Bridging Disciplines: Applications of Forensic Science and Industrial Hemp.
Forensic laboratories are required to have analytical tools to confidently differentiate illegal substances such as marijuana from legal products (i.e., industrial hemp). The Achilles heel of industrial hemp is its association with marijuana. Industrial hemp from the Cannabis sativa L. plant is reported to be one of the strongest natural multipurpose fibers on earth. The Cannabis plant is a vigorous annual crop broadly separated into two classes: industrial hemp and marijuana. Up until the eighteenth century, hemp was one of the major fibers in the United States. The decline of its cultivation and applications is largely due to burgeoning manufacture of synthetic fibers. Traditional composite materials such as concrete, fiberglass insulation, and lumber are environmentally unfavorable. Industrial hemp exhibits environmental sustainability, low maintenance, and high local and national economic impacts. The 2018 Farm Bill made way for the legalization of hemp by categorizing it as an ordinary agricultural commodity. Unlike marijuana, hemp contains less than 0.3% of the cannabinoid, Δ9-tetrahydrocannabinol, the psychoactive compound which gives users psychotropic effects and confers illegality in some locations. On the other hand, industrial hemp contains cannabidiol found in the resinous flower of Cannabis and is purported to have multiple advantageous uses. There is a paucity of investigations of the identity, microbial diversity, and biochemical characterizations of industrial hemp. This review provides background on important topics regarding hemp and the quantification of total tetrahydrocannabinol in hemp products. It will also serve as an overview of emergent microbiological studies regarding hemp inflorescences. Further, we examine challenges in using forensic analytical methodologies tasked to distinguish legal fiber-type material from illegal drug-types.


Improved method for minimizing sulfur loss in analysis of particulate organic sulfur.
The global sulfur cycle depends primarily on the metabolism of marine microorganisms, which release sulfur gas into the atmosphere and thus affect the redistribution of sulfur globally as well as the earth's climate system. To better quantify sulfur release from the ocean, analysis of the production and distribution of organic sulfur in the ocean is necessary. This report describes a wet-based method for accurate analysis of particulate organic sulfur (POS) in the marine environment. The proposed method overcomes the considerable loss of sulfur (up to 80%) that occurs during analysis using conventional methods involving drying. Use of the wet-based POS extraction procedure in conjunction with a sensitive sulfur analyzer enabled accurate measurements of cellular POS. Data obtained using this method will enable accurate assessment of how rapidly sulfur can transfer among pools. Such information will improve understanding of the role of POS in the oceanic sulfur cycle.


Vesical imaging reporting and data system (VI-RADS) could predict the survival of bladder-cancer patients who received radical cystectomy.
Vesical Imaging Reporting and Data System (VI-RADS) shows good potential in determining muscle-invasive bladder cancer (MIBC) patients. However, whether VI-RADS could predict the prognosis of radical cystectomy (RC) patients has not been reported. Our purpose is to determine whether VI-RADS contributed to predict oncologic outcomes. In this retrospective study, we analysed the information of bladder cancer patients who admitted to our centre from June 2012 to June 2022. All patients who underwent multiparametric magnetic resonance imaging (mpMRI) and underwent RC were included. VI-RADS scoring was performed by two radiologists blinded to the clinical data. Patients' clinical features, pathology data, and imaging information were recorded. Kaplan-Meier method was used to estimate patients' overall survival (OS) and progression-free survival (PFS). Log-rank test was used to assess statistical differences. COX regression analysis was used to estimate risk factors. Ultimately, we included 219 patients, with 188 males and 31 females. The median age was 66 (IQR = 61-74.5) years. The VI-RADS scores were as follows: VI-RADS 1, 4 (1.8%); VI-RADS 2, 68 (31.1%); VI-RADS 3, 40 (18.3%); VI-RADS 4, 69 (31.5%); and VI-RADS 5, 38 (17.4%). Patients with VI-RADS ≥ 3 had poorer OS and PFS than those with VI-RADS < 3. The AUC of VI-RADS predicting 3-year OS was 0.804, with sensitivity of 0.824 and negative predictive value of 0.942. Multivariate COX analysis showed that VI-RADS ≥ 3 was risk factors for OS (HR = 3.517, P = 0.003) and PFS (HR = 4.175, P < 0.001). In the MIBC subgroup, patients with VI-RADS ≥ 4 had poorer OS and PFS. In the non-muscle invasive bladder cancer (NMIBC) subgroup, the prognosis of patients with VI-RADS ≥ 3 remained poorer. VI-RADS scores could effectively predict the survival of patients after RC.


"Old friends in new guise": exploiting privileged structures for scaffold re-evolution/refining.
The attempts to increase novel drug productivity through creative discovery technologies have fallen short of producing the satisfactory results. For these reasons, evolved from the concept of drug repositioning, "privileged structure"-guided scaffold re-evolution/refining is a primary strategy to identify structurally novel chemotypes by modifying the central core structure and the side-chain of the existing active compounds, or to exploit undescribed bioactivites by making full use of readily derivatized motifs with well-established synthetic protocols. Herein, we review the basic tricks of exploiting privileged structures for scaffold re-evolution/refining. The power of this strategy is exemplified in the discovery of other new therapeutic applications by refining privileged structures in anti-viral agents.


An atomistic scale simulation study of structural properties in the silk-fibrohexamerin complex.
The use of Bombyx mori silk fibroin in composite materials has been extensively explored in many studies, owing to its remarkable mechanical properties. Recently, the N-glycan-engineered P25 protein was utilized to improve the mechanical properties of silk. However, the mechanism by which N-glycan-engineered P25 protein enhances the mechanical properties of silk remains unclear. This study analyzed the interaction between the P25 protein and silkworm silk using quantum mechanics/molecular mechanics multiscale simulations and discovered stronger hydrogen bonding between the amorphous domain and the P25 protein. The results confirmed that glycoengineering of the mannose molecule in N-glycan in orders of three, five, and seven increased the hydrogen bonding of the amorphous structures. However, P25 has fewer binding interactions with the crystalline domain. Silk amino acids and mannose molecules were analyzed using QM simulations, and hydroxyl and charged amino acids in the amorphous domains were found to have relatively higher reactivity with mannose molecules in N-glycans than basic and aliphatic amino acids in the crystalline domain. This study demonstrates how the N-glycan-engineered P25 protein can improve the mechanical properties of silk fibroin and identifies a key factor for N-glycan-engineered proteins.


[Insertion of permanent perfusion systems for chemotherapy. A ray of hope for the patients].
The number of patients undergoing chemotherapy for tumor disease has considerably increased in the last years. One of the problems of these long-term treatment modalities is the destruction of the peripheral venous system due to the repeated venous punctures for the therapy itself as well as for the laboratory analyses. This has been the motive for the research on permanent perfusion systems which would work at long term in a reliable way. Nowadays, several industrial products are available, devices for the standard implantation intravenously but also devices for intraarterial and intraperitoneal use. In our hands, the access through the subclavian vein with the end of the catheter in the superior caval vein has proven to be a safe and easy method. The port is placed in the triangle between the coracoid process and the clavicula. The large experience made by the centers in Basle and Berne as well as our own experiences in Bienne have clearly demonstrated the benefit of these systems for the patient. Nevertheless, some complications have to be mentioned such as the wellknown complications of the puncture of the subclavian vein. The risk of complete occlusion of the catheter must be expected at the rate of 0.5%. Hematomas immediately after the punction of the port have also been described. We would like to outline that complications of these permanent infusion systems are rare, especially in comparison with the complication rate of the normal percutaneous central venous sets. We therefore strongly advocate the implantation of these devices in the first instance before the beginning of any treatment in order to save the peripheral venous system of these patients.


Enhanced recovery after surgery pathway for abdominal wall reconstruction: pilot study and preliminary outcomes.
Enhanced recovery after surgery (ERAS) pathways represent a multimodal approach to improve the quality of postoperative care by diminishing the stress response to the trauma of an operation, thereby minimizing hospital length of stay and potentially complications. At a time when healthcare costs are being intensely scrutinized, efforts to reduce patient morbidity and hospital stay are imperative and timely. The success of ERAS fast-track surgery pathways-thoroughly studied in the colorectal literature-has led to their application in other fields. Herein, we present our ERAS pathway for patients undergoing abdominal wall repairs, including the rationale and supporting evidence behind each of its components and our early clinical results after implementation. Although hastened patient recovery is clearly multifactorial, our pathway, incorporating alvimopan, early feeding strategies, and multimodal pain therapy with an emphasis on the reduction of opiate usage as well as precise intraoperative nerve block with novel longer-acting local anesthetic Exparel, appears to provide significant improvement in postoperative pain, bowel function recovery, and shorter hospital stay. Although a prospective evaluation of the entire ERAS pathway as well as contribution of its various components is currently ongoing at our Hernia Center, we believe ours or similar ERAS pathways will soon become standard for the vast majority of patients undergoing abdominal wall surgery.


The effects of dietary protein intake on appendicular lean mass and muscle function in elderly men: a 10-wk randomized controlled trial.
Background: The Recommended Daily Allowance (RDA) for protein intake in the adult population is widely promoted as 0.8 g · kg-1 · d-1 Aging may increase protein requirements, particularly to maintain muscle mass.Objective: We investigated whether controlled protein consumption at the current RDA or twice the RDA (2RDA) affects skeletal muscle mass and physical function in elderly men.Design: In this parallel-group randomized trial, 29 men aged >70 y [mean ± SD body mass index (in kg/m2): 28.3 ± 4.2] were provided with a complete diet containing either 0.8 (RDA) or 1.6 (2RDA) g protein · kg-1 · d-1, aimed to balance energy needs. Before treatment and after 10 wk of intervention, whole-body and appendicular lean mass were measured by using dual-energy X-ray absorptiometry. Knee-extension peak power was measured with dynamometry.Results: Both groups were found to have been in a moderate negative energy balance (mean ± SD RDA: 209 ± 213 kcal/d; 2RDA 145 ± 214 kcal/d; P= 0.427 for difference between the groups). In comparison with RDA, whole-body lean mass increased in 2RDA (P = 0.001; 1.49 ± 1.30 kg, P < 0.001 compared with -0.55 ± 1.49 kg, P = 0.149). This difference was mostly accounted for by an increase in trunk lean mass found in 2RDA (+1.39 ± 1.09 kg, P < 0.001). Appendicular lean mass also decreased in RDA compared with 2RDA (P = 0.022), driven by a reduction in RDA (-0.64 ± 0.91 kg, P = 0.005 compared with 0.11 ± 0.57 kg, P = 0.592). Adjusting for energy imbalances did not alter these findings. Knee-extension peak power was also differently affected (P = 0.012; 26.6 ± 47.7 W, P = 0.015 in 2RDA compared with -11.7 ± 31.0 W, P = 0.180 in RDA).Conclusions: Consumption of a diet providing 2RDA for protein compared with the current guidelines was found to have beneficial effects on lean body mass and leg power in elderly men. These effects were not explained by differences in energy balance. This trial was registered at the Australia New Zealand Clinical Trial Registry (www.anzctr.org.au) as ACTRN12616000310460.


