1, 2013, and December 31, 2017. The percentage of Medicare Part D sales subject to inflation penalties in the 340B program was used to perform a regression analysis to estimate the association of inflation penalties with annual drug price changes. The 340B program requires manufacturers to sell their drugs at a lower price to safety-net health care organizations; this lower price includes a base discount and an additional discount equal to the amount of any price increase that is higher than the rate of inflation. Sales to these 340B-eligible health care organizations represent the market share of a drug subject to inflation penalties. Health care organization-level claims data were obtained from the Medicare Provider Utilization and Payment Data-Part D Prescriber database, and organizations were matched to the Office of Pharmacy Affairs Information System of the Health Resources and Services Administration to identify those organizations that were eligible for the 340B program. Price change and drug use data were obtained from the Medicare Part D Drug Spending Dashboard. Name-brand drugs were included in the analysis if they did not have generic competition and were used by more than 5000 individuals with Medicare Part D in 1 calendar year. Data analysis was conducted from January 1 to February 28, 2020. Annual price change was the primary outcome measure; spending changes associated with lower price increases were also estimated. Sales percentage subject to inflation penalties was the primary independent variable, and formulary classification was a control variable. Of 2148 brand-name drugs included in the database, 606 drugs were used by more than 5000 beneficiaries annually, with a mean sales percentage subject to inflation penalties of 12.1%. A higher sales percentage subject to inflation penalties was associated with lower annual price increases (between-effects coefficient, -0.114; 95% CI, -0.205 to -0.023; P = .01; fixed-effects coefficient, -0.380; 95% CI, -0.466 to -0.294; P < .001). Lower price increases owing to inflation penalties were estimated to be associated with a reduction in Medicare Part D pharmacy expenditures of $7.1 billion between 2013 and 2017. In this cross-sectional study, increases in the percentage of drug sales subject to inflation penalties were associated with lower annual price increases. Broader application of inflation penalties may help to reduce drug price increases and decrease overall drug spending.


Effect of lapatinib on hepatic parenchymal enhancement on gadoxetate disodium (EOB)-enhanced MRI scans of the rat liver.
The purpose of this study was to investigate the effect of lapatinib treatment on hepatic parenchymal enhancement on Gd-EOB-MRI scans in rat. Institutional animal review board approval was received prior to the commencement of all studies. Five rats received a single oral dose of 100 mg/kg/day lapatinib for 7 consecutive days. The controls (n = 5) were given 0.5 % (w/v) aqueous hydroxypropyl methyl cellulose containing 0.1 % (v/v) Tween 80 for 7 days. After the acquisition of gadoxetate disodium-enhanced MR images using 0.025 mmol gadolinium/kg, their livers were subjected to pathologic study to determine the expression level of organic anion-transporting polypeptide 1 (oatp1) and multi-drug resistance-associated protein 2 (mrp2). Relative enhancement of the liver was similar in both groups. At the hepatobiliary phase, which in rats occurs 3 min after the injection of Gd-EOB, it was 0.90 ± 0.06 in lapatinib-treated rats and 0.84 ± 0.08 in the controls (p = 0.30). There was also no difference in the expression level of oatp1 and mrp2. In rats, the administration of lapatinib for 7 days had no effect on hepatic parenchymal enhancement on Gd-EOB-MRI scans.


Acute and delayed transplantation of olfactory ensheathing cells promote partial recovery after complete transection of the spinal cord.
The present study was undertaken to determine whether olfactory ensheathing cells (OECs) from the olfactory bulb were capable to promote axonal regeneration and functional recovery when transplanted either acutely or 1 week delayed into the T8 transected rat spinal cord. OEC transplants increased recovery of functional outcomes, as shown electrophysiologically by return of motor evoked potentials and by reduction of hindlimb hyperreflexia, and behaviorally by recovery of movements of hindlimb joints. Axonal regeneration was proven histologically by demonstrating long axonal outgrowth of raphespinal, coerulospinal, and corticospinal tracts within the caudal cord stump. Expression of GFAP and NG2 was down-regulated in perilesional cord segments in transplanted animals, indicating a more suitable environment for axonal regeneration. Overall, earlier recovery and better functional and histological results were observed in rats receiving acute than delayed OEC transplants. The beneficial effects obtained with transplantation after transection are encouraging for the application of OECs in the human injured spinal cord.


Syringomyelia after chemotherapy and radiotherapy for advanced oropharyngeal carcinoma: cause or coincidence?
A patient presented with syringomyelia 18 months after the completion of treatment with both chemotherapy and radiotherapy for an advanced oropharyngeal carcinoma. The link with therapy is discussed.


Do tetrahydroaminoacridine (THA) and physostigmine restore acetylcholine release in Alzheimer brains via nicotinic receptors?
In the presence of 9-amino-1,2,3,4-tetrahydroacridine (THA) 10(-4) M or physostigmine 10(-4) M, the in vitro 3H-Acetylcholine (3H-ACh) release from control cortical slices was significantly reduced. In contrast, THA 10(-4) M and physostigmine 10(-4) M significantly increased the release of 3H-ACh in AD/SDAT brain tissue. This facilitating effect on 3H-ACh release was partially blocked (50%) in the presence of the nicotinic antagonist d-tubocurarine 10(-6) M indicating a possible interaction via nicotinic receptors. The muscarinic antagonist atropine 10(-5) M significantly increased the 3H-ACh release both in control and AD/SDAT brains, thus indicating preservation of muscarinic autoreceptors in the AD/SDAT cortical tissue. In receptor competition studies with 3H-nicotine, 3H-ACh and 3H-quinuclidinyl benzilate (3H-QNB) as receptor ligands, THA interfered with both nicotinic and muscarinic receptor ligand binding, while physostigmine had much less effect.


Clinical outcome evaluation of intraosseous vancomycin in total knee arthroplasty.
Vancomycin is a commonly used prophylactic antibiotic for total joint replacement surgery to protect against methicillin-resistant Staphylococcus aureus. Studies have suggested intraosseous (IO) infusions provide superior local tissue antibiotic concentration compared with intravenous (IV) access in total knee arthroplasty (TKA). We reviewed patients receiving IO vancomycin before TKA, comparing complication rates to a matched group receiving IV prophylactic vancomycin. Retrospective review of TKA patients administered IO vancomycin (500 mg vancomycin in 200 mL normal saline), September 1, 2018 to March 1, 2019, was compared with TKAs performed with prophylactic IV vancomycin, January 1, 2018 to August 31, 2018. Before incision, an IO needle was inserted into the tibial tubercle region, delivering 100 mL of the mixed vancomycin solution. The needle was then removed and inserted into the distal femur, delivering 100 mL of the solution. Evaluation included preoperative and postoperative creatinine values, tourniquet time, and knee-related 30-day and 90-day complications. Data for primary and revision TKA surgery cases were analyzed independently. There were 100 primary and 29 revision TKA cases in the control (IV) arm and 100 primary and 19 revision TKA cases in the intervention (IO) arm, comprising a study group of 248 cases. There were fifteen 30-day complications and eighteen 90-day complications overall. No significant differences in the complication rate or creatinine values were identified between IO and IV groups. IO vancomycin has an adequate safety profile in primary and revision TKA, eliminating the logistical challenge of timely prophylactic antibiotic administration.


Cancer drug response prediction with surrogate modeling-based graph neural architecture search.
Understanding drug-response differences in cancer treatments is one of the most challenging aspects of personalized medicine. Recently, graph neural networks (GNNs) have become state-of-the-art methods in many graph representation learning scenarios in bioinformatics. However, building an optimal handcrafted GNN model for a particular drug sensitivity dataset requires manual design and fine-tuning of the hyperparameters for the GNN model, which is time-consuming and requires expert knowledge. In this work, we propose AutoCDRP, a novel framework for automated cancer drug-response predictor using GNNs. Our approach leverages surrogate modeling to efficiently search for the most effective GNN architecture. AutoCDRP uses a surrogate model to predict the performance of GNN architectures sampled from a search space, allowing it to select the optimal architecture based on evaluation performance. Hence, AutoCDRP can efficiently identify the optimal GNN architecture by exploring the performance of all GNN architectures in the search space. Through comprehensive experiments on two benchmark datasets, we demonstrate that the GNN architecture generated by AutoCDRP surpasses state-of-the-art designs. Notably, the optimal GNN architecture identified by AutoCDRP consistently outperforms the best baseline architecture from the first epoch, providing further evidence of its effectiveness. https://github.com/BeObm/AutoCDRP.


Health and the body: The Ingram Collection at the Royal College of General Practitioners (RCGP), London, UK. (3 March to 29 May 2016).
A new Ingram Collection exhibition, Health and the Body, opened for a period of two months at the Royal College of General Practitioners in London. The exhibition showcased paintings and sculptures by artists such as Eduardo Paolozzi, Barbara Hepworth, Geoffrey Clarke and Leon Underwood the artworks explored representations of the human body, and observed how these intersected with the history of general medical practice.


Detection of MMTV-Like sequences in Moroccan breast cancer cases.
The mouse mammary tumor virus (MMTV) like sequences have been reported to be present in some human breast cancers, but their association with breast cancer development is still controversial. In this retrospective study, we investigated the status of MMTV-like in 42 tumor biopsies and 18 paired normal tissues from Moroccan patients with breast cancer. MMTV-like env sequences were identified by PCR and confirmed by direct DNA sequencing. Specific MMTV-like env sequences were found in 24 (57.14%) cases of breast carcinomas, and 6 (33.3%) cases of matched normal breast tissues. Comparison to sociologic and clinicopathological parameters showed no significant association between the presence of MMTV-like sequences and age, menopausal status, histological subtype, histological grade, tumor size and the expression of hormone receptors (estrogen ER and/or progesterone PgR) and Her 2. However, a significant correlation was found between MMTV-like presence and parity (p = 0.024). This present study confirms the presence of MMTV-like env sequences in breast cancer in Moroccan women, prompting further evaluation, on large sampling, to elucidate the probable causal roles of MMTV-like in breast cancer development.


A Systematic Review of Promising Therapeutic Targets in Hidradenitis Suppurativa: A Critical Evaluation of Mechanistic and Clinical Relevance.
This systematic review identifies and critically evaluates the mechanistic and clinical evidence of new promising therapeutic targets in hidradenitis suppurativa (HS). Evidence for these targets is largely based on observational data with limited ex vivo and translational data from clinical trials. A number of placebo-controlled studies have been completed or are underway utilizing IL-1, IL-23, IL-17, complement, and Jak inhibition, although there is concern regarding elevated placebo response rates and the questionable validity of clinical scores in some participant subsets. Knowledge gaps are identified suggesting a direction for future mechanistic studies in HS, including more comprehensive inflammatory endotype profiling of disease.


Percutaneous left atrial appendage occlusion: impact on left atrial deformation indices.
Percutaneous left atrial appendage occlusion (LAAO) is an accepted alternative to thromboprophylaxis in patients with atrial fibrillation (AF) who are: (i) intolerant to oral anticoagulation (OAC) (e.g. life-threatening haemorrhage), (ii) non-adherent to OAC, or (iii) at a high bleeding risk with OAC. Improvement in LA mechanics was shown post-LAAO in the LAFIT-LARIAT study, using the Lariat device. No significant change was seen in LA mechanics after LAAO with the Watchman device in the LAFIT-Watchman study. The impact of LAAO with the Amplatzer or Amulet device on LA deformation mechanics has not been investigated. To evaluate the impact of LAAO with the Amplatzer or Amulet device on echocardiographic LA deformation indices. All patients undergoing percutaneous LAAO from 2013 to 2021 at a single centre were included from an ongoing clinical registry. LA reservoir (εreservoir), conduit (εconduit) and contractile strain (εcontractile) and strain rate (SRreservoir, SRconduit, SRcontractile) were assessed with two-dimensional speckle tracking echocardiography from an apical four-chamber view. Conduit and contractile strain and strain rates were only recorded for patients without AF at the time of echocardiography. Changes in LA deformation indices over time were compared with a linear mixed model. 28 LAAO recipients (mean age 73 ± 12 years, 68% male) were analysed. 5 (18%) patients had AF pre- or post-procedure. After a mean follow-up of 1.6 ± 1.4 months, the mean LA εreservoir increased from 10.15 ± 6.44% to 10.18 ± 8.72% (p = 0.985), the mean LA εconduit increased from 5.12 ± 5.48% to 5.31 ± 6.11% (p = 0.891) and the mean LA εcontractile decreased from 5.14 ± 4.32% to 4.95 ± 5.30% (p = 0.898). During the same time interval, the mean LA SRreservoir decreased from + 0.54 ± 0.23.s- 1 to + 0.48 ± 0.43.s- 1 (p = 0.566), the mean LA SRconduit remained stable: -0.47 ± 0.41.s- 1 to -0.47 ± 0.32.s- 1 (p = 0.997) and the mean LA SRcontractile decreased from - 0.66 ± 0.50.s- 1 to -0.55 ± 0.46.s- 1 (p = 0.660). No significant improvement in LA mechanical function was seen after LAAO with the Amplatzer or Amulet device. Different LAAO devices therefore appear to have divergent effects on LA deformation, the clinical implications of which may warrant further study.


Transformation products and reaction pathways of carbamazepine during photocatalytic and sonophotocatalytic treatment.
This study examines the degradation of the antiepileptic carbamazepine (CBZ) by sonolysis, TiO2-based heterogeneous photocatalysis under UV-A and simulated solar irradiation, and by the combined use of UV-A and ultrasound irradiation (i.e. sonophotocatalysis) in demineralized water, ground water and effluent wastewater. The processes were compared with respect to substrate conversion rate and the extent of DOC reduction as a measure of mineralization. CBZ was degraded following a pseudo-first order kinetics. Sonophotocatalysis provided the highest rate of CBZ transformation over the time-course of the experiment while the degree of DOC removal in pure water was similar for all the studied treatments (around 40%), and always lower than CBZ conversion. This indicated that a considerable organic load remained in the treated solutions that could also be attributed to the presence of persistent oxidation products. UPLC-(+ESI)-QToF-MS was employed to determine major CBZ-related transformation products. Several recalcitrant hydroxy- and keto-derivatives of CBZ were tentatively identified. A Daphnia magna bioassay was used to evaluate the potential toxicity of the samples collected at different time points showing that the mixtures were highly toxic to D. magna.


Endoscopic retrieval of foreign bodies from the rectum.
A technique is described and illustrated by case reports wherein removal of foreign bodies of the rectum is simplified by using the flexible sigmoidscope. Evidence from the literature indicates that delayed perforation is rare in this situation, and that outpatient management would suffice for most patients.


Glial influences on neural stem cell development: cellular niches for adult neurogenesis.
Neural stem cells continually generate new neurons in very limited regions of the adult mammalian central nervous system. In the neurogenic regions there are unique and highly specialized microenvironments (niches) that tightly regulate the neuronal development of adult neural stem cells. Emerging evidence suggests that glia, particularly astrocytes, have key roles in controlling multiple steps of adult neurogenesis within the niches, from proliferation and fate specification of neural progenitors to migration and integration of the neuronal progeny into pre-existing neuronal circuits in the adult brain. Identification of specific niche signals that regulate these sequential steps during adult neurogenesis might lead to strategies to induce functional neurogenesis in other brain regions after injury or degenerative neurological diseases.


Optic nerve head perfusion changes preceding peripapillary retinal nerve fibre layer thinning in preclinical diabetic retinopathy.
Whether neural or vascular defects occur first in the early onset of diabetic retinopathy (DR) is undetermined. To investigate microcirculation and microstructure differences of optic nerve head (ONH) between diabetic eyes without clinically evident retinopathy and healthy controls using optical coherence tomography angiography (OCTA). Cross-sectional observational study. Sixty eyes of 60 patients with type 2 diabetes and without clinically evident retinopathy and 60 eyes of 60 age-matched healthy controls were included in this study. All participants underwent 4.5 × 4.5-mm rectangle scans centred on the ONH using OCTA (RTVue-XR Avanti; Optovue, Fremont, CA). Peripapillary retinal nerve fibre layer (RNFL) thickness and capillary perfusion density inside the ONH and in the peripapillary region were compared between the two groups. Vessel density values in both peripapillary and inside the disc were significantly lower in diabetic patients without DR compared to normal controls. The reduction of vessel density was prominent in all eight peripapillary sectors in diabetic eyes (all P < 0.05). Thinning of RNFL thickness was significant in the nasal superior (P < 0.001), inferior nasal (P = 0.023) and superior nasal quadrant (P < 0.001) in diabetic eyes in comparison to normal controls. ONH perfusion and peripapillary RNFL thickness were significantly decreased in preclinical DR patients compared to normal controls. Microvascular alterations in ONH may occur earlier than peripapillary RNFL defect in the course of DR.


Cervical vagotomy increased the distal colon distention to urinary bladder inhibitory reflex in male rats.
Many studies have demonstrated the convergence of vagal inputs into brainstem centers with inputs from the urinary bladder and colon, as well as the convergence of vagal inputs into other centers controlling the urinary bladder and colon reflexes. However, the effect of the vagal inputs on the interaction between the urinary bladder and other pelvic organs has not been studied. In this study, the effect of bilateral cervical vagotomy on the distal colon to urinary bladder reflex was examined. Changes to cystometry parameters in response to increased distal colon distensions (1, 2, and 3 ml) were tested in urethane-anesthetized male rats with or without bilateral cervical vagotomy. In animals with intact vagus nerves, 1 and 2 ml distal colon distentions had no significant effects on micturition frequency; however, 3 ml distal colon distention significantly decreased the frequency of micturition cycles. Also, 3 ml distal colon distention inhibited micturition cycles in 37.5 % of these animals. On the other hand, following cervical vagotomy, 1 ml distal colon distention was enough to significantly decrease the frequency of micturition cycles and to inhibit the cycles in 75 % of the animals. These results demonstrate the presence of supraspinal inhibitory regulation, via the vagus nerve, over the distal colon to urinary bladder inhibitory reflex.


Congenital absence of the epiglottis.
The congenital absence of the epiglottis is a very rare anomaly. We present a patient who has a complete absence of the epiglottis, illustrated with an endoscopic photograph, review the literature and discuss the management of patients with this condition.


Severe oropharyngeal trauma caused by toothbrush--case report and review of 13 cases.
Foreign body trauma to the oral cavity is fairly common. However, severe injuries caused by a toothbrush are rarely reported. We report a case of a 35-year-old epileptic patient who suffered seizures while brushing his teeth. During this episode, he self-inflicted a grievous injury to his oro-pharynx with his toothbrush which went unnoticed for 11 months. Thirteen cases of toothbrush induced trauma to this area are reviewed and a classification of these injuries is proposed. Complications related to these injuries are highlighted and their management discussed.