Factors Affecting Total Treatment Time in Patients Treated with Orthognathic Surgery Using the Surgery-First Approach: Multivariable Analysis Using 3D CT and Scanned Dental Casts.
The aim of this study was to analyze factors affecting treatment times in patients treated with the surgery-first approach (SFA) for orthognathic surgery. Fifty skeletal class III patients who had undergone SFA bimaxillary orthognathic surgery were enrolled. Retrospective chart reviews and analysis of 3D CT and digitally scanned casts were conducted to assess the total treatment time. Statistical analysis was then performed with multiple study variables. Longer treatment times were required for patients with severe maxillary or mandibular teeth crowding (p = 0.009), a preoperative anterior open bite (p = 0.021), and those undergoing orthodontic extractions (p < 0.001). Longer treatment times were also observed when setting surgical occlusion in the postoperative anterior open bite (p = 0.007) and in patients with postoperative dental midline deviation (p < 0.001) and transverse maxillary deficiencies (p = 0.035). Treatment times were shorter when a class I molar key was formed in the surgical occlusion setup (p = 0.002) and in bilateral anterior and posterior occlusion with a minimum of four contact points (p < 0.001). The number of contact points, the number of extracted teeth, and postoperative midline deviation were identified as significant predictors. These results suggest that proper patient selection is important when considering SFA and that surgeons can reduce total treatment time with an appropriate surgical occlusion setup.


Ammonia-oxidizing archaea as main drivers of nitrification in cold-water sponges.
The association of archaea with marine sponges was first described 15 years ago and their role in the nitrification process in Mediterranean and tropical sponges has been suggested. Here we explore the occurrence and abundance of potential ammonia-oxidizing archaea (AOA) in four morphologically different cold-water sponges (Phakellia ventilabrum, Geodia barretti, Antho dichotoma and Tentorium semisuberites) from the sublittoral and upper bathyal zone [Correction added on 30 December 2011, after first online publication on 19 December 2011: The term 'mesopelagic zone' has been replaced.] of the Norwegian coast, and relate them to nitrification rates determined in laboratory incubations. Net nitrification rates, calculated from the sum of nitrite and nitrate release during 24 h, were up to 1880 nmol N cm(-3) day(-1); i.e. comparable with those measured in Mediterranean sponges. Furthermore, a high abundance of archaeal cells was determined by fluorescence in situ hybridizations (CARD-FISH) and quantitative PCR, targeting archaeal amoA genes (encoding the alpha subunit of ammonia monooxygenase). AmoA genes as well as amoA transcripts were either exclusively detectable from archaea or were orders of magnitudes higher in abundance than their bacterial counterparts. Phylogenetic analyses of AOA and bacterial nitrite oxidizers (genus Nitrospira) confirmed the presence of specific populations of nitrifying microorganisms in the sponge mesohyl, which either were affiliated with groups detected earlier in marine sponges or were typical inhabitants of cold- and deep-water environments. Estimated cell-specific nitrification rates for P. ventilabrum were 0.6 to 6 fmol N archaeal cell(-1) day(-1), thus comparable with planktonic organisms. Our results identify AOA as the major drivers of nitrification in four cold-water sponges, and indicate that these archaea may be considered as a relevant factor in nitrogen cycling in ocean regions with high sponge biomass.


Venlafaxine and mirtazapine: different mechanisms of antidepressant action, common opioid-mediated antinociceptive effects--a possible opioid involvement in severe depression?
The efficacy of each antidepressant available has been found equal to that of amitriptyline in double-blind studies as far as mild to moderate depression is involved. However, it seems that some antidepressants are more effective than others in the treatment of severe types of depression (i.e., delusional depression and refractory depression). Following studies regarding the antinociceptive mechanisms of various antidepressants, we speculate that the involvement of the opioid system in the antidepressants' mechanism of action may be necessary, in order to prove effective in the treatment of severe depression. Among the antidepressants of the newer generations, that involvement occurs only with venlafaxine (a presynaptic drug which blocks the synaptosomal uptake of noradrenaline and serotonin and, to a lesser degree, of dopamine) and with mirtazapine (a postsynaptic drug which enhances noradrenergic and 5-HT1A-mediated serotonergic neurotransmission via antagonism of central alpha-auto- and hetero-adrenoreceptors). When mice were tested with a hotplate analgesia meter, both venlafaxine and mirtazapine induced a dose-dependent, naloxone-reversible antinociceptive effect following ip administration. Summing up the various interactions of venlafaxine and mirtazapine with opioid, noradrenergic and serotonergic agonists and antagonists, we found that the antinociceptive effect of venlafaxine is influenced by opioid receptor subtypes (mu-, kappa1- kappa3- and delta-opioid receptor subtypes) combined with the alpha2-adrenergic receptor, whereas the antinociceptive effect of mirtazapine mainly involves mu- and kappa3-opioid mechanisms. This opioid profile of the two drugs may be one of the explanations to their efficacy in severe depression, unlike the SSRIs and other antidepressants which lack opioid activity.


Clinical and epidemiological characteristics of human parainfluenza virus infections of children in southern Taiwan.
Human parainfluenza viruses (HPIV) 1-4 had been analyzed as being one of the most frequent causes of hospitalizations for young children with respiratory tract illnesses. This retrospective study was performed from children virologically confirmed as HPIV infection through throat swab or nasopharyngeal aspirates at a tertiary care university hospital, between January 2012 and December 2014. HPIV4 was not checked and analyzed, due to not include in the commercial kit. The demographic, epidemiological, clinical presentations, diagnosis, treatment, outcomes, and laboratory data were analyzed. Totally 398 cases were enrolled, including 39 (9.8%) of HPIV1, 67 (16.8%) of HPIV2, and 292 (73.4%) of HPIV3. The mean age of HPIV-infected children was 2.9 year-old, and 50.5% were among one to three year-old. A total of 56.8% HPIV3-infected children were among one to three years old, however, no HPIV2-infected children was younger than one year-old. The HPIV1-infected patients were more common to develop wheezing and diagnose as acute bronchiolitis. HPIV2-infected children were more likely to have hoarseness (23.9%), and were associated with croup (25.4%). HPIV3 was isolated from two fatal cases, with neurological underlying diseases. The impact caused by HPIVs infections is significant in hospitalized children. In the current study, our results contribute to the epidemiologic, clinical and laboratory information of HPIV infection in children in the important areas of respiratory tract infection that could support the development of optimization management.


Gastroesophageal reflux disease and tooth erosion.
The increasing prevalence of gastroesophageal reflux disease (GERD) in children and adults, and of "silent refluxers" in particular, increases the responsibility of dentists to be alert to this potentially severe condition when observing unexplained instances of tooth erosion. Although gastroesophageal reflux is a normal physiologic occurrence, excessive gastric and duodenal regurgitation combined with a decrease in normal protective mechanisms, including an adequate production of saliva, may result in many esophageal and extraesophageal adverse conditions. Sleep-related GERD is particularly insidious as the supine position enhances the proximal migration of gastric contents, and normal saliva production is much reduced. Gastric acid will displace saliva easily from tooth surfaces, and proteolytic pepsin will remove protective dental pellicle. Though increasing evidence of associations between GERD and tooth erosion has been shown in both animal and human studies, relatively few clinical studies have been carried out under controlled trial conditions. Suspicion of an endogenous source of acid being associated with observed tooth erosion requires medical referral and management of the patient as the primary method for its prevention and control.


Pharmacological activity of C10-substituted analogs of the high-affinity kainate receptor agonist dysiherbaine.
Kainate receptor antagonists have potential as therapeutic agents in a number of neuropathologies. Synthetic modification of the convulsant marine toxin neodysiherbaine A (NDH) previously yielded molecules with a diverse set of pharmacological actions on kainate receptors. Here we characterize three new synthetic analogs of NDH that contain substituents at the C10 position in the pyran ring of the marine toxin. The analogs exhibited high-affinity binding to the GluK1 (GluR5) subunit and lower affinity binding to GluK2 (GluR6) and GluK3 (GluR7) subunits in radioligand displacement assays with recombinant kainate and AMPA receptors. As well, the natural toxin NDH exhibited approximately 100-fold selectivity for GluK2 over GluK3 subunits, which was attributable to the C8 hydroxyl group in NDH. We used molecular dynamic simulations to determine the specific interactions between NDH and residues within the ligand-binding domains of these two kainate receptor subunits that contribute to the divergent apparent affinities for the compound. These data demonstrate that interactions with the GluK1 subunit are preserved in analogs with substitutions at C10 in NDH and further reveal the determinants of selectivity and pharmacological activity of molecules acting on kainate receptor subunits, which could aid in design of additional compounds that target these receptors.


Estimated Maximal Safe Dosages of Tumescent Lidocaine.
Tumescent lidocaine anesthesia consists of subcutaneous injection of relatively large volumes (up to 4 L or more) of dilute lidocaine (≤1 g/L) and epinephrine (≤1 mg/L). Although tumescent lidocaine anesthesia is used for an increasing variety of surgical procedures, the maximum safe dosage is unknown. Our primary aim in this study was to measure serum lidocaine concentrations after subcutaneous administration of tumescent lidocaine with and without liposuction. Our hypotheses were that even with large doses (i.e., >30 mg/kg), serum lidocaine concentrations would be below levels associated with mild toxicity and that the concentration-time profile would be lower after liposuction than without liposuction. Volunteers participated in 1 to 2 infiltration studies without liposuction and then one study with tumescent liposuction totally by local anesthesia. Serum lidocaine concentrations were measured at 0, 2, 4, 6, 8, 10, 12, 14, 16, 18, and 24 hours after each tumescent lidocaine infiltration. Area under the curve (AUC∞) of the serum lidocaine concentration-time profiles and peak serum lidocaine concentrations (Cmax) were determined with and without liposuction. For any given milligram per kilogram dosage, the probability that Cmax >6 μg/mL, the threshold for mild lidocaine toxicity was estimated using tolerance interval analysis. In 41 tumescent infiltration procedures among 14 volunteer subjects, tumescent lidocaine dosages ranged from 19.2 to 52 mg/kg. Measured serum lidocaine concentrations were all <6 μg/mL over the 24-hour study period. AUC∞s with liposuction were significantly less than those without liposuction (P = 0.001). The estimated risk of lidocaine toxicity without liposuction at a dose of 28 mg/kg and with liposuction at a dose of 45 mg/kg was ≤1 per 2000. Preliminary estimates for maximum safe dosages of tumescent lidocaine are 28 mg/kg without liposuction and 45 mg/kg with liposuction. As a result of delayed systemic absorption, these dosages yield serum lidocaine concentrations below levels associated with mild toxicity and are a nonsignificant risk of harm to patients.