Phenyl Pentyl Ketone and m-isobutyl Methoxy Benzoate Produced by Streptomyces Chrestomyceticus ADP4 are Potent Antimicrobial Agents Displaying Broad Spectrum Activities.
Isolation and identification of two antimicrobial compounds, a phenyl pentyl ketone (CP1) and m-isobutyl methoxy benzoate (CP2), from Streptomyces chrestomyceticus ADP4 have been reported. Structure of the compounds were elucidated from analyses of spectral data that included LCMS/MS, NMR, FTIR and UV spectroscopies. Both the compounds displayed significant inhibition of albicans and non-albicans species of Candida (NAC) pathogens including C. auris, which is currently a pathogen of global concern. Also, the compounds showed potent antagonistic activity against Staphylococcus aureus, another significant human pathogen. No in-vitro cytotoxicity against HePG2 cells was observed with either of the compounds. Both displayed favourable drug likeness properties as determined by in-silico ADME and toxicological studies. Also, this is the first report on production of these anti-microbial compounds by an actinobacterium. The online version contains supplementary material available at 10.1007/s12088-023-01068-7.


Intranasal delivery of cationic liposome-protamine complex mRNA vaccine elicits effective anti-tumor immunity.
Immunization with synthetic mRNA encoding tumor-associated antigens is an emerging vaccine strategy for the treatment of cancer. In order to prevent mRNA degradation, promote antigen-presenting cells antigen presentation, and induce an anti-tumor immune response, we investigated the nasal administration of mRNA vaccines with positively charged protamine to concentrate mRNA, form a stable polycation-mRNA complex, and encapsulate the complex with DOTAP/Chol/DSPE-PEG cationic liposomes. Cationic liposome/protamine complex (LPC) showed significantly greater efficiency in uptake of vaccine particles in vitro and stronger capacities to stimulate dendritic cell maturation, which further induced a potent anti-tumor immune response. Intranasal immunization of mice with cationic LPC containing mRNA encoding cytokeratin 19 provoked a strong cellular immune response and slowed tumor growth in an aggressive Lewis lung cancer model. The results of this study provide evidence that cationic LPC can be used as a safe and effective adjuvant and this mRNA formulation provides a basis for anti-cancer vaccination of humans.


Self-reported symptoms among participants in a population-based screening program.
A limited number of studies have explored the association between self-reported symptoms and the risk of breast cancer among participants of population based screening programs. We performed descriptive statistics on recall, screen-detected and interval cancer, positive predictive value and histopathological tumour characteristics by symptom group (asymptomatic, lump, and skin or nipple changes) as reported from 785,642 women aged 50-69 when they attended BreastScreen Norway 1996-2016. Uni- and multivariable mixed effects logistic regression models were used to analyze the association between symptom group and screen-detected or interval cancer. Results were presented as odds ratios and 95% confidence intervals (CI). A lump or skin/nipple change was reported in 6.2% of the 3,307,697 examinations. The rate of screen-detected cancers per 1000 examinations was 45.2 among women with a self-reported lump and 5.1 among asymptomatic women. Adjusted odds ratio of screen-detected cancer was 10.1 (95% CI: 9.3-11.1) and 2.0 (95% CI: 1.6-2.5) for interval cancer among women with a self-reported lump versus asymptomatic women. Tumour diameter, histologic grade and lymph node involvement of screen-detected and interval cancer were less prognostically favourable for women with a self-reported lump versus asymptomatic women. Despite targeting asymptomatic women, 6.2% of the screening examinations in BreastScreen Norway was performed among women who reported a lump or skin/nipple change when they attended screening. The odds ratio of screen-detected cancer was higher for women with versus without symptoms. Standardized follow-up guidelines might be beneficial for screening programs in order to take care of women reporting signs or symptoms of breast cancer when they attend screening.


[Clinical phenotype and genetic analysis of a case of 5q14.3 microdeletion syndrome].
To explore the clinical features and genetic characteristics of a child with 5q14.3 microdeletion syndrome. Whole exome sequencing (WES) and low-coverage massively parallel copy number variation sequencing (CNV-seq) were used to determine the potentially pathogenic variants as well as the copy number variations (CNVs). Candidate CNVs were verified by real-time fluorescence quantitative PCR. The patient presented with psychomotor retardation, epilepsy, peculiar face and hypotonia. The results of WES suggested that he has carried a heterozygous deletion for chr5:86 564 268-88 119 605. CNV-seq indicated that the patient carried a heterozygous deletion of 4.76 Mb heterozygous deletion on chromosome 5q14.3. The MEF2C gene and RASA1 gene in the deletion area were verified by real-time fluorescence quantitative PCR. The results showed that the MEF2C geneand RASA1 gene were heterozygous deletion, which was consistent with the sequencing results. The child was diagnosed with 5q14.3 microdeletion syndrome. Haploinsufficiency of the MEF2C gene may underlie the manifestations of 5q14.3 microdeletion syndrome.


Aging effects on sensorimotor integration: a comparison of effector systems and feedback modalities.
Research on motor aging has focused on visuomotor effects in limb musculature, with few comparisons across effectors or feedback modalities. The authors examined steady fine force control in oral and manual effectors under visual and auditory feedback in 13 young (19-23 years old) and 13 older (60-77 years old) participants, hypothesizing that force variability would increase with aging (a) more in the finger than the lip and (b) for both feedback modalities. The magnitude of variability increased with age for both visuomotor and audiomotor tasks but age-related differences were greater in the lip than the finger. These results point to increased variability as a potential early marker of changing motor function (prior to loss of strength) that extends beyond the visuomotor system.


A method for determining fumonisin B1 in corn using immunoaffinity column clean-up and thin layer chromatography/densitometry.
A method for determining fumonisin B1 (FB1) in corn was developed and the clean-up optimized in order to give an extract suitable for one-dimensional thin layer chromatographic (TLC) analysis. FB1 was extracted with a solution of methanol:water (80:20, v/v), purified through an immunoaffinity column and separated on a C18 reversed phase TLC plate. The FB1 was visualized with 0.1 mol/l sodium tetraborate, 0.40 mg/ml fluorescamine in acetonitrile and 0.01 mol/l boric acid:acetonitrile (2:3, v/v) for fluorescence detection, and quantified by densitometric analysis. Water, acetonitrile:water (1:1 v/v) and acetonitrile:water (4:1 v/v) were evaluated as TLC solvents for running both standards and samples together with derivatization procedures aimed at improving separation, resolution, sensitivity and linearity. The mean recovery for FB1 for spiked samples was found to be 85% and the linear equation of standard calibration curve by densitometric analysis gave an r2 value higher than 0.99. The maximum coefficient of variation for replicate analysis of spiked samples was 19%. The absolute amount of FB1 standard detectable on a TLC plate was 2 ng, giving a detection limit for the method of 0.1 mg/kg. The method has been shown to be robust in the application of FB1 monitoring in corn (214 samples) collected in different regions of the country. FB1 was detected in 99% of these samples in the range of 0.2 to 6 mg/kg.


Cortisol-induced migration of eosinophil leukocytes to lymphoid organs.
Cortisol induces a migration of eosinophil leukocytes from the blood to several lymphoid organs, such as the spleen, lymph nodes and thymus, but not to other tissues. This migration explains the cortisol-induced blood eosinopenia, which is much more pronounced in intact than in splenectomized animals.


Detection of para-chloroaniline, reactive oxygen species, and 1-chloro-4-nitrobenzene in high concentrations of chlorhexidine and in a mixture of chlorhexidine and calcium hydroxide.
Chlorhexidine (CHX) is likely to decompose into reactive by-products. This study evaluated the generation of 4-chloroaniline (pCA), reactive oxygen species (ROS), and 1-chloro-4-nitrobenzene in high concentrations of CHX and in a mixture of CHX and calcium hydroxide at different time points. A gas chromatography method was developed to detect pCA and CHX by-products. Mass spectroscopy was used to elucidate the structure of compounds. The samples, which were kept at 36.5°C and 95% relative humidity during the study, were analyzed immediately and 7 days after preparation. pCA was detected in the 2% CHX solution and in the mixture of CHX and calcium hydroxide at all time points. pCA concentrations increased after storing under those conditions. The 2% CHX solution alone and the mixture of CHX and calcium hydroxide released ROS at all time points, but 1-chloro-4-nitrobenzene was not found. pCA and ROS were identified as by-products of the 2% CHX aqueous solution alone and as ointment base of calcium hydroxide paste.


Metabolic activity of developing rabbit lung.
The uptake and metabolism of [3H]leucine, [U-14C]glucose, and [3H]palmitate were studied in rabbits aged --3, 1, 7, 28, and 90 days up to 1--1.5 years. Although lung composition did not change markedly, there were great differences in lung metabolism between the perinatal period (late fetal and newborn) and later stages of development. Leucine incorporation into lung protein was highest (3.1--3.4 nmol/mg protein/hr) in late fetal and newborn rabbits and decreased rapidly thereafter. Palmitic acid incorporation decreased during the first week after birth from 150 nmol/100 mg/hr to 85 nmol/100 mg/hr at 7 days of age; it increased thereafter to 170 nmol/100 mg/hr at 4 weeks of age and remained at that level throughout the entire period studied. Glucose uptake and lactate production were higher in fetal lungs than in all other age groups. Lipid biosynthesis from glucose was 2--4 times higher in fetal lungs than at all other ages; furthermore, more than 60% of glucose carbon atoms channeled into lipid was incorporated into fatty acids, whereas at all other ages glucose was chiefly a precursor of lipid glycerol.