Structural basis for toxin resistance of beta4-associated calcium-activated potassium (BK) channels.
The functional diversity of large conductance Ca(2+)- and voltage-dependent K(+) (BK) channels arises mainly from co-assembly of the pore-forming mSlo alpha subunits with four tissue-enriched auxiliary beta subunits. The structural basis of the interaction between alpha subunits with beta subunits is not well understood. Using computational and experimental methods, we demonstrated that four mSlo turrets decentralized distally from the channel pore to provide a wide open conformation and that the mSlo and hbeta4 subunits together formed a "helmet" containing three basic residues (Lys-120, Arg-121, and Lys-125), which impeded the entry of charybdotoxin (ChTX) by both the electrostatic interaction and limited space. In addition, the tyrosine insert mutant (in100Y) showed 56% inhibition, with a K(d) = 17 nm, suggesting that the hbeta4 lacks an external ChTX-binding site (Tyr-100). We also found that mSlo had an internal binding site (Tyr-294) in the alpha subunits that could "permanently" block 15% of mSlo+hbeta4 currents in the presence of 100 nm ChTX. These findings provide a better understanding of the diverse interactions between alpha and beta subunits and will improve the design of channel inhibitors.


Modulation of electrostatic interactions to reveal a reaction network unifying the aggregation behaviour of the Aβ42 peptide and its variants.
The aggregation of the amyloid β peptide (Aβ42), which is linked to Alzheimer's disease, can be altered significantly by modulations of the peptide's intermolecular electrostatic interactions. Variations in sequence and solution conditions have been found to lead to highly variable aggregation behaviour. Here we modulate systematically the electrostatic interactions governing the aggregation kinetics by varying the ionic strength of the solution. We find that changes in the solution ionic strength induce a switch in the reaction pathway, altering the dominant mechanisms of aggregate multiplication. This strategy thereby allows us to continuously sample a large space of different reaction mechanisms and develop a minimal reaction network that unifies the experimental kinetics under a wide range of different conditions. More generally, this universal reaction network connects previously separate systems, such as charge mutants of the Aβ42 peptide, on a continuous mechanistic landscape, providing a unified picture of the aggregation mechanism of Aβ42.


Pharmacology of antiepileptic drug polypharmacy.
Therapeutic options for epilepsy are increasing, and all drugs can produce adverse side effects. Physicians should first use monotherapy when treating an epileptic patient. If one drug proves insufficient to control all seizures without intolerable side effects, then careful combination of the fewest drugs possible must be used. Combine drugs with different mechanisms of action rather than drugs with similar mechanisms of action. Closely monitor the patient for adverse side effects, which increase when multiple drugs are taken, and measure antiepileptic blood levels more frequently than with patients who are on monotherapy.


Efficacy and safety of Chinese medicine JCM-16021 for diarrhea-predominant irritable bowel syndrome: study protocol for a multi-center, randomized, double-blind, placebo controlled clinical trial.
Irritable bowel syndrome (IBS) is a common gastrointestinal functional disease. Adults with IBS may experience abdominal pain, change of bowel habits, and abnormal stool form without organic disease. IBS can seriously affect their work productivity and quality of life, especially diarrhea-predominant irritable bowel syndrome (IBS-D). The Chinese medicine JCM-16021 has been shown to be potentially effective in improving the symptoms of IBS-D based on a small scale clinical trial. Hence, a large scale clinical study is designed to further evaluate the efficacy and safety of the Chinese medicine JCM-16021 for IBS-D with traditional Chinese medicine (TCM) pattern of Liver Stagnation and Spleen Deficiency (LSSD). This study is a multi-center, randomized, double-blind, placebo-controlled clinical trial. 392 eligible participants will be enrolled with 2-week run-in, 8-week treatment and 8-week follow-up. After run-in period, participants will be randomized to receive either the Chinese medicine JCM-16021 or placebo for 8 weeks, and will have post-treatment follow up for another 8 weeks. The primary outcome is the improvement rate on the global assessment of improvement (GAI) at week 10. The secondary outcomes consist of changes of IBS-D symptoms, TCM pattern improvement, IBS-Quality of Life (IBS-QoL), IBS-Symptom Severity Score (IBS-SSS), safety, etc. RESULTS: A standard protocol has been developed for the study. The protocol will provided a detailed procedure to conduct a clinical trial and verify if the Chinese medicine JCM-16021 would significantly improve the overall symptoms of IBS-D with LSSD pattern of TCM by relieving abdominal pain, reducing stool frequency, improving the stool consistency and improving quality of life. The consolidated evidence from the study can shed light on the treatment of IBS-D with Chinese medicine. The protocol will provide details for investigators about the study following SPIRIT Statement. High-quality evidence on the efficacy and safety of Chinese medicine JCM-16021 for IBS-D will be provided through strict compliance with the protocol. ClinicalTrial.gov identifier: NCT03457324. Registered 8 February 2018, https://clinicaltrials.gov/ct2/show/NCT03457324?term=NCT03457324&draw=2&rank=1.


Investigating the key indicators for evaluating post-disaster shelter.
This study sought to identify the primary indicators for evaluating shelter assistance following natural disasters and then to develop a shelter evaluation instrument based on these indicators. Electronic databases and the 'grey' literature were scoured for publications with a relation to post-disaster shelter assistance. Indicators for evaluating such assistance were extracted from these publications. In total, 1,525 indicators were extracted from 181 publications. A preliminary evaluation instrument was designed from these 1,525 indicators. Shelter experts checked the instrument for face and content validity, and it was revised subsequently based on their input. The revised instrument comprises a version for use by shelter agencies (48 questions that assess 23 indicators) and a version for use by beneficiaries (52 questions that assess 22 indicators). The instrument can serve as a standardised tool to enable groups to gauge whether or not the shelter assistance that they supply meets the needs of disaster-affected populations.


Factors influencing medication adherence after epilepsy surgery.
In drug-responsive epilepsy patients, treatment non-compliance is a major factor in seizure recurrence, but adherence to prescribed regimens following epilepsy surgery has not been examined. We measured adherence to prescribed antiepileptic drugs (AEDs) after epilepsy surgery and investigated factors influencing treatment non-compliance. Postsurgical epilepsy patients (n=214) were monitored for 18.1±8.1 months. Adherence was measured using the Medication Possession Ratio (MPR) self-report questionnaire, with MPR<0.8 defined as non-adherence. According to the MPR, 58 patients (27.1%) were non-adherent after surgery. There were no differences in demographic and clinical variables, such as age (p=0.057, t=-1.925), duration of illness (p=0.597, t=0.530), gender ratio (p=0.714, χ2=0.134), and place of residence (urban vs. rural; p=0.874, χ2=0.025), between adherent and non-adherent patients. Moreover, adherence was not related to surgical outcome as evaluated by the Engel classification (p=0.635, χ2=1.628) or to the types of AEDs after surgery (p=0.165, χ2=6.530). The most common reasons for non-adherence were seizure-free status for an extended period (26.5%), forgetfulness (19.1%), and an inability to buy the drugs locally (18.6%). Adherence to AEDs is improved after epilepsy surgery compared to presurgical estimates, but is still a common and serious problem. Targeted postsurgical management programs and communication strategies are necessary to improve adherence to AEDs after epilepsy surgery.


Pleuropericarditis and pericardial tamponade associated with inflammatory bowel disease.
Extraintestinal manifestations have been described with inflammatory bowel disease (IBD). Cardiac involvement in IBD is rare and may present as pericardial effusion, myopericarditis and conduction defects. Here we present a case of IBD with asymptomatic pericardial tamponade. A 37-year-old African-American man with ulcerative colitis with history of previous colectomy with ileorectal anastomosis was hospitalized for resection of the stricture of ileorectal anastomosis. The patient was afebrile with stable vitals and modest jugular venous distension, but no pulsus paradoxus. Cardiopulmonary examination was normal. A CT scan done to evaluate rise in liver function tests following removal of stricture showed a large 3.1 cm pericardial effusion. A transthoracic 2-D echocardiogram showed a moderate-sized posterior pericardial effusion limiting left ventricular filling. Central venous pressure was 18 mm Hg and the patient underwent drainage of 300 ml of old bloody pericardial effusion. Pericardial biopsy showed organizing fibrinohemorrhagic chronically inflamed pericardium without granuloma or neoplastic process. Serologies for EBV, Coxsackie virus and hepatitides were negative. Drug-related pericarditis seems less likely as the patient was not on sulfasalazine, and ANA, dsDNA and rheumatoid factor titers were negative. The patient was diagnosed to have pericardial tamponade associated with IBD.


[Morbidity and mortality from external causes in Brazil, 2000].
Since the early 1980s, external causes have been the second greatest cause of death in Brazil. They also place a growing demand on health care services. The current study analyzes morbidity and mortality from external causes in Brazil. The study material consists of 118,367 deaths and 652,249 hospitalizations due to external causes during the year 2000. The data are from the National Mortality Information System and Hospital Information System. The mortality coefficient from external causes was 69.7/ 100 thousand (119.0/100 thousand for males and 21.8/100 thousand for women). Homicides were the leading cause of death (38.3% of the total), with a high coefficient of 26.7/100 thousand, while falls were the leading cause of hospitalizations (42.8% of the total). Motor vehicle accidents were a major cause of both morbidity and mortality. Fractures, mostly occurring in the upper and lower limbs, accounted for 42.6% of hospitalizations. Based on the findings, preventive programs should aim to decrease both mortality and morbidity, with special emphasis on homicides, traffic accidents, and falls.


Mental health indicators among pregnant Aboriginal women in Canada: results from the Maternity Experiences Survey.
There is little research done on mental health among pregnant Aboriginal women. Therefore, the purpose of the study was to examine the prevalence of postpartum depression (PPD) and its determinants, including pre-existing depression among non-Aboriginal and Aboriginal women in Canada. The Maternity Experiences Survey (MES) is a national survey of Canadian women's experiences and practices before conception, up to the early months of parenthood. Predictors of PPD were calculated using the Mantel-Haenszel correction method relative to the risk estimates based on the odds ratio from adjusted regression analysis. The analysis was conducted among women who self-identified as Aboriginal (Inuit, Métis or First Nations living off-reserve) and those who identified as non-Aboriginal. The prevalence of pre-existing depression was higher among self-reported First Nations off-reserve and Métis women than non-Aboriginal women. Inuit women had the lowest prevalence of self-reported pre-existing depression, and Aboriginal women reported a higher prevalence of PPD than non-Aboriginal women. Pre-existing depression was not a predictor for PPD for Inuit or Métis women in this study but was a positive predictor among First Nations off-reserve and non-Aboriginal women. A disproportionally higher number of Aboriginal women reported experiencing abuse, as compared to non-Aboriginal women. Our study demonstrated that common predictors of PPD including anxiety, experiencing stressful life events during pregnancy, having low levels of social support, and a previous history of depression were consistent among non-Aboriginal women. However, with the exception of the number of stressful events among First Nations offreserve, these were not associated with PPD among Aboriginal women. This information can be used to further increase awareness of mental health indicators among Aboriginal women.


Let's all speak together! Exploring the masking effects of various languages on spoken word identification in multi-linguistic babble.
This study aimed to characterize the linguistic interference that occurs during speech-in-speech comprehension by combining offline and online measures, which included an intelligibility task (at a -5 dB Signal-to-Noise Ratio) and 2 lexical decision tasks (at a -5 dB and 0 dB SNR) that were performed with French spoken target words. In these 3 experiments we always compared the masking effects of speech backgrounds (i.e., 4-talker babble) that were produced in the same language as the target language (i.e., French) or in unknown foreign languages (i.e., Irish and Italian) to the masking effects of corresponding non-speech backgrounds (i.e., speech-derived fluctuating noise). The fluctuating noise contained similar spectro-temporal information as babble but lacked linguistic information. At -5 dB SNR, both tasks revealed significantly divergent results between the unknown languages (i.e., Irish and Italian) with Italian and French hindering French target word identification to a similar extent, whereas Irish led to significantly better performances on these tasks. By comparing the performances obtained with speech and fluctuating noise backgrounds, we were able to evaluate the effect of each language. The intelligibility task showed a significant difference between babble and fluctuating noise for French, Irish and Italian, suggesting acoustic and linguistic effects for each language. However, the lexical decision task, which reduces the effect of post-lexical interference, appeared to be more accurate, as it only revealed a linguistic effect for French. Thus, although French and Italian had equivalent masking effects on French word identification, the nature of their interference was different. This finding suggests that the differences observed between the masking effects of Italian and Irish can be explained at an acoustic level but not at a linguistic level.


Investigation of q-dependent dynamical heterogeneity in a colloidal gel by x-ray photon correlation spectroscopy.
We use time-resolved x-ray photon correlation spectroscopy to investigate the slow dynamics of colloidal gels made of moderately attractive carbon black particles. We show that the slow dynamics is temporally heterogeneous and quantify its fluctuations by measuring the variance chi of the instantaneous intensity correlation function. The amplitude of dynamical fluctuations has a nonmonotonic dependence on scattering vector q, in stark contrast with recent experiments on strongly attractive colloidal gels [Duri and Cipelletti, Europhys. Lett. 76, 972 (2006)]. We propose a simple scaling argument for the q-dependence of fluctuations in glassy systems that rationalizes these findings.


Survival analysis between patients with invasive ductal and invasive lobular breast cancer.
Differences in overall survival (OS) and disease-free survival (DFS) between patients with invasive ductal (IDC) and invasive lobular breast cancer (ILC) are controversial. The study population was selected from a database of 5,689 female patients with invasive breast cancer. In order to focus on the impact of tumour histology, all primary metastatic patients and patients with adjuvant chemotherapy or anti-hormonal treatment were excluded. Only patients with pure invasive lobular and invasive ductal histology were included. Multivariate survival analyses of 2,058 eligible patients confirmed tumour histology as an independent prognostic factor for OS in invasive breast cancer (p = 0.046) but not for DFS (p = 0.599). Kaplan-Meier survival analysis of OS between IDC and ILC patients showed a statistically significantly better OS for patients with ILC (p = 0.0302). DFS was not statistically different (p = 0.6659) between IDC and ILC. Univariate survival analyses of tumour size, tumour grading and nodal status in our study population were highly statistically significant for OS and DFS (p < 0.0000). Patients in our study population with ILC have significantly better OS than patients with IDC. Differences in DFS are not statistically significant.


Skin Tears in Older People.
Skin tears are a common occurrence in older people, though many are unfamiliar with them until late in life. These painful wounds are more likely to occur with age as the skin experiences age-related changes. Numerous factors including declining dermal thickness and loss of elasticity contribute to their development. Risk increases in patients who need assistance with activities of daily living or who need help transferring from bed or chair. Polypharmacy is a risk factor. Prevention is the best approach, but once skin tears develop, treatment needs to be tailored to the tear's grade.


Anxiety sensitivity moderates prognostic importance of rhythm-control versus rate-control strategies in patients with atrial fibrillation and congestive heart failure: insights from the Atrial Fibrillation and Congestive Heart Failure Trial.
Patients with high anxiety sensitivity (AS) become extremely anxious with heart rate increases, palpitations, and symptoms of psychological arousal. AS predicts panic attacks. In atrial fibrillation (AF), AS correlates with symptom preoccupation and reduced quality of life. We assessed whether AS is associated with outcomes of rhythm-control versus rate-control in congestive heart failure (CHF) patients with AF. Before random assignment, 933 participants (172 women) in the Atrial Fibrillation and Congestive Heart Failure Trial completed the Anxiety Sensitivity Inventory (ASI). Cox proportional hazards models showed no main effects of treatment (P=0.61) or AS (P=0.72) for time to cardiovascular death, but these factors interacted significantly (P=0.020). High AS patients (upper quartile, ASI ≥33) randomly assigned to rhythm-control had significantly lower cardiovascular mortality than those receiving rate-control (hazard ratio, 0.54; 95% confidence interval, 0.32-0.93; P=0.022). With lower ASI scores (<33), treatments did not differ (hazard ratio, 1.12; 95% confidence interval, 0.83-1.51; P=0.46). The interaction between treatment and dichotomized ASI scores remained significant (P=0.009) after adjustment for covariates including age, sex, hypertension, diabetes, creatinine, ejection fraction, time since first diagnosis of AF, New York Heart Association functional class, depression symptoms, marital status, and baseline β-blockers, angiotensin-converting enzyme inhibitors, oral anticoagulants, and implantable cardioverter-defibrillators. Atrial fibrillation and congestive heart failure patients with high AS had better long-term prognosis with rhythm- than rate-control. If replicated, AS should be considered in treatment selection. Research is also needed concerning mechanisms and possible joint AS-AF treatments. URL: http://www.clinicaltrials.gov. Unique identifier: NCT88597077.


In-vitro cultivation of exoerythrocytic stages of Plasmodium cynomolgi in hepatocytes of Macaca radiata.
Hepatocytes from bonet monkey (Macaca radiata) obtained by perfusion of a liver biopsy were infected in-vitro with Plasmodium cynomolgi bastianellii sporozoites raised in Anopheles stephensi. The development of exoerythrocytic (EE) stages was seen under phase contrast microscope and by Giemsa staining. Multinucleated EE-stages were seen in the cultured hepatocytes on day 7-8 post-sporozoite inoculation.


Molecular structure of the coalescence of liquid interfaces.
When two bodies of liquid merge, their interfaces must also rupture and rearrange into one. Virtually no information is available concerning the small-scale dynamics of this process. Molecular dynamics simulations of coalescence in systems of about 10,000 Lennard-Jones particles have been performed, arranged so as to mimic laboratory experiments on dense liquids. The coalescence event begins when molecules near the boundary of one liquid body thermally fluctuate into the range of attraction of the other, forming a string of mutually attracting molecules. These molecules gradually thicken into a tendril, which continues to thicken as the bodies smoothly combine in a zipper-like merger.


Acute ischemic stroke patterns in infective and nonbacterial thrombotic endocarditis: a diffusion-weighted magnetic resonance imaging study.
Although infective endocarditis (IE) and nonbacterial thrombotic endocarditis (NBTE) are associated with cardioembolic stroke, differences in the nature of these conditions may result in differences in associated stroke patterns. We compared patterns of acute and recurrent ischemic stroke in IE and NBTE, using diffusion-weighted MRI (DWI). Using ICD-9 diagnostic codes and medical record review, we identified 362 patients (387 episodes) with IE and 14 patients with NBTE. Thirty-five patients (with 27 episodes of IE, 9 NBTE) who underwent 36 initial and 29 follow-up DWI scans were selected for this study. DWI lesion size, number, and location were compared between groups and correlated with stroke syndromes and endocarditis features. DWI was abnormal in all but 2 patients. Four acute stroke patterns were identified: (1) single lesion, (2) territorial infarction, (3) disseminated punctate lesions, and (4) numerous small (<10 mm) and medium (10 to 30 mm) or large (>30 mm) lesions in multiple territories. All patients with NBTE exhibited pattern 4, whereas those with IE exhibited patterns 1, 2, 3, and 4 (6, 2, 8 and 9 episodes, respectively). Seventy-five percent of patients with pattern 3 exhibited the clinical syndrome of embolic encephalopathy. Vegetation size, valve, and organisms had no correlation with stroke patterns. DWI has utility in differentiating between IE and NBTE. Patients with NBTE uniformly have multiple, widely distributed, small and large strokes, whereas patients with IE exhibit a panoply of stroke patterns.