Growth, growth hormone and sex steroid secretion in girls with central precocious puberty treated with a gonadotrophin releasing hormone (GnRH) analogue.
We have treated 14 girls with central precocious puberty for a mean period of 2.3 years (range, 0.5-3.9) with intranasal (D-Ser6) GnRH analogue administered in a mean dose of 28 micrograms/kg/day (range, 15-56). With the onset of treatment there was an initial increase in sitting height compared to subischial leg length, but overall there was no significant change in height standard deviation score for bone age. In this respect our results were indistinguishable from untreated children with central precocious puberty. There was a decrease in physiological GH secretion, associated with decreased sex steroid secretion, which probably accounts for the growth deceleration which has been described during GnRH analogue therapy. The effect of this growth deceleration combined with slowing of the rate of epiphyseal maturation may explain the absence of alteration in height prognosis.


The influence of disparities on intensive care outcomes in children with respiratory diseases: A systematic review.
The negative effects of socioeconomic, environmental and ethnic inequalities on childhood respiratory diseases are known in the development of persistent asthma and can result in adverse outcomes. However, little is known about the effects of these disparities on pediatric intensive care unit (PICU) outcomes in respiratory diseases. The purpose of this systematic review is to evaluate the literature on disparities in socioeconomic, environmental and ethnic determinants and PICU outcomes. We hypothesize that these disparities negatively influence the outcomes of children's respiratory diseases at the PICU. A literature search (in PubMed, Embase.com and Web of Science Core Collection) was performed up to September 30, 2022. Two authors extracted the data and independently evaluated the risk of bias with appropriate assessment methods. Articles were included if the patients were below 18 years of age (excluding neonatal intensive care unit admissions), they concerned respiratory diseases and incorporated socioeconomic, ethnic or environmental disparities. Eight thousand seven hundred fourty-six references were reviewed, and 15 articles were included; seven articles on the effect of socioeconomic status, five articles on ethnicity, one on the effect of sex and lastly two on environmental factors. All articles but one showed an unfavorable outcome at the PICU. Disparities in socioeconomic (such as a low-income household, public health insurance), ethnic and environmental factors (such as exposure to tobacco smoke and diet) have been assessed as risk factors for the severity of children's respiratory diseases and can negatively influence the outcomes of these children admitted and treated at the PICU.


Chlordecone metabolism in the pig.
The biotransformation of chlordecone (CD) to chlordecone alcohol (CDOH) occurs in man and gerbils but not in rats, guinea pigs and hamsters [1, 2]. Because of the species differences in CDOH formation and the need for a suitable animal model, pigs were administered CD by intraperitoneal (i.p.) injection. Plasma, gallbladder bile, hepatic bile, liver and feces were collected and analyzed by gas chromatography for CD metabolites. CDOH was present in bile and feces with up to 85% conjugated in the bile but only 15% was conjugated in the feces. Up to 20% of the CD in plasma and bile and less than 3% in feces was in the conjugated form. Both reduction and conjugation of CD in the pig are similar to those in man.


Community- and individual-level correlates of HIV incidence in HPTN 071 (PopART).
Universal HIV testing and treatment aims to identify all people living with HIV and offer them treatment, decreasing the number of individuals with unsuppressed HIV and thus reducing HIV transmission. Longitudinal follow-up of individuals with and without HIV in a cluster-randomized trial of communities allowed for the examination of community- and individual-level measures of HIV risk and HIV incidence. HPTN 071 (PopART) was a three-arm cluster-randomized trial conducted between 2013 and 2018 that evaluated the use of two combination HIV prevention strategies implemented at the community level to reduce HIV incidence compared to the standard of care. The trial, conducted in 21 communities in Zambia and South Africa, measured HIV incidence over 36 months in a population cohort of ∼2000 randomly selected adults per community aged 18-44. Multilevel models were used to assess the association between HIV incidence and community- and individual-level socio-demographic and behavioural risk factors, as well as prevalence of detectable virus (PDV) defined as the estimated proportion of the community with unsuppressed viral load. Overall HIV incidence was 1.49/100 person-years. Communities with less financial wealth and communities with more individuals reporting having sex partners outside of the community or two or more sexual partners had higher HIV incidence. PDV at 2 years of study was 6.8% and was strongly associated with HIV incidence: for every 50% relative reduction in community PDV, there was a 49% (95% confidence interval [CI]: 37%-58%, p < 0.001) relative decrease in HIV incidence. At the individual level; socio-economic status, AUDIT score, medical male circumcision and certain sexual behaviours were associated with HIV risk. Using data from the PopART randomized trial, we found several associations of HIV incidence with community-level measures reflecting the sexual behaviour and socio-economic make-up of each community. We also found a strong association between community PDV and HIV incidence supporting the use of PDV as a tool for monitoring progress in controlling the epidemic. Lastly, we found significant individual-level factors of HIV risk that are generally consistent with previous HIV epidemiological research. These results have the potential to identify high high-incidence communities, inform structural-level interventions, and optimize individual-level interventions for HIV prevention. ClinicalTrials.gov number, NCT01900977, HPTN 071 [PopArt].


Evidence for late development of inhibition in area CA1 of the rat hippocampus.
Development of recurrent inhibition in area CA1 of the rat hippocampus was monitored by a paired-pulse stimulation test. Inhibition of the second response was never observed before postnatal day six. In addition, a type of epileptiform activity, referred to as spontaneous unison firing, was observed frequently, only on postnatal days 4 and 5. Together these observations suggest that the inhibitory interneuronal network of area CA1 becomes effective on about postnatal day 6.


Long non-coding RNA containing ultraconserved genomic region 8 promotes bladder cancer tumorigenesis.
Ultraconserved regions (UCRs) have been shown to originate non-coding RNA transcripts (T-UCRs) that have different expression profiles and play functional roles in the pathophysiology of multiple cancers. The relevance of these functions to the pathogenesis of bladder cancer (BlCa) is speculative. To elucidate this relevance, we first used genome-wide profiling to evaluate the expression of T-UCRs in BlCa tissues. Analysis of two datasets comprising normal bladder tissues and BlCa specimens with a custom T-UCR microarray identified ultraconserved RNA (uc.) 8+ as the most upregulated T-UCR in BlCa tissues, although its expression was lower than in pericancerous bladder tissues. These results were confirmed on BlCa tissues by real-time PCR and by in situ hybridization. Although uc.8+ is located within intron 1 of CASZ1, a zinc-finger transcription factor, the transcribed non-coding RNA encoding uc.8+ is expressed independently of CASZ1. In vitro experiments evaluating the effects of uc.8+ silencing, showed significantly decreased capacities for cancer cell invasion, migration, and proliferation. From this, we proposed and validated a model of interaction in which uc.8+ shuttles from the nucleus to the cytoplasm of BlCa cells, interacts with microRNA (miR)-596, and cooperates in the promotion and development of BlCa. Using computational analysis, we investigated the miR-binding domain accessibility, as determined by base-pairing interactions within the uc.8+ predicted secondary structure, RNA binding affinity, and RNA species abundance in bladder tissues and showed that uc.8+ is a natural decoy for miR-596. Thus uc.8+ upregulation results in increased expression of MMP9, increasing the invasive potential of BlCa cells. These interactions between evolutionarily conserved regions of DNA suggest that natural selection has preserved this potentially regulatory layer that uses RNA to modulate miR levels, opening up the possibility for development of useful markers for early diagnosis and prognosis as well as for development of new RNA-based cancer therapies.


Pacemaker endocarditis due to Haemophilus parainfluenza: case report and literature review.
We report a case of pacemaker infective endocarditis in a 14 month old girl, caused by Haemophilus parainfluenzae. There are no other cases in children reported in the literature. We discuss the issues surrounding the case and the evidence which influenced our management.


Effects of light on retinal pigment epithelial cells, neurosensory retinal cells and Müller cells treated with Brilliant Blue G.
The aim of this study is to evaluate the safety profile of Brilliant Blue G (BBG) with and without exposure to light (L) on three different retinal cell lines. ARPE-19, R28 and MIO-M1 cells were treated with BBG: 0.125 mg/mL (0.5x clinical concentration), 0.25 mg/mL (1x) or 0.5 mg/mL (2x) with or without surgical illumination of halogen light exposure for 10 min, 15 min or 30 min. Cells were further cultured after 24 h and then analysed for cell viability, late stages of apoptosis and mitochondrial damage associated with early apoptosis using assays that measure trypan blue dye exclusion, increases in caspase-3/7 activity or changes in mitochondrial membrane potential (ΔΨm), respectively. All three cell lines that were exposed to BBG in the presence or absence of light exposure for 30 min were found to have cell viability and caspase-3/7 activity levels similar to the untreated cultures. The mitochondrial membrane potential (ΔΨm) was decreased significantly at the 2x + L dose and 2x dose in all three retinal cell lines compared to their respective untreated control cells. At the lower doses of BBG, with or without exposure to light, the ΔΨm values were similar to the untreated control cultures. Exposure to BBG dye concentrations that are used clinically (0.125 mg/mL and 0.25 mg/mL) in the presence up to 30 min of surgically equivalent light intensity is safe for retinal cells.