Information content in the circular dichroism of proteins.
A method is presented for predicting the secondary structure of a protein from its circular dichroism (CD) spectrum. Eight types of secondary structures are considered: helix; parallel and antiparallel beta strand; types I, II, and III beta turn; all other beta turns combined; and "other" structures. The method is based on mathematical calculation of orthogonal basis CD spectra from the CD spectra of proteins with known secondary structure. Five basis CD spectra are needed to reconstruct the 16 original protein CD spectra that extend into the vacuum ultraviolet region to 178 nm. Thus, one can expect to extract five independent pieces of information from the CD spectrum of a protein. Each basis CD spectrum corresponds to a known mixture of secondary structures so that the coefficients that reconstruct the protein CD spectrum can also be used to predict secondary structure. Furthermore, when the same method is applied to protein secondary structure rather than CD, it is found that only five basis secondary structure vectors are needed to reconstruct the original protein secondary structure vectors. Thus there are five independent "superstructures", consisting of a mixture of standard secondary structures, in the proteins studied. It would appear that there is enough information in the CD spectrum of a protein to predict all types of secondary structure. Our CD analyses compare favorably with the X-ray data.


Limitations on the uses of multimedia exposure measurements for multipathway exposure assessment--Part I: Handling observations below detection limits.
Multimedia data from two probability-based exposure studies were investigated in terms of how censoring of nondetects affected estimation of population parameters and associations. Appropriate methods for handling censored below-detection-limit(BDL)values in this context were unclear since sampling weights were involved and since bivariate associations/measures were of interest. Both simple substitution(e.g., using 1/2 or 2/3 of the detection limit(DL)for BDL values)and truncation-based strategies were investigated by creating some artificial DLs and comparing resultant estimates with the original studies'uncensored results. The substitution methods generally outperformed the truncation methods, with the(2/3)DL substitution generally performing best.


A practice research study concerning homeless service user involvement with a programme of social support work delivered in a specialized psychological trauma service.
Homeless persons are known to be highly vulnerable to psychological trauma, in events triggering periods of homelessness and the considerable social isolation and adversity suffered when homeless. This study provides an account of how mental health support work is experienced by homeless service users when it is informed by a person-centred, non-directive approach and implemented by trainee health and social care professionals under the auspices of a specialized psychological trauma service. The study draws upon material gathered from interviews with service users domiciled in supported housing for homeless persons and support workers who practiced on the programme. The service users who participated in the study valued support work that combined practical and relational elements, but would have preferred a longer-term involvement. They also spoke of feelings of disconnection and estrangement from others including their peers in supported housing. The support worker participants valued the flexibility they had when working on the programme to tailor their intervention to service users' individual needs. Practice implications of the study are discussed. These include the need to minimize barriers to accessing support, facilitate informal time between professionals and homeless service users, and manage intervention endings sensitively when temporary staffing arrangements are in place. Homeless people are a population known to be highly vulnerable to trauma, in triggering events to becoming homeless and the considerable social isolation, discrimination, and adversity suffered when homeless. Currently, there is a paucity of research into mental health service delivery to homeless persons and the influence it imparts in individual lives. This article presents a qualitative 'practice research' study into a pilot programme of social support work delivered in a specialized psychological trauma service to homeless service users. The programme was grounded in a non-directive, person-centred approach and staffed by student social workers. The study aim was to explore the support work programme as it was received by service users domiciled in supported housing for homeless persons, encompassing experiencing the programme, worker-service user engagement and contextual influences bearing upon positive outcomes. Narrative interviews gathered the impressions of service users and support workers and the data arising from these interviews was analysed thematically. Service user participants valued support work that combined practical and relational elements, but would have preferred a longer-term involvement. They also spoke of feelings of disconnection and estrangement from their peers in the supported accommodation and their families. The worker participants valued the flexibility of person-centred work tailored to service users' individual needs and echoed service user concerns around the short-term nature of their involvement. Psychiatric nurses carrying out, or supervising, mental health support work with homeless service users should be mindful of the potential impact of temporary staffing arrangements on continuity of care. They should also consider how working from a person-centred perspective and addressing client's practical needs may aid in developing rapport and trust with homeless service users.


Social-specific impairment of negative emotion perception in alexithymia.
Alexithymia has been characterized as an impaired ability of emotion processing and regulation. The definition of alexithymia does not include a social component. However, there is some evidence that social cognition may be compromised in individuals with alexithymia. Hence, emotional impairments associated with alexithymia may extend to socially relevant information. Here, we recorded electrophysiological responses of individuals meeting the clinically relevant cutoff for alexithymia (ALEX; n = 24) and individuals without alexithymia (NonALEX; n = 23) while they viewed affective scenes that varied on the dimensions of sociality and emotional valence during a rapid serial visual presentation task. We found that ALEX exhibited lower accuracy and larger N2 than NonALEX in the perception of social negative scenes. Source reconstruction revealed that the group difference in N2 was localized at the dorsal anterior cingulate cortex. Irrespective of emotional valence, ALEX showed stronger alpha power than NonALEX in social but not non-social conditions. Our findings support the hypothesis of social processing being selectively affected by alexithymia, especially for stimuli with negative valence. Electrophysiological evidence suggests altered deployment of attentional resources in the perception of social-specific emotional information in alexithymia. This work sheds light on the neuropsychopathology of alexithymia and alexithymia-related disorders.


The Protonics Knee Brace Unloads the Quadriceps Muscles in Healthy Subjects.
OBJECTIVE: The Protonics brace is a functional resistance brace designed for rehabilitative use in patients with patellofemoral pain syndrome. Our objective was to determine whether the Protonics brace altered quadriceps muscle activity or knee mechanics in healthy subjects. DESIGN AND SETTING: We used a within-subjects design in a laboratory setting. SUBJECTS: Nineteen recreationally active college students (10 females, 9 males; age = 22.6 +/- 2.8 years; height = 172 +/- 9.0 cm, mass = 69.7 +/- 12.5 kg) with no history of patellofemoral pain syndrome. MEASUREMENTS: A standard-length Protonics brace was fit to each subject's leg. Surface electromyography of the vastus medialis obliquus, vastus lateralis, and rectus femoris muscles was recorded during a lateral step-down exercise. Lower extremity kinematics and ground reaction force were assessed during stair descent. Subjects performed both tasks under 4 conditions: no brace and brace with low, medium, and high resistance. Electromyography values were normalized to a maximum voluntary isometric contraction. The brace moment was determined by passive testing in an isokinetic dynamometer. Changes in the subject's muscular knee-extension moment were determined by subtracting the extension moment provided by the brace from the total knee-extension moment calculated from motion and force data using an inverse dynamics approach. RESULTS: Vastus medialis obliquus activity in the brace at the low- and medium-resistance settings was significantly lower than that measured without the brace. Vastus lateralis activity while wearing the brace at medium resistance was significantly less than in the absence of the brace. Regardless of brace setting, vastus medialis obliquus and vastus lateralis activity in the descending phase of the exercise was less than during the ascending phase. A significant interaction was noted between brace setting and phase of the step-down exercise for rectus femoris activity. Significantly less activity was seen in the descending phase than in the ascending phase. Post hoc testing indicated that, in the descending phase, less activity was demonstrated with the brace at the medium and high settings than at the low setting. Muscle activity at the high setting and activity at low resistance were also significantly less than when the brace was not worn in the ascending phase. Knee flexion and extension moment during stair descent were significantly less at the higher resistance settings. CONCLUSIONS: Wearing the Protonics brace at moderate or high resistance during the lateral step-down exercise produced less quadriceps activity compared with not wearing the brace. The knee extensor mechanism was unloaded when the brace was worn during stair descent. These findings indicate that the Protonics brace may unload the quadriceps and therefore decrease the load on the patellofemoral joint.


In utero exposure to toxic air pollutants and risk of childhood autism.
Genetic and environmental factors are believed to contribute to the development of autism, but relatively few studies have considered potential environmental risks. Here, we examine risks for autism in children related to in utero exposure to monitored ambient air toxics from urban emissions. Among the cohort of children born in Los Angeles County, California, 1995-2006, those whose mothers resided during pregnancy in a 5-km buffer around air toxics monitoring stations were included (n = 148,722). To identify autism cases in this cohort, birth records were linked to records of children diagnosed with primary autistic disorder at the California Department of Developmental Services between 1998 and 2009 (n = 768). We calculated monthly average exposures during pregnancy for 24 air toxics selected based on suspected or known neurotoxicity or neurodevelopmental toxicity. Factor analysis helped us identify the correlational structure among air toxics, and we estimated odds ratios (ORs) for autism from logistic regression analyses. Autism risks were increased per interquartile range increase in average concentrations during pregnancy of several correlated toxics mostly loading on 1 factor, including 1,3-butadiene (OR = 1.59 [95% confidence interval = 1.18-2.15]), meta/para-xylene (1.51 [1.26-1.82]), other aromatic solvents, lead (1.49 [1.23-1.81]), perchloroethylene (1.40 [1.09-1.80]), and formaldehyde (1.34 [1.17-1.52]), adjusting for maternal age, race/ethnicity, nativity, education, insurance type, parity, child sex, and birth year. Risks for autism in children may increase following in utero exposure to ambient air toxics from urban traffic and industry emissions, as measured by community-based air-monitoring stations.


Impact assessment of dredging to remove coal fly ash at the Tennessee Valley Authority Kingston Fossil plant using fathead minnow elutriate exposures.
On December 22, 2008, failure of an earthen containment structure resulted in the release of approximately 4.1 million m(3) of coal fly ash into the Emory River and the surrounding area from the Tennessee Valley Authority Kingston Fossil Plant near Kingston, Tennessee, USA. The purpose of the present study was to assess the potential of dredging activities performed to remove the fly ash from the river to result in increased risk to pelagic fish, with special consideration of mobilization of metals. Elutriates were created using two sources of fly ash by bubbling with air over 10 d. This elutriate preparation method was designed to represent worst-case conditions for oxidation, metal release, and dissolution. Larval and juvenile Pimephales promelas underwent 10-d exposures to these elutriates. Larval end points included survival and biomass, and juvenile end points included survival, length, biomass, liver somatic index, and bioaccumulation. No significant toxicity was observed. Bioaccumulation of metals in juveniles was found to be primarily attributable to metals associated with particles in the gut. Results suggest little potential for toxicity to related fish species due to fly ash removal dredging activities given the extreme conditions represented by the elutriates in the present study.


Focal adhesions are essential to drive zebrafish heart valve morphogenesis.
Elucidating the morphogenetic events that shape vertebrate heart valves, complex structures that prevent retrograde blood flow, is critical to understanding valvular development and aberrations. Here, we used the zebrafish atrioventricular (AV) valve to investigate these events in real time and at single-cell resolution. We report the initial events of collective migration of AV endocardial cells (ECs) into the extracellular matrix (ECM), and their subsequent rearrangements to form the leaflets. We functionally characterize integrin-based focal adhesions (FAs), critical mediators of cell-ECM interactions, during valve morphogenesis. Using transgenes to block FA signaling specifically in AV ECs as well as loss-of-function approaches, we show that FA signaling mediated by Integrin α5β1 and Talin1 promotes AV EC migration and overall shaping of the valve leaflets. Altogether, our investigation reveals the critical processes driving cardiac valve morphogenesis in vivo and establishes the zebrafish AV valve as a vertebrate model to study FA-regulated tissue morphogenesis.


Responsiveness of the anxiety/depression dimension of the 3- and 5-level versions of the EQ-5D in assessing mental health.
Anxiety and depression disorders are associated with significantly lower health-related quality of life (HRQL). The EQ-5D is a commonly used generic measure of HRQL; it captures mental health through a single domain-the anxiety/depression dimension. Evidence on the responsiveness of this measure in assessing changes in mental health changes is limited. To examine the performance of the anxiety/depression dimension (A/D) of the 3- and 5-level (3L and 5L) versions of the EQ-5D in assessing changes in mental health. Data from two patient populations were used: 495 adults post-discharge from general internal medicine ward (EQ-5D-3L), and 225 type 2 diabetes patients who screened positive for depressive symptoms (EQ-5D-5L). Anchor-based approach along with effect sizes (ES) and ROC analysis was used. Anchors included patient health questionnaire 9-items "PHQ9" and generalized anxiety disorder 2-item questionnaire "GAD2" for EQ-5D-3L, and PHQ9 and SF-12 mental composite summary scores (MCS) for EQ-5D-5L. A/D change was quantified as the difference between follow-up and baseline levels. The A/D dimension of the EQ-5D-3L showed limited responsiveness to changes in depressive symptoms measured by PHQ9 and for anxiety symptoms measured by GAD2, whereby in those who improved or deteriorated in either symptom, more than half of the patients did not have an A/D change. In the ROC analysis, the A/D dimension of the EQ-5D-3L showed weak performance with C-indices ranging from 0.58 to 0.63 and probability of detection of depressive or anxiety symptoms ranging between 20 and 40%, which are all well below acceptable ranges. Similar results were observed for the A/D dimension of the EQ-5D-5L; although the performance was slightly better, it was still below acceptable range. In patients who improved or deteriorated based on the PHQ9 or MCS, around a third had no changes on the A/D dimension. The performance of the A/D dimension of the EQ-5D-5L was also very limited with C-indices ranging between 0.67 and 0.76, and probability of detection between 50 and 67%, slightly better than that of the 3L, yet unsatisfactory. Although the A/D of both EQ-5D-3L and 5L was limited in capturing changes in mental health in these populations, the 5L was slightly more responsive than the 3L. While the performance was better for depressive than anxiety symptoms, it varied by the direction of change. Further research using other measures of mental health in other populations is warranted.


Overexpression screens identify conserved dosage chromosome instability genes in yeast and human cancer.
Somatic copy number amplification and gene overexpression are common features of many cancers. To determine the role of gene overexpression on chromosome instability (CIN), we performed genome-wide screens in the budding yeast for yeast genes that cause CIN when overexpressed, a phenotype we refer to as dosage CIN (dCIN), and identified 245 dCIN genes. This catalog of genes reveals human orthologs known to be recurrently overexpressed and/or amplified in tumors. We show that two genes, TDP1, a tyrosyl-DNA-phosphdiesterase, and TAF12, an RNA polymerase II TATA-box binding factor, cause CIN when overexpressed in human cells. Rhabdomyosarcoma lines with elevated human Tdp1 levels also exhibit CIN that can be partially rescued by siRNA-mediated knockdown of TDP1 Overexpression of dCIN genes represents a genetic vulnerability that could be leveraged for selective killing of cancer cells through targeting of an unlinked synthetic dosage lethal (SDL) partner. Using SDL screens in yeast, we identified a set of genes that when deleted specifically kill cells with high levels of Tdp1. One gene was the histone deacetylase RPD3, for which there are known inhibitors. Both HT1080 cells overexpressing hTDP1 and rhabdomyosarcoma cells with elevated levels of hTdp1 were more sensitive to histone deacetylase inhibitors valproic acid (VPA) and trichostatin A (TSA), recapitulating the SDL interaction in human cells and suggesting VPA and TSA as potential therapeutic agents for tumors with elevated levels of hTdp1. The catalog of dCIN genes presented here provides a candidate list to identify genes that cause CIN when overexpressed in cancer, which can then be leveraged through SDL to selectively target tumors.


Investigation of the population structure of the tick vector of Lyme disease Ixodes scapularis (Acari: Ixodidae) in Canada using mitochondrial cytochrome C oxidase subunit I gene sequences.
Genotyping of Ixodes scapularis Say (Acari: Ixodidae) ticks could enhance understanding of the occurrence and genotypes of I. scapularis-borne pathogens. We investigated the utility of mitochondrial (mt) Cytochrome C Oxidase subunit I gene (cox1) sequences as a tool for understanding the population structure of I. scapularis collected in Canada, where we also investigated the geographic occurrence of different cox1 haplotypes. Sequences obtained from 414 ticks were one of 55 unique haplotypes, most of which grouped into one of six clades. Demographic analysis suggested that cox1 sequences have haplotype and nucleotide diversity comparable to other mt genes. All haplotypes were connected in a single minimum spanning network tree. Despite low fixation index values there were significant differences in the frequency of occurrence of haplotypes of different clades among four geographic regions: 1) Alberta to western Ontario, 2) eastern Ontario, 3) Quebec, and 4) Atlantic Provinces; suggesting that cox1 sequences could reveal population structure differences between I. scapularis in geographically separated populations of northeastern and midwestern North America. Spatial clusters of ticks of the same haplotype identified in regions of southern Quebec and southern Ontario where I. scapularis is invading were consistent with population bottlenecks associated with founder events. These findings suggest that cox1 sequences are useful for the study of I. scapularis population structure, are of sufficient diversity that spatial analyses of haplotypes can be used to identify where I. scapularis is emerging in southern Canada, and may be useful for exploring differences between northeastern and midwestern populations of I. scapularis.


[Retinoblastoma as a diagnostic problem in a 16-years-old boy (author's transl)].
A secondary glaucoma due to an intraocular tumour with retinal detachment in a 16-years-old patient whose brother had died of suspected leucaemia illustrates the difficulties in the clinical diagnosis at this age. Although the ophthalmoscopical appearance was that of Coats's lesion a malignant melanoma of the choroid could not be ruled out. The histopathological examination revealed a retinoblastoma.


In vitro bioassays for detecting dioxin-like activity--application potentials and limits of detection, a review.
Use of in vitro assays as screening tool to characterize contamination of a variety of environmental matrices has become an increasingly popular and powerful toolbox in the field of environmental toxicology. While bioassays cannot entirely substitute analytical methods such as gas chromatography-mass spectrometry (GC-MS), the increasing improvement of cell lines and standardization of bioassay procedures enhance their utility as bioanalytical pre-screening tests prior to more targeted chemical analytical investigations. Dioxin-receptor-based assays provide a holistic characterization of exposure to dioxin-like compounds (DLCs) by integrating their overall toxic potential, including potentials of unknown DLCs not detectable via e.g. GC-MS. Hence, they provide important additional information with respect to environmental risk assessment of DLCs. This review summarizes different in vitro bioassay applications for detection of DLCs and considers the comparability of bioassay and chemical analytically derived toxicity equivalents (TEQs) of different approaches and various matrices. These range from complex samples such as sediments through single reference to compound mixtures. A summary of bioassay derived detection limits (LODs) showed a number of current bioassays to be equally sensitive as chemical methodologies, but moreover revealed that most of the bioanalytical studies conducted to date did not report their LODs, which represents a limitation with regard to low potency samples.


[The study on sentinel lymphatic channels by using methylene blue in breast cancer patients].
To explore why sentinel lymph node biopsies (SLNB) produce false negative results in breast cancer patients by studying the anatomical origin of sentinel lymphatic channels (SLCs), as well as the relationship between SLCs and sentinel lymph node (SLN). Sixty-two breast cancer patients consenting to modified radical mastectomies were marked by exit angle (theta(e)) preoperatively and were injected with 3 ml of methylene blue (MB) into the inner edge of the areolae under general anesthesia. SLCs were carefully dissected to retain connections between the areolae and SLN to define the direction, route and number of SLCs and their relationship with the SLN. SLCs and SLN were identified in 52 cases (83.87%) successfully. In 49 of these 52 cases (94.23%) the SLCs exited from the areolae and terminated in axilla with an theta(e) = 31 degrees - 90 degrees , and in 36 of 52 cases (69.23%) with an theta(e) = 61 degrees - 90 degrees . The majority of the time, one SLN was identified (92.31%, n = 48) with two identified SLNs occurring only 7.69% (n = 4) of the time. There were three patterns of connectivity: 1) Two SLCs could connect to one SLN separately; 2) One SLC could divide into several branches before or after entering axilla, which ultimately connected to one SLN; or 3) One SLC could divide into two branches before entering axilla, which connected to one SLN separately and these two SLNs could be located in different parts of axilla. No false negative or false positive was demonstrated by pathological analysis of SLN which was identified according to SLCs. No evidence showed that the mechanism of axillary lymph node metastasis is skip metastasis. We conclude that false negative results from SLNB seems to be associated with the technique used, which may be caused by the incomplete knowledge of the anatomical relationship between SLCs and SLN.