Accidental displacement and migration of endosseous implants into adjacent craniofacial structures: a review and update.
Accidental displacement of endosseous implants into the maxillary sinus is an unusual but potential complication in implantology procedures due to the special features of the posterior aspect of the maxillary bone; there is also a possibility of migration throughout the upper paranasal sinuses and adjacent structures. The aim of this paper is to review the published literature about accidental displacement and migration of dental implants into the maxillary sinus and other adjacent structures. A review has been done based on a search in the main on-line medical databases looking for papers about migration of dental implants published in major oral surgery, periodontal, dental implant and ear-nose-throat journals, using the keywords "implant," "migration," "complication," "foreign body" and "sinus." 24 articles showing displacement or migration to maxillary, ethmoid and sphenoid sinuses, orbit and cranial fossae, with different degrees of associated symptoms, were identified. Techniques found to solve these clinical issues include Cadwell-Luc approach, transoral endoscopy approach via canine fossae and transnasal functional endoscopy surgery. Before removing the foreign body, a correct diagnosis should be done in order to evaluate the functional status of the ostiomeatal complex and the degree of affectation of paranasal sinuses and other involved structures, determining the size and the exact location of the foreign body. After a complete diagnosis, an indicated procedure for every case would be decided.


Fy (a-b-) phenotype in Czechoslovakia.
A family of gypsy origin, with 5 Fy(a-b-) members was found in Czechoslovakia. The involvement of the silen allele, Fy, in paternity testing is discussed.


Sequence composition and location of CRE motifs affect the binding ability of CcpA protein.
Bacillus catabolite control protein (CcpA) mediates carbon catabolite repression (CCR) by binding with catabolite response elements (CREs) of genes or operons. Although numerous CREs had been predicted and identified, the influence of the changes in sequence and structure of CREs on recognition and binding for CcpA has yet to be unclear. This study aimed at revealing how CcpA could bind such diverse sites and focused on the analysis of multiple mutants of the CRE motif derived from the α-amylase promoter. Molecular docking and free energy calculation insights into the binding ability between the CRE sequences composition and CcpA protein. Disruption of conserved nucleotides in the CRE motifs, as well as altering the symmetric structure of the CRE sequences and the relative position of the displaced CRE motifs near the transcription start site contribute to some extent to weakening the strength of CcpA - dependent regulation. These main factors contribute to the understanding of the subtle changes in CRE motifs leading to differential regulatory effects of CcpA. Finally, an engineered promoter with a high level of transcription was obtained, and elevated extracellular enzyme activity was achieved in the expression system of Bacillus amyloliquefaciens, including alkaline protease, keratinase, aminopeptidase and acid-stable alpha amylase. The study also provides a reference for the application of other promoters with CRE motifts.


Passive vs. closed suction drainage after perineal wound closure following abdominoperineal rectal excision for carcinoma. A multicenter, controlled trial. The French Association for Surgical Research.
Because evacuation of effusion or collection could depend on the type of drainage, we compared the effects of closed suction drainage with passive drainage through tubes or undulated drains after abdominoperineal rectal excision for carcinoma on early and late perineal wound healing. Of 234 consecutive patients undergoing abdominoperineal rectal excision for carcinoma between January 1983 and August 1990, unsatisfactory hemostasis or gross intraoperative septic contamination were recorded in 48 patients who were not included in the trial. After rectal excision and closure of the perineum, the remaining 186 patients were randomized to receive passive drainage (PD; n = 96) or closed suction drainage (SD; n = 90). Eighteen patients were withdrawn because of protocol violation, and three were lost to follow-up, leaving 165 (89 PD and 76 SD) patients for analysis. Preoperative factors (sex, age, degree of obesity, weight loss, anemia, or presence of ascites), intraoperative and pathologic findings (Dukes stage), and postoperative courses (recurrence, late mortality) were similar in both groups. All patients were followed up for 12 months or until death. The rate of perineums healed at one month was significantly lower (P < 0.05) in PD (55/89 = 61 percent) compared with SD (54/72 = 75 percent) patients. At three months, the rate of healed perineums no longer differed between the two groups (70/87 = 81 percent vs. 60/72 = 84 percent). The number of vaginal fistulas, secondary reopenings, and perineums not healed at 12 months was similar in both groups. Median duration to complete healing was similar in both groups (23 vs. 21 days, respectively). On the other hand, three retained drains were seen in PD patients only. The median duration of hospital stay was identical in both groups (22 days). Seven patients died in the early postoperative period, including one in the PD group and six in the SD group. There was no significant difference in the number of late deaths (3 vs. 7) in PD and SD patients, respectively. These results suggest that closed suction drainage should be used after abdominoperineal rectal excision with satisfactory hemostasis or absence of gross introperative septic contamination.


Prostaglandins in the pathogenesis and prevention of vascular disease.
Metabolism of arachidonic acid gives rise to a number of products with potent, and sometimes opposing, biological actions. Prostacyclin, the main product of arachidonic acid in vascular tissue, is a vasodilator and inhibitor of platelet aggregation whereas thromboxane A2, produced by the platelet, is a vasoconstrictor and inducer of platelet aggregation. Generation of these products may be modified in certain diseases, such as atherosclerosis and diabetes, so that prostacyclin production is reduced and thromboxane A2 production increased, resulting in a pro-thrombotic condition. Synthesis of arachidonic acid metabolites may be manipulated using drugs such as aspirin or imidazole analogues which selectively inhibit different enzymes in the metabolic pathway. Such drugs have proved beneficial in the treatment of some vascular disorders. Clinical use of prostacyclin has shown it to be effective in the treatment of peripheral vascular disease, Raynaud's Syndrome and pulmonary hypertension. Stable analogues of prostacyclin are being developed which may lead to a separation of the vasodilator and anti-platelet actions of prostacyclin.


Multiple-site and-year analyses of stream insect emergence: a test of ecological theory.
The use of existing data sets to test applicability of existing ecological theory is an uncommon but potentially cost-effective approach for exploitation of previously accumulated knowledge. Studies on the emergence of insects from small streams have been a major research topic in aquatic ecology, particularly in Austria and Germany; the availability of emergence data from these two countries, covering over 1 million identified specimens, from 18 sites, and for 32 collection years is an example of such exploitable information. Concurrent estimates of annual emergence biomass and annual benthic secondary production for 18 aquatic insect populations showed a statistically significant relationship, contradicting the premise that emergence data do not provide any quantitative measure for a given stream area. Therefore, the emergence data were examined to test various predictions from ecological theory. Observed richness of emerging species of three orders of lotic insects - the Ephemeroptera, Plecoptera, and Trichoptera (EPT) - over 15 years at one site did not agree with predictions based on either flow predictability or change in flow and the "habitat templet concept". Trends in observed richness of emerging EPT species over 1 year at 18 sites agreed weakly with predictions using either pH values or the annual temperature amplitude and the "intermediate disturbance hypothesis", or using either annual temperature amplitude or total biomass of EPT emergence and the "disturbance-productivity-diversity model". A prediction of the "river continuum concept" that abundance of the shredder functional-feeding group should decrease and that of grazers should increase along a dense- to open-canopy gradient was not consistently supported by the emergence biomass data. For shredders and grazers of all insects (12 sites) and EPT (18 sites), this trend was apparent (but not significant) only if sites with intermediate canopy density were omitted. We identified three critical elements in our study that generally interfere with such tests of these theoretical constructs: (i) species richness is a poor measure of resource limitation and/or utilization theories; (ii) restrictions of the taxonomic operational window (in our example usually to EPT) causes problems in extrapolation to a larger system (in our example to all insects); and (iii) historical constraints may affect the local result of tests of resource limitation and/or utilization theories simply because species that potentially interact are lacking in the region under examination. Problems notwithstanding, the use of existing data sets to test applicability of currently held ecological theories is a cost-effective and amenable approach for use in a variety of research topics in stream and general ecology. In this context, future tests should focus on: (i) measures that are more robust than just species richness, e.g., on measures commonly used to assign species to strategies such as r, K, or A; (ii) a variety of taxonomic groups; and (iii) gradients in historical constraints on current regional species composition.


Magnesium supplementation for the treatment of restless legs syndrome and periodic limb movement disorder: A systematic review.
Magnesium supplementation is often suggested for restless legs syndrome (RLS) or period limb movement disorder (PLMD) based on anecdotal evidence that it relieves symptoms and because it is also commonly recommended for leg cramps. We aimed to review all articles reporting the effects of magnesium supplementation on changes in RLS and/or PLMD. We conducted a systematic search looking for all relevant articles and then two reviewers read all article titles and abstracts to identify relevant studies. Eligible studies were scored for their quality as interventional trials. We found 855 abstracts and 16 of these could not be definitively excluded for not addressing all aspects of our research question. Seven full-text articles were unlocatable and one was ineligible which left eight studies with relevant data. One was a randomised placebo-controlled trial, three were case series and four were case studies. The RCT did not find a significant treatment effect of magnesium but may have been underpowered. After quality appraisal and synthesis of the evidence we were unable to make a conclusion as to the effectiveness of magnesium for RLS/PLMD. It is not clear whether magnesium helps relieve RLS or PLMD or in which patient groups any benefit might be seen.


Research as Profession and Practice: Frameworks for Guiding the Responsible Conduct of Research.
Programs in the responsible conduct of research (RCR) vary between institutions, demonstrated by disparate structures and goals. These variations may be attributed to the absence of grounding frameworks within which to examine research and RCR education programs. This article examines research as a practice and a profession, using these frames to draw out defining features of research and the moral obligations entailed. Situating research within virtue ethics can clarify how researchers might cultivate the virtues necessary for meeting its obligations and aims. By elucidating these features, these perspectives can serve to guide the development of RCR education programs.


[Combined management of colon cancer local recurrences with using intraabdominal chemotherapy].
The efficacy of intraabdominal chemotherapy in management of local recurrences of colon cancer was studied. Intraabdominal intraoperative and early postoperative chemotherapy made it possible to prolong of the recurrenceless term and to improve the life quality of the patients with local recurrences of colon cancer. There was observed a tendency to increase the five-year survival.


The prognostic value of p53 immunostaining in node-negative breast carcinoma.
P53 plays a key role in cell cycle arrest, apoptosis, DNA repair, and angiogenesis. Although some studies have reported as prognostic factor for poor survival in node-positive breast cancer, controversy about possible prognostic index for node-negative still exists. To look for correlations between the expression of the p53 protein and clinicopathological parameters, and to assess its prognostic value in node-negative invasive ductal breast carcinoma. Immunohistochemistry using formalin-fixed, paraffin-embedded sections from 71 node-negative breast carcinomas in Songklanagarind Hospital. Data were analyzed with respect to tumor size, estrogen receptor, and survival. P53 mutations were found in 12 patients (17%). Expression of p53 was not associated with tumor size, estrogen receptor, and overall survival. Mean follow-up time was 164.4 months (median 163 months). P53 expression was not a significant prognostic factor for survival in node-negative breast carcinoma.


Amygdalin binds to the CD4 receptor as suggested from molecular modeling studies.
The geometrical features of the proposed bioactive conformation of peptide T assessed by computational methods in a previous study, together with available structure-activity studies on peptide T, led us to propose a pharmacophore for the CD4-peptide T interaction. Subsequent, data base searching permitted us to identify amygdalin as a peptide T peptidomimetic.


Comparing Upper Airway Stimulation to Transoral Robotic Base of Tongue Resection for Treatment of Obstructive Sleep Apnea.
Transoral robotic surgery (TORS) and upper airway stimulation (UAS) are modalities for treating tongue base obstruction contributing to obstructive sleep apnea (OSA). We aim to compare patients with OSA undergoing TORS to those undergoing UAS. We retrospectively reviewed patients treated with TORS and UAS using the senior authors' surgical database. We evaluated demographic, preoperative polysomnography (PSG), postoperative PSG, complication, hospital length of stay, and hospital readmission data to compare the two cohorts. Seventy-six patients underwent UAS. This included 50 men and 26 women. The mean age and body mass index were 61.92 and 29.38. The mean pre- versus postoperative apnea hypopnea index (AHI) and O2 nadir were 36.64 versus 7.20 and 80.27% versus 88.77%, respectfully. The rate of surgical success and postoperative AHI less than 15 and 5 were 86.84%, 89.47%, and 59.21. All patients underwent ambulatory surgery, and no one was readmitted. Twenty-four patients underwent TORS. This included 20 men and four women with a mean age and body mass index BMI of 46.42 and 29.63. The mean pre- versus postoperative AHI and O2 nadir were 35.70 versus 20.05 and 80.50% versus 84.10%, respectfully. The rate of surgical success and postoperative AHI less than 15 and 5 were 54.17%, 50.00%, and 20.83%. The mean length of stay was 1.33 days, and four patients were readmitted. We found significant differences in age, postoperative AHI and O2 nadir, surgical success and postoperative AHI less than 15 and 5, length of stay, and rate of readmission. UAS is successful in treating OSA showing improved outcomes, length of stay, and readmission compared to TORS. 3 Laryngoscope, 129:1010-1013, 2019.


Palladium-Catalyzed Asymmetric (3 + 2) Cycloaddition of Vinyl Epoxides with Substituted Propiolates. Enantioselective Formation of 2,3,4-Trisubstituted 2,3-Dihydrofurans.
Alkynyl esters are viable dipolarophiles for the palladium-catalyzed asymmetric (3 + 2) cycloaddition with vinyl epoxides. The chiral dihydrofurans are obtained in high yields and high ee values. The use of a chiral benzylic substituted P,N-ligand is essential. The usefulness of the synthetic method has been demonstrated; 2,3-cis-tetrahydrofuran was also provided.


The role of plant genotype, environment and gender in resistance to a specialist chrysomelid herbivore.
Patchiness in herbivore attack is a well-documented phenomenon. When neighboring plants suffer vastly different levels of attack, then one suspects genotypic differences among plants to be the underlying mechanism. In this study, I use common garden experiments in two natural, but divergent, habitats at the Cedar Creek Natural History Area in central Minnesota to determine the role of plant genotype, environment and gender in plant resistance to a specialist herbivore. Resistance was measured by larval survivorship and weight. Eight clones ofRhus glabra were selected and 12 equal-aged ramets were dug up and planted in two gardens (each garden received 6 ramets per clone). First instarBlepharida rhois (Coleoptera: Chrysomelidae) larvae of known parentage were transferred to ramets and censused every other day. At the end of the experiment, larvae were collected and weighed. Analysis of variance was used to determine the importance of plant genotype, environment and gender on larval mortality and weight. The experiment was repeated in its entirety one month later. Both plant genotype and environment significantly affected larval survivorship in the first run of the experiment. No interactions were significant. Results from the second run indicated marginally significant genotype and environment main effects, and a genotype by environment interaction in larval survivorship. There was a significant genotype by environment interaction in larval weight on the same run. In neither run did clone gender have significant affects on resistance.


Antimicrobial activities of plant essential oil vapours against Acidovorax citrulli and Xanthomonas campestris on Cucurbitaceae, Brassicaceae and Solanaceae seeds.
This study was done to develop a seed decontamination treatment for organic seeds against plant pathogens (Acidovorax citrulli and Xanthomonas campestris) using essential oil (EO) vapours without affecting the seeds' germination rate. By using a diffusion assay and determining minimum inhibitory and lethal concentrations, we screened two EO vapours which were most inhibitory to A. citrulli (cinnamon bark and garlic EO vapours) and X. campestris (onion and garlic EO vapours). After 48 h of exposure to EO vapours at 25°C and 43% or 85% relative humidity (RH), no significant decrease (p > 0.05) in germination rates was observed compared with those of control seeds. It was observed that EO vapour treatment at 25°C and 43% or 85% RH for 48 h caused significant population reductions (p ≤ 0.05) (ca. 0.3-2.6 log colony forming unit/g) compared to those of untreated seeds. Applications of EO vapours showed significant (p ≤ 0.05) antimicrobial effects against A. citrulli and X. campestris on both laboratory mediums and plant seeds without decreasing the germination rate of seeds. This study provides useful information for the development of natural seed sterilization treatments using EO vapours.


Luffolide, a novel anti-inflammatory terpene from the sponge Luffariella sp..
Luffolide (4) is a minor metabolite of the sponge Luffariella sp. from Palau. The structure of luffolide was determined by single crystal X-ray analysis. Luffolide is relatively unstable and undergoes a complex cyclization reaction to give the hexacyclic products 5 and 6. Luffolide (4) has some of the anti-inflammatory properties of manoalide (1): this may help to define the chemical reaction between manoalide (1) and phospholipase A2.


Improved grip myotonia in a patient with myotonic dystrophy type 1 following electroacupuncture therapy: A CARE-compliant case report.
Myotonic dystrophy type 1 (DM1) is an autosomal-dominant disorder associated with a short life expectancy and various symptoms, including grip myotonia. Even though grip myotonia decreases quality of life, activities of daily living (ADLs), and work performance, very few interventions provide symptomatic relief. In this case report, we present a patient with DM1 and gradually worsening grip myotonia. A 35-year-old woman developed grip myotonia at age 27. She had no underlying diseases or family history of relevant conditions, including DM1. She was unresponsive to medication for several years. Her symptoms gradually worsened, and she was finally diagnosed with DM1 via genetic, neurologic, and laboratory testing in a tertiary hospital at age 32. She tried several medication therapies; however, she stopped medication at age 34 due a perceived poor response and several adverse events. At the age of 35, she underwent 29 sessions (10 minutes per session) of electroacupuncture therapy on TE9 acupuncture point with 120 Hz electrical stimulation over 3 months. After 3 months, relaxation time after maximal voluntary isometric contraction decreased from 59 to 2 seconds with treatment. Her Michigan Hand Outcomes Questionnaire score improved (total score, 66.6-75.9; ADL sub-score, 59.7-73.6; function sub-score, 70-90; satisfaction sub-score, 75-91.7). Her Measure Yourself Medical Outcome Profile 2 score also improved from 4.33 to 2. There were no serious adverse events. Electroacupuncture is a potential treatment modality and produced an immediate antimyotonic effect, and cumulative long-term treatment effect, in a patient with DM1 and grip myotonia. Other notable treatment outcomes included improving relaxation time, hand function, ADLs, and overall satisfaction. Electroacupuncture is a potential treatment modality for patients with DM1 and grip myotonia. Further prospective clinical studies are warranted to confirm this hypothesis.