Risk factors for relaparotomy after cesarean delivery and related maternal near-miss event due to bleeding.
Aim: To define the risk factors for relaparotomy after cesarean delivery (RLACD) and related maternal near-miss event due to bleeding.Methods: In this retrospective descriptive case-control study, women who underwent RLACD (n = 46) only for bleeding between 2012 and 2017 were reviewed. Factors that could predict relaparotomy and related near-miss event were evaluated. Maternal characteristics, laboratory findings and surgical features were compared with a control group (n = 230) that included noncomplicated cesarean deliveries (CD). Logistic regression analysis was used to identify independent factors for relaparotomy.Results: RLACD for bleeding was required in 0.26% of patients and the incidence increased gradually over years (0.16% in 2013 versus 0.44% in 2017). Mean interval between CD and subsequent relaparotomy was 15.7 ± 3.2 hours. The sources of bleeding in descending order of frequency included; uterine fundus and placental bed (39.1%), cervix (21.7%), undetermined (17.3%), superior epigastric artery (13%), superficial epigastric artery (8.1%). Longer duration of CD (adjusted odd ratio (aOR) 1.82, 95% CI 1.02-2.53), increased number of prior CDs (aOR 2.51, 95% CI 1.09-5.78), preeclampsia (aOR 3.48, 95% CI 1.21-7.19) were found to be independent risk indicators for RLACD. Moreover, longer duration of interval between CD and relaparotomy (p = .005), longer relaparotomy duration (p = .012) and greater drop in hemoglobin level (p = .001) were found to be the predictors of maternal near-miss event.Conclusions: Patients with identified risk factors should be managed properly in order to prevent relaparotomy and near-miss event after CD. Also, urgent decision of surgical intervention might reduce the risk of maternal near-miss event.


Internal carotid artery thrombosis associated with a fracture.
A case of occlusion of the internal carotid artery after craniocervical trauma with subsequent death of the patient is presented. The patient originally had a mandibular fracture; subsequently an altered sensorium and left-sided hemiparesis developed. The patient died. The typical "lucid interval" was noted. The changes in sensorium are similar to those associated with epidural and subdural hematomas.


Assessment of meibomian glands using a custom-made meibographer in dry eye patients in Ghana.
Meibomian Gland Dysfunction (MGD) is a leading cause of evaporative Dry Eye Disease (DED). This makes non-invasive meibography an important procedure in the clinical evaluation of DED patients. Our purpose was to conduct a lead-off investigation focused on the practicality of performing meibography in a developing country, with limited access to complex ophthalmic imaging systems, using a custom meibographer, as a step to future comparative studies on meibomian glands and DED in Africa. Meibomian glands(MG) in 76 upper eyelids (UL) and 49 lower eyelids (LL) in 1 eye each of 125 patients randomly selected from a patient population presenting with subjective DED symptoms at a clinic were photographed using a custom meibographer. Single frames were captured, and the MG area determined by intensity threshold segmentation and area calculation using Image J software. MG loss (MGL) was quantified by outlining its area and expressing it as a percentage of the total MG per Pult's grading scheme. Dry eye measures included Tear Film Break Up - Time (TUBT), Schirmer's test and Ocular Surface Staining (OSS). Symptoms were evaluated using the SPEED II questionnaire. Correlations between MGL and age, ocular signs and symptoms were analyzed by Pearson's. Differences between comparable groups were analyzed by Mann - Whitney test; p < 0.05 was considered significant. Overall mean MGL was 32.10% ± 25.0% (26.25% ± 22.40% for UL and 40.33% ± 26.70% for LL). MGL correlated significantly with age [r = 0.91, p = 0.001], SPEED scores [r = 0.90, p = 0.001], OSS [r = 0.75, p = 0.001] and TBUT [r = - 0.81, p = 0.001]. MGL scores were significantly higher in the UL than LL [U = 1293.5 p = 0.004]. This study for the first time presents data on the status of Meibomian glands in Africa. It furthermore suggests that it is feasible to examine Meibomian glands using a custom meibographer in developing countries with limited access to complex imaging systems. It also demonstrates the benefit and cost-effectiveness of a simple device by the observed significant relations between meibomian gland loss and DED in these patients.


Community Attitudes Towards Violence Against Women, and Lived Experiences of Family Violence and Abuse During Childhood in Rural Eastern Nigeria: Implications for Policy and Programming.
Violence against women (VAW) has remained an increasingly significant public health problem globally. This study explored childhood experiences of abuse and attitude towards violence against women among adults in a rural community in South-east Nigeria. This was a cross-sectional study conducted in a rural community in Ebonyi, Nigeria. Data were collected from 280 respondents using interviewer-administered questionnaires. Data analysis was performed using SPSS version 25. The mean age of the male participants was 46.5±16.8, while that for the female participants was 43.3±16.9. Most were females (203/280, 72.5%), out of which (83/203, 40.9%) had secondary school as the highest level of education attained. Most participants were females (203/280, 72.5%), married (225/280, 80.4%) with secondary school education (124/280, 44.3%). More than one-tenth (33/280, 11.8%) had ever witnessed parental violence, while 46.4% had been physically abused in childhood. Forced touching and penetrative sex was experienced sometimes by 11.4% (32/280) and 21.8% (61/289), respectively. Overall, the majority (258/280, 92.8%) had a disapproving attitude towards gender-based violence. Most participants disagreed that hitting or insulting woman was not wrong (246/280, 87.9%). The majority of the respondents agreed that women were inferior to men from a cultural perspective (175/280, 62.5%). Almost half strongly agreed (125/2280, 44.6%) and agreed (118/280, 42.1%) that a woman is a man's possession. The predictors of attitude were secondary school education (AOR = 7.74, 95% CI = 1.69-35.54) and monogamous marital setting (AOR = 2.83, 95% CI = 1.08-7.42). This study showed that Nigerian adults had high levels of childhood exposures to family violence, physical and sexual abuse. Overall, the majority disapproved of VAW; however, there were gaps that endorsed patriarchal ideologies. Interventions to address VAW should include components targeted at children exposed to violence and de-bunking patriarchal ideologies that encourage VAW.


Reproducibility of the Veterans Physical Activity Questionnaire in an elderly population.
Quantifying lifetime physical activity using self-reported measures is challenging due to reliance on recall, especially in older populations. The purpose of this study was to determine the 1-year reproducibility of the Veterans Physical Activity Questionnaire (VAPAQ) in a cohort of patients with documented abdominal aortic aneurysm disease (AAA). Subjects included men (n = 52) and women (n = 3) enrolled in AAA STOP, a randomized trial designed to test the ability of supervised exercise training to modify AAA biology and early disease progression. The overall correlation coefficient for lifetime recreational energy expenditure between the 2 examinations was 0.93 (P < .001), with an overall difference of 26 kcal/week, a typical error (standard deviation of the differences) of 171 kcals/week, and a coefficient of variation (CV) of 15.5%. The VAPAQ is a reproducible tool to quantify lifetime energy expenditure in older adults with documented vascular disease.


Mask crisis during the COVID-19 outbreak.
On December 31, 2019, the World Health Organization (WHO) reported a cluster of cases of pneumonia of unknown cause detected in Wuhan City, Hubei Province, China. As of February 29, 2020, the National Health Commission of China has reported 79,389 confirmed cases of SARS-CoV-2 infection in 34 provinces. The masks can be used to block respiratory transmission from human to human, and are an effective way to control influenza. It is, therefore, necessary to wear a mask when respiratory infectious diseases are prevalent. China has a population of 1.4 billion. Assuming that two-thirds of the people in China must wear a mask every day, the daily demand for masks will reach 900 million. The Chinese government has taken many measures to solve these problems. Additionally, more measures should be taken to properly dispose of mask garbage. Although the outbreak originated in China, person-to-person transmission of SARS-CoV-2 has been confirmed, which means that it can be spread to anywhere in the world if prevention measures fail. The issues regarding face mask shortages and garbage in China, therefore, deserve worldwide attention.


Calprotectin expression by gingival epithelial cells.
Calprotectin, a heterodimer of MRP8 and MRP14 with antimicrobial properties, is found in the cytosol of neutrophils, monocytes, and human gingival keratinocytes. During inflammation of the oral mucosa, the expression of immunoreactive calprotectin appears upregulated. Given the possible cell sources, we sought to learn if epithelial cells upregulate calprotectin in response to proinflammmatory agents. First, human gingival keratinocytes were maintained in primary culture until senescence. At each passage, cells were harvested and analyzed for quantitative expression of MRP8 and MRP14 subunit mRNA by RNase protection assays and calprotectin complex by enzyme-linked immunosorbent assay. Calprotectin expression was constitutive in the primary gingival keratinocytes, but calprotectin-specific mRNA and protein tended to increase as the cells neared senescence. To test whether calprotectin expression was inducible, immortalized gingival keratinocyte cultures were treated for 2 to 4 h with lipopolysaccharide (LPS) or interleukin-1 beta (IL-1 beta). As a positive control for inducible expression, immortalized keratinocytes were incubated with phorbol myristate acetate (PMA) (50 ng/ml) for 24 h. Incubation with PMA stimulated increased expression of MRP8 and MRP14 mRNA within 2 h, peaking within 5 h. MRP8- and MRP14-specific mRNA expression by immortalized keratinocytes appeared to be unaffected by LPS or IL-1 beta. In contrast, LPS, IL-1 beta, and PMA each upregulated IL-8. These data show that calprotectin mRNA is expressed constitutively in cultured keratinocytes, while expression by immortalized cells appears to be independent of the exogenous proinflammatory agents LPS and IL-1 beta.


Interference screw fixation strength of a quadrupled hamstring tendon graft is directly related to bone mineral density and insertion torque.
The purpose of this study was to determine whether bone mineral density of the host bone, measured using conventional dual photon absorptiometry techniques, and insertion torque can predict part of the ultimate failure strength of interference screw fixation of quadrupled hamstring tendon grafts. The semitendinosus and gracilis tendons were harvested from 10 human cadaveric knees, mean age 66.5 years (range, 53 to 81). The bone tunnel was sized within 0.5 mm of the graft. The graft was fixed with a biodegradable screw (7 x 25 mm for the femur, and 9 x 25 mm for the tibia) directly against the tendon and at the joint surfaces. Tibial fixation and femoral fixation were tested to failure using a materials testing system. Bone mineral density was measured in the metaphyseal region of the tibia and femur. The results of multiple regression analyses showed that both insertion torque and bone mineral density were related to the maximum load the graft withstood. These two variables explained 77.1% of the maximum load observed. We concluded that bone mineral density measurements of the host bone site are an important determinant of postoperative graft strength and thus have an important, but previously unrecognized, clinical role in establishing individual postsurgery rehabilitation protocols. Insertion torque in this study was a useful predictor of graft fixation strength.