Self-expanding metal stents as palliative treatment of stenotic relapsed gastric cancer after curative surgery in the elderly.
Palliation of inoperable stenotic gastric and/or duodenal cancer remains an open problem due to high operative mortality and diffuse tumor growth. We describe here in 3 cases of stenotic recurrent gastric cancer in the elderly successful treated using self-expanding metal stents.


Relative contributions of central and peripheral factors to fatigue during a maximal sustained effort.
Local muscle fatigue can originate from both peripheral and central factors. The relative contribution of these factors in the course of a fatiguing contraction in 20 healthy subjects was determined. While subjects made a 2-min sustained maximal voluntary contraction (MVC) of the biceps brachii, muscle fibre conduction velocity (MFCV) was determined with surface electromyography (SEMG) as a representation of developing peripheral fatigue. To quantify the amount of peripheral fatigue, the force development following a train of electrical stimuli on the endplate before and after the contraction were compared. To measure force loss caused by central factors, superimposed electrical stimulation was used during the contraction. By two different methods the influence of peripheral fatigue on the superimposed force responses was taken into account. The first method compared the force response with the actual voluntary force, the second -which seemed more valid - used an estimation of peripheral fatigue based on linear interpolation between the force responses during rest before and after sustained contraction. During the contraction, voluntary force decreased to 38%. Peripheral fatigue was responsible for the larger part of this decline (89%). The other part, which was calculated as 12%, was caused by an increase of central activation failure. The decline of MFCV indicated that peripheral fatigue increased predominantly during the first half of the contraction and stayed at a constant level during the latter part. In contrast, central fatigue mainly induced a force decrease in the second part of the contraction. The different mechanisms which could be responsible for this change of emphasis from peripheral to central factors are discussed.


Valgus Osteotomy with Plate-and-Nail Fixation for the Treatment of Proximal Femoral Deformities Due to Fibrous Dysplasia: A Report of Two Cases.
We describe 2 cases of proximal femoral deformity due to fibrous dysplasia that were corrected with osteotomies and a novel combined construct with a blade plate and a retrograde intramedullary nail. A single-stage procedure using a combined construct with a blade plate and a retrograde intramedullary nail is a viable option for correcting and subsequently preventing proximal femoral deformities due to fibrous dysplasia.


Cytoarchitectural characteristic of the frontal eye fields in macaque monkeys.
The cytoarchitecture of the prearcuate gyrus, including the region of the physiologically defined frontal eye fields (FEF), was studied in four macaque monkeys (Macaca fascicularis, M. mulatta) to determine if the FEF could be anatomically identified. Brain sections were stained with standard Nissl and, in some cases, myelin stains. Two nonstandard planes of section were used: one tangential to the prearcuate gyrus and the second normal to the most posterior bend of the prearcuate gyrus. The first plane of section was advantageous for studying the location of the FEF with reference to the entire medial-lateral extent of the gyrus and the second allowed good comparisons of the FEF to adjacent anterior and posterior cortical areas. Frontal plane sections through the prearcuate gyrus were also examined in 15 macaque monkeys for comparison with sections cut normal to the posterior bend of the gyrus and tangential to the gyrus. Intracortical microstimulation was performed in three monkeys. The FEF was defined as the area from which low-threshold (less than or equal to 50 microA) saccades could be evoked. The area extended about 10 mm along the anterior bank of the arcuate sulcus. Within the area, saccade amplitudes were represented in a mediolateral, large-to-small topography. No topography of saccade direction was noted within FEF but reversals of saccade direction for any given electrode pass were found. These results confirm the results from our earlier mapping study of FEF (Bruce et al.: J. Neurophysiol. 54:714-734, '85). Cell bodies of large pyramidal cells in layers III and V of the prearcuate gyri from three hemispheres were measured with the aid of an image-combining computer microscope. The distribution of cells of greater than 22 microns diameter or cross-sectional areas of greater than 500 microns 2 were plotted. In one monkey, marker lesions made at microstimulation sites within the FEF or in adjacent non-FEF areas were also plotted. The location of the FEF appeared to coincide with the concentration of large layer V pyramidal cells in the prearcuate gyrus rather than with any previously mapped cytoarchitectonic area. The numbers of large pyramids in layer V were noticeably reduced along the lip of the prearcuate gyrus and at dorsomedial and ventrolateral locations which were outside the physiologically defined FEF.


Isolation of a cytopathogenic virus from a case of porcine reproductive and respiratory syndrome (PRRS) and its characterization as parainfluenza virus type 2.
From a lung of a fetus of a breeding sow showing PRRS-like symptoms a viral agent could be isolated. It was characterized as an enveloped, hemagglutinating RNA virus. Ultrastructural examination of purified virus revealed paramyxovirus-like pleomorphic virions of approx. 200 nm in diameter. The helical nucleocapsids were about 18 nm in diameter. The virus was found to be antigenically related to simian virus 5 (SV5) a prototype strain of parainfluenza virus type 2, but not to bovine respiratory syncytial virus, parainfluenza virus type 1, parainfluenza virus type 3, and Newcastle disease virus as determined by western blot analysis.


Mutations in each of the tol genes of Pseudomonas putida reveal that they are critical for maintenance of outer membrane stability.
The outer membrane of gram-negative bacteria functions as a permeability barrier that protects cells against a large number of antibacterial agents. OprL protein of Pseudomonas putida has been shown to be crucial to maintain the stability of this cell component (J. J. Rodríguez-Herva, M.-I. Ramos-González, and J. L. Ramos. J. Bacteriol. 178:1699-1706, 1996). In the present study we cloned and mutagenized the orf1, tolQ, tolR, tolA, and tolB genes from P. putida KT2440, which were located upstream of the oprL gene. Polar and nonpolar mutations of the P. putida tolQ, tolR, tolA, and tolB genes were generated in vitro by using the omega-Km(r) interposon, which carries two transcriptional stop signals, or a promoterless xylE cassette, lacking any transcriptional stop signal, respectively. The mutant constructs were used to inactivate, by reverse genetics procedures, the corresponding chromosomal copies of the genes. The phenotype of each mutant strain was analyzed and compared with those of the wild-type strain and the previously characterized P. putida oprL::xylE mutant. All mutant strains exhibited a similar phenotype: altered cell morphology, bleb formation at the cell surface, release of periplasmic and outer membrane proteins to the extracellular medium, increased sensitivity to a variety of compounds (i.e., EDTA, sodium dodecyl sulfate, deoxycholate, and some antibiotics), filament formation, and severely reduced cell motility. Altogether, these results demonstrate the importance of the Tol-OprL system for the maintenance of outer membrane integrity in P. putida and suggest a possible role of these proteins in assembling outer membrane components.


[The so-called shock lung, a disease of lung parenchyma (author's transl)].
Although the pathogenesis of the so-called shock lung is different, from the clinical point of view the syndrome is uniform. Regarding the morphology microcirculation, vascular permeability and surfactant of the lung in shock lung are discussed. The course of the alterations in lung parenchyma is uniform, independent of the different pathogenesis in a single case. Pathology and disturbtion of lung function are conform. The relation of the so-called shock lung to other diseases of lung parenchyma is discussed and finally a definition of the so-called shock-lung recommended.


Fee for home delivery and monitoring of antiretroviral therapy for HIV infection compared with standard clinic-based services in South Africa: a randomised controlled trial.
Home delivery and monitoring of antiretroviral therapy (ART) is convenient, overcomes logistical barriers, and could increase individual ART adherence and viral suppression. With client payment and sufficient health benefits, this strategy could be scalable. The aim of the Deliver Health Study was to test the acceptability and efficacy of a user fee for home ART monitoring and delivery. We conducted a randomised trial, the Deliver Health Study, of a fee for home delivery of ART compared with free clinic ART delivery in South Africa. People with HIV who were 18 years or older and clinically stable (including CD4 count >100 cells per μL and WHO HIV stage 1-3) were randomly assigned to: (1) fee for home delivery and monitoring of ART, including community ART initiation if needed; or (2) clinic-based ART (standard of care). The one-time fee for home delivery (ZAR 30, 60, and 90; equivalent to US$2, 4, 6) was tiered on the basis of participant income. The primary outcomes were recorded fee payment and acceptability assessed via questionnaire. The key virological secondary outcome was viral suppression with the difference between study groups assessed through robust Poisson regression including participants with viral load measured at exit (modified intention-to-treat analysis). This trial is registered on ClinicalTrials.gov (NCT04027153) and is complete, with analyses ongoing. From Oct 7, 2019, to Jan 30, 2020, 162 participants were enrolled; 82 were randomly assigned to the fee for home delivery group and 80 to the clinic-based group, with similar characteristics at baseline. Overall, 87 (54%) participants were men, 101 (62%) were on ART, and 98 (60%) were unemployed. In the home delivery group, 40 (49%), 33 (40%), and nine (11%) participants qualified for the ZAR 30, 60, and 90 fee, respectively. Median follow-up was 47 weeks (IQR 43-50) with 96% retention. 80 (98%) participants paid the user fee, with high acceptability and willingness to pay. In the modified intention-to-treat analysis of 155 (96%) participants who completed follow-up, fee for home delivery and monitoring statistically significantly increased viral suppression from 74% to 88% overall (RR 1·21, 95% CI 1·02-1·42); and from 64% to 84% among men (1·31, 1·01-1·71). Among South African adults with HIV, a fee for home delivery and monitoring of ART significantly increased viral suppression compared with clinic-based ART. Clients' paying a fee for home delivery and monitoring of ART was highly acceptable in the context of low income and high unemployment, and improved health outcomes as a result. Home ART delivery and monitoring, potentially with a user fee to offset costs, should be evaluated as a differentiated service delivery strategy to increase access to care. National Institutes of Mental Health.


Is collectionism a diagnostic clue for Diogenes syndrome?
Diogenes syndrome (DS) is characterized by extreme self-neglect, domestic squalor, and social withdrawal. Despite having been described decades ago, it is still difficult to persue a correct diagnosis in primary care clinics. This paper reports a case of an elderly man with extreme self neglect and an abnormal collecting pattern whose condition remained undetected for many years. His collectionism was manifested with a tendency to store items in an organized manner but without a clear purpose. The authors suggest that the presence of collectionism could be a helpful clue towards diagnosis of DS in similar cases.


Physiological responses to nanoCuO in fungi from non-polluted and metal-polluted streams.
Nanocopper oxide (nanoCuO) is among the most widely used metal oxide nanoparticles which increases their chance of being released into freshwaters. Fungi are the major microbial decomposers of plant litter in streams. Fungal laccases are multicopper oxidase enzymes that are involved in the degradation of lignin and various xenobiotic compounds. We investigated the effects of nanoCuO (5 levels, ≤ 200 mg L(-1)) on four fungal isolates collected from metal-polluted and non-polluted streams by analyzing biomass production, changes in mycelial morphology, laccase activity, and quantifying copper adsorbed to mycelia, and ionic and nanoparticulate copper in the growth media. The exposure to nanoCuO decreased the biomass produced by all fungi in a concentration- and time-dependent manner. Inhibition of biomass production was stronger in fungi from non-polluted (EC₅₀(10 days) ≤ 31 mg L(-1)) than from metal-polluted streams (EC₅₀(10 days) ≥ 65.2 mg L(-1)). NanoCuO exposure led to cell shrinkage and mycelial degeneration, particularly in fungi collected from non-polluted streams. Adsorption of nanoCuO to fungal mycelia increased with the concentration of nanoCuO in the medium and was higher in fungi from non-polluted streams. Extracellular laccase activity was induced by nanoCuO in two fungal isolates in a concentration-dependent manner, and was highly correlated with adsorbed Cu and/or ionic Cu released by dissolution from nanoCuO. Putative laccase gene fragments were also detected in these fungi. Lack of substantial laccase activity in the other fungal isolates was corroborated by the absence of laccase-like gene fragments.


Levofloxacin pharmacokinetics in ESRD and removal by the cellulose acetate high performance-210 hemodialyzer.
No published data are available describing the pharmacokinetics of intravenous levofloxacin in patients with end-stage renal disease (ESRD). Objectives of this study are to determine the pharmacokinetics and dialytic clearance of levofloxacin and develop dosing strategies in these patients. Eight noninfected subjects receiving long-term thrice-weekly hemodialysis, with no measurable residual renal function, were administered intravenous levofloxacin, 250 mg, over 1 hour after a scheduled hemodialysis session. Blood samples were collected serially during the interdialytic period, during the next intradialytic period, and immediately after the next hemodialysis session. Serum concentrations of levofloxacin were determined by high-performance liquid chromatography. Differential equations describing a 2-compartment open-infusion pharmacokinetic model were fit to each individual subject's serum concentration-time data by iterative nonlinear weighted least-squares regression analysis using Adapt II (Biomedical Simulations Resource, University of Southern California, Los Angeles, CA). Ratios of maximum serum concentration (C(max)) to minimum inhibitory concentration (MIC) were calculated for common respiratory pathogens by using MIC for 90% of isolates (MIC90) data from published studies. All subjects completed the study, and no adverse events were reported. Median systemic clearance, volume of distribution at steady state, elimination half-life, and C(max) were 37.0 mL/min (range, 12.8 to 42.7 mL/min), 103.3 L (range, 39.8 to 139.3 L), 34.4 hours (range, 28.4 to 39.3 hours), and 5.2 microg/mL (range, 4.1 to 11.3 microg/mL), respectively. Median dialytic clearance and levofloxacin reduction ratios were 84.4 mL/min (range, 61.8 to 107.6 mL/min) and 0.244 (range, 0.181 to 0.412), respectively. Median C(max)-MIC90 ratios were 10 or greater for Haemophilus influenzae, Moraxella catarrhalis, Enterobacter cloacae, and Klebsiella pneumoniae, approximately 5 for Streptococcus pneumoniae, and less than 1 for Pseudomonas aeruginosa. The administration of levofloxacin to patients with ESRD as 500 mg initially, followed by 250 mg every 48 hours, will provide adequate C(max)-MIC ratios after the first and subsequent doses for most patients with respiratory tract infections caused by organisms with levofloxacin MICs of 1 microg/mL or less.


Comparison of three different automatic defibrillator implantation approaches: pectoral implantation using conscious sedation reduces procedure times and cost.
Recent technological advances in implantable defibrillator systems (ICD) have changed implantation approaches. The aim of this study was to investigate the influence of these improvements on procedure times, implant-related charges, patient recovery, and morbidity. Ninety-six consecutive patients undergoing implantation of a nonthoracotomy ICD were studied. Implantation was performed under general anesthesia with the generator placed abdominally in 22 patients (group I) and pectorally in 40 patients (group II). Thirty-four patients underwent pectoral implantation using conscious sedation (group III). Groups were comparable with respect to clinical variables. Implantation duration and total procedure duration were shorter in group III (67 +/- 21 minutes and 117 +/- 30 minutes) when compared with group I (100 +/- 25 minutes and 157 +/- 39 minutes) and group II (86 +/- 24 minutes and 153 +/- 34 minutes, P < 0.05). Patients in group III did not require admission to the Post-Anesthesia Care Unit. In contrast, patients in groups I and II spent 92 +/- 28 minutes and 91 +/- 31 minutes in the Post-Anesthesia Care Unit. Implantation-related charges were reduced in patients having pectoral implantation using conscious sedation ($1451 +/- 217 vs. $2354 +/- 550 and $2796 +/- 384, P < 0.05). Patients in group III had a lower frequency of postoperative oral analgesic use (3.2 +/- 2.7 doses, P < 0.05) and a shortened post-operative length of stay (1.9 +/- 1.6 days, P < 0.05) when compared with groups I (5.7 +/- 4.0 doses and 3.3 +/- 1.4 days) and II (5.2 +/- 3.5 doses and 2.6 +/- 1.1 days). The overall complication rate was low (6.3%), with no differences between groups. Advances in ICD technology have simplified implantation, leading to shorter, less painful, and less expensive procedures.


Trigeminal nerve hypesthesia after sagittal split osteotomy in setback cases: correlation of postoperative computed tomography and long-term trigeminal somatosensory evoked potentials.
We sought to assess the relationship of the inferior alveolar nerve to the osteotomy site after bilateral sagittal split osteotomy (BSSO) and to correlate the nerve osteotomy relationship as the cause of long-term postoperative hypesthesia. The subjects consisted of 28 patients with mandibular prognathism who underwent BSSO setback surgery. The distance between the ostectomized surface of the mandibular ramus and mandibular canal was measured and scored on a computed tomograph (CT). The relationship between this distance and the presence and degree or absence of trigeminal nerve hypesthesia was objectively evaluated by latency delay of the trigeminal somatosensory evoked potential (TSEP) records. Five of the 56 sides (8.9%) showed latency delays more than 1 year after the operations. Scored CT points between the canal and the split surface strongly correlated with TSEP latency recovery (Y = 1.716X + 41.2). This relationship between the canal and the osteotomy site is related to long-term hypesthesia in BSSO postoperatively.


Sex differences in prefrontal cortex microglia morphology: Impact of a two-hit model of adversity throughout development.
Neuroimmune mechanisms play critical roles in brain development and can be impacted by early life adversity. Microglia are the resident immune cells in the brain, with both sex-specific and region-specific developmental profiles. Since early life adversity is associated with several neuropsychiatric disorders with developmental pathogeneses, here we investigated the degree to which maternal separation (MS) impacted microglia over development. Microglia are dynamic cells that alter their morphology in accordance with their functions and in response to stressors. While males and females reportedly display different microglial morphology in several brain regions over development and following immune and psychological challenges, little is known about such differences in the prefrontal cortex (PFC), which regulates several early life adversity-attributable disorders. Additionally, little is known about the potential for early life adversity to prime microglia for later immune challenges. In the current study, male and female rats were exposed to MS followed by lipopolysaccharide administration in juvenility or adolescence. The prelimbic and infralimbic PFC were then separately analyzed for microglial density and morphology. Typically developing males expressed smaller soma and less arborization than females in juvenility, but larger soma than females in adolescence. MS led to fewer microglia in the infralimbic PFC of adolescent males. Both MS and lipopolysaccharide administration affected morphological characteristics in juvenile males and females, with MS exposure leading to a greater increase in soma size following lipopolysaccharide. Interestingly, effects of MS and lipopolysaccharide were not observed in adolescence, while notable sex differences in PFC microglial morphology were apparent. Taken together, these findings provide insight into how PFC microglia may differentially respond to challenges over development in males and females.