Folic acid supplementation increases survival and modulates high risk HPV-induced phenotypes in oral squamous cell carcinoma cells and correlates with p53 mRNA transcriptional down-regulation.
Although the primary risk factors for developing oral cancers are well understood, less is known about the relationship among the secondary factors that may modulate the progression of oral cancers, such as high-risk human papillomavirus (HPV) infection and folic acid (FA) supplementation. This study examined high-risk HPV and FA supplementation effects, both singly and in combination, to modulate the proliferative phenotypes of the oral cancer cell lines CAL27, SCC25 and SCC15. Using a comprehensive series of integrated in vitro assays, distinct effects of HPV infection and FA supplementation were observed. Both high-risk HPV strains 16 and 18 induced robust growth-stimulating effects in CAL27 and normal HGF-1 cells, although strain-specific responses were observed in SCC25 and SCC15 cells. Differential effects were also observed with FA administration, which significantly altered the growth rate of the oral cancer cell lines CAL27, SCC15, and SCC25, but not HGF-1 cells. Unlike HPV, FA administration induced broad, general increases in cell viability among all cell lines that were associated with p53 mRNA transcriptional down-regulation. None of these cell lines were found to harbor the common C677T mutation in methylenetetrahydrofolate reductase (MTHFR), which can reduce FA availability and may increase oral cancer risk. Increased FA utilization and DNA hypermethylation are common features of oral cancers, and in these cell lines, specifically. The results of this study provide further evidence that FA antimetabolites, such as Fluorouracil (f5U or 5-FU) and Raltitrexed, may be alternative therapies for tumors resistant to other therapies. Moreover, since the incidence of oral HPV infection has been increasing, and can influence oral cancer growth, the relationship between FA bioavailability and concomitant HPV infection must be elucidated. This study is among the first pre-clinical studies to evaluate FA- and HPV-induced effects in oral cancers, both separately and in combination, which provides additional rationale for clinical screening of HPV infection prior to treatment.


[Geriatric dentistry in dental education].
Geriatric patients have both special medical problems (problems with aging and general health problems) and specific dental problems. This requires special skills of dentists who are treating these patients. The medical problems require a dentist with a wide medical education and a friendly attitude towards his patients. The dental problems require a dentist who is more problem orientated on his way of treatment. Both aspects are present in the theoretical teaching in most of the dental schools. For treatment of institutionalized geriatric patients it is advocated to train specialists in geriatric dentistry taking into account the need for a multidisciplinary and specific approach.


Genetic Findings of Potential Donor Origin following Hematopoietic Cell Transplantation: Recommendations on Donor Disclosure and Genetic Testing from the World Marrow Donor Association (WMDA): WMDA Guidelines on Genetic Findings of Donor Origin.
Following hematopoietic cell transplantation, recipients are subjected to extensive genetic testing to monitor the efficacy of the transplant and identify relapsing malignant disease. This testing increasingly includes the use of large gene panels which may lead to incidental identification of genetic and molecular information of potential donor origin. Deciphering whether variants are of donor origin, and if so, whether there are clinical implications for the donor, can prove challenging. In response to queries from donor registries and transplant centers regarding best practice in managing donors when genetic mutations of potential donor origin are identified, the Medical Working Group of the World Marrow Donor Association established an expert group to review available evidence and to develop a framework to aid decision-making. These guidelines aim to provide recommendations on pre-donation consenting, post-donation testing of recipients and informing and managing donors when findings of potential donor origin are identified in recipients post-transplantation. It is recognised that registries will have different access to resources and financing structures. Therefore, where possible, we have made suggestions on how recommendations can be adapted.


Posterior interhemispheric retrocallosal approach to pineal region and posterior fossa lesions in a pediatric population.
The purpose of this study was to evaluate the posterior interhemispheric retrocallosal approach (PIRA) for its safety and efficacy in the resection of pineal region and posterior fossa lesions in children. Twenty-nine PIRAs were performed in 26 children between March 1997 and March 2009, and these cases were retrospectively reviewed. There were 15 girls and 11 boys in the series. The median age at the time of surgery was 7 years (range 7 months-17 years). Twenty-seven cases were treated for tumor, 1 for loculated hydrocephalus, and 1 for an aneurysm. Of the 27 cases treated for tumor, there were 20 (74%) gross-total resections, 5 (19%) subtotal resections, and 2 (7%) biopsies. One bridging vein was sacrificed in 6 cases and 2 bridging veins were divided in 1 case, whereas in 3 cases there was sacrifice of a single deep cerebral vein. No patient developed radiographic evidence of venous infarction. Approach-related complications were low, and included 2 cases of transient homonymous hemianopia. There were no surgery-related deaths. This approach allows for ample access to pineal region and posterior fossa lesions, with low postoperative morbidity.


[Candidiasis and AIDS in Yaounde].
In this preliminary study, we discuss 9 cases of Candidosis diagnosed during a 6 month period in 32 AIDS patients hospitalized in three health Centers in Yaoundé. Most of the patients presented with buccal candidosis and/or dysphagia. Of the 18 strains grown, 17 (94%) are Candida albicans.


Combination of Rheum ribes and Metformin Against Diabetes, Thermal Hyperalgesia, and Tactile Allodynia in a Mice Model.
The prevalence of diabetes mellitus (DM) is increasing. Because of its progressive nature, therapeutic shifts and combinations are often required to reduce the risk of glucose toxicity and avoid serious side effects. To treat DM and its related complications, a combination therapy may offer a promising remedy to counteract those issues. The study was established to evaluate the phytochemical content of a standardized aqueous extract of Rheum ribes (RR) and to determine the antidiabetic, antihyperalgesic, and antimechanical allodynic effects of 50 mg/kg of RR alone, 25 mg/kg of metformin (MTF) alone, and a combination of the 2 substances (MTF+RR) in mice with alloxan-induced diabetes. The research team designed an animal study. The study was performed at the facilities of the faculty of pharmacy at Beirut Arab University (Beirut, Lebanon). The animals were male, Swiss-Webster mice, weighing 22-30 g and aged 12-16 wk. DM was induced in experimental animals by an IP injection of alloxan every 48 h for 3 injections at a total dose of 180 mg/kg. Substudy A measured the acute-0, 0.5, 2, and 6 h-and subchronic-1, 3, 5, and 8 d-effects of a water extract of the RR alone, of the MTF alone, and of the MTF+RR combination on blood-glucose levels (BGLs), body weights, and catalase (CAT) serum levels. The mice were divided into 6 groups of 7 mice each, and each group received various IP injections of the tested samples: (1) group 1, a vehicle control group of normal mice (NORM group) received sterile, cold, 0.9% saline; (2) group 2, a vehicle control group of diabetic mice (VEH group) received sterile, cold, 0.9% saline; (3) group 3, a positive control group of diabetic mice (GB group) received 5 mg/kg of glibenclamide; (4) group 4, an intervention group of diabetic mice (MTF group) received 25 mg/kg of MTF only; (5) group 5, an intervention group of diabetic mice (RR group) received 50 mg/kg of RR only; and (6) group 6, an intervention group (MTF+RR group) of diabetic mice received 25 mg/kg of MTF and 50 mg/kg of RR. Substudy B measured the subchronic-0, 2, 4, 6, and 8 wk-effects of the RR only, of the MTF only, and of the MTF+RR combination on the hot plate and tail flick latencies and on the von Frey paw withdrawal thresholds. Again, they were divided into 6 groups of 7 mice each (groups 7 through 12), and each group received various IP injections of the tested samples, with all of the groups receiving the same treatments as for substudy A, except that group 9, a positive control group of diabetic mice, received 10 mg/kg of tramadol. The BGLs of the mice were monitored acutely for 6 h and subchronically for 8 d. Glycated hemoglobin (HbA1c), inhibition of α-glucosidase, and effects on serum insulin were evaluated. Using tail flick, hot plate latencies, and von Frey paw withdrawal thresholds, thermal hyperalgesia and tactile allodynia were assessed. Using a natural antioxidant, in vivo antioxidant activity was used to evaluate CAT and lipid peroxide (LPO) levels. The reductions in blood glucose, HbA1c, α-glucosidase, and LPO were statistically significant for the MTF+RR. The body weight, serum insulin, tail flick, hot plate latencies, paw withdrawal thresholds, and CAT increased significantly in diabetic mice treated with the combination. Consequently, the combination's potent inhibitory effect on α-glucosidase and serum insulin elevation might be responsible for its hypoglycemic potential, whereas its antioxidant effects might be responsible for the amelioration of painful hyperalgesia and allodynia, suggesting that the combination has better antidiabetic and antinociceptive effects and fewer side effects than treatment with MTF alone. No adverse events were reported. When combined with MTF, RR might be a promising adjuvant for amelioration of DM and related nociceptive complications.


Analysis of immunophenotypic features in hyaline vascular type Castleman disease.
Studies suggested that the immunophenotype of hyaline vascular type Castleman disease (HVCD) lacked characteristics, which was easy to be confused with other diseases. From January 2010 to June 2022, 17 cases of HVCD were selected from the Department of Pathology of Shaanxi Provincial People's Hospital and the Department of Pathology of Shaanxi Provincial Cancer Hospital. 13 cases of reactive hyperplastic lymph nodes (RHL) and 11 cases of follicular lymphoma (FL) were selected as the control group. All cases were performed CD3, CD20, CD21 and BCL2 immunohistochemical staining. (i) In 17 cases of HVCD, the negative area of BCL2 of germinal center was significantly smaller than the negative area of CD3 of germinal center. However, in 13 cases of RHL, the negative area of CD3 of germinal center was basically consistent with the negative area of germinal center of BCL2 of germinal center. In 11 cases of FL, in neoplastic follicles, the negative area of CD3 was basically consistent with the positive area of BCL2. The difference between HVCD group and other two groups of diseases was statistically significant (P < 0.05). (ii) In 17 cases of HVCD, the negative area of BCL2 of germinal center was significantly smaller than the follicular dendritic cell (FDC) meshworks expressed by CD21. However, in 13 cases of RHL, the FDC meshworks expressed by CD21 were basically consistent with the negative area of BCL2 of germinal center. In 11 cases of FL, in neoplastic follicles, the FDC meshworks expressed by CD21 was basically consistent with the positive area of BCL2. The difference between HVCD group and other two groups of disease was statistically significant (P < 0.05). HVCD has unique immunophenotypic characteristics. The negative area of BCL2 of germinal center is significantly smaller than the negative area of CD3. The negative area of the BCL2 of germinal center is significantly smaller than the FDC meshworks expressed by CD21. These two immunophenotypic features in HVCD are very important in diagnosis and differential diagnosis.